Gamma-rays from millisecond pulsars in Globular Clusters

Globular clusters (GCs) with their ages of the order of several billion years contain many final products of evolution of stars such as: neutron stars, white dwarfs and probably also black holes. These compact objects can be at present responsible for the acceleration of particles to relativistic energies. Therefore, gamma-ray emission is expected from GCs as a result of radiation processes occurring either in the inner magnetosperes of millisecond pulsars or in the vicinity of accreting neutron stars and white dwarfs or as a result of interaction of particles leaving the compact objects with the strong radiation field within the GC. Recently, GeV gamma-ray emission has been detected from several GCs by the new satellite observatory Fermi. Also Cherenkov telescopes reported interesting upper limits at the TeV energies which start to constrain the content of GCs. We review the results of these gamma-ray observations in the context of recent scenarios for their origin.Comment: 20 pages, 9 figures, will be published in Astrophysics and Space Science Series (Springer), eds. N. Rea and D.F. Torre

Wet Granular Materials

Most studies on granular physics have focused on dry granular media, with no liquids between the grains. However, in geology and many real world applications (e.g., food processing, pharmaceuticals, ceramics, civil engineering, constructions, and many industrial applications), liquid is present between the grains. This produces inter-grain cohesion and drastically modifies the mechanical properties of the granular media (e.g., the surface angle can be larger than 90 degrees). Here we present a review of the mechanical properties of wet granular media, with particular emphasis on the effect of cohesion. We also list several open problems that might motivate future studies in this exciting but mostly unexplored field.Comment: review article, accepted for publication in Advances in Physics; tex-style change

Correlations of Gene Expression with Blood Lead Levels in Children with Autism Compared to Typically Developing Controls

The objective of this study was to examine the correlation between gene expression and lead (Pb) levels in blood in children with autism (AU, n = 37) compared to typically developing controls (TD, n = 15). We postulated that, though lead levels did not differ between the groups, AU children might metabolize lead differently compared to TD children. RNA was isolated from blood and processed on Affymetrix microarrays. Separate analyses of covariance (ANCOVA) corrected for age and gender were performed for TD, AU, and all subjects (AU + TD). To reduce false positives, only genes that overlapped these three ANCOVAs were considered. Thus, 48 probe sets correlated with lead levels in both AU and TD subjects and were significantly different between the groups (p(Diagnosis × log2 Pb) < 0.05). These genes were related mainly to immune and inflammatory processes, including MHC Class II family members and CD74. A large number (n = 791) of probe sets correlated (P ≤ 0.05) with lead levels in TD but not in AU subjects; and many probe sets (n = 162) correlated (P ≤ 0.05) with lead levels in AU but not in TD subjects. Only 30 probe sets correlated (P ≤ 0.05) with lead levels in a similar manner in the AU and TD groups. These data show that AU and TD children display different associations between transcript levels and low levels of lead. We postulate that this may relate to the underlying genetic differences between the two groups, though other explanations cannot be excluded

Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis

BACKGROUND: Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. METHODS: 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins. RESULTS: mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season. CONCLUSION: The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation

The plausibility of a role for mercury in the etiology of autism: a cellular perspective

Autism is defined by a behavioral set of stereotypic and repetitious behavioral patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. Of course, the evidence is not derived from experimental trials with humans but rather from methods focusing on biomarkers of Hg damage, measurements of Hg exposure, epidemiological data, and animal studies. For ethical reasons, controlled Hg exposure in humans will never be conducted. Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is essential to first establish the biological plausibility of the hypothesis. This review examines the plausibility of Hg as the primary etiological agent driving the cellular mechanisms by which Hg-induced neurotoxicity may result in the physiological attributes of autism. Key areas of focus include: (1) route and cellular mechanisms of Hg exposure in autism; (2) current research and examples of possible genetic variables that are linked to both Hg sensitivity and autism; (3) the role Hg may play as an environmental toxin fueling the oxidative stress found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune dysregulation found in autism. Future research directions that would assist in addressing the gaps in our knowledge are proposed

Delay Of Insulin Addition To Oral Combination Therapy Despite Inadequate Glycemic Control: Delay of Insulin Therapy

