Differences Between Posterior and Anterior Acute Ischaemic Circulation Strokes in 1449 Consecutive Patients

Background: The current data comparing posterior and anterior circulation strokes with regards to clinical, etiological, radiological and outcome factors are conflicting. We searched for distinguishing features between both territories in 1'449 consecutive acute ischemic stroke patients. Methods: All consecutive patients with acute ischemic stroke admitted to a single stroke unit from January 2003 to July 2008 were included in a prospective registry. Territory of acute stroke was determined by a combination of neuroimaging (MRI and / CT / CTP) and clinical symptoms and signs. Patients with uncertain localisation and patients with simultaneous strokes in the anterior and posterior circulation were excluded from this analysis. Results: Of a total of 1728 patients, 466 (17.0%) had had posterior, 983 (56.8%) anterior, 136 (7.9%) unknown territory, and 43 (2.5%) simultaneous posterior and anterior territory stroke. Of 39 variables that were compared, 29 differed significantly in univariate analysis, including less dependency (OR_0.50) and mortality (OR_0.56) at 3 months in posterior stroke. In multivariate analysis (see table), male gender, lacunar mechanism, arterial dissection and endovascular recanalisation were more frequent in posterior stroke, and admission NIHSS and IV-thrombolysis rate were lower. Significant acute arterial pathology (_50% stenosis) was less frequently found on acute imaging in posterior stroke (OR_0.33). Of 633 patients with significant arterial pathology, it was more frequently present intracranially in posterior (OR_1.62) and extracranially in anterior stroke (OR _ 0.87). In 610 patients where recanalisation was assessed at 24 hours, intracranial (OR_0.26), extracranial (OR_0.25) and overall recanalisation (OR_0.34) was less frequent in the posterior circulation. Conclusions: Acute posterior strokes are less severe and recover better, despite lower IV thrombolysis and recanalisation rates. They are more frequently due to lacunes and dissections and have less arterial pathology burden then anterior circulation strokes.

Connectivity differences in brain networks.

The scenario considered here is one where brain connectivity is represented as a network and an experimenter wishes to assess the evidence for an experimental effect at each of the typically thousands of connections comprising the network. To do this, a univariate model is independently fitted to each connection. It would be unwise to declare significance based on an uncorrected threshold of α=0.05, since the expected number of false positives for a network comprising N=90 nodes and N(N-1)/2=4005 connections would be 200. Control of Type I errors over all connections is therefore necessary. The network-based statistic (NBS) and spatial pairwise clustering (SPC) are two distinct methods that have been used to control family-wise errors when assessing the evidence for an experimental effect with mass univariate testing. The basic principle of the NBS and SPC is the same as supra-threshold voxel clustering. Unlike voxel clustering, where the definition of a voxel cluster is unambiguous, 'clusters' formed among supra-threshold connections can be defined in different ways. The NBS defines clusters using the graph theoretical concept of connected components. SPC on the other hand uses a more stringent pairwise clustering concept. The purpose of this article is to compare the pros and cons of the NBS and SPC, provide some guidelines on their practical use and demonstrate their utility using a case study involving neuroimaging data.

Content-specific gender differences in emotion ratings from early to late adulthood.

The investigation of gender differences in emotion has attracted much attention given the potential ramifications on our understanding of sexual differences in disorders involving emotion dysregulation. Yet, research on content-specific gender differences across adulthood in emotional responding is lacking. The aims of the present study were twofold. First, we sought to investigate to what extent gender differences in the self-reported emotional experience are content specific. Second, we sought to determine whether gender differences are stable across the adult lifespan. We assessed valence and arousal ratings of 14 picture series, each of a different content, in 94 men and 118 women aged 20 to 81. Compared to women, men reacted more positively to erotic images, whereas women rated low-arousing pleasant family scenes and landscapes as particularly positive. Women displayed a disposition to respond with greater defensive activation (i.e., more negative valence and higher arousal), in particular to the most arousing unpleasant contents. Importantly, significant interactions between gender and age were not found for any single content. This study makes a novel contribution by showing that gender differences in the affective experiences in response to different contents persist across the adult lifespan. These findings support the "stability hypothesis" of gender differences across age.

