Abundances of Baade's Window Giants from Keck/HIRES Spectra: I. Stellar Parameters and [Fe/H] Values

We present the first results of a new abundance survey of the Milky Way bulge based on Keck/HIRES spectra of 27 K-giants in the Baade's Window ($l = 1$, $b = -4$) field. The spectral data used in this study are of much higher resolution and signal-to-noise than previous optical studies of Galactic bulge stars. The [Fe/H] values of our stars, which range between -1.29 and $+0.51$, were used to recalibrate large low resolution surveys of bulge stars. Our best value for the mean [Fe/H] of the bulge is $-0.10 \pm 0.04$. This mean value is similar to the mean metallicity of the local disk and indicates that there cannot be a strong metallicity gradient inside the solar circle. The metallicity distribution of stars confirms that the bulge does not suffer from the so-called ``G-dwarf'' problem. This paper also details the new abundance techniques necessary to analyze very metal-rich K-giants, including a new Fe line list and regions of low blanketing for continuum identification.Comment: Accepted for publication in January 2006 Astrophysical Journal. Long tables 3--6 withheld to save space (electronic tables in journal paper). 53 pages, 10 figures, 9 table

Effects of lesions of the subthalamic nucleus/zona incerta area and dorsomedial striatum on attentional set-shifting in the rat

This work was supported by The Wellcome Trust (project Grant 051945/z/97). Andrew Blackwell was in receipt of a BBSRC Studentship.Patients with Parkinson’s disease show cognitive impairments, including difficulty in shifting attention between perceptual dimensions of complex stimuli. Inactivation of the subthalamic nucleus (STN) has been shown to be effective in ameliorating the motor abnormalities associated with striatal dopamine depletion, but it is possible that STN inactivation might result in additional, perhaps attentional, deficits. This study examined the effects of: dopamine depletion from the dorsomedial striatum (DMS); lesions of the STN area; and the effects of the two lesions together, on the ability to shift attentional set in the rat. In a single session, rats performed the intradimensional/extradimensional (ID/ED) test of attentional set-shifting. This comprises a series of seven, two-choice discriminations, including acquisitions of novel discriminations in which the relevant stimulus is either in the currently-attended dimension (ID) or the currently-unattended dimension (ED shift) and reversals following each acquisition stage. Bilateral lesions were made by injection of 6-hydroxydopamine into the DMS, resulting in a selective impairment in reversal learning. Large bilateral ibotenic acid lesions centred on the STN resulted in an increase in trials to criterion in the initial stages, but learning rate improved within the session. There was no evidence of a ‘cost’ of set-shifting – the ED stage was completed in fewer trials than the ID stage – and neither was there a cost of reversal learning. Strikingly, combined lesions of both regions did not resemble the effects of either lesion alone and resulted in no apparent deficits.Publisher PDFPeer reviewe

Changes in CEBPB expression in circulating leukocytes following eccentric elbow-flexion exercise

This is the final version of the article. Available from Springer via the DOI in this record.In mouse models, CCAAT enhancer-binding protein beta (CEBPB) is necessary for M2 macrophage-mediated regeneration after muscle injury. In humans, CEBPB expression in blood was strongly associated with muscle strength. In this study we aimed to test whether CEBPB expression in blood in people is increased 2 days after exercise designed to induce muscle damage and subsequent repair. Sixteen healthy male volunteers undertook elbow flexor exercises designed to induce acute muscle micro-damage. Peripheral blood samples were collected at baseline and days 1, 2, 4 and 7 following exercise. Expression of CEBPB and related genes were analysed by qRT-PCR. Extent of muscle damage was determined by decline in maximal voluntary isometric torque and by plasma creatine kinase activity. Nine subjects had peak (day 4) creatine kinase activity exceeding 10,000 U/l. In this subgroup, CEBPB expression was elevated from baseline to 2 days post exercise (paired-samples t (1,8) = 3.72, p = 0.006). Related expression and selected cytokine changes after exercise did not reach significance. Muscle-damaging exercise in humans can be followed by induction of CEBPB transcript expression in peripheral blood. Associations between CEBPB expression in blood and muscle strength may be consistent with the CEBPB-dependent muscle repair process.Wellcome TrustNational Institute for Health Researc

Assessment of cognitive safety in clinical drug development

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks

Methylphenidate improves response inhibition but not reflection–impulsivity in children with attention deficit hyperactivity disorder (ADHD)

Impulsivity is a cardinal feature of attention deficit hyperactivity disorder (ADHD), which is thought to underlie many of the cognitive and behavioural symptoms associated with the disorder. Impairments on some measures of impulsivity have been shown to be responsive to pharmacotherapy. However, impulsivity is a multi-factorial construct and the degree to which different forms of impulsivity contribute to impairments in ADHD or respond to pharmacological treatments remains unclear.The aims of the study were to assess the effects of methylphenidate (MPH) on the performance of children with ADHD on measures of reflection-impulsivity and response inhibition and to compare with the performance of healthy volunteers.Twenty-one boys (aged 7-13 years) diagnosed with ADHD underwent a double-blind, placebo-controlled trial of MPH (0.5 mg/kg) during which they performed the Information Sampling Task (IST) and the Stop Signal Task. A healthy age- and education-matched control group was tested on the same measures without medication.Children with ADHD were impaired on measures of response inhibition, but did not demonstrate reflection-impulsivity on the IST. However, despite sampling a similar amount of information as their peers, the ADHD group made more poor decisions. MPH improved performance on measures of response inhibition and variability of response, but did not affect measures of reflection-impulsivity or quality of decision-making.MPH differentially affected two forms of impulsivity in children with ADHD and failed to ameliorate their poor decision-making on the information sampling test.</p

