To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research.Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017.A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes.3) and central subfield thickness (CST) (μm).Volumes of segmented features . First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA.We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure–function correlations. These data will be made publicly available for replication and future investigation by the AMD research community. The advent of high-resolution in vivo OCT imaging has driven research to identify novel anatomic biomarkers in neovascular age-related macular degeneration (AMD).,,OCT-derived parameters such as central subfield thickness (CST) have been used to inform re-treatment decisions in clinical trials.,25Clinical trials such as Comparison of Age-Related Macular Degeneration Treatments Trials and HARBOR used macular fluid presence as a qualitative OCT parameter in their re-treatment protocols (in the pro re nata arms); this involved the manual detection of IRF or SRF from macular OCT scans.,In 2018, an artificial intelligence (AI)-derived system by De Fauw et al,The Moorfields AMD dataset for this study included all treatment-naive eyes that began anti-VEGF therapy for neovascular AMD between June 1, 2012, and June 30, 2017.www.aaojournal.org). Receiver operating characteristic curves were plotted for the diagnostic accuracy of the segmentation model, using only scans where the retinal specialists agreed. The IRF and SRF were defined as present at ≥ 453 voxels (0.0007 mm3) and ≥ 5199 voxels (0.0075 mm3), respectively, based on the operating point closest to the upper left corner . Of 524 scans for which the experts agreed on the presence or absence of SRF, the model also agreed in 90.3% of scans. Of 487 scans for which the experts agreed on presence or absence of IRF, the model also agreed in 72.7% of scans .All scans were input into the previously described 3-dimensional (3D) segmentation network.U test was used to compare observed volumes between first-treated and second-treated eyes. Univariable regression and Spearman’s rank correlation were used to examine the associations between segmented features and age and VA, respectively. Statistical significance was set at P ≤ 0.05, with Bonferroni correction applied to the statistical tests in the regression and correlation analyses. The following analyses were considered exploratory. Stepwise multivariable linear regression was used to determine whether VA could be predicted using segmented features and demographic data: categoric variables were dummy coded, and backward elimination of features was used to determine significant variables with P ≤ 0.05. Kruskal–Wallis and post hoc Dunn’s tests were used for comparisons between ethnicities grouped into White, Asian, Black, and “Other or Unknown.” Spearman’s rank correlation coefficient was used to assess the relationships between paired feature volumes. All analysis was performed using Python 3.6. De-identified data for this study will be publicly available from the Dryad Digital Repository (https://doi.org/10.5061/dryad.2rbnzs7m4). The Moorfields Eye Hospital NHS Foundation Trust also intends to make the raw data shared with DeepMind openly available to researchers as part of the Ryan Initiative for Macular Research.The mean, standard deviation (SD), median, and interquartile range were calculated for each segmented feature, separately for first-treated and second-treated eyes. Boxplots were used to visualize the distribution of feature volumes between subgroups of eyes, according to age, race/ethnicity, VA, and first-treated versus second-treated eyes. These were displayed on a logarithmic scale to visualize a range in volume that spans several orders of magnitude between the segmented features. For the primary analyses, the relationships between first- and second-treated eyes, VA and feature volume, and age and feature volume were assessed. The distributions of the segmented features were non-normal, as assessed using the Shapiro–Wilk test. Nonparametric tests were used for statistical analysis. The Mann–Whitney www.aaojournal.org).,www.aaojournal.org), alongside data collated from major clinical trials.,,,,39A total of 2966 baseline OCT scans from 2966 eyes of 2580 patients were evaluated. Of these images, 2473 (83.4%) were first-treated eyes and 493 (19.1%) were second-treated eyes. A total of 387 individuals contributed both a first-treated eye and second-treated eye to the analyses. The demographic characteristics of the patients are presented in P < 0.001). Volumes in individuals with both first- and second-treated eyes (n = 387) are presented in www.aaojournal.org).Significant differences in baseline volumes between first-treated and second-treated eyes were observed for every segmented feature analyzed except HRF . With thThe coefficients of Spearman’s correlation analyses between paired segmented features are presented as matrices in www.aaojournal.org) and discussed in detail in the following sections.The distributions of segmented features volumes in first-treated eyes, stratified by VA subgroups, are shown in P < 0.001), with the exception of sPED, RPE, and drusen, which presented weak positive correlations. Univariable linear regression analysis showed CST had the greatest association with VA  of all features considered . The strongest volumetric correlation was observed between SHRM and VA for both first- and second-treated eyes . Likewise, univariable linear regression showed SHRM had the greatest association with VA in second-treated eyes  . Apart from NSR, sPED, RPE, and drusen, which had positive correlations with VA, all other volumes had weakly negative correlations with VA in second-treated eyes  .Multivariable linear regression analysis, with VA as the dependent variable, yielded a model with adjusted www.aaojournal.org).The distributions of segmented feature volumes in first-treated eyes, stratified by age groups, are shown in rs = −0.257, P < 0.001), sPED , NSR , and SRF  were observed. The IRF and drusen were significantly positively correlated with age . Univariable linear regression analysis showed RPE had the greatest association with age  of all features considered. In second-treated eyes , RPE , sPED , fvPED , and SRF . Similar to first-treated eyes, IRF in second-treated eyes also had a significantly positive correlation with age . Univariable linear regression analysis showed RPE and NSR had the greatest association with age  of all features considered.In first-treated eyes , weak neted eyes , parametwww.aaojournal.org). Significant differences in volumes for RPE, SRF, fvPED, and sPED were found between the different ethnic groups. Eyes from Black patients had significantly higher volumes of SRF (P < 0.05) and RPE (P < 0.05) than all other groups and greater sPED volumes when compared with White and other/unknown ethnicities (P < 0.05). For fvPED, only volumes in White patients versus other/unknown patients were significant in post hoc tests (P < 0.05).The distributions of segmented feature volumes in the first-treated eyes, stratified by race/ethnicity, are shown in www.aaojournal.org).,,,The results of the proportion of eyes with IRF or SRF present  at baseline are displayed in ,,The accumulation of vast quantities of imaging data has become both a major challenge and an exciting opportunity for ophthalmology in the 21st century. At Moorfields Eye Hospital alone, there has been a substantial 14-fold increase in the number of OCT scans captured per year since 2008, from 23 582 scans to 339 639 in 2016.,,,,,The IRF, SRF, PED, and SHRM are important indicators of disease activity in macular neovascularization (MNV). With the use of our clinical threshold of fluid presence, the majority of eyes had both IRF and SRF present at the time of diagnosis in first-treated eyes. The fluid volumes demonstrated a wide distribution, particularly for IRF, and were likely influenced by different lesion types,,,Approximately one-fourth of first-treated eyes had SRF alone, likely representing a mixture of type 1 MNV (where SRF is thought to be the first exudative sign) and type 2 MNV (particularly when the ELM is intact).,,,,,,Visual acuity was more strongly associated with IRF than SRF, consistent with previous studies.,P < 0.05). This could be explained not only by earlier disease detection in second-treated eyes but also by the natural progression of dry AMD before conversion, which in both cases results in a greater drusen volume.Our comparison between first- and second-treated eyes at their first injection visit revealed that second-treated eyes had significantly smaller volumes of IRF, SRF, SHRM, fvPED, and sPED compared with first-treated eyes, suggesting detection at an earlier stage of the disease. A later presentation in first-treated eyes may be associated with a more advanced stage of lesion maturity and higher degrees of fibrosis or atrophy. This is likely related to the close surveillance of second-treated eyes, whereas first-treated eyes are undergoing treatment; neovascular conversion in second-treated eyes might be detected at an earlier stage, even before the onset of visual symptoms.,,In both first- and second-treated eyes, fvPED volume correlated moderately with SRF volume and correlated poorly (first-treated eyes) or did not correlate (second-treated eyes) with IRF volume. This may relate to the pathophysiology of each fluid type, where SRF presumably arises directly from a vascularized PED, but IRF may come from a vascularized PED but may also arise from leakage from intraretinal vasculature or a type 3 MNV.,Hyperreflective foci showed the strongest volumetric correlation with IRF and vice versa. The origins of HRF in neovascular AMD are unclear, but one hypothesis is that they represent intraretinal hard exudates secondary to disruption of the blood–retinal barrier,,The NSR volume had a moderate positive correlation with RPE volume in both first- and second-treated eyes. In cases in which macular atrophy accompanies neovascular AMD, lower volumes of both RPE and NSR might be observed.Pigment epithelium detachment has increasingly been considered a relevant parameter for progressive neovascular activity. There is no consistent defining criteria for PED among studies, and most do not classify the PED by subtype.,Central subfield thickness had the highest association with VA in first-treated eyes. At baseline, higher CST usually correlates with poor VA, but this correlation becomes less evident during follow-up.,The limitations for this study include its retrospective nature, the variability in the time that patients present, and the lack of reading center grading for the individual segmented features. Additionally, we have not included the location of the segmented features within the retinal volume, which could provide further insights into the pathophysiology of the disease and visual prognosis.www.aaojournal.org). Discrepancies observed could arise from differences in methodologies, study design, and data interpretation, for example, the use of different OCT devices and scan protocols, as well as the difference in cohort demographics. Therefore, making this comprehensive dataset openly available will be particularly interesting for ophthalmologists to compare our findings on the baseline OCT characteristics of a large real-world cohort with those from clinical trials. This could help the clinical community determine whether these trials have enrolled patients who are representative of real-world practice. Additionally, it will also allow others to replicate our findings and conduct their own novel analyses. Potential clinical uses of the segmentation system may include diagnosis and stratification of neovascular AMD. In uncertain cases and recent conversion to neovascular AMD, the system could detect and quantify subtle or high-risk features of exudation. In addition, quantification of volumes may aid monitoring efficacy of treatment, provide insight to aid anti-VEGF drug choice, and help optimize re-treatment intervals. Furthermore, the system could allow clinicians to see where the eye in question is in terms of the usual spectrum of eyes with neovascular AMD seen in real-world practice.The segmentation outputs from this study have been made openly available for the ophthalmic and AMD research community to download together with this article. This endorses the worldwide effort to inspire community progress in the healthcare sector. We compared our results with prior work that calculated tissue and fluid volumes and thicknesses (In this study, we presented the results of a large-scale analysis using an automated deep learning 3D segmentation system that classifies and quantifies multiple features within an OCT volume scan. Our large cohort was extracted from the Moorfields AMD database, which is perhaps the largest single-center dataset of patients with neovascular AMD.


No evaluated therapeutic approaches, that can efficiently be established in routine mental healthcare, are currently available for traumatised adolescent refugees in Germany. This study evaluates the efficacy of the Stress-Traumasymptoms-Arousal-Regulation-Treatment (START) programme to reduce trauma-related symptoms and psychological distress in traumatised adolescent refugees based in Germany.This randomised, waiting-list-controlled, multicentre trial with a 12-week follow-up will include 174 refugee minors with partial or full post-traumatic stress disorder who are fluent in either Arabic, Dari, English, German or Somali. Eligible refugee minors will be randomised to the START or waiting-list control groups. The manualised 8-week START programme is based on techniques of dialectical behaviour therapy (DBT), fosters adaptive coping with emotional distress and traumatic symptoms and comprises eight therapy modules and a booster session. Study assessments are planned at baseline, post-treatment , booster session at week 12 or 12-week waiting time, and at the 12-week follow-up. Primary and coprimary outcomes are changes in psychological distress and traumatic symptoms at post-treatment and will be analysed as response variables in linear mixed regression models. Secondary outcomes are changes in further trauma-related and other psychopathological symptoms, emotion regulation and intermediate effects of the programme at follow-up. We will also assess effects of the programme with ecological momentary assessments and on neuroendocrine stress parameters using hair cortisol.This study has been approved by the lead ethics committee of Rhineland-Palatinate and the ethics committees of participating sites. The study results will be disseminated through peer-reviewed publications and scientific conferences.DRKS00020771. Randomised waiting-list controlled multicentre trial with follow-up.Manualised DBT-based psychotherapeutic programme with patient material available in Arabic, Dari, English, German and Somali.Multimodal assessment approach of intervention effects on symptoms, functioning and daily living outcomes by psychometric evaluations, electronic ambulatory assessments (e-diaries) and neuroendocrine stress parameters.Restriction of study participation to refugee minors with language skills in Arabic, Dari, English, German and Somali.Among the forcibly displaced persons worldwide there is a high number of children and adolescents under the age of 18 years.The manualised Stress-Traumasymptoms-Arousal-Regulation-Treatment (START) programme was developed from clinical work with traumatised unaccompanied refugee minors in Germany to promote coping with traumatic distress and emotional irritability.The primary aim of this RCT is to evaluate the efficacy of the START programme in reducing psychological distress and trauma symptoms in traumatised adolescent refugees compared with a waiting-list control group (WL). Main secondary aims are to assess whether treatment effects will remain stable for at least 12 weeks after programme termination (follow-up at week 24) and to assess whether the participants of the START groups improve emotion regulation strategies and mental health compared with WL. As stress and emotions are context-dependent and highly dynamic,wwwmentalhealth4refugeesde. The presented paper reports on the START Adolescents protocol  and has been conceived according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.The study is part of the START research consortium, which evaluates distress-reducing psychotherapeutic group and preventive family interventions in traumatised toddler, adolescent and young adult refugees and aims to contribute to improved evidence-based therapeutic interventions for refugees within a stepped mental healthcare approach. The consortium comprises the START Adolescent Study, the START Childcare Study,10.1136/bmjopen-2021-057968.supp1Supplementary dataThe original START programme was developed from clinical work with highly traumatised unaccompanied refugee minors of different countries of origin, who had recently arrived in Germany.The study is conducted as a 12 weeks, two-arm, randomised, WL-controlled, multicentre trial with a 12-week follow-up and six participating outpatient departments in Germany, all of which are experienced in treating traumatised adolescent refugees. The study is coordinated by the Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany. The study intervention comprises an adapted version of the START programme.Key stopping rules for patients are a withdrawal of informed consent, unwillingness to further participate in the trial, any factors affecting the patient’s or others’ well-being, for example, acute suicidality or acute endangerment to others, onset of other acute severe mental disorders, alcohol or substance abuse, inpatient treatment of over 2 days, start of concurrent psychotherapy and more than two psychotherapeutic crisis interventions. Key stopping rules for participating centres are non-adherence with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use: Guidelines for Good Clinical Practice (ICH-GCP)We will allocate 174 participants to the trial and expect that we will have to screen 240 adolescent refugees for eligibility. Inclusion criteria are: informed consent by adolescents and caregivers, flight background, age between 13.00 and 17.11 years, verbal communication skills and reading comprehension in one of the study languages, non-verbal IQ ≥70, partial or full PTSD, PTSD symptoms are the clinically most impairing condition with at least moderate clinical symptom severity. We kept the exclusion criteria to a minimum, to foster the applicability of the programme in routine care as much as possible. Exclusion criteria are: current substance use disorder and/or harmful alcohol abuse, primary severe mental disorders other than PTSD, acute suicidality or danger to others, unstable psychotropic medication (change of psychotropic medication within the last 2 weeks before baseline assessment), current ongoing psychotherapy, inpatient status or study participation in another clinical trial, unaccompanied refugee minor without a legal representative, known pregnancy. Participants, who attend all assessment visits, will be given a study compensation. Participants will be insured by a clinical trial insurance during the time of study participation. Please see for detailed information about the assessment of eligibility criteria also the sections ‘screening’ and ‘psychometric instruments’. The participants’ study flow is provided in For recruitment, study information is provided to schools, child and adolescent psychotherapists/psychiatrists, social workers, youth welfare providers, at conferences, professional working group meetings, in newspaper articles or interviews, on the institutions’ homepages and on social media. All participants’ information about the study is provided in a caregiver and adolescents’ version in all study languages.For a summary of trial flow and assessment visits please see the SPIRIT flow diagram, http://randomizer.at).Assessment of informed consent for study participation, inclusion and exclusion criteria, demographic and medical data. Inclusion of eligible participants, randomisation to the intervention (START) or WL using a web-based randomisation system with permuted blocks stratified by centre (T0 takes place between one and 2 weeks after randomisation (WL) or before the first programme session (START), T1 within 1 week after the 8-week programme (START) or within 8–9 weeks after T0 (WL), T2 within 1 week after the booster session (START) or 4–5 weeks after T1 (WL) and T3 follow-up visits within 12 weeks after T2 (START/WL). At T0 only, the Post-Migration Living Difficulties Questionnaire (PMLD) and Questionnaire on Therapy Expectation are assessed. At the T0(T1)–T3 visits primary endpoints, trauma symptoms, emotion regulation, general psychopathology, overall clinical severity of mental disorders, suicidality and endangerment to others are assessed and 1 week e-diaries are applied. Hair cortisol is assessed at T0, T2 and T3. Adverse events are assessed at T0–T3 visits and weekly until T1.Details of the START Adolescents programme are provided in The original START Adolescents programme comprised five modules with psychoeducation on trauma, stress, distressing emotions and crises, mindfulness training, arousal regulation, stress reduction techniques, and handling nightmares. For the current study, the START manualFor details of the instruments including psychometric properties, please see 10.1136/bmjopen-2021-057968.supp2Supplementary dataInclusion and exclusion