Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Sociodemographic and Other Characteristics Associated With Behavioural Risk Factors of HIV Infection Among Male Mountain-Climbing Porters in Kilimanjaro Region, Tanzania.

BACKGROUND: Alcohol consumption, marijuana use, unprotected sex, and multiple concurrent sexual partnerships are prevalent among youth globally. These factors are regarded as important behavioural risk factors for HIV infection. The aim of this study was to assess the sociodemographic and other characteristics associated with behavioural risk factors of HIV infection among male mountain-climbing porters working on Mount Kilimanjaro in Tanzania. METHODS: This cross-sectional study enrolled a representative sample of 384 male mountain-climbing porters from 7 tour companies in the Kilimanjaro region using a multi-stage sampling technique. Local interviewers completed a structured questionnaire with porters in the local language, Kiswahili. The questionnaire covered demographics, alcohol and marijuana use, sexual history, sexual partners, and condom use. In-person interviews were completed between April and May 2013. Univariate and bivariate analysis were used to describe data and determine significant predictors of behavioural risk factors of HIV infection. RESULTS: Of 384 participants, 381 (99.2%) were sexually experienced, 353 (92.6%) were sexually active, and 168 (44.1%), reported condom use at last sex. The prevalence of ever-use of alcohol was 62%, and 68% of participants reported being current alcohol users. The prevalence of ever-use of marijuana was 15%, and 49% of participants reported being current marijuana users, with 12% reporting daily use. Age, marital status, working duration as a porter, transactional sex practices, and number of concurrent sexual partners were factors that were significantly associated with unprotected sex, alcohol consumption, and marijuana use (P<.05). CONCLUSIONS: Age, marital status, working duration, transactional sex practices, and number of concurrent sexual partners were significantly associated with unprotected sex, alcohol consumption, and marijuana use, among porters in this setting. The findings suggest the need for efforts to motivate sexually active male porters to engage in HIV prevention interventions, including condom use and reduction of multiple concurrent sexual partners, transactional sexual practices, alcohol consumption, and marijuana use

Effect of substrate thermal resistance on space-domain microchannel

In recent years, Fluorescent Melting Curve Analysis (FMCA) has become an almost ubiquitous feature of commercial quantitative PCR (qPCR) thermal cyclers. Here a micro-fluidic device is presented capable of performing FMCA within a microchannel. The device consists of modular thermally conductive blocks which can sandwich a microfluidic substrate. Opposing ends of the blocks are held at differing temperatures and a linear thermal gradient is generated along the microfluidic channel. Fluorescent measurements taken from a sample as it passes along the micro-fluidic channel permits fluorescent melting curves to be generated. In this study we measure DNA melting temperature from two plasmid fragments. The effects of flow velocity and ramp-rate are investigated, and measured melting curves are compared to those acquired from a commercially available PCR thermocycler

Using Support Vector Machines with Multiple Indices of Diffusion for Automated Classification of Mild Cognitive Impairment

Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical

Sustaining a new model of acute stroke care : A mixed-method process evaluation of the Melbourne Mobile Stroke Unit

Background Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care. Methods Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted. Results There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (β = 0.61), not experiencing pressure/tension about working on the MSU (β = 0.17) and thinking they did well working within the team model (β = 0.17) were significantly associated with wanting to continue working within the MSU model [R2 = 0.76; F(15, 60) = 12.76, P < .001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity. Conclusion Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability

Multi-wavelength diagnostic properties of Galactic Planetary Nebulae detected by GLIMPSE-I

We uniformly analyze 136 optically detected PNe and candidates from the GLIMPSE-I survey in order to to develop robust, multi-wavelength, classification criteria to augment existing diagnostics and provide pure PN samples. PNe represent powerful astrophysical probes. They are important dynamical tracers, key sources of ISM chemical enrichment, windows into late stellar evolution, and potent cosmological yardsticks. But their utility depends on separating them unequivocally from the many nebular mimics which can strongly resemble bona fide PNe in traditional optical images and spectra. We merge new PNe from the carefully evaluated, homogeneous MASH-I and MASH-II surveys, which offer a wider evolutionary range of PNe than hitherto available, with previously known PNe classified by SIMBAD. Mid-infrared (MIR) measurements vitally complement optical data because they reveal other physical processes and morphologies via fine-structure lines, molecular bands and dust. MIR colour-colour planes, optical emission line ratios and radio fluxes show the unambiguous classification of PNe to be complex, requiring all available evidence. Statistical trends provide predictive value and we offer quantitative MIR criteria to determine whether an emission nebula is most likely to be a PN or one of the frequent contaminants such as compact HII regions or symbiotic systems. Prerequisites have been optical images and spectra but MIR morphology, colours, environment and a candidate's MIR/radio flux ratio provide a more rigorous classification. Our ultimate goal is to recognize PNe using only MIR and radio characteristics, enabling us to trawl for PNe effectively even in heavily obscured regions of the Galaxy.Comment: 32 pages, 18 figures, 10 table

The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics:Analysis of the CREDENCE trial

Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease, and is associated with significant mortality and morbidity. In the CREDENCE trial, canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In the current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of heart failure or CV disease, and the use of loop diuretics or glucagon-like peptide-1 receptor agonists (all p(interaction) > .114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5 years vs. 20 fewer events in those without CV disease) or advanced kidney disease (estimated glomerular filtration rate [eGFR] 30-45 mL/min/1.73m(2): 61 events prevented/1000 patients treated over 2.5 years vs. 23 events in eGFR 60-90 mL/min/1.73m(2)). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk

What factors influence HIV testing? Modeling preference heterogeneity using latent classes and class-independent random effects.

