articles+ search results

HEART failure patients, PATIENT reported outcome measures, PATIENTS' attitudes, CLINICAL trials, HEART failure, and QUALITY of life

There are many consequences of heart failure (HF), including symptoms, impaired health‐related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient‐reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This 'minimal clinically important difference' requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed. [ABSTRACT FROM AUTHOR]

SEPTIC shock, INTERLEUKIN-7, LYMPHOCYTE count, LYMPHOPENIA, T cells, and INTRAVENOUS therapy

Background: Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days. Results: Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because three of fifteen patients receiving intravenous CYT107 developed fever and respiratory distress approximately 5–8 h after drug administration. Intravenous administration of CYT107 resulted in a two–threefold increase in absolute lymphocyte counts (including in both CD4+ and CD8+ T cells (all p < 0.05)) compared to placebo. This increase was similar to that seen with intramuscular administration of CYT107, was maintained throughout follow-up, reversed severe lymphopenia and was associated with increase in organ support free days (OSFD). However, intravenous CYT107 produced an approximately 100-fold increase in CYT107 blood concentration compared with intramuscular CYT107. No cytokine storm and no formation of antibodies to CYT107 were observed. Conclusion: Intravenous CYT107 reversed sepsis-induced lymphopenia. However, compared to intramuscular CYT107 administration, it was associated with transient respiratory distress without long-term sequelae. Because of equivalent positive laboratory and clinical responses, more favorable pharmacokinetics, and better patient tolerability, intramuscular administration of CYT107 is preferable. Trial registration: Clinicaltrials.gov, NCT03821038. Registered 29 January 2019, https://clinicaltrials.gov/ct2/show/NCT03821038?term=NCT03821038&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

MEDULLOBLASTOMA, HIPPOCAMPUS (Brain), CHILD patients, VOLUMETRIC-modulated arc therapy, BRAIN tumors, and SUBSTANCE abuse relapse

Background: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole‐brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri‐hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri‐hippocampal relapse in pediatric patients with medulloblastoma (MB). Methods and materials: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri‐hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ‐1), 6 to 10 mm (HZ‐2), and >10 mm (HZ‐3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard‐risk patients with MB were planned using either volumetric‐modulated arc therapy (VMAT) or intensity‐modulated proton therapy (IMPT) plans. Results: Thirty‐eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ‐1. The crude incidence of peri‐hippocampal failure was 8%. Both HA‐VMAT and HA‐IMPT plans were associated with significantly reduced mean dose to the hippocampi (p <.05). HA‐VMAT and HA‐IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. Conclusions: Peri‐hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. Plain Language Summary: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial. The incidence of peri‐hippocampal failures in patients treated with proton radiotherapy for pediatric medulloblastoma was 8%.Hippocampal sparing plans were associated with significant reduction in the mean dose to the right and left hippocampi. [ABSTRACT FROM AUTHOR]

TELECOMMUNICATION, DIGITAL technology, PRIMARY care, ONCOLOGISTS, and ELECTRONIC health records

Healthcare providers have reported challenges with coordinating care for patients with cancer. Digital technology tools have brought new possibilities for improving care coordination. A web- and text-based asynchronous system (eOncoNote) was implemented in Ottawa, Canada for cancer specialists and primary care providers (PCPs). This study aimed to examine PCPs' experiences of implementing eOncoNote and how access to the system influenced communication between PCPs and cancer specialists. As part of a larger study, we collected and analyzed system usage data and administered an end-of-discussion survey to understand the perceived value of using eOncoNote. eOncoNote data were analyzed for 76 shared patients (33 patients receiving treatment and 43 patients in the survivorship phase). Thirty-nine percent of the PCPs responded to the cancer specialist's initial eOncoNote message and nearly all of those sent only one message. Forty-five percent of the PCPs completed the survey. Most PCPs reported no additional benefits of using eOncoNote and emphasized the need for electronic medical record (EMR) integration. Over half of the PCPs indicated that eOncoNote could be a helpful service if they had questions about a patient. Future research should examine opportunities for EMR integration and whether additional interventions could support communication between PCPs and cancer specialists. [ABSTRACT FROM AUTHOR]

Background Hybrid immunity is associated with more durable protection against coronavirus disease 2019 (COVID-19). We describe the antibody responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated and unvaccinated individuals. Methods The 55 vaccine arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens (ancestral and variants of concern [VOCs]) were assessed on disease day 1 (DD1) and 28 days later (DD29). Results The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post–first dose. For vaccine group cases, there was a 1.88-fold rise in ancestral antispike bAbs 1 month post–disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 antispike and antinucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group. Conclusions Following COVID-19, vaccinated participants had higher levels and greater breadth of antispike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series. [ABSTRACT FROM AUTHOR]

LEFT heart ventricle, PATIENT aftercare, CAUSES of death, CONFIDENCE intervals, MAGNETIC resonance imaging, GLOBAL longitudinal strain, SYSTEMIC scleroderma, TERTIARY care, DESCRIPTIVE statistics, RESEARCH funding, LOGISTIC regression analysis, ODDS ratio, LEFT heart atrium, HEART failure, and PROPORTIONAL hazards models

Objective This study aimed to determine whether lower values of feature-tracking cardiovascular magnetic resonance (CMR)-derived left atrial reservoir strain (LARS) and impaired left ventricular (LV) global longitudinal strain (GLS) were associated with the presence of symptoms and long-term prognosis in patients with SSc. Methods A total of 100 patients {54 [interquartile range (IQR) 46–64] years, 42% male} with SSc who underwent CMR imaging at two tertiary referral centres were included. All patients underwent analysis of LARS and LV GLS using feature-tracking on CMR and were followed-up for the occurrence of all-cause mortality. Results The median LV GLS was –21.8% and the median LARS was 36%. On multivariable logistic regression, LARS [odds ratio (OR) 0.964 per %, 95% CI 0.929, 0.998, P  = 0.049] was independently associated with New York Heart Association (NYHA) class II–IV heart failure symptoms. Over a median follow-up of 37 (21–62) months, a total of 24 (24%) patients died. Univariable Cox regression analysis demonstrated that LARS [hazard ratio (HR) 0.94 per 1%, 95% CI 0.91, 0.97, P  < 0.0001) and LV GLS (HR 1.10 per %, 95% CI 1.03, 1.17, P  = 0.005) were associated with all-cause mortality, while LV ejection fraction was not. Likelihood ratio tests demonstrated that LARS provided incremental value over prognostically important clinical and imaging parameters, including late gadolinium enhancement. Conclusion In patients with SSc, LARS was independently associated with the presence of NYHA class II–IV heart failure symptoms. Although both LARS and LV GLS were associated with all-cause mortality, only LARS provided incremental value over all evaluated variables known to be prognostically important in patients with SSc. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., SARS-CoV-2 Omicron variant, IMMUNOGLOBULINS, and DURABILITY

Solid organ transplant recipients (SOTRs) have reduced immunogenicity to SARS-CoV-2 vaccines and are at increased risk of severe COVID-19 when compared to the general population.[1] Previously, a fourth dose (D4) of SARS-CoV-2 vaccine has shown improved antibody responses in SOTRs, but given the decreasing titers seen by 6 months post-dose 2 and 3, immune responses achieved after D4 could decrease in a similar fashion.[[2]] This study assesses the durability and kinetics of vaccine-induced antibody responses in SOTRs post-D4 and evaluates these responses in the context of the Omicron variant, which requires higher levels of antibody to neutralize. In this study of antibody responses after a fourth dose of SARS-CoV-2 vaccine in SOTRs with 6 months of follow up, 61% demonstrated antibody titers associated in prior studies with potential SARS-CoV-2 Omicron variant neutralization at 3 months. 3 c 5/18 SOTRs with low titers and 8/39 SOTRs with high titers were unable to provide titers at 3-months post-D4. [Extracted from the article]

Background: Mild Cognitive Impairment with Suspected non‐Alzheimer's Pathophysiology (SNAP‐MCI) represents a group of patients with Alzheimer's disease (AD) like neurodegeneration without beta‐amyloid pathology. While this group likely has a heterogeneous etiology, tau pathology, as in Primary Age‐Related Tauopathy (PART), has been hypothesized to play a major role. We investigate tau positron emission tomography (PET) uptake in the medial temporal lobe (MTL) in SNAP‐MCI and the association of MTL Tau‐PET uptake with structural measures and delayed recall in beta‐amyloid negative (A‐) MCI patients. Method: 237 MCI patients and 301 A‐ controls with available beta‐amyloid and tau PET and magnetic resonance images (within 200 days) were included. Baseline hippocampal volume and entorhinal cortex (ERC) and Brodmann areas (BA)35 thickness were obtained using an in‐house developed pipeline and annualized atrophy rates were estimated in an unbiased fashion using follow‐up MRIs within 4.5 years. Βeta‐amyloid status (A+/‐) was determined by a standard cut‐off (Florbetapir: 1.11; Florbetaben: 1.08) and neurodegeneration status (N+/‐) by hippocampal volumes, corrected for intracranial volume, using the 90th percentile of A+ AD patients as the cut‐off. Tau‐PET standardized uptake value ratio (SUVR) in the ERC/BA35 was calculated. A composite z‐score of delayed recall at baseline and change over 2 years was obtained. Result: SNAP‐MCI had significantly higher ERC/BA35 Tau‐PET SUVR than A‐ controls (Table 1, corrected for age) and qualitatively higher than A‐N‐ MCI (p=0.10). ERC/BA35 Tau‐PET SUVR in A‐N‐ MCI was not significantly different from A‐ controls. In A‐ MCI patients, ERC/BA35 Tau‐PET SUVR was significantly associated with BA35 thickness and hippocampal, ERC and BA35 atrophy rates, corrected for beta‐amyloid PET SUVR (Table 2; Figure 1). MTL structural measures, but not ERC/BA35 Tau‐PET SUVR, were associated with cross‐sectional and longitudinal delayed recall measures (Table 3; Figure 2). Conclusion: SNAP‐MCI had elevated ERC/BA35 Tau‐PET SUVR and ERC/BA35 Tau‐PET SUVR was associated with MTL structural measures in A‐ MCI patients. This indicates that tau pathology might be an important driver of neurodegeneration in the absence of beta‐amyloid pathology, supporting the notion that PART contributes to SNAP‐MCI. Additionally, MTL structure was associated with memory performance, consistent with SNAP not being a benign condition. [ABSTRACT FROM AUTHOR]

Background: While previous studies have demonstrated the effect of Alzheimer's disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management. Method: The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling. Result: Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers. Conclusion: This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, ANTIBODY formation, HEART transplant recipients, LUNG transplantation, HIV seroconversion, and BOOSTER vaccines

Antibody response to a third dose of SARS-CoV-2 vaccine in heart and lung transplant recipients Morbidity and mortality from SARS-CoV-2 infection in heart (HT) and lung transplant (LT) recipients are high, especially for LT recipients, despite vaccination.[1] Despite severe COVID-19 outcomes, HT/LT recipients represent <10% of solid organ transplant recipients (SOTRs) included in cohort studies evaluating two and three dose regimens.[2] There is now strong evidence to support that SOTRs in a greater immunosuppressed state (common among HT/LT recipients) are at increased risk for persistent seronegative state post-D3.[[3]] Therefore, we evaluated antispike antibody responses before and after a third vaccine dose (D3) in HT/LT recipients to quantify post-D3 antibody responses. Effect of Mycophenolate mofetil dosing on antibody response to SARS-CoV-2 vaccination in heart and lung transplant recipients. [Extracted from the article]

TELECOMMUNICATION, CANCER, PRIMARY care, ELECTRONIC health records, and MEDICAL personnel

Previous research has identified communication and care coordination problems for patients with cancer. Healthcare providers (HCPs) have reported communication issues due to the incompatibility of electronic medical records (EMR) software and not being consistently copied on patient reports. We evaluated an asynchronous web-based communication system ("eOncoNote") for primary care providers and cancer specialists to improve cancer care coordination. The objectives were to examine patients' perceptions of the role of eOncoNote in their healthcare, and HCPs' experiences of implementing eOncoNote. Qualitative interviews were conducted with patients with breast and prostate cancer, primary care providers, and cancer specialists. Eighteen patients and fourteen HCPs participated. Six themes were identified from the patient interviews focusing on HCP and patient roles related to care coordination and patient awareness of communication among their HCPs. Four themes were identified from HCP interviews related to the context of care coordination and experience with eOncoNote. Both patients and HCPs described the important role patients and caregivers play in care coordination. The results show that patients were often unaware of the communication between their HCPs and assumed they were communicating. HCPs encountered challenges incorporating eOncoNote into their workflow. [ABSTRACT FROM AUTHOR]

NURSING licensure, OCCUPATIONAL roles, PROFESSIONAL ethics, TEAMS in the workplace, STATISTICS, EVALUATION of human services programs, NURSING, PROFESSIONS, RESEARCH methodology, HUMAN services programs, PRE-tests & post-tests, LEARNING strategies, INTERPROFESSIONAL relations, COMMUNICATION, QUESTIONNAIRES, DESCRIPTIVE statistics, INTERDISCIPLINARY education, NURSING students, STUDENT attitudes, STATISTICAL sampling, DATA analysis software, THEMATIC analysis, and TRAINING of athletic trainers

