a systematic review protocol

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. Trial registration number CRD4201502614

Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): a qualitative study of experiences of COVID-19 among people who inject drugs

BACKGROUND: : People who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour. METHODS: : Telephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis. RESULTS: : Concern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to ‘stay home’ led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources. CONCLUSION: : This study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services

Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing

High-acuity αβT cell receptor (TCR) recognition of peptides bound to major histocompatibility complex molecules (pMHCs) requires mechanosensing, a process whereby piconewton (pN) bioforces exert physical load on αβTCR–pMHC bonds to dynamically alter their lifetimes and foster digital sensitivity cellular signaling. While mechanotransduction is operative for both αβTCRs and pre-TCRs within the αβT lineage, its role in γδT cells is unknown. Here, we show that the human DP10.7 γδTCR specific for the sulfoglycolipid sulfatide bound to CD1d only sustains a significant load and undergoes force-induced structural transitions when the binding interface-distal γδ constant domain (C) module is replaced with that of αβ. The chimeric γδ–αβTCR also signals more robustly than does the wild-type (WT) γδTCR, as revealed by RNA-sequencing (RNA-seq) analysis of TCR-transduced Rag2−/− thymocytes, consistent with structural, single-molecule, and molecular dynamics studies reflective of γδTCRs as mediating recognition via a more canonical immunoglobulin-like receptor interaction. Absence of robust, force-related catch bonds, as well as γδTCR structural transitions, implies that γδT cells do not use mechanosensing for ligand recognition. This distinction is consonant with the fact that their innate-type ligands, including markers of cellular stress, are expressed at a high copy number relative to the sparse pMHC ligands of αβT cells arrayed on activating target cells. We posit that mechanosensing emerged over ∼200 million years of vertebrate evolution to fulfill indispensable adaptive immune recognition requirements for pMHC in the αβT cell lineage that are unnecessary for the γδT cell lineage mechanism of non-pMHC ligand detection

Responding to global challenges in food, energy, environment and water: Risks and options assessment for decision-Making

We analyse the threats of global environmental change, as they relate to food security. First, we review three discourses: (i) ‘sustainable intensification’, or the increase of food supplies without compromising food producing inputs, such as soils and water; (ii) the ‘nexus’ that seeks to understand links across food, energy, environment and water systems; and (iii) ‘resilience thinking’ that focuses on how to ensure the critical capacities of food, energy and water systems are maintained in the presence of uncertainties and threats. Second, we build on these discourses to present the causal, risks and options assessment for decision-making process to improve decision-making in the presence of risks. The process provides a structured, but flexible, approach that moves from problem diagnosis to better risk-based decision-making and outcomes by responding to causal risks within and across food, energy, environment and water systems

A survey of root knot nematodes and resistance to Meloidogyne incognita in sweet potato varieties from Kenyan fields

AbstractThe root knot nematode, Meloidogyne is one of the most economically damaging plant parasitic nematode groups, and are widely distributed in Kenyan agro-ecosystems. The aim of this study was to determine the diversity of Meloidogyne species in Kenyan sweet potato fields and identify sweet potato varieties that exhibit resistance to M. incognita. Meloidogyne species were collected from Nyanza, Western, Eastern and Central Provinces of Kenya. Mitochondrial DNA was used to differentiate Meloidogyne species. The most common species in all sampled regions was M. incognita. Meloidogyne hapla was recorded for the first time in Kenyan sweet potato growing areas (Mosocho, Matayos, Teso South, Manyatta, and Nzaui sub-counties), while M. enterolobii was observed in Kiharu, Matayos and Mosocho sub-counties and a novel Meloidogyne sp. was identified in Kiharu sub-county. Seventy-two sweet potato varieties collected from both agricultural fields and research stations in Kenya were evaluated for resistance to M. incognita under greenhouse conditions in two separate trials. Known susceptible (Beauregard) and resistant (Tanzania) sweet potato varieties were included as controls. Responses of sweet potato varieties to M. incognita infection was assessed by the number of eggs present and level of galling on a scale of 1–5, where 0 = 0 galls and 5 ≥ 100 galls. The reproduction index (RI) was used to classify the varieties as resistant or susceptible. There was a significant difference (P < 0.001) in the number of eggs, GI and RI among the varieties tested. Forty nine sweet potato varieties were considered very resistant and may be used in breeding programs to incorporate resistance against M. incognita into commercial cultivars of sweet potato or to use them in crop rotation programmes for management of RKN. The results on Meloidogyne species diversity in Kenyan sweet potato fields will also be useful in nematode management programs

A camera‐based method for estimating absolute density in animals displaying home range behaviour

1. The measurement of animal density may take advantage of recent technological achievements in wildlife video recording. Fostering the theoretical links between the patterns depicted by cameras and absolute density is required to exploit this potential. 2. We explore the applicability of the Hutchinson–Waser’s postulate (i.e. when animal density is stationary at a given temporal and spatial scale, the absolute density is given by the average number of animals counted per frame), which is a counterintuitive statement for most ecologists and managers who are concerned with counting the same individual more than once. We aimed to reconcile such scepticism for animals displaying home range behaviour. 3. The specific objectives of this paper are to generalize the Hutchinson–Waser’s postulate for animals displaying home range behaviour and to propose a Bayesian implementation to estimate density from counts per frame using video cameras. 4. Accuracy and precision of the method was evaluated by means of computer simulation experiments. Specifically, six animal archetypes displaying well-contrasted movement features were considered. The simulation results demonstrate that density could be accurately estimated after an affordable sampling effort (i.e. number of cameras and deployment time) for a great number of animals across taxa. 5. The proposed method may complement other conventional methods for estimating animal density. The major advantages are that identifying an animal at the individual level and precise knowledge on how animals move are not needed, and that density can be estimated in a single survey. The method can accommodate conventional camera trapping data. The major limitations are related to some implicit assumptions of the underlying model: the home range centres should be homogeneously distributed, the detection probability within the area surveyed by the camera should be known, and animals should move independently to one another. Further improvements for circumventing these limitations are discussed.Ministerio de Educación, Cultura y Deporte, Grant/Award Number: FPU13/01440; Ministerio de Economía y Competitividad Juan de la Cierva Postdoctoral Grant, Grant/Award Number: FJCI-2014-21 and CTM2015-69126-C2-1-R

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

Risk factors for Coronavirus Disease 2019 (COVID-19) death in a population cohort study from the Western Cape Province, South Africa

BACKGROUND. Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. METHODS. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates. RESULTS. Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID- 19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1). CONCLUSIONS. While our findings may overestimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both living with HIV and having current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex, and other comorbidities and COVID-19 mortality were similar to those in other settings.The Western Cape Provincial Health Data Centre from the Western Cape Department of Health, the US National Institutes for Health (grant numbers R01 HD0804, the Bill and Melinda Gates Foundation, the United States Agency for International Development and the Wellcome Trust.https://academic.oup.com/cid/am2023Veterinary Tropical Disease