Genetic contribution to radiographic severity in osteoarthritis of the knee

Objective Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10–8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases. Methods 3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index. Results No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011). Conclusions Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors

Normalization and centering of array-based heterologous genome hybridization based on divergent control probes

<p>Abstract</p> <p>Background</p> <p>Hybridization of heterologous (non-specific) nucleic acids onto arrays designed for model-organisms has been proposed as a viable genomic resource for estimating sequence variation and gene expression in non-model organisms. However, conventional methods of normalization that assume equivalent distributions (such as quantile normalization) are inappropriate when applied to non-specific (heterologous) hybridization. We propose an algorithm for normalizing and centering intensity data from heterologous hybridization that makes no prior assumptions of distribution, reduces the false appearance of homology, and provides a way for researchers to confirm whether heterologous hybridization is suitable.</p> <p>Results</p> <p>Data are normalized by adjusting for Gibbs free energy binding, and centered by adjusting for the median of a common set of control probes assumed to be equivalently dissimilar for all species. This procedure was compared to existing approaches and found to be as successful as Loess normalization at detecting sequence variations (deletions) and even more successful than quantile normalization at reducing the accumulation of false positive probe matches between two related nematode species, <it>Caenorhabditis elegans </it>and <it>C. briggsae</it>. Despite the improvements, we still found that probe fluorescence intensity was too poorly correlated with sequence similarity to result in reliable detection of matching probe sequence.</p> <p>Conclusions</p> <p>Cross-species hybridizations can be a way to adapt genome-enabled tools for closely related non-model organisms, but data must be appropriately normalized and centered in a way that accommodates hybridization of nucleic acids with diverged sequence. For short, 25-mer probes, hybridization intensity alone may be insufficiently correlated with sequence similarity to allow reliable inference of homology at the probe level.</p

The Economics of Regional Poverty-Environment Programs: An Application for Lao People's Democratic Republic

Program administrators are often faced with the difficult problem of allocating scarce resources among regions in a country when interventions are aimed at addressing multiple objectives. One main concern is the tradeoff between poverty reduction and improvement of environmental quality. To provide a framework for analysis, the authors develop a model of optimal budget allocation that allows for variations in three factors: administrators'valuation of objectives; their willingness to accept tradeoffs among objectives and regional allotments; and regional administrative costs. The results from an application of this model using information for Lao People's Democratic Republic show that simple poverty indicators alone do not provide consistent guidelines for policy. However, when different poverty indicators are embedded in an optimizing model that incorporates preferences and costs, the resulting provincial allocations are very similar. This suggests that adoption of a formal analytical approach to resource allocation can help promote the harmonization of regional policy guidelines.Poverty Reduction Strategies,Public Health Promotion,Health Economics&Finance,Environmental Economics&Policies,Poverty Monitoring&Analysis,Environmental Economics&Policies,Poverty Assessment,Poverty Reduction Strategies,Poverty Monitoring&Analysis,Health Economics&Finance

Wanting other attitudes: actual–desired attitude discrepancies predict feelings of ambivalence and ambivalence consequences

The experience of attitudinal ambivalence (subjective ambivalence) is important because it predicts key consequences of attitudes (e.g., attitude–behavior correspondence, attitude stability). However, the field's understanding of the antecedents of subjective ambivalence is still developing. We explore an unexamined antecedent of subjective ambivalence. Specifically, we examined discrepancies between participants' actual attitudes and their desired attitudes as antecedents of subjective ambivalence and ambivalence consequences. Six studies using a variety of attitude objects were conducted to test these ideas. The first four studies demonstrated that actual–desired attitude discrepancies predicted subjective ambivalence over its previously documented antecedents. Critically, two additional studies showed that actual–desired attitude discrepancies predicted important consequences of ambivalence. As actual–desired attitude discrepancies increased, participants' attitude–behavior correspondence decreased (Study 5), and desire to reduce attitudinal conflict increased (Study 6). Process data in these latter studies revealed indirect effects through subjective ambivalence that held after controlling for the objective presence of evaluative conflict

Low Pressure Greenhouse Concepts for Mars

A project was initiated to begin testing some environmental limits for managing plant growth systems. These limits will help determine some of the concepts for building plant enclosures for use on Mars. In particular, this study focuses on the effects of reduced atmospheric pressures. Structural design is considered as it relates to the biological processes that would occur within that structure. The design must be closely tied to the functionality of the biological system and has a few primary concerns that need to be tested to resolve the question as to the path of the design. Early tests indicate that plants can survive and grow at low (greater than 76 mb) pressure

Candidate genes mediating magnetoreception in rainbow trout ( Oncorhynchus mykiss )

Diverse animals use Earth's magnetic field in orientation and navigation, but little is known about the molecular mechanisms that underlie magnetoreception. Recent studies have focused on two possibilities: (i) magnetite-based receptors; and (ii) biochemical reactions involving radical pairs. We used RNA sequencing to examine gene expression in the brain of rainbow trout ( Oncorhynchus mykiss ) after exposure to a magnetic pulse known to disrupt magnetic orientation behaviour. We identified 181 differentially expressed genes, including increased expression of six copies of the frim gene, which encodes a subunit of the universal iron-binding and trafficking protein ferritin. Functions linked to the oxidative effects of free iron (e.g. oxidoreductase activity, transition metal ion binding, mitochondrial oxidative phosphorylation) were also affected. These results are consistent with the hypothesis that a magnetic pulse alters or damages magnetite-based receptors and/or other iron-containing structures, which are subsequently repaired or replaced through processes involving ferritin. Additionally, some genes that function in the development and repair of photoreceptive structures (e.g. crggm3 , purp , prl , gcip , crabp1 and pax6 ) were also differentially expressed, raising the possibility that a magnetic pulse might affect structures and processes unrelated to magnetite-based magnetoreceptors

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Ammonia Emissions from USA Broiler Chicken Barns Managed with New Bedding, Built-up Litter, or Acid-Treated Litter

Poultry producers in the United States have attempted to maintain barn aerial ammonia (NH3) levels below 25 ppm to improve air quality, and more recently to decrease aerial emissions to the atmosphere. Our objective was to investigate the influence of litter management strategies on NH3 emissions from commercial broiler barns employing new bedding, acid-treated built-up litter (sodium bisulphate), or untreated built-up litter (normal practice). Nearly 400 barn-days of NH3 emissions data were collected from 12 broiler barns on four farms monitored in 48-hour episodes over one year. On each study farm, the barns were paired for repetition of conditions. Emission was calculated as the product of gas concentration of the exhaust air and barn ventilation rate. Use of new bedding for every flock led to consistently lower NH3 emission (averaging 0.35 g NH3/(bird d)) at day 21 of the 42-day flock grow-outs, followed by flocks raised on the annual cleanout with new bedding (0.52 g NH3/(bird d)). Built-up litter without any treatment had the highest emission (0.73 g NH3/(bird d)), followed by the built-up litter with acid treatment (0.63 g NH3/(bird d)). One study site was managed with two barns using litter treatment and two identical barns with untreated, built-up litter for a side-by-side comparison of results under field conditions. Ammonia emissions from treated built-up litter barns were similar to those from untreated built-up litter barns, however, the temporal pattern of emissions provided evidence that ammonia held in the acid-treated litter at the beginning of the flock was released during the latter period of the flock cycle