An Adiabatic Theorem without a Gap Condition

The basic adiabatic theorems of classical and quantum mechanics are over-viewed and an adiabatic theorem in quantum mechanics without a gap condition is described.Comment: Talk at QMath 7, Prague, 1998. 10 pages, 7 figure

Genetic linkage analysis in the age of whole-genome sequencing

For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was largely supplanted by the wide adoption of genome-wide association studies (GWASs). However, with the recent increased use of whole-genome sequencing (WGS), linkage analysis is again emerging as an important and powerful analysis method for the identification of genes involved in disease aetiology, often in conjunction with WGS filtering approaches. Here, we review the principles of linkage analysis and provide practical guidelines for carrying out linkage studies using WGS data

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Early Metabolic Flare in Squamous Cell Carcinoma after Chemotherapy is a Marker of Treatment Sensitivity In Vitro

PURPOSE: Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes. METHODS: Three squamous cell carcinoma cell lines and one nontumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1-6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated. RESULTS: The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line. CONCLUSION: A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity

Direct and indirect effects of Johne's disease on farm and animal productivity in an Irish dairy herd

Johne's disease (JD) is caused by infection with the organism Mycobacterium avium spp. paratuberculosis, leading to chronic diarrhoea and ill thrift in adult cattle. JD is considered to adversely affect farm performance and profitability. This retrospective case study was undertaken on a single commercial dairy herd in the south west of Ireland. Animal production records were interrogated to assess the effect of JD on milk yield (total kg per lactation), somatic cell count (the geometric mean over the lactation), reasons for culling, cull price and changes in herd parity structure over time. JD groups were defined using clinical signs and test results. One control animal was matched to each case animal on parity number and year. Specific lactations (clinical, pre-clinical and test-positive only) from 1994 to 2004 were compared between JD case and control cows. A significantly lower milk yield (1259.3 kg/lactation) was noted from cows with clinical JD in comparison to their matched control group. Clinical animals had an average cull price of €516 less than animals culled without signs of clinical disease. In contrast, little effect was noted for sub-clinical infections. These direct effects of JD infections, in combination with increased culling for infertility and increasing replacement rates, had a negative impact on farm production. Results from this study provide preliminary information regarding the effects of JD status on both herd and animal-level performance in Ireland

Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma

Background Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism. Case presentation A 65-year-old patient with metastatic melanoma who progressed through two immunotherapy strategies with immune checkpoint inhibitor antibodies was enrolled in a phase I study (NCT02285101) and treated with 2 mg/kg intravenously, weekly pegylated recombinant arginase (BCT-100). The patient experienced no toxicities > grade 2 and entered a complete remission which is sustained for over 30 months. RNA-sequencing identified a number of transcriptomic pathway alterations compared to control samples. The tumour had absent expression of the recycling enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC) indicating a state of arginine auxotrophy, which was reconfirmed by immunohistochemistry, and validation in a larger cohort of melanoma tumour samples. Conclusions Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy

Molecular gas kinematics within the central 250 pc of the Milky Way

Using spectral-line observations of HNCO, N2H+, and HNC, we investigate the kinematics of dense gas in the central ~250 pc of the Galaxy. We present SCOUSE (Semi-automated multi-COmponent Universal Spectral-line fitting Engine), a line fitting algorithm designed to analyse large volumes of spectral-line data efficiently and systematically. Unlike techniques which do not account for complex line profiles, SCOUSE accurately describes the {l, b, v_LSR} distribution of CMZ gas, which is asymmetric about Sgr A* in both position and velocity. Velocity dispersions range from 2.6 km/s28. The gas is distributed throughout several "streams", with projected lengths ~100-250 pc. We link the streams to individual clouds and sub-regions, including Sgr C, the 20 and 50 km/s clouds, the dust ridge, and Sgr B2. Shell-like emission features can be explained by the projection of independent molecular clouds in Sgr C and the newly identified conical profile of Sgr B2 in {l ,b, v_LSR} space. These features have previously invoked supernova-driven shells and cloud-cloud collisions as explanations. We instead caution against structure identification in velocity-integrated emission maps. Three geometries describing the 3-D structure of the CMZ are investigated: i) two spiral arms; ii) a closed elliptical orbit; iii) an open stream. While two spiral arms and an open stream qualitatively reproduce the gas distribution, the most recent parameterisation of the closed elliptical orbit does not. Finally, we discuss how proper motion measurements of masers can distinguish between these geometries, and suggest that this effort should be focused on the 20 km/s and 50 km/s clouds and Sgr C

Illness perceptions and explanatory models of viral hepatitis B & C among immigrants and refugees: a narrative systematic review.

© 2015 Owiti et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants' knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. METHODS: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman's explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. RESULTS: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. CONCLUSION: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia