Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics.

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.ConclusionsThis population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia

Building development and roads: implications for the distribution of stone curlews across the Brecks

Background: Substantial new housing and infrastructure development planned within England has the potential to conflict with the nature conservation interests of protected sites. The Breckland area of eastern England (the Brecks) is designated as a Special Protection Area for a number of bird species, including the stone curlew (for which it holds more than 60% of the UK total population). We explore the effect of buildings and roads on the spatial distribution of stone curlew nests across the Brecks in order to inform strategic development plans to avoid adverse effects on such European protected sites. Methodology: Using data across all years (and subsets of years) over the period 1988 – 2006 but restricted to habitat areas of arable land with suitable soils, we assessed nest density in relation to the distances to nearest settlements and to major roads. Measures of the local density of nearby buildings, roads and traffic levels were assessed using normal kernel distance-weighting functions. Quasi-Poisson generalised linear mixed models allowing for spatial auto-correlation were fitted. Results: Significantly lower densities of stone curlew nests were found at distances up to 1500m from settlements, and distances up to 1000m or more from major (trunk) roads. The best fitting models involved optimally distance-weighted variables for the extent of nearby buildings and the trunk road traffic levels. Significance : The results and predictions from this study of past data suggests there is cause for concern that future housing development and associated road infrastructure within the Breckland area could have negative impacts on the nesting stone curlew population. Given the strict legal protection afforded to the SPA the planning and conservation bodies have subsequently agreed precautionary restrictions on building development within the distances identified and used the modelling predictions to agree mitigation measures for proposed trunk road developments

Effect of response format for clinical vignettes on reporting quality of physician practice

<p>Abstract</p> <p>Background</p> <p>Clinical vignettes have been used widely to compare quality of clinical care and to assess variation in practice, but the effect of different response formats has not been extensively evaluated. Our objective was to compare three clinical vignette-based survey response formats – open-ended questionnaire (A), closed-ended (multiple-choice) questionnaire with deceptive response items mixed with correct items (B), and closed-ended questionnaire with only correct items (C) – in rheumatologists' pre-treatment assessment for tumor-necrosis-factor (TNF) blocker therapy.</p> <p>Methods</p> <p><b><it>Study design</it></b>: Prospective randomized study. <b><it>Setting</it></b>: Rheumatologists attending the 2004 French Society of Rheumatology meeting. Physicians were given a vignette describing the history of a fictitious woman with active rheumatoid arthritis, who was a candidate for therapy with TNF blocking agents, and then were randomized to receive questionnaire A, B, or C, each containing the same four questions but with different response formats, that asked about their pretreatment assessment. <b><it>Measurements</it></b>: Long (recommended items) and short (mandatory items) checklists were developed for pretreatment assessment for TNF-blocker therapy, and scores were expressed on the basis of responses to questionnaires A, B, and C as the percentage of respondents correctly choosing explicit items on these checklists. <b><it>Statistical analysis</it></b>: Comparison of the selected items using pairwise Chi-square tests with Bonferonni correction for variables with statistically significant differences.</p> <p>Results</p> <p>Data for all surveys distributed (114 As, 118 Bs, and 118 Cs) were complete and available for analysis. The percentage of questionnaire A, B, and C respondents for whom data was correctly complete for the short checklist was 50.4%, 84.0% and 95.0%, respectively, and was 0%, 5.0% and 5.9%, respectively, for the long version. As an example, 65.8%, 85.7% and 95.8% of the respondents of A, B, and C questionnaires, respectively, correctly identified the need for tuberculin skin test (p < 0.0001).</p> <p>Conclusion</p> <p>In evaluating clinical practice with use of a clinical vignette, a multiple-choice format rather than an open-ended format overestimates physician performance. The insertion of deceptive response items mixed with correct items in closed-ended (multiple-choice) questionnaire failed to avoid this overestimation.</p

On chains in HH-closed topological pospaces

We study chains in an $H$-closed topological partially ordered space. We give sufficient conditions for a maximal chain $L$ in an $H$-closed topological partially ordered space such that $L$ contains a maximal (minimal) element. Also we give sufficient conditions for a linearly ordered topological partially ordered space to be $H$-closed. We prove that any $H$-closed topological semilattice contains a zero. We show that a linearly ordered $H$-closed topological semilattice is an $H$-closed topological pospace and show that in the general case this is not true. We construct an example an $H$-closed topological pospace with a non-$H$-closed maximal chain and give sufficient conditions that a maximal chain of an $H$-closed topological pospace is an $H$-closed topological pospace.Comment: We have rewritten and substantially expanded the manuscrip

Do differences in profiling criteria bias performance measurements? Economic profiling of medical clinics under the Korea National Health Insurance program: An observational study using claims data

<p>Abstract</p> <p>Background</p> <p>With a greater emphasis on cost containment in many health care systems, it has become common to evaluate each physician's relative resource use. This study explored the major factors that influence the economic performance rankings of medical clinics in the Korea National Health Insurance (NHI) program by assessing the consistency between cost-efficiency indices constructed using different profiling criteria.</p> <p>Methods</p> <p>Data on medical care benefit costs for outpatient care at medical clinics nationwide were collected from the NHI claims database. We calculated eight types of cost-efficiency index with different profiling criteria for each medical clinic and investigated the agreement between the decile rankings of each index pair using the weighted kappa statistic.</p> <p>Results</p> <p>The exclusion of pharmacy cost lowered agreement between rankings to the lowest level, and differences in case-mix classification also lowered agreement considerably.</p> <p>Conclusions</p> <p>A medical clinic may be identified as either cost-efficient or cost-inefficient, even when using the same index, depending on the profiling criteria applied. Whether a country has a single insurance or a multiple-insurer system, it is very important to have standardized profiling criteria for the consolidated management of health care costs.</p

Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models

Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci, separately, in mouse models of nasopharyngeal carriage or pneumonia. Passaged pneumococci became more effective colonizers of the respiratory tract and we observed several examples of potential parallel evolution. The cell wall-modifying glycosyltransferase LafA was under strong selection during lung passage, whereas the surface expressed pneumococcal vaccine antigen gene pvaA and the glycerol-3-phosphate dehydrogenase gene gpsA were frequent targets of mutation in nasopharynx-passaged pneumococci. These mutations were not identified in pneumococci that were separately evolved by serial passage on laboratory agar. We focused on gpsA, in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We describe a new role for this gene in nasopharyngeal carriage and show that the identified single nucleotide change confers resistance to oxidative stress and enhanced nasopharyngeal colonization potential. We demonstrate that polymorphisms in gpsA arise and are retained during human colonization. These findings highlight how within-host environmental conditions can determine trajectories of bacterial evolution. Relative invasiveness or attack rate of pneumococcal lineages may be defined by genes that make niche-specific contributions to bacterial fitness. Experimental evolution in animal infection models is a powerful tool to investigate the relative roles played by pathogen virulence and colonization factors within different host niches

Impact of chronic pain on patients’ quality of life: A comparative mixed-methods study

Background: Chronic pain has become a common problem within primary care and can negatively impact patients’ lives. Objective: To assess and explore the impact of chronic pain on patients’ quality of life (QoL) using quantitative and qualitative data, respectively. Methods: A convergent parallel mixed-methods design was used. Chronic pain patients were recruited from a community-based pain clinic located in the North of England. Quality of life was assessed using Short-Form 36 version 2. Quality of life data were also extracted from the Third Oxford and Lifestyles Survey and Welsh Health Survey to allow comparison of QoL of chronic pain patients with that of the general population and patients with long-term conditions. Qualitative interviews were conducted face-to-face using a semistructured topic guide. Quantitative data were analyzed using SPSS version 24 and qualitative data were analyzed thematically. Results: Seventy-nine patients participated in the quantitative phase. The mean (standard deviation) age was 46.5 (14.5). Lower back (54; 68.3%) followed by lower limb were the most common pain sites. Compared with the general population and patients with long-term conditions, chronic pain patients had significantly lower mean QoL scores across all domains of SF-36 (All P < .05). Six themes emerged from qualitative data: interference with physical functioning, interference with professional life, interference with relationships and family life, interference with social life, interference with sleep, and interference with mood. Conclusion: The multidimensional negative impact of chronic pain leads to poorer QoL among patients with chronic pain compared to the general population and patients with other long-term conditions

Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis

Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings

Assessing connectivity between an overlying aquifer and a coal seam gas resource using methane isotopes, dissolved organic carbon and tritium

Coal seam gas (CSG) production can have an impact on groundwater quality and quantity in adjacent or overlying aquifers. To assess this impact we need to determine the background groundwater chemistry and to map geological pathways of hydraulic connectivity between aquifers. In south-east Queensland (Qld), Australia, a globally important CSG exploration and production province, we mapped hydraulic connectivity between the Walloon Coal Measures (WCM, the target formation for gas production) and the overlying Condamine River Alluvial Aquifer (CRAA), using groundwater methane (CH4) concentration and isotopic composition (δ13C-CH4), groundwater tritium (3H) and dissolved organic carbon (DOC) concentration. A continuous mobile CH4 survey adjacent to CSG developments was used to determine the source signature of CH4 derived from the WCM. Trends in groundwater δ13C-CH4 versus CH4 concentration, in association with DOC concentration and 3H analysis, identify locations where CH4 in the groundwater of the CRAA most likely originates from the WCM. The methodology is widely applicable in unconventional gas development regions worldwide for providing an early indicator of geological pathways of hydraulic connectivity

Utilization of the PICO framework to improve searching PubMed for clinical questions

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