articles+ search results

Pollination, Agricultural productivity, Crop yields, Sustainable agriculture, Pollinators, Apple orchards, Factorial experiment designs, and Orchards

The alarming loss of pollinator diversity world‐wide can reduce the productivity of pollinator‐dependent crops, which could have economic impacts. However, it is unclear to what extent the loss of a key native pollinator species affects crop production and farmer's profits.By experimentally manipulating the presence of colonies of a native bumblebee species Bombus pauloensis in eight apple orchards in South Argentina, we evaluated the impact of losing natural populations of a key native pollinator group on (a) crop yield, (b) pollination quality, and (c) farmer's profit. To do so, we performed a factorial experiment of pollinator exclusion (yes/no) and hand pollination (yes/no).Our results showed that biotic pollination increased ripe fruit set by 13% when compared to non‐biotic pollination. Additionally, fruit set and the number of fruits per apple tree was reduced by less than a half in those orchards where bumblebees were absent, even when honeybees were present at high densities. Consequently, farmer's profit was 2.4‐fold lower in farms lacking bumblebees than in farms hosting both pollinator species. The pollination experiment further suggested that the benefits of bumblebees could be mediated by improved pollen quality rather than quantity.Synthesis and applications. This study highlights the pervasive consequences of losing key pollinator functional groups, such as bumblebees, for apple production and local economies. Adopting pollinator‐friendly practices such as minimizing the use of synthetic inputs or restoring/maintaining semi‐natural habitats at farm and landscape scales, will have the double advantage of promoting biodiversity conservation, and increasing crop productivity and profitability for local farmers. Yet because the implementation of these practices can take time to deliver results, the management of native pollinator species can be a provisional complementary strategy to increase economic profitability of apple growers in the short term. [ABSTRACT FROM AUTHOR]

The contamination of water sources by pharmaceutically active compounds (PhACs) and their effect on aquatic communities and human health have become an environmental concern worldwide. Membrane bioreactors (MBRs) are an alternative to improve biological removal of recalcitrant organic compounds from municipal sewage. Their efficiency can be increased by using high retention membranes such as forward osmosis (FO) and membrane distillation (MD). Thus, this research aimed to evaluate the performance of an anaerobic osmotic MBR coupled with MD (OMBR-MD) in the treatment of municipal sewage containing PhACs and estrogenic activity. A submerged hybrid FO-MD module was integrated into the bioreactor. PhACs removal was higher than 96% due to biological degradation, biosorption and membrane retention. Biological removal of the PhACs was affected by the salinity build-up in the bioreactor, with reduction in biodegradation after 32 d. However, salinity increment had little or no effect on biosorption removal. The anaerobic OMBR-MD removed >99.9% of estrogenic activity, resulting in a distillate with 0.14 ng L−1 E2-eq, after 22 d, and 0.04 ng L−1 E2-eq, after 32 d. OMBR-MD treatment promoted reduction in environmental and human health risks from high to low, except for ketoprofen, which led to medium acute environmental and human health risks. Carcinogenic risks were reduced from unacceptable to negligible, regarding estrogenic activity. Thus, the hybrid anaerobic OMBR-MD demonstrated strong performance in reducing risks, even when human health is considered. [Display omitted] • Biological removal of estrogenic compounds was governed mainly by biodegradation. • Biological removal of micropollutants (MP) was affected by the salinity build-up. • MgCl 2 as draw solute reduced the negative impacts on biological removal of MP. • Ketoprofen in distillate led to medium acute environmental and human health risks. • Carcinogenic risk, regarding estrogenicity, reduced from unacceptable to negligible. [ABSTRACT FROM AUTHOR]

BIPOLAR disorder, MENTAL depression, DEPRESSED persons, ANTIPSYCHOTIC agents, and MENTAL health

Abstract: Introduction: Although depressive moods are recognised as a very broad condition, there is still only one definition in international classifications for describing a major depressive episode (MDE). However, there is currently some controversy surround the treatment of depressive states. This includes SSRIs and suicide in adolescents, and more specifically in bipolar disorders where some depressions are made worse by antidepressants. New data has suggested that depressive states in BP patients can be improved by atypical antipsychotics. Aim: We aimed to assess 1) whether it is possible to distinguish different forms of bipolar depression using a dimensional approach, and 2) if, yes, whether there are different patterns of treatment response. Method: We characterised 60 bipolar patients with a Major Depressive Episode (DSM-IV) using a new tool (MATHYS: Multidimensional Assessment of Thymic States) assessing five fundamental dimensions (emotional reactivity, cognitive speed, psycho-motricity, motivation and senses perception) of mood states (full description elsewhere). Results: A cluster analysis using the items of the dimensional scale revealed two types of depressive states. One group (G1; N =38), which had a low score, is characterised by an inhibition in all dimensions, whereas the other group (G2; N =22) is characterised by an over-activation. Emotional reactivity is a useful dimension for discriminating these two types of depression (G1: hyporeactivity; G2: hyperreactivity) whereas sadness is not. A lower score on the MAThyS scale at day 1 was associated with a good response to antidepressant treatment, whereas higher scores were linked to a good response to a mood stabilizers alone or in combination with an antipsychotic. Conclusion: Bipolar depressive states are not homogeneous and this heterogeneity can explain various patterns of treatment response. A dimensional approach could be useful for discriminating the different forms of bipolar depression and to help manage treatment. [Copyright &y& Elsevier]

ETHICS, PSYCHIATRISTS, MENTAL health personnel, PSYCHIATRY, and PSYCHOTHERAPISTS

Abstract: In legal proceedings the expert witness testimony may be considered a medical act only if the expert conducts his clinical observations within the limits established by the medical code of ethics. This will then allow the psychiatrist to help the judge reach a more informed legal decision. The difficulty inherent in this process is for the expert to give an exact answer (“yes” or “no”) to the questions formulated in order for the judge to arrive at an accurate decision. To better understand the evidence presented, the judge may ask empirical questions that require the expert witness to give testimony going beyond the information directly gathered through clinical observations. It is the expert witness'' responsibility to determine what amount of interpretation of material drawn from a clinical observation is appropriate to help the judge make a legal decision. This requires defining legal standards such as credibility, truth, and suggestibility. One must also recognize that the clinical observation of a victim is often the person''s first contact with a psychiatrist. [Copyright &y& Elsevier]

DRUG discovery, DATA mining, and CHEMINFORMATICS

INTONATION (Phonetics), PROSODIC analysis (Linguistics), CATALAN language, INTERROGATIVE (Grammar), ROMANCE languages, SENTENCES (Grammar), MODALITY (Linguistics), and CORPORA

In this work, the intonation of broad focus statements and information-seeking yes-no questions of Catalan obtained using an induced corpus (ICD) is analyzed. The study is carried out within the framework of the AMPERCAT project (Contini et al., 2002; Fernández Planas, 2005). Data obtained with DCT are compared with those obtained through textual elicitation in AMPER and other prosodic studies of Catalan (Prieto et al., 2015). The majority nuclear contours for the broad focus statements is L*L%, while for the interrogatives there are different contours: two falling contours (H+L*L% and ¡H+L*L%) and two raising patterns (L*H% and H+L*LH%). [ABSTRACT FROM AUTHOR]

Health risk assessment, Endocrine disruptors, Water purification, Water supply, and Drinking water quality

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been detected in drinking water from various countries. Although various water treatment processes can remove EDCs, chemicals can also migrate from pipes that transport water and contaminate drinking water. This study investigated the estrogenic activity in drinking water from various distribution points in Pretoria (City of Tshwane) (n = 40) and Cape Town (n = 40), South Africa, using the recombinant yeast estrogen screen (YES) and the T47D-KBluc reporter gene assay. The samples were collected seasonally over four sampling periods. The samples were also analysed for bisphenol A (BPA), nonylphenol (NP), di(2-ethylhexyl) adipate (DEHA), dibutyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), diisononylphthalate (DINP), 17β-estradiol (E 2 ), estrone (E 1 ) and ethynylestradiol (EE 2 ) using ultra-performance liquid chromatography-tandem mass spectrophotometry (UPLC-MS/MS). This was followed by a scenario based health risk assessment to assess the carcinogenic and toxic human health risks associated with the consumption of distribution point water. None of the water extracts from the distribution points were above the detection limit in the YES bioassay, but the EEq values ranged from 0.002 to 0.114 ng/L using the T47D-KBluc bioassay. BPA, DEHA, DBP, DEHP, DINP E 1 , E 2, and EE 2 were detected in distribution point water samples. NP was below the detection limit for all the samples. The estrogenic activity and levels of target chemicals were comparable to the levels found in other countries. Overall the health risk assessment revealed acceptable health and carcinogenic risks associated with the consumption of distribution point water. [ABSTRACT FROM AUTHOR]

RHINOPLASTY, CLEFT lip, PATIENT satisfaction, RESPIRATION, and QUESTIONNAIRES

Secondary rhinoplasty on patients with cleft is a challenging procedure, and the most important criterion for evaluating the surgery success is patient satisfaction even if it's subjective. To evaluate patient satisfaction following secondary cleft rhinoplasty with a specific assessment for patients with Unilateral Cleft Lip and Palate (UCLP). Our retrospective cross-sectional study is composed of 29 patients with UCLP with a mean age of 23 years old, who underwent secondary rhinoplasty between 2010 and 2021 in our department. The survey was conducted postoperatively using a cleft-nose specific custom designed questionnaire based on the Byrne questionnaire, over the phone. This satisfaction questionnaire comprises six questions about physical appearance and one question about functional aspect. Patients were asked to answer "yes" or "no" or to rate from 0 (no improvement) to 10 (perfect result) depending on the question. Twenty out of 29 people responded to the questionnaire, representing an answer rate of 69%. The average score given by the patient for nasolabial scar improvement was 7.2/10, and the one concerning global improvement was 8.2/10. All patients would be ready to undergo the same procedure again, knowing the final result. A functional improvement concerning breathing or snoring was reported in 45% of cases. All dorsum or tip issues were improved after surgery (P = 0,07). Our results demonstrate high patient satisfaction after cleft rhinoplasty, which encourages the continuation of this surgery. We would recommend the use of this simple questionnaire to allow a more accurate evaluation of patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The newborn undergoing a surgery is exposed to the development of infections. The serum lactate has been recommended as a diagnostic criterion of sepsis. Objective: To determine the magnitude of association of the value of serum lactate with sepsis in the newborn undergoing a surgery. Methods: Study conducted from 2013 to 2016 in "William Soler" Pediatric Teaching Hospital, to 307 newborns whom underwent surgery. The variables were grouped in: clinical (gestational age, birth weight, cause of surgical intervention, location of the infection) and paraclinical (causative microorganisms, serum lactate). The partial Pearson's test of linear correlation was applied and it was estimated the odds ratio with the control of the variable infection (yes and no) to identify correlation between serum lactate values in the preoperative and postoperative results. Results: Of the newborns, 63 were under weight (20.52%) and 55 were preterm infants (17.92%). In the infected newborns, 20.83% were operated due to digestive conditions (n= 35); systemic infections reached 67.74% (n= 42), caused in 45.24% by Candida sp. The rate of change of the values of serum lactate in infected subjects (p= 0.001) meant that for each unit in mmol/L in which increased the preoperative lactate, the postoperative increased 0.489 mmol/L; and these changes were due in a 16.9% to the values of preoperative lactate. Conclusions: The serum lactate is associated to the infection in newborns that underwent surgery and is a useful biomarker of sepsis in neonatal intensive care. [ABSTRACT FROM AUTHOR]

ULCER treatment, COMBINATORIAL optimization, SURGICAL emergencies, ORAL diseases, HOSPITAL care, and PHYSICIAN practice patterns

Résumé: La prise en charge chirurgicale de l’escarre en France demeure très coûteuse même si les mesures de prévention et l’amélioration du parcours de soins ont permis de limiter les dépenses dans ce domaine ces dernières années. Depuis 2004, le mode de financement des établissements de santé français par la tarification à l’acte (TAA) et la maîtrise médicalisée des dépenses de soins hospitaliers nous obligent forcément à nous intéresser à ces considérations purement économiques et parfois à nuancer nos besoins en durée d’hospitalisation ou en soins spécialisés pour optimiser le groupe homogène de séjour (GHS) d’un patient. Cela ne risque-t-il pas à l’avenir d’obliger le chirurgien à biaiser les réels besoins du patient au profit de l’établissement hospitalier ? Au travers d’une analyse médico-économique de nos pratiques, réalisée dans le service de chirurgie plastique du CHU de Toulouse, nous avons tenté d’identifier comment optimiser la prise en charge chirurgicale de l’escarre en termes de valorisation de séjour. L’objectif étant néanmoins de rester critique sur les dérives que cela pourrait instaurer à l’avenir pour notre activité clinique. [ABSTRACT FROM AUTHOR]

SECOND language acquisition, DOMINANT language, CHINESE language, LANGUAGE & languages, NATIVE language, and NATURAL languages

And even though I do not think that most domain-general models of L SB 1 sb /L SB 2 sb acquisition are going to come under further scrutiny, Mazuka's distinction is likely to be valuable for domain-specific models of acquisition (of phonology). Yes, L SB 2 sb learners do not parse de-RCs in the same way as native speakers do, but that only indicates that they have not achieved ultimate attainment; not that there are fundamental differences in L SB 1 sb and L SB 2 sb processing. Martohardjono, Valian and Klein (MVK) take up the deficit and transfer accounts (d/t) of L SB 2 sb acquisition in their chapter, while looking at acquisition of tense. [Extracted from the article]

TALAROMYCES, CACAO, FUNGAL growth, NATURAL resources, SOIL pollution, and SOILS

Inorganic pollutants in Colombian cocoa (Theobroma cacao L.) agrosystems cause problems in the production, quality, and exportation of this raw material worldwide. There has been an increased interest in bioprospecting studies of different fungal species focused on the biosorption of heavy metals. Furthermore, fungi constitute a valuable, profitable, ecological, and efficient natural soil resource that could be considered in the integrated management of cadmium mitigation. This study reports a new species of Talaromyces isolated from a cocoa soil sample collected in San Vicente de Chucurí, Colombia. T. santanderensis is featured by Lemon Yellow (R. Pl. IV) mycelium on CYA, mono-to-biverticillade conidiophores, and acerose phialides. T. santanderensis is distinguished from related species by its growth rate on CYAS and powdery textures on MEA, YES and OA, high acid production on CREA and smaller conidia. It is differentiated from T. lentulus by its growth rate on CYA medium at 37 °C without exudate production, its cream (R. PI. XVI) margin on MEA, and dense sporulation on YES and CYA. Phylogenetic analysis was performed using a polyphasic approach, including different phylogenetic analyses of combined and individual ITS, CaM, BenA, and RPB2 gene sequences that indicate that it is new to science and is named Talaromyces santanderensis sp. nov. This new species belongs to the Talaromyces section and is closely related to T. lentulus, T. soli, T. tumuli, and T. pratensis (inside the T. pinophilus species complex) in the inferred phylogeny. Mycelia growth of the fungal strains was subjected to a range of 0–400 mg/kg Cd and incorporated into malt extract agar (MEA) in triplicates. Fungal radial growth was recorded every three days over a 13-day incubation period and In vitro cadmium tolerance tests showed a high tolerance index (0.81) when the mycelium was exposed to 300 mg/kg of Cd. Results suggest that T. santanderensis showed tolerance to Cd concentrations that exceed the permissible limits for contaminated soils, and it is promising for its use in bioremediation strategies to eliminate Cd from highly contaminated agricultural soils. [ABSTRACT FROM AUTHOR]

