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Selenium (Se) is an essential element for human health. However, our knowledge of the prevalence of Se deficiency is less than for other micronutrients of public health concern such as iodine, iron and zinc, especially in sub-Saharan Africa (SSA). Studies of food systems in SSA, in particular in Malawi, have revealed that human Se deficiency risks are widespread and influenced strongly by geography. Direct evidence of Se deficiency risks includes nationally representative data of Se concentrations in blood plasma and urine as population biomarkers of Se status. Long-range geospatial variation in Se deficiency risks has been linked to soil characteristics and their effects on the Se concentration of food crops. Selenium deficiency risks are also linked to socio-economic status including access to animal source foods. This review highlights the need for geospatially-resolved data on the movement of Se and other micronutrients in food systems which span agriculture–nutrition–health disciplinary domains (defined as a GeoNutrition approach). Given that similar drivers of deficiency risks for Se, and other micronutrients, are likely to occur in other countries in SSA and elsewhere, micronutrient surveillance programmes should be designed accordingly.
Stressful experiences affect biological stress systems, such as the hypothalamic–pituitary–adrenal (HPA) axis. Life stress can potentially alter regulation of the HPA axis and has been associated with poorer physical and mental health. Little, however, is known about the relative influence of stressors that are encountered at different developmental periods on acute stress reactions in adulthood. In this study, we explored three models of the influence of stress exposure on cortisol reactivity to a modified version of the Trier Social Stress Test (TSST) by leveraging 37 years of longitudinal data in a high-risk birth cohort (N = 112). The cumulative stress model suggests that accumulated stress across the lifespan leads to dysregulated reactivity, whereas the biological embedding model implicates early childhood as a critical period. The sensitization model assumes that dysregulation should only occur when stress is high in both early childhood and concurrently. All of the models predicted altered reactivity, but do not anticipate its exact form. We found support for both cumulative and biological embedding effects. However, when pitted against each other, early life stress predicted more blunted cortisol responses at age 37 over and above cumulative life stress. Additional analyses revealed that stress exposure in middle childhood also predicted more blunted cortisol reactivity.
We derive the surface and basal radar reflectance and backscatter coefficients of the southern McMurdo Ice Shelf (SMIS) and part of the nearby Ross Ice Shelf (RIS), Antarctica, from radar statistical reconnaissance using a 60-MHZ airborne survey. The surface coefficients are further inverted in terms of snow density and roughness, providing a spatial distribution of the processes contributing to the surface boundary conditions. We disentangle the basal coefficients from surface transmission losses, and we provide the basal coherent content, an indicator of the boundary geometric disorder that is also self-corrected from englacial attenuation. The basal radar properties exhibit sharp gradients along specific iso-depths, suggesting an abrupt modification of the ice composition and geometric structure. We interpret this behavior as locations where the pressure-melting point is reached, outlining fields of freezing and melting ice. Basal steps are observed at both SMIS and RIS, suggesting a common geometric expression of widespread basal processes. This technique offers a simultaneous view of both the surface and basal boundary conditions to help investigate the ice-shelf stability, while its application to airborne data significantly improves coverage of the difficult-to-observe ice–ocean boundary. It also provides constraints on thermohaline circulation in ice shelves cavities, which are analogs for ice-covered ocean worlds.
Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health issue, with foodborne transmission causing >1 million illnesses worldwide each year. We conducted a systematic review and meta-analysis (PROSPERO registry # CRD42017074239), to determine the relative association of different food types with sporadic illnesses caused by STEC. Searches were conducted from 01 August to 30 September 2017, using bibliographic and grey literature databases, websites and expert consultation. We identified 22 case-control studies of sporadic STEC infection in humans, from 10 countries within four World Health Organization subregions, from 1985 to 2012. We extracted data from 21 studies, for 237 individual measures in 11 food categories and across three status types (raw or undercooked, not raw and unknown). Beef was the most significant food item associated with STEC illness in the Americas and Europe, but in the Western Pacific region, chicken was most significant. These findings were not significantly moderated by the raw or cooked status of the food item, nor the publication year of the study. Data from the African, South-East Asian and Eastern Mediterranean subregions were lacking and it is unclear whether our results are relevant to these regions.
Norovirus is a predominant cause of infectious gastroenteritis in countries worldwide [1–5]. It accounts for approximately 50% of acute gastroenteritis (AGE) and >90% of viral gastroenteritis outbreaks [6, 7]. The incubation period ranges between 10 and 48 h and illness duration is generally 1–3 days with self-limiting symptoms; however, this duration is often longer (e.g. 4–6 days) in vulnerable populations such as hospital patients or young children [2, 8]. Symptomatic infection of norovirus presents as acute vomiting, diarrhoea, abdominal cramps and nausea, with severe vomiting and diarrhoea (non-bloody) being most common [2, 5, 9].
A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.
To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).
After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.
This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.
As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.
Declaration of interest
I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.
Urbanisation and climate change are altering the pattern of California serogroup viruses in North America. As La Crosse virus (LACV) is the most pathogenic of the California serogroup, it is important to identify changes in distribution, transmission and pathogenesis. A scoping review (ScR) was prioritised to summarise the global evidence on LACV. A comprehensive search strategy was used, identified references were screened for relevance and relevant articles were characterised. Each step was conducted by two independent reviewers using pre-tested forms. Analysis identified areas of research saturation and gaps. The ScR included 481 research articles that were mostly journal articles (78.2%) conducted in North America (90.9%) from 1969 to 2016. Most evidence focused on epidemiology (44.9%), virus characteristics (25.8%), transmission conditions (18.7%) and pathogenesis of LACV in hosts (18.3%). Fewer studies evaluated the accuracy of diagnostic tests (8.7%), the efficacy of treatments (3.5%), prevention and control strategies (3.1%), the economic burden of infection (0.6%) and social impact (0.2%) of LACV. None of the literature predicted the impact of climate change on LACV, nor were any cases reported in Canada. These findings are intended to guide research to close knowledge gaps and inform evidence-based decisions surrounding activities for the prevention and control of LACV.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.
Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.
Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.
Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.
Epstein Barr virus (EBV) infects 95% of the global population and is associated with up to 2% of cancers globally. Immunoglobulin G (IgG) antibody levels to EBV have been shown to be heritable and associated with developing malignancies. We, therefore, performed a pilot genome-wide association analysis of anti-EBV IgG traits in an African population, using a combined approach including array genotyping, whole-genome sequencing and imputation to a panel with African sequence data. In 1562 Ugandans, we identify a variant in human leukocyte antigen (HLA)-DQA1, rs9272371 (p = 2.6 × 10−17) associated with anti-EBV nuclear antigen-1 responses. Trans-ancestry meta-analysis and fine-mapping with European-ancestry individuals suggest the presence of distinct HLA class II variants driving associations in Uganda. In addition, we identify four putative, novel, very rare African-specific loci with preliminary evidence for association with anti-viral capsid antigen IgG responses which will require replication for validation. These findings reinforce the need for the expansion of such studies in African populations with relevant datasets to capture genetic diversity.
Attention deficit hyperactivity disorder (ADHD) is overrepresented in prison, making it imperative to identify a screening tool that can be quickly applied to efficiently detect the disorder. We explored the discrimination ability of a widely used ADHD screen, the Barkley Adult ADHD Rating Scale (BAARS-IV), against a clinical diagnostic interview. A brief version of the screen was then developed in order to simplify its use in the prison context, and maximize its diagnostic properties.
A cross-sectional study of 390 male prison inmates was performed in the UK, all participants were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2).
A total of 47 (12.1%) inmates screened positive for ADHD using the full BAARS-IV, and 96 (24.6%) were clinically diagnosed, for a sensitivity of 37.9 and a specificity of 96.3. Our models identified the six items that most predicted ADHD diagnosis, with adjusted odds ratios ranging from 2.66 to 4.58. Sensitivity, specificity and accuracy were 0.82, 0.84 and 0.84, respectively, for the developed brief scale, and 0.71, 0.85 and 0.81 for its validation. Weighted probability scores produced an area under the curve of 0.89 for development, and 0.82 for validation of the brief scale.
The original BAARS-IV performed poorly at identifying prison inmates with ADHD. Our developed brief scale substantially improved diagnostic accuracy. The brief screening instrument has great potential to be used as an accurate and resource-effective tool to screen young people and adults for likely ADHD in the criminal justice system.
The burden and aetiology of type 2 diabetes (T2D) and its microvascular complications may be influenced by varying behavioural and lifestyle environments as well as by genetic susceptibility. These aspects of the epidemiology of T2D have not been reliably clarified in sub-Saharan Africa (SSA), highlighting the need for context-specific epidemiological studies with the statistical resolution to inform potential preventative and therapeutic strategies. Therefore, as part of the Human Heredity and Health in Africa (H3Africa) initiative, we designed a multi-site study comprising case collections and population-based surveys at 11 sites in eight countries across SSA. The goal is to recruit up to 6000 T2D participants and 6000 control participants. We will collect questionnaire data, biophysical measurements and biological samples for chronic disease traits, risk factors and genetic data on all study participants. Through integrating epidemiological and genomic techniques, the study provides a framework for assessing the burden, spectrum and environmental and genetic risk factors for T2D and its complications across SSA. With established mechanisms for fieldwork, data and sample collection and management, data-sharing and consent for re-approaching participants, the study will be a resource for future research studies, including longitudinal studies, prospective case ascertainment of incident disease and interventional studies.
The room temperature electronic characteristics of resonant tunneling diodes (RTDs) containing AlAs/InGaAs quantum wells are studied. Differences in the peak current and voltages, associated with device-to-device variations in the structure and width of the quantum well are analyzed. A method to use these differences between devices is introduced and shown to uniquely identify each of the individual devices under test. This investigation shows that quantum confinement in RTDs allows them to operate as physical unclonable functions.
The Durban Diabetes Study (DDS) is a population-based cross-sectional survey of an urban black population in the eThekwini Municipality (city of Durban) in South Africa. The survey combines health, lifestyle and socioeconomic questionnaire data with standardised biophysical measurements, biomarkers for non-communicable and infectious diseases, and genetic data. Data collection for the study is currently underway and the target sample size is 10 000 participants. The DDS has an established infrastructure for survey fieldwork, data collection and management, sample processing and storage, managed data sharing and consent for re-approaching participants, which can be utilised for further research studies. As such, the DDS represents a rich platform for investigating the distribution, interrelation and aetiology of chronic diseases and their risk factors, which is critical for developing health care policies for disease management and prevention. For data access enquiries please contact the African Partnership for Chronic Disease Research (APCDR) at firstname.lastname@example.org or the corresponding author.
A broad consensus exists among modern scholars that the role of the devil in Socrates's ‘Historia Ecclesastica’ is limited and that he explains the origins of religious controversy in terms of human causation. This paper argues that the modern consensus requires revision based on the devil's role in chapter i.22 on Manichaeism and on the correspondences between that chapter and the presentation of heresies elsewhere in the ‘History’. If this interpretation of those correspondences is accepted, it should further nuance perceptions of Socrates's approach to heresies and his reputation for ‘tolerance’, while also highlighting his use of religious polemic.