Evaluation of the Geothermal Potential of the Western Snake River Plain Based on a Deep Corehole on the Mountain Home AFB Near Mountain Home, Idaho

A geothermal exploration corehole was drilled to a total depth of 1821.5 m on the Mountain Home Air Force Base near Mountain Home, Idaho. The corehole was used to collect an unusually large amount of data, including uniaxial compressive stress (UCS) experiments on core samples, to evaluate the geothermal potential of the western Snake River Plain. In addition, unlike many exploration holes in this region, a fluid entry was encountered at 1745.3 m and flowed artesian to the surface. A maximum temperature of 149.4 °C was calculated for the entry. A temperature log run on the corehole from 3 to 1675 m is nearly linear with little variation. The average geothermal gradient is 73 °C/km, and the average heat flow between 200 and 1500 m is 102 ± 15 mW/m2. Chemical analyses of a sample from the fluid entry suggest that a significant proportion of the water is not meteoric. Five geothermometers show equilibrium temperature in the range of 133–157 °C. Furthermore, based on the unconfined UCS experiments on basalt core samples, a brittle unit was found to comprise the fractured reservoir that the geothermal water flows from, while an overlying ductile unit acts as a hydrothermal caprock. This implies that the reservoir/caprock pair may be a target for future exploration wells drilled to delineate the extent of the potential resource and the boundaries of the connected fracture network

New Approaches to Olefin Cross-Metathesis

New methodology for the selective cross-metathesis (CM) of terminal olefins employing ruthenium benzylidene 1 is described.1 CM with symmetric internal olefins was found to provide a useful means for homologating terminal olefins to protected allylic alcohols, amines, and esters. Due to the limited commercial availability of symmetric internal olefins, a two-step CM procedure was developed in which terminal olefins were first homodimerized prior to the CM reaction. Terminal olefins with allylic methyl substituents were observed to provide CM products in diminished yield albeit with markedly improved trans-selectivity. Reaction rates were measured for CM reactions utilizing butenediol and allyl alcohol derivatives, and the results demonstrated distinct advantages in reaction rate and stereoselectivity for reactions employing the disubstituted olefins. In the course of studies of substrates with allylic oxygen substituents, a new CM application was discovered involving the metathesis of acrolein acetal derivatives with terminal olefins. Acrolein acetals, including asymmetric variants derived from tartaric acid, proved to be exceptionally robust and trans-selective CM substrates. In related work, a pinacol-derived vinyl boronate was also found to be a reactive CM partner, providing a novel means for converting terminal olefins into precursors for the Suzuki coupling reaction

Data for Genetic Analysis Workshop 18: human whole genome sequence, blood pressure, and simulated phenotypes in extended pedigrees

Genetic Analysis Workshop 18 (GAW18) focused on identification of genes and functional variants that influence complex phenotypes in human sequence data. Data for the workshop were donated by the T2D-GENES Consortium and included whole genome sequences for odd-numbered autosomes in 464 key individuals selected from 20 Mexican American families, a dense set of single-nucleotide polymorphisms in 959 individuals in these families, and longitudinal data on systolic and diastolic blood pressure measured at 1-4 examinations over a period of 20 years. Simulated phenotypes were generated based on the real sequence data and pedigree structures. In the design of the simulation model, gene expression measures from the San Antonio Family Heart Study (not distributed as part of the GAW18 data) were used to identify genes whose mRNA levels were correlated with blood pressure. Observed variants within these genes were designated as functional in the GAW18 simulation if they were nonsynonymous and predicted to have deleterious effects on protein function or if they were noncoding and associated with mRNA levels. Two simulated longitudinal phenotypes were modeled to have the same trait distributions as the real systolic and diastolic blood pressure data, with effects of age, sex, and medication use, including a genotype-medication interaction. For each phenotype, more than 1000 sequence variants in more than 200 genes present on the odd-numbered autosomes individually explained less than 0.01-2.78% of phenotypic variance. Cumulatively, variants in the most influential gene explained 7.79% of trait variance. An additional simulated phenotype, Q1, was designed to be correlated among family members but to not be associated with any sequence variants. Two hundred replicates of the phenotypes were simulated, with each including data for 849 individuals

Art therapy with refugee children: a qualitative study explored through the lens of art therapists and their experiences

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Art Therapy on 9-11-2018, available online: https://doi.org/10.1080/17454832.2018.1533571This article sets out to explore the use of art therapy with refugee children, from the perspective of art therapists and their experiences. Three semi-structured interviews were conducted to gain insights by capturing experiences and stories. Using thematic analysis, five themes were identified: (1) giving voice; (2) rebuilding trust, opening wounds; (3) sharing stories, healing pain; (4) exploring identity, discovering new-self; and (5) understanding art therapy. Upon reflection, two key aspects of art therapy were established, these were identified as: (1) providing refugee children with a safe space to heal and discover new-self, and (2) giving refugee children a voice to express and share stories. Despite the last of the five themes (understanding art therapy) being established as a factor that limits the use of art therapy, this has created an avenue for further research. From the findings, it was concluded that art therapy can be a useful form of psychotherapy for refugee children. Art therapy can provide these children with a safe space to heal, and give them a voice to be heard