BACKGROUND: Patients and providers may be reluctant to escalate to insulin therapy despite inadequate glycemic control. OBJECTIVES: To determine the proportion of patients attaining and maintaining glycemic targets after initiating sulfonylurea and metformin oral combination therapy (SU/MET); to assess insulin initiation among patients failing SU/MET; and to estimate the glycemic burden incurred, stratified by whether HbA(1c) goal was attained and maintained. DESIGN: Longitudinal observational cohort study. SUBJECTS: Type 2 diabetes patients, 3,891, who newly initiated SU/MET between 1 January 1996 and 31 December 2000. MEASUREMENTS: Subjects were followed until insulin was added, health plan disenrolment, or until 31 December 2005. We calculated the number of months subjects continued SU/MET therapy alone, in total, and during periods of inadequate glycemic control; the A1C reached during those time periods; and total glycemic burden, defined as the estimated cumulative monthly difference between measured A1C and 8%. RESULTS: During a mean follow-up of 54.6 ± 28.6 months, 41.9% of the subjects added insulin, and 11.8% received maximal doses of both oral agents. Over half of SU/MET patients attained but failed to maintain A1C of 8%, yet continued SU/MET therapy for an average of nearly 3 years, sustaining glycemic burden equivalent to nearly 32 months of A1C levels of 9%. Another 18% of patients never attained the 8% goal with SU/MET, yet continued that therapy for an average of 30 months, reaching mean A1C levels of 10%. CONCLUSIONS: Despite inadequate glycemic control, a minority of patients added insulin or maximized oral agent doses, thus, incurring substantial glycemic burden on SU/MET. Additional studies are needed to examine the benefits of rapid titration to maximum doses and earlier initiation of insulin therapy

Body Mass Index and Employment-Based Health Insurance

<p>Abstract</p> <p>Background</p> <p>Obese workers incur greater health care costs than normal weight workers. Possibly viewed by employers as an increased financial risk, they may be at a disadvantage in procuring employment that provides health insurance. This study aims to evaluate the association between body mass index [BMI, weight in kilograms divided by the square of height in meters] of employees and their likelihood of holding jobs that include employment-based health insurance [EBHI].</p> <p>Methods</p> <p>We used the 2004 Household Components of the nationally representative Medical Expenditure Panel Survey. We utilized logistic regression models with provision of EBHI as the dependent variable in this descriptive analysis. The key independent variable was BMI, with adjustments for the domains of demographics, social-economic status, workplace/job characteristics, and health behavior/status. BMI was classified as normal weight (18.5–24.9), overweight (25.0–29.9), or obese (≥ 30.0). There were 11,833 eligible respondents in the analysis.</p> <p>Results</p> <p>Among employed adults, obese workers [adjusted probability (AP) = 0.62, (0.60, 0.65)] (<it>P </it>= 0.005) were more likely to be employed in jobs with EBHI than their normal weight counterparts [AP = 0.57, (0.55, 0.60)]. Overweight workers were also more likely to hold jobs with EBHI than normal weight workers, but the difference did not reach statistical significance [AP = 0.61 (0.58, 0.63)] (<it>P </it>= 0.052). There were no interaction effects between BMI and gender or age.</p> <p>Conclusion</p> <p>In this nationally representative sample, we detected an association between workers' increasing BMI and their likelihood of being employed in positions that include EBHI. These findings suggest that obese workers are more likely to have EBHI than other workers.</p

Using quantile regression to investigate racial disparities in medication non-adherence