Background: The purpose of this article is to describe the development, implementation, and evaluation of a Simulation Interprofessional Education (Sim‐IPE) activity for healthcare students from different disciplines (athletic training [AT] and nursing). The objective for the Sim‐IPE activity was to engage AT and prelicensure nursing students in a realistic healthcare scenario to enhance knowledge about one another's profession, develop interprofessional skills, collaborate with one another, and communicate effectively as a team as they performed care. Methods: This mixed methods study employed a one‐time posttest design for a convenience sample of AT and prelicensure nursing students following a simulation intervention. Students completed the Student Perceptions of Interprofessional Clinical Education‐Revised (SPICE‐R) survey and answered open‐ended response questions. Results: Thirteen students (N = 13) from Cohort 1 and 12 students (N = 12) from Cohort 2 completed the SPICE‐R survey. Most students strongly agreed/agreed for each of the SPICE‐R survey questions. Qualitative findings indicated the students positively perceived the Sim‐IPE activity as it helped them discover the value of interprofessional patient care. Discussion: The quantitative findings indicated that the students found the Sim‐IPE an effective learning methodology to achieve the objectives while the qualitative findings gave further insight into the students' perceptions of interprofessional teamwork and the value of the prebrief session conducted before the simulation. The findings will inform future Sim‐IPE activities involving additional groups of healthcare students. [ABSTRACT FROM AUTHOR]

GENETIC variation, SLEEP, MISSENSE mutation, GENETIC testing, CLOCK genes, SLEEP disorders, and EXOMES

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10-8; and had a 57-minute earlier midpoint sleep, P = 5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population. Author summary: Clinically ascertained family-based studies have previously identified rare genetic variation associated with causing life-long sleep conditions, specifically shorter sleep, and earlier or later sleep timing. However, the effects of previously reported genetic variants on sleep duration and timing when identified incidentally through population-based studies are not known. Here, we take advantage of up to 191,929 individuals from four population-based studies, including the UK Biobank, to estimate the effects of these variants on sleep duration and timing using self-reported and accelerometer-based sleep estimates coupled with sequencing data. Our analysis revealed no association between variants previously reported and extreme sleep conditions. Two variants located in two genes (PER3 and CRY1) showed evidence of association with sleep timing, but their estimated effects (~5 to 7 minutes) on sleep timing are much smaller relative to those previously reported. Our results indicate that previously reported variants are not causal for extreme sleep conditions in the general population. Finally, although we were unable to analyse a previously reported variant in the PER2 gene associated with sleep timing, additional analysis in the UK Biobank revealed carries of protein-truncating variants in this gene have an approximately 1-hour earlier sleep midpoint compared to non-carriers. These population-based estimates are important because of the recent dramatic increase in direct-to-consumer and health service genome-wide genetic testing. [ABSTRACT FROM AUTHOR]

ALCOHOL drinking, ENERGY consumption, WARNING labels, INCOME, WEIGHT gain, and CONSUMPTION (Economics)

Background: Alcohol is a discretionary, energy dense, dietary component. Compared to non-drinkers, people who consume alcohol report higher total energy intake and may be at increased risk of weight gain, overweight, and obesity, which are key preventable risk factors for illness. However, accurate consumer knowledge of the energy content in alcohol is low. To inform future behaviour change interventions among drinkers, this study investigated individual characteristics associated with changing alcohol consumption due to energy-related concerns.Methods: An online survey was undertaken with 801 Australian adult drinkers (18-59 years, 50.2% female), i.e. who consumed alcohol at least monthly. In addition to demographic and health-related characteristics, participants reported past-year alcohol consumption, past-year reductions in alcohol consumption, frequency of harm minimisation strategy use (when consuming alcohol), and frequency of changing alcohol consumption behaviours because of energy-related concerns.Results: When prompted, 62.5% of participants reported changing alcohol consumption for energy-related reasons at least 'sometimes'. Women, those aged 30-44 years, metropolitan residents, those with household income $80,001-120,000, and risky/more frequent drinkers had increased odds of changing consumption because of energy-related concerns, and unemployed respondents had reduced odds.Conclusions: Results indicate that some sociodemographic groups are changing alcohol consumption for energy-related reasons, but others are not, representing an underutilised opportunity for health promotion communication. Further research should investigate whether messaging to increase awareness of alcohol energy content, including through systems-based policy actions such as nutritional/energy product labelling, would motivate reduced consumption across a broader range of drinkers. [ABSTRACT FROM AUTHOR]

TRANSPLANTATION of organs, tissues, etc., COVID-19 vaccines, MESSENGER RNA, VACCINATION, and ANTIBODY formation

Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS‐CoV‐2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA‐1273; D3‐mRNA) versus heterologous (Ad.26.COV2.S; D3‐JJ) D3 among 377 SARS‐CoV‐2‐infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti‐spike titers and used weighted Poisson regression to evaluate seroconversion and development of high‐titers, comparing D3‐JJ to D3‐mRNA, at 1‐, 3‐, and 6 month post‐D3. 1‐month post‐D3, seroconversion (63% vs. 52%, p =.3) and development of high‐titers (29% vs. 25%, p =.7) were comparable between D3‐JJ and D3‐mRNA recipients. 3 month post‐D3, D3‐JJ recipients were 1.4‐fold more likely to seroconvert (80% vs. 57%, weighted incidence‐rate‐ratio: wIRR = 1.101.401.77, p =.006) but not more likely to develop high‐titers (27% vs. 22%, wIRR = 0.440.921.93, p =.8). 6 month post‐D3, D3‐JJ recipients were 1.41‐fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.411.93, p =.029) and 2.63‐fold more likely to develop high‐titers (59% vs. 21%, wIRR = 1.382.635.00, p =.003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3. Solid organ transplant recipients with negative anti‐spike antibody after a two‐dose mRNA SARS‐CoV‐2 vaccine series are more likely to seroconvert after receiving a third dose of the heterologous vaccine Ad.26.COV2.S, compared to a homologous mRNA vaccine. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., IMMUNE response, MESSENGER RNA, and SARS-CoV-2 Delta variant

Heterologous vaccination has been explored in small populations of solid organ transplant recipients (SOTRs),1-4 yet 38% of participants had persistently suboptimal response indicating potential role for further vaccine doses.1 The US CDC currently recommends immunocompromised adults who received an Ad26.COV2.S prime to receive one additional dose of SARS-CoV-2 mRNA vaccine, either BNT162b2 or mRNA-1273, followed by two mRNA vaccine boosters, although the efficacy of this strategy in immunocompromised persons is not known. A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid organ transplant recipients. Immunogenicity of Ad26.COV2.S prime and two subsequent doses of mRNA SARS-CoV-2 vaccines in solid organ transplant recipients: A case series. [Extracted from the article]

SEDENTARY lifestyles, GLOBAL Positioning System, HOME environment, SCHOOL environment, BUILT environment, SOCIAL support, CROSS-sectional method, SELF-evaluation, POPULATION geography, PHYSICAL activity, SOCIAL context, ACCELEROMETRY, SELF-efficacy, QUESTIONNAIRES, DESCRIPTIVE statistics, STATISTICAL models, and ADOLESCENCE

Background: A better understanding of the extent to which psychosocial and environmental correlates of physical activity are specific to locations would inform intervention optimization. Purpose: To investigate cross-sectional associations of location-general and location-specific variables with physical activity and sedentary time in three common locations adolescents spend time. Methods: Adolescents (N = 472,Mage = 14.1,SD = 1.5) wore an accelerometer and global positioning systems (GPS) tracker and self-reported on psychosocial (e.g., self-efficacy) and environmental (e.g., equipment) factors relevant to physical activity and sedentary time. We categorized each survey item based on whether it was specific to a location to generate psychosocial and environmental indices that were location-general or specific to either school, non-school, or home location. Physical activity (MVPA) and sedentary time were based on time/location match to home, school, or all "other" locations. Mixed-effects models investigated the relation of each index with location-specific activity. Results: The location-general and non-school physical activity psychosocial indices were related to greater MVPA at school and "other" locations. The school physical activity environment index was related to greater MVPA and less sedentary time at school. The home activity environment index was related to greater MVPA at home. The non-school sedentary psychosocial index was related to less sedentary time at home. Interactions among indices revealed adolescents with low support on one index benefited (i.e., exhibited more optimal behavior) from high support on another index (e.g., higher scores on the location-general PA psychosocial index moderated lower scores on the home PA environment index). Concurrent high support on two indices did not provide additional benefit. Conclusions: No psychosocial or environment indices, including location-general indices, were related to activity in all locations. Most of the location-specific indices were associated with activity in the matching location(s). These findings provide preliminary evidence that psychosocial and environmental correlates of activity are location specific. Future studies should further develop location-specific measures and evaluate these constructs and whether interventions may be optimized by targeting location-specific psychosocial and environmental variables across multiple locations. [ABSTRACT FROM AUTHOR]

MATURITY onset diabetes of the young, GRANULE cells, INSULIN, STEM cells, and INTRACELLULAR calcium

Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of β-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient β-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient β-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in β-cells null for HNF1A, β-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies. hPSCs model of Maturity Onset Diabetes of the Young caused by mutations in the transcription factor HNF1A (HNF1A-MODY), regulates the expression of genes required for the formation of dense-core insulin granules and calcium-dependent insulin secretion, demonstrating a basis to treat HNF1A-MODY patients with sulfonylureas. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., VACCINES, and IMMUNE response

Fewer than 45% of solid organ transplant recipients (SOTRs) mount a detectable antispike antibody level after two doses of mRNA SARS-CoV-2 vaccination (D2).1 Various vaccination strategies, including mixing platforms, have been proposed, but there is no consensus on the optimal vaccination sequence to improve immunogenicity.2,3 Although using similar technology, the mRNA-1273 vaccine has been associated with higher peak antibody responses than the use of BNT162b2 in immunosuppressed populations, potentially related to a higher vaccine antigen dose.3,4 We therefore studied whether the use of mRNA-1273 versus BNT162b2 as a third primary vaccine dose (D3) might generate a more robust antibody response in SOTR who remained seronegative after two doses of BNT162b2. Improved humoral immunogenicity with mRNA-1273 versus BNT162b2 as third vaccine dose among solid organ transplant recipients seronegative after two BNT162b2 doses METHODS From our national observational study, approved by the Johns Hopkins Institutional Review Board (IRB00248540),4 we included adult SOTRs who tested seronegative after two doses of BNT162b2 and received either a D3-BNT162b2 or D3-mRNA-1273. [Extracted from the article]

MOTHERS, PARENT attitudes, SOCIAL norms, AGE distribution, CROSS-sectional method, INTERNET, FATHERS, SEX distribution, PARENTING, ALCOHOL drinking, DESCRIPTIVE statistics, PARENT-child relationships, and PARENTS

Aims This study aimed to examine perceived social norms, the effect of parental drinking on these norms, alcohol use in front of children, and how norms and consumption vary based on child age and gender of the parent. Methods A cross-sectional online panel survey was undertaken with n  = 1000 Australian adults (including 670 parents) aged 18–59 years. The survey assessed: alcohol consumption in front of children; normative attitudes towards drinking in the presence of children; and perceived social norms. Results Overall, 33.9% of parents reported drinking a glass of alcohol each day or a couple of times a week, 18.2% reported getting slightly drunk and 7.8% indicated getting visibly drunk each day or a couple of times a week with their children present. In total, 37.5% reported drinking in front of their children at least weekly. Fathers were more likely to drink in front of children than mothers. Most parents deemed drinking small amounts of alcohol in front of children as acceptable but did not accept drunkenness. Respondents were less concerned about a father drinking one or two drinks in front of their children than a mother. Social expectations were not related to child age, but norms related to others' perceived behaviour were. Conclusions Many parents, particularly fathers consume alcohol in front of their children. There is a need to target health promotion strategies to adults and parents consuming in excess of health guidelines, and to the many parents who are consuming alcohol at higher levels in front of their children. [ABSTRACT FROM AUTHOR]

BLACK feminism, HISTORY of feminism, FEMINISM, BLACK feminists, WORLD history, CONVERSATION, and RACISM

This roundtable stems from a Zoom event, "New Directions in Feminism and Global Race Studies (a Book Conversation)" with authors Tiffany N. Florvil, Kaiama L. Glover, Annette K. Joseph-Gabriel, Katherine M. Marino, Robin Mitchell, and Jacqueline-Bethel Tchouta Mougoué, hosted by Samantha Pinto. These scholars discussed their recently published books, which expand how we think about transnational feminism and global Black feminisms in the Americas, the Caribbean, Africa, and Europe. The lightly edited transcript of the conversation explores how putting Black women at the center of histories of global feminisms and race studies transforms these fields and the questions that are usually asked. The authors also discussed navigating research challenges and confronting racism in the sources and in the archives. The conversation underscores the importance of intellectual community, as well as the relevance and urgency of Black feminist scholarship today. [ABSTRACT FROM AUTHOR]

The left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. The goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM. Patients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize. A total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro–B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05). LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]

COVID-19, SARS-CoV-2, and REMDESIVIR

Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir. [ABSTRACT FROM AUTHOR]

TEACHERS, TEACHING of controversial topics, STUDENTS, DISCUSSION in education, and SOCIAL conditions of students

Controversial topics may be uncomfortable for teachers to include in their in-class discussions. However, there are considerable cognitive and social-emotional benefits to engagement in controversial conversations, or classroom discussion about controversial topics. It is critical that teachers support students in respectful discussion to help them develop skills such as problem solving, critical thinking, and the ability to consider issues from multiple perspectives. These skills can enable students to meet larger educational goals such as engaged citizenship. The goal of this article is to highlight the benefits of controversial conversations in the classroom and describe teaching approaches that facilitate effective controversial conversations. First, we identify important factors for teachers' consideration in supporting effective and beneficial controversial conversations. Second, we provide examples of topics of conversations that may be appropriate for students of varying ages. Third, we review how the structure of conversation, scaffolding, classroom context, relationships, and students' individual differences can shape controversial conversations. [ABSTRACT FROM AUTHOR]

