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(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm (TAA). The current study evaluated intra- and interobserver reproducibility of 4D flow MRI-derived hemodynamic parameters (normalized flow displacement, flow jet angle, wall shear stress (WSS) magnitude, axial WSS, circumferential WSS, WSS angle, vorticity, helicity, and local normalized helicity (LNH)) in TAA patients; (2) Methods: The thoracic aorta of 20 patients was semi-automatically segmented on 4D flow MRI data in 5 systolic phases by 3 different observers. Each time-dependent segmentation was manually improved and partitioned into six anatomical segments. The hemodynamic parameters were quantified per phase and segment. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated; (3) Results: A total of 2400 lumen segments were analyzed. The mean aneurysm diameter was 50.8 ± 2.7 mm. The intra- and interobserver analysis demonstrated a good reproducibility (COV = 16–30% and ICC = 0.84–0.94) for normalized flow displacement and jet angle, a very good-to-excellent reproducibility (COV = 3–26% and ICC = 0.87–1.00) for all WSS components, helicity and LNH, and an excellent reproducibility (COV = 3–10% and ICC = 0.96–1.00) for vorticity; (4) Conclusion: 4D flow MRI-derived hemodynamic parameters are reproducible within the thoracic aorta in TAA patients.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

The COVID-19 pandemic has posed challenges to maintaining medical care for patients with Parkinson’s disease (PD). The Parkinson’s Disease during the COVID-19 Pandemic (ParCoPa) survey was conducted as an online, nationwide, cross-sectional survey from December 2020 to March 2021 and aimed to assess the impact of the pandemic on the medical care of PD patients from the physicians’ perspective. Invitations containing a randomly generated registration code were mailed to healthcare professionals from sixty-seven specialty centers in Germany. Confounders for the worsening of subjective treatment quality, perceived health risk due to the profession, and adequate protective measures against SARS-CoV-2 were assessed using logistic regression analysis. Of all forty physicians who responded, 87.5% reported a worsening of motor and nonmotor symptoms in their patients, 97.5% experienced cancellation of appointments, and difficulties in organizing advanced and supplementary therapies were reported by over 95%. Participants offered alternative consultation options, mostly in the form of telephone (77.5%) or online (64.1%) consultations, but telephone consultations were the most accepted by patients (“broadly accepted”, 40.0%). We identified pandemic-related deficits in providing care for patients with PD and areas of improvement to ensure continued care for this vulnerable patient population.

BackgroundAnimal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults.Methodology/principal findingsStandardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations.ConclusionIn subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall.

BackgroundEgypt is a country of nearly 100 million citizens, and there are less than 1000 registered psychiatrists. The mental health care system is under resourced and nearly inaccessible for the majority of the population. In addition, youth under the age of 25 years represent 50% of Egyptian citizens; however, there are no specific services addressing their unique needs. How can the needs of the largest population in the Middle East be effectively addressed? Is a web-based framework an option for Egyptian psychiatrists to serve the population? ObjectiveThe aims of this study were to better understand the opinions of psychiatrists on the current state of mental health care services in Egypt and their current knowledge on electronic mental health (EMH); assess the attitudes of Egyptian psychiatrists toward web-based interventions and telemedicine for mental health; and identify perceived advantages and barriers of EMH development in Egypt. MethodsA cross-sectional survey was conducted online among 640 Egyptian psychiatrists. It included a total of 36 items within a set of 16 questions asking about EMH literacy, integrating EMH into the mental health care system, and the perceived priorities and barriers of EMH. The sampling was supported by Tanta University, a large academic institution close to Cairo. Statistical analysis was performed using SPSS 25 (IBM Corp). Descriptive statistics, the chi-square test, the independent sample t test, and analysis of variance were applied. ResultsA total of 188 participants responded (response rate of 29.4%), of which 54.2% (102/188) were female and 54.3% (102/188) were between 30 and 45 years old. Less than half of the participants thought that the current health care system was efficient for adults (69/155, 44.4%), and even less thought it was efficient for youth (44/155, 28.3%). Almost all participants agreed that EMH would be beneficial for patient care (147/155, 94.8%) and that integrating EMH into the current health care system would be a good idea (118/155, 76.2%). The highest rated utility of web-based solutions was documentation, followed by psychoeducation and communication with professionals. The main advantages were to improve access to care in rural areas of the country and its convenience. ConclusionsThere is scarcity of mental health resources in Egypt. Egyptian psychiatrists are interested in EMH and believe web-based platforms can become part of the solution for the Egyptian mental health care system.