<p>Abstract</p> <p>Background</p> <p>Many studies have investigated racial/ethnic disparities in medication non-adherence in patients with type 2 diabetes using common measures such as medication possession ratio (MPR) or gaps between refills. All these measures including MPR are quasi-continuous and bounded and their distribution is usually skewed. Analysis of such measures using traditional regression methods that model mean changes in the dependent variable may fail to provide a full picture about differential patterns in non-adherence between groups.</p> <p>Methods</p> <p>A retrospective cohort of 11,272 veterans with type 2 diabetes was assembled from Veterans Administration datasets from April 1996 to May 2006. The main outcome measure was MPR with quantile cutoffs Q1-Q4 taking values of 0.4, 0.6, 0.8 and 0.9. Quantile-regression (QReg) was used to model the association between MPR and race/ethnicity after adjusting for covariates. Comparison was made with commonly used ordinary-least-squares (OLS) and generalized linear mixed models (GLMM).</p> <p>Results</p> <p>Quantile-regression showed that Non-Hispanic-Black (NHB) had statistically significantly lower MPR compared to Non-Hispanic-White (NHW) holding all other variables constant across all quantiles with estimates and p-values given as -3.4% (p = 0.11), -5.4% (p = 0.01), -3.1% (p = 0.001), and -2.00% (p = 0.001) for Q1 to Q4, respectively. Other racial/ethnic groups had lower adherence than NHW only in the lowest quantile (Q1) of about -6.3% (p = 0.003). In contrast, OLS and GLMM only showed differences in mean MPR between NHB and NHW while the mean MPR difference between other racial groups and NHW was not significant.</p> <p>Conclusion</p> <p>Quantile regression is recommended for analysis of data that are heterogeneous such that the tails and the central location of the conditional distributions vary differently with the covariates. QReg provides a comprehensive view of the relationships between independent and dependent variables (i.e. not just centrally but also in the tails of the conditional distribution of the dependent variable). Indeed, without performing QReg at different quantiles, an investigator would have no way of assessing whether a difference in these relationships might exist.</p

Correlations Between Gene Expression and Mercury Levels in Blood of Boys With and Without Autism

Gene expression in blood was correlated with mercury levels in blood of 2- to 5-year-old boys with autism (AU) compared to age-matched typically developing (TD) control boys. This was done to address the possibility that the two groups might metabolize toxicants, such as mercury, differently. RNA was isolated from blood and gene expression assessed on whole genome Affymetrix Human U133 expression microarrays. Mercury levels were measured using an inductively coupled plasma mass spectrometer. Analysis of covariance (ANCOVA) was performed and partial correlations between gene expression and mercury levels were calculated, after correcting for age and batch effects. To reduce false positives, only genes shared by the ANCOVA models were analyzed. Of the 26 genes that correlated with mercury levels in both AU and TD boys, 11 were significantly different between the groups (P(Diagnosis*Mercury) ≤ 0.05). The expression of a large number of genes (n = 316) correlated with mercury levels in TD but not in AU boys (P ≤ 0.05), the most represented biological functions being cell death and cell morphology. Expression of 189 genes correlated with mercury levels in AU but not in TD boys (P ≤ 0.05), the most represented biological functions being cell morphology, amino acid metabolism, and antigen presentation. These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children

Mindful "Vitality in Practice": an intervention to improve the work engagement and energy balance among workers; the development and design of the randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Modern working life has become more mental and less physical in nature, contributing to impaired mental health and a disturbed energy balance. This may result in mental health problems and overweight. Both are significant threats to the health of workers and thus also a financial burden for society, including employers. Targeting work engagement and energy balance could prevent impaired mental health and overweight, respectively.</p> <p>Methods/Design</p> <p>The study population consists of highly educated workers in two Dutch research institutes. The intervention was systematically developed, based on the Intervention Mapping (IM) protocol, involving workers and management in the process. The workers' needs were assessed by combining the results of interviews, focus group discussions and a questionnaire with available literature. Suitable methods and strategies were selected resulting in an intervention including: eight weeks of customized mindfulness training, followed by eight sessions of e-coaching and supporting elements, such as providing fruit and snack vegetables at the workplace, lunch walking routes, and a buddy system. The effects of the intervention will be evaluated in a RCT, with measurements at baseline, six months (T1) and 12 months (T2). In addition, cost-effectiveness and process of the intervention will also be evaluated.</p> <p>Discussion</p> <p>At baseline the level of work engagement of the sample was "average". Of the study population, 60.1% did not engage in vigorous physical activity at all. An average working day consists of eight sedentary hours. For the Phase II RCT, there were no significant differences between the intervention and the control group at baseline, except for vigorous physical activity. The baseline characteristics of the study population were congruent with the results of the needs assessment. The IM protocol used for the systematic development of the intervention produced an appropriate intervention to test in the planned RCT.</p> <p>Trial registration number</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2199">NTR2199</a></p