82 research outputs found

    Re-Considering State-Society Dynamics in Turkey’s Kurdish Southeast

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    State-society relations in Turkey’s Kurdish southeast have long been characterized as pitting a powerful and determined state against a reluctant, resistant, but largely overwhelmed population. Such an image of a binary, state versus society relationship is readily substantiated by a myriad historical and contemporary examples: multiple Kurdish rebellions against the central state, cultural and political dissent articulated from poetry to political parties, emergency rule law in Kurdish-major..

    Linking Monitoring and Data Analysis to Predictions and Decisions for the Range-wide Eastern Black Rail Status Assessment

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    The US Fish and Wildlife Service (USFWS) has initiated a re-envisioned approach for providing decision makers with the best available science and synthesis of that information, called the Species Status Assessment (SSA), for endangered species decision making. The SSA report is a descriptive document that provides decision makers with an assessment of the current and pre - dicted future status of a species. These analyses support all manner of decisions under the US Endangered Species Act, such as listing, reclassification, and recovery planning. Novel scientific analysis and predictive modeling in SSAs could be an important part of rooting conservation decisions in current data and cutting edge analytical and modeling techniques. Here, we describe a novel analysis of available data to assess the current condition of eastern black rail Laterallus jamai censis jamai cen sis across its range in a dynamic occupancy analysis. We used the results of the ana lysis to develop a site occupancy projection model where the model parameters (initial occupancy, site persistence, colo nization) were linked to environmental covariates, such as land management and land cover change (sea-level rise, development, etc.). We used the projection model to predict future status under multiple sea-level rise and habitat management scenarios. Occupancy probability and site colonization were low in all analysis units, and site persistence was also low, suggesting low resiliency and redundancy currently. Extinction probability was high for all analysis units in all simulated scenarios except one with significant effort to preserve existing habitat, suggesting low future re siliency and redundancy. With the results of these data analyses and predictive models, the USFWS concluded that protections of the Endangered Species Act were warranted for this subspecies

    Moving Cages Further Offshore: Effects on Southern Bluefin Tuna, T. maccoyii, Parasites, Health and Performance

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    The effects of offshore aquaculture on SBT health (particularly parasitic infections and haematology) and performance were the main aim of this study. Two cohorts of ranched Southern Bluefin tuna (SBT) (Thunnus maccoyii) were monitored throughout the commercial season, one maintained in the traditional near shore tuna farming zone and one maintained further offshore. SBT maintained offshore had reduced mortality, increased condition index at week 6 post transfer, reduced blood fluke and sealice loads, and haematological variables such as haemoglobin or lysozyme equal to or exceeding near shore maintained fish. The offshore cohort had no Cardicola forsteri and a 5% prevalence of Caligus spp., compared to a prevalence of 85% for Cardicola forsteri and 55% prevalence for Caligus spp. near shore at 6 weeks post transfer. This study is the first of its kind to examine the effects of commercial offshore sites on farmed fish parasites, health and performance

    Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

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    Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting ∼10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3′-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50–6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders

    Early detection and counselling intervention of asthma symptoms in preschool children: study design of a cluster randomised controlled trial

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    Background. Prevention of childhood asthma is an important public health objective. This study evaluates the effectiveness of early detection of preschool children with asthma symptoms, followed by a counselling intervention at preventive child health centres. Early detection and counselling is expected to reduce the prevalence of asthma symptoms and improve health-related quality of life at age 6 years. Methods/design. This cluster randomised controlled trial was embedded within the Rotterdam population-based prospective cohort study Generation R in which 7893 children (born between April 2002 and January 2006) participated in the postnatal phase. Sixteen child health centres are involved, randomised into 8 intervention and 8 control centres. Since June 2005, an early detection tool has been applied at age 14, 24, 36 and 45 months at the intervention centres. Children who met the intervention criteria received counselling intervention (personal advice to parents to prevent smoke exposure of the child, and/or referral to the general practitioner or asthma nurse). The primary outcome was asthma diagnosis at age 6 years. Secondary outcomes included frequency and severity of asthma symptoms, health-related quality of life, fractional exhaled nitric oxide and airway resistance at age 6 years. Analysis was according to the intention-to-treat principle. Data collection will be completed end 2011. Discussion. This study among preschool children provides insight into the effectiveness of early detection of asthma symptoms followed by a counselling intervention at preventive child health centres. Trial registration. Current Controlled Trials ISRCTN15790308

    Molecular Ecology and Natural History of Simian Foamy Virus Infection in Wild-Living Chimpanzees

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    Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) and Ebola virus. Simian foamy viruses (SFVs) are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes) using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724) were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706) or viral nucleic acids (n = 392). SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz); however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp), pol-RT (717 bp), and pol-IN (425 bp) sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey species, indicating cross-species transmission of SFVs in the wild. These data indicate that SFVcpz (i) is widely distributed among all chimpanzee subspecies; (ii) is shed in fecal samples as viral RNA; (iii) is transmitted predominantly by horizontal routes; (iv) is prone to superinfection and recombination; (v) has co-evolved with its natural host; and (vi) represents a sensitive marker of population structure that may be useful for chimpanzee taxonomy and conservation strategies

    Constitutional dynamics and partisan conflict:A comparative assessment of multi-level systems in Europe

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    publication-status: Publishedtypes: ArticleThe case studies revealed that the constitutional nature of a multi-level system indeed shapes its modes of day-to-day intergovernmental coordination and, with it, the way competences are (re)allocated in the longer term. Both in federal arrangements and in confederations, the ‘subunits’ – whose status is constitutionally protected – could more easily defend their decision-making capacity within their areas of jurisdiction because they can veto changes in the allocation of competences, an advantage lower-level governments in regionalized systems do not enjoy. Similarly, in federal and confederal systems day-to-day interaction in Inter Governmental Relations (IGR) predominantly took place in multilateral structures, while in regionalized systems bilateralism was more pronounced. The relative influence of party-political (in)congruence on IGR, in contrast, was more varied than theoretically expected

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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