A Randomized, Controlled Trial of Indinavir, Zidovudine, and Lamivudine in Adults with Advanced Human Immunodeficiency Virus Type 1 Infection and Prior Antiretroviral Therapy

A randomized, double-blind, multicenter study of indinavir, zidovudine, and lamivudine was conducted in 320 adults with human immunodeficiency virus type 1 (HIV-1) infection, ⩽50 CD4 cells/mm3, and extensive prior zidovudine therapy. Patients received indinavir, 800 mg every 8 h; zidovudine, 200 mg every 8 h, and lamivudine, 150 mg twice daily; or all 3 drugs for 24 weeks. In an intention-to-treat analysis, proportions of patients with HIV-1 RNA <500 and <50 copies/mL, respectively, at week 24 were 56% and 45% in the indinavir-zido-vudine-lamivudine group, 3% and 2% in the indinavir group, and 0% in the zidovudinelamivudine group. Observed mean CD4 cell increases were 95, 78, and 6 cells/mm3 in the three-, one-, and two-drug arms, respectively. Regimens were generally well tolerated. Patients with advanced HIV-1 infection benefit from triple therapy with indinavir, zidovudine, and lamivudine, although the proportion with optimal response appeared to be lower in patients with low CD4 cell count

Aryl Hydrocarbon Hydroxylase, Epoxide Hydrolase, and Benzo[a]pyrene Metabolism in Human Epidermis: Comparative Studies in Normal Subjects and Patients with Psoriasis

Prior studies have shown that human skin possesses a cytochrome P-450-dependent microsomal enzyme that is capable of metabolizing drugs and polycyclic aromatic hydrocarbon (PAH) carcinogens. This study characterized benzo[a]pyrene (BP) metabolism in human epidermis of normal and psoriatic individuals. The basal level of the cytochrome P-450-dependent microsomal enzyme aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH) were measured in freshly keratomed epidermis from 12 normal individuals and from uninvolved skin sites of 12 patients with psoriasis. The induction response of AHH following the in vitro addition of the PAH benz[A]anthracene (BA) was also assessed. The basal activity (mean ± SE) of AHH in normal epidermis was 62.1 ± 5.6 units (fmol 3-hydroxybenzo[a]pyrene, 3-OH-BP/min/mg protein) whereas the activity in uninvolved skin of psoriatic individuals was 62.9 ± 5.1 units (NS), Epoxide hydrolase activity was 25.1 ± 1.1 (pmol BP 4,5-diol/min/mg protein) units in normal epidermis and 24.8 ± 2.1 units in epidermis from patients with psoriasis (NS). Following addition of BA (100μM), in vitro, AHH activity in normal epidermis increased by a mean value of 165% whereas activity in nonlesional epidermis of psoriatic individuals increased 320%. Kinetic studies in normal epidermis revealed that the AHH reaction was linear up to 60 min and to 50 μg protein, had a pH optimum of 7.4, and the Km for BP was 0.62 MM. High-performance liquid chromatography (HPLC) confirmed that the pattern of metabolism of BP was quite similar in epidermal microsomes prepared from normal and psoriatic individuals, insofar as the formation of diols, phenols, and quinones was concerned. These studies indicate that human epidermis is capable of metabolizing BP and that there is no significant difference between normal individuals and patients with psoriasis insofar as basal AHH activity or total BP metabolism is concerned. Furthermore, the epidermal enzyme system in patients with psoriasis has a greater responsiveness to environmental PAH than does that of normal individuals

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Count every newborn; a measurement improvement roadmap for coverage data.

BACKGROUND: The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity. METHODS: In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout. RESULTS: ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care. CONCLUSIONS: The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks

Comparing tropical precipitation simulated by the Met Office NWP and climate models with satellite observations

Forecasts of precipitation and water vapor made by the Met Office global numerical weather prediction (NWP) model are evaluated using products from satellite observations by the Special Sensor Microwave Imager/Sounder (SSMIS) and Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) for June–September 2011, with a focus on tropical areas (308S–308N). Consistent with previous studies, the predicted diurnal cycle of precipitation peaks too early (by ;3 h) and the amplitude is too strong over both tropical ocean and land regions. Most of the wet and dry precipitation biases, particularly those over land, can be explained by the diurnal-cycle discrepancies. An overall wet bias over the equatorial Pacific and Indian Oceans and a dry bias over the western Pacific warmpool and India are linked with similar biases in the climate model, which shares common parameterizations with the NWP version. Whereas precipitation biases develop within hours in the NWP model, underestimates in water vapor (which are assimilated by the NWP model) evolve over the first few days of the forecast. The NWP simulations are able to capture observed daily-to-intraseasonal variability in water vapor and precipitation, including fluctuations associated with tropical cyclones

The role of snow cover affecting boreal-arctic soil freeze–thaw and carbon dynamics

Northern Hemisphere permafrost affected land areas contain about twice as much carbon as the global atmosphere. This vast carbon pool is vulnerable to accelerated losses through mobilization and decomposition under projected global warming. Satellite data records spanning the past 3 decades indicate widespread reductions (~ 0.8–1.3 days decade−1) in the mean annual snow cover extent and frozen-season duration across the pan-Arctic domain, coincident with regional climate warming trends. How the soil carbon pool responds to these changes will have a large impact on regional and global climate. Here, we developed a coupled terrestrial carbon and hydrology model framework with a detailed 1-D soil heat transfer representation to investigate the sensitivity of soil organic carbon stocks and soil decomposition to climate warming and changes in snow cover conditions in the pan-Arctic region over the past 3 decades (1982–2010). Our results indicate widespread soil active layer deepening across the pan-Arctic, with a mean decadal trend of 6.6 ± 12.0 (SD) cm, corresponding to widespread warming. Warming promotes vegetation growth and soil heterotrophic respiration particularly within surface soil layers (≤ 0.2 m). The model simulations also show that seasonal snow cover has a large impact on soil temperatures, whereby increases in snow cover promote deeper (≥ 0.5 m) soil layer warming and soil respiration, while inhibiting soil decomposition from surface (≤ 0.2 m) soil layers, especially in colder climate zones (mean annual T ≤ −10 °C). Our results demonstrate the important control of snow cover on northern soil freeze–thaw and soil carbon decomposition processes and the necessity of considering both warming and a change in precipitation and snow cover regimes in characterizing permafrost soil carbon dynamics

Distinct effects of AMPA receptor subunit depletion on spatial memory

Pharmacological studies established a role for AMPARs in the mammalian forebrain in spatial memory performance. Here we generated global GluA1/3 double knockout mice (Gria1/3−/−) and conditional knockouts lacking GluA1 and GluA3 AMPAR subunits specifically from principal cells across the forebrain (Gria1/3ΔFb). In both models, loss of GluA1 and GluA3 resulted in reduced hippocampal GluA2 and increased levels of the NMDAR subunit GluN2A. Electrically-evoked AMPAR-mediated EPSPs were greatly diminished, and there was an absence of tetanus-induced LTP. Gria1/3−/− mice showed premature mortality. Gria1/3ΔFb mice were viable, and their memory performance could be analyzed. In the Morris water maze (MWM), Gria1/3ΔFb mice showed profound long-term memory deficits, in marked contrast to the normal MWM learning previously seen in single Gria1−/− and Gria3−/− knockout mice. Our results suggest a redundancy of function within the pool of available ionotropic glutamate receptors for long-term spatial memory performance

Future Decreases in Freezing Days across North America

This study used air temperatures from a suite of regional climate models participating in the North American Climate Change Assessment Program (NARCCAP) together with two atmospheric reanalysis datasets to investigate changes in freezing days (defined as days with daily average temperature below freezing) likely to occur between 30-yr baseline (1971–2000) and midcentury (2041–70) periods across most of North America. Changes in NARCCAP ensemble mean winter temperature show a strong gradient with latitude, with warming of over 4°C near Hudson Bay. The decline in freezing days ranges from less than 10 days across north-central Canada to nearly 90 days in the warmest areas of the continent that currently undergo seasonally freezing conditions. The area experiencing freezing days contracts by 0.9–1.0 × 106 km2 (5.7%–6.4% of the total area). Areas with mean annual temperature between 2° and 6°C and a relatively low rate of change in climatological daily temperatures (−) near the time of spring thaw will encounter the greatest decreases in freezing days. Advances in the timing of spring thaw will exceed the delay in fall freeze across much of the United States, with the reverse pattern likely over most of Canada

A Reappraisal of Children’s ‘Potential’

What does it mean for a child to fulfil his or her potential? This article explores the contexts and implications of the much-used concept of potential in educational discourses. We claim that many of the popular, political and educational uses of the term in relation to childhood have a problematic blind spot: interpersonality, and the necessary coexistence for the concept to be receivable of all children’s ‘potentials’. Rather than advocating abandoning the term—a futile gesture given its emotive force—we argue that the concept of children’s potential must be profoundly rethought to be workable as a philosophical notion in education. In an era marked by the unspoken assumption that ‘unlimited potential’ is always a good thing, we argue that it might be necessary to think about the limitations of the notion of individual potential; namely, the moment when it comes into contact with other people’s projects. We propose a conceptualisation of potential as the negotiated, situated, ever-changing creation of a group of individuals, in a process marked by conflict, and which remains essentially difficult.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11217-016-9508-