criteria are assessed with the Essen Trauma Inventory for Children and Adolescents,Psychological distress is assessed with the Perceived Stress Scale, 10-item version (PSS-10), a validated self-report questionnaire, that measures the intensity with which individuals appraise their daily life as stressful, unpredictable, uncontrollable and overloaded. Reliability and validity for the Arabic, English and German version have been shown to be sufficient or good.We assess trauma-related psychosocial impairment and PTSD criteria according to Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) with the Child and Adolescent Trauma Screen-2,We assess adverse life experiences related to migration with the adapted German version of the self-rated PMLD,We use smartphone-based electronic (e)-diaries to assess aversive inner tension, emotional intensity, trauma symptoms , cognitive and behavioural avoidance of triggering situations in daily environments, sleep quality, stressfulness, content and number of nightmares, self-efficacy, self-esteem, rumination and somatisation.If additional informed consent for hair cortisol collection is provided by study participants and their legal representatives, we collect thin hair strands from the posterior vertex of the head cut as close to the scalp as possible. Hair strands are tied together, sealed, and stored in a dry and dark place. Prior to analyses, they will be cut into a 2 cm segment proximal to the scalp, representing cumulative cortisol secretion of the last 2 months.The study procedures are monitored by the Coordination Centre for Clinical Trials (KKS) Heidelberg according to the ICH-GCPManual adherence across different therapists and participating centres is ensured by training all therapists on the START Adolescents programme and regular supervision with standardised assessments of manual adherence. We require a certain level of professional training from the therapists, of whom at least one per group must be a graduated psychologist, pedagogue, or physician.The quality of psychometric assessments, tests and interviews is ensured by training the raters on the study assessments. Raters must have a bachelor’s or master’s degree in psychology or a comparable standard. Raters with a bachelor’s degree in psychology will administer questionnaires and psychological tests, raters with a Master‘s degree in psychology will administer the study interviews.The KKS Heidelberg is responsible for data management and analysis as well as data security and data transfer processes. All procedures are implemented in accordance with ICH-GCP guidelines and the Declaration of Helsinki.The research data generated during this study will be available on reasonable request by the study coordinating centre at the Department of Child and Adolescent Psychiatry, University Medical Center, Mainz, Germany. Anonymised data use by other researchers not involved in the study may be done with prior agreement.d=0.63 for the PSS-10 and of d=0.56 for the IES-R score at T1. This results in a required sample size of n=84 (PSS-10) and n=104 (IES-R) for a one-sided test at an α=0.025 level with a power of 80% to detect such differences. The START pilot trial showed a drop-out rate <10% and was conducted as a one-centre single-arm naturalistic trial with mostly inpatients.The sample size calculation is based on the coprimary outcomes of emotional distress (PSS-10) and traumatic symptoms (IES-R) at T1. Based on available studiesAll randomised participants will be included in the full-analysis set as allocated. All randomised participants, who finish the study according to the study protocol until T2 as planned with no missing values for T1 (primary endpoint) will be included in the per-protocol set for analysis as allocated. All randomised participants will be included in the safety population according to the applied intervention.α=0.025. The primary analysis will be repeated in the per-protocol population as a sensitivity analysis. Since the different timing of the T0 baseline examination in the study groups after randomisation could cause biases in the effect estimates, that cannot be estimated or modelled, additional sensitivity analyses will be performed, such as repeating the primary analysis using the screening value instead of the baseline value. Secondary outcomes will be analysed in the full-analysis set. Missing values will not be imputed. The stability of treatment effects up to T3 will be assessed by calculating confidence intervals on the T1–T3 and T2–T3 difference for the PSS-10 and IES-R total scores in the intervention group. Psychometric scales used for assessment of secondary outcomes and hair cortisol concentrations will be analysed according to primary endpoints or descriptively. For the analysis of e-diary data, multilevel models will be used to characterise momentary mechanisms and context-dependent affective experiences, which allow a nested data structure (momentary experiences within participants), and enable different numbers of ratings per participant to be handled quite well.Baseline characteristics will be analysed descriptively for the safety, full-analysis, and per-protocol set in the intervention and control group. The primary and coprimary endpoints will be analysed in the full-analysis set. Missing values will be imputed. Endpoints will be assessed as response variables in linear mixed regression models with site and psychotherapeutic group as random effects, intervention group, sex and region of origin as fixed effects, and age, PSS-10 and IES-R baseline scores, respectively, as linear effects with a hierarchical testing procedure that maintains the overall significance level of The study protocol, patient recruitment procedures, patients’ information and informed consent material have been approved by the lead ethics committee of Rhineland-Palatinate (ID 2019-14709) and the ethics committees of participating sites. For every substantial protocol modification approval of all ethics committees is required. The study will be conducted according to ICH-GCPRecruitment started 1 October 2020.Evidence-based, evaluated, low-threshold and culture-sensitive psychotherapeutic treatment programmes, that reduce distress caused by traumatic experiences that can be efficiently established in routine mental healthcare, would represent valuable therapeutic interventions to support refugee minors with trauma-related symptoms and emotion regulation difficulties. However, such interventions are currently lacking. The primary aim of this study is to evaluate the clinical efficacy and intermediate outcome of the distress-reducing psychotherapeutic START programme and to contribute to improved evidence-based therapeutic interventions for adolescent refugees within a stepped-care mental health approach in Germany. If shown to be effective, the first rigorously evaluated manualised intervention programme for traumatised adolescent refugees will be available, which will have widespread implications for clinical practice.Some limitations for the application of the programme in mental health routine care in host countries may be that the therapeutic study groups are limited only to traumatised refugees, which may not reflect clinical reality. Another limitation is the restriction of study participation to refugee minors with language skills in Arabic, Dari, English, German and Somali. Thus, the study will not provide information on the effectiveness of the programme if applied to refugee minors with a different cultural or language background. However, since all programme materials are available in Arabic, Dari, English, German and Somali, the START programme will provide a treatment option not only in German-speaking or English-speaking host countries that care for refugee minors but also in refugee camps based in Arabic-speaking, Dari-speaking or Somali-speaking countries, where is a huge need for easy-to-apply psychotherapeutic treatment options.Beyond effects on the symptom level, we will analyse intervention effects on psychosocial functioning and everyday behaviour through the use of e-diaries and on the neuroendocrine stress system by analysing hair cortisol. The multimodal assessment approach of symptoms, functioning, daily living outcomes, context variables and neuroendocrine effects, as well as the follow-up assessment, will enable us to analyse immediate and intermediate treatment effects not only on the phenomenological clinical level but also on the biological and daily living level. This will extend our understanding of intervention effects, influencing factors and the course of trauma-related mental health problems in refugee minors.