SOFT robotics, LYMPHEDEMA, SLEEVES, AIR pressure, MICROFLUIDICS, VALVES, MICROFLUIDIC devices, and DRAINAGE

A proof of concept of a novel air microfluidics-enabled soft robotic sleeve to enable lymphedema treatment is presented. Compression sleeves represent the current, suboptimal standard of care, and stationary pumps assist with lymph drainage; however, effective systems that are truly wearable while performing daily activities are very scarce. This problematic trade-off between performance and wearability requires a new solution, which is addressed by an innovative microfluidic device. Its novelty lies in the use of light, small, and inexpensive air microfluidic chips (35 × 20 × 5 mm3 in size) that bring three major advantages compared to their traditional counterparts. First, each chip is designed with 16 fluidic channels with a cross-sectional area varying from 0.04 to 1 mm2, providing sequential inflation and uniform deflation capability to eight air bladders, thereby producing intentional gradient compression to the arm to facilitate lymph fluid circulation. The design is derived from the fundamentals of microfluidics, in particular, hydraulic resistance and paths of least resistance. Second, the air microfluidic chip enables miniaturization of at least eight bulky energy-consuming valves to two miniature solenoid valves for control increasing wearability. Third, the air microfluidic chip has no moving parts, which reduces the noise and energy needed. The cost, simplicity, and scale-up potential of developing methods for making the system are also detailed. The sequential inflation, uniform deflation, and pressure gradient are demonstrated, and the resulted compression and internal air bladder pressure were evaluated. This air microfluidics-enabled sleeve presents tremendous potential toward future improvements in self-care lymphedema management. [ABSTRACT FROM AUTHOR]

COMMUNICABLE diseases, INFECTIOUS arthritis, HOSPITAL patients, CELLULITIS, DRUG abuse, DRUGS, and FISHER exact test

Injection drug use poses a public health challenge. Clinical experience indicates that people who inject drugs (PWID) are hospitalized frequently for infectious diseases, but little is known about outcomes when admitted. Charts were identified from local hospitals between 2013–2018 using consultation lists and hospital record searches. Included individuals injected drugs in the past six months and presented with infection. Charts were accessed using the hospital information system, undergoing primary and secondary reviews using Research Electronic Data Capture (REDCap). The Wilcoxon rank-sum test was used for comparisons between outcome categories. Categorical data were summarized as count and frequency, and compared using Fisher's exact test. Of 240 individuals, 33% were admitted to the intensive care unit, 36% underwent surgery, 12% left against medical advice (AMA), and 9% died. Infectious diagnoses included bacteremia (31%), abscess (29%), endocarditis (29%), cellulitis (20%), sepsis (10%), osteomyelitis (9%), septic arthritis (8%), pneumonia (7%), discitis (2%), meningitis/encephalitis (2%), or other (7%). Sixty-six percent had stable housing and 60% had a family physician. Fifty-four percent of patient-initiated discharges were seen in the emergency department within 30 days and 29% were readmitted. PWID are at risk for infections. Understanding their healthcare trajectory is essential to improve their care. [ABSTRACT FROM AUTHOR]

COVID-19, SEDENTARY behavior, PHYSICAL activity, HOSPITAL care, and PATIENTS' attitudes

Many patients with COVID-19 experience severe and even fatal disease. Survivors may have long-term health consequences, but data on physical activity and sedentary behaviour are scarce. Therefore, we objectively assessed physical activity (PA) patterns among post-hospitalised patients with COVID-19 and explored associations with patient characteristics, disease severity and cardiac dysfunction. We objectively assessed PA, sedentary behaviour and sleep duration for 24 h/day during 8 days at 3-6 months after COVID-19 hospitalisation. PA and sedentary time were compared across pre-defined subgroups based on patient and disease characteristics, cardiac biomarker release during hospitalisation, abnormal transthoracic echocardiogram at 3-6 months post-hospitalisation and persistence of symptoms post-discharge. PA and sedentary behaviour were assessed in 37 patients (60 ± 10 years old; 78% male). Patients spent 4.2 [3.2; 5.3] h/day light-intensity PA and 1.0 [0.8; 1.4] h/day moderate-to-vigorous intensity PA. Time spent sitting was 9.8 [8.7; 11.2] h/day, which was accumulated in 6 [5; 7] prolonged sitting bouts (≥30 min) and 41 [32; 48] short sitting bouts (<30 min). No differences in PA and sedentary behaviour were found across subgroups, but sleep duration was higher in patients with versus without persistent symptoms (9.1 vs. 8.3 h/day, p = 0.02). Taken together, high levels of sedentary time are common at 3–6 months after COVID-19 hospitalisation, whilst PA and sedentary behaviour are not impacted by patient or disease characteristics. [ABSTRACT FROM AUTHOR]

DISABILITY awareness, PEOPLE with disabilities, CRITICAL thinking, RESEARCH personnel, and STRATEGIC planning

Objective: The main objectives were to 1) search and map current disability awareness and training activities in Quebec, Canada, 2) collectively reflect on these practices, and 3) develop a five-year strategic plan.Methods: We used an integrated knowledge translation approach whereby researchers and community partners were involved in all stages. This project consisted of two sequential phases: 1) an environmental scan (web review and interview) of current practices, and 2) a reflection process with an external expert-facilitator in social transformation. Outcome results and process data are reported.Results: We identified 129 activities (71 training, 58 awareness) from 39 organizations (from 123 organizations initially invited). A wide range of characteristics were collected for each activity which allowed for the identification of gaps. The working group met seven times in one year to discuss results from phase 1 and co-create a five-year strategic plan. Main priorities are 1) the development of a methodology for measuring collective impact and 2) content synchronization of activities.Conclusion: Involvement of partners and researchers enabled a concerted and efficient approach to the development of a five-year strategic plan.Practice Implications: A transition committee led by partners will ensure implementation and sustainability of the plan across the province. [ABSTRACT FROM AUTHOR]

ANTIBODY formation, VACCINE effectiveness, HEART transplant recipients, SARS-CoV-2, and MESSENGER RNA

While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p <.001). Priming dose antibody response was associated with younger recipient age (p =.04), transplant-to-vaccination time ≥6 years (p <.01), and lack of anti-metabolite maintenance immunosuppression (p <.001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed. [ABSTRACT FROM AUTHOR]

PROFESSIONAL education, IDENTITY (Psychology), PROFESSIONAL identity, INTERPERSONAL conflict, CONFLICT management, and CURRICULUM

This article describes the development and assessment of teaching strategies to enhance student professional identity development by shifting the pedagogical focus from content knowledge to the practice of interpersonal and conflict resolution skills, and reflection to create awareness, observe growth, and find meaning. [ABSTRACT FROM AUTHOR]

GENDER mainstreaming and REHABILITATION

Marketers, filmmakers, and cinema-goers assume that genre has a large effect on how the audience responds to and engages with a film. However, trait measures such as transportability suggest that, in some cases, individual differences may shape audience engagement more than genre does. To investigate this disparity, we compared viewers' enjoyment, identification with characters, and story world absorption (including three subscales: Transportation, Attention, and Emotional Engagement) for film clips from two very different genres (an emotional family film vs. an action chase scene) in a within-subjects design. Across two studies--an exploratory study and a preregistered replication--we found that participants' feelings of being transported into the narrative (a dimension of story world absorption) were more highly correlated across films than other measures were and tended to be less related to genre preference than the other audience response measures were. This pattern of results suggests that feelings of transportation may be more dependent on individual differences, and less sensitive to genre, than other forms of audience response. An exploratory analysis of a short scale measuring trait transportability suggested this measure was not the basis of the individual differences theorized to underlie transportation. Our results further highlight the importance of examining viewer engagement with narrative as a multidimensional, rather than unitary, concept. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic, MEDICAL personnel, PEOPLE with epilepsy, SOCIAL distancing, and CAREGIVER attitudes

• The COVID-19 and Epilepsy (COV-E) global surveys were launched in Brazil during the first wave of the pandemic. • People with epilepsy reported worsening seizure control, psychosocial stress, and impaired mental health. • There were difficulties in obtaining drug supplies because of canceled appointments. • Discussion of risk, including SUDEP, was infrequent even before the pandemic. • The surveys remain open to enable new participants to enter data providing insights as the pandemic evolves. The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from May to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy. Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53), and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or canceled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19. Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic. [ABSTRACT FROM AUTHOR]

GENETIC variation, REWARD (Psychology), and BRAIN imaging

PATIENT advocacy, EMPATHY, INTERVIEWING, INTERNSHIP programs, UNDERGRADUATES, UNIVERSITIES & colleges, NURSING students, STUDENT attitudes, THEMATIC analysis, and BULLYING

The two aims of this study were, first, to explore nursing students' experiences and perspectives of reporting poor care and second, examine the process by which they raised concerns. The nursing literature is replete with studies which explore nursing students' experiences of clinical placement. However only a small number explore students experiences of challenging poor care and how this is enacted in the practice setting. Fourteen nursing students from undergraduate pre-registration nursing programs across three universities, two in the United Kingdom (UK) and one in Australia. This paper reports findings from narrative interviews about students' clinical experiences of reporting poor care. Data were audio recorded, transcribed verbatim and analyzed using a constant comparison approach. Emerging themes were identified, discussed and verified by the researchers. Four montages from the narratives highlight the overarching themes: bullying, patient advocacy, lack of empathy and poor care. They demonstrate how, driven by an ethical imperative, students speak up when they witness poor care despite the difficulties of doing so: in some cases, the students in this study were prepared to continue speaking out even when initial concerns were dismissed. Both practice and university teams have a responsibility to support students' development as ethical and courageous practitioners, able to recognize when care falls below an acceptable standard. • This paper highlights the vital role that students play in highlighting poor nursing care practices. • Nursing students are capable of reporting poor nursing care even when it might come at a cost to themselves. • Clinicians and academics must support students to challenge poor nursing care practices. [ABSTRACT FROM AUTHOR]

COVID-19, TRANSPLANTATION of organs, tissues, etc., COVID-19 pandemic, SARS-CoV-2, and MEDICAL research

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID‐19, as suggested by recent case series. We compared 45 SOT vs. 2427 non‐SOT patients who were admitted with COVID‐19 to our health‐care system (March 1, 2020 ‐ August 21, 2020), evaluating hospital length‐of‐stay and inpatient mortality using competing‐risks regression. We compared trajectories of WHO COVID‐19 severity scale using mixed‐effects ordinal logistic regression, adjusting for severity score at admission. SOT and non‐SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p <.001), hypertension (69% vs. 44%, p =.001), HIV (7% vs. 1.4%, p =.024), and peripheral vascular disorders (19% vs. 8%, p =.018). There were no statistically significant differences between SOT and non‐SOT in maximum illness severity score (p =.13), length‐of‐stay (sHR: 0.91.11.4, p =.5), or mortality (sHR: 0.10.41.6, p =.19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non‐SOT (median [IQR] 4 [3–4]) (p =.042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.760.810.86, p <.001) compared with non‐SOT patients. These findings have implications for transplant decision‐making during the COVID‐19 pandemic, and insights about the impact of SARS‐CoV‐2 on immunosuppressed patients. [ABSTRACT FROM AUTHOR]

COVID-19, MEDICAL research, COVID-19 treatment, VIRUS diseases, and COMMUNICABLE diseases

Keywords: clinical research/practice; infection and infectious agents; infection and infectious agents - viral; infectious disease EN clinical research/practice infection and infectious agents infection and infectious agents - viral infectious disease 2306 2306 1 06/07/21 20210601 NES 210601 I To the Editor: i We thank Drs. The 45 SOT recipients included 28 kidney, six liver, two liver/kidney, five lung, three heart, and one composite tissue allograft recipient. Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States. [Extracted from the article]

DROWSINESS, ALZHEIMER'S disease, GENOME-wide association studies, SLEEP, RESEARCH, SEQUENCE analysis, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, and RESEARCH funding

Background: It is established that Alzheimer's disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD.Methods: We used the largest published genome-wide association studies of self-reported and accelerometer-measured sleep traits (chronotype, duration, fragmentation, insomnia, daytime napping and daytime sleepiness), and AD. Mendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured sleep parameters on AD risk.Results: Overall, there was little evidence to support a causal effect of sleep traits on AD risk. There was some suggestive evidence that self-reported daytime napping was associated with lower AD risk [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.50-0.99). Some other sleep traits (accelerometer-measured 'eveningness' and sleep duration, and self-reported daytime sleepiness) had ORs of a similar magnitude to daytime napping, but were less precisely estimated.Conclusions: Overall, we found very limited evidence to support a causal effect of sleep traits on AD risk. Our findings provide tentative evidence that daytime napping may reduce AD risk. Given that this is the first MR study of multiple self-report and objective sleep traits on AD risk, findings should be replicated using independent samples when such data become available. [ABSTRACT FROM AUTHOR]

ANTIBODY formation, VIRAL vaccines, COVID-19 pandemic, IMMUNE response, TRANSPLANTATION of organs, tissues, etc., MESSENGER RNA, and VACCINATION

This follow-up study measures the antibody response following the second dose of SARS-CoV-2 mRNA vaccine in recipients of solid organ transplants. [ABSTRACT FROM AUTHOR]

ANTIBODY formation, VACCINES, MESSENGER RNA, COVID-19, IMMUNOCOMPROMISED patients, and TRANSPLANTATION of organs, tissues, etc.

