Public Health in the Age of Ebola in West Africa

The Ebola epidemic, with its fast-growing toll and real potential for spreading into much of Africa, including major cities, has the makings of a “Black Swan” event. Such events, using the term coined by Nassim Nicholas Taleb, are: 1) unpredictable, outside the realm of regular expectations; 2) have a major impact, and; 3) are rationalized after the fact as being explainable and predictable. We have learned from this outbreak the potential for an infectious disease to be politically, economically, and socially destabilizing, and that what kills us may be very different from what frightens us or substantially affects our social systems. This has important implications for resource allocation. Health threats like Ebola may not have historically have not killed large numbers of people, but because of possible scenarios under which they can have a devastating impact, require a greater share of limited resources, such as for developing a vaccine. More creative imagination is needed in considering future infectious disease scenarios and in planning accordingly. Further, this Ebola epidemic could transform global governance for health. It demonstrates the need for fundamental reform at the WHO, including for greater funding, as WHO\u27s response–unable to mobilize sufficient funding, too slow to declare this a Public Health Emergency of International Concern–indicates that the Organization is presently poorly positioned to fulfill its constitutional role as the global health authority. Meanwhile, the leadership role that the United Nations is assuming suggests the emergence of an era of direct United Nations engagement in health threats that could destabilize nations and regions

The relevance of spatial variation in ecotourism attributes for the economic sustainability of protected areas

In contemporary society, protected areas are increasingly expected to justify their existence through the services that they provide to society. Protected areas offer many important cultural services, but appraisal of these nonmaterial benefits has generally proven difficult and most studies have focused on single case studies. Data on tourist numbers across multiple camps and protected areas provide a tractable and previously unexploited case study for better understanding the economic sustainability of cultural service provision and the relevance of potentially confounding variables (e.g., location and infrastructure) for park sustainability. We used redundancy analysis and linear models to relate a 5-yr monthly data set (2007–2012) of tourist numbers and tourism-derived income in all camps in South African national parks to a set of largely GIS-derived, determinant attributes that captured key elements of location, biodiversity, infrastructure, and accommodation cost at a camp level. Our analysis suggests that the degree to which cultural services can be converted into revenue for conservation is strongly contingent on infrastructure, location, and the business model that the park adopts. When considered alone, ecological attributes explained 14.2% and 3% of day and overnight visitation rates, respectively. In contrast, models that considered ecosystems in combination with other elements could explain 53% and 67% of variation. Linear models confirmed the existence of complex interactions between groups of variables and highlighted individual covariates that affected visitation rates. Significant variables included ecological features that provided aesthetic services, number of water bodies, elevation, available units, unit costs, and distance to the coast, airports, and other national parks. Taken in context our results suggest that it may be simpler than expected to make predictions about the potential future economic viability of protected areas under alternative models of management, illustrate how ecological variables may represent the “supply” side in cultural services, and highlight the complex interplay between ecological and built infrastructure. Encouragingly, this in turn suggests that relatively small, targeted investments in infrastructure could lead to disproportionate increases in tourist visitation rates and hence in increased revenue for conservation

Concert recording 2012-11-05

[Track 01]. Danse macabre / Camille Saint-Saens -- [Track 02]. Mazurka / Francis Poulenc -- [Track 03]. Now sleeps the crimson petal / Roger Quilter -- [Track 04]. O cessate di piagarmi / Alessandro Scarlatti -- [Track 05]. Widmung / Robert Schumann -- [Track 06]. Pique dame. Pauline\u27s aria / Peter IIlyich Tchaikovsky -- [Track 07]. Don Giovanni. Deh vieni alla finestra / Wolfgang Amadeus Mozart -- [Track 08]. Manon. Epouse quelque brave fille / Jules Massenet -- Die tote Stadt. Tanzlied des pierrot / Erick Wolfgang Korngold -- [Track 09]. Die Forelle / Franz Schubert -- [Track 10]. Ici-bas / Gabriel Faure -- [Track 11]. Un ballo in maschera. Saper vorreste / Guiseppe Verdi -- [Track 12]. Il Floriodo. Per pieta / Alessandro Stradella -- [Track 13]. Mein schoner stern/ Robert Schumann -- [Track 14]. Fleur jetee / Gabriel Faure -- [Track 15]. A view from the bridge. New York lights / William Bolcom -- [Track 16]. Les nuits d\u27ete. Vilanelle / Hector Berlioz -- [Track 17]. Ständchen / Joseph Marx -- Will there really be a morning? / Andre Previn -- The trees on the mountain / Carlisle Floyd

Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results

Etravirine (ETR), an NNRTI approved for 200 mg BID dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing

The Impact of Yoga on Quality of Life after Stroke

poster abstractAbstract Objective: Evaluate the effect of an innovative 8 week yoga-based rehabilitation intervention on 1) stroke specific quality of life (QoL) and 2) activity and participation scores in veterans with chronic stroke. Rationale/Background: Declines in Quality of Life (QoL), activity, and participation are common after stroke. Such declines are related to increased mortality, dependence, and costs. As more people live with long-term effects of stroke, it is necessary to develop innovative and evidence-based rehabilitation and occupational therapy interventions to improve QoL, activity, and participation in people with chronic stroke. Methods: • Participants- Participants included veterans with chronic stroke (>9 months) who had completed all occupational and physical therapy after stroke, reported some residual disability or functional loss after stroke; and scored >4 out of 6 on the Short Mini Mental Status Exam. • Setting- All data were collected in the Rehabilitation and Integrative Therapy lab at an urban university. • Design- This was a mixed methods pilot study of an 8 week yoga-based rehabilitation intervention. Data were collected before and after the 8 week yoga intervention. Data collection was completed by a trained research assistant. We used paired t-tests and Wilcoxon non-parametirc tests as appropriate to compare group change in scores over the 8-weeks. • Measure(s)- Measures included the Stroke Specific Quality of Life scale (SSQoL) (high score=better QoL) to measure QoL and activity and participation were measured with the ICF Measure of Participation and Activity (IMPACT) (low score=less limitations in activity and participation). Both are valid and reliable instruments. Qualitative comments were collected during focus groups after the intervention. Supportive qualitative comments regarding improved QoL and activity and participation are included. All qualitative comments were reviewed by two researchers, and exemplar quotes are included

A Research and Development (R&D) roadmap for influenza vaccines: Looking toward the future

Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation. Each section identifies barriers, gaps, strategic goals, milestones, and additional R&D priorities germane to that area. The roadmap includes 113 specific R&D milestones, 37 of which have been designated high priority by the IVR expert taskforce. This report summarizes the major issues and priority areas of research outlined in the IVR. By identifying the key issues and steps to address them, the roadmap not only encourages research aimed at new solutions, but also provides guidance on the use of innovative tools to drive breakthroughs in influenza vaccine R&D.publishedVersio

Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066)

Oral preexposure prophylaxis (PrEP) trials report disparate efficacy attributed to variable adherence. HPTN 066 was conducted to establish objective, quantitative benchmarks for discrete, regular levels of adherence using directly observed dosing of tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC). Healthy, HIV-uninfected men and women were randomized to one of four oral regimens of fixed-dose TDF 300 mg/FTC 200 mg tablet for 5 weeks with all doses observed: one tablet weekly (one/week), one tablet twice weekly (two/week), two tablets twice weekly (four/week), or one tablet daily (seven/week). Trough serum TFV and FTC, peripheral blood mononuclear cell (PBMC), and CD4+ TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) concentrations were determined throughout dosing and 2 weeks after the last dose. Rectosigmoidal, semen, and cervicovaginal samples were collected for drug assessment at end of dosing and 2 weeks later in a subset of participants. The 49 enrolled participants tolerated the regimens well. All regimens achieved steady-state concentrations by the second dose for serum TFV/FTC and by 7 days for PBMC TFV-DP/FTC-TP. Steady-state median TFV-DP predose concentrations demonstrated dose proportionality: one/week 1.6 fmol/106 PBMCs, two/week 9.1, four/week 18.8, seven/week, 36.3. Further, TFV-DP was consistently quantifiable 2 weeks after the last dose for the ≥4/week regimens. Adherence benchmarks were identified using receiver operating characteristic curves, which had areas under the curve ≥0.93 for all analytes in serum and PBMCs. Intersubject and intrasubject coefficients of variation (%CV) ranged from 33% to 63% and 14% to 34%, respectively, for all analytes in serum and PBMCs. Steady-state PBMC TFV-DP was established earlier and at lower concentrations than predicted and was the only analyte demonstrating predose concentration dose proportionality. Steady-state daily dosing serum TFV and PBMC TFV-DP was consistent with highly effective PrEP clinical trials. HPTN 066 provides adherence benchmarks for oral TFV/FTC regimens to assist interpreting study outcomes

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery