DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1

DNA single-strand breaks (SSBs) are the commonest DNA lesions arising spontaneously in cells, and if not repaired may block transcription or may be converted into potentially lethal/clastogenic DNA double-strand breaks (DSBs). Recently, evidence has emerged that defects in the rapid repair of SSBs preferentially impact the nervous system. In particular, spinocerebellar ataxia with axonal neuropathy (SCAN1) is a human disease that is associated with mutation of TDP1 (tyrosyl DNA phosphodiesterase 1) protein and with a defect in repairing certain types of SSBs. Although SCAN1 is a rare neurodegenerative disorder, understanding the molecular basis of this disease will lead to better understanding of neurodegenerative processes. Here we review recent progress in our understanding of TDP1, single-strand break repair (SSBR), and neurodegenerative disease

The development and preliminary psychometric properties of two positive psychology outcome measures for people with dementia: the PPOM and the EID-Q.

Background: Positive psychology research in dementia care has largely been confined to the qualitative literature because of the lack of robust outcome measures. The aim of this study was to develop positive psychology outcome measures for people with dementia. Methods: Two measures were each developed in four stages. Firstly, literature reviews were conducted to identify and operationalise salient positive psychology themes in the qualitative literature and to examine existing measures of positive psychology. Secondly, themes were discussed within a qualitative study to add content validity for identified concepts (n = 17). Thirdly, draft measures were submitted to a panel of experts for feedback (n = 6). Finally, measures were used in a small-scale pilot study (n = 33) to establish psychometric properties. Results: Salient positive psychology themes were identified as hope, resilience, a sense of independence and social engagement. Existing measures of hope and resilience were adapted to form the Positive Psychology Outcome Measure (PPOM). Due to the inter-relatedness of independence and engagement for people with dementia, 28 items were developed for a new scale of Engagement and Independence in Dementia Questionnaire (EID-Q) following extensive qualitative work. Both measures demonstrated acceptable internal consistency (α = .849 and α = .907 respectively) and convergent validity. Conclusions: Two new positive psychology outcome measures were developed using a robust four-stage procedure. Preliminary psychometric data was adequate and the measures were easy to use, and acceptable for people with dementia

Characteristics of undernourished older medical patients and the identification of predictors for undernutrition status

<p>Abstract</p> <p>Background</p> <p>Undernutrition among older people is a continuing source of concern, particularly among acutely hospitalized patients. The purpose of the current study is to compare malnourished elderly patients with those at nutritional risk and identify factors contributing to the variability between the groups.</p> <p>Methods</p> <p>The study was carried out at the Soroka University Medical Center in the south of Israel. From September 2003 through December 2004, all patients 65 years-of-age or older admitted to any of the internal medicine departments, were screened within 72 hours of admission to determine nutritional status using the short version of the Mini Nutritional Assessment (MNA-SF). Patients at nutritional risk were entered the study and were divided into malnourished or 'at risk' based on the full version of the MNA. Data regarding medical, nutritional, functional, and emotional status were obtained by trained interviewers.</p> <p>Results</p> <p>Two hundred fifty-nine elderly patients, 43.6% men, participated in the study; 18.5% were identified as malnourished and 81.5% were at risk for malnutrition according to the MNA. The malnourished group was less educated, had a higher depression score and lower cognitive and physical functioning. Higher prevalence of chewing problems, nausea, and vomiting was detected among malnourished patients. There was no difference between the groups in health status indicators except for subjective health evaluation which was poorer among the malnourished group. Lower dietary score indicating lower intake of vegetables fruits and fluid, poor appetite and difficulties in eating distinguished between malnourished and at-risk populations with the highest sensitivity and specificity as compare with the anthropometric, global, and self-assessment of nutritional status parts of the MNA. In a multivariate analysis, lower cognitive function, education <12 years and chewing problems were all risk factors for malnutrition.</p> <p>Conclusion</p> <p>Our study indicates that low food consumption as well as poor appetite and chewing problems are associated with the development of malnutrition. Given the critical importance of nutritional status in the hospitalized elderly, further intervention trials are required to determine the best intervention strategies to overcome these problems.</p

Chemical Signatures of Melt–Rock Interaction in the Root of a Magmatic Arc

Identification of melt–rock interaction during melt flux through crustal rocks is limited to field relationships and microstructural evidence, with little consideration given to characterising the geochemical signatures of this process. We examine the mineral and whole-rock geochemistry of four distinct styles of melt–rock interaction during melt flux through the Pembroke Granulite, a gabbroic gneiss from the Fiordland magmatic arc root, New Zealand. Spatial distribution, time-integrated flux of melt and stress field vary between each melt flux style. Whole-rock metasomatism is not detected in three of the four melt flux styles. The mineral assemblage and major element mineral composition in modified rocks are dictated by inferred P–T conditions, as in sub-solidus metamorphic systems, and time-integrated volumes of melt flux. Heterogeneous mineral major and trace element compositions are linked to low time-integrated volumes of melt flux, which inhibits widespread modification and equilibration. Amphibole and clinozoisite in modified rocks have igneous-like REE patterns, formed by growth and/or recrystallisation in the presence of melt and large equilibration volumes provided by the grain boundary network of melt. Heterogeneities in mineral REE compositions are linked to localisation of melt flux by deformation and resulting smaller equilibration volumes and/or variation in the composition of the fluxing melt. When combined with microstructural evidence for the former presence of melt, the presence of igneous-like mineral REE chemical signatures in a metamorphic rock are proposed as powerful indicators of melt–rock interaction during melt flux

Integrated Multi-Parameter Exploration Footprints of the Canadian Malartic Disseminated Au, McArthur River-Millennium Unconformity U, and Highland Valley Porphyry Cu Deposits: Preliminary Results from the NSERC-CMIC Mineral Exploration Footprints Research Network

Mineral exploration in Canada is increasingly focused on concealed and deeply buried targets, requiring more effective tools to detect large-scale ore-forming systems and to vector from their most distal margins to their high grade cores. A new generation of ore system models is required to achieve this. The Mineral Exploration Footprints Research Network is a consortium of 70 faculty, research associates, and students from 20 Canadian universities working with 30 mining, mineral exploration, and mining service providers to develop new approaches to ore system modelling based on more effective integration and visualization of multi-parameter geological-structural-mineralogical-lithogeochemical-petrophysical-geophysical exploration data. The Network is developing the next generation ore system models and exploration strategies at three sites based on integrated data visualization using self-consistent 3D Common Earth Models and geostatistical/machine learning technologies. Thus far over 60 footprint components and vectors have been identified at the Canadian Malartic stockwork-disseminated Au deposit, 20–30 at the McArthur-Millennium unconformity U deposits, and over 20 in the Highland Valley porphyry Cu system. For the first time, these are being assembled into comprehensive models that will serve as landmark case studies for data integration and analysis in the today’s challenging exploration environment

Markov chain Monte Carlo inversion of mantle temperature and source composition, with application to Reykjanes Peninsula, Iceland

The compositions and volumes of basalt generated by partial melting of the Earth's mantle provide fundamental constraints on the thermo-chemical conditions of the upper mantle. However, using melting products to interpret uniquely these conditions is challenging given the complexity of the melting and melt aggregation processes. Forward models simulating melting of lithologically heterogeneous mantle sources can account for this complexity, but require assumptions about key model input parameters, and the quality of the model fits to the observations are rarely, if at all, considered. Alternatively, inverse melting models can provide estimates of the quality of model fits to the observations, but as of yet, do not account for the presence of lithologic heterogeneity in the mantle source. To overcome these limitations, we present an inverse method coupling a Markov chain Monte Carlo (MCMC) sampling method with the REEBOX PRO forward mantle melting model. We use this tool to constrain mantle potential temperature, melt volumes, and the trace element and isotopic compositions of mantle source lithologies beneath the Reykjanes Peninsula of Iceland. We consider a range of plausible pyroxenite compositions (KG1, G2, and MIX1G) that span much of the range of natural pyroxenite compositions, and constrain the mantle potential temperature between 1455 and 1480 °C and pyroxenite abundance between 6.5 and 8.5%. These results are independent of the choice of pyroxenite composition and indicate that elevated potential temperatures and modest pyroxenite abundances are robust features of the Reykjanes Peninsula mantle source. The permitted ranges of pyroxenite trace element compositions vary as a function of pyroxenite fertility and mineralogy, but differ from the compositions of subduction-modified recycled oceanic crust typically used in previous models, indicating a more complex petrogenetic origin for the pyroxenite source than previously considered. As all of the pyroxenites employed here yield equally good fits to the geochemical and geophysical observations along the Reykjanes Peninsula, forward models should not be used to constrain the major element character of pyroxenite present in mantle source regions based solely on the trace element/isotopic compositions (and volumes) of basalts. Given the range of lithologies included in REEBOX PRO and the flexibility of MCMC inversion, this method may be applied to constrain thermal and compositional source characteristics in a wide variety of basalt source regions