This study quantifies antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic, LIVER transplantation, COVID-19, MEDICAL care, and PANDEMICS

COVID‐19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID‐19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020‐8/31/2020 to expected values based on historical trends 1/2016‐1/2020, stratified by statewide COVID‐19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = 0.84 0.890.93), LDLTs were 49% fewer (IRR = 0.37 0.510.72), and DDLTs were 9% fewer (IRR = 0.85 0.910.97). In May, new listings were 21% fewer (IRR = 0.74 0.790.84), LDLTs were 42% fewer (IRR = 0.39 0.580.85) and DDLTs were 13% more (IRR = 1.07 1.151.23). Centers in states with the highest incidence 3/15‐4/30 had 59% more waitlist deaths (IRR = 1.09 1.592.32) and 34% fewer DDLTs (IRR = 0.50 0.660.86). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID‐affected states endured major transplant practice changes, later in the pandemic the newly COVID‐affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care. This registry‐based study of liver transplantation in the United States describes the substantial impact of the COVID‐19 pandemic on waitlist events over time and highlights the resiliency of the transplant community. [ABSTRACT FROM AUTHOR]

BIOSIMILARS, DRUG efficacy, PRODUCT safety, PRODUCT reviews, and INFORMATION sharing

The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019–2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a "reliance" concept and/or joint review for the assessment and approval of biosimilars; (3) review and reassessment of the products already approved before the establishment of a regulatory framework for biosimilar approval; and (4) setting appropriate regulatory oversight for good pharmacovigilance, which is essential for the identification of problems with products and establishing the safety and efficacy of interchangeability of biosimilars. [ABSTRACT FROM AUTHOR]

SOFT contact lenses, CONTACT lenses, ALLERGIC conjunctivitis, BLEPHARITIS, EYE diseases, MEIBOMIAN glands, DIAGNOSIS, DISEASE complications, OPTOMETRY, DRY eye syndromes, CORNEA diseases, CONJUNCTIVA, and TEARS (Body fluid)

Contact lens-related complications are common, affecting around one third of wearers, although most are mild and easily managed. Contact lenses have well-defined anatomical and physiological effects on the ocular surface and can result in other consequences due to the presence of a biologically active material. A contact lens interacts with the tear film, ocular surface, skin, endogenous and environmental microorganisms, components of care solutions and other antigens which may result in disease specific to contact lens wear, such as metabolic or hypersensitivity disorders. Contact lens wear may also modify the epidemiology or pathophysiology of recognised conditions, such as papillary conjunctivitis or microbial keratitis. Wearers may also present with intercurrent disease, meaning concomitant or pre-existing conditions unrelated to contact lens wear, such as allergic eye disease or blepharitis, which may complicate the diagnosis and management of contact lens-related disease. Complications can be grouped into corneal infection (microbial keratitis), corneal inflammation (sterile keratitis), metabolic conditions (epithelial: microcysts, vacuoles, bullae, tight lens syndrome, epithelial oedema; stromal: superficial and deep neovascularisation, stromal oedema [striae/folds], endothelial: blebs, polymegethism/ pleomorphism), mechanical (corneal abrasion, corneal erosion, lens binding, warpage/refractive error changes; superior epithelial arcuate lesion, mucin balls, conjunctival epithelial flaps, ptosis, discomfort), toxic and allergic disorders (papillary conjunctivitis, solution-induced corneal staining, incomplete neutralisation of peroxide, Limbal Stem Cell Deficiency), tear resurfacing disorders/dry eye (contact lens-induced dry eye, Meibomian gland dysfunction, lid wiper epitheliopathy, lid parallel conjunctival folds, inferior closure stain, 3 and 9 o'clock stain, dellen, dimple veil) or contact lens discomfort. This report summarises the best available evidence for the classification, epidemiology, pathophysiology, management and prevention of contact lens-related complications in addition to presenting strategies for optimising contact lens wear. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic, PEOPLE with epilepsy, AT-risk people, EPILEPSY, MEDICAL care, and COVID-19

• The COVID-19 and Epilepsy (COV-E) global surveys were launched in May 2020. • UK respondents (n = 463) report changes in seizure frequency, mental health, and sleep. • Discussion of risk, including of SUDEP, was infrequent even before the pandemic. • COVID-19 is having far-reaching consequences on people with epilepsy. • Our study exemplifies the importance of delivering optimal care to mitigate risk. The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management. We aim to understand the impact that COVID-19 has had on the health and well-being of people with epilepsy focusing on exposure to increased risk of seizures, associated comorbidity, and mortality. We designed two online surveys with one addressing people with epilepsy directly and the second for caregivers to report on behalf of a person with epilepsy. The survey is ongoing and has yielded 463 UK-based responses by the end of September 2020. Forty percent of respondents reported health changes during the pandemic (n = 185). Respondents cited a change in seizures (19%, n = 88), mental health difficulties (34%, n = 161), and sleep disruption (26%, n = 121) as the main reasons. Thirteen percent found it difficult to take medication on time. A third had difficulty accessing medical services (n = 154), with 8% having had an appointment canceled (n = 39). Only a small proportion reported having had discussions about epilepsy-related risks, such as safety precautions (16%, n = 74); mental health (29%, n = 134); sleep (30%, n = 140); and Sudden Unexpected Death in Epilepsy (SUDEP; 15%, n = 69) in the previous 12 months. These findings suggest that people with epilepsy are currently experiencing health changes, coupled with inadequate access to services. Also, there seems to be a history of poor risk communication in the months preceding the pandemic. As the UK witnesses a second COVID-19 wave, those involved in healthcare delivery must ensure optimal care is provided for people with chronic conditions, such as epilepsy, to ensure that avoidable morbidity and mortality is prevented during the pandemic, and beyond. [ABSTRACT FROM AUTHOR]

KIDNEY transplantation, URINARY tract infections, NOSOLOGY, and DIAGNOSIS

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post‐KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare‐primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD‐9) codes. The cumulative incidence of a post‐KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five‐year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5‐year death‐censored graft failure (DCGF) was 20.6% vs 10.1% (P <.001). This translated to a 2.22‐fold higher mortality risk (adjusted hazard ratio [aHR]: 2.152.222.29, P <.001) and 1.92‐fold higher DCGF risk (aHR: 1.841.911.98, P <.001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11‐fold higher mortality risk for sepsis vs 1.62‐fold for a UTI). Post‐KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow‐up to mitigate these risks. This national study of kidney transplant recipients shows that infections are common, are associated with approximately twofold increased risk of both mortality and death‐censored graft failure, and thus are still an important driver of posttransplant outcomes. [ABSTRACT FROM AUTHOR]

COVID-19, SOCIAL responsibility, LIBRARY school students, and STAY-at-home orders

Population of the study The online intervention classes focused mainly on Library and Information Science Students from across universities in Africa. Among the 100 level students, few of the excerpts of the responses are presented below: I did not have any experience in Library and Information Science as some of my classmates do. Among the 300 Level Students, participants discussed more about the insight they have on careers they could pursue in the field of Library and Information Science. All the students are studying Library and Information Science in their respective universities. [Extracted from the article]

KIDNEY transplantation, ORGAN donors, PEDIATRICS, KIDNEY failure, TRANSPLANTATION of organs, tissues, etc., STATISTICAL significance, DESCRIPTIVE statistics, and COVID-19 pandemic

Background: In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. Methods: Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. Results: We saw an initial decrease in DDKT and LDKT by 47% and 82% compared with expected events and then a continual increase, with numbers reaching expected prepandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR 0.49 0.65 0.85) and LDKT (IRR 0.17 0.38 0.84) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel–reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. Conclusions: The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect. [ABSTRACT FROM AUTHOR]

Background: Vascular dementia (VaD) is often difficult to distinguish from Alzheimer's disease (AD).[O'Brien_2015] Areas of cognitive/clinical decline due to cerebrovascular diseases depend on the frequency and location of the lesions, and may overlap with those found in AD.[Suri_2014] Moreover, AD and cerebrovascular diseases frequently occur simultaneously, leading to heterogeneous 'mixed dementia (MixD)'.[Wang_2012][Langa_2004] It is unclear whether the presence of both neurodegenerative and cerebrovascular pathologies further aggravates dementia‐related imaging abnormalities. We investigated whether the lobar distribution of white matter hyperintensities (WMHs) on MRI differed among AD, VaD and MixD. Method: N=17 participants (cross‐sectional; subtypes:7 MixD/5 Subcortical VaD/5 AD; Sex: 11M/6F; Age: 75±8yrs) were scanned on a 3T Philips Achieva. T1‐weighted MP‐RAGE images were processed with Freesurfer 6.0. Areas of WMHs were segmented on Fluid Attenuated Inversion Recovery (3D‐FLAIR) images using a combination of intensity thresholding and manual correction. Left and right frontal, temporal, occipital and parietal lobes plus basal ganglia volumes were constructed using the Freesurfer segmentation outputs. Individual WMH masks were transformed to their respective T1‐weighted spaces, and the ratios of WMH volumes to different lobar volumes were calculated. Result: Average WMH volumes were (mean±SD) AD: 5191±4693mm3, MixD: 34680±17059mm3 (sig. greater than AD), SVaD: 20896±14920mm3 (n.s. from MixD or AD). We used a linear model to predict the ratios of WMH to lobar volumes from the diagnosis subtypes, adjusting for age and sex. A significant diagnosis‐subtype effect was found in both the left and right frontal lobes. (p=0.012 and 0.045, respectively). In the left frontal lobe, the proportion of WMHs was significantly greater in the MixD subgroup compared to the AD (p=0.0045) or the VaD (p=0.026) subtypes. In the right frontal lobe, the proportion was greater in the MixD subtype compared to the AD (p=0.018) but not compared to VaD (p=0.074) subtype. AD vs. VaD were not significantly different in either sides (p=0.5). Conclusion: The MixD subtype of our pilot study cohort was characterized by a significantly greater presence of WMHs in the frontal lobar areas. Future studies are warranted to investigate the characteristics of underlying tissue abnormalities that could be specific to the diagnosis subtypes. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) with cerebrovascular disease is known as 'mixed' dementia (MixD).[Wang_2012][Langa_2004] MixD can have heterogeneous clinical/imaging presentations. This makes it difficult to distinguish MixD from AD or vascular dementia (VaD) using structural markers such as atrophy or white matter hyperintensity (WMH) volumes. [Suri_2014] We explored whether WM tissue properties on MRI, represented by R2* and diffusion‐tensor (DTI) images, could distinguish MixD from AD or VaD. Method: N=17 participants (cross‐sectional; 7 MixD/5 Subcortical VaD/5 AD; Sex: 11M/6F; Age: 75±8yrs) were scanned on a 3T Philips Achieva. WMHs were segmented on 3D‐Fluid Attenuated Inversion Recovery images. T1‐weighted MP‐RAGE images were segmented into the grey/white‐matters using SPM12. These outputs were combined to construct WMH and normal‐appearing WM (NAWM) masks. DTI images were processed using FSL. R2* images were computed using in‐house software. For each participant, the average R2*, fractional anisotropy (FA) and mean diffusivity (MDf) values were calculated within the WMH and NAWM masks. Result: Average WMH volumes were (mean±SD) AD: 5191±4693mm3, MD: 34680±17059mm3 (p<.05 compared to AD), SVaD: 20896±14920mm3 (p>.05 compared to MixD or AD). A linear model was used to predict the measured R2*, FA or MDf values from the diagnosis subtypes, adjusting for age and sex. R2* results: Pairwise t‐tests revealed significantly lower R2* values within the WMHs compared to NAWM (all subtypes p<0.0005). MixD had significantly lower WMH R2* values compared to AD (p=0.01) or VaD (p=0.02) subgroups. DTI results: Pairwise t‐tests revealed significantly higher MDf values within the WMHs compared to NAWM (all subtypes p<0.009). FA values were significantly lower within the WMHs compared to NAWM for the MixD (p=0.0002) and VaD (p=0.03) but not the AD (p=0.09) subtype. Conclusion: Our MixD cohort was characterized by potentially disrupted fiber integrity (represented by decreased FA) and increased water content (represented by lower R2*) within the WMH areas. These abnormalities likely represent etiologies caused by both neurodegenerative and cerebrovascular factors. Future studies that incorporate measures of neurodegeneration or neuroinflammation, such as biofluid markers, may help to further characterize WM tissue abnormalities in MixD compared to those found in 'pure' AD or VaD. [ABSTRACT FROM AUTHOR]