CATALAN language, OPTIMALITY theory (Linguistics), LANGUAGE & languages, ACCOMMODATIONISM, and AUTOSEGMENTAL theory (Linguistics)

This paper aims at contributing to ascertain the principles of intonational grammar that lie behind the realization of nuclear contours and at presenting them in terms of Optimality Theory constraints. In order to do so, we analyse the prosody of the nuclear configuration of Southern Valencian Catalan yes-no questions, with special emphasis on situations where text-tune accommodation phenomena take place. The empirical data, which are analysed according to the principles of the autosegmental-metrical model, show a complex interplay of different phenomena at the text-tune interface, like vowel lengthening, tonal spreading, tonal retraction and intonation-driven schwa epenthesis. We argue that the variation detected in the data can be accounted for by the interaction of nine constraints (i.e., Max-IO(µp), Dep-IO(µs), Anchor(T%,Rt,IP,Rt), Anchor(L*,Rt,ˈσ,Rt), *Anchor(T,C), *Anchor(T,-voice), Share(T*,NC), Dep-IO(Associate), Max-IO(Associate)), whose ranking is established by means of a Stochastic Optimality Theory analysis. [ABSTRACT FROM AUTHOR]

LIVER cells, HOMEOSTASIS, NON-alcoholic fatty liver disease, YAP signaling proteins, GENETIC overexpression, NUCLEOTIDE synthesis, and METABOLIC regulation

A primary role of the liver is to regulate whole body glucose homeostasis. Glucokinase (GCK) is the main hexokinase (HK) expressed in hepatocytes and functions to phosphorylate the glucose that enters via GLUT transporters to become glucose-6-phosphate (G6P), which subsequently commits glucose to enter downstream anabolic and catabolic pathways. In the recent years, hexokinase domain-containing-1 (HKDC1), a novel 5th HK, has been characterized by our group and others. Its expression profile varies but has been identified to have low basal expression in normal liver but increases during states of stress including pregnancy, nonalcoholic fatty liver disease (NAFLD), and liver cancer. Here, we have developed a stable overexpression model of hepatic HKDC1 in mice to examine its effect on metabolic regulation. We found that HKDC1 overexpression, over time, causes impaired glucose homeostasis in male mice and shifts glucose metabolism towards anabolic pathways with an increase in nucleotide synthesis. Furthermore, we observed these mice to have larger liver sizes due to greater hepatocyte proliferative potential and cell size, which in part, is mediated via yes-associated protein (YAP) signaling. [ABSTRACT FROM AUTHOR]

ACADEMIC medical centers, CANCER genetics, CHI-squared test, CONFIDENCE intervals, EMPLOYMENT, GENETIC counseling, HEALTH services accessibility, HEALTH status indicators, HEALTH insurance, MARITAL status, MEDICAL care use, MEDICAL referrals, METROPOLITAN areas, MULTIVARIATE analysis, RACISM, LOGISTIC regression analysis, ELECTRONIC health records, DESCRIPTIVE statistics, ODDS ratio, and DISEASE risk factors

Purpose: Genetic counseling (GC) provides critical risk prediction information to women at-risk of carrying a genetic alternation; yet racial/ethnic and socioeconomic disparities persist with regard to GC uptake. This study examined patterns of GC uptake after a referral in a racially diverse population. Materials and Methods: In an urban academic medical center, medical records were reviewed between January 2016 and December 2017 for women who were referred to a genetic counselor for hereditary breast and ovarian cancer. Study outcomes were making an appointment (yes/no) and keeping an appointment. We assessed sociodemographic factors and clinical factors. Associations between factors and the outcomes were analyzed using chi square, and logistic regression was used for multivariable analysis. Results: A total of 510 women were referred to GC and most made appointments. More than half were white (55.3%) and employed (53.1%). No significant associations were observed between sociodemographic factors and making an appointment. A total of 425 women made an appointment and 268 kept their appointment. Insurance status ( p = 0.003), marital status ( p = 0.000), and work status ( p = 0.039) were associated with receiving GC. In the logistic model, being married (odds ratio [OR] 2.119 [95% confidence interval, CI 1.341–3.347] p = 0.001) and having insurance (OR 2.203 [95% CI 1.208–4.016] p = 0.021) increased the likelihood of receiving counseling. Conclusions: Racial disparities in GC uptake were not observed in this sample. Unmarried women may need additional support to obtain GC. Financial assistance or other options need to be discussed during navigation as a way to lessen the disparity between women with insurance and those without. [ABSTRACT FROM AUTHOR]

ATTITUDE (Psychology), CULTURE, EXPERIENTIAL learning, FAMILY psychotherapy, HOSPITAL medical staff, INTERPROFESSIONAL relations, INTERVIEWING, MEDICAL personnel, PROFESSIONS, SELF-efficacy, SUPERVISION of employees, PEER relations, and THEMATIC analysis

This article explores family therapy trainees' subjective experiences of working as cotherapists with a supervisory‐level therapist in a Chinese context, regarding their perceptions of and positioning in it and also their opinions on the benefits and/or pitfalls of cotherapy. Individual interviews with a total of six cotherapists revealed three themes: (1) Cotherapy was perceived as an experiential learning journey that evolved from anxiety and excitement to empowerment and nurturing; (2) a collaborative master–apprentice relationship of openness, trust, and mutual respect was developed with both sides' interactive effort, which included common commitment and concern for the client, the supervisor's awareness and explicit address of the role hierarchy, principle setting prior to the cooperation, and honest pre‐ and‐postsession sharing and discussion; (3) the dual‐purpose supervisor–trainee cotherapy brought direct benefits for all involved parties and for others. The findings have useful implications for integrating treatment and training for optimal training/learning outcomes and for advancing knowledge transfer from senior to junior and from academia to the field, with reference to local cultural characteristics.comment="AUTHOR: Please suggest whether the terms ‘co‐therapy, co‐learning, and cotherapist’ could be changed to ‘cotherapy, colearning, and cotherapist’ throughout the article as per style sheet requirement."comment="Dear Editor,Yes, I think these terms could be changed as suggested according to the style sheet requirement, as the meaning remains the same. Thank you.Best regards,Lily" [ABSTRACT FROM AUTHOR]

CROP genetics, SOYBEAN, SWEETPOTATO whitefly, DISEASE resistance of plants, BIOLOGICAL control of plant parasites, ANTIBIOSIS, OVIPARITY, GREENHOUSE plants, and TRICHOMES

Since it was first reported in Brazil in the 1990s, the B biotype of silverleaf whitefly (Bemisia tabaci [Genn.], Hemiptera Aleyrodidae) has been recognized as an important pest in soybeans (Glycine max L.), reducing the productivity of this legume species in some areas of the country. As an alternative to chemical control, the use of resistant genotypes represents an important tool for integrated pest management (IPM). This study evaluated the performance of 10 soybean genotypes prior to whitefly infestation, by testing attractiveness and preference for oviposition in the greenhouse and antibiosis in the laboratory. In a multiple-choice test, 'IAC-17' was the least attractive to insects. In a no-choice test, 'IAC-17' was the least attractive for egg deposition, indicating the occurrence of non-preference for oviposition on this genotype. Trichome density was positively correlated with the oviposition site and may be associated with the resistance of 'IAC-17' to infestation. The genotypes 'IAC-PLI', 'IAC-19', 'Conquista', 'IAC-24' and 'IAC-17' extended the insect's life cycle, indicating occurrence of a small degree of antibiosis and/or non-preference for feeding. [ABSTRACT FROM AUTHOR]

DIABETIC retinopathy, VISUAL acuity, VISION, CAPILLARIES, and RETINAL diseases

Background/Aim. The relationship between the foveal avascular zone (FAV) and visual acuity (VA) in retinal diseases remains a matter of discussion. The aim of this study was to determine the impact of diabetic macular ischemia (DMI) on VA through the analysis of the perifoveal capillary network in various stages of diabetic retinopathy - DR (non-proliferative diabetic retinopathy – NPDR and proliferative diabetic retinopathy – PDR). Methods. Qualitative and quantitative analysis of 143 angiograms of patients with different stages of DR was performed. The degree of macular ischemia was assessed by the analysis of 2 parameters: perifoveal capillary ring, ie, the FAZ outline irregularity, and capillary loss. Finally, a comparison was made between the degree of macular ischemia with the best-corrected VA, depending on macular thickness. Results. In the eyes with mild and moderate NPDR, without significant macular thickening, no statistically significant decrease in VA caused by macular ischemia was noticed (p = 0.81). Opposite, in a subgroup with severe NPDR and PDR, without significant macular thickening, a statistically significant difference was presented among eyes with moderate and severe macular ischemia compared to e yes with l ower g rades of m acular i schemia (p = 0.021 and p = 0.018, respectively). In the eyes with moderate NPDR and mild macular ischemia, the increase in macular thickness resulted in a statistically insignificant decrease in VA compared to eyes with a normal macular thickness (p = 0.088). However, in the eyes with severe NPDR, every pathological increase in macular thickness caused a statistically significant decrease in VA, regardless of the degree of macular ischemia (p = 0.018–0.040). A similar relationship was also found in the eyes with PDR (p = 0.017–0.042). In the eyes with a statistically significant decrease in VA, most of the examined eyes (98%) had the FAZ outline irregularity in the nasal perifoveal subfield. Conclusion. In the absence of significant macular thickening, the destruction of one-half of the perifoveal capillary network, or greater, is associated with reduced VA. The location of macular ischemic changes in the nasal parts of the perifoveal capillary ring plays a crucial role in its effects on visual function. [ABSTRACT FROM AUTHOR]

The waltz of Afrikaans "a" with "l" The present study is a follow-up of previous ones on the rounding of the long low /a/ vowel in Afrikaans, a relatively new sound variation. Against the background of existing descriptions I report a similar tendency of rounding of short /a/ vowel, specifically when followed by the lateral consonant /l/. I suggest an explanation of such rounding as being the result of a process of coarticulation, specifically under the influence of a distinct dark, retroflex quality of this lateral. A post hoc investigation with an ultrasound scanner and lip video camera confirmed this to be the case. The vowel productions of a single speaker, known to be a clear rounding of long /a/ was explored in an extensively designed case study. The phenomenon of /a/-rounding implies a qualitative change of the /a/ to [ɒ] as in [jɒ] (ja; "yes") and in [snɒks (snaaks; "funny"). Apart from superficial references to its existence in linguistic handbooks, such as De Villiers and Ponelis (1987:100), the first systematic study was done by Wissing (2006), followed-up by more recent other studies (Wissing 2010; 2013). Rounding is currently seemingly limited to the speech of young adult female speakers of Afrikaans, but it appears as if it has lately been spreading to the broader Afrikaans speaking community at a rather noticeable pace. It is provoking extremely negative reactions in especially the case of older, or more conservative Afrikaans speaking persons. On the other hand, younger users of Afrikaans do not even seem to notice the existence of this phenomenon, especially in their own language use. Such a vowel change is apparently part of a larger vowel shift which has recently been taking place, viz. the lowering of the front-mid vowel /ε/ to almost the position of the short low /a/, or the shifting of /u/ from a back to a more centralised position (cf. Wissing 2010). Broadly defined, language change is a topic that integrates the social as well as the cognitive aspects of what it means to be human. A central feature of a language in the process of change is variation. During a period of change, there is variation in the language between forms that represent the current/previous stage and forms that represent the innovative/new stage of the language. Consequently, the rounding of /a/ could be of linguistic significance when considered against this general linguistic backdrop. The present investigation aims in particular at both broadening, developing and understanding of /a/-rounding to [ɒ] in modern Afrikaans. In order to achieve this, firstly the existing knowledge concerning this phenomenon was summarised, whereafter a variety of carefully constructed stimuli were used in an in-depth case study of the pronunciation of a young female radio presenter at Radio Sonder Grense, the leading Afrikaans public broadcaster (hence referred to as C). The testing material was created with a view to obtaining a fuller understanding of /a/- rounding to [ɒ] in Afrikaans in two respects. Firstly, the stimulus series concerning the degree to which long /a/ vowels are subjected to such rounding was expanded considerably. Secondly, stimuli were included with the aim of examining the possible co-articulatory influence of the rounding of /a/ followed by the lateral consonant /l/ (characterised as a dark l in the case of English pronunciation) on especially the short /ɑ/-vowel, as in wals ("waltz"). Dark /l/ has received much attention in literature. Moreover, word frequency also has been shown (Lin, Beddor & Coetzee 2013) to influence the magnitude of the tongue tip gesture in laterals, especially with regard to /l/ vocalization. It might be applicable on the case of /l/-velarisation as well. Degree of darkness, differences in articulatory closure, dorsopalatal contact size, closure duration, relative timing of events and formant frequency (cf. Recasens & Espinosa 2005) are some of the important factors to take into account when studying this consonant and its co-articulatory effects on phonetic environment. Up until now none of these have been mentioned in Afrikaans phonetic literature. In the present article I superficially touch on some of them. Obviously these facets deserve fundamental attention. I utilised three different types of recording tasks, namely firstly the reading of carrier phrases containing a focus form with the structure /sVs/ (eg. among others, saas and sas); secondly, the naming of the letters of the alphabet (with an interest in a, h, k; all pronounced with a long [a]), and thirdly, the reading of a variety of isolated words and phrases, mostly containing words relevant to this study. In some cases C was prompted to orally complete a task, for example, a noun like val was to be read, but its diminutive (valletjie) and plural forms (valle) were to be completed without visual stimulus. Syllable structure was controlled systematically. In the case of val, /a/ appears in a closed syllable, but in valletjie and valle the syllables are open. These tasks had to be carried out twice. Recordings were done with high quality equipment, in use by RSG. Processing and acoustic analyses of the recordings were performed by means of standard procedures. As is conventional in studies of this nature, acoustic characteristics of the production of long /a/ and short /Q/ were investigated via vowel formant frequencies, F1 as well as F2. F1, the first formant, corresponds to vowel openness (vowel height). An open vowel, such as /a/, has high F1 frequencies, while close vowels, like /i/, have low F1 frequencies. The second formant, F2, corresponds to the front positions of a vowel. Back vowels, which are normally at the same time also rounded, have low F2 frequencies, in contrast to front vowels, which have high F2 frequencies. Generally the results clearly confirm the audible perception that C is a strong rounder of the long /a/. There is a very positive correlation between C's acoustic measurements and that previously found for another young female individual (Wissing 2006) as well as that of twenty others of about the same age (Wissing 2013). This finding strongly suggests a restriction on the number of participants as well as the range of required stimuli in instances of experiments of this kind, especially in the case of pilot studies. The role of syllable structure was found to be of limited importance. The short /a / was rounded to a significant degree when followed by /l/ in open as well as closed syllables, but to a small degree as in the case of open syllables. Of special importance is the finding that F1 also plays a significant role in the expression of degree of roundedness of the /a/ vowel, albeit not quite to the same extent as is the case with F2, generally considered to be the sole carrier of roundedness. The fact that the rounded [594;] is frequently misinterpreted (as the rounded vowel [ɔ] (in kom "come")), from a perceptual angle supports the current results of the analysis of the rounded [594;] in Afrikaans. Of course, [ɔ] is characterised inter alia by a higher F1 than that of the unrounded [a]. In many languages the existence of dark /l/ ([ɫ]) is well-known (cf. Hamann 2003; also Lin, Beddor & Coetzee 2014 and references cited by them). With regard to Afrikaans, a co-articulatory effect of this lateral was found to be clearly manifested in the present study on the rounding to [...] of the short /a/, but also of the long /a/. In a broader linguistic perspective the present findings should be of distinctive importance to those interested in language change in general, and more specifically in sound variation. [ABSTRACT FROM AUTHOR]