Physiological differences between cycling and running

This review compares the differences in systemic responses (VO2max, anaerobic threshold, heart rate and economy) and in underlying mechanisms of adaptation (ventilatory and hemodynamic and neuromuscular responses) between cycling and running. VO2max is specific to the exercise modality. Overall, there is more physiological training transfer from running to cycling than vice-versa. Several other physiological differences between cycling and running are discussed: HR is different between the two activities both for maximal and sub-maximal intensities. The delta efficiency is higher in running. Ventilation is more impaired in cycling than running due to mechanical constraints. Central fatigue and decrease in maximal strength are more important after prolonged exercise in running than in cycling.

Iowa Utilities Board Fiscal Year 2005 Regulatory Plan Pursuant to Executive Order Nine, August 2, 2004

Regulatory Plan for Fiscal Year 2005

Iowa Utilities Board Fiscal Year 2003 Regulatory Plan Prepared Pursuant to Executive Order Nine, August 26, 2002

Regulatory Plan for Fiscal Year 2003

The Swiss regulatory framework for pædiatric health research

Medical research on minors entails both risks and benefits. Under Swiss law, clinical trials on children, including nontherapeutic drug trials, are permissible. However, ethics committees must systematically verify that all clinical studies have a favorable risk-benefit profile. Additional safeguards are designed to ensure that children are not unnecessarily involved in research and that proper consent is always obtained. Federal Swiss law is undergoing revision to extend these protections beyond clinical trials to a broad array of health research. The Swiss drug agency also seeks to improve the incentives for pharmaceutical firms to develop new paediatric drugs and relevant paediatric drug labels.

Immunosuppressive effects of streptozotocin-induced diabetes result in absolute lymphopenia and a relative increase of T regulatory cells.

OBJECTIVE Streptozotocin (STZ) is the most widely used diabetogenic agent in animal models of islet transplantation. However, the immunomodifying effects of STZ and the ensuing hyperglycemia on lymphocyte subsets, particularly on T regulatory cells (Tregs), remain poorly understood. RESEARCH DESIGN AND METHODS This study evaluated how STZ-induced diabetes affects adaptive immunity and the consequences thereof on allograft rejection in murine models of islet and skin transplantation. The respective toxicity of STZ and hyperglycemia on lymphocyte subsets was tested in vitro. The effect of hyperglycemia was assessed independently of STZ in vivo by the removal of transplanted syngeneic islets, using an insulin pump, and with rat insulin promoter diphtheria toxin receptor transgenic mice. RESULTS Early lymphopenia in both blood and spleen was demonstrated after STZ administration. Direct toxicity of STZ on lymphocytes, particularly on CD8(+) cells and B cells, was shown in vitro. Hyperglycemia also correlated with blood and spleen lymphopenia in vivo but was not lymphotoxic in vitro. Independently of hyperglycemia, STZ led to a relative increase of Tregs in vivo, with the latter retaining their suppressive capacity in vitro. The higher frequency of Tregs was associated with Treg proliferation in the blood, but not in the spleen, and higher blood levels of transforming growth factor-β. Finally, STZ administration delayed islet and skin allograft rejection compared with naive mice. CONCLUSIONS These data highlight the direct and indirect immunosuppressive effects of STZ and acute hyperglycemia, respectively. Thus, these results have important implications for the future development of tolerance-based protocols and their translation from the laboratory to the clinic.