Background: Increased burden of white‐matter hyperintensities (WMHs) on MRI is common among different types of dementia. WMHs can be caused by various underlying etiologies and are non‐specific markers of tissue abnormality. Therefore, global measures such as WMH burdens may not distinguish between degrees of cognitive impairment. We explored the associations between lobar‐specific WMH volumes and cognitive dysfunction across different dementia subtypes. Method: N=57 participants (7 Alzheimer's disease [AD]/5 subcortical vascular dementia [SVaD]/7 mixed dementia [MixD]/38 vascular cognitive impairment [VCI]; Sex:34M/23F; Age:73±8yrs; pooled from three independent studies) were scanned on 3T MRI. WMHs were segmented on 3D‐FLAIR (MixD/AD/SVaD) or dual‐echo PD/T2‐weighted (VCI) images. T1‐weighted images were processed with Freesurfer 6.0. Left and right frontal, temporal, occipital and parietal lobes plus basal ganglia volumes were constructed using the Freesurfer segmentation outputs. We calculated the proportion of WMH burden within each lobe, i.e. the ratio of lobar WMH volume over the lobar volume. The Montreal Cognitive Assessment (MoCA) was used as a measure of cognitive function. We used a general linear model to determine the association between the WMH/lobar volume ratios and the MoCA scores. Covariates included age, sex, and presence of AD‐related (yes for MixD/AD, no for rest) and vascular‐related conditions (yes for SVaD/VCI/MixD, no for AD). Additionally, we assessed the relationship between the MoCA scores and the ratio of total WMH burden over the whole‐brain parenchymal volume. Result: The model yielded a significant association between the MoCA scores and WMH/lobar ratios within the left (p=0.031) and the right (p=0.035) frontal lobes, with higher ratios predicting lower MoCA scores. The effect was not significant within the temporal, occipital, parietal lobes and the basal ganglia. The effect was insignificant at the whole‐brain level (p=0.08). Conclusion: We found a significant association between the frontal lobe WMH burden and the MoCA scores, especially sensitive to frontal executive functions. This suggests that region‐specific assessments of WMHs may provide improved imaging‐cognitive correlations over the global WMH burden. Future studies with more consistent imaging protocols and broader cognitive/clinical assessments are warranted to further characterize the relationship between WMHs and cognitive impairment. [ABSTRACT FROM AUTHOR]

COVID-19, TRANSPLANTATION of organs, tissues, etc., SARS-CoV-2, CRITICALLY ill, and KIDNEYS

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID‐19 on transplant recipients and center‐level practices. We therefore conducted a six‐week follow‐up survey May 7‐15, 2020, and linked responses to the COVID‐19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID‐19–positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS‐CoV‐2. Our findings demonstrate persistent heterogeneity in center‐level response to COVID‐19 even as transplant activity resumes, making ongoing national data collection and real‐time analysis critical to inform best practices. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic, KIDNEY transplantation, COVID-19, MACHINE learning, and PANDEMICS

Clinical decision‐making in kidney transplant (KT) during the coronavirus disease 2019 (COVID‐19) pandemic is understandably a conundrum: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. To quantify the benefit/harm of KT in this context, we conducted a simulation study of immediate‐KT vs delay‐until‐after‐pandemic for different patient phenotypes under a variety of potential COVID‐19 scenarios. A calculator was implemented (http://www.transplantmodels.com/covid%5fsim), and machine learning approaches were used to evaluate the important aspects of our modeling. Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority when modeling deceased donor KT) had greatest influence on benefit/harm. In most scenarios of COVID‐19 dynamics and patient characteristics, immediate KT provided survival benefit; KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (eg, ≥50% fatality) than for waitlist registrants. Our simulations suggest that KT could be beneficial in many centers if local resources allow, and our calculator can help identify patients who would benefit most. Furthermore, as the pandemic evolves, our calculator can update these predictions. This simulation study and interactive online tool model the survival benefit or harm of kidney transplantation in the context of COVID‐19, based on epidemic parameters and individual patient characteristics. McElroy et al comment on page 2971. [ABSTRACT FROM AUTHOR]

KIDNEY transplantation, COVID-19, COVID-19 pandemic, and EXPECTED returns

In March 2020, coronavirus disease 2019 (COVID‐19) spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center levels, accounting statistically for waitlist composition. Using Scientific Registry of Transplant Recipients data, we compared data on observed waitlist registrations, waitlist mortality, and living‐donor and deceased‐donor kidney transplants (LDKT/DDKT) March 15‐April 30, 2020 to expected events calculated from preepidemic data January 2016‐February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all P <.001). Only 12 centers performed LDKT March 15‐31; by April 30, 40 centers had resumed LDKT. The decline in new listings and DDKT was greater among states with higher per capita confirmed COVID‐19 cases. The number of waitlist deaths was 2.2‐fold higher than expected in the 5 states with highest COVID‐19 burden (P <.001). DCD DDKT and regional/national imports declined nationwide but most steeply in states with the highest COVID‐19 burden. The COVID‐19 epidemic has resulted in substantial changes to KT; we must adapt and learn rapidly to continue to provide safe access to transplantation and limit the growing indirect toll of an already deadly disease. The authors present national‐ and center‐level data on reduced kidney transplant activity early in the COVID‐19 pandemic and link findings to state‐level COVID‐19 burden. [ABSTRACT FROM AUTHOR]

ACCELEROMETERS, FOOD habits, GLOBAL Positioning System, HEALTH behavior, INGESTION, POPULATION geography, SCHOOL environment, BUILT environment, HOME environment, CROSS-sectional method, SEDENTARY lifestyles, PHYSICAL activity, DESCRIPTIVE statistics, and ADOLESCENCE

Background: Investigation of physical activity and dietary behaviors across locations can inform "setting-specific" health behavior interventions and improve understanding of contextual vulnerabilities to poor health. This study examined how physical activity, sedentary time, and dietary behaviors differed across home, school, and other locations in young adolescents. Methods: Participants were adolescents aged 12–16 years from the Baltimore-Washington, DC and the Seattle areas from a larger cross-sectional study. Participants (n = 472) wore an accelerometer and Global Positioning Systems (GPS) tracker (Mean days = 5.12, SD = 1.62) to collect location-based physical activity and sedentary data. Participants (n = 789) completed 24-h dietary recalls to assess dietary behaviors and eating locations. Spatial analyses were performed to classify daily physical activity, sedentary time patterns, and dietary behaviors by location, categorized as home, school, and "other" locations. Results: Adolescents were least physically active at home (2.5 min/hour of wear time) and school (2.9 min/hour of wear time) compared to "other" locations (5.9 min/hour of wear time). Participants spent a slightly greater proportion of wear time in sedentary time when at school (41 min/hour of wear time) than at home (39 min/hour of wear time), and time in bouts lasting ≥30 min (10 min/hour of wear time) and mean sedentary bout duration (5 min) were highest at school. About 61% of daily energy intake occurred at home, 25% at school, and 14% at "other" locations. Proportionately to energy intake, daily added sugar intake (5 g/100 kcal), fruits and vegetables (0.16 servings/100 kcal), high calorie beverages (0.09 beverages/100 kcal), whole grains (0.04 servings/100 kcal), grams of fiber (0.65 g/100 kcal), and calories of fat (33 kcal/100 kcal) and saturated fat (12 kcal/100 kcal) consumed were nutritionally least favorable at "other" locations. Daily sweet and savory snacks consumed was highest at school (0.14 snacks/100 kcal). Conclusions: Adolescents' health behaviors differed based on the location/environment they were in. Although dietary behaviors were generally more favorable in the home and school locations, physical activity was generally low and sedentary time was higher in these locations. Health behavior interventions that address the multiple locations in which adolescents spend time and use location-specific behavior change strategies should be explored to optimize health behaviors in each location. [ABSTRACT FROM AUTHOR]

ON-site evaluation, STREAMING video & television, VIDEO excerpts, and MEDICAL technology

Introduction: Telecytology using real‐time microscopy has gained popularity for rapid on‐site evaluations (ROSE). Although proficiency testing is routinely used in cytopathology, no established means of competency assessment is currently available for telecytology. Our aim was to determine the feasibility of a dynamic (real‐time) platform to assess telecytology competency. Methods: Remote Medical Technology dynamic (real‐time) video streaming platform for ROSE is used at our institution, and short video clips of telecytology cases were recorded using Camtasia Studio 8 software during different ROSE sessions. Selected MP4 videos (range 13‐88 seconds, mean 33 seconds), along with clinical histories, were used to build a multiple‐choice question test with one training case and 20 test cases, utilising Tutor (Philips) software to host the web‐based test. The test was voluntary for cytopathologists and cytotechnologists. Answers and feedback from test takers were analysed. Results: Thirteen participants—four cytopathologists and nine cytotechnologists—previously trained to use telecytology, volunteered to take the test. Individual scores ranged from 10 (50%) to 19 (95%) with a median of 16 (80%). Most feedback received involved technical difficulties. Conclusions: We present, to the best of our knowledge, the first tool to assess telecytology competency for ROSE using pre‐recorded dynamic streaming videos. Despite technical challenges related to incorporating videos into a web‐based test, the test was feasible and provided users with valuable feedback about their ROSE performance. Future effort will be devoted to establishing a more user‐friendly test platform and establishing a benchmark for passing scores. This paper illustrates that an assessment tool for telecytology competency for ROSE using pre‐recorded dynamic streaming videos is feasible. In addition, the novel test provided users with valuable feedback about their ROSE performance and provides feedback on the challenges related to telecytology ROSE. [ABSTRACT FROM AUTHOR]

SCHOOL children, CHILDREN with dyslexia, EMERGENT literacy, PHONOLOGICAL awareness, NOISE, and ARTIFICIAL satellite tracking

Humans' propensity to acquire literacy relates to several factors, including the ability to understand speech in noise (SiN). Still, the nature of the relation between reading and SiN perception abilities remains poorly understood. Here, we dissect the interplay between (1) reading abilities, (2) classical behavioral predictors of reading (phonological awareness, phonological memory, and rapid automatized naming), and (3) electrophysiological markers of SiN perception in 99 elementary school children (26 with dyslexia). We demonstrate that, in typical readers, cortical representation of the phrasal content of SiN relates to the degree of development of the lexical (but not sublexical) reading strategy. In contrast, classical behavioral predictors of reading abilities and the ability to benefit from visual speech to represent the syllabic content of SiN account for global reading performance (i.e., speed and accuracy of lexical and sublexical reading). In individuals with dyslexia, we found preserved integration of visual speech information to optimize processing of syntactic information but not to sustain acoustic/phonemic processing. Finally, within children with dyslexia, measures of cortical representation of the phrasal content of SiN were negatively related to reading speed and positively related to the compromise between reading precision and reading speed, potentially owing to compensatory attentional mechanisms. These results clarify the nature of the relation between SiN perception and reading abilities in typical child readers and children with dyslexia and identify novel electrophysiological markers of emergent literacy. Humans' propensity to acquire literacy relates to several factors, one of which is the ability to understand speech in noise. This neuroimaging study reveals that reading abilities and neuronal traces of speech processing in noise are related in multiple specific ways. [ABSTRACT FROM AUTHOR]

PREMATURE labor, BIRTH weight, LOW birth weight, BIRTH intervals, COHORT analysis, CHORIOAMNIONITIS, and CHILDBIRTH at home

Background: Approximately 20.5 million infants were born weighing <2500 g (defined as low birthweight or LBW) in 2015, primarily in low- and middle-income countries (LMICs). Infants born LBW, including those born preterm (<37 weeks gestation), are at increased risk for numerous consequences, including neonatal mortality and morbidity as well as suboptimal health and nutritional status later in life. The objective of this study was to identify predictors of LBW and preterm birth among infants in rural Uganda. Methods: Data were derived from a prospective birth cohort study conducted from 2014–2016 in 12 districts across northern and southwestern Uganda. Birth weights were measured in triplicate to the nearest 0.1 kg by trained enumerators within 72 hours of delivery. Gestational age was calculated from the first day of last menstrual period (LMP). Associations between household, maternal, and infant characteristics and birth outcomes (LBW and preterm birth) were assessed using bivariate and multivariable logistic regression with stepwise, backward selection analyses. Results: Among infants in the study, 4.3% were born LBW (143/3,337), and 19.4% were born preterm (744/3,841). In multivariable analysis, mothers who were taller (>150 cm) (adjusted Odds Ratio (aOR) = 0.42 (95% CI = 0.24, 0.72)), multigravida (aOR = 0.62 (95% CI = 0.39, 0.97)), or with adequate birth spacing (>24 months) (aOR = 0.60 (95% CI = 0.39, 0.92)) had lower odds of delivering a LBW infant Mothers with severe household food insecurity (aOR = 1.84 (95% CI = 1.22, 2.79)) or who tested positive for malaria during pregnancy (aOR = 2.06 (95% CI = 1.10, 3.85)) had higher odds of delivering a LBW infant. In addition, in multivariable analysis, mothers who resided in the Southwest (aOR = 0.64 (95% CI = 0.54, 0.76)), were ≥20 years old (aOR = 0.76 (95% CI = 0.61, 0.94)), with adequate birth spacing (aOR = 0.76 (95% CI = 0.63, 0.93)), or attended ≥4 antenatal care (ANC) visits (aOR = 0.56 (95% CI = 0.47, 0.67)) had lower odds of delivering a preterm infant; mothers who were neither married nor cohabitating (aOR = 1.42 (95% CI = 1.00, 2.00)) or delivered at home (aOR = 1.25 (95% CI = 1.04, 1.51)) had higher odds. Conclusions: In rural Uganda, severe household food insecurity, adolescent pregnancy, inadequate birth spacing, malaria infection, suboptimal ANC attendance, and home delivery represent modifiable risk factors associated with higher rates of LBW and/or preterm birth. Future studies on interventions to address these risk factors may be warranted. [ABSTRACT FROM AUTHOR]

COVID-19, COVID-19 pandemic, KIDNEY transplantation, TRANSPLANTATION of organs, tissues, etc., and INVESTIGATIONAL therapies

COVID‐19 is a novel, rapidly changing pandemic: consequently, evidence‐based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center‐level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID‐19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID‐19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID‐19. Shortage of COVID‐19 tests was reported by 42.5%. Respondents reported a total of 148 COVID‐19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center‐level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence‐based practices. In this national survey of transplant centers during the COVID‐19 pandemic, the authors report substantial reduction in transplant activity, wide variation in COVID‐19 testing practices, and use of off‐label or investigational therapies in the treatment of 148 COVID‐19‐SOT recipients. [ABSTRACT FROM AUTHOR]

CLOSTRIDIOIDES difficile, GLUTAMATE dehydrogenase, TREATMENT duration, and ENZYME-linked immunosorbent assay

A proportion of patients suspected of Clostridium difficile infection are unnecessarily placed in contact isolation. By introducing a random-access glutamate dehydrogenase (GDH) test for C. difficile, we aimed to reduce isolation time. In addition, we investigated whether the result of the toxin A&B enzyme immunoassay (EIA) was associated with the decision to initiate antibiotic treatment against C. difficile. This retrospective pre- and post-implementation study was from June 3, 2016, to June 4, 2018. Pre-implementation, only a NAAT was performed. In the post-implementation period, a GDH test was performed; if positive, a toxin A&B EIA followed the same day and subsequently a NAAT. Contact isolation for CDI was discontinued when the GDH test was negative. Median time in isolation was 50.8 h pre-implementation (n = 189) versus 28.0 h post-implementation (n = 119), p < 0.001. The GDH test had a negative predictive value of 98.8% (95% CI 97.9–99.4). In 7/31 (22.6%) patients with a positive NAAT and GDH test and a negative toxin A&B EIA, no antibiotics against C. difficile were initiated versus 4/28 (14.3%) patients who were NAAT, GDH and toxin A&B EIA positive. Introducing a random-access screening test resulted in a significant decrease in patient isolation time. The GDH test had a high negative predictive value making it suitable to determine whether contact isolation can be discontinued. Furthermore, the result of a toxin A&B EIA had limited added value on the percentage of patients in whom antibiotic treatment against C. difficile was initiated. [ABSTRACT FROM AUTHOR]

HIV infection epidemiology, RESEARCH, RESEARCH evaluation, SOCIAL media, RESEARCH methodology, DISEASE incidence, EVALUATION research, MEDICAL cooperation, COMPARATIVE studies, and RESEARCH funding

Background: Adolescents and young adults in the age range of 13-24 years are at the highest risk of developing HIV infections. As social media platforms are extremely popular among youths, researchers can utilize these platforms to curb the HIV epidemic by investigating the associations between the discourses on HIV infections and the epidemiological data of HIV infections.Objective: The goal of this study was to examine how Twitter activity among young men is related to the incidence of HIV infection in the population.Methods: We used integrated human-computer techniques to characterize the HIV-related tweets by male adolescents and young male adults (age range: 13-24 years). We identified tweets related to HIV risk and prevention by using natural language processing (NLP). Our NLP algorithm identified 89.1% (2243/2517) relevant tweets, which were manually coded by expert coders. We coded 1577 HIV-prevention tweets and 17.5% (940/5372) of general sex-related tweets (including emojis, gifs, and images), and we achieved reliability with intraclass correlation at 0.80 or higher on key constructs. Bivariate and multivariate analyses were performed to identify the spatial patterns in posting HIV-related tweets as well as the relationships between the tweets and local HIV infection rates.Results: We analyzed 2517 tweets that were identified as relevant to HIV risk and prevention tags; these tweets were geolocated in 109 counties throughout the United States. After adjusting for region, HIV prevalence, and social disadvantage index, our findings indicated that every 100-tweet increase in HIV-specific tweets per capita from noninstitutional accounts was associated with a multiplicative effect of 0.97 (95% CI [0.94-1.00]; P=.04) on the incidence of HIV infections in the following year in a given county.Conclusions: Twitter may serve as a proxy of public behavior related to HIV infections, and the association between the number of HIV-related tweets and HIV infection rates further supports the use of social media for HIV disease prevention. [ABSTRACT FROM AUTHOR]

LUNGS, LONGITUDINAL method, HISTORY, and LUNG transplantation

Summary: The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post‐transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X‐rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2/FiO2 ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long‐term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized. [ABSTRACT FROM AUTHOR]

Nearly 6.5 million Americans are living with heart failure (HF), the leading cause of hospitalization among adults aged 65 and older. Despite advancements in medical therapy, HF patient outcomes remain of concern. HF readmission rates remain high and only half of patients diagnosed with heart failure are expected to live beyond 5 years of diagnosis. Increasing prevalence and poor outcomes provide significant opportunities for improvement. Hospital participation in a quality initiative designed to improve care by promoting adherence to the scientific guidelines, such as Get With the Guidelines®-Heart Failure (GWTG-HF), assists hospitals in effectively delivering high quality care to improve patient outcomes. The objective of this project is to form multidisciplinary collaboratives that will rapidly implement evidence-based guidelines to develop best practices that can be shared to improve heart failure patient outcomes. The AHA will lead a quality improvement initiative for transforming heart failure care in three major cities including Chicago, Milwaukee and St. Louis. • A retrospective review was conducted using GWTG-HF on measures with low adherence from participating hospitals in the metro markets. • Baseline data of specific HF measures from Quarter 1, 2018 were analyzed and to determine areas of improvement needed. • Using regional and 1:1 hospital meetings, AHA will lead a quality improvement initiative to transform HF patient care. • The HF project will focus on professional education, enhancing systems of care and facilitating the sharing of best practices. • The patient population will include patients from GWTG-HF with a principal/primary diagnosis of heart failure. The project goal within the 2-year timeframe of this initiative is to achieve 20% improvement from baseline data OR achieve AHA's 85% adherence threshold in each measure. AHA Quality staff will observe and monitor market-level data within GWTG-HF to uncover and recommend improvements, provide consultation to clinicians, deliver targeted training and resources such as webinars, conferences, toolkits, care pathways, educational materials and to foster best-practice sharing to address common barriers. Participating hospitals vary in size, discharge volume, GWTG participation tenure, FTE support and resources • *There is incomplete baseline date for the three thirty day follow up measures • Initiative implementation may vary slightly in 3 metro markets The two-year multi-city quality initiative will bring together multiple hospitals to share best practices, develop resources and analyze Get With The Guidelines data for performance improvement to accelerate heart failure patient outcomes. Further investigation is merited evaluating the effectiveness of quality collaboratives to enhance care. [ABSTRACT FROM AUTHOR]

TOXOPLASMA, POLYMERS, TUBULINS, MICROTUBULES, and XENOPUS

Background: TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25α and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella. Results: We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a "C"-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or "C"-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite. Conclusions: These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion. [ABSTRACT FROM AUTHOR]

PHASED array antennas, OPTICAL images, COHERENCE (Optics), BEAM steering, SILICON solar cells, and PHOTONICS

Recent advances in silicon photonics have enabled large-scale optical phased arrays for applications such as beam steering and directional light detection. However, to date, these results have only been applied to coherent light. Many applications, including passive imaging with natural illumination, require operation using incoherent and/or broadband light. Here, we implement an optical phased array designed for these applications using a planar, fractal, path length-matching architecture known as an "H-tree." We demonstrate electronic beamsteering and natural light imaging using this flat, broadband, photonic-integrated device. [ABSTRACT FROM AUTHOR]

ERYTHROCYTES, BLOOD platelets, BLOOD groups, ANTIGENS, and POLYMERASE chain reaction

Background: Genotyping has expanded the number red blood cell (RBC) and platelet (PLT) antigens that can readily be typed, but often represents an additional testing cost. The analysis of existing genomic data offers a cost-effective approach. We recently developed automated software (bloodTyper) for determination of RBC and PLT antigens from whole genome sequencing. Here we extend the algorithm to whole exome sequencing (WES).Study Design and Methods: Whole exome sequencing was performed on samples from 75 individuals. WES-based bloodTyper RBC and PLT typing was compared to conventional polymerase chain reaction (PCR) RHD zygosity testing and serologic and single-nucleotide polymorphism (SNP) typing for 38 RBC antigens in 12 systems (17 serologic and 35 SNPs) and 22 PLT antigens (22 SNPs). Samples from the first 20 individuals were used to modify bloodTyper to interpret WES followed by blinded typing of 55 samples.Results: Over the first 20 samples, discordances were noted for C, M, and N antigens, which were due to WES-specific biases. After modification, bloodTyper was 100% accurate on blinded evaluation of the last 55 samples and outperformed both serologic (99.67% accurate) and SNP typing (99.97% accurate) reflected by two Fyb and one N serologic typing errors and one undetected SNP encoding a Jknull phenotype. RHD zygosity testing by bloodTyper was 100% concordant with a combination of hybrid Rhesus box PCR and PCR-restriction fragment length polymorphism for all samples.Conclusion: The automated bloodTyper software was modified for WES biases to allow for accurate RBC and PLT antigen typing. Such analysis could become a routing part of future WES efforts. [ABSTRACT FROM AUTHOR]

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-β, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38–1) and 85% specificity (95%CI 0.75–0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58–1) sensitivity and 61% (95%CI 0.39–0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts. [ABSTRACT FROM AUTHOR]

IMMUNOGLOBULIN M, URINE, TUBERCULOSIS, ANTIBODY formation, IMMUNOGLOBULINS, and BODY fluids

Background: Simple methods for the accurate triaging and screening of HIV-associated tuberculosis (TB) are urgently needed. We hypothesized that combining serum antibody with urine lipoarabinomannan (U-LAM) detection can improve the detection of HIV-associated TB. Methods: We performed a case-control study with sampling from a prospective study of South African HIV-infected subjects who were screened for TB prior to initiating antiretroviral therapy. Sera from all available TB cases (n = 74) and randomly selected non-TB controls (n = 30), all tested for U-LAM, sputum microscopy, GeneXpert, and cultures, were evaluated for antibodies to LAM and arabinomannan (AM). Diagnostic logistic regression models for TB were developed based on the primary test results and the additive effect of antibodies with leave-one-out cross-validation. Results: Antibody responses to LAM and AM correlated strongly (p<0.0001), and IgG and IgM reactivities were significantly higher in TB than non-TB patients (p<0.0001). At 80% specificity, the target specificity for a non-sputum-based simple triage/screening test determined by major TB stakeholders, combining U-LAM with IgG detection significantly increased the sensitivity for HIV-associated TB to 92% compared to 30% for U-LAM alone (p<0.001). Sputum microscopy combined with IgG detection increased sensitivity to 88% compared to 31% for microscopy alone, and Xpert with IgG increased sensitivity to 96% and 99% compared to 57% for testing one, and 70% for testing two sputa with Xpert alone, respectively. Conclusion: Combining U-LAM with serum antibody detection could provide a simple low-cost method that meets the requirements for a non-sputum-based test for the screening of HIV-associated TB. [ABSTRACT FROM AUTHOR]

CHILDREN and AGE

Introduction and Aims: Parental role modelling of alcohol use is known to influence alcohol consumption in adolescence and in later life. This study aimed to assess relationships between parental status, child age and alcohol consumption, which have not been well documented.Design and Methods: Data were sourced from the 2013 Australian National Drug Strategy Household Survey. Analyses were conducted for 25-55 year olds (n = 11 591) by parental status, gender and age of youngest child in the household, controlling for socio-demographic factors.Results: Parents were less likely than non-parents to exceed the alcohol guideline for increased lifetime risk (18.2% vs. 24.2%) and short-term risk: at least weekly (14.2% vs. 21.2%); and at least monthly (27.5% vs. 35.9%). Fathers were just as likely to exceed the guidelines for lifetime risk as other men, but those with children aged 0-2, were less likely to exceed the guideline for short-term risk. Women were least likely to exceed the guideline for lifetime risk if they had children aged 0-2, 6-11 or 15 years and over, or the guideline for short-term risk, if they had children aged 0-2, or 15 years and over in the household. Parents were more likely to report drinking in the home.Discussion and Conclusions: Parents were less likely to exceed alcohol guidelines than non-parents, especially mothers whose youngest child was an infant or in high school or older. Consistent with population rates in men, fathers were more likely to exceed alcohol guidelines than mothers, and this excess consumption warrants public health attention. [ABSTRACT FROM AUTHOR]

CLINICAL competence, COMMUNICATION, NURSING, QUALITY assurance, TEACHING methods, HUMAN services programs, EVALUATION of human services programs, DESCRIPTIVE statistics, and OUTPATIENT medical care nursing

Supplemental digital content is available in the text. BACKGROUND/PURPOSE: Ongoing dissatisfaction with anonymous peer feedback led to problem solving to equip nurses to provide and receive respectful and meaningful feedback during face-to-face peer review. PROBLEM: Giving and receiving feedback about other's performance and collaboration are a vital aspect of teambuilding; yet, no programmatic training existed to prepare and equip nurses to feel confident and comfortable in providing or receiving face-to-face peer feedback. A search of the literature demonstrated a dearth of evidence related to developing these teambuilding relationships. The facilitator role appeared in some literature outside nursing but was poorly articulated and yet appeared important to the process. METHODS: This was a quality improvement project that utilized online surveys with both multiple-choice and open-ended questions for data collection across 3 time points for 2 different cohorts over a 2-year implementation period. Strategies included education related to providing feedback with positive intent regardless of feedback type. A facilitator role was used to ensure effective communication and provide support to the peers during the process. RESULTS: Nurse participants described increased comfort and knowledge related to providing/receiving face-to-face feedback. Training and use of a facilitator provided the necessary support; 75% of participants reported comfort with giving face-to-face feedback. However, the greater majority, 80% to 92%, of participants reported increased comfort with receiving face-to-face feedback. CONCLUSIONS: Using active peer-to-peer support has become an accepted standard for face-to-face peer feedback as an aspect of the annual review process. [ABSTRACT FROM AUTHOR]