In 2012, the Digital Universe Study reported that ‘less than 1% of the World’s data is analyzed and less than 20% is protected’ and recommended that management plans were needed to harness the potential within these data streams . Life schttps://elixir-europe.org/), the European infrastructure for life science data, has worked to address these challenges by bringing Europe’s national centers and core bioinformatics resources into a single, coordinated infrastructure. Many European countries have long-established national bioinformatics infrastructures that provide tools, data resources and cloud services to national and international users. ELIXIR invests in and aims to sustain these vital resources and ensure a level of interoperability that facilitates scientific discovery. Indeed, for research to thrive in a world of data abundance, all components  must be FAIR—findable, accessible, interoperable and reusable . Some ELIXIR Nodes predate ELIXIR, such as EMBL-EBI and the Swiss Institute of Bioinformatics. In many other countries, ELIXIR has contributed to the formation of new national bioinformatics infrastructures, e.g. de.NBI  and ELIXIR Czech Republic (https://www.elixir-czech.cz/), both launched in 2015. The participating countries contribute membership fees, proportional to the countries Net National Income (NNI), provide ELIXIR with a technical budget that is used to fund development of shared services that support and link the nationally funded bioinformatics resources.Fundamentally, ELIXIR is connecting national bioinformatic networks, known within ELIXIR as Nodes  and the Communities (https://elixir-europe.org/communities). The ELIXIR Platforms  are supported by Technical Coordinators located at the ELIXIR Headquarters, with vision and strategy led by senior scientists in the Nodes. As part of joining ELIXIR, each Node contributes a set of services (https://elixir-europe.org/services) that are aligned with the Platforms, e.g. Human Protein Atlas (https://research.csc.fi/) (Compute Platform—ELIXIR Finland), Identifiers.org  that develop services and bring benefit to key user communities , the ESFRI for European Plant Phenotyping, and the CGIAR (https://www.cgiar.org/), the world’s largest global agricultural research organization.For instance, the ELIXIR Plant Sciences Community has built a common technical infrastructure and associated social practices to support plant genotype-phenotype analysis with the goal to make plant genotypic and phenotypic data easier to find, integrate and analyze, by making them FAIR , which brings developers together from different Platforms and Communities to collaborate on preselected projects.The Bioschemas convention, set up in 2015 to improve FAIRness of data, is driven by the ELIXIR Interoperability Platform as an open international community initiative. Bioschemas improves the findability of data in the life science resources by extending a Schema.org markup to specific biological data types. This markup can be introduced into websites, without the need for specific technical expertise, such that they become readily indexable by search engines and other services . ELIXIR https://elixir-europe.org/services/compute/aai). AAI facilitates data access that requires specific authorization on account of its sensitive nature, e.g. human genomic data. Before data access authorization and delivery can be carried out, a researcher needs to be identified and their identity authenticated to a sufficient level of assurance. AAI provides this function. ELIXIR AAI is still in development, but already has 603 enabled identity providers and 2470 registered users organized in 423 groups, with 59 production services connected to it.ELIXIR also funds strategic infrastructure projects such as AAI, the Authorization and Authentication Infrastructure (https://elixir-europe.org/communities/rare-diseases), in partnership with RD-CONNECT (http://rd-connect.eu/), BBMRI-ERIC (http://bbmri-eric.eu/) and E-Rare (http://www.erare.eu/), is creating a federated infrastructure that will enable researchers to discover, access and analyze different rare disease repositories across Europe. This community is using Beacon . ELIXIR has been a formal contributor to the generation of GA4GH products (https://www.ga4gh.org/genomic-data-toolkit/) since the formation of the alliance. The ELIXIR Beacon project was one of the first GA4GH Driver Projects (https://elixir-europe.org/news/elixir-and-ga4gh-expand-collaboration), building on the existing collaboration, and will facilitate the access to sensitive data across Europe, in order to help create virtual cohorts with tens of millions of participants. The coordinated development and deployment of the ELIXIR Beacon and ELIXIR AAI standards along with the suite of standards from the GA4GH Work Streams will help translate this vision into reality.GA4GH is an international, nonprofit alliance formed in 2013 to accelerate the potential of research and medicine to advance human health (https://elixir-europe.org/about-us/what-we-do/elixir-programme) include that ‘ELIXIR Core Data Resources will be the global standard for bioinformatics resource management and the foundation for an international funding and life cycle management strategy that secures the long-term sustainability of those resources’. Defined according to a protocol based on 23 indicators described in the article ‘Identifying ELIXIR Core Data Resources’ (https://elixir-europe.org/platforms/data/core-data-resources) are a set of European data resources of fundamental importance to the wider life science community and the long-term preservation of biological data.ELIXIR’s mission includes ensuring that all of Europe’s life science projects have access to long-term sustainable infrastructure for data management  to facilitate interoperability of life science data, to support the principles of FAIR data management, and to enable maximal reuse, and thereby value, of life science data, in the long term.The long-term sustainability of the life science data ecosystem depends also on the adoption of standardized file formats, metadata, vocabularies and identifiers across data resources. Consequently, ELIXIR has established a portfolio of Recommended Interoperability Resources (https://elixir-europe.org/about-us/what-we-do/elixir-programme-2014-2018) was supported by ELIXIR Core funding and the Horizon 2020 ELIXIR-EXCELERATE grant , enabling the evolution from a nascent to an established research infrastructure. As shown through the examples mentioned above, ELIXIR has laid the foundation for a sustainable life science ecosystem that underpins its 2019–2023 Scientific Programme (https://elixir-europe.org/about-us/what-we-do/elixir-programme). The 2019–2023 Programme transitions ELIXIR initiatives from the proof-of-concept stage to operating at scale.The first ELIXIR Scientific Programme 2014–2018 (Federated Human Data Implementation Study (https://elixir-europe.org/about-us/implementation-studies/federated-human-data) engages 26 collaborators in 13 Nodes organized into five work packages, and will run for 31 months. The plan includes a structured roadmap for ELIXIR Nodes to join the European Genome-phenome Archive (EGA) federated network by providing the necessary technical, logistical and training coordination across the network. This will enable population-scale genomic, phenotypic and biomolecular data to be accessible across international borders and provide a foundation for major initiatives such as the recent declaration by 21 European countries to transnationally provide access to at least 1 million human genomes from national programs by 2022 , addresses the need for a stable infrastructure for unifying software container solutions within ELIXIR. This infrastructure will provide an access point for end-users to find, generate, store, monitor and even benchmark software container solutions. Such studies drive collaboration: the technical experts in ELIXIR’s Compute and Tools Platforms will work with developers and researchers in the Galaxy, Metabolomics and Proteomics Communities. In both of these examples, the scale of adoption and participation, as well as the ambition for generating reusable infrastructure across diverse communities is only possible because of the groundwork done over the 5 years.Connecting secure, federated clouds with open tool registries, packaging and workflow execution standards will enable analysis workflows to operate on data across national borders. Open repositories and support for good development practice will drive data reproducibility and provenance, which are of high importance in both research and clinical practices. The ELIXIR Implementation Study https://ec.europa.eu/info/sites/info/files/research_and_innovation/gso_progress_report_2017.pdf) and brings together people, expertise and resources from more than 220 institutes. A key feature of ELIXIR’s strategy is to build long-term investments around services identified as strategically important, via community consultation. ELIXIR’s focus on connecting and adding value to the national Nodes via a jointly defined portfolio of shared services lays a foundation for long-term sustainable operations—grounded in national research infrastructure roadmaps. This contrasts with other initiatives such as the US-based BigData to Knowledge (BD2K) program . This project will engage every Node across ELIXIR, and highlights ELIXIR’s vital role in driving good data management, reproducibility and reuse in a distributed and heterogeneous funding landscape.ELIXIR has embarked upon its second Scientific Programme (2019–2023), which lays out the scientific direction jointly agreed between ELIXIR Nodes. Significantly, ELIXIR has been awarded an EU H2020 3-year grant for data sharing and management, ELIXIR-CONVERGE (https://www.ejprarediseases.org/) (EJP-RD) and Common Infrastructure for National Cohorts in Europe, Canada and Africa (https://www.cineca-project.eu/) (CINECA) and ensuring wider adoption of Node services and tools within the health system. ELIXIR is also coordinating the FAIRplus (https://fairplus-project.eu/) project, establishing FAIR data practices, increasing discovery, accessibility and reusability of data from selected projects funded by the EU’s Innovative Medicine Initiative, and internal data from seven pharmaceutical industry partners.In the biomedical domain, ELIXIR’s experience in operating large infrastructure consortia provides the basis to translate genomics from biomedical research into routine application in healthcare systems. ELIXIR Nodes are involved in several large European-funded genomic health projects such as European Joint Programme on Rare Diseases , where the 13 ESFRI life sciences Infrastructures in Europe (https://www.esfri.eu/) join forces to create an open collaborative digital space for life science in the EOSC. The project aims to publish data from the life sciences Infrastructure facilities and centers as FAIR Data Resources in the cloud, link reusable Tools and Workflows to standardized compute services in national life science clouds, connect all users across Europe to a single login AAI system, and to develop joint data policies to preserve and deepen the trust given by research participants and patients volunteering their data and samples.ELIXIR is coordinating the EOSC-Life project . In addition, it is establishing new collaboration strategies with national data infrastructures in key international countries such as the Australian Bioinformatics Commons Initiative (https://h3africa.org/), whose vision is to support a network of pan-continental labs to study the complex interplay between environment and genetic factors, and investigate disease susceptibility and drug response across Africa.ELIXIR has well-established collaborations with a number of international initiatives such as GA4GH (see above) and the RDA (Research Data Alliance; In conclusion, ELIXIR is established as a sustainable infrastructure for managing and analyzing large and geographically distributed datasets based on global standards and shared components that add value to national investments. The commitment from ELIXIR’s member countries, as described in the ELIXIR 2019–2023 Programme, is to jointly provide services that enable European researchers and their collaborators to routinely access, analyze and reuse large, complex and geographically distributed datasets. Over the next 5 years, ELIXIR will deepen the existing partnerships and open up collaborations with new areas such as single-cell genomics, artificial intelligence and machine learning, and biodiversity research, to drive the vision to support life science research and its translation to society, the bioindustry, environment and medicine.