SYMMETRY (Physics), INVARIANT measures, DE Bruijn graph, ENTROPY, and LATTICE constants

We investigate the following questions: Given a measure $$\mu _\Lambda $$ on configurations on a subset $$\Lambda $$ of a lattice $$\mathbb {L}$$ , where a configuration is an element of $$\Omega ^\Lambda $$ for some fixed set $$\Omega $$ , does there exist a measure $$\mu $$ on configurations on all of $$\mathbb {L}$$ , invariant under some specified symmetry group of $$\mathbb {L}$$ , such that $$\mu _\Lambda $$ is its marginal on configurations on $$\Lambda $$ ? When the answer is yes, what are the properties, e.g., the entropies, of such measures? Our primary focus is the case in which $$\mathbb {L}=\mathbb {Z}^d$$ and the symmetries are the translations. For the case in which $$\Lambda $$ is an interval in $$\mathbb {Z}$$ we give a simple necessary and sufficient condition, local translation invariance ( LTI), for extendibility. For LTI measures we construct extensions having maximal entropy, which we show are Gibbs measures; this construction extends to the case in which $$\mathbb {L}$$ is the Bethe lattice. On $$\mathbb {Z}$$ we also consider extensions supported on periodic configurations, which are analyzed using de Bruijn graphs and which include the extensions with minimal entropy. When $$\Lambda \subset \mathbb {Z}$$ is not an interval, or when $$\Lambda \subset \mathbb {Z}^d$$ with $$d>1$$ , the LTI condition is necessary but not sufficient for extendibility. For $$\mathbb {Z}^d$$ with $$d>1$$ , extendibility is in some sense undecidable. [ABSTRACT FROM AUTHOR]

CANCER treatment, SMALL cell lung cancer, OLDER patients, CANCER chemotherapy, POPULATION health, and DRUG toxicity

Background: Twenty percent of all newly diagnosed patients with small-cell lung cancer (SCLC) are >75 years. Elderly patients may show more toxicity due to co-morbidity. We evaluated motives for adherence to treatment guidelines, completion of treatment and toxicity.Patients and methods: Population-based data from patients aged ≥75 years and diagnosed with SCLC in 1997–2004 in The Netherlands were used (368 limited disease and 577 extensive disease). Additional data on co-morbidity (Adult Co-morbidity Evaluation 27), World Health Organisation performance status (PS), treatment, motive for no chemotherapy, adaptations and underlying motive and grade 3 or 4 toxicity were gathered from the medical records.Results: Forty-eight percent did not receive chemotherapy. The most common motives were refusal by the patient or family, short life expectancy or a combination of high age, co-morbidity and poor PS. Although only relatively fit elderly were selected for chemotherapy, 60%–75% developed serious toxicity, and two-thirds of all patients could not complete the full chemotherapy.Conclusions: We hypothesise that a better selection by proper geriatric assessments is needed to achieve a more favourable balance between benefit and harm. [ABSTRACT FROM AUTHOR]

GAIT disorders, ANATOMICAL planes, CEREBRAL palsy, THERAPEUTICS, and INTER-observer reliability

Aim: To assess interobserver reliability in the interpretation of three-dimensional gait analysis (3DGA) of children with gait disorders within a single institution.Method: Seven experienced interpreters in our institution participated in a quality-assurance program reviewing one unique patient's 3DGA data every 3 months. Between 2014 and 2017, 15 patients' data were interpreted (14 with spastic cerebral palsy, 1 with myelodysplasia). Interpreters were asked to select 'yes', 'no', or 'indeterminate' from a list of problems and treatment recommendations. Kappa and percent agreement calculations were performed to evaluate consistency.Results: Average percentage agreement in problem identification and treatment recommendation was greater than 84 percent and 90 percent for all interpreters respectively. Average kappa for the 10 most consistently identified problems and recommended treatments were 0.69 and 0.59 respectively. Interpreter consistency was moderate or better for the most commonly performed operations at our institution (0.44-0.59). Sagittal plane abnormalities of the hip and knee had the highest consistency.Interpretation: When institutional differences in data collection and regional variations in management philosophies are removed, interobserver consistency in 3DGA interpretation is moderate to substantial for many commonly selected items. Identification of areas with poor consistency may help address underlying causes and improve data processes.What This Paper Adds: Consistency in three-dimensional gait analysis interpretation and treatment recommendation is high within a single institution. There is moderate or better consistency for most commonly identified problems and recommended treatments. Sagittal plane problem identification of the hip and knee have the highest consistency. Lower consistency is seen in areas with poor objective measures, such as dystonia and balance. [ABSTRACT FROM AUTHOR]

KINASES, YAP signaling proteins, FIBROBLAST growth factor 2, FIBROBLAST growth factor receptors, HIPPO signaling pathway, DRUG toxicity, and CHOLANGIOCARCINOMA

There is an unmet need to develop novel, effective medical therapies for cholangiocarcinoma (CCA). The Hippo pathway effector, Yes-associated protein (YAP), is oncogenic in CCA, but has historically been difficult to target therapeutically. Recently, we described a novel role for the LCK proto-oncogene, Src family tyrosine kinase (LCK) in activating YAP through tyrosine phosphorylation. This led to the hypothesis that LCK is a viable therapeutic target in CCA via regulation of YAP activity. A novel tyrosine kinase inhibitor with relative selectivity for LCK, NTRC 0652-0, was pharmacodynamically profiled in vitro and in CCA cells. A panel of eight CCA patient-derived organoids were characterized and tested for sensitivity to NTRC 0652-0. Two patient-derived xenograft models bearing fibroblast growth factor receptor 2 (FGFR2)-rearrangements were utilized for in vivo assessment of pharmacokinetics, toxicity, and efficacy. NTRC 0652-0 demonstrated selectivity for LCK inhibition in vitro and in CCA cells. LCK inhibition with NTRC 0652-0 led to decreased tyrosine phosphorylation, nuclear localization, and co-transcriptional activity of YAP, and resulted in apoptotic cell death in CCA cell lines. A subset of tested patient-derived organoids demonstrated sensitivity to NTRC 0652-0. CCAs with FGFR2 fusions were identified as a potentially susceptible and clinically relevant genetic subset. In patient-derived xenograft models of FGFR2 fusion-positive CCA, daily oral treatment with NTRC 0652-0 resulted in stable plasma and tumor drug levels, acceptable toxicity, decreased YAP tyrosine phosphorylation, and significantly decreased tumor growth. A novel LCK inhibitor, NTRC 0652-0, inhibited YAP signaling and demonstrated preclinical efficacy in CCA cell lines, and patient-derived organoid and xenograft models. Although aberrant YAP activation is frequently seen in CCA, YAP targeted therapies are not yet clinically available. Herein we show that a novel LCK-selective tyrosine kinase inhibitor (NTRC 0652-0) effectively inhibits YAP tyrosine phosphorylation and cotranscriptional activity and is well tolerated and cytotoxic in multiple preclinical models. The data suggest this approach may be effective in CCA with YAP dependence or FGFR2 fusions, and these findings warrant further investigation in phase I clinical trials. [Display omitted] • LCK is a novel therapeutic target in cholangiocarcinoma. • Cholangiocarcinoma organoid and xenograft tumor models respond to LCK inhibition. • FGFR2-altered cholangiocarcinomas have enriched YAP activity and are sensitive to LCK inhibition. [ABSTRACT FROM AUTHOR]

ACUTE otitis media, ANTIBIOTICS, DISEASE relapse, DRUG efficacy, DRUG prescribing, and THERAPEUTICS

Objective: Antibiotic treatment of acute otitis media (AOM) has been suggested to increase the risk of future AOM episodes by causing unfavorable shifts in microbial flora. Because current evidence on this topic is inconclusive and long-term follow-up data are scarce, we wanted to estimate the effect of antibiotic treatment for a first AOM episode occurring during infancy on AOM recurrences and AOM-related health care utilization later in life. Methods: We obtained demographic information and risk factors from data of the Wheezing Illnesses Study Leidsche Rijn, a prospective birth cohort study in which all healthy newborns born in Leidsche Rijn (between 2001 and 2012), The Netherlands, were enrolled. These data were linked to children’s primary care electronic health records up to the age of four. Children with at least one family physician-diagnosed AOM episode before the age of two were included in analyses. The exposure of interest was the prescription of oral antibiotics (yes vs no) for a child’s first AOM episode before the age of two years. Results: 848 children were included in analyses and 512 (60%) children were prescribed antibiotics for their first AOM episode. Antibiotic treatment was not associated with an increased risk of total AOM recurrences (adjusted rate ratio: 0.94, 95% CI: 0.78–1.13), recurrent AOM (≥3 episodes in 6 months or ≥4 in one year; adjusted risk ratio: 0.79, 95% CI: 0.57–1.11), or with increased AOM-related health care utilization during children’s first four years of life. Conclusions: Oral antibiotic treatment of a first AOM episode occurring during infancy does not affect the number of AOM recurrences and AOM-related health care utilization later in life. This information can be used when weighing the pros and cons of various AOM treatment options. [ABSTRACT FROM AUTHOR]

DE facto doctrine, ADMINISTRATIVE law, CONSTITUTIONAL law, CHARTERING, and CORPORATION law

Despite over 200 years of deliberation and debate, the United States has not adopted a federal corporate chartering law. Instead, Delaware is the "Federal Option" for corporate law and adjudication. The contemporary federal corporate chartering debate is, in part, a referendum on its role. Although the federal government has regulated other aspects of interstate commerce and has the power to charter corporations and preempt Delaware pursuant to its Commerce Clause power, it has not done so. Despite the rich and robust scholarly discussion of Delaware's jurisdictional dominance, its role as a de facto national regulator remains underdeveloped. This Article addresses a vexing question: Can Delaware, a haven for incorporation and adjudication, serve as an effective national regulator? Following an analysis of federal chartering alternatives, such as the Nader Plan, the Warren Plan, the Sanders Plan, and other modes of regulation, the answer is yes, but with some caveats and qualifications. Delaware's adequate, if imperfect, performance as a surrogate national regulator of corporate internal affairs argues against the upheaval of the existing corporate law framework federal chartering would bring. Even in the contemporary moment where longstanding concerns about corporate power, purpose, accountability, and the uneasy relationship between corporations and society are amplified, Delaware can continue to perform an important agency-like role in collaboration with federal regulators and regulated firms. A deeper examination comparing the merits of federal corporate chartering with Delaware's de facto agency function illuminates the potential of existing and future reforms. This Article concludes that federal chartering proposals have an important impact despite not being adopted for centuries. First, federal chartering proposals encourage policymakers to look beyond the status quo toward greater hybridization in regulatory design. Second, elements of previous federal chartering proposals have historically become successful "à la carte" reforms or part of other successful reform measures. Third, federal chartering proposals provide value as a bargaining tool where the threat of more intrusive federal regulation makes other reform methods more palatable to diverse corporate constituencies. [ABSTRACT FROM AUTHOR]

MEDICAL care costs, EPIDERMAL growth factor receptors, BREAST cancer, HORMONE receptors, HOSPITAL costs, and CANCER treatment

Objectives: Policy makers increasingly seek to complement data from clinical trials with information from routine care. This study aims to provide a detailed account of the hospital resource use and associated costs of patients with advanced breast cancer in The Netherlands.Methods: Data from 597 patients with advanced breast cancer, diagnosed between 2010 and 2014, were retrieved from the Southeast Netherlands Advanced Breast Cancer Registry. Database lock for this study was in October 2017. We report the observed hospital costs for different resource categories and the lifetime costs per patient, adjusted for censoring using Lin's method. The relationship between patients' characteristics and costs was studied using multivariable regression.Results: The average (SE) lifetime hospital costs of patients with advanced breast cancer were €52 709 (405). Costs differed considerably between patient subgroups, ranging from €29 803 for patients with a triple-negative subtype to €92 272 for patients with hormone receptor positive and human epidermal growth factor receptor 2 positive cancer. Apart from the cancer subtype, several other factors, including age and survival time, were independently associated with patient lifetime costs. Overall, a large share of costs was attributed to systemic therapies (56%), predominantly to a few expensive agents, such as trastuzumab (15%), everolimus (10%), and bevacizumab (9%), as well as to inpatient hospital days (20%).Conclusions: This real-world study shows the high degree of variability in hospital resource use and associated costs in advanced breast cancer care. The presented resource use and costs data provide researchers and policy makers with key figures for economic evaluations and budget impact analyses. [ABSTRACT FROM AUTHOR]

LUNG transplantation, TRANSPLANTATION of organs, tissues, etc., BIOMARKERS, PERFUSION, and LUNGS

Biomarker-based scoring algorithms have been reported throughout the EVLP literature; however, the role that prediction models play in influencing surgical decision-making is not known. Herein, we sought to assess the impact of biomarker scoring on EVLP-decisions in a retrospective, single center study. A total of n=20 clinical EVLP cases were used in this study. Each case was independently assessed by n=15 study participants that included surgeons, surgical fellows, organ perfusion specialists, and EVLP assistants. Each EVLP case was de-identified and presented alongside an intended recipient. Participants were asked to determine the suitability of the lung for transplant (yes/no) based on standard EVLP assessments alone and their impression of the organ on a scale from 0-10. Biomarker scores were then revealed and participants were then asked to re-answer the transplant and lung suitability questions. There were a total of n=300 transplant decisions in this study with and without biomarker scoring. The use of biomarker scoring greatly increased the recommendation to transplant lungs predicted to result in post-transplant extubation <72h [OR=13; 95%CI:4-45] and significantly increased a participant's lung suitability score [+1.0; 95%CI:0.4-1.5]. For lungs predicted to have excellent recipient outcomes and the historical decision was to transplant the organ, there was a 6.7% increase in transplant recommendation. Importantly, there was a net 13.3% increase in transplant recommendation when the historical decision was to decline an organ likely to result in a good outcome. Conversely, there was a 13.3% decrease in the recommendation to transplant lungs likely to produce poor outcomes (i.e., prolonged ventilation or PGD 3) using biomarker scores (OR=0.4; 95%CI:0.16-0.98). This study demonstrates that the inclusion of biomarker scoring during EVLP can lead to an increase in organ acceptance following EVLP. Furthermore, we demonstrate that organs that were associated with poor patient outcomes are less likely to be transplanted as a result of biomarker scoring being included in EVLP assessments. Taken together, this study provides strong rationale for the adoption of biomarker scoring algorithms during EVLP. [ABSTRACT FROM AUTHOR]

PATIENT satisfaction, MEDICAL quality control, BREAST cancer, MEDICAL communication, and AGE factors in disease

Objectives: The Medical University of South Carolina implemented a patient-centered multidisciplinary breast clinic program (MDBC) in August 2012. In this study, patient satisfaction with the MDBC care delivery model and communication with healthcare providers was examined to inform the refinement of the MDBC program. Methods: During the first 10 months of the MDBC, patients were asked to complete a 14-question postconsultation telephone survey. A statistical analysis was performed to explore potential associations between age, race, and stage with overall patient satisfaction scores. Results: Overall, patients (N = 52, 56% white, 42% African American, 2% Hispanic; mean age 61 years) rated the quality of care highly (mean 4.7, range [1 = poor to 5 = excellent]) and felt comfortable with their plan of care (mean 1.63, range [1 = extremely comfortable to 5 = not at all comfortable]). No statistically significant differences in overall satisfaction were found by age, race, or stage; however, patient responses were commonly not optimal (ie, either "no" or "yes, but not as much as I would like") when asked if the care team addressed the impact of their diagnosis on personal relationships (40.4%) or emotional health (28.9%). Conclusions: Patients were highly satisfied with the care they received in the MDBC program. Findings suggest that this model is well suited to a diverse patient population and have highlighted quality improvement targets such as increased emphasis on providers' communication about psychosocial issues. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcoma is a rare but serious side-effect of radiotherapy to treat breast cancer, and rates are increasing in the USA. We evaluated potential co-factors in two complimentary cohorts of US breast cancer survivors.Methods: In this retrospective cohort study, we sourced data from the Kaiser Permanente (KP) cohort and the Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort, both in the USA. The KP cohort included 15 940 women diagnosed with breast cancer from Jan 1, 1990, to Dec 31, 2016, in KP Colorado, KP Northwest (which serves Oregon and Southwest Washington state), or KP Washington, with detailed treatment data and comorbidities (including hypertension and diabetes at or before breast cancer diagnosis) from electronic medical records. The SEER cohort included 457 300 women diagnosed with breast cancer from Jan 1, 1992, to Dec 31, 2016, within the 13 SEER registries across the USA, with initial treatment data (yes vs no or unknown). Eligibility criteria in both cohorts were female breast cancer survivors (stage I-III) aged 20-84 years at diagnosis who had breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis. The outcome of interest was any second thoracic soft tissue sarcoma (angiosarcomas and other subtypes) that developed at least 1 year after breast cancer diagnosis. Risk factors for thoracic soft tissue sarcoma were assessed using multivariable Poisson regression models.Findings: In the KP cohort, median follow-up was 9·3 years (IQR 5·7-13·9) and 19 (0·1%) of 15 940 eligible, evaluable women developed a thoracic soft tissue sarcoma (11 angiosarcomas, eight other subtypes). Most (94·7%; 18 of 19) thoracic soft tissue sarcomas occurred in women treated with radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (relative risk [RR] 8·1 [95% CI 1·1-60·4]; p=0·0052), but there was no association with prescribed dose, fractionation, or boost. The RR of angiosarcoma after anthracyclines was 3·6 (95% CI 1·0-13·3; p=0·058). Alkylating agents were associated with an increased risk of developing other sarcomas (RR 7·7 [95% CI 1·2-150·8]; p=0·026). History of hypertension (RR 4·8 [95% CI 1·3-17·6]; p=0·017) and diabetes (5·3 [1·4-20·8]; p=0·036) were each associated with around a five-times increased risk of angiosarcoma. In the SEER cohort, 430 (0·1%) of 457 300 patients had subsequent thoracic soft tissue sarcomas (268 angiosarcomas and 162 other subtypes) after a median follow-up of 8·3 years (IQR 4·3-13·9). Most (77·9%; 335 of 430) cases occurred after radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (RR 3·0 [95% CI 2·4-3·8]; p<0·0001) and, for angiosarcomas, the RR for breast-conserving surgery plus radiotherapy versus mastectomy plus radiotherapy was 1·9 (1·1-3·3; p=0·012). By 10 years after radiotherapy, the cumulative incidence of thoracic soft tissue sarcoma was 0·21% (95% CI 0·12-0·34) in the KP cohort and 0·15% (95% CI 0·13-0·17) in SEER.Interpretation: Radiotherapy was the strongest risk factor for thoracic soft tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance.Funding: US National Cancer Institute and National Institutes of Health. [ABSTRACT FROM AUTHOR]

SMELL disorders, COVID-19, CENTRAL nervous system viral diseases, ODORS, and OLFACTOMETRY

Anosmia has been recognized as a prevalent and early symptom by many COVID-19 patients. However, most researchers have recorded smell dysfunction solely as present or absent and based on subjective evaluation by patients. We described the results of 57 consecutive COVID-19 patients seen at FIOCRUZ, Rio de Janeiro, Brazil, from April to May 2020. Data about the presence of smell loss, the onset of smell loss and other COVID-19 symptoms such as ageusia and nasal congestion or rhinorrhea were recorded. All patients at the initial consultation and 34 healthy controls underwent the Q-SIT, which is a quick disposable three-item smell identification test, by a trained physician. We compared three groups: healthy controls, COVID+ patients with reported smell loss (COVID w/ SL) and COVID+ patients without smell loss (COVID+ w/o SL). The mean age of patients was 41.4 years (SD ± 10.4), and 54.4% were women. Smell loss was reported by 40.4% of COVID-19 patients. We observed a gradual effect with higher Q-SIT scores in healthy controls, followed by COVID+ w/o SL and COVID+ w/ SL (medians = 3, 2 and 0; respectively, p < 0.001). Anosmia or severe microsmia (Q-SIT≤1) was present in 11.1% (CI: 3.1%–26.1%) of controls, 32.4% (CI: 17.4%–50.5%) of COVID-19 w/o SL and 87% (CI: 66.4%–97.2%) of COVID+ w/ SL (p < 0.001). This study provides evidence that olfactory dysfunction in COVID-19 is common and more prevalent than what is perceived by patients. Q-SIT is a quick and reliable screening test for the detection of smell dysfunction during the pandemics. • Smell dysfunction is frequent in COVID-19 patients. • Subtle olfactory dysfunction is frequently not perceived by patients when inquired during medical visits. • Q-SIT is a quick and reliable screening test for the detection of smell dysfunction during the pandemics. [ABSTRACT FROM AUTHOR]

REPRODUCIBLE research, ULTRASONIC imaging, UTERUS abnormalities, COHORT analysis, LONGITUDINAL method, and COHEN'S kappa coefficient (Statistics)

Objective Purpose of this study is to determine the interobserver and intraobserver variability of 3D GIS in the assessment of intrauterine abnormalities. Study design Forty five 3D volumes were randomly selected from a larger prospective cohort study that studied the diagnostic accuracy of 3D GIS in addition to 2D GIS. To study interobserver agreement volumes were reviewed by two independent examiners. One examiner reviewed these samples twice with an interval of 1 month in a random order. Interobserver and intraobserver agreement were tested with Cohen's kappa coefficient and shown in Bland and Altman plots. Quality of the 3D volumes was evaluated. Results Cohen's kappa for interobserver variability for type of abnormalities (none, polyp, fibroid, other) was 0.64 and for presence of a fibroid (fibroid yes/no) 0.77. Agreement on type of fibroid was 0.59. Intraobserver agreement was almost perfect for type of abnormality (Cohen's kappa of 1.0) and good for fibroid diameter. Quality of the 3D volumes was poor in 11 out of 45 cases. Reproducibility increased when poor quality images were excluded. Conclusion Substantial interobserver and intraobserver agreement for 3D GIS in the diagnoses of intrauterine abnormalities was found. 3D GIS interobserver and intraobserver agreement are good for fibroid diameter and moderate for volume and protrusion. [ABSTRACT FROM AUTHOR]

RESPIRATORY infections, OTITIS media, MEDICAL care, PEDIATRICS, and PRIMARY care

Background Daycare attendance is an established risk factor for upper respiratory tract infections (URTI) and acute otitis media (AOM). Whether this results in higher use of healthcare resources during childhood remains unknown. We aim to assess the effect of first year daycare attendance on the timing and use of healthcare resources for URTI and AOM episodes during early childhood. Methods In the Wheezing-Illnesses-STudy-LEidsche-Rijn birth cohort, 2,217 children were prospectively followed up to age six years. Children were categorized according to first-year daycare attendance (yes versus no) and age at entry when applicable (age 0 to 2 months, 3 to 5 months and 6 to 12 months). Information on general practitioner (GP) diagnosed URTI and AOM, GP consultations, antibiotic prescriptions and specialist referral was collected from medical records. Daycare attendance was recorded by monthly questionnaires during the first year of life. Results First-year daycare attendees and non-attendees had similar total six-year rates of GPdiagnosed URTI and AOM episodes (59/100 child-years, 95% confidence interval 57 to 61 versus 56/100 child-years, 53 to 59). Daycare attendees had more GP-diagnosed URTI and AOM episodes before the age of one year and fewer beyond the age of four years than nonattendees (Pinteraction <0.001). Daycare attendees had higher total six-year rates for GP consultation (adjusted rate ratio 1.15, 1.00 to 1.31) and higher risk for specialist referrals (hazard ratio:1.43, 1.01 to 2.03). The number of antibiotic prescriptions in the first six years of life was only significantly increased among children who entered daycare between six to twelve months of age (rate ratio 1.32, 1.04 to 1.67). This subgroup of child-care attendees also had the highest overall URTI and AOM incidence rates, GP consultation rates and risk for specialist referral. Conclusions Children who enter daycare in the first year of life, have URTI and AOM at an earlier age, leading to higher use of healthcare resources compared to non-attendees, especially when entering daycare between six to twelve months. These findings emphasize the need for improved prevention strategies in daycare facilities to lower infection rates at the early ages. [ABSTRACT FROM AUTHOR]

CARDIOVASCULAR diseases risk factors, MYELOPEROXIDASE, CORONARY disease, CARDIOVASCULAR diseases, CIRCULATING tumor DNA, and HDL cholesterol

Introduction: Neutrophil extracellular traps (NETs) are DNA scaffolds enriched with antimicrobial proteins. NETs have been implicated in the development of various diseases, such as cardiovascular disease. Here, we investigate the association of demographic and cardiovascular (CVD) risk factors with NETs in the general population. Material and methods: Citrated plasma was collected from 6449 participants, aged ≥55 years, as part of the prospective population-based Rotterdam Study. NETs were quantified by measuring MPO-DNA complex using an ELISA. We used linear regression to determine the associations between MPO-DNA complex and age, sex, cardio-metabolic risk factors, and plasma markers of inflammation and coagulation. Results: MPO-DNA complex levels were weakly associated with age (log difference per 10 year increase: -0.04 mAU/mL, 95% confidence interval [CI] -0.06;-0.02), a history of coronary heart disease (yes versus no: -0.10 mAU/mL, 95% CI -0.17;-0.03), the use of lipid-lowering drugs (yes versus no: -0.06 mAU/mL, 95% CI -0.12;-0.01), and HDL-cholesterol (per mmol/l increase: -0.07 mAU/mL/, 95% CI -0.12;-0.03). Conclusions: Older age, a history of coronary heart disease, the use of lipid-lowering drugs and higher HDL-cholesterol are weakly correlated with lower plasma levels of NETs. These findings show that the effect of CVD risk factors on NETs levels in a general population is only small and may not be of clinical relevance. This supports that NETs may play a more important role in an acute phase of disease than in a steady state situation. [ABSTRACT FROM AUTHOR]

The article discusses the issue of education youth and adults (EJA). The objective is to analyze, from the perspective of students, as Mossoro campus IFRN comes materializing the proposed curriculum of integrated technical course in Building the EJA modality, offered under the National Programme Vocational Education Integration with Basic Education in the Modality Youth and Adult education (PROEJA). Methodologically, the study is included in the exploratory-descriptive category, based on dialectics. The sources of information are the Pedagogical Project of the Course and the data (questionnaires and interviews) collected from students last semester of the first class of the course. Considering the pedagogical practices developed by teachers, it appears that there is no concrete evidence of an integrated curriculum in the course and, yes, that only a few didactic actions, very specific and not systematic or planned collectively contribute to this end. [ABSTRACT FROM AUTHOR]

Sewage disposal plants, Sewage purification, Refuse disposal facilities, Environmental impact charges, Water quality management, Water utilities, Hospitals, Steroids, and Hormones

Influent and effluent samples originating from two wastewater treatment plants (WWTPs) (treating hospital wastewater and domestic wastewater, Belgium) have been analyzed in order to estimate their steroid hormone content. The natural estrogens estrone (E1), 17β-estradiol (E2), and the synthetic 17α-ethinylestradiol (EE2) together with other steroid hormones progesterone (P) and testosterone (T) metabolites were detected in these samples. The hormone concentrations in both the hospital and the domestic WWTP samples were not significantly different and ranged from <0.2 ng EE2/L to 114 ng EE2/L, from <0.2 ng E1/L to 58 ng E1/L and from <0.2 ng P/L to >100 ng P/L. E2 was detected once at a concentration of 17 ng/L. In the domestic WWTP which comprises a conventional activated sludge treatment in parallel with a membrane bioreactor, no differences in estrogen removal efficiency could be observed for both treatments. In comparison to chemical analysis data, the Yeast Estrogen Screen (YES) appears to underestimate the influent estrogen concentrations, probably due to influent toxicity for the YES. Effluent estrogen concentrations, on the other hand, were overestimated by the YES test, probably due to the presence of other estrogenic compounds in the effluent. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post‐discharge outcomes.Of 8298 patients in the European Society of Cardiology Heart Failure Long‐Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non‐use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and beta‐blockers. In‐hospital death occurred in 3.3%. The prevalence of hyponatraemia and in‐hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in‐hospital mortality 6.9%), 11% Yes/No (in‐hospital mortality 4.9%), 8% No/Yes (in‐hospital mortality 4.7%), and 72% No/No (in‐hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In‐hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12‐month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35–1.89), Yes/No 1.35 (1.14–1.59), and No/Yes 1.18 (0.96–1.45). For death or heart failure hospitalization they were 1.38 (1.21–1.58), 1.17 (1.02–1.33), and 1.09 (0.93–1.27), respectively.Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in‐hospital and post‐discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk. [ABSTRACT FROM AUTHOR]

BRAIN physiology, ELECTROENCEPHALOGRAPHY, MEMORY, RECOGNITION (Psychology), STATISTICAL sampling, RANDOMIZED controlled trials, PROMPTS (Psychology), REPEATED measures design, and ONE-way analysis of variance

Items that are produced (e.g., read aloud) during encoding typically are better remembered than items that are not produced (e.g., read silently). This "production effect" has been explained by distinctiveness: Produced items have more distinct features than nonproduced items, leading to enhanced retrieval. The goal of the current study was to use electroencephalography (EEG) to examine the neural basis of the production effect. During study, participants were presented with words that they were required to read silently, read aloud, or sing while EEG data were recorded. Subsequent memory performance was tested using a yes/no recognition test. Analysis focused on the event-related brain potentials (ERPs) evoked by the encoding instruction cue for each instruction condition. Our data revealed enhanced memory performance for produced items and a greater P300 ERP amplitude for instructions to sing or read aloud compared with instructions to read silently. Our results demonstrate that the amplitude of the P300 is modulated by at least 1 aspect of production, vocalization (singing/reading aloud relative to reading silently), and are consistent with the distinctiveness account of the production effect. The ERP methodology is a viable tool for investigating the production effect. [ABSTRACT FROM AUTHOR]

HUNTINGTON disease, YAP signaling proteins, HIPPO signaling pathway, HUMAN embryonic stem cells, and MEDICAL model

The Hippo pathway, a highly conserved signaling cascade that functions as an integrator of molecular signals and biophysical states, ultimately impinges upon the transcription coactivator Yes-associated protein 1 (YAP). Hippo-YAP signaling has been shown to play key roles both at the early embryonic stages of implantation and gastrulation, and later during neurogenesis. To explore YAP's potential role in neurulation, we used self-organizing neuruloids grown from human embryonic stem cells on micropatterned substrates. We identified YAP activation as a key lineage determinant, first between neuronal ectoderm and nonneuronal ectoderm, and later between epidermis and neural crest, indicating that YAP activity can enhance the effect of BMP4 stimulation and therefore affect ectodermal specification at this developmental stage. Because aberrant Hippo-YAP signaling has been implicated in the pathology of Huntington's Disease (HD), we used isogenic mutant neuruloids to explore the relationship between signaling and the disease. We found that HD neuruloids demonstrate ectopic activation of gene targets of YAP and that pharmacological reduction of YAP's transcriptional activity can partially rescue the HD phenotype. [ABSTRACT FROM AUTHOR]

HELP-seeking behavior, TINNITUS, and HEARING disorders

Knowledge on characteristics of people that seek help for tinnitus is scarce. The primary objective of this study was to describe differences in characteristics between people with tinnitus that seek help compared to those who do not seek help. Next, we described differences in characteristics between those with and without tinnitus. In this cross-sectional study, we sent a questionnaire on characteristics in different domains; demographic, tinnitus-specific, general- and psychological health, auditory and noise- and substance behaviour. We assessed if participants had sought help or planned to seek help for tinnitus. Tinnitus distress was defined with the Tinnitus Functional Index. Differences between groups (help seeking: yes/no, tinnitus: yes/no) were described. 932 people took part in our survey. Two hundred and sixteen participants were defined as having tinnitus (23.2%). Seventy-three of those sought or planned to seek help. A constant tinnitus pattern, a varying tinnitus loudness, and hearing loss, were described more frequently in help seekers. Help seekers reported higher TFI scores. Differences between help seekers and people not seeking help were mainly identified in tinnitus- and audiological characteristics. These outcomes might function as a foundation to explore the heterogeneity in tinnitus patients. [ABSTRACT FROM AUTHOR]

HEMATOPOIETIC stem cell transplantation, HOMOGRAFTS, MYELODYSPLASTIC syndromes, ACUTE myeloid leukemia, BLOOD donors, AZACITIDINE, COMPARATIVE studies, and DISEASE risk factors

Standard first-line therapy for older patients with high-risk myelodysplastic syndrome (MDS) includes hypomethylating agents, such as azacitidine (AZA). However, the only approach with curative potential remains allogeneic hematopoietic cell transplantation (HCT). To date, no direct comparison of both strategies has been reported. The outcomes of 2 well-balanced cohorts of patients with high-risk MDS defined by age (60-70 years), performance status (Eastern Cooperative Oncology Group score ≤2), and donor availability (yes/no) were compared, including 103 patients undergoing HCT and 75 patients without this option who received AZA. The estimated 2-year overall survival after the start of treatment was 39% (95% confidence interval, 30%-50%) for the patients undergoing HCT and 23% (95% confidence interval, 14%-40%) for the patients receiving AZA therapy. In a multivariate Cox regression analysis of all patients (n = 178), Eastern Cooperative Oncology Group score (0 versus 1 versus 2; hazard ratio [HR], 2.9/3.9; P <  .001), cytogenetics (good versus intermediate versus poor; HR, 1.2/1.7; P = .026), and treatment (HCT versus AZA; HR, 0.3; P = .007) were associated with overall survival. This retrospective cohort analysis suggests a survival advantage for allogeneic HCT compared with AZA therapy in medically fit patients with high-risk MDS age 60-70 years. Prospective controlled studies are warranted. [ABSTRACT FROM AUTHOR]

RHINITIS, WHEEZE, MILK allergy, EXERCISE-induced asthma, METERED-dose inhalers, FOOD allergy, and PROGNOSIS

