Strengthening the Paediatricians Project 1: The need, content and process of a workshop to address the Priority Mental Health Disorders of adolescence in countries with low human resource for health

<p>Abstract</p> <p>Objective</p> <p>World Health Organization has identified <it>Priority Mental Health Disorders </it>(PMHD) of adolescence. To effectively address these disorders at the primary care level paediatricians have to be trained in the low-income countries, which often have paucity of mental health resources. We studied: (1) the need of psychiatric training required among paediatricians; (2) if the content and process of the model workshop suits them to identify and treat these disorders.</p> <p>Methods</p> <p>Forty-eight paediatricians completed evaluation questionnaire at the end of a 3-day workshop on adolescent psychiatry. They participated in a focused group discussion addressing the areas in psychiatry that needs to be strengthened in these workshops, the changes in the content and process of the workshop to bolster their learning. Qualitative and descriptive analyses were appropriately used.</p> <p>Results</p> <p>Training in adolescent psychiatry was considered necessary among the paediatricians at zonal level frequently to develop their private practice, treat psychiatric disorders confidently, make correct referrals, and learn about counselling. Prioritizing training from under and postgraduate training, integrate psychiatry training with conference, conducting special workshops or Continuing Medical Education were suggested as ways of inculcating adolescent psychiatry proficiency. Mental status examination, psychopathology and management of the PMHD were considered by the respondents as important content that need to be addressed in the program but aspects of behavioural problems and developmental disabilities were also identified as areas of focus to gain knowledge and skill. Appropriate group size, flexibility in management decisions to fit the diverse clinical practice- settings was appreciated. Lack of skills in giving clinical reasoning in relation to PMHD, time management and feedback to individuals were identified as required components in the collaborative effort of this manner. Providing delegates with basic information on adolescent psychiatry prior to the workshop was suggested to make the workshop more valuable.</p> <p>Conclusions</p> <p>There is a need to expand training for paediatricians from various backgrounds in adolescent psychiatry to strengthen their clinical skills to address the PMHD at the primary-care level. The evaluation suggests that the design and collaborative approach evident in this programme have merit as a model for training paediatricians in adolescent psychiatry in countries with low human resource for health.</p

Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

Background/objectivesThe common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.MethodsFor immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.ResultsHomozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.ConclusionsIn sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression

A low-cost, community knowledge approach to estimate maternal and jaundice-associated mortality in rural Bangladesh

Copyright © 2018 by The American Society of Tropical Medicine and Hygiene. In the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged 3 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method’s sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged 3 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority

Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells

Wiring metabolic signaling circuits in thymocytes Cell differentiation is often accompanied by metabolic changes. Yang et al. report that generation of double-positive (DP) thymocytes from double-negative (DN) cells coincides with dynamic regulation of glycolytic and oxidative metabolism. Given the central role of mechanistic target of rapamycin complex 1 (mTORC1) signaling in regulating metabolic changes, they examined the role of mTORC1 pathway in thymocyte development by conditionally deleting RAPTOR, the key component of the mTORC1 complex, in thymocytes. Loss of RAPTOR impaired the DN-to-DP transition, but unexpectedly also perturbed the balance between αβ and γδ T cells and promoted the generation of γδ T cells. Their studies highlight an unappreciated role for mTORC1-dependent metabolic changes in controlling thymocyte fates. The interaction between extrinsic factors and intrinsic signal strength governs thymocyte development, but the mechanisms linking them remain elusive. We report that mechanistic target of rapamycin complex 1 (mTORC1) couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages, the αβ and γδ T cells. Developing thymocytes dynamically engage metabolic programs including glycolysis and oxidative phosphorylation, as well as mTORC1 signaling. Loss of RAPTOR-mediated mTORC1 activity impairs the development of αβ T cells but promotes γδ T cell generation, associated with disrupted metabolic remodeling of oxidative and glycolytic metabolism. Mechanistically, we identify mTORC1-dependent control of reactive oxygen species production as a key metabolic signal in mediating αβ and γδ T cell development, and perturbation of redox homeostasis impinges upon thymocyte fate decisions and mTORC1-associated phenotypes. Furthermore, single-cell RNA sequencing and genetic dissection reveal that mTORC1 links developmental signals from T cell receptors and NOTCH to coordinate metabolic activity and signal strength. Our results establish mTORC1-driven metabolic signaling as a decisive factor for reciprocal αβ and γδ T cell development and provide insight into metabolic control of cell signaling and fate decisions. Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1. Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1

Preventing Attacks on Machine Readable Travel Documents (MRTDs)

After the terror attacks of 9/11, the U.S. Congress passed legislation that requires in the US Visa Waiver Program to begin issuing issuing machine readable passports that are tamper resistant and incorporate biometric and document authentication identifiers. The International Civil Aviation Organization (ICAO) has issued specifications for Machine Readable Travel Documents (MRTD) that are equipped with a smart card processor to perform biometric identification of the holder. Some countries, such as the United States, will issue machine readable passports that serve only as passports. Other countries, such as the United Kingdom, intend to issue more sophisticated, multi-application passports that can also serve as national identity cards. We have conducted a detailed security analysis of these specificationsm, and we illustrate possible scenarios that could cause a compromise in the security and privacy of holders of such travel documents. Finally, we suggest improved cryptographic protocols and high-assurance smart card operating systems to prevent these compromises and to support electronic visas as well as passports

Bringing Analysis Closer to Data: Developing a Visualization Tool for L2 Earth Science Satellite Data

Earth Science satellite missions provide a unique opportunity for scientists to visualize complex and multifaceted observations projected geospatially across maps of the Earth. While visualization tools can help scientists comprehend, analyze, and share data, visualizing Level-2 Earth Sciences data poses its own specific set of challenges. Since the geospatial information in Level-2 data files is stored as independent variables, the plotting process involves matching dimensional information from latitude and longitude with a desired variable. Variables are stored in different ways across various Earth Science data file formats, which complicates the process of extracting data and plotting variables from a given file without requiring extensive user input and prerequisite familiarity with the file type variable structure. In coordination with NASAs Goddard Earth Sciences Data Information Services Center (GES DISC), the team developed a Level-2 Earth Science data visualization tool that aims to address some of the complexities associated with plotting Level-2 data. This tool offers command-line and user interface support for file and variable selection to accommodate varying use cases and degrees of user familiarity with the structure of a given file. The visualization tool is written in Python 3 and utilizes a modular approach to facilitate continued expansion and reuse. In addressing some common complications involved in plotting Level-2 Earth Sciences data, the tool aims to help to link the process of analysis more directly with data acquisition and visualization, bringing analysis closer to data across levels of processing

Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

Background: Studies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression. Methods: Individuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin–norepinephrine reuptake inhibitors [SNRIs], and others). Findings: A total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]). Interpretation: Within-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians’ benefit-risk assessments when prescribing antidepressants