Self-medication, a worldwide practice, has both benefits and risks. Many countries have regulated non-prescription medications available for use in self-medication. However, in countries such as Rwanda, where prescriptions are not required to purchase medications, prescription, non-prescription and traditional medications have been used for self-medication.To determine the reported self-medication use in Rwanda and to determine attitudes and reasons associated with parental decisions to self-medicate their children.A cross-sectional multi-center questionnaire based quantitative study of 154 parents/caregivers of children under ten years undertaken in private and public health facilities.The use of self-medication was reported to be 77.9%. Among these parents/caregivers, 50.8% used modern self-medication only, 15.8% used traditional self-medication only and 33.3% used both types of self-medication. Paracetamol was the most commonly used drug in modern self-medication; the traditional drugs used were Rwandan local herbs. Parents/caregivers who used modern medicines had slightly more confidence in self-medication than self-medication users of traditional medicines (p=0.005). Parents/caregivers who used modern self-medication reported barriers to consultation as a reason to self-medicate more frequently than those who used traditional drugs. Having more than one child below 10 years of-age was the only socio-demographic factor associated with having used self-medication . Being above 30 years  and living in Kigali  were factors associated with preference of modern self- medication compared to traditional self-medication.Self-medication is common in Rwanda. Parents/caregivers are involved in this practice regardless of their socio-demographic background. Since the declaration of Alma-Ata in 1978, the principles of self-care, individual participation, responsibility and involvement in one's own health care have been recognized as important elements of primary healthcareResponsible self-medication implies the use of approved, safe, and effective drugs, accompanied by information to direct users Factors associated with the parental choice to self-medicate their children vary, but include: parents/caregivers perceiving their child's illness as being mild and not requiring health professional consultation, lack of time to attend consultations, high consultation fees, clinic waiting time, emergency treatment, use of old prescriptions available in the home, parent comfort in recognizing their children's disease based on the symptoms and having experience with the medication Pediatric self-medication is a worldwide practice with a reported prevalence between 32–98% in Madagascar, India, Greece, and Australia There is also a difference in education and economic factors associated with the choice to self-medicate. Studies from Spain, Finland, Italy, and MadagascarThere is insufficient literature describing the use of self-medication in pediatric populations in Sub-Saharan Africa. In Rwanda, self-medication is being used by parents/caregivers for their children Objectives The present study aimed at determining the proportion of parents/caregivers who reported self-medicating their children before consulting private and public health facilities in Rwanda and to determine attitudes and reasons associated with parental decisions to self-medicate their children.Study Design: We conducted a cross-sectional study from July to September 2018. Reporting has been verified in accordance with the STROBE  checklist Study Sites/settings: We conducted a multi-center study in three facilities: i) a provincial referral hospital, two hours from Kigali, the capital of Rwanda, ii) a vaccination clinic in an urban public health center in Kigali city and iii) a private pediatric clinic in Kigali, which serves a larger proportion of educated parents/caregivers with high socioeconomic level. This selection was done to increase the representativeness and generalizability of the results to the Rwandan Population.Study population: The study aimed to recruit parents/caregivers of both unwell and well children with different socioeconomic status. Unwell children were recruited at out and in-patient units of one private and one public health facility. Parents/caregivers of well children were approached at a vaccination clinic in a health center.Inclusion criteria: All Rwandan parents/caregivers of children aged one month to 10 years of life and who accepted to participate in the study were eligible to be included. Parents/caregivers who were not primary caregivers of the children were excluded as they would not be able to describe fully the self-treatment of the children. We excluded from the analysis the participants who consented but did not fully complete the questionnaire.Sampling: Non-probability convenience sampling was used to recruit study subjects on working days (Monday to Friday) during working hours (8am to 5pm).Procedures for enrollment: Eligible parents/caregivers were approached in the waiting area, prior to their consultation, and they were given a verbal explanation of the purpose and the methods of the study. All participants who signed the written consent form were then included. No data was kept on the number of participants who declined to participate.Administering the questionnaire: Questionnaires were given to parents/caregivers by the PI or a trained data collector (DC) who was available to answer questions regarding the questionnaire. For parents/caregivers who couldn't read or who preferred to be assisted, the DC read the questions and completed the questionnaires on behalf of the participant. The questionnaires were completed in the waiting area of the respective health facility. When the questionnaire was filled by the DC, this was indicated on the form.Variables: Dependent (outcome) variable were the percentage of parents/caregivers using self-medication, reasons of parental self-medication and common drugs used in self-medication. Independent variables were age, sex, province of origin, level of education, socioeconomic status, number of children under 10 years of age; health insurance, determinant/predictors of parental self-medication, relationship with the child, marital status. Potential confounders were site of interview and mode of completing questionnaire Data collection tool (Questionnaire): A questionnaire was developed specifically for this study. To ensure content validity of our data collection tool, it was first built by the Principal Investigator (PI) (JU) using previously published studiesThe questionnaires used 5-point Likert-scales to assess the parental attitudes and perceptions about self-medication. The responses given to the Likert-scale questions from each of the barriers (five questions) and confidence (six questions) domains were combined to create total “barriers to consultation” and total “confidence in self-medicating” scores.Translation and piloting of questionnaires: The questionnaire was initially prepared in English and translated into the national language (Kinyarwanda) by the PI. It was then back-translated in English for accuracy by an independent, non-medical translator. It was piloted on five subjects and amendments were then made based on this piloting, including changes in wording and the addition of further Likert-items.Sample size calculation: Sample-size was calculated for the prevalence of self-medicating, with a predicted baseline of 69% of parents/caregivers of children under-five years of age reported in Tanzania Data management: EpiData Entry 3.1 Software was used for data entry and storage. The data was then exported into Statistical Package for the Social Sciences , for statistical analysis.Statistical analysis: For continuous numerical data, means and standard deviation were reported; for categorical data, frequency tables, percentages and graphs were reported. Comparison was made between responses on the modern-medicine and traditional-medicine questionnaires. Therefore, parents/caregivers, who self-medicated with both modalities, were included in both arms of the analysis For confidence and barrier questions, Likert-scale items were converted into means and compared using Mann-Whitney U test due to the non-normal distribution of the data. Categorical variables were analyzed using Chi-square test or Fisher's exact test. Odds ratio were reported to identify associations. To account for multiple confounders logistic regression analysis was undertaken including variables with p-value <0.2.Study period: Recruitment took place from July to September 2018 with all sites being visited twice, gaining a total of 162 subjects who were enrolled  self-completed the questionnaire with 140 (91%) needing assistance with verbal completion of the questionnaire. The mean age of respondents was 33 years (SD: 6.7). Mothers represented the majority (86.4%) of respondent and most respondents were married (94%) (ed (94%) .Self-medication indications and practices: Among 154 participants, 120 caregivers (78%) reported to have used self-medication for their children, Sixty-one of them (51%) used only modern drugs in self-medication, 19 (16%) used only traditional drugs while 40 (33%) used both types. Thirty-four caregivers had never used self-medication (22%) .Many parents/caregivers decided to self-medicate with modern medications without seeking advice from anyone. Whereas, for traditional self-medication, friends and relatives served as the main sources of advice . All traReasons for using self-medication: There was a statistically significant difference in reasons for choosing modern and traditional self-medication among our participants, with participants choosing modern medications having slightly more confidence in self-medication than self-medication providers of traditional medicines (p=0.005) and parents/caregivers who used modern self-medication reporting barriers to consultation more frequently as reason to self-medicate than parents/caregivers who used traditional self-prescription (p=0.028) (p=0.028) .Non-self-prescribers: Parents/caregivers who choose not to self-medicate reported most frequently that they don't use self-medication because “non-prescription drugs are dangerous”. Access to pharmacy, traditional healer, traditional medication shop or cost, were not found to be reasons to not use self-medication .Social demographic association with use of non-prescription drug: The association between different demographic characteristics and the use of self-medication was analyzed. In bivariate analysis the factors that were statistically significantly associated with use of non-prescription drugs included being from Kigali and having more than one child less than 10 years of age. In the multivariate analysis of factors that were significant in the bivariate analysis (with cut-off p<0.2), the only factor associated with increased use of self-prescribed drugs was having more than 1 child under the age of 10 years (10 years .Association of socio-demographic factors with the use of modern versus. Traditional medication: The association between socio-demographic factors and the use of modern only vs. traditional only drugs was analyzed. In bivariate analysis the factors associated with use of exclusive modern rather than exclusive traditional drugs in self-medication were: caregivers in private clinic, caregivers from Kigali, advanced education, high social economic class, having private health insurance, and being older than 30 years. e included all factors with a p-value<0.2 in a multivariate analysis and after adjusting for confounders only age above 30 and living in Kigali remained associated with the preference of exclusive modern self-medication compared to exclusive traditional self-medication (dication .This study aimed to determine the reported self-medication use in children in private and public health facilities in Rwanda and to determine attitudes and reasons associated with parental decisions to self-medicate their children. Our study showed that 78% of participants have used self-medication for their children. Both modern and traditional drugs were used. This is similar to 77% reported in Pakistan In our study 51% of parents/caregivers who used self-medication used only modern medicines, 16% used only traditional self-medicines and 33% used both. Our findings show that we had a lower rate of parents/caregivers who used only modern medicines compared to previous studies conducted in Sudan and Saudi Arabia where 84% and 86.7% of parents/caregivers reported using modern medicines over traditional ones Self-medication has many potential benefits, for example medications such as paracetamol can be effectively used. However, self-medication can result in ineffective medications being used, wasting parental resources and potentially delaying a child receiving appropriate care. Cough syrups were the second most widely used self-medication. This is of concern, particularly in young children as cough suppressants in this age group are known to be ineffective and to have potentially harmful effectsThere is a difference between education and economic factors associated with the choice to self-medicate. Studies from Spain, Finland, Italy, and MadagascarFurthermore, our study showed that having more than one child less than 10 years of age was associated with the practice of self-medication. No other factor was shown to be associated with parental use of self-medication. Caregiver's age above 30 years of age were found to be associated with the use of modern self-medication compared to traditional ones. In contrast to our findings, being female and younger were associated with the practice of self-medication in Italy and Spain We observed that coming from Kigali city was associated with the preference of modern drugs over traditional ones, which can be explained by the fact that most of our study participants were from Kigali where there is a wider availability of pharmacies dispensing modern medicines than in areas outside Kigali.Our analysis to identify associated factors did not include the group of parents/caregivers who used both types of self-medication. The internal validity could have been compromised by the high rate of verbal completion of the questionnaire, with participants being potentially prone to acquiescence bias. Recall bias may have also limited caregiver responses. All regional provinces of Rwanda were not represented.Self-medication, a worldwide practice, is also common in Rwanda. Parents/caregivers are involved in this practice for their children regardless of their socio-demographic background. Consideration should be given to regulating drugs used in self-medication as well as the education of the population with the goal of minimizing the risks of self- medication and maximizing benefits.