Molecular changes underlying mammalian phenotypic innovation

Mammals are characterized by specific phenotypic traits that include lactation, hair, and relatively large brains with unique structures. Individual mammalian lineages have, in turn, evolved characteristic traits that distinguish them from others. These include obvious anatom¬ical differences but also differences related to reproduction, life span, cognitive abilities, be¬havior. and disease susceptibility. However, the molecular basis of the diverse mammalian phenotypes and the selective pressures that shaped their evolution remain largely unknown. In the first part of my thesis, I analyzed the genetic factors associated with the origin of a unique mammalian phenotype lactation and I studied the selective pressures that forged the transition from oviparity to viviparity. Using a comparative genomics approach and evolutionary simulations, I showed that the emergence of lactation, as well as the appear¬ance of the casein gene family, significantly reduced selective pressure on the major egg-yolk proteins (the vitellogenin family). This led to a progressive loss of vitellogenins, which - in oviparous species - act as storage proteins for lipids, amino acids, phosphorous and calcium in the isolated egg. The passage to internal fertilization and placentation in therian mam¬mals rendered vitellogenins completely dispensable, which ended in the loss of the whole gene family in this lineage. As illustrated by the vitellogenin study, changes in gene content are one possible underlying factor for the evolution of mammalian-specific phenotypes. However, more subtle genomic changes, such as mutations in protein-coding sequences, can also greatly affect the phenotypes. In particular, it was proposed that changes at the level of gene reg¬ulation could underlie many (or even most) phenotypic differences between species. In the second part of my thesis, I participated in a major comparative study of mammalian tissue transcriptomes, with the goal of understanding how evolutionary forces affected expression patterns in the past 200 million years of mammalian evolution. I showed that, while com¬parisons of gene expressions are in agreement with the known species phylogeny, the rate of expression evolution varies greatly among lineages. Species with low effective population size, such as monotremes and hominoids, showed significantly accelerated rates of gene expression evolution. The most likely explanation for the high rate of gene expression evolution in these lineages is the accumulation of mildly deleterious mutations in regulatory regions, due to the low efficiency of purifying selection. Thus, our observations are in agreement with the nearly neutral theory of molecular evolution. I also describe substantial differences in evolutionary rates between tissues, with brain being the most constrained (especially in primates) and testis significantly accelerated. The rate of gene expression evolution also varies significantly between chromosomes. In particular, I observed an acceleration of gene expression changes on the X chromosome, probably as a result of adaptive processes associated with the origin of therian sex chromosomes. Lastly, I identified several individual genes as well as co-regulated expression modules that have undergone lineage specific expression changes and likely under¬lie various phenotypic innovations in mammals. The methods developed during my thesis, as well as the comprehensive gene content analyses and transcriptomics datasets made available by our group, will likely prove to be useful for further exploratory analyses of the diverse mammalian phenotypes.

Recent human evolution has shaped geographical differences in susceptibility to disease

Background: Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies.Results: We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions: Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.

Methodology for studying the numerical speed of sound in finite differences schemes

The space and time discretization inherent to all FDTD schemesintroduce non-physical dispersion errors, i.e. deviations ofthe speed of sound from the theoretical value predicted bythe governing Euler differential equations. A generalmethodologyfor computing this dispersion error via straightforwardnumerical simulations of the FDTD schemes is presented.The method is shown to provide remarkable accuraciesof the order of 1/1000 in a wide variety of twodimensionalfinite difference schemes.

Division of Workers' Compensation Regulatory Plan for State Fiscal Year, 2005

This plan is intended to implement Governor Vilsack’s Executive Order Number 9, V, signed September 14, 1999. This plan provides the Division of Workers’ Compensation anticipated regulatory actions for potential rule making activity for State Fiscal Year 2005, which began July 1, 2004, and thereafter.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS: THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

Demographic and geographic vascular risk factor differences in European young adults with ischemic stroke: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. METHODS: We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. RESULTS: In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. CONCLUSIONS: Primary preventive strategies for ischemic stroke in young adults-having high rate of modifiable risk factors-should be targeted according to sex and age at continental level.