Flexible epidemiological model for estimates and short-term projections in generalised HIV/AIDS epidemics

International audienceObjective UNAIDS and country analysts use a simple infectious disease model, embedded in the Estimation and Projection Package (EPP), to generate annual updates on the global HIV/AIDS epidemic. Our objective was to develop modifications to the current model that improve fit to recently observed prevalence trends across countries. Methods Our proposed alternative to the current EPP approach simplifies the model structure and explicitly models changes in average infection risk over time, operationalised using penalised B-splines in a Bayesian framework. We also present an alternative approach to initiating the epidemic that improves standardisation and efficiency, and add an informative prior distribution for changes in infection risk beyond the last data point that enhances the plausibility of short-term extrapolations. Results The spline-based model produces better fits than the current model to observed prevalence trends in settings that have recently experienced levelling or rising prevalence following a steep decline, such as Uganda and urban Rwanda. The model also predicts a deceleration of the decline in prevalence for countries with recent experience of steady declines, such as Kenya and Zimbabwe. Estimates and projections from our alternative model are comparable to those from the current model where the latter performs well. Conclusions A more flexible epidemiological model that accommodates changing infection risk over time can provide better estimates and short-term projections of HIV/AIDS incidence, prevalence and mortality than the current EPP model. The alternative model specification can be incorporated easily into existing analytical tools that are used to produce updates on the global HIV/AIDS epidemic

Creating the Future of Health

Creating the Future of Health is the fascinating story of the first fifty years of the Cumming School of Medicine at the University of Calgary. Founded on the recommendation of the Royal Commission on Health Services in 1964 the Cumming School has, from the very beginning, focused on innovation and excellence in health education. With a pioneering focus on novel, responsive and systems-based approaches, it was one of the first faculties to pilot multi-year training programs in family medicine and remains one of only two three-year medical schools in North America. Drawing on interviews with key players and extensive research into documents and primary material, Creating the Future of Health traces the history of the school through the leadership of its Deans. This is a story of perseverance through fiscal turbulence, sweeping changes to health care and health care education, and changing ideas of what health services are and what they should do. It is a story of triumph, of innovation, and of the tenacious spirit that thrives to this day at the Cumming School of Medicine

Transcriptional networks specifying homeostatic and inflammatory programs of gene expression in human aortic endothelial cells.

Endothelial cells (ECs) are critical determinants of vascular homeostasis and inflammation, but transcriptional mechanisms specifying their identities and functional states remain poorly understood. Here, we report a genome-wide assessment of regulatory landscapes of primary human aortic endothelial cells (HAECs) under basal and activated conditions, enabling inference of transcription factor networks that direct homeostatic and pro-inflammatory programs. We demonstrate that 43% of detected enhancers are EC-specific and contain SNPs associated to cardiovascular disease and hypertension. We provide evidence that AP1, ETS, and GATA transcription factors play key roles in HAEC transcription by co-binding enhancers associated with EC-specific genes. We further demonstrate that exposure of HAECs to oxidized phospholipids or pro-inflammatory cytokines results in signal-specific alterations in enhancer landscapes and associate with coordinated binding of CEBPD, IRF1, and NFκB. Collectively, these findings identify cis-regulatory elements and corresponding trans-acting factors that contribute to EC identity and their specific responses to pro-inflammatory stimuli

Seeking the Ultraviolet Ionizing Background at z~3 with the Keck Telescope

We describe the initial results of a deep long-slit emission line search for redshifted (2.7<z<4.1) Lyman-alpha. These observations are used to constrain the fluorescent Ly-alpha emission from the population of clouds whose absorption produces the higher-column-density component of the Ly-alpha forest in quasar spectra. We use the results to set an upper limit on the ultraviolet ionizing background. Our spectroscopic data obtained with the Keck II telescope at lambda/(Delta lambda FWHM)~2000 reveals no candidate Ly-alpha emission over the wavelength range of 4500-6200 Ang along a 3 arcmin slit in a 5400 s integration. Our 3 sigma upper bound on the mean intensity of the ionizing background at the Lyman limit is J(nu 0) < 2E-21 erg/s/cm**2/Hz/sr for 2.7<z<3.1 (where we are most sensitive), assuming Lyman limit systems have typical radii of 70 kpc (q_0=0.5, H_0=50 km/s/Mpc). This constraint is more than an order of magnitude more stringent than any previously published direct limit. However, it is still a factor of three above the ultraviolet background level expected due to the integrated light of known quasars at z~3. This pilot study confirms the conclusion of Gould \& Weinberg (1996) that integrations of several hours on a 10-m class telescope should be capable of measuring J(nu 0) at high redshift.Comment: 22 pages, 2 postscipt figures. Latex requires aaspp4.sty and epsf.sty (included). Accepted for publication in the Astronomical Journal (Nov 1998