Pickling cucumbers are susceptible to chilling injury (CI) during postharvest refrigerated storage, which would result in quality degradation and economic loss. It is, thus, desirable to remove the defective fruit before they are marketed as fresh products or processed into pickled products. Chlorophyll fluorescence is sensitive to CI in green fruits, because exposure to chilling temperatures can induce detectable alterations in chlorophylls of tissues. This study evaluated the feasibility of using a dual-band chlorophyll fluorescence imaging (CFI) technique for detecting CI-affected pickling cucumbers. Chlorophyll fluorescence images at 675 nm and 750 nm were acquired from pickling cucumbers under the excitation of ultraviolet-blue light. The raw images were processed for vignetting corrections through bi-dimensional empirical mode decomposition and subsequent image reconstruction. The fluorescence images were effective for ascertaining CI-affected tissues, which appeared as dark areas in the images. Support vector machine models were developed for classifying pickling cucumbers into two or three classes using the features extracted from the fluorescence images. Fusing the features of fluorescence images at 675 nm and 750 nm resulted in overall accuracies of 96.9% and 91.2% for two-class  and three-class  classification, respectively, which are statistically significantly better than those obtained using the features at a single wavelength, especially for the three-class classification. Furthermore, a subset of features, selected based on the neighborhood component feature selection technique, achieved the highest accuracies of 97.4% and 91.3% for the two-class and three-class classification, respectively. This study demonstrated that dual-band CFI is an effective modality for CI detection in pickling cucumbers. In the U.S., cucumber production falls into two types, i.e., fresh-market and processing for pickled products. Pickling cucumbers account for more than half of the total production of cucumbers in the nation, valued at $144 million at the farmgate in 2019 . CI resuCurrently, no automated or rapid methods are being commercially used for CI detection of pickling cucumbers. Development of non-destructive optical techniques for CI detection would be beneficial for enhancing quality inspection of pickling cucumbers and pickled products. Hyperspectral imaging has been extensively researched for quality and safety assessment of horticultural products ,11. ChenFluorescence techniques provide a sensitive sensing modality for detecting stress-induced defects or disorders for horticultural products ,17, whic0  and low Fv (variable fluorescence) and Fv/Fm, and the fluorescence image of F0/Fv (the map of the ratio of the two fluorescence parameters F0 and Fv) allowed discriminating between diseased and healthy areas. Obenland and Neipp (2005) reported that the chlorophyll fluorescence images of F0 and Fm were effective for detecting hot water-induced skin damage for lemons that had been immersed in 55 °C water for 5 min  were selected for this study.As shown in Based on the visual inspection of CI symptoms for the chilled fruit after image acquisition for each date, the pickling cucumbers were categorized into three injury levels: 0 , 1 (mildly injured) and 2 (severely injury). i CEL5500-Fiber, Digital Light Innovations, Austin, TX, USA) via a UV-visible light efficient liquid light guide  to provide uniform illumination over the sample. A back-illuminated electron-multiplying CCD camera with a resolution of 1024 × 1024 pixels , attached with a 35-mm C-mount fixed focal length lens , was used for acquiring fluorescence images. Based on an earlier study . Because of the randomness of feature dataset partitions (Support vector machine (SVM) is commonly used for various classification tasks due to its high accuracy and the ability to model high-dimensional, complex data. Compared to other advanced machine learning algorithms like convolutional neural networks, SVM requires less computational resources and can be sufficiently optimized in a timely manner. There are different versions of SVM depending on whether and how kernel tricks  are implemented for solving linear or nonlinear problems . In thisrtitions , it woulTo reduce the model complexity while boosting its accuracy, feature selection or reduction was done for each of the two-class and three-class modeling scenarios, where the best test accuracy was obtained with a full set of features. No extensive feature selection efforts for all the modeling scenarios were made, as it would be beyond the scope of the present research. Instead, a feature selection method based on neighborhood component analysis (NCA)  was usedThe classification performance of SVM models was evaluated in terms of true positive (TP), true negative (TN), and overall accuracy (ACC) . The TP All the analyses for image preprocessing, feature extraction and machine learning were performed in Matlab R2018b .The NCA feature selection algorithm was applied to the feature set of FI675-FI750 for two-class and three-class classification, respectively. Classification results obtained using the full sets or downsized sets of features demonstrated that the dual-band CFI technique is a potentially viable tool for the detection of CI in pickling cucumbers. The feature fusion, which concatenates the features at different wavebands together, was found effective for boosting the model accuracy, especially in the more challenging three-class classification. Based on feature selection, the overall accuracy of 97.4% in the two-class classification compare favorably with those attained by using hyperspectral imaging for CI detection of cucumber fruit ,13,14, aThis study demonstrated that dual-band chlorophyll fluorescence imaging (CFI) at 675 nm and 750 nm is an effective modality for the detection of chilling injury (CI) in pickling cucumbers. After chilling and post-chilling treatments, pickling cucumbers had developed symptoms such as skin pitting, water-soaked spots, browning and decay, which were manifested as darker areas in the fluorescence images. Image vignetting corrections improved the overall quality of fluorescence images. Linear support vector machine (SVM) models, built using the fusion of features at 675 nm and 750 nm extracted from the fluorescence images, resulted in overall accuracies of 96.9% and 91.2% in the two-class and three-class classification, respectively. The feature fusion was effective for significantly boosting model accuracies, especially for the three-class classification, compared to using the features for single wavelengths. Better results for the two-class and three-class classification were attained with overall accuracies of 97.4% and 91.3%, respectively, by selecting a subset of features for SVM modeling. Further research is needed, so that dual-band CFI can be used for real-time inspection of pickling cucumbers for chilling injury.


