Frequent use of paracetamol and risk of allergic disease among women in an Ethiopian population

Introduction The hypothesis that paracetamol might increase the risk of asthma and other allergic diseases have gained support from a range of independent studies. However, in studies based in developed countries, the possibility that paracetamol and asthma are associated through aspirin avoidance is difficult to exclude. Objectives To explore this hypothesis among women in a developing country, where we have previously reported aspirin avoidance to be rare. Methods In 2005/6 a population based cohort of 1065 pregnant women was established in Butajira, Ethiopia and baseline demographic data collected. At 3 years post birth, an interview-based questionnaire administered to 945 (94%) of these women collected data on asthma, eczema, and hay fever in the past 12 month, frequency of paracetamol use and potential confounders. Allergen skin tests to Dermatophagoides pteronyssinus and cockroach were also performed. The independent effects of paracetamol use on allergic outcomes were determined using multiple logistic regression analysis. Findings The prevalence of asthma, eczema and hay fever was 1.7%, 0.9% and 3.8% respectively; of any one of these conditions 5.5%, and of allergen sensitization 7.8%. Paracetamol use in the past month was reported by 29%, and associations of borderline significance were seen for eczema (adjusted OR (95% CI) = 8.51 (1.68 to 43.19) for 1–3 tablets and 2.19 (0.36 to 13.38) for ≥4 tablets, compared to no tablets in the past month; overall p = 0.055) and for ‘any allergic condition’ (adjusted OR (95% CI) = 2.73 (1.22 to 6.11) for 1–3 tablets and 1.35 (0.67 to 2.70) for ≥4 tablets compared to 0 in the past month; overall p = 0.071). Conclusions This study provides further cross-sectional evidence that paracetamol use increases the risk of allergic disease

GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate $\gamma$-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E

It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible. A gradual increase with each generation of the ε2 and ε3 alleles of the gene at the expense of the ε4 allele was predicted from the model. The ε2 allele frequency was found to increase slightly more rapidly than that for ε3, although there was no statistically significant difference between the two. Our result may explain the recent evolutionary history of the epsilon 2, 3 and 4 alleles of the apolipoprotein E gene and has wider relevance for genes affecting human longevity

Where do firms manage earnings?

Despite decades of research on how, why, and when companies manage earnings, there is a paucity of evidence about the geographic location of earnings management within multinational firms. In this study, we examine where companies manage earnings using a sample of 2,067 U.S. multinational firms from 1994 to 2009. We predict and find that firms with extensive foreign operations in weak rule of law countries have more foreign earnings management than companies with subsidiaries in locations where the rule of law is strong. We also find some evidence that profitable firms with extensive tax haven subsidiaries manage earnings more than other firms and that the earnings management is concentrated in foreign income. Apart from these results, we find that most earnings management takes place in domestic income, not foreign income.Arthur Andersen (Firm) (Arthur Andersen Faculty Fund

Replacement of Retinyl Esters by Polyunsaturated Triacylglycerol Species in Lipid Droplets of Hepatic Stellate Cells during Activation

Activation of hepatic stellate cells has been recognized as one of the first steps in liver injury and repair. During activation, hepatic stellate cells transform into myofibroblasts with concomitant loss of their lipid droplets (LDs) and production of excessive extracellular matrix. Here we aimed to obtain more insight in the dynamics and mechanism of LD loss. We have investigated the LD degradation processes in rat hepatic stellate cells in vitro with a combined approach of confocal Raman microspectroscopy and mass spectrometric analysis of lipids (lipidomics). Upon activation of the hepatic stellate cells, LDs reduce in size, but increase in number during the first 7 days, but the total volume of neutral lipids did not decrease. The LDs also migrate to cellular extensions in the first 7 days, before they disappear. In individual hepatic stellate cells. all LDs have a similar Raman spectrum, suggesting a similar lipid profile. However, Raman studies also showed that the retinyl esters are degraded more rapidly than the triacylglycerols upon activation. Lipidomic analyses confirmed that after 7 days in culture hepatic stellate cells have lost most of their retinyl esters, but not their triacylglycerols and cholesterol esters. Furthermore, we specifically observed a large increase in triacylglycerol-species containing polyunsaturated fatty acids, partly caused by an enhanced incorporation of exogenous arachidonic acid. These results reveal that lipid droplet degradation in activated hepatic stellate cells is a highly dynamic and regulated process. The rapid replacement of retinyl esters by polyunsaturated fatty acids in LDs suggests a role for both lipids or their derivatives like eicosanoids during hepatic stellate cell activation

