Higher-order dimensions of psychopathology in a neurodevelopmental transdiagnostic sample.

Funder: Brain Sciences Unit University of CambridgeHierarchical dimensional models of psychopathology derived for adult and child community populations offer more informative and efficient methods for assessing and treating symptoms of mental ill health than traditional diagnostic approaches. It is not yet clear how many dimensions should be included in models for youth with neurodevelopmental conditions. The aim of this study was to delineate the hierarchical dimensional structure of psychopathology in a transdiagnostic sample of children and adolescents with learning-related problems, and to test the concurrent predictive value of the model for clinically, socially, and educationally relevant outcomes. A sample of N = 403 participants from the Centre for Attention Learning and Memory (CALM) cohort were included. Hierarchical factor analysis delineated dimensions of psychopathology from ratings on the Conner's Parent Rating Short Form, the Revised Children's Anxiety and Depression Scale, and the Strengths and Difficulties Questionnaire. A hierarchical structure with a general p factor at the apex, broad internalizing and broad externalizing spectra below, and three more specific factors (specific internalizing, social maladjustment, and neurodevelopmental) emerged. The p factor predicted all concurrently measured social, clinical, and educational outcomes, but the other dimensions provided incremental predictive value. The neurodevelopmental dimension, which captured symptoms of inattention, hyperactivity, and executive function and emerged from the higher-order externalizing factor, was the strongest predictor of learning. This suggests that in struggling learners, cognitive and affective behaviors may interact to influence learning outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Preparing to Learn: Structuring the Basic Course to Increase Student Preparation and Learning

This manuscript investigates whether frequent quizzing might facilitate greater preparation and learning in the Basic Course and tests variations of frequent quizzing through a series of three separate studies in order to identify best practices for using such quizzes. The first study showed that students who were given frequent quizzes performed better on the final exam than students who were given a midterm. The second study showed that frequent online quizzes can be just as effective as frequent in-class quizzes. In the final study, students were given skeletal notes to fill out as they prepared for class, and the results showed that students who were allowed to use their notes performed better than those who could note use their notes on quizzes, but those who did not use their notes on quizzes performed better on the final exam and had greater long-term retention

Can mother-to-child transmission of HIV be eliminated without addressing the issue of stigma? Modeling the case for a setting in South Africa.

BACKGROUND: Stigma and discrimination ontinue to undermine the effectiveness of the HIV response. Despite a growing body of evidence of the negative relationship between stigma and HIV outcomes, there is a paucity of data available on the prevalence of stigma and its impact. We present a probabilistic cascade model to estimate the magnitude of impact stigma has on mother-to-child-transmission (MTCT). METHODS: The model was parameterized using 2010 data from Johannesburg, South Africa, from which loss-to-care at each stage of the antenatal cascade were available. Three scenarios were compared to assess the individual contributions of stigma, non-stigma related barriers, and drug ineffectiveness on the overall number of infant infections. Uncertainty analysis was used to estimate plausible ranges. The model follows the guidelines in place in 2010 when the data were extracted (WHO Option A), and compares this with model results had Option B+ been implemented at the time. RESULTS: The model estimated under Option A, 35% of infant infections being attributed to stigma. This compares to 51% of total infections had Option B+ been implemented in 2010. Under Option B+, the model estimated fewer infections than Option A, due to the availability of more effective drugs. Only 8% (Option A) and 9% (Option B+) of infant infections were attributed to drug ineffectiveness, with the trade-off in the proportion of infections being between stigma and non-stigma-related barriers. CONCLUSIONS: The model demonstrates that while the effect of stigma on retention of women at any given stage along the cascade can be relatively small, the cumulative effect can be large. Reducing stigma may be critical in reaching MTCT elimination targets, because as countries improve supply-side factors, the relative impact of stigma becomes greater. The cumulative nature of the PMTCT cascade results in stigma having a large effect, this feature may be harnessed for efficiency in investment by prioritizing interventions that can affect multiple stages of the cascade simultaneously

Serum concentrations of the biomarkers CA125, CA15-3, CA72-4, tPSA and PAPP-A in natural and stimulated ovarian cycles

