8,048 research outputs found

    PMH60 A PHARMACOECONOMIC COMPARISON OF ESCITALOPRAM AND DULOXETINE IN TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD) IN THE UNITED KINGDOM

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    Extension and approximation of mm-subharmonic functions

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    Let ΩCn\Omega\subset \mathbb C^n be a bounded domain, and let ff be a real-valued function defined on the whole topological boundary Ω\partial \Omega. The aim of this paper is to find a characterization of the functions ff which can be extended to the inside to a mm-subharmonic function under suitable assumptions on Ω\Omega. We shall do so by using a function algebraic approach with focus on mm-subharmonic functions defined on compact sets. We end this note with some remarks on approximation of mm-subharmonic functions

    Removal of ecotoxicity of 17α-ethinylestradiol using TAML/peroxide water treatment

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    17α -ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent. Ozone and activated carbon provide effective wastewater treatments, but their energy intensities and capital/operating costs are formidable barriers to adoption. Here we describe the technical and environmental performance of a fast- developing contender for mitigation of EE2 contamination of wastewater based upon smallmolecule, full-functional peroxidase enzyme replicas called “TAML activators”. From neutral to basic pH, TAML activators with H2O2 efficiently degrade EE2 in pure lab water, municipal effluents and EE2-spiked synthetic urine. TAML/H2O2 treatment curtails estrogenicity in vitro and substantially diminishes fish feminization in vivo. Our results provide a starting point for a future process in which tens of thousands of tonnes of wastewater could be treated per kilogram of catalyst. We suggest TAML/H2O2 is a worthy candidate for exploration as an environmentally compatible, versatile, method for removing EE2 and other pharmaceuticals from municipal wastewaters.Heinz Endowments, the Swiss National Science Foundation, the Steinbrenner Institute for a Steinbrenner Doctoral Fellowship. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)

    Novel clinicopathological characteristics differentiate dementia with Lewy bodies from Parkinson's disease dementia

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    Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) known as Lewy body dementias have overlapping clinical and neuropathological features. Neuropathology in both includes combination of Lewy body and Alzheimer's disease (AD) pathology. Cerebral amyloid angiopathy (CAA), often seen in AD, is increasingly recognised for its association with dementia. AIMS: This study investigated clinical and neuropathological differences between DLB and PDD. METHODS: 52 PDD and 16 DLB cases from the Queen Square Brain Bank (QSBB) for Neurological disorders were included. Comprehensive clinical data of motor and cognitive features were obtained from medical records. Neuropathological assessment included examination of CAA, Lewy body and AD pathology. RESULTS: CAA was more common in DLB than in PDD (p = 0.003). The severity of CAA was greater in DLB than in PDD (p = 0.009), with significantly higher CAA scores in the parietal lobe (p = 0.043), and the occipital lobe (p = 0.008), in DLB than in PDD. The highest CAA scores were observed in cases with APOE ε4/4 and ε2/4. Survival analysis showed worse prognosis in DLB, as DLB reached each clinical milestone sooner than PDD. Absence of dyskinesia in DLB is linked to the significantly lower lifetime cumulative dose of levodopa in comparison with PDD. CONCLUSIONS: This is the first study which identified prominent concurrent CAA pathology as a pathological substrate of DLB. More prominent CAA and rapid disease progression as measured by clinical milestones distinguish DLB from PDD

    Dose prescription with spatial uncertainty for peripheral lung SBRT.

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    Current clinical practice is to prescribe to 95% of the planning target volume (PTV) in 4D stereotactic body radiotherapy (SBRT) for lung. Frequently the PTV margin has a very low physical density so that the internal target volume (ITV) receives an unnecessarily high dose. This study investigates the alternative of prescribing to the ITV while including the effects of positional uncertainties. Five patients were retrospectively studied with volumetric modulated arc therapy treatment plans. Five plans were produced for each patient: a static plan prescribed to PTV D95% , three probabilistic plans prescribed to ITV D95% and a static plan re-prescribed to ITV D95% after inverse planning. For the three probabilistic plans, the scatter kernel in the dose calculation was convolved with a spatial uncertainty distribution consisting of either a uniform distribution extending ±5 mm in the three orthogonal directions, a distribution consisting of delta functions at ±5 mm, or a Gaussian distribution with standard deviation 5 mm. Median ITV D50% is 23% higher than the prescribed dose for static planning and only 10% higher than the prescribed dose for prescription to the ITV. The choice of uncertainty distribution has less than 2% effect on the median ITV dose. Re-prescribing a static plan and evaluating with a probabilistic dose calculation results in a median ITV D95% which is 1.5% higher than when planning probabilistically. This study shows that a robust probabilistic approach to planning SBRT lung treatments results in the ITV receiving a dose closer to the intended prescription. The exact form of the uncertainty distribution is not found to be critical

    The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

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    <p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

    How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

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    Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

    Molecular dynamics simulations of oscillatory Couette flows with slip boundary conditions

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    The effect of interfacial slip on steady-state and time-periodic flows of monatomic liquids is investigated using non-equilibrium molecular dynamics simulations. The fluid phase is confined between atomically smooth rigid walls, and the fluid flows are induced by moving one of the walls. In steady shear flows, the slip length increases almost linearly with shear rate. We found that the velocity profiles in oscillatory flows are well described by the Stokes flow solution with the slip length that depends on the local shear rate. Interestingly, the rate dependence of the slip length obtained in steady shear flows is recovered when the slip length in oscillatory flows is plotted as a function of the local shear rate magnitude. For both types of flows, the friction coefficient at the liquid-solid interface correlates well with the structure of the first fluid layer near the solid wall.Comment: 31 pages, 11 figure

    Gravitational redshift of galaxies in clusters as predicted by general relativity

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    The theoretical framework of cosmology is mainly defined by gravity, of which general relativity is the current model. Recent tests of general relativity within the \Lambda Cold Dark Matter (CDM) model have found a concordance between predictions and the observations of the growth rate and clustering of the cosmic web. General relativity has not hitherto been tested on cosmological scales independent of the assumptions of the \Lambda CDM model. Here we report observation of the gravitational redshift of light coming from galaxies in clusters at the 99 per cent confidence level, based upon archival data. The measurement agrees with the predictions of general relativity and its modification created to explain cosmic acceleration without the need for dark energy (f(R) theory), but is inconsistent with alternative models designed to avoid the presence of dark matter.Comment: Published in Nature issued on 29 September 2011. This version includes the Letter published there as well as the Supplementary Information. 23 pages, 7 figure
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