Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

Mechanisms for inclusive governance

How mechanisms for inclusive governance are understood is built on the framing choices that are made about governance and that which is being governed. This chapter unpacks how governance can be understood and considers different historical and contemporary framings of water governance. A framing of “governance as praxis” is developed as a central element in the chapter. What makes governance inclusive is explored, drawing on theoretical, practical and institutional aspects before elucidating some of the different mechanisms currently used or proposed for creating inclusive water governance (though we argue against praxis based on simple mechanism). Finally, the factors that either constrain or enable inclusive water governance are explored with a focus on systemic concepts of learning and feedback

Climate change promotes parasitism in a coral symbiosis.

Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Low validity of self-report in identifying recent mental health diagnosis among U.S. service members completing Pre-Deployment Health Assessment (PreDHA) and deployed to Afghanistan, 2007: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Since 1998, the U.S. Armed Forces has used the mandatory Pre-Deployment Health Assessment (PreDHA) screening questionnaire as a means of assessing the health and suitability of U.S. service members for deployment. Limited data exists to quantify the validity of the self-reported PreDHA. This study was conducted to assess the validity of self-reporting in PreDHA to identify deployed service members who have had a recent mental health disorder diagnosis.</p> <p>Methods</p> <p>A retrospective cohort study was conducted on 15,195 U.S. service members deployed in support of combat and reconstruction operations in Afghanistan. The Defense Medical Surveillance System (DMSS), the DoD's longitudinal medical surveillance database, was queried to identify cases among the cohort with a recent diagnosis of a pertinent mental health disorder and to obtain those subjects' responses to the PreDHA.</p> <p>Results</p> <p>Of the study cohort, 11,179 (73.6%) subjects had a PreDHA available within the DMSS at the time of analysis. A total of 615 subjects (4.0%) had one or more mental health disorder diagnoses during the pre-deployment period. Out the 615 subjects with diagnosed mental health disorders, 465 had a PreDHA. Among these, only 224, not quite half, answered in the affirmative to the PreDHA question: <it>"During the past year, have you sought counseling or care for your mental health?"</it></p> <p>Conclusion</p> <p>This study demonstrates that the self-reported PreDHA has low validity for identifying service members with diagnosed mental health disorders. The development of electronic decision-support systems which automatically screen electronic health records to identify high-risk service members may prove a valuable component of improved pre-deployment screening processes.</p

Effectiveness of the Strengthening Families Programme 10–14 in Poland for the prevention of alcohol and drug misuse: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Alcohol and other drug use and misuse is a significant problem amongst Polish youth. The SFP10-14 is a family-based prevention intervention that has positive results in US trials, but questions remain about the generalizability of these results to other countries and settings.</p> <p>Methods/Design</p> <p>A cluster randomized controlled trial in community settings across Poland. Communities will be randomized to a SFP10-14 trial arm or to a control arm. Recruitment and consent of families, and delivery of the SFP10-14, will be undertaken by community workers. The primary outcomes are alcohol and other drug use and misuse. Secondary (or intermediate) outcomes include parenting practices, parent–child relations, and child problem behaviour. Interview-based questionnaires will be administered at baseline, 12 and 24 months.</p> <p>Discussion</p> <p>The trial will provide information about the effectiveness of the SFP10-14 in Poland.</p> <p>Trial registration</p> <p>International Standard Randomised Controlled Trial Number: ISRCTN89673828</p