Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis.

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disease affecting >4,00,000 individuals in the United States. Population and family-based studies have suggested that there is a strong genetic component. Numerous genomic linkage screens have identified regions of interest for MS loci. Our own second-generation genome-wide linkage study identified a handful of non-major histocompatibility complex regions with suggestive linkage. Several of these regions were further examined using single-nucleotide polymorphisms (SNPs) with average spacing between SNPs of approximately 1.0 Mb in a dataset of 173 multiplex families. The results of that study provided further evidence for the involvement of the chromosome 1q43 region. This region is of particular interest given linkage evidence in studies of other autoimmune and inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus. In this follow-up study, we saturated the region with approximately 700 SNPs (average spacing of 10 kb per SNP) in search of disease-associated variation within this region. We found preliminary evidence to suggest that common variation within the RGS7 locus may be involved in disease susceptibility

Mitochondrial DNA Polymorphism A4917G Is Independently Associated with Age-Related Macular Degeneration

The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20–3.91, p = 0.01). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms

Fatigue strength of common tibial intramedullary nail distal locking screws

Premature failure of either the nail and/or locking screws with unstable fracture patterns may lead to angulation, shortening, malunion, and IM nail migration. Up to thirty percent of all unreamed nail locking screws can break after initial weight bearing is allowed at 8–10 weeks if union has not occurred. The primary problem this presents is hardware removal during revision surgery. The purposes of our study was to evaluate the relative fatigue resistance of distal locking screws and bolts from representative manufacturers of tibial IM nail systems, and develop a relative risk assessment of screws and materials used. Evaluations included quantitative and qualitative measures of the relative performance of these screws

'A foundation-hatched black elite’: Obama, the US establishment and foreign policy

US foreign policy has a largely unacknowledged racial dimension due to the racial characteristics of the US foreign policy establishment, and in shared mindsets in a soon-to-be ‘majority-minority’ nation. White Anglo-Saxon Protestant (WASP) racial-ethnic and class factors produce managed change through socialisation in an attenuated meritocratic order, adapting to challenges to elite dominance by incorporating rising talent, without altering broader patterns of power. The greatest success of such a system would be the assimilation of the most elite minority individuals, even as the bulk of those groups’ members continue to experience discrimination. Such success would be compounded by election to the highest office of a minority US president extolling the virtues of post-racial politics. President Barack Obama represents a ‘Wasp-ified’ black elite, assimilated into the extant structures of power that remain wedded to a more secular, non-biologically-racial, version of Anglo-Saxonism or, more broadly, liberal internationalism. Hence, it should occasion little surprise that there has been so little change in US foreign policies during Obama’s two-term presidency

Health inequalities, physician citizens and professional medical associations: an Australian case study

<p>Abstract</p> <p>Background</p> <p>As socioeconomic health inequalities persist and widen, the health effects of adversity are a constant presence in the daily work of physicians. Gruen and colleagues suggest that, in responding to important population health issues such as this, defining those areas of professional obligation in contrast to professional aspiration should be on the basis of evidence and feasibility. Drawing this line between obligation and aspiration is a part of the work of professional medical colleges and associations, and in doing so they must respond to members as well as a range of other interest groups. Our aim was to explore the usefulness of Gruen's model of physician responsibility in defining how professional medical colleges and associations should lead the profession in responding to socioeconomic health inequalities.</p> <p>Methods</p> <p>We report a case study of how the Royal Australian College of General Practitioners is responding to the issue of health inequalities through its work. We undertook a consultation (80 interviews with stakeholders internal and external to the College and two focus groups with general practitioners) and program and policy review of core programs of College interest and responsibility: general practitioner training and setting of practice standards, as well as its work in public advocacy.</p> <p>Results</p> <p>Some strategies within each of these College program areas were seen as legitimate professional obligations in responding to socioeconomic health inequality. However, other strategies, while potentially professional obligations within Gruen's model, were nevertheless contested. The key difference between these lay in different moral orientations. Actions where agreement existed were based on an ethos of care and compassion. Actions that were contested were based on an ethos of justice and human rights.</p> <p>Conclusion</p> <p>Colleges and professional medical associations have a role in explicitly leading a debate about values, engaging both external stakeholder and practicing member constituencies. This is an important and necessary step in defining an agreed role for the profession in addressing health inequalities.</p

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

SUPPORT Tools for Evidence-informed Policymaking in health 6: Using research evidence to address how an option will be implemented