Table of contents: WORKSHOP 4: Challenging clinical scenarios (CS01–CS06) CS01 Bullous lesions in two children: solitary mastocytoma S. Tolga Yavuz, Ozan Koc, Ali Gungor, Faysal Gok CS02 Multi‐System Allergy (MSA) of cystic fibrosis: our institutional experience Jessica Hawley, Christopher O'Brien, Matthew Thomas, Malcolm Brodlie, Louise Michaelis CS03 Cold urticaria in pediatric age: an invisible cause for severe reactions Inês Mota, Ângela Gaspar, Susana Piedade, Graça Sampaio, José Geraldo Dias, Miguel Paiva, Mário Morais‐Almeida CS04 Angioedema with C1 inhibitor deficiency in a girl: a challenge diagnosis Cristina Madureira, Tânia Lopes, Susana Lopes, Filipa Almeida, Alexandra Sequeira, Fernanda Carvalho, José Oliveira CS05 A child with unusual multiple organ allergy disease: what is the primer? Fabienne Gay‐Crosier CS06 A case of uncontrolled asthma in a 6‐year‐old patient Ioana‐Valentina Nenciu, Andreia Florina Nita, Alexandru Ulmeanu, Dumitru Oraseanu, Carmen Zapucioiu ORAL ABSTRACT SESSION 1: Food allergy (OP01–OP06) OP01 Food protein‐induced enterocolitis syndrome: oral food challenge outcomes for tolerance evaluation in a Pediatric Hospital Adrianna Machinena, Olga Domínguez Sánchez, Montserrat Alvaro Lozano, Rosa Jimenez Feijoo, Jaime Lozano Blasco, Mònica Piquer Gibert, Mª Teresa Giner Muñoz, Marcia Dias da Costa, Ana Maria Plaza Martín OP02 Characteristics of infants with food protein‐induced enterocolitis syndrome and allergic proctocolitis Ebru Arik Yilmaz, Özlem Cavkaytar, Betul Buyuktiryaki, Ozge Soyer, Cansin Sackesen OP03 The clinical and immunological outcomes after consumption of baked egg by 1–5 year old egg allergic children: results of a randomised controlled trial MerrynNetting, Adaweyah El‐Merhibi, Michael Gold, PatrickQuinn, IrmeliPenttila, Maria Makrides OP04 Oral immunotherapy for treatment of egg allergy using low allergenic, hydrolysed egg Stavroula Giavi, Antonella Muraro, Roger Lauener, Annick Mercenier, Eugen Bersuch, Isabella M. Montagner, Maria Passioti, Nicolò Celegato, Selina Summermatter, Sophie Nutten, Tristan Bourdeau, Yvonne M. Vissers, Nikolaos G. Papadopoulos OP05 Chemical modification of a peanut extract results in an increased safety profile while maintaining efficacy Hanneke van der Kleij, Hans Warmenhoven, Ronald van Ree, Raymond Pieters, Dirk Jan Opstelten, Hans van Schijndel, Joost Smit OP06 Administration of the yellow fever vaccine in egg allergic children Roisin Fitzsimons, Victoria Timms, George Du Toit ORAL ABSTRACT SESSION 2: Asthma (OP07–OP12) OP07 Previous exacerbation is the most important risk factor for future exacerbations in school‐age children with asthma S. Tolga Yavuz, Guven Kaya, Mustafa Gulec, Mehmet Saldir, Osman Sener, Faysal Gok OP08 Comparative study of degree of severity and laboratory changes between asthmatic children using different acupuncture modalities Nagwa Hassan, Hala Shaaban, Hazem El‐Hariri, Ahmed Kamel Inas E. Mahfouz OP09 The concentration of exhaled carbon monoxide in asthmatic children with different controlled stadium Papp Gabor, Biro Gabor, Kovacs Csaba OP10 Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomised clinical trial Bo Chawes, Klaus Bønnelykke, Jakob Stokholm, Lene Heickendorff, Susanne Brix, Morten Rasmussen, Hans Bisgaard OP11 Lung function development in childhood Henrik Wegener Hallas, Bo Chawes, Lambang Arianto, Hans Bisgaard OP12 Is the effect of maternal and paternal asthma different in female and male children before puberty? Maike Pincus, Thomas Keil, Andreas Reich, Ulrich Wahn, Susanne Lau, Linus Grabenhenrich ORAL ABSTRACT SESSION 3: Epidemiology—genetics (OP13–OP18) OP13 Lifestyle is associated with incidence and category of allergen sensitisation: the ALADDIN birth cohort Sara Fagerstedt, Helena Marell Hesla, Emelie Johansson, Helen Rosenlund, Axel Mie, Annika Scheynius, Johan Alm OP15 Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance Jorge Esparza‐Gordillo, Anja Matanovic, Ingo Marenholz, Anja Bauerfeind, Klaus Rohde, Katja Nemat, Min‐Ae Lee‐Kirsch, Magnus Nordenskjöld, Marten C. G. Winge, Thomas Keil, Renate Krüger, Susanne Lau, Kirsten Beyer, Birgit Kalb, Bodo Niggemann, Norbert Hübner, Heather J. Cordell, Maria Bradley, Young‐Ae Lee OP16 Allergic multimorbidity of asthma, rhinitis and eczema in the first 2 decades of the German MAS birth cohort Thomas Keil, Hannah Gough, Linus Grabenhenrich, Dirk Schramm, Andreas Reich, John Beschorner, Antje Schuster, Carl‐Peter Bauer, Johannes Forster, Fred Zepp, Young‐Ae Lee, Renate Bergmann, Karl Bergmann, Ulrich Wahn, Susanne Lau OP17 Childhood anaphylaxis: a growing concern Filipe Benito Garcia, Inês Mota, Susana Piedade, Ângela Gaspar, Natacha Santos, Helena Pité, Mário Morais‐Almeida OP18 Indoor exposure to molds and dampness in infancy and its association to persistent atopic dermatitis in school age. Results from the Greek ISAAC II study Athina Papadopoulou, Despina Mermiri, Elpida Xatziagorou, Ioannis Tsanakas, Stavroula Lampidi, Kostas Priftis ORAL ABSTRACT SESSION 4: Pediatric rhinitis—immunotherapy (OP19–OP24) OP19 Associations between residential greenness and childhood allergic rhinitis and aeroallergen sensitisation in seven birth cohorts Elaine Fuertes, Iana Markevych, Gayan Bowatte, Olena Gruzieva, Ulrike Gehring, Allan Becker, Dietrich Berdel, Michael Brauer, Chris Carlsten, Barbara Hoffmann, Anita Kozyrskyj, Caroline Lodge, Göran Pershagen, Alet Wijga, Heinrich Joachim OP20 Full symptom control in pediatric patients with allergic rhinitis and asthma: results of a 2‐year sublingual allergen immunotherapy study Zorica Zivkovic, Ivana Djuric‐Filipovic, Jasmina Jocić‐Stevanovic, Snežana Zivanovic OP21 Nasal epithelium of different ages of atopic subjects present increased levels of oxidative stress and increased cell cytotoxicity upon rhinovirus infection Styliani Taka, Dimitra Kokkinou, Aliki Papakonstantinou, Panagiota Stefanopoulou, Anastasia Georgountzou, Paraskevi Maggina, Sofia Stamataki, Vassiliki Papaevanggelou, Evangelos Andreakos, Nikolaos G. Papadopoulos OP22 Cluster subcutaneous immunotherapy schedule: tolerability profile in children Monica Piquer Gibert, Montserrat Alvaro Lozano, Jaime Lozano Blasco, Olga Domínguez Sánchez, Rosa Jiménez Feijoo, Marcia Dias da Costa, Mª Teresa Giner Muñoz, Adriana Machinena Spera, Ana Maria Plaza Martín OP23 Rhinitis as a risk factor for asthma severity in 11‐year old children: population‐based cohort study Matea Deliu, Danielle Belgrave, Angela Simpson, Adnan Custovic OP24 The Global Lung Function Initiative equations in airway obstruction evaluation of asthmatic children João Gaspar Marques, Pedro Carreiro‐Martins, Joana Belo, Sara Serranho, Isabel Peralta, Nuno Neuparth, Paula Leiria‐Pinto POSTER DISCUSSION SESSION 1: Food allergy (PD01–PD05) PD01 Allergen‐specific humoral and cellular responses in children who fail egg oral immunotherapy due to allergic reactions Marta Vazquez‐Ortiz, Mariona Pascal, Ana Maria Plaza, Manel Juan PD02 FoxP3 epigenetic features in children with cow milk allergy Lorella Paparo, Rita Nocerino, Rosita Aitoro, Ilaria Langella, Antonio Amoroso, Alessia Amoroso, Carmen Di Scala, Roberto Berni Canani PD04 Combined milk and egg allergy in early childhood: let them eat cake? Santanu Maity, Giuseppina Rotiroti, Minal Gandhi PD05 Introduction of complementary foods in relation to allergy and gut microbiota in farm and non‐farm children Karin Jonsson, Annika Ljung, Bill Hesselmar, Ingegerd Adlerbert, Hilde Brekke, Susanne Johansen, Agnes Wold, Ann‐Sofie Sandberg POSTER DISCUSSION SESSION 2: Asthma and wheeze (PD06–PD16) PD06 The association between asthma and exhaled nitric oxide is influenced by genetics and sensitisation Björn Nordlund, Cecilia Lundholm, Villhelmina Ullemar, Marianne van Hage, Anne Örtqvist, Catarina Almqvist PD09 Prevalence patterns of infant wheeze across Europe Anna Selby, Kate Grimshaw, Thomas Keil, Linus Grabenhenrich, Michael Clausen, Ruta Dubakiene, Alessandro Fiocchi, Marek Kowalski, Nikos Papadopoulos, Marta Reche, Sigurveig Sigurdardottir, Aline Sprikkleman, Paraskevi Xepapadaki, Clare Mills, Kirsten Beyer, Graham Roberts PD10 Epidemiologic changes in recurrent wheezing infants Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Carolina Dela Bianca, Carolina Aranda, Nelson Augusto Rosário, Dirceu Solé, Javier Mallol, Luis García Marcos PD13 A single nucleotide polymorphism in the GLCCI1 gene is associated with response to asthma treatment in children IvanaBanic, Matija Rijavec, Davor Plavec, Peter Korosec, Mirjana Turkalj PD14 Pollen induced asthma: Could small molecules in pollen exacerbate the protein‐mediated allergic response? Alen Bozicevic, Maria De Mieri, Matthias Hamburger PD15 A qualitative study to understand how we can empower teenagers to better self‐manage their asthma Simone Holley, Ruth Morris, Frances Mitchell, Rebecca Knibb, Susan Latter, Christina Liossi, Graham Roberts PD16 Polymorphism of endothelial nitric oxide synthase (eNOS) gene among Egyptian children with bronchial asthma Mostafa M. M. Hassan POSTER DISCUSSION SESSION 3: Mechanisms—Epidemiology (PD17–PD21) PD17 Pregnancy outcomes in relation to development of allergy in a Swedish birth cohort Malin Barman, Anna Sandin, Agnes Wold, Ann‐Sofie Sandberg PD18 Evolution of the IgE response to house dust mite molecules in childhood Daniela Posa, Serena Perna, Carl‐Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, Ulrich Wahn, Thomas Keil, Susanne Lau, Kuan‐Wei Chen, Yvonne Resch, Susanne Vrtala, Rudolf Valenta, Paolo Maria Matricardi PD19 Antibody recognition of nsLTP‐molecules as antigens but not as allergens in the German‐MAS birth cohort Olympia Tsilochristou, Alexander Rohrbach, Antonio Cappella, Stephanie Hofmaier, Laura Hatzler, Carl‐Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, RaffaeleD'Amelio, Ulrich Wahn, Thomas Keil, Susanne Lau, Paolo Maria Matricardi PD20 Early life colonization with Lactobacilli and Staphylococcus aureus oppositely associates with the maturation and activation of FOXP3+ CD4 T‐cells Sophia Björkander, Maria A. Johansson, Gintare Lasaviciute, Eva Sverremark‐Ekström PD21 Genome‐wide meta‐analysis identifies 7 susceptibility loci involved in the atopic march Ingo Marenholz, Jorge Esparza‐Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P. Strachan, Ben D. Spycher, Hansjörg Baurecht, Patricia Margaritte‐Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C Matheson, Jin Li, Sven Michel, Wei Q. Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C. de Jongste, Dirkje S Postma, Charlotte Braun‐Fahrländer, Elisabeth Horak, Ludmila M. Ogorodova, Valery P. Puzyrev, Elena Yu Bragina, Thomas J Hudson, Charles Morin, David L Duffy, Guy B Marks, Colin F Robertson, Grant W Montgomery, Bill Musk, Philip J Thompson, Nicholas G. Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster‐Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M Nöthen, Craig E Pennell, Peter D Sly, Carsten O Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G. Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel AR Ferreira, Catherine Laprise, Maxim B. Freidin, Jon Genuneit, Gerard H Koppelman, Erik Melén, Marie‐Hélène Dizier, A. John Henderson, Young Ae Lee POSTER DISCUSSION SESSION 4: Food allergy—Anaphylaxis (PD22–PD26) PD22 Atopy patch test in food protein induced enterocolitis caused by solid food Purificacion González‐Delgado, Esther Caparrós, Fernando Clemente, Begoña Cueva, Victoria M. Moreno, Jose Luis Carretero, Javier Fernández PD23 Watermelon allergy: a novel presentation Kate Swan, George Du Toit PD24 A pilot study evaluating the usefulness of a guideline template for managing milk allergy in primary care Mudiyur Gopi, Tim Smith, Edara Ramesh, Arun Sadasivam PD26 Efficacy and safety of cow's milk oral immunotherapy protocol Inês Mota, Filipe Benito Garcia, Susana Piedade, Angela Gaspar, Graça Sampaio, Cristina Arêde, Luís Miguel Borrego, Graça Pires, Cristina Santa‐Marta, Mário Morais‐Almeida POSTER DISCUSSION SESSION 5: Prevention and treatment—Allergy (PD27–PD36) PD27 Allergy‐protection by the lactic acid bacterium Lactococcus lactis G121: mode‐of‐action as revealed in a murine model of experimental allergy Stephanie Brand, Karina Stein, Holger Heine, Marion Kauth PD29 The relationship between quality of life and morning salivary cortisol after acute bronchiolitis in infancy Leif Bjarte Rolfsjord, Egil Bakkeheim, Johan Alm, Håvard Ove Skjerven, Kai‐Håkon Carlsen, Jon Olav Hunderi, Teresa Løvold Berents, Petter Mowinckel, Karin C. Lødrup Carlsen PD30 Randomised trial of the efficacy of MP29‐02* compared with fluticasone propionate nasal spray in children aged ≥6 years to <12 years with allergic rhinitis Ulrich Wahn, Ullrich Munzel, William Berger PD31 10 mg of oral bilastine in 2 to 11 years old children has similar exposure to the adult therapeutic dose (20 mg) Ulrich Wahn, Román Valiente, Valvanera Vozmediano, John C. Lukas, Mónica Rodríguez PD33 Daily symptoms, nocturnal symptoms, activity limitations and reliever therapies during the three steps of IOEASMA programme: a comparison Sebastiano Guarnaccia, Luigi Vitale, Ada Pluda, Emanuele D'Agata, Denise Colombo, Stefano Felici, Valeria Gretter, Susanna Facchetti, Gaia Pecorelli, Cristina Quecchia PD34 Sensitisation to an inert aeroallergen in weaning rats and longstanding disease, in a sensitisation‐tolerant and easily tolerisable rodent strain George Guibas, Evangelia Spandou, Spyridon Megremis, Peter West, Nikolaos Papadopoulos PD35 Bacterial and fungi exposure in school and allergic sensitisation in children João Cavaleiro Rufo, Joana Madureira, Inês Paciência, Lívia Aguiar, Patrícia Padrão, Mariana Pinto, Luís Delgado, Pedro Moreira, João Paulo Teixeira, Eduardo Oliveira Fernandes, André Moreira PD36 Comparative study of allergy rhinitis between two populations: children vs. adults Adriana Izquierdo Dominguez, Antonio Valero, Joaquim Mullol, Alfonso Del Cuvillo, Javier Montoro, Ignacio Jauregui, Joan Bartra, Ignacio Davila, Marta Ferrer, Joaquin Sastre POSTER VIEWING SESSION 1: Inflammation—Genetics—Immunology—Dermatology (PP01–PP09) PP01 Immune profile in late pregnancy: immunological markers in atopic asthmaticwomen as risk factors for atopy in the progeny Catarina Martins, Jorge Lima, Maria José Leandro, Glória Nunes, Jorge Cunha Branco, Hélder Trindade, Luis Miguel Borrego PP02 The impact of neonatal sepsis on development of allergic diseases Secil Conkar, Mehtap Kilic, Canan Aygun, Recep Sancak PP03 Clinical overview of selective IgE deficiency in childhood Athina Papadopoulou, Eleni Tagalaki, Lambros Banos, Anna Vlachou, Fotini Giannoula, Despina Mermiri PP04 Inverse relationship between serum 25(ΟΗ) vitamin D3 and total IgE in children and adolescence Athina Papadopoulou, Stavroula Lampidi, Marina Pavlakou, Maria Kryoni, Kostas Makris PP05 PP06 PP07 Asthma control questionnaire and specific IgE in children Snezhina Lazova, Guergana Petrova, Dimitrinka Miteva, Penka Perenovska PP08 Features of chronic urticaria of adolescents Aliya Klyucharova, Olesya Skorohodkina PP09 Cutaneous mastocytosis in children: a clinical analysis of 8 cases in Greece Dimitra Koumaki, Alkisti Manousaki, Maria Agrapidi, Lida Iatridou, Omima Eruk, Konstantinos Myridakis, Emmanouil Manousakis, Vasiliki Koumaki POSTER VIEWING SESSION 2: Food allergy—Anaphylaxis (PP10–PP47) PP10 Prognostic factors in egg allergy Maria Dimou, Maria Ingemansson, Gunilla Hedlin PP11 Evaluation of the efficacy of an amino acid‐based formula in infants who are intolerant to extensively hydrolysed protein formula Nitida Pastor, Delphine de Boissieu, Jon Vanderhoof, Nancy Moore, Kaitlin Maditz PP12 Anaphylaxis and epinephrine auto‐injector use: a survey of pediatric trainees Adeli Mehdi, Shaza Elhassan, Carolin Beck, Ahmed Al‐Hammadi PP13 Anaphylaxis in children: acute management in the Emergency Department Ioana Maris, Ronan O'Sullivan, Jonathan Hourihane, PP14 Understanding Cumbrian schools preparedness in managing children at risk of anaphylaxis in order to provide training and support which will create healthy and safe environments for children with allergies George Raptis, Louise Michaelis PP15 A new valid and reliable parent and child questionnaire to measure the impact of food protein enterocolitis syndrome on children: the FPIES Quality of Life Questionnaire (FPIESQL), Parent and Child Short Form Audrey DunnGalvin, Matthew Greenhawt, Carina Venter, Jonathan Hourihane PP16 An in‐depth case study investigation of the experiences of teenagers and young adults in growing up and living with food allergy with emphasis on coping, management and risk, support, and social and self‐identity Evelyn O'Regan, Duncan Cronin, Jonathan Hourihane, Anna O'Reilly, Audrey DunnGalvin PP17 Cow's milk protein allergy in Constantine. A retrospective study of 62 cases between 1996 and 2013 Foued Abdelaziz, Dounia Khelifi‐Touhami, Nihad Selim, Tahar Khelifi‐Touhami PP18 PP19 Cow's milk and egg oral immunotherapy in children older than 5 years Pablo Merida, Ana Mª Plaza, Juan Heber Castellanos, Adrianna Machinena, Montserrat Alvaro Lozano, Jaime Lozano, Olga Dominguez, Monica Piquer, Rosa Jimenez, Mª Teresa Giner PP20 Professionals' awareness of management of Cow's Milk Protein Allergy (CMPA) in North Wales Hospitals Konstantinos Kakleas, Manohar Joishy, Wendmu Maskele, Huw R. Jenkins PP21 PP22 Anaphylaxis: the great unknown for teachers. Presentation of a protocol for schools Mercedes Escarrer, Agustín Madroñero, Maria Teresa Guerra, Juan Carlos Julia, Juan Carlos Cerda, Javier Contreras, Eulalia Tauler, Maria Jesus Vidorreta, Ana Rojo, Silvia Del Valle PP23 Challenges facing children with food allergies and their parents in out of school activity sectors Niamh Flynn PP24 A review of food challenges at a Regional Irish Centre Gary Foley, Carol Harmon, John Fitzsimons PP25 The use of epinephrine in infants with anaphylaxis Krasimira Baynova, Ávila Maria Del Robledo, Labella Marina PP26 PP27 PP28 Mother's psychological state predicts the expression of symptoms in food allergic children Aaron Cortes, Alicia Sciaraffia, Angela Castillo PP29 The correlation between sIgE towards tree nuts and birch pollen in a Danish Pediatric Allergy Clinic Nanna Juel‐Berg, Kirsten Skamstrup Hansen, Lars Kærgaard Poulsen PP30 Food allergy in children: evaluation of parents' use of online social media Andreia Florina Nita, Ioana Valentina Nenciu, Adina Lazar, Dumitru Oraseanu PP31 The impact of food allergy on quality of life: FAQLQ questionnaire Rita Aguiar, Anabela Lopes, Maria J. Paes, Amélia S. Santos, M. A. Pereira‐Barbosa PP32 An unexpected cause of anaphylaxis: potato Hatice Eke Gungor, Salih Uytun, Umit Murat Sahiner, Yasemin Altuner Torun PP33 Is it clinical phenotype of allergic diseases determined by sensitisation to food? Mirjana Zivanovic, Marina Atanasković‐Marković PP34 PP35 Prescribing adrenaline auto‐injectors in children in 2014: the data from regional pediatricians Tina Vesel, Mihaela Nahtigal, Andreja Obermayer‐Temlin, Eva Šoster Križnik, Mirjana Maslar, Ruben Bizjak, Marjeta Tomšič‐Matic, Sonja Posega‐Devetak, Maja Skerbinjek‐Kavalar, Mateja Predalič, Tadej Avčin PP36 Who should have an adrenaline autoinjector? Adherence to the European and French guidelines among 121 allergists from the Allergy Vigilance Network Guillaume Pouessel, Etienne Beaudouin, Anne M. Moneret‐Vautrin, Antoine Deschildre, Allergy Vigilance Network PP37 Anaphylaxis by Anacardium Occidentale Marta Viñas, Bartolomé Borja, Nora Hernández, Mª José Castillo, Adriana Izquierdo, Marcel Ibero PP38 Anaphylaxis with honey in a child S. Tolga Yavuz, Ali Gungor, Betul Buyuktiryaki, Ozan Koc, Can Naci Kocabas, Faysal Gok PP39 Evaluation of courses adopted to children on prevention, recognition and management of anaphylaxis Tina Vesel, Mihaela Nahtigal PP40 Symptomatic dust mites and shrimp allergy: three pediatric case reports