BackgroundPublic health emergencies like epidemics put enormous pressure on health care systems while revealing deep structural and functional problems in the organization of care. The current coronavirus disease (COVID-19) pandemic illustrates this at a global level. The sudden increased demand on delivery systems puts unique pressures on pre-established care pathways. These extraordinary times require efficient tools for smart governance and resource allocation. ObjectiveThe aim of this study is to develop an innovative web-based solution addressing the seemingly insurmountable challenges of triaging, monitoring, and delivering nonhospital services unleashed by the COVID-19 pandemic. MethodsAn adaptable crisis management digital platform was envisioned and designed with the goal of improving the system’s response on the basis of the literature; an existing shared health record platform; and discussions between health care providers, decision makers, academia, and the private sector in response to the COVID 19 epidemic. ResultsThe Crisis Management Platform was developed and offered to health authorities in Ontario on a nonprofit basis. It has the capability to dramatically streamline patient intake, triage, monitoring, referral, and delivery of nonhospital services. It decentralizes the provision of services (by moving them online) and centralizes data gathering and analysis, maximizing the use of existing human resources, facilitating evidence-based decision making, and minimizing the risk to both users and providers. It has unlimited scale-up possibilities (only constrained by human health risk resource availability) with minimal marginal cost. Similar web-based solutions have the potential to fill an urgent gap in resource allocation, becoming a unique asset for health systems governance and management during critical times. They highlight the potential effectiveness of web-based solutions if built on an outcome-driven architecture. ConclusionsData and web-based approaches in response to a public health crisis are key to evidence-driven oversight and management of public health emergencies.

Social anxiety disorder (SAD) is serious psychiatric condition with a genetic background. Insight into the neurobiological alterations underlying the disorder is essential to develop effective interventions that could relieve SAD-related suffering. In this expert review, we consider recent neuroimaging work on SAD. First, we focus on new results from magnetic resonance imaging studies dedicated to outlining biomarkers of SAD, including encouraging findings with respect to structural and functional brain alterations associated with the disorder. Furthermore, we highlight innovative studies in the field of neuroprediction and studies that established the effects of treatment on brain characteristics. Next, we describe novel work aimed to delineate endophenotypes of SAD, providing insight into the genetic susceptibility to develop the disorder. Finally, we outline outstanding questions and point out directions for future research.

Background: Social anxiety disorder (SAD) is a mental illness with a complex, partially genetic background. Differences in characteristics of white matter (WM) microstructure have been reported in patients with SAD compared to healthy controls. Also, WM characteristics are moderately to highly heritable. Endophenotypes are measurable characteristics on the road from genotype to phenotype, putatively reflective of genetically based disease mechanisms. In search of candidate endophenotypes of SAD we used a unique sample of SAD patients and their family members of two generations to explore microstructure of WM tracts as candidate endophenotypes. We focused on two endophenotype criteria: co-segregation with social anxiety within the families, and heritability. Methods: Participants (n = 94 from 8 families genetically vulnerable for SAD) took part in the Leiden Family Lab Study on Social Anxiety Disorder (LFLSAD). We employed tract-based spatial statistics to examine structural WM characteristics, being fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD), in three a-priori defined tracts of interest: uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF). Associations with social anxiety symptoms and heritability were estimated. Results: Increased FA in the left and right SLF co-segregated with symptoms of social anxiety. These findings were coupled with decreased RD and MD. All characteristics of WM microstructure were estimated to be at least moderately heritable. Conclusion: These findings suggest that alterations in WM microstructure in the SLF could be candidate endophenotypes of SAD, as they co-segregated within families genetically vulnerable for SAD and are heritable. These findings further elucidate the genetic susceptibility to SAD and improve our understanding of the overall etiology.

Potato spindle tuber viroid and other pospiviroids can cause serious diseases in potato and tomato crops. Consequently, pospiviroids are regulated in several countries. Since seed transmission is considered as a pathway for the introduction and spread of pospiviroids, some countries demand for the testing of seed lots of solanaceous crops for the presence of pospiviroids. A real-time RT-PCR test, named PospiSense, was developed for testing pepper (Capsicum annuum) and tomato (Solanum lycopersicum) seeds for seven pospiviroid species known to occur naturally in these crops. The test consists of two multiplex reactions running in parallel, PospiSense 1 and PospiSense 2, that target Citrus exocortis viroid (CEVd), Columnea latent viroid (CLVd), pepper chat fruit viroid (PCFVd), potato spindle tuber viroid (PSTVd), tomato apical stunt viroid (TASVd), tomato chlorotic dwarf viroid (TCDVd) and tomato planta macho viroid (TPMVd, including the former Mexican papita viroid). Dahlia latent viroid (DLVd) is used as an internal isolation control. Validation of the test showed that for both pepper and tomato seeds the current requirements of a routine screening test are fulfilled, i.e. the ability to detect one infested seed in a sample of c.1000 seeds for each of these seven pospiviroids. Additionally, the PospiSense test performed well in an inter-laboratory comparison, which included two routine seed-testing laboratories, and as such provides a relatively easy alternative to the currently used tests.

Tomato brown rugose fruit virus (ToBRFV) is a Tobamovirus that was first observed in 2014 and 2015 on tomato plants in Israel and Jordan respectively. Since the first description, the virus has been reported from all continents except Oceania and Antarctica, and has been found infecting both tomato and pepper crops. In October 2019, the Dutch National Plant Protection Organization received a ToBRFV infected tomato sample as part of a generic survey targeting tomato pests. Presence of the virus was verified using Illumina sequencing. A follow-up survey was initiated to determine the extent of ToBRFV presence in the Dutch tomato horticulture and identify possible linkages between ToBRFV genotypes, companies and epidemiological traits. Nextstrain was used to visualize these potential connections. By November 2019, 68 companies had been visited of which 17 companies were found to be infected. The 50 ToBRFV genomes from these outbreak locations group in three main clusters, which are hypothesized to represent three original sources. No correlation was found between genotypes, companies and epidemiological traits, and the source(s) of the Dutch ToBRFV outbreak remain unknown. This paper describes a Nextstrain build containing ToBRFV genomes up to and including November 2019. Sharing data with this interactive online tool will enable the plant virology field to better understand and communicate the diversity and spread of this new virus. Organizations are invited to share data or materials for inclusion in the Nextstrain build, which can be accessed at https://nextstrain.nrcnvwa.nl/ToBRFV/20191231.

Social anxiety disorder (SAD) runs in families, but the neurobiological pathways underlying the genetic susceptibility towards SAD are largely unknown. Here, we employed an endophenotype approach, and tested the hypothesis that amygdala hyperreactivity to faces conditioned with a social-evaluative meaning is a candidate SAD endophenotype. We used data from the multiplex, multigenerational Leiden Family Lab study on Social Anxiety Disorder (eight families, n = 105) and investigated amygdala activation during a social-evaluative conditioning paradigm with high ecological validity in the context of SAD. Three neutral faces were repeatedly presented in combination with socially negative, positive or neutral sentences. We focused on two endophenotype criteria: co-segregation of the candidate endophenotype with the disorder within families, and heritability. Analyses of the fMRI data were restricted to the amygdala as a region of interest, and association analyses revealed that bilateral amygdala hyperreactivity in response to the conditioned faces co-segregated with social anxiety (SA; continuous measure) within the families; we found, however, no relationship between SA and brain activation in response to more specific fMRI contrasts. Furthermore, brain activation in a small subset of voxels within these amygdala clusters was at least moderately heritable. Taken together, these findings show that amygdala engagement in response to conditioned faces with a social-evaluative meaning qualifies as a neurobiological candidate endophenotype of social anxiety. Thereby, these data shed light on the genetic vulnerability to develop SAD.