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin

Prova tipográfica (In Press)Multiple sclerosis (MS) is a demyelinating disease that affects about one in 500 young Europeans. In order to test the previously proposed influence of the APOE and SCA2 loci on susceptibility to MS, we studied these loci in 243 Portuguese patients and 192 healthy controls and both parents of 92 patients. We did not detect any significant difference when APOE and SCA2 allele frequencies of cases and controls were compared, or when we compared cases with different forms of the disease. Disequilibrium of transmission was tested for both loci in the 92 trios, and we did not observe segregation distortion. To test the influence of the APOE o4 and SCA2 22 CAGs alleles on severity of disease, we compared age at onset and progression rate between groups with and without those alleles. We did not observe an association of the o4 or the 22 CAGs alleles with rate of progression in our total patient population; allele o4 was associated with increased rate of progression of MS in a subset of patients with less than 10 years of the disease. However, globally in the Portuguese population, the APOE and SCA2 genes do not seem to be useful in the clinical context as prognostic markers of this disorder.Fundação para a Ciência e a Tecnologia (FCT) - grant SFRH/BD/9111/2002.Serono Portugal

Intervention mapping for development of a participatory return-to-work intervention for temporary agency workers and unemployed workers sick-listed due to musculoskeletal disorders

BACKGROUND: In the past decade in activities aiming at return-to-work (RTW), there has been a growing awareness to change the focus from sickness and work disability to recovery and work ability. To date, this process in occupational health care (OHC) has mainly been directed towards employees. However, within the working population there are two vulnerable groups: temporary agency workers and unemployed workers, since they have no workplace/employer to return to, when sick-listed. For this group there is a need for tailored RTW strategies and interventions. Therefore, this paper aims to describe the structured and stepwise process of development, implementation and evaluation of a theory- and practise-based participatory RTW program for temporary agency workers and unemployed workers, sick-listed due to musculoskeletal disorders (MSD). This program is based on the already developed and cost-effective RTW program for employees, sick-listed due to low back pain. METHODS: The Intervention Mapping (IM) protocol was used to develop a tailor-made RTW program for temporary agency workers and unemployed workers, sick-listed due to MSD. The Attitude-Social influence-self-Efficacy (ASE) model was used as a theoretical framework for determinants of behaviour regarding RTW of the sick-listed worker and development of the intervention. To ensure participation and facilitate successful adoption and implementation, important stakeholders were involved in all steps of program development and implementation. Results of semi-structured interviews and 'fine-tuning' meetings were used to design the final participatory RTW program. RESULTS: A structured stepwise RTW program was developed, aimed at making a consensus-based RTW implementation plan. The new program starts with identifying obstacles for RTW, followed by a brainstorm session in which the sick-listed worker and the labour expert of the Social Security Agency (SSA) formulate solutions/possibilities for suitable (therapeutic) work. This process is guided by an independent RTW coordinator to achieve consensus. Based on the resulting RTW implementation plan, to create an actual RTW perspective, a vocational rehabilitation agency is assigned to find a matching (therapeutic) workplace. The cost-effectiveness of this participatory RTW program will be evaluated in a randomised controlled trial. CONCLUSION: IM is a promising tool for the development of tailor-made OHC interventions for the vulnerable working populatio

Azotobacter genomes: the genome of Azotobacter chroococcum NCIMB 8003 (ATCC 4412)

The genome of the soil-dwelling heterotrophic N2-fixing Gram-negative bacterium Azotobacter chroococcum NCIMB 8003 (ATCC 4412) (Ac-8003) has been determined. It consists of 7 circular replicons totalling 5,192,291 bp comprising a circular chromosome of 4,591,803 bp and six plasmids pAcX50a, b, c, d, e, f of 10,435 bp, 13,852, 62,783, 69,713, 132,724, and 311,724 bp respectively. The chromosome has a G+C content of 66.27% and the six plasmids have G+C contents of 58.1, 55.3, 56.7, 59.2, 61.9, and 62.6% respectively. The methylome has also been determined and 5 methylation motifs have been identified. The genome also contains a very high number of transposase/inactivated transposase genes from at least 12 of the 17 recognised insertion sequence families. The Ac-8003 genome has been compared with that of Azotobacter vinelandii ATCC BAA-1303 (Av-DJ), a derivative of strain O, the only other member of the Azotobacteraceae determined so far which has a single chromosome of 5,365,318 bp and no plasmids. The chromosomes show significant stretches of synteny throughout but also reveal a history of many deletion/insertion events. The Ac-8003 genome encodes 4628 predicted protein-encoding genes of which 568 (12.2%) are plasmid borne. 3048 (65%) of these show > 85% identity to the 5050 protein-encoding genes identified in Av-DJ, and of these 99 are plasmid-borne. The core biosynthetic and metabolic pathways and macromolecular architectures and machineries of these organisms appear largely conserved including genes for CO-dehydrogenase, formate dehydrogenase and a soluble NiFe-hydrogenase. The genetic bases for many of the detailed phenotypic differences reported for these organisms have also been identified. Also many other potential phenotypic differences have been uncovered. Properties endowed by the plasmids are described including the presence of an entire aerobic corrin synthesis pathway in pAcX50f and the presence of genes for retro-conjugation in pAcX50c. All these findings are related to the potentially different environmental niches from which these organisms were isolated and to emerging theories about how microbes contribute to their communities