3,195 research outputs found

    Sign-reversal of the in-plane resistivity anisotropy in hole-doped iron pnictides

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    The in-plane anisotropy of the electrical resistivity across the coupled orthorhombic and magnetic transitions of the iron pnictides has been extensively studied in the parent and electron-doped compounds. All these studies universally show that the resistivity ρa\rho_{a} across the long orthorhombic axis aOa_{O} - along which the spins couple antiferromagnetically below the magnetic transition temperature - is smaller than the resistivity ρb\rho_{b} of the short orthorhombic axis bOb_{O}, i. e. ρa<ρb\rho_{a}<\rho_{b}. Here we report that in the hole-doped compounds Ba1x_{1-x}Kx_{x}Fe2_{2}As2_{2}, as the doping level increases, the resistivity anisotropy initially becomes vanishingly small, and eventually changes sign for sufficiently large doping, i. e. ρb<ρa\rho_{b}<\rho_{a}. This observation is in agreement with a recent theoretical prediction that considers the anisotropic scattering of electrons by spin-fluctuations in the orthorhombic/nematic state.Comment: This paper has been replaced by the new version offering new explanation of the experimental results first reported her

    Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

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    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

    Elite or middling? International students and migrant diversification

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    Student migrants from former sending regions now form a substantial share of non-European Union migration flows to Europe. These flows represent the convergence of extensive internationalisation of higher education with increasing restrictions on family and labour migration. This article provides the first examination of student migrants? early socio-cultural and structural integration by following recently arrived Pakistani students in London over an 18-month period. We use latent class analysis to identify both elite and two ?middling? types ? middle class and network-driven ? within our student sample. We then ask whether these types experience early socio-cultural and structural integration trajectories that differ in the ways that the elite and middling transnational literatures would suggest. We find differences in structural, but less in socio-cultural outcomes. We conclude that to understand the implications of expanding third country student migration across the European Union, it is important to recognize both the distinctiveness of this flow and its heterogeneity

    Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses

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    The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1. The screen revealed that small molecule inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription of PAI-1 without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs by using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provide evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.</p

    Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study

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    Background\textbf{Background} Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies—especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)—more commonly than do healthy controls. Methods\textbf{Methods} We recruited patients aged 14–35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABAA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK. Findings\textbf{Findings} Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8–7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibody-negative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months. Interpretation\textbf{Interpretation} Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.Medical Research Counci

    Response characteristics in the apex of the gerbil cochlea studied through auditory nerve recordings

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    In this study, we analyze the processing of low-frequency sounds in the cochlear apex through responses of auditory nerve fibers (ANFs) that innervate the apex. Single tones and irregularly spaced tone complexes were used to evoke ANF responses in Mongolian gerbil. The spike arrival times were analyzed in terms of phase locking, peripheral frequency selectivity, group delays, and the nonlinear effects of sound pressure level (SPL). Phase locking to single tones was similar to that in cat. Vector strength was maximal for stimulus frequencies around 500 Hz, decreased above 1 kHz, and became insignificant above 4 to 5 kHz. We used the responses to tone complexes to determine amplitude and phase curves of ANFs having a characteristic frequency (CF) below 5 kHz. With increasing CF, amplitude curves gradually changed from broadly tuned and asymmetric with a steep low-frequency flank to more sharply tuned and asymmetric with a steep high-frequency flank. Over the same CF range, phase curves gradually changed from a concave-upward shape to a concave-downward shape. Phase curves consisted of two or three approximately straight segments. Group delay was analyzed separately for these segments. Generally, the largest group delay was observed near CF. With increasing SPL, most amplitude curves broadened, sometimes accompanied by a downward shift of best frequency, and group delay changed along the entire range of stimulus frequencies. We observed considerable across-ANF variation in the effects of SPL on both amplitude and phase. Overall, our data suggest that mechanical responses in the apex of the cochlea are considerably nonlinear and that these nonlinearities are of a different character than those known from the base of the cochlea

    Erosion consequences on beach functions along the Maresme coast (NW Mediterranean, Spain)

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    A methodology to analyse the influence of erosion on beach functions at a regional scale is presented. The method considers erosion hazards at different timescales and assesses consequences by evaluating impacts on recreation and protection functions. To provide useful information to decision makers for managing these functions, hazard and consequences are integrated at the municipal level within a risk matrix. This methodology is applied at the Maresme, a 45-km sandy coast situated northward of Barcelona, which supports a strong urban and infrastructure development as well as an intensive beach recreational use. Obtained results indicate differentiated erosion implications along the region, depending on the management target considered. Thus, southern municipalities are more prone to erosion affecting the protection function of the beach and leisure use by the local population, whereas erosion will have a greater effect on foreign tourism in the northern municipalities. These results highlight the necessity to employ an articulated erosion risk assessment focusing on specific targets depending on the site in question. This methodology can help coastal managers to adopt tailored measures to manage erosion impacts towards specific goals, in a more efficient and sustainable manner

    Exploring the current and future role of the pharmacists in osteoporosis screening and management in Malaysia

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    Background Several studies have found that pharmacists can assist in screening and prevention of osteoporosis by referring patients for bone mineral density scans and counselling on lifestyle changes. In Malaysia, screening osteoporosis in all elderly women is not mandatory due to its cost. One approach to address this gap is to develop a pharmacist-led osteoporosis screening and prevention program. However, there is a paucity of data on the perspectives of Malaysian pharmacists in this area. Objective To explore the perspective of stakeholders (policy makers, doctors, pharmacists, nurses and patients) towards the role of pharmacists in osteoporosis screening and management. Setting A primary care clinic located within a teaching hospital in Kuala Lumpur, Malaysia. Method Patients (n = 20), nurses (n = 10), pharmacists (n = 11), doctors (n = 10) and policy makers (n = 5) were individually interviewed using a semi-structured topic guide. Purposive sampling was used. Interviews were transcribed verbatim and analysed using thematic analysis. Main outcome measure Perspective of stakeholders on the current and future role of pharmacists. Results All participants perceived pharmacists to be suppliers of medication, although there was some recognition of roles in providing medication advice. Nonetheless, these stakeholders were eager for pharmacists to expand their non-dispensing roles towards counselling, creating awareness and screening of osteoporosis. Interviewed pharmacists referred to their current role as ‘robotic dispensers’ and unanimously agreed to spread out to osteoporosis management role. Conclusion Under stakeholders there is a willingness to expand the role of pharmacists in Malaysia to non-dispensing roles, particularly in osteoporosis screening and management

    Diagnosis and aetiology of congenital muscular dystrophy: we are halfway there

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    OBJECTIVES: To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and Next Generation Sequencing (NGS) technologies. METHODS: 123 CMD patients were investigated using the traditional approaches of histology, immunohistochemical analysis of muscle biopsy and candidate gene sequencing. Undiagnosed patients available for further testing were investigated using NGS. RESULTS: Muscle biopsy and immunohistochemical analysis found deficiencies of laminin α2, α-dystroglycan or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39/123). Of 85 patients presenting in the last 20 years, 28 of 51 who lacked a confirmed genetic diagnosis (55%) consented to NGS studies, leading to confirmed diagnoses in a further 11 patients. Using the combination of approaches, a confirmed genetic diagnosis was achieved in 51% (43/85). The diagnoses within the cohort were heterogeneous. 45/59 probands with confirmed or probable diagnoses had variants in genes known to cause CMD (76%), and 11/59 (19%) had variants in genes associated with congenital myopathies, reflecting overlapping features of these conditions. One patient had a congenital myasthenic syndrome and two had microdeletions. Within the cohort, five patients had variants in novel (PIGY and GMPPB) or recently published genes (GFPT1 and MICU1) and seven had variants in TTN or RYR1; large genes that are technically difficult to Sanger sequence. INTERPRETATION: These data support NGS as a first-line tool for genetic evaluation of patients with a clinical phenotype suggestive of CMD, with muscle biopsy reserved as a second-tier investigation. This article is protected by copyright. All rights reserved
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