Recursive partitioning models for linkage in COGA data

We have developed a recursive-partitioning (RP) algorithm for identifying phenotype and covariate groupings that interact with the evidence for linkage. This data-mining approach for detecting gene × environment interactions uses genotype and covariate data on affected relative pairs to find evidence for linkage heterogeneity across covariate-defined subgroups. We adapted a likelihood-ratio based test of linkage parameterized with relative risks to a recursive partitioning framework, including a cross-validation based deviance measurement for choosing optimal tree size and a bootstrap sampling procedure for choosing robust tree structure. ALDX2 category 5 individuals were considered affected, categories 1 and 3 unaffected, and all others unknown. We sampled non-overlapping affected relative pairs from each family; therefore, we used 144 affected pairs in the RP model. Twenty pair-level covariates were defined from smoking status, maximum drinks, ethnicity, sex, and age at onset. Using the all-pairs score in GENEHUNTER, the nonparametric linkage tests showed no regions with suggestive linkage evidence. However, using the RP model, several suggestive regions were found on chromosomes 2, 4, 6, 14, and 20, with detection of associated covariates such as sex and age at onset

On-site sanitation density and groundwater quality: Evidence from remote sensing and in situ observations in the thiaroye aquifer, Senegal

© 2020 The Authors. In rapidly urbanising low-income towns and cities, there remains an absence of scientific evidence and regulatory structures to sustain the quality and quantity of groundwater used for low-cost water supplies and to reconcile this with continued use of the subsurface for low-cost sanitation. Here, we analyse the relationship between the density of on-site sanitation and shallow groundwater quality in the Thiaroye aquifer of Quaternary sands in Dakar, Senegal. On-site sanitation was mapped using object-oriented classification and visual interpretation of high-resolution, optical satellite images and ground-truthing surveys. Groundwater quality was assessed over a three-year period (2017–2019) from a network of 61 sources comprising boreholes, dug-wells, hand tubewells and piezometers. More than 253,000 on-site sanitation facilities are identified over an area of 520 km2 with densities ranging from 1 to 70 per hectare. A moderate, statistically significant linear relationship (r2 = 0.55, p « 0.01) is found between the density of on-site sanitation facilities and nitrate concentrations in sampled groundwater sources. Groundwater contamination beyond the WHO drinking-water guideline value (50 mg/L) occurs where densities of on-site sanitation facilities exceed 4 (±4) per hectare, a threshold commonly surpassed in peri-urban areas underlain by the Thiaroye aquifer of Dakar

Imaging Coulomb Islands in a Quantum Hall Interferometer

In the Quantum Hall regime, near integer filling factors, electrons should only be transmitted through spatially-separated edge states. However, in mesoscopic systems, electronic transmission turns out to be more complex, giving rise to a large spectrum of magnetoresistance oscillations. To explain these observations, recent models put forward that, as edge states come close to each other, electrons can hop between counterpropagating edge channels, or tunnel through Coulomb islands. Here, we use scanning gate microscopy to demonstrate the presence of quantum Hall Coulomb islands, and reveal the spatial structure of transport inside a quantum Hall interferometer. Electron islands locations are found by modulating the tunneling between edge states and confined electron orbits. Tuning the magnetic field, we unveil a continuous evolution of active electron islands. This allows to decrypt the complexity of high magnetic field magnetoresistance oscillations, and opens the way to further local scale manipulations of quantum Hall localized states

Transcultural adaptation to the Brazilian Portuguese of the Postpartum Bonding Questionnaire for assessing the postpartum bond between mother and baby

The establishment of the bond between mother and baby in the postpartum period is important for ensuring the physical and psychological health of both. This short communication reports the first phase of the cross-cultural translation and adaptation to the Brazilian context of the Postpartum Bonding Questionnaire (PBQ). Four aspects of equivalence between the original scale and the Portuguese version were evaluated: the conceptual, semantic, operational and item equivalences. Literature review, the study of PBQ history, translation, expert evaluation, back-translation and pretests involving 30 mothers with children aging up to 7 months using a primary healthcare unit were conducted. Each step demonstrated the need for adjustments, which were made during the adaptation process. At the end of the study, a version of PBQ in Brazilian Portuguese equivalent to the original one was obtained, offering promise for national studies on the mother-baby bond, and its influence on health, and for use in health services

Perceptions of door-to-door HIV counselling and testing in Botswana

Prevalence of HIV infection in Botswana is among the highest in the world, at 23.9% of 15 - 49-year-olds. Most HIV testing is conducted in voluntary counselling and testing centres or medical settings. Improved access to testing is urgently needed. This qualitative study assessed and documented community perceptions about the concept of door-to-door HIV counselling and rapid testing in two of the highest-prevalence districts of Botswana. Community members associated many positive benefits with home-based, door-to-door HIV testing, including convenience, confidentiality, capacity to increase the number of people tested, and opportunities to increase knowledge of HIV transmission, prevention and care through provision of correct information to households. Community members also saw the intervention as increasing opportunities to engage and influence family members and to role model positive behaviours. Participants also perceived social risks and dangers associated with home-based testing including the potential for conflict, coercion, stigma, and psychological distress within households. Community members emphasised the need for individual and community preparation, including procedures to protect confidentiality, provisions for psychological and social support, and links to appropriate services for HIV-positive persons

Osteosarcoma in the distal femur two years after an ipsilateral femoral shaft fracture: a case report

<p>Abstract</p> <p>Introduction</p> <p>The duration of symptoms preceding a definitive diagnosis of osteosarcoma is quite long. Pathological radiological signs are often evident by the time of diagnosis. Although several case reports have been published on osteosarcoma of the femur, to the best of our knowledge this report is the first one with such an unusual clinical course.</p> <p>Case presentation</p> <p>We describe the case of a 58-year-old Caucasian man who presented with a femoral shaft fracture. Two years post-trauma osteosarcoma in the ipsilateral distal femur was diagnosed. Was it coincidence? We think that the history of the trauma is crucial to answering this question.</p> <p>Conclusion</p> <p>This case report underlines the need to keep up awareness of pathological fractures in emergency medicine and trauma surgery. When radiographs do not raise any suspicion but the history of trauma or the physical examination does, we recommend further radiological and/or histological diagnostic examinations.</p

Macrophage reprogramming for therapy.

Funder: MRC UK Dementia Research Institute ProfessorshipDysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage-targeted approaches in human disease

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value