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from ‘The Cognitive decline in Older Patients with End stage renal disease’ (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Background: Social anxiety disorder (SAD) is a disabling psychiatric condition with a genetic background. Brain alterations in gray matter (GM) related to SAD have been previously reported, but it remains to be elucidated whether GM measures are candidate endophenotypes of SAD. Endophenotypes are measurable characteristics on the causal pathway from genotype to phenotype, providing insight in genetically-based disease mechanisms. Based on a review of existing evidence, we examined whether GM characteristics meet two endophenotype criteria, using data from a unique sample of SAD-patients and their family-members of two generations. First, we investigated whether GM characteristics co-segregate with social anxiety within families genetically enriched for SAD. Secondly, heritability of the GM characteristics was estimated. Methods: Families with a genetic predisposition for SAD participated in the Leiden Family Lab study on SAD; T1-weighted MRI brain scans were acquired (n = 110, 8 families). Subcortical volumes, cortical thickness and cortical surface area were determined for a-priori determined regions of interest (ROIs). Next, associations with social anxiety and heritabilities were estimated. Findings: Several subcortical and cortical GM characteristics, derived from frontal, parietal and temporal ROIs, co-segregated with social anxiety within families (uncorrected p-level) and showed moderate to high heritability. Interpretation: These findings provide preliminary evidence that GM characteristics of multiple ROIs, which are distributed over the brain, are candidate endophenotypes of SAD. Thereby, they shed light on the genetic vulnerability for SAD. Future research is needed to confirm these results and to link them to functional brain alterations and to genetic variations underlying these GM changes. Fund: Leiden University Research Profile ‘Health, Prevention and the Human Life Cycle’. Keywords: Social anxiety disorder, Family study, Endophenotypes, Structural MRI

Abstract Background Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment. Methods Forty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups. Results LV KEiEDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P

Social anxiety disorder is an invalidating psychiatric disorder characterized by extreme fear and avoidance of one or more social situations in which patients might experience scrutiny by others. The goal of this two-generation family study was to delineate behavioral and electrocortical endophenotypes of social anxiety disorder related to social evaluation. Nine families of patients with social anxiety disorder (their spouse and children, and siblings of these patients with spouse and children) performed a social judgment paradigm in which they believed to be evaluated by peers. For each peer, participants indicated their expectation about the evaluative outcome, after which they received social acceptance or rejection feedback. Task behavior, as well as the feedback-related EEG brain potentials (N1, FRN, P3) and theta power were tested as candidate endophenotypes based on two criteria: co-segregation with social anxiety disorder within families and heritability. Results indicated that reaction time for indicating acceptance-expectations might be a candidate behavioral endophenotype of social anxiety disorder, possibly reflecting increased uncertainty or self-focused attention and vigilance during the social judgment paradigm. N1 in response to expected rejection feedback and P3 in response to acceptance feedback might be candidate electrocortical endophenotypes of social anxiety disorder, although the heritability analyses did not remain significant after correcting for multiple tests. Increased N1 possibly reflects hypervigilance to socially threatening stimuli, and increased P3 might reflect that positive feedback is more important for, and/or less expected by, participants with social anxiety disorder. Finally, increased feedback-related negativity and theta power in response to unexpected rejection feedback compared to the other conditions co-segregated with social anxiety disorder, but these EEG measures were not heritable. The candidate endophenotypes might play a new and promising role in future research on genetic mechanisms, early detection and/or prevention of social anxiety disorder. Keywords: Endophenotype, Event-related potential, Social anxiety disorder, Social evaluation, Theta power