Structure and functional composition of macroinvertebrate communities in coastal plain streams across a precipitation gradient

Climate change is expected to alter rainfall and temperature regimes across the world. The hydrology and riparian zone vegetation of lotic ecosystems are tightly linked to rainfall and a mechanistic understanding of the effects of rainfall on lotic ecosystems is needed to forecast the ecological impacts of climate change. However, it is difficult to isolate rainfall effects from other environmental variables that covary across climates. To address this, we leveraged a unique steep rainfall gradient with few covarying changes in elevation, temperature, and geology to evaluate the effects of rainfall on stream invertebrate communities. We surveyed nine streams in the Texas Gulf Coast Prairie distributed along a 550–1,350 mm/year rainfall gradient. Four sites were classified as drier semi-arid streams (\u3c750 mm annual rainfall) and five sites were classified as wetter sub-humid streams (\u3e750 mm annual rainfall). A suite of characteristics including benthic invertebrate community metrics, flow conditions, and water quality variables were assessed monthly for 14 months at each site to relate precipitation regime to stream structure and function. Precipitation regime was observed to be a master explanatory variable. As annual rainfall increased, the flow environment became more stable within seasons and predictable across seasons, influencing spatial structure and temporal variability of invertebrate community composition. Wetter streams were dominated by slower growing taxa without adaptions for desiccation resistance and strong dispersal. Wetter sites displayed seasonal variation in community composition and species richness, whereas temporal variation in communities in drier streams was controlled by stochastic variation in flow conditions. These observations show that differences in local annual rainfall correlated with major changes to community structure and functional composition. We hypothesise that this association is related to the connection of rainfall to hydrological stability, particularly the frequency of low flow disturbances, and the subsequent effects on riparian vegetation and temporally available niches to stream invertebrates. Our work adds to evidence that alterations in precipitation patterns associated with climate change have sweeping impacts on lotic fauna

Examining the patient and caregiver experience with diazepam nasal spray for seizure clusters: Results from an exit survey of a phase 3, open-label, repeat-dose safety study

BACKGROUND: Ideal rescue treatments for acute treatment of seizure clusters should be easy to administer, so it is important to assess user perceptions of these treatments. Diazepam nasal spray is designed to have a rapid, noninvasive, and socially acceptable route of administration. Patient and caregiver (including care partner) responses to surveys from a phase 3 safety study of diazepam nasal spray are reported. METHODS: The study enrolled patients aged 6-65 years with seizure clusters. Surveys distributed to patients and caregivers at study end, completion, or discontinuation collected data on comfort using diazepam nasal spray outside the home, timing of administration and return to their usual selves, and comfort of use compared with rectal diazepam. Safety was assessed. RESULTS: Of 175 patients enrolled at the October 31, 2019, interim cutoff, 158 received diazepam nasal spray. Sixty-seven (42.4%) patients and 84 (53.2%) caregivers responded to the surveys (including 35 matched pairs). Most patients (78.8%, 52/66) responded that they were very comfortable doing activities outside the home with diazepam nasal spray available; 59.4% of patients returned to their usual selves within an hour of administration. Twenty-seven (40.3%) of these patients reported self-administration, 48% doing so at the first sign of a seizure. Administration of diazepam nasal spray was rated extremely or very easy by 93.8% of caregivers. Safety profile was consistent with diazepam rectal gel; no patient discontinued owing to treatment-emergent adverse events. Nasal discomfort was typically mild and transient. Among patients who had used diazepam rectal gel, most were not at all comfortable using it outside the home (86.7%) or at home (64.5%) compared with diazepam nasal spray, whereas caregivers reported that diazepam rectal gel was not at all easy to use compared with diazepam nasal spray. CONCLUSIONS: This survey from the phase 3 safety study of diazepam nasal spray shows that patients and caregivers were satisfied with, and more comfortable using, diazepam nasal spray than rectal diazepam in public. NCT02721069

The significance of motivation in student-centred learning : a reflective case study

The theoretical underpinnings of student-centred learning suggest motivation to be an integral component. However, lack of clarification of what is involved in motivation in education often results in unchallenged assumptions that fail to recognise that what motivates some students may alienate others. This case study, using socio-cognitive motivational theory to analyse previously collected data, derives three fuzzy propositions which, collectively, suggest that motivation interacts with the whole cycle of episodes in the teachinglearning process. It argues that the development of the higherlevel cognitive competencies that are implied by the term, student-centred learning, must integrate motivational constructs such as goal orientation, volition, interest and attributions into pedagogical practices

Adoption of Mobile Apps for Depression and Anxiety: Cross-Sectional Survey Study on Patient Interest and Barriers to Engagement

BACKGROUND: Emerging research suggests that mobile apps can be used to effectively treat common mental illnesses like depression and anxiety. Despite promising efficacy results and ease of access to these interventions, adoption of mobile health (mHealth; mobile device-delivered) interventions for mental illness has been limited. More insight into patients\u27 perspectives on mHealth interventions is required to create effective implementation strategies and to adapt existing interventions to facilitate higher rates of adoption. OBJECTIVE: The aim of this study was to examine, from the patient perspective, current use and factors that may impact the use of mHealth interventions for mental illness. METHODS: This was a cross-sectional survey study of veterans who had attended an appointment at a single Veterans Health Administration facility in early 2016 that was associated with one of the following mental health concerns: unipolar depression, any anxiety disorder, or posttraumatic stress disorder. We used the Veteran Affairs Corporate Data Warehouse to create subsets of eligible participants demographically stratified by gender (male or female) and minority status (white or nonwhite). From each subset, 100 participants were selected at random and mailed a paper survey with items addressing the demographics, overall health, mental health, technology ownership or use, interest in mobile app interventions for mental illness, reasons for use or nonuse, and interest in specific features of mobile apps for mental illness. RESULTS: Of the 400 potential participants, 149 (37.3%, 149/400) completed and returned a survey. Most participants (79.9%, 119/149) reported that they owned a smart device and that they use apps in general (71.1%, 106/149). Most participants (73.1%, 87/149) reported interest in using an app for mental illness, but only 10.7% (16/149) had done so. Paired samples t tests indicated that ratings of interest in using an app recommended by a clinician were significantly greater than general interest ratings and even greater when the recommending clinician was a specialty mental health provider. The most frequent concerns related to using an app for mental illness were lacking proof of efficacy (71.8%, 107/149), concerns about data privacy (59.1%, 88/149), and not knowing where to find such an app (51.0%, 76/149). Participants expressed interest in a number of app features with particularly high-interest ratings for context-sensitive apps (85.2%, 127/149), and apps focused on the following areas: increasing exercise (75.8%, 113/149), improving sleep (73.2%, 109/149), changing negative thinking (70.5%, 105/149), and increasing involvement in activities (67.1%, 100/149). CONCLUSIONS: Most respondents had access to devices to use mobile apps for mental illness, already used apps for other purposes, and were interested in mobile apps for mental illness. Key factors that may improve adoption include provider endorsement, greater publicity of efficacious apps, and clear messaging about efficacy and privacy of information. Finally, multifaceted apps that address a range of concerns, from sleep to negative thought patterns, may be best received

The diet of powerful owls (Ninox strenua) and prey availability in a continuum of habitats from disturbed urban fringe to protected forest environments in south-eastern Australia

This study investigates the diet of six breeding pairs of powerful owls in the Yarra Valley Corridor in Victoria, Australia, and compares prey consumption with prey availability. The six sites represent a continuum of habitats, ranging from urban Melbourne, through the urban fringe interface to a more forested landscape. We found that powerful owls in the Yarra Valley Corridor are reliant almost exclusively on arboreal marsupial prey as their preferred diet, with 99% of their overall diet comprising four arboreal marsupial species. These four species (the common ringtail possum, common brushtail possum, sugar glider and greater glider) were also the most abundant species observed while spotlighting; however, their abundance varied along the continuum. There was a strong positive relationship with the presence of these species in the diet and their site-specific availability, indicating that the powerful owl is a generalist hunter, preying on the most available prey at a given site and in a given season. This study suggests that food resources are high in these disturbed urban fringe sites and it is unlikely that food availability in urban environments will limit the potential survival of urban powerful owls.<br /