Efforts to eliminate the HIV epidemic will require increased HIV testing rates among high-risk populations. To inform the design of HIV testing interventions, a discrete choice experiment (DCE) with six policy-relevant attributes of HIV testing options elicited the testing preferences of 300 female barworkers and 440 male Kilimanjaro mountain porters in northern Tanzania. Surveys were administered between September 2017 and July 2018. Participants were asked to complete 12 choice tasks, each involving first- and second-best choices from 3 testing options. DCE responses were analyzed using a random effects latent class logit (RELCL) model, in which the latent classes summarize common participant preference profiles, and the random effects capture additional individual-level preference heterogeneity with respect to three attribute domains: (a) privacy and confidentiality (testing venue, pre-test counseling, partner notification); (b) invasiveness and perceived accuracy (method for obtaining the sample for the HIV test); and (c) accessibility and value (testing availability, additional services provided). The Bayesian Information Criterion indicated the best model fit for a model with 8 preference classes, with class sizes ranging from 6% to 19% of participants. Substantial preference heterogeneity was observed, both between and within latent classes, with 12 of 16 attribute levels having positive and negative coefficients across classes, and all three random effects contributing significantly to participants' choices. The findings may help identify combinations of testing options that match the distribution of HIV testing preferences among high-risk populations; the methods may be used to systematically design heterogeneity-focused interventions using stated preference methods

The Interdependency and Co-Regulation of the Vitamin D and Cholesterol Metabolism

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-28, pub-electronic 2021-08-06Publication status: PublishedFunder: Harold Hyam Wingate Foundation; Grant(s): 16412Vitamin D and cholesterol metabolism overlap significantly in the pathways that contribute to their biosynthesis. However, our understanding of their independent and co-regulation is limited. Cardiovascular disease is the leading cause of death globally and atherosclerosis, the pathology associated with elevated cholesterol, is the leading cause of cardiovascular disease. It is therefore important to understand vitamin D metabolism as a contributory factor. From the literature, we compile evidence of how these systems interact, relating the understanding of the molecular mechanisms involved to the results from observational studies. We also present the first systems biology pathway map of the joint cholesterol and vitamin D metabolisms made available using the Systems Biology Graphical Notation (SBGN) Markup Language (SBGNML). It is shown that the relationship between vitamin D supplementation, total cholesterol, and LDL-C status, and between latitude, vitamin D, and cholesterol status are consistent with our knowledge of molecular mechanisms. We also highlight the results that cannot be explained with our current knowledge of molecular mechanisms: (i) vitamin D supplementation mitigates the side-effects of statin therapy; (ii) statin therapy does not impact upon vitamin D status; and critically (iii) vitamin D supplementation does not improve cardiovascular outcomes, despite improving cardiovascular risk factors. For (iii), we present a hypothesis, based on observations in the literature, that describes how vitamin D regulates the balance between cellular and plasma cholesterol. Answering these questions will create significant opportunities for advancement in our understanding of cardiovascular health

Using discrete choice experiments to design interventions for heterogeneous preferences: protocol for a pragmatic randomised controlled trial of a preference-informed, heterogeneity-focused, HIV testing offer for high-risk populations.

INTRODUCTION: Approximately one million undiagnosed persons living with HIV in Southern and Eastern Africa need to test for HIV. Novel approaches are necessary to identify HIV testing options that match the heterogeneous testing preferences of high-risk populations. This pragmatic randomised controlled trial (PRCT) will evaluate the efficacy of a preference-informed, heterogeneity-focused HIV counselling and testing (HCT) offer, for improving rates of HIV testing in two high-risk populations. METHODS AND ANALYSIS: The study will be conducted in Moshi, Tanzania. The PRCT will randomise 600 female barworkers and 600 male Kilimanjaro mountain porters across three study arms. All participants will receive an HIV testing offer comprised of four preference-informed testing options, including one 'common' option-comprising features that are commonly available in the area and, on average, most preferred among study participants-and three options that are specific to the study arm. Options will be identified using mixed logit and latent class analyses of data from a discrete choice experiment (DCE). Participants in Arm 1 will be offered the common option and three 'targeted' options that are predicted to be more preferred than the common option and combine features widely available in the study area. Participants in Arm 2 will be offered the common option and three 'enhanced' options, which also include HCT features that are not yet widely available in the study area. Participants in Arm 3, an active control arm, will be offered the common option and three predicted 'less preferred' options. The primary outcome will be uptake of HIV testing. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Duke University Health System IRB, the University of South Carolina IRB, the Ethics Review Committee at Kilimanjaro Christian Medical University College, Tanzania's National Institute for Medical Research, and the Tanzania Food & Drugs Authority (now Tanzania Medicines & Medical Devices Authority). Findings will be published in peer-reviewed journals. The use of rigorous DCE methods for the preference-based design and tailoring of interventions could lead to novel policy options and implementation science approaches. TRIAL REGISTRATION NUMBER: NCT02714140