Supramolecular networks stabilise and functionalise black phosphorus

The limited stability of the surface of black phosphorus (BP) under atmospheric conditions is a significant constraint on the exploitation of this layered material and its few layer analogue, phosphorene, as an optoelectronic material. Here we show that supramolecular networks stabilised by hydrogen bonding can be formed on BP, and that these monolayer-thick films can passivate the BP surface and inhibit oxidation under ambient conditions. The supramolecular layers are formed by solution deposition and we use atomic force microscopy to obtain images of the BP surface and hexagonal supramolecular networks of trimesic acid and melamine cyanurate (CA.M) under ambient conditions. The CA.M network is aligned with rows of phosphorus atoms and forms large domains which passivate the BP surface for more than a month, and also provides a stable supramolecular platform for the sequential deposition of 1,2,4,5-tetrakis(4-carboxyphenyl)benzene to form supramolecular heterostructures

Increasing socioeconomic inequalities in first acute myocardial infarction in Scotland, 1990–92 and 2000–02

<p>Background: Despite substantial declines, Ischaemic Heart Disease (IHD) remains the largest cause of death in Scotland and mortality rates are among the worst in Europe. There is evidence of strong, persisting regional and socioeconomic inequalities in IHD mortality, with the majority of such deaths being due to Acute Myocardial Infarction (AMI). We examine the changes in socioeconomic and geographic inequalities in first AMI events in Scotland and their interactions with age and gender.</p> <p>Methods: We used linked hospital discharge and death records covering the Scottish Population (5.1 million). Risk ratios (RR) of AMI incidence by area deprivation and age for men and women were estimated using multilevel Poisson modelling. Directly standardised rates were presented within these stratifications.</p> <p>Results: During 1990–92 74,213 people had a first AMI event and 56,995 in 2000–02. Adjusting for area deprivation accounted for 59% of the geographic variability in AMI incidence rates in 1990–92 and 33% in 2000–02. Geographic inequalities in male incidence reduced; RR for smaller areas (comparing area on 97.5th centile to 2.5th) reduced from 1.42 to 1.19. This was not true for women; RR increased from 1.45 to 1.59. The socioeconomic gradient in AMI incidence increased over time (p-value < 0.001) but this varied by age and gender. The gradient across deprivation categories for male incidence in 1990–92 was most pronounced at younger ages; RR of AMI in the most deprived areas compared to the least was 2.6 (95% CI: 1.6–4.3) for those aged 45–59 years and 1.6 (1.1–2.5) at 60–74 years. This association was also evident in women with even stronger socioeconomic gradients; RRs for these age groups were 4.4 (3.4–5.5), and 1.9 (1.7–2.2). Inequalities increased by 2000–02 for both sexes; RR for men aged 45–59 years was 3.3 (3.0–3.6) and for women was 5.6 (4.1–7.7)</p> <p>Conclusion: Relative socioeconomic inequalities in AMI incidence have increased and gradients are steepest in young women. The geographical patterning of AMI incidence cannot be fully explained by socioeconomic deprivation. The reduction of inequalities in AMI incidence is key to reducing overall inequalities in mortality and must be a priority if Scotland is to achieve its health potential.</p&gt

Odor Fear Conditioning Modifies Piriform Cortex Local Field Potentials Both during Conditioning and during Post-Conditioning Sleep

BACKGROUND: Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning. METHODOLOGY/PRINCIPAL FINDINGS: We examined piriform cortical odor responses using local field potentials (LFPs) from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naïve animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naïve rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day. CONCLUSIONS/SIGNIFICANCE: The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56

Oral Rabies Vaccination in North America: Opportunities, Complexities, and Challenges

Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues toward the development and testing of new bait-vaccine combinations that increase the chance for improved delivery and performance in the diverse meso-carnivore rabies reservoir complex in the US