Abstract Background Tricuspid valve (TV) regurgitation (TR) is a common complication of pulmonary hypertension and right-sided congenital heart disease, associated with increased morbidity and mortality. Estimation of TR severity by echocardiography and conventional cardiovasvular magnetic resonance (CMR) is not well validated and has high variability. 4D velocity-encoded (4D-flow) CMR was used to measure tricuspid flow in patients with complex right ventricular (RV) geometry and varying degrees of TR. The aims of the present study were: 1) to assess accuracy of 4D-flow CMR across the TV by comparing 4D-flow CMR derived TV effective flow to 2D-flow derived effective flow across the pulmonary valve (PV); 2) to assess TV 4D-flow CMR reproducibility, and 3) to compare TR grade by 4D-flow CMR to TR grade by echocardiography. Methods TR was assessed by both 4D-flow CMR and echocardiography in 21 healthy subjects (41.2 ± 10.5 yrs., female 7 (33%)) and 67 RV pressure-load patients (42.7 ± 17.0 yrs., female 32 (48%)). The CMR protocol included 4D-flow CMR measurement across the TV, 2D-flow measurement across the PV and conventional planimetric measurements. TR grading on echocardiographic images was performed based on the international recommendations. Bland-Altman analysis and intra-class correlation coefficients (ICC) were used to asses correlations and agreement. Results TV effective flow measured by 4D-flow CMR showed good correlation and agreement with PV effective flow measured by 2D-flow CMR with ICC = 0.899 (p

Targeted school-based programs seem to be a promising approach to help adolescents in need. Nevertheless, successful implementation and evaluation of such programs is challenging. However, there is limited knowledge about (overcoming) the challenges of implementation and experimental evaluation of school-based programs. The goal of the present paper is, therefore, to improve future research by describing the challenges encountered and lessons learned during two randomized controlled trials (RCTs) to study the effectiveness of two skills-training programs reducing school or social stress. In this way, we aim to inform others who plan to implement and evaluate such programs in schools using an RCT design. Some of the challenges encountered apply to all effectiveness studies, such as the recruitment and retention of participants; others are more "intervention at school" specific, such as scheduling the programs and assessments. Our experiences show that it is possible to effectively implement and evaluate targeted programs promoting adolescent mental health in secondary schools with RCTs, even during a worldwide health pandemic, but that it requires investing sufficient time in keeping close and regular contact as well as clear communication between the involved parties. Moreover, high levels of flexibility are needed in adjusting scheduled meetings for intervention and research while keeping track of the entire process for each school and individual participant. [ABSTRACT FROM AUTHOR]

High-throughput sequencing (HTS) technologies and bioinformatic analyses are of growing interest to be used as a routine diagnostic tool in the field of plant viruses. The reliability of HTS workflows from sample preparation to data analysis and results interpretation for plant virus detection and identification must be evaluated (verified and validated) to approve this tool for diagnostics. Many different extraction methods, library preparation protocols, and sequence and bioinformatic pipelines are available for virus sequence detection. To assess the performance of plant virology diagnostic laboratories in using the HTS of ribosomal RNA depleted total RNA (ribodepleted totRNA) as a diagnostic tool, we carried out an interlaboratory comparison study in which eight participants were required to use the same samples, (RNA) extraction kit, ribosomal RNA depletion kit, and commercial sequencing provider, but also their own bioinformatics pipeline, for analysis. The accuracy of virus detection ranged from 65% to 100%. The false-positive detection rate was very low and was related to the misinterpretation of results as well as to possible cross-contaminations in the lab or sequencing provider. The bioinformatic pipeline used by each laboratory influenced the correct detection of the viruses of this study. The main difficulty was the detection of a novel virus as its sequence was not available in a publicly accessible database at the time. The raw data were reanalysed using Virtool to assess its ability for virus detection. All virus sequences were detected using Virtool in the different pools. This study revealed that the ribodepletion target enrichment for sample preparation is a reliable approach for the detection of plant viruses with different genomes. A significant level of virology expertise is needed to correctly interpret the results. It is also important to improve and complete the reference data.

