PINEX: The pinhole neutron experiment

The pinhole neutron experiment is sometimes called ``Pinex``, a name which has also been used to describe the pin method of measuring the time required for imploding metals to travel to certain locations in space. The two experiments are not related and should not be confused with each other. The pinhole neutron experiment is very similar to the optical pinhole camera in which light passing through a pinhole in an opaque screen produces an inverted image of the source. In the pinhole neutron experiment 14 Mev neutrons from a thermonuclear device travel in straight.lines from their respective points of origin outward in all directions. Those which pass through a pinhole in an opaque neutron shield make an inverted neutron image of the source. Some of the neutrons which form the image are captured by threshold detector plates which have been suitably located behind the pinhole. Neutrons that have sufficient energy react with the nuclei of the detector plate to form radioactive nuclei that by their decay locate the position of the image on the plate. The image may be made visible by autoradiography or counting techniques. In the autoradiograph, an x-ray film is placed in contact with the image plate. As the radioactive nuclei decay, they expose the film. The image is visible when the film has been adequately exposed and developed. In the counting method, the image plate is cut into small pieces; each the size of a resolution element. Each piece is separately counted. The number of neutrons causing its radioactivity is determined and plotted on a drawing of the plate. These numbers indicate the shape of the D-T plasma at the time of ``burn``. It is the object of this paper to discuss the factors affecting the various parameters in the experiment and what information is required to optimize these parameters for a given set of conditions. Formulae are written in many alternative ways to emphasize the effect to be expected from a change in any one of the many parameters

Protocol for a realist review of General Practitioners’ Role in Advancing Practice in Care Homes (GRAPE study)

Introduction: Older people who live in care homes have a high level of need with complex health conditions. In addition to providing medical care to residents, general practitioners (GPs) play a role as gatekeeper for access to services, as well as leadership within healthcare provision. This review will describe how GPs were involved in initiatives to change arrangements of healthcare services in order to improve quality and experience of care. Methods and analysis: Following RAMESES quality and publication guidelines standards, we will proceed with realist review to develop theories of how GPs work with care home staff to bring about improvements. We identify when improvement in outcomes does not occur and why this may be the case. The first stage will include interviews with GPs to ask their views on improvement in care homes. These interviews will enable development of initial theories and give direction for the literature searches. In the second stage, we will use iterative literature searches to add depth and context to the early theories; databases will include Medline, Embase, CINAHL, PsycINFO and ASSIA. In stage 3, evidence that is judged as rigorous and relevant will be used to test the initial theories, and through the process, refine the theory statements. In the final stage, we will synthesise findings and provide recommendations for practice and policy-making. During the review, we will invite a context expert group to reflect on our findings. This group will have expertise in current trends in primary care and the care home sector both in UK and internationally. Ethics and dissemination: The study was approved by University of Nottingham Faculty of Medicine and Health Sciences Research Ethics Committee: 354-1907. Findings will be shared through stakeholder networks, published in National Institute for Health Research journal and submitted for peer-reviewed journal publication

School-based mental health supports during COVID-19: School professional perspectives

The present study explored the ways school professionals adapted school-based mental health supports and services for remote delivery during the coronavirus disease 2019 (COVID-19) pandemic. We surveyed 81 school professionals (e.g., counselors, psychologists, and social workers) and conducted in-depth interviews with a subsample of professionals (n = 14) to explore their perceptions and experiences of supporting youth with mental health concerns and suicide-related risk during the fall and winter of the 2020–2021 school year. Commonly endorsed school-based mental health interventions (e.g., counseling services and checking in), ways of communicating (phone and email), and individuals delivering support and services to students with suicide-related risk (e.g., counselors and teachers) were identified based on school professional survey responses. Qualitative findings point to facilitators (e.g., specific platforms for connecting with students and families) and barriers (e.g., limited communication) to successful service delivery during COVID-19. Findings highlight the creative ways school support professionals adapted to provide school-based mental health supports. Implications for remote school-based mental health services during and following the pandemic are discussed

Big Data Analytics, Infectious Diseases and Associated Ethical Impacts

The exponential accumulation, processing and accrual of big data in healthcare are only possible through an equally rapidly evolving field of big data analytics. The latter offers the capacity to rationalize, understand and use big data to serve many different purposes, from improved services modelling to prediction of treatment outcomes, to greater patient and disease stratification. In the area of infectious diseases, the application of big data analytics has introduced a number of changes in the information accumulation models. These are discussed by comparing the traditional and new models of data accumulation. Big data analytics is fast becoming a crucial component for the modelling of transmission—aiding infection control measures and policies—emergency response analyses required during local or international outbreaks. However, the application of big data analytics in infectious diseases is coupled with a number of ethical impacts. Four key areas are discussed in this paper: (i) automation and algorithmic reliance impacting freedom of choice, (ii) big data analytics complexity impacting informed consent, (iii) reliance on profiling impacting individual and group identities and justice/fair access and (iv) increased surveillance and population intervention capabilities impacting behavioural norms and practices. Furthermore, the extension of big data analytics to include information derived from personal devices, such as mobile phones and wearables as part of infectious disease frameworks in the near future and their potential ethical impacts are discussed. Considered together, the need for a constructive and transparent inclusion of ethical questioning in this rapidly evolving field becomes an increasing necessity in order to provide a moral foundation for the societal acceptance and responsible development of the technological advancement

Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

BACKGROUND: New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. METHODS: Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. RESULTS: A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. CONCLUSION: These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB

Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review

Based on a systematic review, Madhukar Pai and colleagues conclude that none of the commercial immune-based tests for pulmonary tuberculosis so far evaluated perform well enough to replace sputum smear microscopy

Biomarkers for Clinical and Incipient Tuberculosis: Performance in a TB-Endemic Country

Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB

Meta-ethnography of experiences of early discharge, with a focus on paediatric febrile neutropenia

PURPOSE (STATING THE MAIN PURPOSES AND RESEARCH QUESTION): Many children have no significant sequelae of febrile neutropenia. A systematic review of clinical studies demonstrated patients at low risk of septic complications can be safely treated as outpatients using oral antibiotics with low rates of treatment failure. Introducing earlier discharge may improve quality of life, reduce hospital acquired infection and reduce healthcare service pressures. However, the review raised concerns that this might not be acceptable to patients, families and healthcare professionals. METHODS: This qualitative synthesis explored experiences of early discharge in paediatric febrile neutropenia, including reports from studies of adult febrile neutropenia and from other paediatric conditions. Systematic literature searching preceded meta-ethnographic analysis, including reading the studies and determining relationships between studies, translation of studies and synthesis of these translations. RESULTS: Nine papers were included. The overarching experience of early discharge is that decision-making is complex and difficult and influenced by fear, timing and resources. From this background, we identified two distinct themes. First, participants struggled with practical consequences of treatment regimens, namely childcare, finances and follow-up. A second theme identified social and emotional issues, including isolation, relational and environmental challenges. Linking these, participants considered continuity of care and the need for information important. CONCLUSIONS: Trust and confidence appeared interdependent with resources available to families-both are required to manage early discharge. Socially informed resilience is relevant to facilitating successful discharge strategies. Interventions which foster resilience may mediate the ability and inclination of families to accept early discharge. Services have an important role in recognising and enhancing resilience

Whole genome identification of Mycobacterium tuberculosis vaccine candidates by comprehensive data mining and bioinformatic analyses

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium tuberculosis</it>, the causative agent of tuberculosis (TB), infects ~8 million annually culminating in ~2 million deaths. Moreover, about one third of the population is latently infected, 10% of which develop disease during lifetime. Current approved prophylactic TB vaccines (BCG and derivatives thereof) are of variable efficiency in adult protection against pulmonary TB (0%–80%), and directed essentially against early phase infection.</p> <p>Methods</p> <p>A genome-scale dataset was constructed by analyzing published data of: (1) global gene expression studies under conditions which simulate intra-macrophage stress, dormancy, persistence and/or reactivation; (2) cellular and humoral immunity, and vaccine potential. This information was compiled along with revised annotation/bioinformatic characterization of selected gene products and <it>in silico </it>mapping of T-cell epitopes. Protocols for scoring, ranking and prioritization of the antigens were developed and applied.</p> <p>Results</p> <p>Cross-matching of literature and <it>in silico</it>-derived data, in conjunction with the prioritization scheme and biological rationale, allowed for selection of 189 putative vaccine candidates from the entire genome. Within the 189 set, the relative distribution of antigens in 3 functional categories differs significantly from their distribution in the whole genome, with reduction in the Conserved hypothetical category (due to improved annotation) and enrichment in Lipid and in Virulence categories. Other prominent representatives in the 189 set are the PE/PPE proteins; iron sequestration, nitroreductases and proteases, all within the Intermediary metabolism and respiration category; ESX secretion systems, resuscitation promoting factors and lipoproteins, all within the Cell wall category. Application of a ranking scheme based on qualitative and quantitative scores, resulted in a list of 45 best-scoring antigens, of which: 74% belong to the dormancy/reactivation/resuscitation classes; 30% belong to the Cell wall category; 13% are classical vaccine candidates; 9% are categorized Conserved hypotheticals, all potentially very potent T-cell antigens.</p> <p>Conclusion</p> <p>The comprehensive literature and <it>in silico</it>-based analyses allowed for the selection of a repertoire of 189 vaccine candidates, out of the whole-genome 3989 ORF products. This repertoire, which was ranked to generate a list of 45 top-hits antigens, is a platform for selection of genes covering all stages of <it>M. tuberculosis </it>infection, to be incorporated in rBCG or subunit-based vaccines.</p