CANCER relapse, NON-small-cell lung carcinoma, NEOPLASTIC cell transformation, CELL proliferation, and ADENOCARCINOMA

Recurrent broad-scale heterozygous deletions are frequently observed in human cancer. Here we tested the hypothesis that compound haploinsufficiency of neighboring genes at chromosome 8p promotes tumorigenesis. By targeting the mouse orthologs of human DOK2 and DUSP4 genes, which were co-deleted in approximately half of human lung adenocarcinomas, we found that compound-heterozygous deletion of Dok2 and Dusp4 in mice resulted in lung tumorigenesis with short latency and high incidence, and that their co-deletion synergistically activated MAPK signaling and promoted cell proliferation. Conversely, restoration of DOK2 and DUSP4 in lung cancer cells suppressed MAPK activation and cell proliferation. Importantly, in contrast to downregulation of DOK2 or DUSP4 alone, concomitant downregulation of DOK2 and DUSP4 was associated with poor survival in human lung adenocarcinoma. Therefore, our findings lend in vivo experimental support to the notion that compound haploinsufficiency, due to broad-scale chromosome deletions, constitutes a driving force in tumorigenesis. [ABSTRACT FROM AUTHOR]

SEISMOLOGY, MASS-wasting (Geology), ACOUSTIC signal processing, VOLCANIC ash, tuff, etc., DEBRIS avalanches, and ROCKFALL

Abstract Surficial mass movements, such as debris avalanches, rock falls, lahars, pyroclastic flows, and outburst floods, are a dominant hazard at many volcanoes worldwide. Understanding these processes, cataloging their spatio-temporal occurrence, and detecting, tracking, and characterizing these events would advance the science of volcano monitoring and help mitigate hazards. Seismic and acoustic methods show promise for achieving these objectives: many surficial mass movements generate observable seismic and acoustic signals, and many volcanoes are already monitored. Significant progress has been made toward understanding, modeling, and extracting quantitative information from seismic and infrasonic signals generated by surficial mass movements. However, much work remains. In this paper, we review the state of the art of the topic, covering a range of scales and event types from individual rock falls to sector collapses. We consider a full variety of volcanic settings, from submarine to subaerial, shield volcano to stratovolcano. Finally, we discuss future directions toward operational seismo-acoustic monitoring of surficial mass movements at volcanoes. Highlights • Surficial mass movements are common in volcanic areas and generate signals that are recorded by seismic and acoustic arrays. • Our understanding of the relation of these signals to characteristics of the mass movement is limited but improving. • We review the literature on the study of mass movements at volcanoes using seismic and acoustic monitoring. • We discuss future research directions and steps toward operational monitoring. [ABSTRACT FROM AUTHOR]

BODY image in women, WOMEN college students, FOOD habits, AEROBIC exercises, BODY size, SELF-esteem in women, EXERCISE & psychology, INGESTION, BODY image, BREAKFASTS, COMPARATIVE studies, RESEARCH methodology, MEDICAL cooperation, RESEARCH, SATISFACTION, SELF-perception, EVALUATION research, RANDOMIZED controlled trials, and PSYCHOLOGY

Food intake and exercise have been shown to alter body satisfaction in a state-dependent manner. One-time consumption of food perceived as unhealthy can be detrimental to body satisfaction, whereas an acute bout of moderate-intensity aerobic exercise can be beneficial. The current study examined the effect of exercise on state body image and appearance-related self-esteem following consumption of isocaloric foods perceived as healthy or unhealthy in 36 female college students (18-30 years old) in the Northeastern United States. Using a randomized-controlled design, participants attended six study sessions with breakfast conditions (healthy, unhealthy, no food) and activity (exercise, quiet rest) as within-participants factors. Body image questionnaires were completed prior to breakfast condition, between breakfast and activity conditions, and following activity condition. Results showed that consumption of an unhealthy breakfast decreased appearance self-esteem and increased body size perception, whereas consumption of a healthy breakfast did not influence appearance self-esteem but increased body size perception. Exercise did not influence state body image attitudes or perceptions following meal consumption. Study findings suggest that morning meal type, but not aerobic exercise, influence body satisfaction in college-aged females. [ABSTRACT FROM AUTHOR]

LUNG disease diagnosis, LUNG transplantation, ALLOCATION of organs, tissues, etc., PULMONARY hypertension, ORGAN transplant waiting lists, and PATIENTS

Summary: Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine‐tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty‐three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET. [ABSTRACT FROM AUTHOR]

BONE marrow and MULTIPLE myeloma

Bone marrow niches support multiple myeloma, providing signals and cell-cell interactions essential for disease progression. A 3D bone marrow niche model was developed, in which supportive multipotent mesenchymal stromal cells and their osteogenic derivatives were co-cultured with endothelial progenitor cells. These co-cultured cells formed networks within the 3D culture, facilitating the survival and proliferation of primary CD138+ myeloma cells for up to 28 days. During this culture, no genetic drift was observed within the genomic profile of the primary myeloma cells, indicating a stable outgrowth of the cultured CD138+ population. The 3D bone marrow niche model enabled testing of a novel class of engineered immune cells, so called TEGs (αβT cells engineered to express a defined γδTCR) on primary myeloma cells. TEGs were engineered and tested from both healthy donors and myeloma patients. The added TEGs were capable of migrating through the 3D culture, exerting a killing response towards the primary myeloma cells in 6 out of 8 donor samples after both 24 and 48 hours. Such a killing response was not observed when adding mock transduced T cells. No differences were observed comparing allogeneic and autologous therapy. The supporting stromal microenvironment was unaffected in all conditions after 48 hours. When adding TEG therapy, the 3D model surpassed 2D models in many aspects by enabling analyses of specific homing, and both on- and off-target effects, preparing the ground for the clinical testing of TEGs. The model allows studying novel immunotherapies, therapy resistance mechanisms and possible side-effects for this incurable disease. [ABSTRACT FROM AUTHOR]

MYELIN basic protein genetics, RNA helicase, OLIGODENDROGLIA, GENETIC transcription regulation, MESSENGER RNA, and PROGENITOR cells

In the central nervous system, oligodendroglial expression of myelin basic protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly at the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (also known as p68) in a complex with Mbp mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with Mbp mRNA in the cell body and processes. Manipulation of the amount of DDX5 protein inversely affects the level of MBP. We present evidence that DDX5 is involved in post-transcriptional regulation of MBP protein synthesis, with implications for oligodendroglial development. In addition, knockdown of DDX5 results in an increased abundance of MBP isoforms containing exon 2 in immature oligodendrocytes, most likely by regulating alternative splicing of Mbp. Our findings contribute to the understanding of the complex nature of MBP posttranscriptional control in immature oligodendrocytes where DDX5 appears to affect the abundance of MBP proteins via distinct but converging mechanisms. [ABSTRACT FROM AUTHOR]

INFANT mortality, ANTHROPOMETRY, HUMAN body composition, PLETHYSMOGRAPHY, LOGISTIC regression analysis, and MALNUTRITION in infants

Background: With the greatest burden of infant undernutrition and morbidity in low and middle income countries (LMICs), there is a need for suitable approaches to monitor infants in a simple, low-cost and effective manner. Anthropometry continues to play a major role in characterising growth and nutritional status. Methods: We developed a range of models to aid in identifying neonates at risk of malnutrition. We first adopted a logistic regression approach to screen for a composite neonatal morbidity, low and high body fat (BF%) infants. We then developed linear regression models for the estimation of neonatal fat mass as an assessment of body composition and nutritional status. Results: We fitted logistic regression models combining up to four anthropometric variables to predict composite morbidity and low and high BF% neonates. The greatest area under receiver-operator characteristic curves (AUC with 95% confidence intervals (CI)) for identifying composite morbidity was 0.740 (0.63, 0.85), resulting from the combination of birthweight, length, chest and mid-thigh circumferences. The AUCs (95% CI) for identifying low and high BF% were 0.827 (0.78, 0.88) and 0.834 (0.79, 0.88), respectively. For identifying composite morbidity, BF% as measured via air displacement plethysmography showed strong predictive ability (AUC 0.786 (0.70, 0.88)), while birthweight percentiles had a lower AUC (0.695 (0.57, 0.82)). Birthweight percentiles could also identify low and high BF% neonates with AUCs of 0.792 (0.74, 0.85) and 0.834 (0.79, 0.88). We applied a sex-specific approach to anthropometric estimation of neonatal fat mass, demonstrating the influence of the testing sample size on the final model performance. Conclusions: These models display potential for further development and evaluation in LMICs to detect infants in need of further nutritional management, especially where traditional methods of risk management such as birthweight for gestational age percentiles may be variable or non-existent, or unable to detect appropriately grown, low fat newborns. [ABSTRACT FROM AUTHOR]

ROTAVIRUS vaccines, ZINC supplements, PROBIOTICS, IMMUNE response, and INFANT diseases

Background Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. Methods Infants 5 weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5 mg), probiotic (10 10 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14 weeks of age based on detection of VP6-specific IgA at ≥20 U/ml in previously seronegative infants or a fourfold rise in concentration. Results The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): −1.4%, 16.2%), p = 0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: −4.4%, 13.2%), p = 0.272). 16 serious adverse events were recorded, none related to study interventions. Conclusions Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. Trial registration The trial was registered in India (CTRI/2012/05/002677). [ABSTRACT FROM AUTHOR]

POPULATION health, DATA extraction, and SUSTAINABILITY

Background and Purpose: Over the last decade, the field of implementation science (IS) has yielded an array of theoretical approaches to clarify and understand how factors influence the application and scaling-up of evidence-based practice in health care. These developments have led to questions about whether IS theories and frameworks might be of value to population health researchers and decision makers. The purpose of this research was to conduct a critical interpretive synthesis to explore, if, and how, key IS theories and frameworks might inform population health interventions aimed at reducing the burden of illness across populations. Methods: An initial list of theories and frameworks was developed based on previous published research and narrowed to focus on theories considered as formative for the field of IS. A standardized data extraction form was used to gather key features of the theories and critically appraise their relevance to population health interventions. Results: Ten theories were included in the review and six deemed most applicable to population health based on their consideration of broader contextual and system-level factors. The remaining four were determined to have less relevant components for population health due to their limited consideration of macro-level factors, often focusing on micro (individual) and meso (organizational) level factors. Conclusions: Theories and frameworks are important to guide the implementation and sustainability of population health interventions. The articulation of meso level factors common in IS theories may be of value to interventions targeted at the population level. However, some of the reviewed theories were limited in their consideration of broader contextual factors at the macro level (community, policy or societal). This critical interpretive synthesis also found that some theories lacked provision of practical guidance to address interventions targeting structural factors such as key social determinants of health (e.g., housing, income). [ABSTRACT FROM AUTHOR]

LUNG transplantation, PERFUSION, LUNG diseases, ORGAN donors, and TRANSPLANTATION of organs, tissues, etc.

Ex vivo lung perfusion ( EVLP) is currently used for both standard and extended-criteria donor ( ECD) lungs. To enlarge the donor pool, we might have to extend the threshold for ECD donation. The purpose of this study was to estimate how many additional ECD lungs could be recruited by EVLP. We reviewed all multi-organ donors ( MODs) from our collaborative donor hospitals (January 2010-June 2015). All unused lung donors were categorized using registered donor data and evaluated by two independent investigators to identify which lungs could be transplanted after EVLP. 584 MODs were registered at our transplant center. 268 (45.9%) were declined as lung donor at the moment of registration, and 316 (54.1%) were considered as a donor for lung transplantation. In the latter, lungs from 220 (37.7%) donors were transplanted and 96 donors (16.4%) were not. We identified 78 of 364 declined donors (21.4%) whose lungs could potentially become transplantable after EVLP. With this retrospective database analysis of unused lung donors, we identified a large potential for EVLP to further increase the donor pool in transplant centers where the majority of donor lungs are already extended. [ABSTRACT FROM AUTHOR]

HYPOTHYROIDISM, WEIGHT gain, CONSTIPATION, LEVOTHYROXINE, THYROID hormones, HYPOTHYROIDISM diagnosis, HORMONES, RESEARCH funding, THERAPEUTICS, DISEASE management, and THYROXINE

Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The definition of hypothyroidism is based on statistical reference ranges of the relevant biochemical parameters and is increasingly a matter of debate. Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms. The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors. The standard treatment is thyroid hormone replacement therapy with levothyroxine. However, a substantial proportion of patients who reach biochemical treatment targets have persistent complaints. In this Seminar, we discuss the epidemiology, causes, and symptoms of hypothyroidism; summarise evidence on diagnosis, long-term risk, treatment, and management; and highlight future directions for research. [ABSTRACT FROM AUTHOR]

VEGETATION dynamics, GRASSLANDS, PLANT species diversity, ACID soils, and BIOLOGICAL extinction

