ALBERT

Description: Background: Medication-overuse headache (MOH) is a common problem in primary care. Brief intervention (BI) has successfully been used for detoxification from overuse of alcohol and drugs. The aim of this pilot study was to develop and test methodology, acceptability and logistics for a BI for MOH in primary care.FindingsObservational feasibility study of an intervention in a Norwegian general practice population.Six general practitioners (GPs) were recruited. A screening questionnaire for MOH was sent to all 18-50 year old patients on these GPs` list. GPs were taught BI, which was applied to MOH patients as follows: Severity of dependence scale (SDS) scores were collected and individual feedback was given of the relationship between the SDS, medication overuse and headache. Finally, advice to reduce medication was given. Patients were invited to a headache interview three months after the BI. Main outcomes were feedback from GPs/patients about the feasibility and logistics of the study design, screening/recruitment process, BI and headache interviews. Efficacy and patient-related outcomes were not focused. The patients reported a high degree of acceptability of the methodology. The GPs reported the BI to be feasible to implement within a busy practice and to represent a new and improved instrument for communication with MOH patients. The BI requires further testing in a randomised controlled trial (RCT) in order to provide evidence of efficacy. Conclusion: This feasibility study will be used to improve the BI for MOH and the design of a cluster-RCT.Trial registration: ClinicalTrials.gov: NCT01078012 (Initially registered as controlled efficacy trial but changed to observational study).

Description: : We explored the use of genotyping by sequencing (GBS) on a recombinant inbred line population (GPMx) derived from a cross between the two rowed barley cultivar 'Golden Promise' (ari-e.GP/Vrs1) and the six-rowed cultivar 'Morex' (Ari-e/vrs1) to map plant height. We identified three Quantitative Trait Loci (QTL), the first in a region encompassing the spike architecture gene Vrs1 on chromosome 2H, the second in an uncharacterised centromeric region on chromosome 3H, and the third in a region of chromosome 5H coinciding with the previously described dwarfing gene Breviaristatum-e (Ari-e). Background: Barley cultivars in North-western Europe largely contain either of two dwarfing genes; Denso on chromosome 3H, a presumed ortholog of the rice green revolution gene OsSd1, or Breviaristatum-e (ari-e) on chromosome 5H. A recessive mutant allele of the latter gene, ari-e.GP, was introduced into cultivation via the cv. 'Golden Promise' that was a favourite of the Scottish malt whisky industry for many years and is still used in agriculture today. Results: Using GBS mapping data and phenotypic measurements we show that ari-e.GP maps to a small genetic interval on chromosome 5H and that alternative alleles at a region encompassing Vrs1 on 2H along with a region on chromosome 3H also influence plant height. The location of Ari-e is supported by analysis of near-isogenic lines containing different ari-e alleles. We explored use of the GBS to populate the region with sequence contigs from the recently released physically and genetically integrated barley genome sequence assembly as a step towards Ari-e gene identification. Conclusions: GBS was an effective and relatively low-cost approach to rapidly construct a genetic map of the GPMx population that was suitable for genetic analysis of row type and height traits, allowing us to precisely position ari-e.GP on chromosome 5H. Mapping resolution was lower than we anticipated. We found the GBS data more complex to analyse than other data types but it did directly provide linked SNP markers for subsequent higher resolution genetic analysis.

Description: IntroductionNutrient availability, assimilation, and allocation can have important and lasting effects on the immune system development of growing animals. Though carotenoid pigments have immunostimulatory properties in many animals, relatively little is known regarding how they influence the immune system during development. Moreover, studies linking carotenoids to health at any life stage have largely been restricted to birds and mammals. We investigated the effects of carotenoid supplementation on multiple aspects of immunity in juvenile veiled chameleons (Chamaeleo calyptratus). We supplemented half of the chameleons with lutein (a xanthophyll carotenoid) for 14 weeks during development and serially measured multiple aspects of immune function, including: agglutination and lysis performance of plasma, wound healing, and plasma nitric oxide concentrations before and after wounding. Results: Though lutein supplementation effectively elevated circulating carotenoid concentrations throughout the developmental period, we found no evidence that carotenoid repletion enhanced immune function at any point. However, agglutination and lysis scores increased, while baseline nitric oxide levels decreased, as chameleons aged. Conclusions: Taken together, our results indicate that body mass and age, but not carotenoid access, may play an important role in immune performance of growing chameleons. Hence, studying well-understood physiological processes in novel taxa can provide new perspectives on alternative physiological processes and nutrient function.

Description: Background: Pedigree reconstruction using genetic analysis provides a useful means to estimate fundamental population biology parameters relating to population demography, trait heritability and individual fitness when combined with other sources of data. However, there remain limitations to pedigree reconstruction in wild populations, particularly in systems where parent-offspring relationships cannot be directly observed, there is incomplete sampling of individuals, or molecular parentage inference relies on low quality DNA from archived material. While much can still be inferred from incomplete or sparse pedigrees, it is crucial to evaluate the quality and power of available genetic information a priori to testing specific biological hypotheses. Here, we used microsatellite markers to reconstruct a multi-generation pedigree of wild Atlantic salmon (Salmo salar L.) using archived scale samples collected with a total trapping system within a river over a 10 year period. Using a simulation-based approach, we determined the optimal microsatellite marker number for accurate parentage assignment, and evaluated the power of the resulting partial pedigree to investigate important evolutionary and quantitative genetic characteristics of salmon in the system. Results: We show that at least 20 microsatellites (ave. 12 alleles / locus) are required to maximise parentage assignment and to improve the power to estimate reproductive success and heritability in this study system. We also show that 1.5 fold differences can be detected between groups simulated to have differing reproductive success, and that it is possible to detect moderate heritability values for continuous traits (h2 ~ 0.40) with more than 80% power when using 28 moderately to highly polymorphic markers. Conclusion: The methodologies and work flow described provide a robust approach for evaluating archived samples for pedigree-based research, even where only a proportion of the total population is sampled. The results demonstrate the feasibility of pedigree-based studies to address challenging ecological and evolutionary questions in free-living populations, where genealogies can be traced only using molecular tools, and that significant increases in pedigree assignment power can be achieved by using higher numbers of markers.

Description: Background: Homopolymeric tracts, particularly poly dA.dT, are enriched within the intergenic sequences of eukaryotic genomes where they appear to act as intrinsic regulators of nucleosome positioning. A previous study of the incomplete genome of the human malarial parasite Plasmodium falciparum reports a higher than expected enrichment of poly dA.dT tracts, far above that anticipated even in this highly AT rich genome. Here we report an analysis of the relative frequency, length and spatial arrangement of homopolymer tracts for the complete P. falciparum genome, extending this analysis to twelve additional genomes of Apicomplexan parasites important to human and animal health. In addition, using nucleosome-positioning data available for P. falciparum, we explore the correlation of poly dA.dT tracts with nucleosome-positioning data over key expression landmarks within intergenic regions. Results: We describe three apparent lineage-specific patterns of homopolymeric tract organization within the intergenic regions of these Apicomplexan parasites. Moreover, a striking pattern of enrichment of overly long poly dA.dT tracts in the intergenic regions of Plasmodium spp. uniquely extends into protein coding sequences. There is a conserved spatial arrangement of poly dA.dT immediately flanking open reading frames and over predicted core promoter sites. These key landmarks are all relatively depleted in nucleosomes in P. falciparum, as would be expected for poly dA.dT acting as nucleosome exclusion sequences. Conclusions: Previous comparative studies of homopolymer tract organization emphasize evolutionary diversity; this is the first report of such an analysis within a single phylum. Our data provide insights into the evolution of homopolymeric tracts and the selective pressures at play in their maintenance and expansion.

Description: Background: Childhood cancer relies heavily on inpatient hospital services to deliver tumor-directed therapy and manage toxicities. Hospitalizations have increased over the past decade, though not uniformly across childhood cancer diagnoses. Analysis of the reasons for admission of children with cancer could enhance comparison of resource use between cancers, and allow clinical practice data to be interpreted more readily. Such comparisons using nationwide data sources are difficult because of numerous subdivisions in the International Classification of Diseases Clinical Modification (ICD-9) system and inherent complexities of treatments. This study aimed to develop a systematic approach to classifying cancer-related admissions in administrative data into categories that reflected clinical practice and predicted resource use. Methods: We developed a multistep algorithm to stratify indications for childhood cancer admissions in the Kids Inpatient Databases from 2003, 2006 and 2009 into clinically meaningful categories. This algorithm assumed that primary discharge diagnoses of cancer or cytopenia were insufficient, and relied on procedure codes and secondary diagnoses in these scenarios. Clinical Classification Software developed by the Healthcare Cost and Utilization Project was first used to sort thousands of ICD-9 codes into 5 mutually exclusive diagnosis categories and 3 mutually exclusive procedure categories, and validation was performed by comparison with the ICD-9 codes in the final admission indication. Mean cost, length of stay, and costs per day were compared between categories of indication for admission. Results: A cohort of 202,995 cancer-related admissions was grouped into four categories of indication for admission: chemotherapy (N=77,791, 38%), to undergo a procedure (N=30,858, 15%), treatment for infection (N=30,380, 15%), or treatment for other toxicities (N=43,408, 21.4%). The positive predictive value for the algorithm was 〉95% for each category. Admissions for procedures had higher mean hospital costs, longer hospital stays, and higher costs per day compared with other admission reasons (p

Description: Background: Because of the difficulties involved in learning and using 3D modeling and rendering software,many scientists hire programmers or animators to create models and animations. This both slowsthe discovery process and provides opportunities for miscommunication. Working with multiplecollaborators, a tool was developed (based on a set of design goals) to enable them to directly constructmodels and animations. Results: SketchBio is presented, a tool that incorporates state-of-the-art bimanual interaction and drop shadowsto enable rapid construction of molecular structures and animations. It includes three novel features:crystal-by-example, pose-mode physics, and spring-based layout that accelerate operations commonin the formation of molecular models. Design decisions and their consequences are presented,including cases where iterative design was required to produce effective approaches. Conclusions: The design decisions, novel features, and inclusion of state-of-the-art techniques enabled SketchBioto meet all of its design goals. These features and decisions can be incorporated into existing and newtools to improve their effectiveness.