595 research outputs found

    Adoption and Foster Care by Gay and Lesbian Parents in the United States

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    Discussion and debate about adoption and foster care by gay, lesbian, and bisexual (GLB) parents occurs frequently among child welfare policymakers, social service agencies, and social workers. They all need better information about GLB adoptive and foster parents and their children as they make individual and policy-level decisions about placement of children with GLB parents. This report provides new information on GLB adoption and foster care from the U.S. Census 2000, the National Survey of Family Growth (2002), and the Adoption and Foster Care Analysis and Reporting System (2004)

    Variable stroke timing of rubber fins' duty cycle improves force

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    Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.

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    The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extends to the germline is unknown. Here, we show that germline deletion of Nanog reduces PGC numbers 5-fold at midgestation. Despite this quantitative depletion, Nanog-null PGCs can complete germline development in contrast to previous findings. PGC-like cell (PGCLC) differentiation of Nanog-null ESCs is also impaired, with Nanog-null PGCLCs showing decreased proliferation and increased apoptosis. However, induced expression of Esrrb restores PGCLC numbers as efficiently as Nanog. These effects are recapitulated in vivo: knockin of Esrrb to Nanog restores PGC numbers to wild-type levels and results in fertile adult mice. These findings demonstrate that Esrrb can replace Nanog function in germ cells

    Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum

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    BACKGROUND: The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved. RESULTS: We reassessed the central carbon metabolism of P. falciparum asexual and sexual blood stages, by metabolically labeling each stage with (13)C-glucose and (13)C-glutamine, and analyzing isotopic enrichment in key pathways using mass spectrometry. In contrast to previous findings, we found that carbon skeletons derived from both glucose and glutamine are catabolized in a canonical oxidative TCA cycle in both the asexual and sexual blood stages. Flux of glucose carbon skeletons into the TCA cycle is low in the asexual blood stages, with glutamine providing most of the carbon skeletons, but increases dramatically in the gametocyte stages. Increased glucose catabolism in the gametocyte TCA cycle was associated with increased glucose uptake, suggesting that the energy requirements of this stage are high. Significantly, whereas chemical inhibition of the TCA cycle had little effect on the growth or viability of asexual stages, inhibition of the gametocyte TCA cycle led to arrested development and death. CONCLUSIONS: Our metabolomics approach has allowed us to revise current models of P. falciparum carbon metabolism. In particular, we found that both asexual and sexual blood stages utilize a conventional TCA cycle to catabolize glucose and glutamine. Gametocyte differentiation is associated with a programmed remodeling of central carbon metabolism that may be required for parasite survival either before or after uptake by the mosquito vector. The increased sensitivity of gametocyte stages to TCA-cycle inhibitors provides a potential target for transmission-blocking drugs

    Influence of real-world characteristics on outcomes for patients with methicillin-resistant Staphylococcal skin and soft tissue infections:a multi-country medical chart review in Europe

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    BACKGROUND: Patient-related (demographic/disease) and treatment-related (drug/clinician/hospital) characteristics were evaluated as potential predictors of healthcare resource use and opportunities for early switch (ES) from intravenous (IV)-to-oral methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic therapy and early hospital discharge (ED). METHODS: This retrospective observational medical chart study analyzed patients (across 12 European countries) with microbiologically confirmed MRSA complicated skin and soft tissue infections (cSSTI), ≥3 days of IV anti-MRSA antibiotics during hospitalization (July 1, 2010-June 30, 2011), and discharged alive by July 31, 2011. Logistic/linear regression models evaluated characteristics potentially associated with actual resource use (length of IV therapy, length of hospital stay [LOS], IV-to-oral antibiotic switch), and ES and ED (using literature-based and expert-verified criteria) outcomes. RESULTS: 1542 patients (mean ± SD age 60.8 ± 16.5 years; 61.5% males) were assessed with 81.0% hospitalized for MRSA cSSTI as the primary reason. Several patient demographic, infection, complication, treatment, and hospital characteristics were predictive of length of IV therapy, LOS, IV-to-oral antibiotic switch, or ES and ED opportunities. Outcomes and ES and ED opportunities varied across countries. Length of IV therapy and LOS (r = 0.66, p < 0.0001) and eligibilities for ES and ED (r = 0.44, p < 0.0001) showed relatively strong correlations. IV-to-oral antibiotic switch patients had significantly shorter length of IV therapy (−5.19 days, p < 0.001) and non-significantly shorter LOS (−1.86 days, p > 0.05). Certain patient and treatment characteristics were associated with increased odds of ES (healthcare-associated/ hospital-acquired infection) and ED (patient living arrangements, healthcare-associated/ hospital-acquired infection, initiating MRSA-active treatment 1–2 days post cSSTI index date, existing ED protocol), while other factors decreased the odds of ES (no documented MRSA culture, ≥4 days from admission to cSSTI index date, IV-to-oral switch, IV line infection) and ED (dementia, no documented MRSA culture, initiating MRSA-active treatment ≥3 days post cSSTI index date, existing ES protocol). CONCLUSIONS: Practice patterns and opportunity for further ES and ED were affected by several infection, treatment, hospital, and geographical characteristics, which should be considered in identifying ES and ED opportunities and designing interventions for MRSA cSSTI to reduce IV days and LOS while maintaining the quality of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-476) contains supplementary material, which is available to authorized users

    Antibiotic treatment patterns across Europe in patients with complicated skin and soft-tissue infections due to meticillin-resistant <em>Staphylococcus aureus</em>:a plea for implementation of early switch and early discharge criteria

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    AbstractThis retrospective observational medical chart review aimed to describe country-specific variations across Europe in real-world meticillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) treatment patterns, antibiotic stewardship activity, and potential opportunities for early switch (ES) from intravenous (i.v.) to oral formulations and early discharge (ED) from hospital using standardised data collection and criteria and economic implications of these opportunities. Patients were randomly sampled from 12 countries (Austria, Czech Republic, France, Germany, Greece, Ireland, Italy, Poland, Portugal, Slovakia, Spain and the UK), aged ≥18 years, with documented MRSA cSSTI, hospitalised between 1 July 2010 and 30 June 2011, discharged alive by 31 July 2011. Of 1502 patients, 1468 received MRSA-targeted therapy. Intravenous-to-oral switch rates ranged from 2.0% to 20.2%, i.v. length of therapy from 10.1 to 18.6 days and hospital length of stay (LoS) from 15.2 to 25.0 days across Europe. Of 341 sites, 82.9% had antibiotic steering committees, 23.7% had i.v.-to-oral switch antibiotic protocols and 12.9% had ED protocols for MRSA cSSTI. ES and ED eligibility ranged from 12.0% (Slovakia) to 56.3% (Greece) and from 10% (Slovakia) to 48.2% (Portugal), respectively. Potential cost savings per ED-eligible patient ranged from €414 (Slovakia) to €2703 (France). MRSA cSSTI treatment patterns varied widely across countries, but further reductions in i.v. therapy, hospital LoS and associated costs could be realised. These data provide insight into clinical practice patterns across diverse European healthcare systems and identify potential opportunities for local clinicians and policy-makers to improve clinical care and cost-effectiveness of this therapeutic area

