Magnitude of the First and Second Neighbour Magnetic Interactions in the Spin Chain Compound Li2CuO2

State-of-the-art molecular quantum chemical techniques have been applied to the solid-state compound Li2CuO2 in order to derive accurate estimates of the in-chain magnetic interactions. In the present work, the magnitude of the nearest neighbour and next nearest neighbour magnetic coupling constants is investigated from first principles embedded cluster calculations. The convergence of the results is carefully tested for the cluster size. In contrast to the earlier findings, it is predicted that J2 is only ~15% of J1. In particular, it is shown that a large J2 appears when the Li+ ions are not explicitly included in the calculation

Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study

<p>Abstract</p> <p>Background</p> <p>Methylergonovine is an ergot alkaloid widely used in postpartum women. It is also an active metabolite of methysergide and previous studies suggest that it could be effective against refractory headache and cluster headache. The purpose of the present study was to assess the potential therapeutic effectiveness of methylergonovine in the emergency treatment of severe migraine.</p> <p>Methods</p> <p>One hundred and twenty five female patients with migraine attending the emergency department received 0.15 mg of methylergonovine intravenously. Pain intensity, heart rate, blood pressure, and methylergonovine side effects were checked 5, 10, 15, 30 and 60 minutes after drug administration. An additional 0.075 mg dose of methylergonovine was administered to those patients who did not experienced relevant pain relief 15 minutes after dosing. </p> <p>Results</p> <p>Pain intensity decreased markedly from the first minutes after dosing, the 74.4% of patients being pain free at 60 minutes. Only seven patients required an additional dose of methylergonovine. Nausea and vomiting were the most relevant side effects related with methylergonovine administration (84% of patients). A substantial decrease (10 to 25 mmHg) in systolic blood pressure values was observed in 56% of the patients. A significant correlation (p < 0.0001) was found between the decrease in pain intensity and the reduction of systolic blood pressure.</p> <p>Conclusion</p> <p>Although limited by the non-controlled design of the study, our data suggest that intravenous methylergonovine can be an effective and safe drug in the management of severe migraine attacks in the emergency room.</p

Removing the Microlensing Blending-Parallax Degeneracy Using Source Variability

Microlensing event MACHO 97-SMC-1 is one of the rare microlensing events for which the source is a variable star, simply because most variable stars are systematically eliminated from microlensing studies. Using observational data for this event, we show that the intrinsic variability of a microlensed star is a powerful tool to constrain the nature of the lens by breaking the degeneracy between the microlens parallax and the blended light. We also present a statistical test for discriminating the location of the lens based on the \chi^2 contours of the vector \Lambda, the inverse of the projected velocity. We find that while SMC self lensing is somewhat favored over halo lensing, neither location can be ruled out with good confidence.Comment: 15 text pages + 2 tables + 7 figures. Published in the Astrophysical Journa

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Systematic care for caregivers of people with dementia in the ambulatory mental health service: designing a multicentre, cluster, randomized, controlled trial

Contains fulltext : 81435.pdf (publisher's version ) (Open Access)BACKGROUND: Care for people with dementia and their informal caregivers is a challenging aim in healthcare. There is an urgent need for cost-effective support programs that prevent informal caregivers of people with dementia from becoming overburdened, which might result in a delay or decrease of patient institutionalization. For this reason, we have developed the Systematic Care Program for Dementia (SCPD). The SCPD consists of an assessment of caregiver's sense of competence and suggestions on how to deal with competence deficiencies. The efficiency of the SCPD will be evaluated in our study. METHODS AND DESIGN: In our ongoing, cluster, randomized, single-blind, controlled trial, the participants in six mental health services in four regions of the Netherlands have been randomized per service. Professionals of the ambulatory mental health services (psychologists and social psychiatric nurses) have been randomly allocated to either the intervention group or the control group. The study population consists of community-dwelling people with dementia and their informal caregivers (patient-caregiver dyads) coming into the health service. The dyads have been clustered to the professionals. The primary outcome measure is the patient's admission to a nursing home or home for the elderly at 12 months of follow-up. This measure is the most important variable for estimating cost differences between the intervention group and the control group. The secondary outcome measure is the quality of the patient's and caregiver's lives. DISCUSSION: A novelty in the SCPD is the pro-active and systematic approach. The focus on the caregiver's sense of competence is relevant to economical healthcare, since this sense of competence is an important determinant of delay of institutionalization of people with dementia. The SCPD might be able to facilitate this with a relatively small cost investment for caregivers' support, which could result in a major decrease in costs in the management of dementia. Implementation on a national level will be started if the SCPD proves to be efficient. TRIAL REGISTRATION: NCT00147693

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Differential early subcortical involvement in genetic FTD within the GENFI cohort

Background: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. / Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). / Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). / Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms