Association between Residences in U.S. Northern Latitudes and Rheumatoid Arthritis: A Spatial Analysis of the Nurses’ Health Study

Background: The etiology of rheumatoid arthritis (RA) remains largely unknown, although epidemiologic studies suggest genetic and environmental factors may play a role. Geographic variation in incident RA has been observed at the regional level. Objective: Spatial analyses are a useful tool for confirming existing exposure hypotheses or generating new ones. To further explore the association between location and RA risk, we analyzed individual-level data from U.S. women in the Nurses’ Health Study, a nationwide cohort study. Methods: Participants included 461 incident RA cases and 9,220 controls with geocoded addresses; participants were followed from 1988 to 2002. We examined spatial variation using addresses at baseline in 1988 and at the time of case diagnosis or the censoring of controls. Generalized additive models (GAMs) were used to predict a continuous risk surface by smoothing on longitude and latitude while adjusting for known risk factors. Permutation tests were conducted to evaluate the overall importance of location and to identify, within the entire study area, those locations of statistically significant risk. Results: A statistically significant area of increased RA risk was identified in the northeast United States (p-value = 0.034). Risk was generally higher at northern latitudes, and it increased slightly when we used the nurses’ 1988 locations compared with those at the time of diagnosis or censoring. Crude and adjusted models produced similar results. Conclusions: Spatial analyses suggest women living in higher latitudes may be at greater risk for RA. Further, RA risk may be greater for locations that occur earlier in residential histories. These results illustrate the usefulness of GAM methods in generating hypotheses for future investigation and supporting existing hypotheses

Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure

Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2–36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans

A decision analytical cost analysis of offering ECV in a UK district general hospital

OBJECTIVE: To determine the care pathways and implications of offering mothers the choice of external cephalic version (ECV) at term for singleton babies who present with an uncomplicated breech pregnancy versus assisted breech delivery or elective caesarean. DESIGN: A prospective observational audit to construct a decision analysis of uncomplicated full term breech presentations. SETTING: The North Staffordshire NHS Trust. SUBJECTS: All women (n = 176) who presented at full term with a breech baby without complications during July 1995 and June 1997. MAIN OUTCOME MEASURES: The study determined to compare the outcome in terms of the costs and cost consequences for the care pathways that resulted from whether a women chose to accept the offer of ECV or not. All the associated events were then mapped for the two possible pathways. The costs were considered only within the hospital setting, from the perspective of the health care provider up to the point of delivery. RESULTS: The additional costs for ECV, assisted breech delivery and elective caesarean over and above a normal birth were £186.70, £425.36 and £1,955.22 respectively. The total expected cost of the respective care pathways for "ECV accepted" and "ECV not accepted" (including the probability of adverse events) were £1,452 and £1,828 respectively, that is the cost of delivery through the ECV care pathways is less costly than the non ECV delivery care pathway. CONCLUSIONS: Implementing an ECV service may yield cost savings in secondary care over and above the traditional delivery methods for breech birth of assisted delivery or caesarean section. The scale of these expected cost savings are in the range of £248 to £376 per patient. This converts to a total expected cost saving of between £43,616 and £44,544 for the patient cohort considered in this study

Thyroid function tests in patients taking thyroid medication in Germany: Results from the population-based Study of Health in Pomerania (SHIP)