    DARIAH Beyond Europe

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    International audienceDARIAH, the digital humanities infrastructure with origins and an organisational home in Europe, is nearing the completion of its implementation phase. The significant investment from the European Commission and member countries has yielded a robust set of technical and social infrastructures, ranging from working groups, various registries, pedagogical materials, and software to support diverse approaches to digital humanities scholarship. While the funding and leadership of DARIAH to date has come from countries in, or contiguous with, Europe, the needs that drive its technical and social development are widely shared within the international digital humanities community beyond Europe. Scholars on every continent would benefit from well-supported technical tools and platforms, directories for facilitating access to information and resources, and support for working groups.The DARIAH Beyond Europe workshop series, organised and financed under the umbrella of the DESIR project (“DARIAH ERIC Sustainability Refined,” 2017–2019, funded by the European Union’s Horizon 2020 Research and Innovation Program), convened three meetings between September 2018 and March 2019 in the United States and Australia. These workshops served as fora for cross-cultural exchange, and introduced many non-European DH scholars to DARIAH; each of the workshops included a significant delegation from various DARIAH bodies, together with a larger number of local presenters and participants. The local contexts for these workshops were significantly different in their embodiment of research infrastructures: on the one hand, in the U.S., a private research university (Stanford) and the de facto national library (the Library of Congress), both in a country with a history of unsuccessful national-scale infrastructure efforts; and in Australia, a system which has invested substantially more in coordinated national research infrastructure in science and technology, but very little on a national scale in the humanities and arts. Europe is in many respects ahead of both host countries in terms of its research infrastructure ecosystem both at the national and pan-European levels.The Stanford workshop had four main topics of focus: corpus management; text and image analysis; geohumanities; and music, theatre, and sound studies. As the first of the workshops, the Stanford group also took the lead in proposing next steps toward exploring actionable “DARIAH beyond Europe” initiatives, including the beginnings of a blog shared among participants from all the workshops, extra-European use of DARIAH’s DH Course Registry, and non-European participation in DARIAH Working Groups.The overall theme of the Library of Congress workshop was “Collections as Data,” building on a number of U.S.-based initiatives exploring how to enhance researcher engagement with digital collections through computationally-driven research. In Washington, D.C., the knowledge exchange sessions focussed on digitised newspapers and text analysis, infrastructural challenges for public humanities, and the use of web-archives in DH research. As at Stanford, interconnecting with DARIAH Working Groups was of core interest to participants, and a new Working Group was proposed to explore global access and use of digitised historical newspapers. A further important outcome was the agreement to explore collaboration between the U.S.-based “Collections as Data” initiatives and the Heritage Data Reuse Charter in Europe. The third and final workshop in the series took place in March 2019 in Australia, hosted by the National Library of Australia in Canberra. Convened by the Australian Academy of the Humanities (AAH), together with the Australian Research Data Commons (ARDC) and DARIAH, this event was co-located with the Academy’s second annual Humanities, Arts and Culture Data Summit. The first day of the event, targeted at research leadership and policy makers, was intended to explore new horizons for data-driven humanities and arts research, digital cultural collections and research infrastructure. The two subsequent days focused on engaging with a wide variety of communities, including (digital) humanities researchers and cultural heritage professionals. Organised around a series of Knowledge Exchange Sessions, combined with research-led lightning talks, the participants spoke in detail about how big ideas can be implemented practically on the ground. This poster reflects on the key outcomes and future directions arising from these three workshops, and considers what it might look like for DARIAH to be adopted as a fundamental DH infrastructure in a complex variety of international, national, and regional contexts, with diverse funding models, resources, needs, and expectations. One major outcome of all workshops was the shared recognition that, in spite of extensive funding, planning, and goodwill, these workshops were not nearly global enough in their reach: most importantly they were not inclusive of the Global South. Our new DARIAH beyond Europe community has a strong shared commitment to address this gap

    The interaction between vortices and a biomimetic flexible fin

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    The fluid-structure interaction of flexible bodies in steady and unsteady flow is a key area of interest for the development of underwater vehicles. In the design of marine vehicles the flow can often be seen as an obstacle to overcome, whilst in nature a fish interacts with the flow and is capable of achieving a high level of efficiency. Therefore by understanding how fish – or flexible bodies – interact with the flow we may be able to achieve a better level of co-operation between our vehicles and their environment, potentially attaining a better efficiency in design

    Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening

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    The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a heterodimer that drives virus-host membrane fusion. Here, we analyze the role of each amino acid in E1E2 function, expressing 545 individual alanine mutants of E1E2 in human cells, incorporating them into infectious viral pseudoparticles, and testing them against 37 different monoclonal antibodies (MAbs) to ascertain full-length translation, folding, heterodimer assembly, CD81 binding, viral pseudoparticle incorporation, and infectivity. We propose a model describing the role of each critical residue in E1E2 functionality and use it to examine how MAbs neutralize infection by exploiting functionally critical sites of vulnerability on E1E2. Our results suggest that E1E2 is a surprisingly fragile protein complex where even a single alanine mutation at 92% of positions disrupts its function. The amino-acid-level targets identified are highly conserved and functionally critical and can be exploited for improved therapies and vaccines
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