Myocardial layer-specific strain can identify myocardial ischemia. Global myocardial work efficiency (GWE) based on non-invasive left ventricular (LV) pressure-strain loops is a novel parameter to determine LV function considering afterload. The study aimed to compare the diagnostic value of GWE and myocardial layer-specific strain during treadmill exercise stress testing to detect significant coronary artery disease (CAD) with normal baseline wall motion.Eighty-nine patients who referred for coronary angiography due to suspected of CAD were included. Forty patients with severe coronary artery stenosis were diagnosed with significant CAD, and 49 were defined as non-significant CAD. Stress echocardiography was performed 24 h before angiography. Layer-specific longitudinal strains were assessed from the endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Binary logistic regression analyses were performed to evaluate the association between significant CAD and echocardiographic parameters. A receiver operating characteristic curve was used to assess the capability of layer-specific strain and GWE to diagnose significant CAD.p = 0.006) and peak GWE  were associated with significant CAD. Receiver operating characteristic curves showed peak GWE to be superior to mid-myocardial, epicardial, and endocardial GLS in identifying significant CAD. Further, adding peak GWE to endocardial GLS could improve diagnostic capabilities.Patients with significant CAD had the worse function in all three myocardial layers at peak exercise compared with those with non-significant CAD when assessed with global longitudinal strain (GLS). At the peak exercise and recovery periods, GWE was lower in patients with significant CAD than in patients with non-significant CAD. In multivariable binary logistic regression analysis, peak endocardial GLS (OR: 1.35, Both GWE and endocardial GLS contribute to improving the diagnostic performance of exercise stress echocardiography. Furthermore, adding peak GWE to peak endocardial GLS provides incremental diagnostic value during a non-invasive screening of significant CAD before radioactive or invasive examinations. Coronary artery disease (CAD) is one of the leading global causes of mortality and morbidity. Concerning the diagnostics of CAD, coronary angiography (CAG), which despite being considered the gold standard, only confirmed significant CAD in 38% of suspected patients . Stress The newly developed and explored –5 quantiHowever, as strain is load-dependent, increasing the afterload may underestimate the left ventricular (LV) function; therefore, myocardial work (MW), which combines strain and non-invasive LV pressure, could overcome the limitation. Global myocardial work efficiency (GWE) is one of the major MW parameters and is derived from the percentage ratio of constructive work to the sum of constructive work and wasted work. Recently, significantly lower GWE values were reported in patients with CAD, heart failure, hypertension with left ventricle hypertrophy, and COVID-19 –10, and Due to the limited data available, this study aims to compare the diagnostic value of GWE with myocardial layer-specific global longitudinal strain during exercise stress to detect significant CAD with normal baseline wall motion.The study was conducted in a single tertiary coronary care center with 89 patients without known ischemic heart disease who were referred with angina pectoris and had plans to undergo treadmill exercise stress testing and CAG. Patients with the following criteria were excluded: age <18 years; baseline LV ejection fraction <50%; abnormal baseline wall motion; previous myocardial infarction; prior coronary artery bypass grafting or coronary interventional therapy; left bundle branch block; atrial fibrillation; sustained severe arrhythmia; severe valvular dysfunction; inability to undergo exercise testing; absence of any of apical four-chamber, three-chamber, and two-chamber views; and inadequate image quality. All patients underwent two-dimensional (2D) echocardiography , and a treadmill exercise stress test followed by CAG.Written informed consent was given by all study participants or their legal representatives. The study complied with the Declaration of Helsinki and was approved by the Ethics Committees of Fuwai Hospital (no. 2018-1121).3 – (LV end-diastolic diameter)3] + 0.6}. LV mass was then indexed for body surface area to generate the LV mass index. LV ejection fraction was measured using Simpson's biplane method from apical four- and two-chamber views. Early trans-mitral velocity (E wave) and late trans-mitral velocity (A wave) were measured by pulsed-wave Doppler from the apical four-chamber view with the sample volume positioned at the tip of the mitral leaflets. Mitral inflow E/A ratio was calculated as E wave divided by A wave.Comprehensive conventional echocardiography was performed  using a The treadmill exercise stress test was conducted utilizing the standard Bruce protocol  whereby From each of the three apical views at rest and during exercise, the cardiac loop with the best representation of the LV wall was identified and analyzed in the commercially available software ; initially with automated function imaging (AFI) and subsequently with the 2D strain software. AFI identified and tracked the endocardium automatically to generate the LV global longitudinal strain (GLS), and the regional speckle area of interest was adjusted manually where the tracking was poor. For 2D strain analysis, the endocardial borders were manually delineated by the operator and then traced by the software in the end-systolic frame for the analyses of longitudinal endocardial, mid-myocardial, and epicardial strains . Images Global myocardial work efficiency was calculated from a combination of the 2D LV GLS (based on AFI) and a non-invasively estimated LV pressure, using the commercially obtained software  . BrachiaThe images from CAG were interpreted visually by an experienced cardiologist blinded to patients' echocardiographic data. Significant CAD was defined as ≥70% luminal diameter narrowing in one or more major epicardial vessels or ≥50% in the left main coronary .Intra- and interobserver variabilities were determined with 15 randomly selected patients, where the analysis was repeated by the same investigator 2 weeks later and by a second investigator blinded to the initial results of the first investigator, respectively.t-test or Mann–Whitney U-test, as appropriate, whereas categorical variables were compared with the chi-squared test or Fisher's exact test. Correlation between continuous variables was performed using Pearson's or Spearman's correlation coefficient. Univariate binary logistic regression analyses were performed to evaluate the association between the presence of significant CAD and the echocardiographic variables. After excluding variables that showed collinearity (Pearson's or Spearman's correlation coefficient ≥ 0.60 or variance inflation factor > 10), all variables that found to be significant on univariate binary logistic regression were considered for multiple binary regression analysis using the forward selection method. Receiver operating characteristic curve analysis and Youden's index were used to assess the optimal cutoff points for layer-specific strain and GWE in predicting significant CAD. The comparisons of AUCs were performed using the method described by DeLong et al.  when not normally distributed. Categorical variables are presented as absolute numbers and percentages. Normal distribution was verified by the Shapiro–Wilk test. Continuous variables were compared using Student's g et al. . Intraclp < 0.05 was considered statistically significant.Analyses were performed using SPSS, version 25.0 , MedCalc, version 18.2.1 , and GraphPad Prism 8 . All statistical tests were two-sided, and a p > 0.05) between the two groups regarding age, gender, heart rate, blood pressure, coronary dominance, and exercise ECG results. Patients with significant CAD showed a larger body surface area and body mass index (both p < 0.05) and a higher incidence of dyslipidemia (p < 0.05) compared with those in the non-significant CAD group  between the two groups for the conventional echocardiographic parameters of LV end-diastolic or end-systolic dimensions, LV septal thickness in end-diastole, LV mass index, mitral early-diastole velocity, mitral late-diastole velocity, and the ratio of mitral early-diastole velocity to late-diastole velocity. LV posterior wall thickness in end-diastole was significantly larger in the significant CAD group than that of the non-significant CAD group  compared with those in the non-significant group, although there were no significant differences observed during the rest or recovery periods  had significantly lower absolute values during peak exercise in the significant CAD group (p < 0.001), although the differences between the two groups were not significant at rest or during recovery , although at rest, the values of the two groups had no significant differences  and a good negative correlation with peak GLS using AFI  all presented modest positive correlations with peak GLS using AFI .Peak GWE showed modest negative correlations with peak endocardial, mid-myocardial, and epicardial GLS , peak GWE, and recovery GWE were significantly associated with significant CAD .p = 0.006) and peak GWE  were significantly associated with significant CAD  that was superior to peak mid-myocardial and epicardial GLS . However, the addition of peak GWE to peak endocardial GLS significantly increased the AUC over that of peak endocardial GLS  for the detection of significant CAD . The participants or their legal representatives provided their written informed consent to participate in this study.WW, ZZ, and HW contributed to the conception, design, supervision of the study, and revised the manuscript critically for intellectual content. JL drafted the manuscript. LG, JH, LN, YZ, XL, and JW contributed to the collection and interpretation of data. JL, ML, and YC contributed to statistical analysis. All authors contributed to the article and approved the submitted version.This study was supported by the Beijing Municipal Science and Technology Commission (Grant No. Z171100001017213) and Construction Research Project of Key Laboratory (Cultivation) of Chinese Academy of Medical Sciences (Grant No. 2019PT310025).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Undergraduate emergency medicine (EM) training is important because all medical graduates are expected to have basic emergency knowledge and skills regardless of their future speciality. EM clerkship should provide opportunities to improve not only knowledge and skills but also the self-efficacy of learners. This study aims to evaluate the expectations, opinions, and self-efficacy beliefs of medical students during a 4-week mandatory EM clerkship.This study used a prospective longitudinal design with quantitative and qualitative survey methods. It includes final year medical students of the 2015–2016 academic year. Voluntary de-identified pre- and post-clerkship surveys included 25 statements. The post-clerkship survey included two open-ended questions asking participants to identify the best and worst three aspects of EM clerkship. Responses were analysed to determine themes or commonalities in participant comments indicative of the EM clerkship learning experiences and environment.p value < 0.001). The only exception was the duration of clerkship, which was deemed insufficient both at the beginning and at the end . The students perceived that their self-efficacy improved significantly in the majority of basic EM skills and procedures . Emergent qualitative themes in the study also supported these results.Sixty-seven out of seventy-nine (85%) students responded to both pre- and post-clerkship surveys. Medical students’ expectations of EM clerkships’ effect on knowledge and skill acquisition were high, and a 4-week mandatory EM clerkship was able to meet their expectations. Medical students had very high expectations of EM clerkships’ educational environment. In most aspects, their experiences significantly exceeded their expectations (This study showed that a 4-week mandatory EM clerkship increased medical students' perceived self-efficacy in basic emergency management skills. The EM clerkship met students' expectations on knowledge and skill acquisition, and exceeded students’ expectations on educational environment. Undergraduate emergency medicine (EM) training is important because all medical graduates, regardless of their future speciality, are likely to have to deal with unexpected emergencies at some point in their careers. In addition to their professional duties in the hospital, medical graduates in many countries have an ethical obligation to provide medical care if they encounter out-of-hospital emergencies , 2. FurtTo improve medical students’ acute care management skills and confidence, EM clerkships, where medical students are exposed to unique acute care encounters, are essential components of medical school curricula , 5. HoweSelf-efficacy, a central concept of social cognitive theory, refers to an individual’s self-belief or self-confidence in performing a specific task to attain a certain standard , 13. TheEM clerkships can provide learning opportunities in various learning environments ranging from classroom-based learning to authentic clinical experience, which are necessary tools for increased self-efficacy. However, the interplay among multiple influences on self-efficacy, including intrapersonal influences and environmental forces, affects self-effıcacy development , 16. VicThis study aims to evaluate the expectations, opinions and self-efficacy beliefs of medical students during a 4-week mandatory EM clerkship and has two research questions: (1) to what extent can an EM clerkship meet students’ expectations regarding knowledge and skill acquisition, and educational environment? and (2) to what extent can an EM clerkship increase medical students' self-efficacy in basic emergency skills?This study is approved by The United Arab Emirates University (UAEU) Research and Graduate Studies Ethics Committee (ERS_2017_5496).This study was based on the EM clerkship experience of the 2015–2016 final year medical students of the College of Medicine and Health Sciences, UAEU, Al Ain, United Arab Emirates [The medical education department establishes the student groups at the beginning of each academic year. For the 2015–2016 academic year, there were three female and two male student groups. Each group has 12 to 19 students. The groups rotate through the five senior clinical clerkships of EM (4 weeks), family medicine (4 weeks), pediatrics (8 weeks), internal medicine (8 weeks), and surgery (8 weeks).Our EM clerkship is 4 weeks long and is undertaken during the final (sixth) year of medical school. The clerkship’s teaching and learning activities are designed according to international undergraduate curriculum recommendations , 21. In This study used prospective longitudinal design with quantitative and qualitative survey methods. A previously published survey  was adapp value. Two of the authors manually analysed the qualitative data for congruence and faithful representation of emerging themes..To compare students’ responses between the pre-clerkship and post-clerkship surveys, the non-parametric Wilcoxon signed-rank test was used. The internal consistency reliability of the survey was calculated using Cronbach’s alpha coefficient. To measure the strength and direction of the association between two variables, Spearman’s rank correlation was used. The Statistical Package for the Social Sciences  was used for quantitative analysis. Statistical significance is accepted at a level less than 0.05 of Seventy-nine final year medical students attended a 4-week mandatory EM clerkship during the study period of which 54 (68%) were female and 25 (32%) were male. The number of students in each of the five groups ranged from 12 to 19. Sixty-seven students (85%) responded to both pre-clerkship and post-clerkship surveys and were included in the analysis. A Cronbach’s alpha of 0.89 was observed for the pre-clerkship survey, indicating good internal consistency of this survey.Wilcoxon signed ranks test, p value: 0.33). Students’ scores on the educational environment of EM clerkship improved significantly . However, students’ scores on the appropriateness of the EM clerkship duration did not change after the clerkship .Table Wilcoxon Signed Ranks test, p value < 0.001). After the clerkship, students’ scores improved significantly in eight out of 13 statements. The scores for formulating a differential diagnosis list, developing an appropriate management plan, inserting a Foley catheter and inserting IV cannula/venipuncture were improved but did not show a significant change.Table Spearman’s Rho 0.53, p value < 0.001). Pre-clerkship scores of educational environment showed a weak correlation with pre-clerkship scores of perceived self-efficacy .The students’ pre-clerkship scores of perceived knowledge and skill acquisition were moderately correlated with pre-clerkship scores of perceived self-efficacy . Post-clerkship scores of educational environment showed moderate correlation with students’ post-clerkship scores of perceived self-efficacy .The students’ post-clerkship scores of perceived knowledge and skill acquisition showed a strong correlation with post-clerkship scores of perceived self-efficacy . The difference between post- and pre-clerkship scores of educational environment were moderately correlated with difference between post- and pre-clerkship scores on perceived self-efficacy .The difference between post- and pre-clerkship scores of knowledge and skills acquisition were moderately correlated with the difference between post- and pre-clerkship scores of perceived self-efficacy (In qualitative analysis, emerging themes about positive aspects of EM clerkship included numerous and diverse opportunities for hands-on training including patient encounters and procedures; helpful and supportive program director, and healthcare staff including attending physicians, residents and nurses; an organised and well-structured clerkship; high quality and diversity of teaching methods and materials. Additionally, the students stated that EM clerkship increased knowledge and confidence in patient management and procedures. Their main complaint was the short duration of EM clerkship. In addition, sleep deprivation due to shifts, difficulty filling logbook due to computer-based systems, and the suboptimal attitude of some healthcare staff were emerging themes. Also, students stated that they wished to receive additional EM training in the early years of medical school.Our results showed that medical students’ expectations on knowledge and skill acquisition were high and a 4-week mandatory EM clerkship was able to meet expectations. Similarly, they had very high expectations on educational environment. In most aspects of the educational environment, their experience exceeded their expectation significantly. The only exception was the duration of clerkship, which was deemed insufficient both at the beginning and at the end. The students perceived that their self-efficacy in the majority of basic skills and procedures improved significantly. These results were also supported by emergent qualitative themes in the study.Medical students’ expectations of EM clerkships are affected by many factors. EM’s popularity by mainstream and social media, students’ previous exposure to emergency departments, and previous students’ positive experiences with EM clerkship may affect students' expectations –27. In oThe implementation of EM clerkships in medical school curricula vary significantly. In the United States, a pioneer in EM training, the percentage of medical schools implementing mandatory EM clerkships was only 52% as of 2014 . In addiEM clerkship provides an excellent opportunity for medical students to practice fundamental topics and procedures and facilitates knowledge acquisition and self-efficacy in basic procedures and patient management skills –35. SimiThere are several ways to boost the self-efficacy of a learner. Previous successes, performed by self or observations of others, raise self-efficacy, while failures lower it . In our Self-efficacy is associated with motivation, which greatly facilitates learning. In undergraduate medical education, a higher level of motivation increases academic success and performance . The motIn addition to its relation to motivation and expectancy beliefs, self-efficacy has a sophisticated relation to performance . Mavis  examinedFirst, this was a single-center study conducted over one academic year having a small sample size. Second, there was no control group to compare the effect of mandatory versus elective clerkships, different clerkship durations and different EM clerkship years. Third, we did not use a previously validated self-efficacy scale, which may provide more structured and objective information [Fourth, we did not compare OSCE and written assessment scores with students' self-efficacy belief scores, which could give additional information regarding students' actual gain in the clerkship. Instead, we measured subjective expectations and opinions on knowledge and skills acquisition, and educational environment. Fifth, the clerkship is modelled after international undergraduate curriculum recommendations, which may differ from the curricula used at other institutions, limiting the generalisability of the study. Finally, we acknowledge there is scope for longitudinal research, evaluating a broader set of related constructs and changes in self-efficacy.There are some limitations in our study. ormation , 48. CogThis study has shown that a 4-week mandatory EM clerkship increased medical students' perceived self-efficacy in basic emergency management and skills. It also met students’ expectations on knowledge and skill acquisition and exceeded students' expectations on the educational environment. Considering their contributions to learning, motivation, and performance, self-efficacy and expectations of educational environment and activities are valuable factors in developing and measuring EM clerkships. Future studies could focus on how changes to the curricula could affect self-efficacy beliefs and could also look at whether there is a correlation between self-efficacy beliefs and performance by comparing the self-efficacy scores of students to OSCE, work-based assessments, or written test scores.