Assessing effectiveness of international biodiversity targets requires long-term monitoring of species to identify changes in their abundance. Grasslands cover large areas of many countries, provide high levels of provisioning ecosystem services and are an important habitat for many species. While grasslands are often anthropogenic in nature, human-induced environmental perturbations are acknowledged threats to their biodiversity and functioning. Using a repeat survey of grassland plots in Scotland, UK we identified long-term changes in community composition and species indices over a 40 year period (1973–2013). Scottish grasslands were found to have changed significantly over this time. Species richness increased, while diversity declined as dominant species increased in cover. Nitrogen-demanding and moisture-requiring species increased, possibly reflecting increases in atmospheric nitrogen deposition and rainfall over this time. In Acid and Nardus grasslands species with low tolerance to very acidic soils increased, possibly reflecting a decrease in sulphur deposition. Overall β-diversity showed no change, indicating that contrary to trends in other habitats, homogenisation has not occurred. In general bryophytes and low-growing forb and grass species declined while taller species increased. This may reflect either the decline in grazing in recent years or the increase in atmospheric nitrogen deposition. Species richness increased but the majority of species declined in cover while a few dominant species increased suggesting that an extinction debt may be establishing. The trade-offs between increased management to reduce the extinction debt and abandonment with increased shrub cover which might be beneficial to other wildlife is discussed. [ABSTRACT FROM AUTHOR]

INTRANASAL medication, OXYTOCIN, AUTISM, AUTISM spectrum disorders, and NEUROPEPTIDES

Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment. [ABSTRACT FROM AUTHOR]

FORECASTING, EARTH system science, RELIABILITY in engineering, PHYSICAL constants, and DYNAMICAL time (Astronomy)

Members in ensemble forecasts differ due to the representations of initial uncertainties and model uncertainties. The inclusion of stochastic schemes to represent model uncertainties has improved the probabilistic skill of the ECMWF ensemble by increasing reliability and reducing the error of the ensemble mean. Recent progress, challenges and future directions regarding stochastic representations of model uncertainties at ECMWF are described in this article. The coming years are likely to see a further increase in the use of ensemble methods in forecasts and assimilation. This will put increasing demands on the methods used to perturb the forecast model. An area that is receiving greater attention than 5-10 years ago is the physical consistency of the perturbations. Other areas where future efforts will be directed are the expansion of uncertainty representations to the dynamical core and other components of the Earth system, as well as the overall computational efficiency of representing model uncertainty. [ABSTRACT FROM AUTHOR]

CARBAPENEMASE, ENTEROBACTER cloacae, KLEBSIELLA, ENTEROBACTERIACEAE, CARBAPENEMS, and BETA lactamases

The article discusses a research study on an IMI-2 carbapenemase in a Klebsiella variicola strain isolated in Great Britain. The strain was isolated from an intensive therapy unit patient in 2011 from a soft tissue infection of the buttock. It is stated that this is the first report of an IMI carbapenemase outside of the Enterobacter cloacae complex in Britain.

ALCOHOL drinking, SCHOOL children, CROSS-sectional method, STUDENT health, DRINKING behavior, FORECASTING, FRIENDSHIP, HEALTH education, SCHOOLS, STUDENTS, and DISEASE prevalence

Background: Alcohol consumption by young people (particularly early initiation) is a predictor for poorer health in later life. In addition, evidence now clearly shows a causal link between alcohol and cancer. This study investigated prevalence, predictors of alcohol consumption among adolescents including perceptions of the link between alcohol and cancer, and the role of parents and peers.Methods: A sample of Australian school students aged 12-17 years participated in a survey (n = 2885). Logistic regression analysis was undertaken to determine predictors.Results: Alcohol use increased with age and by 16, most had tried alcohol with 33.1% of students aged 12-17 reporting that they drank at least occasionally (95% CI = 31.0-35.2). Awareness of the link between alcohol and cancer was low (28.5%). Smoking status and friends' approval were predictive of drinking, whereas parental disapproval was protective. Those aged 14-17 who did not think the link between alcohol and cancer was important were more likely to drink, as were those living in areas of least disadvantage. The only factors that predicted recent drinking were smoking and the perception that alcohol was easy to purchase.Conclusions: An education campaign highlighting the link between alcohol and cancer may have positive flow-on effects for young people, and schools should incorporate this messaging into any alcohol education programs. Consideration should be given to factors that serve to regulate under-aged accessibility of alcohol. [ABSTRACT FROM AUTHOR]

COMMITMENT (Psychology), MENTAL depression, PSYCHOSES, QUALITY of life, SCHIZOPHRENIA, ANTIDEPRESSANTS, ANTIPSYCHOTIC agents, COMPARATIVE studies, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PSYCHOLOGICAL tests, PSYCHOLOGY, RESEARCH, RESEARCH funding, STATISTICAL sampling, PILOT projects, EVALUATION research, ACCEPTANCE & commitment therapy, RANDOMIZED controlled trials, TREATMENT effectiveness, BLIND experiment, and RESEARCH evaluation

Background: Depression is one of the major contributors to poorer quality of life amongst individuals with psychosis and schizophrenia. The study was designed as a Pilot Trial to determine the parameters of a larger, definitive pragmatic multi-centre randomised controlled trial of Acceptance and Commitment Therapy for depression after psychosis (ACTdp) for individuals with a diagnosis of schizophrenia who also meet diagnostic criteria for major depression.Methods: Participants were required to meet criteria for schizophrenia and major depression. Blinded follow-ups were undertaken at 5-months (end of treatment) and at 10-months (5-months posttreatment). Primary outcomes were depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS) and the Beck Depression Inventory (BDI).Results: A total of 29 participants were randomised to ACTdp + Standard Care (SC) (n=15) or SC alone (n=14). We did not observe significant differences between groups on the CDSS total score at 5-months (Coeff=-1.43, 95%CI -5.17, 2.32, p=0.45) or at 10-months (Coeff=1.8, 95%CI -2.10, 5.69, p=0.36). In terms of BDI, we noted a statistically significant effect in favour of ACTdp+SC at 5-months (Coeff=-8.38, 95%CI -15.49, -1.27, p=0.02) but not at 10-months (Coeff=-4.85, 95%CI -12.10, 2.39, p=0.18). We also observed significant effects on psychological flexibility at 5-months (Coeff=-8.83, 95%CI -14.94, -2.71, p<0.01) but not 10-months (Coeff=-4.92, 95%CI -11.09, 1.25, p=0.11).Implications: In this first RCT of a psychological therapy with depression as the primary outcome, ACT is a promising intervention for depression in the context of psychosis. A further large-scale definitive randomised controlled trial is required to determine effectiveness.Trial Registration: ISRCTN: 33306437. [ABSTRACT FROM AUTHOR]

ACUTE myeloid leukemia, IMMUNOLOGICAL tolerance, SUPPRESSOR cells, CYTOGENETICS, CELL cycle proteins, MICRORNA genetics, LABORATORY mice, and PATIENTS

Myeloid-derived suppressor cells (MDSCs) play a critical role in promoting immune tolerance and disease growth. The mechanism by which tumor cells evoke the expansion of MDSCs in acute myeloid leukemia (AML) has not been well described. We have demonstrated that patients with AML exhibit increased presence of MDSCs in their peripheral blood, in comparison with normal controls. Cytogenetic studies demonstrated that MDSCs in patients with AML may be derived from leukemic or apparently normal progenitors. Engraftment of C57BL/6 mice with TIB-49 AML led to an expansion of CD11b+ Gr1+ MDSCs in bone marrow and spleen. Coculture of the AML cell lines MOLM-4, THP-1 or primary AML cells with donor peripheral blood mononuclear cells elicited a cell contact-dependent expansion of MDSCs. MDSCs were suppressive of autologous T-cell responses as evidenced by reduced T-cell proliferation and a switch from a Th1 to a Th2 phenotype. We hypothesized that the expansion of MDSCs in AML is accomplished by tumor-derived extracellular vesicles (EVs). Using tracking studies, we demonstrated that AML EVs are taken-up myeloid progenitor cells, resulting in the selective proliferation of MDSCs in comparison with functionally competent antigen-presenting cells. The MUC1 oncoprotein was subsequently identified as the critical driver of EV-mediated MDSC expansion. MUC1 induces increased expression of c-myc in EVs that induces proliferation in the target MDSC population via downstream effects on cell cycle proteins. Moreover, we demonstrate that the microRNA miR34a acts as the regulatory mechanism by which MUC1 drives c-myc expression in AML cells and EVs. [ABSTRACT FROM AUTHOR]

OCCUPATIONAL therapy, PRIMARY care, MEDICAL rehabilitation, PHYSICAL therapy, and MEDICAL care

Background: Primary healthcare (PHC) is central to increased access and transformation in South African healthcare. There is limited literature about services required by occupational therapists in PHC. Despite policy being in place, the implementation of services at grassroots level does not always occur adequately. Objectives: This study aimed at gaining an understanding of the challenges of being disabled and the services required by occupational therapists (OTs) in rural communities in order to better inform the occupational therapy (OT) training curriculum. Method: An exploratory, descriptive qualitative design was implemented using purposive sampling to recruit 23 community healthcare workers from the uGu district. Snowball sampling was used to recruit 37 members of the uGu community, which included people with disability (PWD) and caregivers of PWDs. Audio-recorded focus groups and semi-structured interviews were used to collect data, which were thematically analysed. Ethical approval was obtained from the Biomedical and Research Ethics Committee of the University of KwaZulu-Natal (BE248/14). Results: Two main themes emerged namely: firstly, the challenges faced by the disabled community and secondly appropriate opportunities for intervention in PHC. A snapshot of the social and physical inaccessibility challenges experienced by the community was created. Challenges included physical and sexual abuse, discrimination and marginalisation. Community-based rehabilitation and ideas for health promotion and prevention were identified as possible strategies for OT intervention. Conclusion: The understanding of the intervention required by OT in PHC was enhanced through obtaining the views of various stakeholders' on the role. This study highlighted the gaps in community-based services that OTs should offer in this context. [ABSTRACT FROM AUTHOR]

POST-traumatic stress disorder, SEPTEMBER 11 Terrorist Attacks, 2001, PSYCHOLOGICAL typologies, MENTAL depression, VIGILANCE (Psychology), and DISEASE prevalence

Posttraumatic stress disorder (PTSD) is a debilitating and often chronic psychiatric disorder. Following the 9/11/2001 World Trade Center (WTC) attacks, thousands of individuals were involved in rescue, recovery and clean-up efforts. While a growing body of literature has documented the prevalence and correlates of PTSD in WTC responders, no study has evaluated predominant typologies of PTSD in this population. Participants were 4352 WTC responders with probable WTC-related DSM-IV PTSD. Latent class analyses were conducted to identify predominant typologies of PTSD symptoms and associated correlates. A 3-class solution provided the optimal representation of latent PTSD symptom typologies. The first class, labeled “High-Symptom (n = 1,973, 45.3%),” was characterized by high probabilities of all PTSD symptoms. The second class, “Dysphoric (n = 1,371, 31.5%),” exhibited relatively high probabilities of emotional numbing and dysphoric arousal (e.g., sleep disturbance). The third class, “Threat (n = 1,008, 23.2%),” was characterized by high probabilities of re-experiencing, avoidance and anxious arousal (e.g., hypervigilance). Compared to the Threat class, the Dysphoric class reported a greater number of life stressors after 9/11/2001 (OR = 1.06). The High-Symptom class was more likely than the Threat class to have a positive psychiatric history before 9/11/2001 (OR = 1.7) and reported a greater number of life stressors after 9/11/2001 (OR = 1.1). The High-Symptom class was more likely than the Dysphoric class, which was more likely than the Threat class, to screen positive for depression (83% > 74% > 53%, respectively), and to report greater functional impairment (High-Symptom > Dysphoric [Cohen d = 0.19], Dysphoric > Threat [Cohen d = 0.24]). These results may help inform assessment, risk stratification, and treatment approaches for PTSD in WTC and disaster responders. [ABSTRACT FROM AUTHOR]

POST-traumatic stress disorder, PSYCHOLOGICAL adaptation, PSYCHOSOCIAL factors, PSYCHOLOGY of disaster victims, RISK assessment, and SEPTEMBER 11 Terrorist Attacks, 2001

Trajectories of disaster-related posttraumatic stress disorder (PTSD) symptoms are often heterogeneous, and associated with common and unique risk factors, yet little is known about potentially modifiable psychosocial characteristics associated with low-symptom and recovering trajectories in disaster responders. A total of 4487 rescue and recovery workers (1874 police and 2613 non-traditional responders) involved during and in the aftermath of the unprecedented World Trade Center (WTC) attacks, were assessed an average of 3, 6, 8, and 12 years post-9/11/2001. Among police responders, WTC-related PTSD symptoms were characterized by four trajectories, including no/low-symptom (76.1%), worsening (12.1%), improving (7.5%), and chronic (4.4%) trajectories. In non-traditional responders, a five-trajectory solution was optimal, with fewer responders in a no/low-symptom trajectory (55.5%), and the remainder in subtly worsening (19.3%), chronic (10.8%), improving (8.5%), and steeply worsening (5.9%) trajectories. Consistent factors associated with symptomatic PTSD trajectories across responder groups included Hispanic ethnicity, pre-9/11 psychiatric history, greater WTC exposure, greater medical illness burden, life stressors and post-9/11 traumas, and maladaptive coping (e.g., substance use, avoidance coping). Higher perceived preparedness, greater sense of purpose in life, and positive emotion-focused coping (e.g., positive reframing, acceptance) were negatively associated with symptomatic trajectories. Findings in this unique cohort indicate considerable heterogeneity in WTC-related PTSD symptom trajectories over 12 years post-9/11/2001, with lower rates of elevated PTSD symptoms in police than in non-traditional responders. They further provide a comprehensive risk prediction model of PTSD symptom trajectories, which can inform prevention, monitoring, and treatment efforts in WTC and other disaster responders. [ABSTRACT FROM AUTHOR]