Student performance is related to motivation to learn. As motivation generally declines during lower secondary education, one might expect performance to decline as well during this period. Though, until now, it has been unclear whether this pattern exists. In the present study, we examined student performance during the early years of secondary education from a developmental perspective. Participants were 1,544 Dutch secondary school students across three grades (grades 7 to 9). To investigate student performance trends, we analysed report card grades by using hierarchical linear modelling with two levels (level 1, time point; level 2, student). Potential moderators to be examined were (1) gender, (2) school type and (3) initial level. A linear decline in report card grades from grade 7 to 9 was found for boys and girls, in all school types, and regardless of initial level. Two variables moderated the steepness of the decline: school type and initial level. Gender and school type had a main effect on performance level. The same pattern was observed for the subset of "core subjects"--Dutch, English and mathematics. Motivational and cognitive factors that may explain the performance decline are discussed.

Adolescents become increasingly sensitive to social evaluation. Some previous studies have related this change to pubertal development. The present longitudinal study examined the role of sociocognitive development. We investigated whether or not the transition to recursive thinking, the ability to think about (others') thoughts, would be associated with changes in the magnitude and timing of the cortisol response to social evaluation. Salivary cortisol was obtained during the Leiden Public Speaking Task. The task was administered twice with a 2-year interval to 221 participants, aged 9-17 years at Time 1. The area under the curve was computed to assess the magnitude of the overall cortisol response. Two difference scores, reflecting speech anticipation and speech delivery, were computed to assess the timing of the cortisol response. Recursive thinking was measured with a cartoon description task. Regression analyses with clustered bootstrap controlling for pubertal development, age, and general cognitive functioning showed that the transition to recursive thinking predicted an increase in the cortisol response to speech anticipation, but was unrelated to the magnitude of the overall cortisol response. This is in line with the view that increasing sensitivity to social evaluation in adolescence is mainly due to the effects of pubertal hormones on affective regions of the brain. Sociocognitive development affected the timing rather than the magnitude of the cortisol response. The results suggest that recursive thinking enables earlier realization of social-evaluative threat.

Abstract Background Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013–08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. Methods The BOOG 2013–08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1–2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. Discussion If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. Trial registration The BOOG 2013–08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828

Background:. Nerve injuries in the hand are common and often pose a challenge for the upper extremity surgeon. A range of reconstructive options exist for nerve repair, but proper matching of nerve diameter is important for many of these techniques. The purposes of this study were to (1) describe the nerve diameters of the hand and their relative differences and (2) investigate whether there is a relationship between nerve diameter and external hand dimensions or body mass index. Methods:. We utilized 18 freshly frozen cadaveric hands from adult donors aged 20–86 of both sexes for this study. Two independent observers measured each nerve diameter to the nearest 0.1 mm using a digital caliper. Results:. Using the flexor zones as boundaries, a total of 33 nerve measurements were performed for each cadaveric hand. Nerve diameter increased from the distal to the proximal flexor zones. The internal common digital nerves in flexor zone 3 were larger than the external digital nerves. The median nerve was found to be nearly 2 times larger than the ulnar nerve at 2 locations within the wrist. There was a positive correlation between body mass index, hand span, hand width, and nerve diameter at several measured locations. Conclusions:. This study provides reference values for nerve diameters of the hand and wrist and describes their relative differences. It is important for surgeons to be aware of these differences and to consider this information as we advance our efforts to reconstruct the hand and develop technologies for nerve repair.

While much is known about the factors related to student performance beyond Grade 3 less is known about the factors that are related to student performance in early childhood education and the early years in primary school. As part of the 'I go to school' project in South Australia, this study tracked children attending integrated preschool/childcare centres -- known as Children's Centres -- as they made their transition to school. Results indicated that children who attended early childhood education programs that were of higher quality -- as characterised by higher staff qualifications and a greater range and more engaging children's activities -- showed a greater gain in cognitive development than children who attended lower quality programs. Findings also suggested that children who benefitted the most from attendance in these programs were children from backgrounds of greater social disadvantage than children from less disadvantaged backgrounds.