Objective: Biomarkers associated with cancer screening (CA125, CA15-3, CA72-4, total prostate specific antigen [tPSA]) and the monitoring of pregnancy (pregnancy associated plasma protein-A [PAPP-A]) were measured during natural and stimulated ovarian cycles in disease-free non-pregnant women to determine if they could reflect normal events relating to ovulation and/or endometrial changes. Methods: A total of 73 blood samples (10 women) collected throughout the natural menstrual cycle, and 64 blood samples (11 women) taken during stimulated ovarian cycles, were analysed on the Roche Cobas e411 automated analyser. Results: Detectable levels of tPSA were measured in at least one point in the cycle in 6/10 of women in the natural cycle and 10/11 of women in stimulated cycles, and CA72-4 was detected in only 12/21 women tested. Concentrations of CA125, tPSA, CA15-3 and CA72-4 showed no significant difference between the natural and stimulated ovarian cycle groups. On average the mean PAPP-A of the natural group was (2.41±0.58) mIU/L higher than the stimulated group (t=4.10, P\u3c 0.001). CA125 and CA15-3 results were both significantly influenced by the stage of the cycle (P\u3c0.0001), whereas tPSA and PAPP-A concentrations revealed no significant changes (P≥0.65). CA72-4 was not affected by the stage of the cycle nor ovarian stimulation. Conclusion: Ovarian stimulation reduced serum PAPP-A levels, CA125 and CA15-3 levels were generally unaffected by ovarian stimulation but displayed cyclical changes throughout both natural and stimulated cycles, whilst tPSA and CA72-4 were not affected by the stage of the cycle or ovarian stimulation

Repetitive negative thinking in the perinatal period and its relationship with anxiety and depression

Background: Rumination and worry represent two types of repetitive negative thinking (RNT), and their predictive and maintaining roles are well-established in depression and anxiety, respectively. Furthermore, there is an emerging literature on the link between RNT and psychological wellbeing in the perinatal period. Methods: We conducted a scoping review of studies that have investigated the relationship between RNT and perinatal depression and anxiety. We identified 87 papers eligible for inclusion in the review; they included cross-sectional and longitudinal studies, as well as treatment evaluations (pilot trials and randomised controlled trials). Results: Cross-sectional studies provided evidence of an association between RNT (i.e., rumination and worry) and depression and anxiety, in both pregnancy and postpartum. Longitudinal findings were mixed. Whilst antenatal worry consistently predicted subsequent depression and anxiety (both later in pregnancy and postpartum), rumination did not consistently predict depression. However, there was some evidence that RNT interacted with other processes to predict later psychopathology. Three randomised controlled trials evaluated whether psychological treatments reduce RNT in the perinatal period, only one of which included a clinical sample. Limitations: No experimental investigations were eligible for inclusion in the review. Conclusions: Further studies are needed to further our understanding of the nature and role of RNT in pregnancy and postpartum, and its consequences for maternal mental health. These include (but are not limited to) experimental investigations, studies with large clinical samples, and RCTs evaluating the effectiveness of psychological interventions targeting RNT to prevent and treat perinatal depression and anxiety

Efficacy and moderators of efficacy of trauma-focused cognitive behavioural therapies in children and adolescents: protocol for an individual participant data meta-analysis from randomised trials.

INTRODUCTION: Trauma-focused cognitive behavioural therapies are the first-line treatment for posttraumatic stress disorder (PTSD) in children and adolescents. Nevertheless, open questions remain with respect to efficacy: why does this first-line treatment not work for everyone? For whom does it work best? Individual clinical trials often do not provide sufficient statistical power to examine and substantiate moderating factors. To overcome the issue of limited power, an individual participant data meta-analysis of randomised trials evaluating forms of trauma-focused cognitive behavioural therapy in children and adolescents aged 6-18 years will be conducted. METHODS AND ANALYSIS: We will update the National Institute for Health and Care Excellence guideline literature search from 2018 with an electronic search in the databases PsycINFO, MEDLINE, Embase, Cochrane Central Register of Controlled Trials and CINAHL with the terms (trauma* OR stress*) AND (cognitive therap* OR psychotherap*) AND (trial* OR review*). Electronic searches will be supplemented by a comprehensive grey literature search in archives and trial registries. Only randomised trials that used any manualised psychological treatment-that is a trauma-focused cognitive behavioural therapy for children and adolescents-will be included. The primary outcome variable will be child-reported posttraumatic stress symptoms (PTSS) post-treatment. Proxy-reports (teacher, parent and caregiver) will be analysed separately. Secondary outcomes will include follow-up assessments of PTSS, PTSD diagnosis and symptoms of comorbid disorders such as depression, anxiety-related and externalising problems. Random-effects models applying restricted maximum likelihood estimation will be used for all analyses. We will use the Revised Cochrane Risk of Bias tool to measure risk of bias. ETHICS AND DISSEMINATION: Contributing study authors need to have permission to share anonymised data. Contributing studies will be required to remove patient identifiers before providing their data. Results will be published in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER: CRD42019151954

