Gamma-Ray Telescopes (in "400 Years of Astronomical Telescopes")

The last half-century has seen dramatic developments in gamma-ray telescopes, from their initial conception and development through to their blossoming into full maturity as a potent research tool in astronomy. Gamma-ray telescopes are leading research in diverse areas such as gamma-ray bursts, blazars, Galactic transients, and the Galactic distribution of aluminum-26.Comment: 11 pages, 6 figures/ in "400 Years of Astronomical Telescopes: A Review of History, Science and Technology", ed. B.R. Brandl, R. Stuik, & J.K. Katgert-Merkeli (Exp. Astron. 26, 111-122 [2009]

The contribution of diet and genotype to iron status in women:a classical twin study

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04)

Calibration estimation in dual-frame surveys

Survey statisticians make use of auxiliary information to improve estimates. One important example is calibration estimation, which constructs new weights that match benchmark constraints on auxiliary variables while remaining “close” to the design weights. Multiple-frame surveys are increasingly used by statistical agencies and private organizations to reduce sampling costs and/or avoid frame undercoverage errors. Several ways of combining estimates derived from such frames have been proposed elsewhere; in this paper, we extend the calibration paradigm, previously used for single-frame surveys, to calculate the total value of a variable of interest in a dual-frame survey. Calibration is a general tool that allows to include auxiliary information from two frames. It also incorporates, as a special case, certain dual-frame estimators that have been proposed previously. The theoretical properties of our class of estimators are derived and discussed, and simulation studies conducted to compare the efficiency of the procedure, using different sets of auxiliary variables. Finally, the proposed methodology is applied to real data obtained from the Barometer of Culture of Andalusia survey.Ministerio de Educación y CienciaConsejería de Economía, Innovación, Ciencia y EmpleoPRIN-SURWE

An enigmatic hypoplastic defect of the maxillary lateral incisor in recent and fossil orangutans from Sumatra (Pongo abelii) and Borneo (Pongo pygmaeus)

Developmental dental pathologies provide insight into health of primates during ontogeny, and are particularly useful for elucidating the environment in which extant and extinct primates matured. Our aim is to evaluate whether the prevalence of an unusual dental defect on the mesiolabial enamel of the upper lateral incisor, thought to reflect dental crowding during maturation, is lesser in female orangutans, with their smaller teeth, than in males; and in Sumatran orangutans, from more optimal developmental habitats, than in those from Borneo. Our sample includes 49 Pongo pygmaeus (87 teeth), 21 P. abelii (38 teeth), Late Pleistocene paleo-orangutans from Sumatra and Vietnam (67 teeth), Late Miocene catarrhines Lufengpithecus lufengensis (2 teeth), and Anapithecus hernyaki (7 teeth). Methods include micro-CT scans, radiography, and dental metrics of anterior teeth. We observed fenestration between incisor crypts and marked crowding of unerupted crowns, which could allow tooth-to-tooth contact. Tooth size does not differ significantly in animals with or without the defect, implicating undergrowth of the jaw as the proximate cause of dental crowding and defect presence. Male orangutans from both islands show more defects than do females. The defect is significantly more common in Bornean orangutans (71 %) compared to Sumatran (29 %). Prevalence among fossil forms falls between these extremes, except that all five individual Anapithecus show one or both incisors with the defect. We conclude that maxillary lateral incisor defect is a common developmental pathology of apes that is minimized in optimal habitats and that such evidence can be used to infer habitat quality in extant and fossil apes

Building nonparametric nn-body force fields using Gaussian process regression

Constructing a classical potential suited to simulate a given atomic system is a remarkably difficult task. This chapter presents a framework under which this problem can be tackled, based on the Bayesian construction of nonparametric force fields of a given order using Gaussian process (GP) priors. The formalism of GP regression is first reviewed, particularly in relation to its application in learning local atomic energies and forces. For accurate regression it is fundamental to incorporate prior knowledge into the GP kernel function. To this end, this chapter details how properties of smoothness, invariance and interaction order of a force field can be encoded into corresponding kernel properties. A range of kernels is then proposed, possessing all the required properties and an adjustable parameter $n$ governing the interaction order modelled. The order $n$ best suited to describe a given system can be found automatically within the Bayesian framework by maximisation of the marginal likelihood. The procedure is first tested on a toy model of known interaction and later applied to two real materials described at the DFT level of accuracy. The models automatically selected for the two materials were found to be in agreement with physical intuition. More in general, it was found that lower order (simpler) models should be chosen when the data are not sufficient to resolve more complex interactions. Low $n$ GPs can be further sped up by orders of magnitude by constructing the corresponding tabulated force field, here named "MFF".Comment: 31 pages, 11 figures, book chapte

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

Dominant role of greenhouse-gas forcing in the recovery of Sahel rainfall

Sahelian summer rainfall, controlled by the West African monsoon, exhibited large-amplitude multidecadal variability during the twentieth century. Particularly important was the severe drought of the 1970s and 1980s, which had widespread impacts1–6. Research into the causes of this drought has identified anthropogenic aerosol forcing3,4,7 and changes in sea surface temperatures (SSTs; refs 1,2,6,8–11) as the most important drivers. Since the 1980s, there has been some recovery of Sahel rainfall amounts2–6,11–14, although not to the pre-drought levels of the 1940s and 1950s. Here we report on experiments with the atmospheric component of a state-of-the-art global climate model to identify the causes of this recovery. Our results suggest that the direct influence of higher levels of greenhouse gases in the atmosphere was the main cause, with an additional role for changes in anthropogenic aerosol precursor emissions. We find that recent changes in SSTs, although substantial, did not have a significant impact on the recovery. The simulated response to anthropogenic greenhouse-gas and aerosol forcing is consistent with a multivariate fingerprint of the observed recovery, raising confidence in our findings. Although robust predictions are not yet possible, our results suggest that the recent recovery in Sahel rainfall amounts is most likely to be sustained or amplified in the near term

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

Turnover rate of cerebrospinal fluid in female sheep: changes related to different light-dark cycles

<p>Abstract</p> <p>Background</p> <p>Sheep are seasonal breeders. The key factor governing seasonal changes in the reproductive activity of the ewe is increased negative feedback of estradiol at the level of the hypothalamus under long-day conditions. It has previously been demonstrated that when gonadotropin secretions are inhibited during long days, there is a higher concentration of estradiol in the cerebrospinal fluid (CSF) than during short days. This suggests an involvement of the CSF and choroid plexus in the neuroendocrine regulatory loop, but the mechanisms underlying this phenomenon remain unknown. One possible explanation of this difference in hormonal content is an effect of concentration or dilution caused by variations in CSF secretion rate. The aim of this study was thus to investigate changes in the CSF turnover rate related to light-dark cycles.</p> <p>Methods</p> <p>The turnover rate of the CSF was estimated by measuring the time taken for the recovery of intraventricular pressure (IVP) after removal of a moderate volume (0.5 to 2 ml) of CSF (slope in mmHg/min). The turnover rate was estimated three times in the same group of sheep: during a natural period of decreasing day-length corresponding to the initial period when gonadotropin activity is stimulated (SG1), during a long-day inhibitory period (IG), and finally during a short-day stimulatory period (SG2).</p> <p>Results</p> <p>The time taken and the speed of recovery of initial IVP differed between groups: 8 min 30 sec, 0.63 ± 0.07 mmHg/min(SG1), 11 min 1 sec, 0.38 ± 0.06 mmHg/min (IG) and 9 min 0 sec, 0.72 ± 0.15 mmHg/min (SG2). Time changes of IVP differed between groups (ANOVA, p < 0.005, SG1 different from IG, <it>p </it>< 0.05). The turnover rate in SG2: 183.16 ± 23.82 μl/min was not significantly different from SG1: 169. 23 ± 51.58 μl/min (Mann-Whitney test, <it>p </it>= 0.41), but was significantly different from IG: 71.33 ± 16.59 μl/min (<it>p </it>= 0.016).</p> <p>Conclusion</p> <p>This study shows that the turnover rate of CSF in ewes changes according to the light-dark cycle; it is increased during short day periods and reduced in long day periods. This phenomenon could account for differences in hormonal concentrations in the CSF in this seasonal species.</p

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag