The pathway to secondary prevention of Alzheimer\u27s disease

Alzheimer\u27s disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer\u27s Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Lessons learnt from comprehensive evaluation of community-based education in Uganda: a proposal for an ideal model community-based education for health professional training institutions

<p>Abstract</p> <p>Background</p> <p>Community-based education (CBE) can provide contextual learning that addresses manpower scarcity by enabling trainees acquire requisite experiences, competence, confidence and values. In Uganda, many health professional training institutions conduct some form of community-based education (CBE). However, there is scanty information on the nature of the training: whether a curriculum exists (objectives, intended outcomes, content, implementation strategy), administration and constraints faced. The objective was to make a comprehensive assessment of CBE as implemented by Ugandan health professional training institutions to document the nature of CBE conducted and propose an ideal model with minimum requirements for health professional training institutions in Uganda.</p> <p>Methods</p> <p>We employed several methods: documentary review of curricula of 22 institutions, so as to assess the nature, purpose, outcomes, and methods of instruction and assessment; s<it>ite visits </it>to these institutions and their CBE sites, to assess the learning environment (infrastructure and resources); in-depth interviews with key people involved in running CBE at the institutions and community, to evaluate CBE implementation, challenges experienced and perceived solutions.</p> <p>Results</p> <p>CBE was perceived differently ranging from a subject, a course, a program or a project. Despite having similar curricula, institutions differ in the administration, implementation and assessment of CBE. Objectives of CBE, the curricula content and implementation strategies differ in similar institutions. On collaborative and social learning, most trainees do not reside in the community, though they work on group projects and write group reports. Lectures and skills demonstrations were the main instruction methods. Assessment involved mainly continuous assessment, oral or written reports and summative examination.</p> <p>Conclusion</p> <p>This assessment identified deficiencies in the design and implementation of CBE at several health professional training institutions, with major flaws identified in curriculum content, supervision of trainees, inappropriate assessment, trainee welfare, and underutilization of opportunities for contextual and collaborative learning. Since CBE showed potential to benefit the trainees, community and institutions, we propose a model that delivers a minimum package of CBE and overcomes the wide variation in the concept, conduct and implementation of CBE.</p

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further

A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39–73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2–5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer

Ascospore discharge, germination and culture of fungal partners of tropical lichens, including the use of a novel culture technique

A total of 292 lichen samples, representing over 200 species and at least 65 genera and 26 families, were collected, mainly in Thailand; 170 of the specimens discharged ascospores in the laboratory. Generally, crustose lichens exhibited the highest discharge rates and percentage germination. In contrast, foliose lichen samples, although having a high discharge rate, had a lower percentage germination than crustose species tested. A correlation with season was indicated for a number of species. Continued development of germinated ascospores into recognizable colonies in pure culture was followed for a selection of species. The most successful medium tried was 2 % Malt-Yeast extract agar (MYA), and under static conditions using a liquid culture medium, a sponge proved to be the best of several physical carriers tested; this novel method has considerable potential for experimental work with lichen mycobionts

“Beyond words”: a researcher’s guide to using photo elicitation in psychology

The use of photo elicitation is limited within the field of psychology despite its theoretical and practical potential. It offers significant benefits as a qualitative method that could present a new and interesting way of exploring previously understood topics within the discipline. Within our discussions, we present a Step-by-Step guide in which we outline the key practical stages, as well as ethical assurances involved in photo elicitation research, using our ongoing research as an illustrative example. It is intended that this could be used as a model of good practice for developing research paradigms beyond those typically used within the psychology discipline

Human immunodeficiency virus and AIDS and other important predictors of maternal mortality in Mulago Hospital Complex Kampala Uganda

BACKGROUND: Women with severe maternal morbidity are at high risk of dying. Quality and prompt management and sometimes luck have been suggested to reduce on the risk of dying. The objective of the study was to identify the direct and indirect causes of severe maternal morbidity, predictors of progression from severe maternal morbidity to maternal mortality in Mulago hospital, Kampala, Uganda. METHODS: This was a longitudinal follow up study at the Mulago hospital's Department of Obstetrics and Gynaecology. Participants were 499 with severe maternal morbidity admitted in Mulago hospital between 15th November 2001 and 30th November 2002 were identified, recruited and followed up until discharge or death. Potential prognostic factors were HIV status and CD4 cell counts, socio demographic characteristics, medical and gynaecological history, past and present obstetric history and intra- partum and postnatal care. RESULTS: Severe pre eclampsia/eclampsia, obstructed labour and ruptured uterus, severe post partum haemorrhage, severe abruptio and placenta praevia, puerperal sepsis, post abortal sepsis and severe anaemia were the causes for the hospitalization of 499 mothers. The mortality incidence rate was 8% (n = 39), maternal mortality ratio of 7815/100,000 live births and the ratio of severe maternal morbidity to mortality was 12.8:1.The independent predictors of maternal mortality were HIV/AIDS (OR 5.1 95% CI 2-12.8), non attendance of antenatal care (OR 4.0, 95% CI 1.3-9.2), non use of oxytocics (OR 4.0, 95% CI 1.7-9.7), lack of essential drugs (OR 3.6, 95% CI 1.1-11.3) and non availability of blood for transfusion (OR 53.7, 95% CI (15.7-183.9) and delivery of amale baby (OR 4.0, 95% CI 1.6-10.1). CONCLUSION: The predictors of progression from severe maternal morbidity to mortality were: residing far from hospital, low socio economic status, non attendance of antenatal care, poor intrapartum care, and HIV/AIDS.There is need to improve on the referral system, economic empowerment of women and to offer comprehensive emergency obstetric care so as to reduce the maternal morbidity and mortality in our community

Soil surface temperatures reveal moderation of the urban heat island effect by trees and shrubs

Urban areas are major contributors to air pollution and climate change, causing impacts on human health that are amplified by the microclimatological effects of buildings and grey infrastructure through the urban heat island (UHI) effect. Urban greenspaces may be important in reducing surface temperature extremes, but their effects have not been investigated at a city-wide scale. Across a midsized UK city we buried temperature loggers at the surface of greenspace soils at 100 sites, stratified by proximity to city centre, vegetation cover and land-use. Mean daily soil surface temperature over 11 months increased by 0.6 °C over the 5 km from the city outskirts to the centre. Trees and shrubs in non-domestic greenspace reduced mean maximum daily soil surface temperatures in the summer by 5.7 °C compared to herbaceous vegetation, but tended to maintain slightly higher temperatures in winter. Trees in domestic gardens, which tend to be smaller, were less effective at reducing summer soil surface temperatures. Our findings reveal that the UHI effects soil temperatures at a city-wide scale, and that in their moderating urban soil surface temperature extremes, trees and shrubs may help to reduce the adverse impacts of urbanization on microclimate, soil processes and human health

Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1–5 of a 3-weekly cycle in patients with advanced solid tumours

XR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 weeks to patients with advanced solid tumours. Patients were treated with escalating doses of XR11576 at doses ranging from 30