214 research outputs found

    The Death of Private Corporations Having Capital Stock

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    Lunar Precursor Robotic Program: A Robotic Focus To The Vision

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    In April 2006, NASA, with help from the commercial and international communities, began developing a global Lunar Exploration Strategy. These activities resulted in themes that expanded on why we should return to the Moon and objectives that identify what we should do when we get there. NASA used these results to develop a Lunar Architecture designed to achieve the subset of the global Lunar Exploration Strategy objectives that fit within NASA's scope. A component of this architecture is the Lunar Precursor Robotic Program. This Program, anticipated to consist of both lunar orbiters and landers, is intended to meet many of NASA's lunar exploration objectives

    Path Forward to Space Solar Power using the O'Neill - Glaser Model Modified for Climate Change Demand and Considering the Increasing Risk of Human Self-Extinction if Confined to Earth

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    The cost of energy is humanity's economic exchange rate with the universe. Space solar power is the first great step that our technological species has to utilize the energy of its star. The classic Peter Glaser Solar Power Satellite, SPS, and later designs collect a large area of solar energy in space and beam it back to Earth for use in the electric grid, but even with optimistic launch costs and technology innovation a clear economic path is not evident using Earth launch of SPS. O Neill in 1969 solved the transportation costs problem by a model that uses lunar and asteroid materials to build SPS and locates the labor force permanently in space (O Neill free space habitats). This solution closes the economics and predicts large profits after 17-35 years. However the costs of time have up to now prevented this solution. We discuss a strategy to move forward in SPS with the motivations to stop global warming and prevent human selfextinction. There are near term steps that can be taken that place us on this path forward. First, we must reevaluate the technologies for the classic model and update the parameters to current technology. As technological capability continues to increase exponentially, we need to understand when the monetary potential energy hills are small as the technology gets larger. But the chance for self-extinction, if humanity remains in a single vulnerable habitat, also increased exponentially with time. The path forward is to identify investment points while assessing the risks of non-action

    Estimated clinical outcomes and cost-effectiveness associated with provision of addiction treatment in US primary care clinics

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    IMPORTANCE: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown. OBJECTIVE: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids. DESIGN, SETTING, AND PARTICIPANTS: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine the following treatment strategies: (1) PCP services with external referral to addiction care (status quo), (2) PCP services plus onsite buprenorphine prescribing with referral to offsite harm reduction kits (BUP), and (3) PCP services plus onsite buprenorphine prescribing and harm reduction kits (BUP plus HR). Model inputs were derived from clinical trials and observational cohorts, and costs were discounted annually at 3%. The cost-effectiveness was evaluated over a lifetime from the modified health care sector perspective, and sensitivity analyses were performed to address uncertainty. Model simulation began January 1, 2021, and ran for the entire lifetime of the cohort. MAIN OUTCOMES AND MEASURES: Life-years (LYs), hospitalizations, mortality from sequelae (overdose, severe skin and soft tissue infections, and endocarditis), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: The simulated cohort included 2.25 million people and reflected the age and gender of US persons who inject opioids. Status quo resulted in 6.56 discounted LYs at a discounted cost of 203 500perperson(95203 500 per person (95% credible interval, 203 000-222 000).Eachstrategyextendeddiscountedlifeexpectancy:BUPby0.16yearsandBUPplusHRby0.17years.Comparedwithstatusquo,BUPplusHRreducedsequelae−relatedmortalityby33222 000). Each strategy extended discounted life expectancy: BUP by 0.16 years and BUP plus HR by 0.17 years. Compared with status quo, BUP plus HR reduced sequelae-related mortality by 33%. The mean discounted lifetime cost per person of BUP and BUP plus HR were more than that of the status quo strategy. The dominating strategy was BUP plus HR. Compared with status quo, BUP plus HR was cost-effective (ICER, 34 400 per LY). During a 5-year time horizon, BUP plus HR cost an individual PCP practice approximately $13 000. CONCLUSIONS AND RELEVANCE: This modeling study of integrated addiction service in primary care found improved clinical outcomes and modestly increased costs. The integration of addiction service into primary care practices should be a health care system priority

    A custom-made guide-wire positioning device for Hip Surface Replacement Arthroplasty: description and first results

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    <p>Abstract</p> <p>Background</p> <p>Hip surface replacement arthroplasty (SRA) can be an alternative for total hip arthroplasty. The short and long-term outcome of hip surface replacement arthroplasty mainly relies on the optimal size and position of the femoral component. This can be defined before surgery with pre-operative templating. Reproducing the optimal, templated femoral implant position during surgery relies on guide wire positioning devices in combination with visual inspection and experience of the surgeon. Another method of transferring the templated position into surgery is by navigation or Computer Assisted Surgery (CAS). Though CAS is documented to increase accurate placement particularly in case of normal hip anatomy, it requires bulky equipment that is not readily available in each centre.</p> <p>Methods</p> <p>A custom made neck jig device is presented as well as the results of a pilot study.</p> <p>The device is produced based on data pre-operatively acquired with CT-scan. The position of the guide wire is chosen as the anatomical axis of the femoral neck. Adjustments to the design of the jig are made based on the orthopedic surgeon's recommendations for the drill direction. The SRA jig is designed as a slightly more-than-hemispherical cage to fit the anterior part of the femoral head. The cage is connected to an anterior neck support. Four knifes are attached on the central arch of the cage. A drill guide cylinder is attached to the cage, thus allowing guide wire positioning as pre-operatively planned.</p> <p>Custom made devices were tested in 5 patients scheduled for total hip arthroplasty. The orthopedic surgeons reported the practical aspects of the use of the neck-jig device. The retrieved femoral heads were analyzed to assess the achieved drill place in mm deviation from the predefined location and orientation compared to the predefined orientation.</p> <p>Results</p> <p>The orthopedic surgeons rated the passive stability, full contact with neck portion of the jig and knife contact with femoral head, positive. There were no guide failures. The jig unique position and the number of steps required to put the guide in place were rated 1, while the complexity to put the guide into place was rated 1-2. In all five cases the guide wire was accurately positioned. Maximum angular deviation was 2.9° and maximum distance between insertion points was 2.1 mm.</p> <p>Conclusions</p> <p>Pilot testing of a custom made jig for use during SRA indicated that the device was (1) successfully applied and user friendly and (2) allowed for accurate guide wire placement according to the preoperative plan.</p

    Distribution of the invasive bryozoan Schizoporella japonica in Great Britain and Ireland and a review of its European distribution

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    The bryozoan Schizoporella japonica Ortmann (1890) was first recorded in European waters in 2010 and has since been reported from further locations in Great Britain (GB) and Norway. This paper provides a new earliest European record for the species from 2009, a first record from Ireland and presence and absence records from a total of 231 marinas and harbours across GB, Ireland, the Isle of Man, France and Portugal. This species is typically associated with human activity, including commercial and recreational vessels, aquaculture equipment, and both wave and tidal energy devices. It has also been observed in the natural environment, fouling rocks and boulders. The species has an extensive but widely discontinuous distribution in GB and Ireland. Although found frequently in marinas and harbours in Scotland, it inhabits only a few sites in England, Wales and Ireland, interspersed with wide gaps that are well documented as genuine absences. This appears to be a rare example of a southward-spreading invasion in GB and Ireland. The species has been reported from the Isle of Man and Norway but has not been found in France or Portugal. In the future we expect S. japonica to spread into suitable sections of the English, Welsh and Irish coasts, and further within Europe. The species’ capability for long-distance saltatory spread and potential for negative impact on native ecosystems and economic activity suggests that S. japonica should now be considered invasive in GB and Ireland. As such, it is recommended that biosecurity procedures alongside effective surveillance and monitoring should be prioritised for regions outside the species’ current distribution

