The Late Miocene-Early Pliocene Biogenic Bloom: An Integrated Study in the Tasman Sea

The Late Miocene-Early Pliocene Biogenic Bloom (∼9–3.5 Ma) was a paleoceanographic phenomenon defined by anomalously high accumulations of biological components at multiple open ocean sites, especially in certain regions of the Indian, and Pacific oceans. Its temporal and spatial extent with available information leaves fundamental questions about driving forces and responses unanswered. In this work, we focus on the middle part of the Biogenic Bloom (7.4–4.5 Ma) at International Ocean Discovery Program Site U1506 in the Tasman Sea, where we provide an integrated age model based on orbital tuning of the Natural Gamma Radiation, benthic foraminiferal oxygen isotopes, and calcareous nannofossil biostratigraphy. Benthic foraminiferal assemblages suggest changes in deep water oxygen concentration and seafloor nutrient supply during generally high export productivity conditions. From 7.4 to 6.7 Ma, seafloor conditions were characterized by episodic nutrient supply, perhaps related to seasonal phytoplankton blooms. From 6.7 to 4.5 Ma, the regime shifted to a more stable interval characterized by eutrophic and dysoxic conditions. Combined with seismic data, a regional change in paleoceanography is inferred at around 6.7 Ma, from stronger and well-oxygenated bottom currents to weaker, oxygen-depleted bottom currents. Our results support the hypothesis that the Biogenic Bloom was a complex, multiphase phenomenon driven by changes in ocean currents, rather than a single uniform period of sustained sea surface water productivity. Highly resolved studies are thus fundamental to its understanding and the disentanglement of local, regional, and global imprints

Mucosal Therapy of Multi-Drug Resistant Tuberculosis With IgA and Interferon-γ

New evidence has been emerging that antibodies can be protective in various experimental models of tuberculosis. Here, we report on protection against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) infection using a combination of the human monoclonal IgA 2E9 antibody against the alpha-crystallin (Acr, HspX) antigen and mouse interferon-gamma in mice transgenic for the human IgA receptor, CD89. The effect of the combined mucosal IgA and IFN-γ; treatment was strongest (50-fold reduction) when therapy was applied at the time of infection, but a statistically significant reduction of lung bacterial load was observed even when the therapy was initiated once the infection had already been established. The protection involving enhanced phagocytosis and then neutrophil mediated killing of infected cells was IgA isotype mediated, because treatment with an IgG version of 2E9 antibody was not effective in human IgG receptor CD64 transgenic mice. The Acr antigen specificity of IgA antibodies for protection in humans has been indicated by their elevated serum levels in latent tuberculosis unlike the lack of IgA antibodies against the virulence-associated MPT64 antigen. Our results represent the first evidence for potential translation of mucosal immunotherapy for the management of MDR-TB

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The global distribution and burden of dengue.

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation

Treatment Outcome in Patients Receiving Assertive Community Treatment

In an observational study of severely mentally ill patients treated in assertive community treatment (ACT) teams, we investigated how treatment outcome was associated with demographic factors, clinical factors, and motivation for treatment. To determine psychosocial outcome, patients were routinely assessed using the Health of the Nation Outcome Scales (HoNOS). Trends over time were analyzed using a mixed model with repeated measures. The HoNOS total score was modeled as a function of treatment duration and patient-dependent covariates. Data comprised 637 assessments of 139 patients; mean duration of follow-up was 27.4 months (SD = 5.4). Substance abuse, higher age, problems with motivation, and lower educational level were associated with higher HoNOS total scores (i.e., worse outcome). To improve treatment outcome, we recommend better implementation of ACT, and also the implementation of additional programs targeting subgroups which seem to benefit less from ACT

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Protocol for the SEED-trial: Supported Employment and preventing Early Disability

Background: Early withdrawal or exclusion from the labor market leads to significant personal and societal costs. In Norway, the increasing numbers of young adults receiving disability pension is a growing problem. While a large body of research demonstrates positive effects of Supported Employment (SE) in patients with severe mental illness, no studies have yet investigated the effectiveness of SE in young adults with a range of social and health conditions who are receiving benefits. Methods/design: The SEED-trial is a randomized controlled trial (RCT) comparing traditional vocational rehabilitation (TVR) to SE in 124 unemployed individuals between the ages of 18-29 who are receiving benefits due to various social- or health-related problems. The primary outcome is labor market participation during the first year after enrollment. Secondary outcomes include physical and mental health, health behaviors, and well-being, collected at baseline, 6, and 12 months. A cost-benefit analysis will also be conducted. Discussion: The SEED-trial is the first RCT to compare SE to TVR in this important and vulnerable group, at risk of being excluded from working life at an early age

Employment of ex-prisoners with mental health problems, a realistic evaluation protocol

Background Offenders with a mental illness are routinely excluded from vocational services due to their mental health. Employment has shown to be very important in improving mental health, reducing recidivism, and connecting people to society. This study examines the effectiveness of an established intervention which is relatively untested in this population, Individual Placement and Support (IPS), to help offenders with mental health problems into competitive employment. The overall research question is whether IPS is effective in gaining and sustaining competitive employment for offenders with a Severe Mental Illness (SMI). The context is an English criminal justice setting across different populations. The study will also measure non-vocational outcomes such as recidivism, mental health and social stability. Methods/Design A Realistic Evaluation (RE) design will address the questions “What works, for whom, and in what circumstances?” This study includes pre and post comparisons for a cohort of approximately 20 people taking part in IPS, and a similar number of controls, over a one year period. The RE also consists of interviews with practitioners and offenders in order to understand how IPS works and develops within the criminal justice system (CJS). By applying this framework the research can go from discovering whether IPS works, to how and why (or why not) IPS works. This is achieved by examining where the intervention is occurring (Context (C)), the mechanisms (M) that create particular behaviours, and how the outcomes (O) from the intervention all come together (CMOs). Employment outcomes will also be examined for all participants. Discussion By applying RE the research will permit inferences to be drawn about how and why (or why not) IPS works, by examining context, mechanisms and outcomes. IPS has never been implemented within the CJS in the United Kingdom. As a result, this evaluative research will not only provide a novel insight into the core research areas, but also how the intervention can be improved for others in the future