<p>Abstract</p> <p>Background</p> <p>Studies from iodine-sufficient areas have shown that a high proportion of patients taking medication for thyroid diseases have thyroid stimulating hormone (TSH) levels outside the reference range. Next to patient compliance, inadequate dosing adjustment resulting in under- and over-treatment of thyroid disease is a major cause of poor therapy outcomes. Using thyroid function tests, we aim to measure the proportions of subjects, who are under- or over-treated with thyroid medication in a previously iodine-deficient area.</p> <p>Findings</p> <p>Data from 266 subjects participating in the population-based Study of Health in Pomerania (SHIP) were analysed. All subjects were taking thyroid medication. Serum TSH levels were measured using immunochemiluminescent procedures. TSH levels of < 0.27 or > 2.15 mIU/L in subjects younger than 50 years and < 0.19 or > 2.09 mIU/L in subjects 50 years and older, were defined as decreased or elevated, according to the established reference range for the specific study area. Our analysis revealed that 56 of 190 (29.5%) subjects treated with thyroxine had TSH levels outside the reference range (10.0% elevated, 19.5% decreased). Of the 31 subjects taking antithyroid drugs, 12 (38.7%) had TSH levels outside the reference range (9.7% elevated, 29.0% decreased). These proportions were lower in the 45 subjects receiving iodine supplementation (2.2% elevated, 8.9% decreased). Among the 3,974 SHIP participants not taking thyroid medication, TSH levels outside the reference range (2.8% elevated, 5.9% decreased) were less frequent.</p> <p>Conclusion</p> <p>In concordance with previous studies in iodine-sufficient areas, our results indicate that a considerable number of patients taking thyroid medication are either under- or over-treated. Improved monitoring of these patients' TSH levels, compared to the local reference range, is recommended.</p

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Communicating population health statistics through graphs: a randomised controlled trial of graph design interventions

BACKGROUND: Australian epidemiologists have recognised that lay readers have difficulty understanding statistical graphs in reports on population health. This study aimed to provide evidence for graph design improvements that increase comprehension by non-experts. METHODS: This was a double-blind, randomised, controlled trial of graph-design interventions, conducted as a postal survey. Control and intervention participants were randomly selected from telephone directories of health system employees. Eligible participants were on duty at the listed location during the study period. Controls received a booklet of 12 graphs from original publications, and intervention participants received a booklet of the same graphs with design modifications. A questionnaire with 39 interpretation tasks was included with the booklet. Interventions were assessed using the ratio of the prevalence of correct responses given by the intervention group to those given by the control group for each task. RESULTS: The response rate from 543 eligible participants (261 intervention and 282 control) was 67%. The prevalence of correct answers in the control group ranged from 13% for a task requiring knowledge of an acronym to 97% for a task identifying the largest category in a pie chart. Interventions producing the greatest improvement in comprehension were: changing a pie chart to a bar graph (3.6-fold increase in correct point reading), changing the y axis of a graph so that the upward direction represented an increase (2.9-fold increase in correct judgement of trend direction), a footnote to explain an acronym (2.5-fold increase in knowledge of the acronym), and matching the y axis range of two adjacent graphs (two-fold increase in correct comparison of the relative difference in prevalence between two population subgroups). CONCLUSION: Profound population health messages can be lost through use of overly technical language and unfamiliar statistical measures. In our study, most participants did not understand age standardisation and confidence intervals. Inventive approaches are required to address this problem

Cryptic Disc Structures Resembling Ediacaran Discoidal Fossils from the Lower Silurian Hellefjord Schist, Arctic Norway

The Hellefjord Schist, a volcaniclastic psammite-pelite formation in the Caledonides of Arctic Norway contains discoidal impressions and apparent tube casts that share morphological and taphonomic similarities to Neoproterozoic stem-holdfast forms. U-Pb zircon geochronology on the host metasediment indicates it was deposited between 437 ± 2 and 439 ± 3 Ma, but also indicates that an inferred basal conglomerate to this formation must be part of an older stratigraphic element, as it is cross-cut by a 546 ± 4 Ma pegmatite. These results confirm that the Hellefjord Schist is separated from underlying older Proterozoic rocks by a thrust. It has previously been argued that the Cambrian Substrate Revolution destroyed the ecological niches that the Neoproterozoic frond-holdfasts organisms occupied. However, the discovery of these fossils in Silurian rocks demonstrates that the environment and substrate must have been similar enough to Neoproterozoic settings that frond-holdfast bodyplans were still ecologically viable some hundred million years later

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon

<p>Abstract</p> <p>Background</p> <p>Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials.</p> <p>Methods</p> <p>Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests.</p> <p>Results</p> <p>Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort.</p> <p>Conclusion</p> <p>The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low.</p> <p>Trial registration</p> <p>Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial) and NCT ID # 00167843 (Lambaréné Trial), <url>http://www.clinicaltrials.gov</url>.</p