    Identifying the physical features of marina infrastructure associated with the presence of non-native species in the UK

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    Marine invasive non-native species (NNS) are one of the greatest threats to global marine biodiversity, causing significant economic and social impacts. Marinas are increasingly recognised as key reservoirs for invasive NNS. They provide submersed artificial habitat that unintentionally supports the establishment of NNS introduced from visiting recreational vessels. While ballast water and shipping vectors have been well documented, the role of recreational vessels in spreading NNS has been relatively poorly studied. Identification of the main physical features found within marinas, which relate to the presence of NNS, is important to inform the development of effective biosecurity measures and prevent further spread. Towards this aim, physical features that could influence the presence of NNS were assessed for marinas throughout the UK in July 2013. Thirty-three marine and brackish NNS have been recorded in UK marinas, and of the 88 marinas studied in detail, 83 contained between 1 and 13 NNS. Significant differences in freshwater input, marina entrance width and seawall length were associated with the presence of NNS. Additionally, questionnaires were distributed to marina managers and recreational vessel owners to understand current biosecurity practices and attitudes to recreational vessel biosecurity. The main barriers to biosecurity compliance were cited as cost and time. Further work identifying easily distinguished features of marinas could be used as a proxy to assess risk of invasion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00227-016-2941-8) contains supplementary material, which is available to authorized users

    Enzymatic Analysis of Recombinant Japanese Encephalitis Virus NS2B(H)-NS3pro Protease with Fluorogenic Model Peptide Substrates

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    Background Japanese encephalitis virus (JEV), a member of the Flaviviridae family, causes around 68,000 encephalitis cases annually, of which 20–30% are fatal, while 30–50% of the recovered cases develop severe neurological sequelae. Specific antivirals for JEV would be of great importance, particularly in those cases where the infection has become persistent. Being indispensable for flaviviral replication, the NS2B-NS3 protease is a promising target for design of anti-flaviviral inhibitors. Contrary to related flaviviral proteases, the JEV NS2B-NS3 protease is structurally and mechanistically much less characterized. Here we aimed at establishing a straightforward procedure for cloning, expression, purification and biochemical characterization of JEV NS2B(H)-NS3pro protease. Methodology/Principal Findings The full-length sequence of JEV NS2B-NS3 genotype III strain JaOArS 982 was obtained as a synthetic gene. The sequence of NS2B(H)-NS3pro was generated by splicing by overlap extension PCR (SOE-PCR) and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H)-NS3pro, expressed in E. coli as soluble protein, was purified to &gt;95% purity by a single-step immobilized metal affinity chromatography. SDS-PAGE and immunoblotting of the purified enzyme demonstrated NS2B(H)-NS3pro precursor and its autocleavage products, NS3pro and NS2B(H), as 36, 21, and 10 kDa bands, respectively. Kinetic parameters, Km and kcat, for fluorogenic protease model substrates, Boc-GRR-amc, Boc-LRR-amc, Ac-nKRR-amc, Bz-nKRR-amc, Pyr-RTKR-amc and Abz-(R)4SAG-nY-amide, were obtained using inner filter effect correction. The highest catalytic efficiency kcat/Km was found for Pyr-RTKR-amc (kcat/Km: 1962.96±85.0 M−1 s−1) and the lowest for Boc-LRR-amc (kcat/Km: 3.74±0.3 M−1 s−1). JEV NS3pro is inhibited by aprotinin but to a lesser extent than DEN and WNV NS3pro. Conclusions/Significance A simplified procedure for the cloning, overexpression and purification of the NS2B(H)-NS3pro was established which is generally applicable to other flaviviral proteases. Kinetic parameters obtained for a number of model substrates and inhibitors, are useful for the characterization of substrate specificity and eventually for the design of high-throughput assays aimed at antiviral inhibitor discovery
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