Filipa Almeida, Susana Lopes, Cristina Madureira, Tânia Lopes, Fernanda Carvalho PP41 Poor identification rates of nuts by high risk individuals: a call for improved education and support for families Camille Heming, Emily Garrett, Adam Blackstock, Santanu Maity, Rahul Chodhari PP42 DAFALL: database of food allergies in the Czech Republic Simona Belohlavkova, Eliska Kopelentova, Petr Visek, Ivana Setinova, Ivana Svarcova PP43 Serological cross‐reactivity between grass and wheat is not only caused by profilins and CCDs Sigrid Sjölander, Nora Nilsson, Malin Berthold, Helena Ekoff, Gunilla Hedlin, Magnus Borres, Caroline Nilsson PP44 Oil body associated proteins in children with nuts allergy. Allergens to consider in IgE‐mediated nuts allergy Loreto González Domínguez, Cristina Muñoz Archidona, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire PP45 PP46 Protective effect of helicobacter pylori infection against food allergy in children Olga Vrani, Antigone Mavroudi, Maria Fotoulaki, Maria Emporiadou, Kleomenis Spiroglou, Ioannis Xinias PP47 Anaphylaxis pathway: A road tryp‐tase to success? Helyeh A. Sadreddini, Mia Warnes, Donna Traves POSTER VIEWING SESSION 3: Miscellaneous (PP48–PP58) PP48 Surveillance study on safety of SLIT in pediatric population Ivana Djuric‐Filipovic, Zorica Zivkovic, Snežana Zivanovic, Gordana Kostić, Đorđe Filipovic PP49 Efficacy and safety of mixed mite subcutaneous immunotherapy among allergic rhinitis patients in the Northeastern Thailand Sawapon Sittisomwong, Siripong Sittisomwong PP50 Effect of inhaled beclomethasone or placebo on brain stem activity in a patient chronically treated with steroids: preliminary report Zygmunt Podolec, Marcin Hartel, Daria Panek, Magdalena Podolec‐Rubiś, Tomasz Banasik PP51 Sensitisation to aeroallergens in patients with allergic rhinitis, asthma and atopic dermatitis in Shiraz, Southwestern Iran Elham Abbasi, Mozhgan Moghtaderi PP52 Referring a child for allergy test: how appropriate are we? Phani Sanneerappa, Alina Deliu, Moosa Kutty, Nagabathula Ramesh PP53 EBV lymphoproliferative disease and cardiac lymphoma in a STK4 deficient patient Roya Sherkat, Mohammad Reza Sabri, Bahar Dehghan, Hamid Bigdelian, Nahid Raeesi, Mino Afshar, Hamid Rahimi, Christoph Klein PP54 A case study: the effect of massive honeybees attack on various body parameters atopic girl including allergy Mohemid Al‐Jebouri PP55 The role of TLR9, NLRP3 and proIL‐1β in activation of antiviral innate immunity Oxana A. Svitich, Daria O. Zubacheva, Dmitrii A. Potemkin, Ludmila V. Gankovskaya, Vitalii V. Zverev PP56 Overnight pulse oximetry, as a screening tool to diagnose obstructive sleep apnoea. How effective is it? Phani Sanneerappa, Elaine OB Doyle, Paul Gallagher, Nagabathula Ramesh PP57 The presentation and management of acute urticaria and allergic reactions in children in a multi‐ethnic, inner city Emergency Department (ED) Sherine Dewlett, Kin Man, Minal Gandhi, James Pocock, Anna Gerrardhughes PP58 Food allergens responsible for delayed‐type sensitisation in atopy patch test in children diagnosed with autism spectrum disorder Jolanta Wasilewska, Maciej Kaczmarski, Dariusz Lebensztejn POSTER VIEWING SESSION 4: Asthma—Rhinitis (PP59–PP87) PP59 Systematic review of incense as a trigger factor for asthma Chandramani Thuraisingham, Davendralingam Sinniah PP60 Increased risks of mood and anxiety disorders in children with asthma Yue Chen, Xiaomei Mei PP61 PP62 Asthma Control Test (ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) association in children Sebnem Ozdogan, Pinar Karadeniz, Durdugul Ayyildiz‐Emecen, Ummuhan Oncul PP63 Seasonal and gender variations in vitamin D levels in children with asthma and its association with pulmonary function tests Sebnem Ozdogan, Gizem Sari, Sabanur Cavdar PP64 Defining treatment response in childhood asthma: rationale and design of the Pharmacogenomics in the Childhood Asthma (PiCA) consortium Niloufar Farzan, Susanne J. Vijverberg, Colin J. Palmer, Kelan G. Tantisira, Anke‐Hilseon Maitland‐van der Zee behalf of the PiCA consortium PP65 Prevalence of asthma and allergic disease in patients with inflammatory disease compared to celiac disease Fatma Yavuzyilmaz, Sebnem Ozdogan, Nafiye Urganci, Merve Usta PP66 A severe case with cystic fibrosis (CF) asthma Mehmet Hoxha, Maksim Basho PP67 Severe asthma exacerbation complicated with pneumothorax in a child with uncontrolled asthma due to poor treatment compliance Ioana Valentina Nenciu, Andreia Florina Nita, Adina Lazar, Alexandru Ulmeanu, Carmen Zapucioiu, Dumitru Oraseanu PP68 Evaluation of the Pediatric Quality of Life inventory (PedsQL) asthma module among low income asthmatic children and adolescents in Sao Paolo, Brazil Gustavo F. Wandalsen, Fernanda Monteiro, Dirceu Solé PP69 Early initiation of specific immunotherapy in asthma patients leads to higher benefits Blerta Lame, Eris Mesonjesi, Arjeta Sherri PP70 Treatment resistant asthma and rhinosinusitis with recurrent pulmonary infections. Is it primary ciliary dyskinesia? Alkerta Ibranji, Laert Gjati, Gjustina Loloci, Ardii Bardhi PP71 The comparison of sensitisation to animal allergens in children‐ and adult‐ onset patients with asthma Behnam Moghtaderi, Shirin Farjadian, Dorna Eghtedari PP72 Characterisation of children less than five years with wheezing episodes in Cali, Colombia Manuela Olaya, Laura Del Mar Vasquez, Luis Fernando Ramirez, Carlos Daniel Serrano PP73 Evaluation of the patients with recurrent croup Belgin Usta Guc, Suna Asilsoy, Fulya Ozer PP74 Obesity in adolescence compromising the asthma control Guergana Petrova, Sylvia Shopova, Vera Papochieva, Snezhina Lazova, Dimitrinka Miteva, Penka Perenovska PP75 Sleep behavior in children with persistent allergic rhinitis Gustavo F. Wandalsen, Jessica Loekmanwidjaja, Márcia Mallozi, Dirceu Solé PP76 Randomised trial of the safety of MP29‐02* compared with fluticasone propionate nasal spray in children aged ≥4 years to <12 years with allergic rhinitis William Berger, Ulrich Wahn, Paul Ratner, Daniel Soteres PP77 Safety and tolerability evaluation of bilastine 10 mg in children from 2 to 11 years of age with allergic rhinoconjunctivitis or urticaria Zoltán Novák, Anahí Yáñez, Kiss Ildikó, Piotr Kuna, Miguel Tortajada, Román Valiente, the Bilastine Pediatric Safety Study Group PP78 Sensitisation to Alternaria alternata: Is it a risk factor for severe rhinitis? Susana Lopes, Filipa Almeida, Tânia Lopes, Cristina Madureira, José Oliveira, Fernanda Carvalho PP79 Validation of the Patient Benefit Index (PBI) for the assessment of patient‐related outcomes in allergic rhinitis in children Julia Feuerhahn, Christine Blome, Meike Hadler, Efstrathios Karagiannis, Anna Langenbruch, Matthias Augustin PP80 Efficacy of sublingual tablet of house dust mite allergen extracts in adolescents with house dust mite‐associated allergic rhinitis Michel Roux, Shinji Kakudo, Efstrathios Karagiannis, Robert K. Zeldin PP81 Lung function improvement in a child treated with omalizumab for bronchial asthma Anna Sokolova, Tiago Milheiro Silva PP82 How to treat a child suffering from asthma, allergic rhinitis, allergy to peanuts and diabetes at the same time? Snezana S. Zivanovic, Vesna Cvetkovic, Ivana Nikolic, Sonja J. Zivanovic PP83 Nitric oxide in exhaled air in the relationship of the degree of sensitisation to aeroallergens Snezana S. Zivanovic, Ljiljana Saranac, Ivana Nikolic, Sonja J. Zivanovic, Zorica Zivkovic PP84 Clinical basis of diagnostic errors in pediatric asthma Zoia Nesterenko PP85 PP86 Childhood asthma control in Serbia and organised Asthma Educational Intervention (AEI) Snezana Radic, Branislava Milenkovic, Spomenka Smiljanic, Milka Micic‐Stanijevic, Olivera Calovic PP87 Experience from a group of adolescents with severe allergic asthma treated with Omalizumab Anne Marie Bro Hofbauer, Lone Agertoft THEMATIC POSTER SESSION 1: Prevention and Treatment—Epidemiology (TP01–TP18) TP01 A cost effective primary school asthma education program: pilot study from inner London schools Lucy Everson, Jessica Kearney, Jonny Coppel, Simon Braithwaite, Rahul Chodhari TP02 The prevalence of allergic diseases among 14–15 years old adolescents in two Danish birth cohorts 14 years apart Elisabeth S. Christiansen, Henrik Fomsgaard Kjaer, Esben Eller, Charlotte G. Mørtz, Susanne Halken TP03 Does pattern of sensitisation to phleum pratense change with age? Is it different in children with allergic rhinitis or asthma? Cristina Román India, Ana Moreira Jorge, Loreto González Domínguez, Cristina Muñoz Archidona, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Juana Jiménez Jiménez, Luis Echeverría Zudaire TP04 Practicalities of prevention of peanut allergy: modelling a national response to LEAP Cathal O'Connor, Jonathan Hourihane TP05 Comparison of the influence of sunflower seed oil and skin care lotion on the skin barrier function of newborns: a randomised controlled trial Varvara Kanti, Lena Lünnemann, Günther Malise, Laine Ludriksone, Andrea Stroux, Wolfgang Henrich, Michael Abu‐Dakn, Ulrike Blume‐Peytavi, Natalie Garcia Bartels TP06 The effect of daily skin care on skin barrier properties in infants with dry skin and risk for atopic dermatitis Varvara Kanti, Lena Lünnemann, Laine Ludriksone, Marianne Schario, Andrea Stroux, Ulrike Blume‐Peytavi, Natalie Garcia Bartels TP07 Change in sum total aeroallergen skin prick test wheal diameters at 6 months predicts which children will respond to subcutaneous immunotherapy by three years Thorsten Stanley, Nicolien Brandenbarg TP08 Are mobile apps regarding adrenaline auto‐injectors accessed by adolescents for support and education in the community? Alia Boardman, Gary McGreevy, Emily Rodger, Katherine Knight, Victoria Timms, Trisha Taylor, Gemma Scanlan, Roisin Fitzsimons TP09 TP10 Prevention of early atopic dermatitis among low‐atopy‐risk infants by immunoactive prebiotics is not sustained after the first year of life Grüber Christoph, Ulrich Wahn, Margriet van Stuivenberg, Fabio Mosca, Guido Moro, Gaetano Chirico, Christian P. Braegger, Joseph Riedler, Yalcin Yavuz, Günther Boehm TP11 TP12 TP13 Treatment with Omalizumab in a 16‐year‐old Caucasian girl with refractory solar urticaria Stefania Arasi, Giuseppe Crisafulli, Lucia Caminiti, Federica Porcaro, Giovanni Battista Pajno TP14 Ultra‐pure soft water ameliorates skin conditions of adult and child patients with atopic dermatitis Akane Tanaka, Yaei Togawa, Kumiko Oida, Naotomo Kambe, Peter Arkwright, Yosuke Amagai, Naoki Shimojo, Yasunori Sato, Hiroyuki Mochizuki, Hyosun Jang, Saori Ishizaka, Hiroshi Matsuda TP15 Potential adjuvant effect of immunomodulator to improve specific immunotherapy in asthmatic child Wisnu Barlianto, Ery Olivianto, H. M. S. Chandra Kusuma TP16 How can Component Resolved Diagnosis (CRD) influence in Specific Immunotherapy (SIT) prescription, in a Spanish children population Ana Moreira Jorge, Cristina Román India, Loreto González Domínguez, Cristina Muñoz Archidona, Juana Jiménez Jiménez, Teresa Bracamonte Bermejo, Sergio Quevedo Teruel, Luis Echeverría Zudaire TP17 Mitochondrial dysfunction in food allergy: effects of L. rhamnosus GG in a mice model of peanut allergy Rosita Aitoro, Mariapia Mollica, Roberto Berni Canani, Giovanna Trinchese, Elena Alfano, Antonio Amoroso, Lorella Paparo, Francesco Amato, Claudio Pirozzi, Antonio Calignano, Rosaria Meli TP18 Prediction of atopic diseases in childhood: elevated blood eosinophils in infancy in a high risk birth cohort Siri Rossberg, Kerstin Gerhold, Kurt Zimmermann, Mohammad Zaino, Thomas Geske, Eckard Hamelmann, Susanne Lau THEMATIC POSTER SESSION 2: Food allergy—Anaphylaxis (TP19–TP38) TP19 TP20 TP21 Double‐blind provocation tests in non‐IgE mediated cow's milk allergy and the occurrence of placebo reactions Sarah Bogovic, Jochem van den Berg, Chantal Janssen TP22 Gradual introduction of baked egg (BE) in egg allergic patients under 2 years old Angela Claver TP23 Randomised controlled trial of SOTI with raw hen's egg in children with persistent egg allergy I: safety and efficacy of daily vs. weekly protocols of induction Mª Flor Martin‐Muñoz, C. Martorell, M. T. Belver, E. Alonso Lebrero, L. Zapatero, V. Fuentes, M. Piqué, A. Plaza, C. Muñoz, A. Martorell, Cristina Blasco, B. Villa, C. Gómez, S. Nevot, J. M. García, L. Echeverria TP24 Randomised controlled trial of SOTI with raw hen's egg in children with persistent egg allergy II: a randomised controlled trial to study a safer, more effective and easy to perform maintenance (daily vs. every two days) pattern of egg SOTI Mª Flor Martin‐Muñoz, C. Martorell, M. T. Belver, E. Alonso Lebrero, L. Zapatero, V. Fuentes, M. Piqué, A. Plaza, C. Muñoz, A. Martorell, Cristina Blasco, B. Villa, C. Gómez, S. Nevot, J. M. García, L. Echeverria TP25 Determining the safety of baked egg home reintroduction for children with mild egg allergy Brenda DeWitt, Judith Holloway, Donald Hodge TP26 Demographics, investigations and patterns of sensitisation in children with oral allergy syndrome in a London Teaching Hospital Sian Ludman, Merhdad Jafari‐Mamaghani, Rosemary Ebling, Adam T. Fox, Gideon Lack, George Du Toit TP27 Airborne peanut challenge in children: allergic reactions are rare Sofia Lovén Björkman, Caroline Nilsson, Natalia Ballardini TP28 The nutty question on Pediatric Wards: to be or "nut" to be? Supriyo Basu, Jenny Hallet, Jyothi Srinivas TP29 TP30 TP31 Allergy education in nursery schools Hazel Stringer, Nicola Jay TP32 Food allergy in the first year of life Tânia Lopes, Cristina Madureira, Filipa Almeida, Susana Lopes, Paula Fonseca, Clara Vieira, Fernanda Carvalho TP33 Prevalence and geographic distribution of oral allergy syndrome in Italian children: a multicenter study Carla Mastrorilli, Carlo Caffarelli, Riccardo Asero, Salvatore Tripodi, Arianna Dondi, Gianpaolo Ricci, Carlotta Povesi Dascola, Elisabetta Calamelli, Francesca Cipriani, Andrea Di Rienzo Businco, Annamaria Bianchi, Paolo Candelotti, Tullio Frediani, Carmen Verga, Paolo Maria Matricardi TP34 Are common standardised allergen extracts used in skin test enough in the diagnosis of nuts allergy? Cristina Muñoz Archidona, Loreto González Domínguez, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire TP35 Evaluation of IgE sensitisation in children with allergic proctocolitis and its relationship to atopic dermatitis Despina Mermiri, Paraskevi Korovessi, Skevi Tiliakou, Evaggelia Tavoulari, Kalliopi‐Maria Moraiti, Fotini Giannoula, Athina Papadopoulou TP36 Food allergy in children: are we managing them appropriately in the Emergency Department? Wan Jean Tee, Samir Deiratany, Raymond Seedhoo, Roisin McNamara, Ike Okafor TP37 Importance of oil body associated allergenic proteins in nuts suspected allergy children Loreto González Domínguez, Ana Moreira Jorge, Cristina Muñoz Archidona, Teresa Bracamonte Bermejo, Sergio Quevedo Teruel, Fernando Pineda de la Losa, Miriam Castillo Fernández, Luis Ángel Echeverría Zudaire TP38 Practical application of basophil activation test in children with food allergy Ekaterina Khaleva, Gennady Novic, Natalia Bychkova THEMATIC POSTER SESSION 3: Asthma (TP39–TP57) TP39 Effect of corticosteroid therapy upon serum magnesium level in chronic asthmatic children Amany Abd Al‐Aziz, Amany Fatouh, Ayat Motawie, Eman El Bostany, Amr Ibrahim TP40 ADAM33 in Bulgarian children with asthma Guergana Petrova, Dimitrinka Miteva, Snezhina Lazova, Penka Perenovska, Sylvia Andonova, Alexey Savov TP41 TP42 The impact of vitamin D serum levels in asthma and allergic rhinitis Maria Zoto, Marialena Kyriakakou, Paraskevi Xepapadaki, Nikolaos G. Papadopoulos TP43 Life‐threatening, first reported, paradoxical bronchospasm after nebulised Salbutamol in a 10 year old child Paraskevi Korovessi, Mariza Vassilopoulou, Athina Balaska, Lambros Banos, Stavroula Kostaridou, Despina Mermiri TP44 TP45 Asthma symptoms in children with treatment for allergic rhinoconjunctivitis Jorien Wartna, Arthur M. Bohnen, Gijs Elshout, David H. J. Pols, Patrick J. E. Bindels Erasmus MC, Rotterdam, The Netherlands TP46 Atopy increased the risk of developing exercise‐induced bronchoconstriction in young athletes Sven F. Seys; Ellen Dilissen, Sarah Van der Eycken, An‐Sofie Schelpe, Gudrun Marijsse, Thierry Troosters, Vincent Vanbelle, Sven Aertgeerts, Jan L. Ceuppens, Lieven J. Dupont, Koen Peers, Dominique M. Bullens TP47 The effect of higher BMI on risk for asthma and treatment outcome in overweight and obese children Ivana Banic, Sandra Bulat Lokas, Jelena Zivkovic, Boro Nogalo, Iva Mrkic Kobal, Davor Plavec, Mirjana Turkalj TP48 TP49 TP50 TP51 TP52 The impact of a multidisciplinary project intended to change the culture of nebulisers towards pressurised metered dose inhalers Georgeta Oliveira, Katharine Pike, Alda Melo, Tomás Amélia, José Carlos Cidrais Rodrigues, Cristina Serrano, José Manuel Lopes dos Santos, Carla Lopes TP53 TP54 TP55 TP56 Increased asthma control in patients with severe persistent allergic asthma after 12 month of nightly temperature controlled laminar airflow (TLA) Eckard Hamelmann, Uwe Schauer, Karl‐Christian Bergmann TP57 THEMATIC POSTER SESSION 4: Drug allergy—Dermatology (TP58–TP77) TP58 Should we proceed directly to provocation challenges to diagnose drug allergy? Our experience says yes Luis Moral, Teresa Toral, Nuria Marco, Beléns García Avilés, Mª Jesús Fuentes, Jesús Garde, Cristina Montahud, Javier Perona, Mª José Forniés TP59 Anaphylaxis to 13‐valent pneumococcal vaccine Esozia Arroabarren, Marta Anda, Maria Luisa Sanz, Maria Teresa Lizaso, Candida Arregui TP60 Intrapartum antibiotic exposure for treatment of group B streptococcus was not associated with the development of penicillin allergy in children Sara May, Martha Hartz, Avni Joshi, Miguel A. Park TP61 Evaluation of suspected drug hypersensitivity reactions in 169 children referred to the General Hospital Sonja Posega Devetak, Tina Vesel, Anja Koren Jeverica, Tadej Avčin TP62 Drug provocation testing: experience of a tertiary hospital Leonor Castro, Carolina Gouveia, Ana Carvalho Marques, Antonio Jorge Cabral TP63 Perioperative anaphylaxis: a growing concern in pediatric population Luis Amaral, Fabrícia Carolino, Eunice Castro, Madalena Passos, Josefina R. Cernadas TP64 Raising awareness of hypersensitivity to non‐steroidal anti‐inflammatory drugs in the pediatric age Fabrícia Carolino, Luís Amaral, Eunice Dias de Castro, Josefina R. Cernadas TP65 Perioperative anaphylaxis in young children: how to confirm the suspicion Josefina R. Cernadas, Fabrícia Carolino, Luís Amaral, Fernando Pineda, Armanda Gomes TP66 A case study of a child suspected to be penicillin allergic‐digging deeper Katherine Knight, Roisin Fitzsimons, Helen Brough TP67 Prevalence, characteristics and risk factors of hypersensitivity reactions to antibiotics in patients with cystic fibrosis Jobst Röhmel, Carsten Schwarz, Anne Mehl, Philippe Stock, Doris Staab TP68 Antibiotic drug hypersensitivity in cystic fibrosis: A pilot study using cellular allergy tests for diagnostics Jobst Röhmel, Carsten Schwarz, Christine Seib, Doris Staab, Philippe Stock TP69 Oral antibiotics challenges in children Anita Critchlow, Alyson Barber, Nicola Jay TP70 Hypersensitivity reaction to vancomycin: a new successful desensitization protocol Belen Delavalle, Teresa Garriga, Blanca Vilá, Cristina Blasco TP71 TP72 Clinical phenotypes according to FLG gene loss of function mutations in children with atopic dermatitis Francesca Cipriani, Annalisa Astolfi, Costanza Di Chiara, Elisabetta Calamelli, Iria Neri, Annalisa Patrizi, Gianpaolo Ricci TP73 TP74 Urticaria in children: clinical and epidemiological features Katerina Neskorodova, Asya Kudryavtseva TP75 TP76 Acute urticaria at the Pediatrics Emergency Department: is it allergy? Esozia Arroabarren, Jorge Alvarez, Marta Anda, Miriam Palacios, Marta Martinez‐Merino, Ibone Vaquero TP77 [ABSTRACT FROM AUTHOR]