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

BACKGROUND During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.This study was supported by funding from the National Health and Medical Research Council (NHMRC) (1011136) of Australia and National Institutes of Health (NIH) USA grant 3U01DK094526-04S1 (PI A P McMahon). Author Danica Ryan was the recipient of the Biomedicine Discovery Scholarship from Monash University and author Megan R. Sutherland was supported by a NHMRC CJ Martin Fellowship

Comparison of quality control methods for automated diffusion tensor imaging analysis pipelines

© 2019 Haddad et al. The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, various levels of motion artifacts, and thermal noise. Variability was also examined in 20 DTI datasets acquired in subjects with vascular cognitive impairment (VCI) from the multi-site Ontario Neurodegenerative Disease Research Initiative (ONDRI). The mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated in global brain grey matter (GM) and white matter (WM) regions. For the simulated DTI datasets, the measure used to evaluate the performance of the pipelines was the normalized difference between the mean DTI metrics measured in GM and WM regions and the corresponding ground truth DTI value. The performance of the proposed pipelines was very similar, particularly in FA measurements. However, the pipeline based on the RESTORE algorithm was the most accurate when analyzing the artifact containing DTI datasets. The pipeline that combined the DTIPrep protocol and the RESTORE algorithm produced the lowest standard deviation in FA measurements in normal appearing WM across subjects. We concluded that this pipeline was the most robust and is preferred for automated analysis of multisite brain DTI data

Fabrication and characterisation of drug-loaded electrospun polymeric nanofibers for controlled release in hernia repair

The chemical distribution and mechanical effects of drug compounds in loaded electrospun scaffolds, a potential material for hernia repair mesh, were characterised and the efficacy of the material was evaluated. Polycaprolactone electrospun fibres were loaded with either the antibacterial agent, irgasan, or the broad-spectrum antibiotic, levofloxacin. The samples were subsequently characterised by rheological studies, scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle goniometry (CAG), in vitro drug release studies, antibacterial studies and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Increased linear viscoelastic regions observed in the rheometry studies suggest that both irgasan and levofloxacin alter the internal structure of the native polymeric matrix. In vitro drug release studies from the loaded polymeric matrix showed significant differences in release rates for the two drug compounds under investigation. Irgasan showed sustained release, most likely driven by molecular diffusion through the scaffold. Conversely, levofloxacin exhibited a burst release profile indicative of phase separation at the edge of the fibres. Two scaffold types successfully inhibited bacterial growth when tested with strains of E. coli and S. aureus. Electrospinning drug-loaded polyester fibres is an alternative, feasible and effective method for fabricating non-woven fibrous meshes for controlled release in hernia repair

Developing a decision aid to guide public sector health policy decisions: A study protocol

<p>Abstract</p> <p>Background</p> <p>Decision aids have been developed in a number of health disciplines to support evidence-informed decision making, including patient decision aids and clinical practice guidelines. However, policy contexts differ from clinical contexts in terms of complexity and uncertainty, requiring different approaches for identifying, interpreting, and applying many different types of evidence to support decisions. With few studies in the literature offering decision guidance specifically to health policymakers, the present study aims to facilitate the structured and systematic incorporation of research evidence and, where there is currently very little guidance, values and other non-research-based evidence, into the policy making process. The resulting decision aid is intended to help public sector health policy decision makers who are tasked with making evidence-informed decisions on behalf of populations. The intent is not to develop a decision aid that will yield uniform recommendations across jurisdictions, but rather to facilitate more transparent policy decisions that reflect a balanced consideration of all relevant factors.</p> <p>Methods/design</p> <p>The study comprises three phases: a modified meta-narrative review, the use of focus groups, and the application of a Delphi method. The modified meta-narrative review will inform the initial development of the decision aid by identifying as many policy decision factors as possible and other features of methodological guidance deemed to be desirable in the literatures of all relevant disciplines. The first of two focus groups will then seek to marry these findings with focus group members' own experience and expertise in public sector population-based health policy making and screening decisions. The second focus group will examine issues surrounding the application of the decision aid and act as a sounding board for initial feedback and refinement of the draft decision aid. Finally, the Delphi method will be used to further inform and refine the decision aid with a larger audience of potential end-users.</p> <p>Discussion</p> <p>The product of this research will be a working version of a decision aid to support policy makers in population-based health policy decisions. The decision aid will address the need for more structured and systematic ways of incorporating various evidentiary sources where applicable.</p