Measurement error in a multi-level analysis of air pollution and health: a simulation study.

BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

Similarities between structural distortions under pressure and chemical doping in superconducting BaFe2As2

The discovery of a new family of high Tc materials, the iron arsenides (FeAs), has led to a resurgence of interest in superconductivity. Several important traits of these materials are now apparent, for example, layers of iron tetrahedrally coordinated by arsenic are crucial structural ingredients. It is also now well established that the parent non-superconducting phases are itinerant magnets, and that superconductivity can be induced by either chemical substitution or application of pressure, in sharp contrast to the cuprate family of materials. The structure and properties of chemically substituted samples are known to be intimately linked, however, remarkably little is known about this relationship when high pressure is used to induce superconductivity in undoped compounds. Here we show that the key structural features in BaFe2As2, namely suppression of the tetragonal to orthorhombic phase transition and reduction in the As-Fe-As bond angle and Fe-Fe distance, show the same behavior under pressure as found in chemically substituted samples. Using experimentally derived structural data, we show that the electronic structure evolves similarly in both cases. These results suggest that modification of the Fermi surface by structural distortions is more important than charge doping for inducing superconductivity in BaFe2As2

A computationally inspired in-vivo approach identifies a link between amygdalar transcriptional heterogeneity, socialization and anxiety

Pharmaceutical breakthroughs for anxiety have been lackluster in the last half-century. Converging behavior and limbic molecular heterogeneity has the potential to revolutionize biomarker-driven interventions. However, current in vivo models too often deploy artificial systems including directed evolution, mutations and fear induction, which poorly mirror clinical manifestations. Here, we explore transcriptional heterogeneity of the amygdala in isogenic mice using an unbiased multidimensional computational approach that segregates intra-cohort reactions to moderate situational adversity and intersects it with high content molecular profiling. We show that while the computational approach stratifies known features of clinical anxiety including nitric oxide, opioid and corticotropin signaling, previously unrecognized druggable biomarkers emerge, such as calpain11 and scand1. Through ingenuity pathway analyses, we further describe a role for neurosteroid estradiol signaling, heat shock proteins, ubiquitin ligases and lipid metabolism. In addition, we report a remarkable behavioral pattern that maps to molecular features of anxiety in mice through counterphobic social attitudes, which manifest as increased, yet spatially distant socialization. These findings provide an unbiased approach for interrogating anxiolytics, and hint toward biomarkers underpinning behavioral and social patterns that merit further exploration

Self-rated health in middle-aged and elderly Chinese : distribution, determinants and associations with cardio-metabolic risk factors

Background: Self-rated health (SRH) has been demonstrated to be an accurate reflection of a person's health and a valid predictor of incident mortality and chronic morbidity. We aimed to evaluate the distribution and factors associated with SRH and its association with biomarkers of cardio-metabolic diseases among middle-aged and elderly Chinese. Methods: Survey of 1,458 men and 1,831 women aged 50 to 70 years, conducted in one urban and two rural areas of Beijing and Shanghai in 2005. SRH status was measured and categorized as good (very good and good) vs. not good (fair, poor and very poor). Determinants of SRH and associations with biomarkers of cardio-metabolic diseases were evaluated using logistic regression. Results: Thirty two percent of participants reported good SRH. Males and rural residents tended to report good SRH. After adjusting for potential confounders, residence, physical activity, employment status, sleep quality and presence of diabetes, cardiovascular disease, and depression were the main determinants of SRH. Those free from cardiovascular disease (OR 3.68; 95%CI 2.39; 5.66), rural residents (OR 1.89; 95% CI 1.47; 2.43), non-depressed participants (OR 2.50; 95% CI 1.67; 3.73) and those with good sleep quality (OR 2.95; 95% CI 2.22; 3.91) had almost twice or over the chance of reporting good SRH compared to their counterparts. There were significant associations -and trend- between SRH and levels of inflammatory markers, insulin levels and insulin resistance. Conclusion: Only one third of middle-aged and elderly Chinese assessed their health status as good or very good. Although further longitudinal studies are required to confirm our findings, interventions targeting social inequalities, lifestyle patterns might not only contribute to prevent chronic morbidity but as well to improve populations' perceived health