ELECTRONIC health records, ACUTE leukemia, HEMORRHAGE, HEMOGLOBINS, and BLOOD transfusion

Introduction: Electronic health care data offers the opportunity to study rare events, although detecting these events in large datasets remains difficult. We aimed to develop a model to identify leukemia patients with major hemorrhages within routinely recorded health records. Methods: The model was developed using routinely recorded health records of a cohort of leukemia patients admitted to an academic hospital in the Netherlands between June 2011 and December 2015. Major hemorrhage was assessed by chart review. The model comprised CT-brain, hemoglobin drop, and transfusion need within 24 hours for which the best discriminating cut off values were taken. External validation was performed within a cohort of two other academic hospitals. Results: The derivation cohort consisted of 255 patients, 10,638 hospitalization days, of which chart review was performed for 353 days. The incidence of major hemorrhage was 0.22 per 100 days in hospital. The model consisted of CT-brain (yes/no), hemoglobin drop of ≥0.8 g/dl and transfusion of ≥6 units. The C-statistic was 0.988 (CI 0.981–0.995). In the external validation cohort of 436 patients (19,188 days), the incidence of major hemorrhage was 0.46 per 100 hospitalization days and the C-statistic was 0.975 (CI 0.970–0.980). Presence of at least one indicator had a sensitivity of 100% (CI 95.8–100) and a specificity of 90.7% (CI 90.2–91.1). The number of days to screen to find one case decreased from 217.4 to 23.6. Interpretation: A model based on information on CT-brain, hemoglobin drop and need of transfusions can accurately identify cases of major hemorrhage within routinely recorded health records. [ABSTRACT FROM AUTHOR]

EXPERT evidence and PART-time employment

Background First-line afatinib significantly improved median progression-free survival (PFS) in pts with EGFRm+ NSCLC vs chemotherapy (CT) in LUX-Lung (LL) 3/6 (HR [95% CI]: 0.58 [0.43, 0.78]/0.28 [0.20, 0.39]), and vs gefitinib in LL7 (0.73 [0.57, 0.95]). We conducted a phase IIIb study of afatinib in a broader patient population, similar to real-world practice, of treatment-naïve or CT pre-treated pts with EGFRm+ NSCLC. Here we present an interim analysis. Methods EGFR TKI-naïve pts with locally advanced/metastatic EGFRm+ NSCLC and ECOG PS 0–2 received afatinib 40 mg/day; dose reduction was permitted (min. 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was assessed and post-hoc subgroup analysis conducted. Results 479 pts were included (data cut-off: 30/04/18): Caucasian/Asian: 97%/2%; female: 66%; 1st/2nd/≥3rd-line therapy: 78%/17%/5%; ECOG PS 0 or 1/2: 92%/8%; brain metastases: 17%; common/uncommon [C/U] mutations: 87%/13%. Median time on afatinib: 359 days. Objective response rate: 46%. Disease control rate: 86%. Median time to symptomatic progression (TTSP) and PFS were 14.9 (95% CI: 13.8, 17.6) and 13.4 (11.8, 14.5); subgroup analysis is in the table. Most common grade ≥3 afatinib-related AEs were diarrhea (16%) and rash (11%). AEs led to dose reduction in 258 (54%) pts (most frequently diarrhea 25%, rash 11%) and to afatinib discontinuation in 105 (22%) pts (malignant neoplasm progression 3%, diarrhea 3% [rash 0.8%]). Afatinib-related serious AEs occurred in 39 (8%) pts. Conclusions This analysis indicates a predictable and manageable safety profile for afatinib, consistent with the pivotal LL trials, and encouraging efficacy findings in this broad patient population. As expected, TTSP/PFS were longer for pts with ECOG PS 0/1 vs 2, and for pts with Del 19 or L858R mutations, vs those with uncommon mutations, which may be due to the high prevalence (44%) of pts with exon 20 insertions included in this study. Table: 482P   TTSP, mos   PFS, mos   Baseline characteristic (n)  Median  95% CI  Median  95% CI  Line of tx          1 (374)  15.6  14.1, 18.5  13.8  12.6, 15.2  2 (81)  14.7  11.3, 20.6  13.2  8.3, 17.7  ≥3 (24)  8.1  3.7, 14.4  6.6  3.2, 12.6  Mutations a           Del 19 b (232)  19.3  15.6, 21.8  15.9  13.9, 19.1  L858R b (162)  14.5  12.7, 17.9  13.1  11.5, 15.2  U c (84)  7.4  5.7, 9.0  6.0  4.2, 8.1  ECOG PS, inc. mutations          0–1 (442) a   15.8  14.4, 18.8  13.8  12.8, 15.2  C b (364)  18.2  15.5, 19.8  15.2  13.8, 17.7  U (77)  7.4  5.7, 9.7  6.6  4.6, 8.2  2 (36)  8.9  5.7, 13.2  6.2  2.5, 11.6  C b (30)  8.9  5.7, 13.9  7.7  3.9, 13.2  U (6)  7.0  0.9, 13.0  1.4  0.4, 6.0  Brain mets a           No (395)  15.8  14.1, 18.8  13.9  12.7, 15.5  Yes (83)  13.7  9.7, 17.2  10.1  8.2, 13.9    TTSP, mos   PFS, mos   Baseline characteristic (n)  Median  95% CI  Median  95% CI  Line of tx          1 (374)  15.6  14.1, 18.5  13.8  12.6, 15.2  2 (81)  14.7  11.3, 20.6  13.2  8.3, 17.7  ≥3 (24)  8.1  3.7, 14.4  6.6  3.2, 12.6  Mutations a           Del 19 b (232)  19.3  15.6, 21.8  15.9  13.9, 19.1  L858R b (162)  14.5  12.7, 17.9  13.1  11.5, 15.2  U c (84)  7.4  5.7, 9.0  6.0  4.2, 8.1  ECOG PS, inc. mutations          0–1 (442) a   15.8  14.4, 18.8  13.8  12.8, 15.2  C b (364)  18.2  15.5, 19.8  15.2  13.8, 17.7  U (77)  7.4  5.7, 9.7  6.6  4.6, 8.2  2 (36)  8.9  5.7, 13.2  6.2  2.5, 11.6  C b (30)  8.9  5.7, 13.9  7.7  3.9, 13.2  U (6)  7.0  0.9, 13.0  1.4  0.4, 6.0  Brain mets a           No (395)  15.8  14.1, 18.8  13.9  12.7, 15.5  Yes (83)  13.7  9.7, 17.2  10.1  8.2, 13.9  a Missing n = 1. b Del 19/L858R only. c Includes, n (%): ex 20 ins: 37 (44). Table: 482P   TTSP, mos   PFS, mos   Baseline characteristic (n)  Median  95% CI  Median  95% CI  Line of tx          1 (374)  15.6  14.1, 18.5  13.8  12.6, 15.2  2 (81)  14.7  11.3, 20.6  13.2  8.3, 17.7  ≥3 (24)  8.1  3.7, 14.4  6.6  3.2, 12.6  Mutations a           Del 19 b (232)  19.3  15.6, 21.8  15.9  13.9, 19.1  L858R b (162)  14.5  12.7, 17.9  13.1  11.5, 15.2  U c (84)  7.4  5.7, 9.0  6.0  4.2, 8.1  ECOG PS, inc. mutations          0–1 (442) a   15.8  14.4, 18.8  13.8  12.8, 15.2  C b (364)  18.2  15.5, 19.8  15.2  13.8, 17.7  U (77)  7.4  5.7, 9.7  6.6  4.6, 8.2  2 (36)  8.9  5.7, 13.2  6.2  2.5, 11.6  C b (30)  8.9  5.7, 13.9  7.7  3.9, 13.2  U (6)  7.0  0.9, 13.0  1.4  0.4, 6.0  Brain mets a           No (395)  15.8  14.1, 18.8  13.9  12.7, 15.5  Yes (83)  13.7  9.7, 17.2  10.1  8.2, 13.9    TTSP, mos   PFS, mos   Baseline characteristic (n)  Median  95% CI  Median  95% CI  Line of tx          1 (374)  15.6  14.1, 18.5  13.8  12.6, 15.2  2 (81)  14.7  11.3, 20.6  13.2  8.3, 17.7  ≥3 (24)  8.1  3.7, 14.4  6.6  3.2, 12.6  Mutations a           Del 19 b (232)  19.3  15.6, 21.8  15.9  13.9, 19.1  L858R b (162)  14.5  12.7, 17.9  13.1  11.5, 15.2  U c (84)  7.4  5.7, 9.0  6.0  4.2, 8.1  ECOG PS, inc. mutations          0–1 (442) a   15.8  14.4, 18.8  13.8  12.8, 15.2  C b (364)  18.2  15.5, 19.8  15.2  13.8, 17.7  U (77)  7.4  5.7, 9.7  6.6  4.6, 8.2  2 (36)  8.9  5.7, 13.2  6.2  2.5, 11.6  C b (30)  8.9  5.7, 13.9  7.7  3.9, 13.2  U (6)  7.0  0.9, 13.0  1.4  0.4, 6.0  Brain mets a           No (395)  15.8  14.1, 18.8  13.9  12.7, 15.5  Yes (83)  13.7  9.7, 17.2  10.1  8.2, 13.9  a Missing n = 1. b Del 19/L858R only. c Includes, n (%): ex 20 ins: 37 (44). Clinical trial identification NCT01853826. Editorial acknowledgement Christina Jennings of GeoMed, an Ashfield company, part of UDG Healthcare plc. Legal entity responsible for the study Boehringer Ingelheim. Funding Boehringer Ingelheim. Disclosure F. De Marinis: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Advisory / Consultancy: Takeda; Research grant / Funding (institution): Boehringer Ingelheim. M. Hochmair: Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Pfizer. M.R. Migliorino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: B.I.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: ROCHE; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: PFIZER. G.Z. Mukhametshina: Advisory / Consultancy: Association of oncologists of Russian Federation; Full / Part-time employment: State Autonomous Healthcare Institution «Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan». M. Schumacher: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca. S. Novello: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BI; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda. R. Dziadziuszko: Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb. W. Tang: Full / Part-time employment: Boehringer Ingelheim. L. Clementi: Full / Part-time employment: Boehringer Ingelheim Italia SpA. A. Cseh: Full / Part-time employment: Boehringer Ingelheim. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]