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

A proposed mechanism for progesterone regulation of trophoblast MMP2 transcription independent of classical progesterone response elements on its promoter

BACKGROUND: Progesterone receptor act as ligand-inducible transcription factor in the respective target cells by binding to specific progesterone response elements in the promoter of the target genes. However, despite the lack of the classical progesterone response elements on matrix-metalloproteinase-2 promoter, progesterone has been shown to decrease the activity of this promoter PRESENTATION OF THE HYPOTHESIS: It has recently been suggested that in addition to interacting with their classical co-activators and co-repressors, progesterone receptor are capable of binding to several transcription factors. By interacting with other classes of transcription factors, progesterone receptor is capable of transcriptional activation through the transcription factors cognate DNA binding site. TESTING THE HYPOTHESIS: Exploring transcription factors and transcription binding sites, interacting with the progesterone receptor in modulation of the matrix-metalloproteinase promoter. IMPLICATIONS OF THE HYPOTHESIS: Identification of additional endogenous progesterone target genes makes it possible to further explore the signaling mechanisms by which the hormone regulates biological actions. Furthermore, the concepts of ligand-driven conformational diversity and selective tissue actions can be exploited in the future for drug development which selectively regulate orphan receptors from the nuclear receptor family

The Outcomes of Hypertransfusion in Major ABO Incompatible Allogeneic Stem Cell Transplantation

Major ABO incompatibility may be potentially associated with immediate or delayed hemolysis and delayed onset of erythropoiesis in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To determine if hemolysis can be prevented by the inhibition of graft erythropoiesis, we performed hypertransfusion and assessed red cell transfusion requirement and independence. Between October 1995 and December 2001, 28 consecutive patients receiving major ABO incompatible HSCT at Samsung Medical Center were hypertransfused to maintain their hemoglobin levels at 15 g/dL or more. We retrospectively compared the outcomes of these patients with those of 47 patients at Asan Medical Center whose target hemoglobin levels were 10 g/dL. Reticulocyte engraftment was significantly delayed in hypertransfused group (51 days vs. 23 days; p=.001). There was no significant difference in the total amount of red cells transfused within 90 days post-HSCT (25 units vs. 26 units; p=.631). No significant difference in the time to red cell transfusion independence was observed between the two groups (63 days vs. 56 days; p=.165). In conclusion, we failed to improve red cell transfusion requirement and independence in major ABO incompatible HSCT with hypertransfusion

Associations between subspecialty fellowship interest and knowledge of internal medicine: A hypothesis-generating study of internal medicine residents

<p>Abstract</p> <p>Background</p> <p>Little is known about whether and how medical knowledge relates to interest in subspecialty fellowship training. The purpose of this study was to examine the relationships between residents' interest in subspecialty fellowship training and their knowledge of internal medicine (IM).</p> <p>Methods</p> <p>A questionnaire was emailed to 48 categorical postgraduate-year (PGY) two and three residents at a New York university-affiliated IM residency program in 2007 using the Survey Monkey online survey instrument. Overall and content area-specific percentile scores from the IM in-training examination (IM-ITE) for the same year was used to determine objective knowledge.</p> <p>Results</p> <p>Forty-five of 48 residents (response rate was 93.8%) completed the survey. Twenty-two (49%) were PG2 residents and 23(51%) were PGY3 residents. Sixty percent of respondents were male. Six (13%) residents were graduates of U.S. medical schools. Eight (18%) reported formal clinical training prior to starting internal medicine residency in the U.S. Of this latter group, 6 (75%) had training in IM and 6 (75) % reported a training length of 3 years or less. Thirty-seven of 45 (82%) residents had a subspecialty fellowship interest. Residents with a fellowship interest had a greater mean overall objective knowledge percentile score (56.44 vs. 31.67; p = 0.04) as well as greater mean percentile scores in all content areas of IM. The adjusted mean difference was statistically significant (p < 0.02) across three content areas.</p> <p>Conclusions</p> <p>More than half of surveyed residents indicated interest in pursuing a subspecialty fellowship. Fellowship interest appears positively associated with general medical knowledge in this study population. Further work is needed to explore motivation and study patterns among internal medicine residents.</p

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations

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