DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe

STUDY OBJECTIVE Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN Retrospective case-control study. SETTING A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

The Social Imaginary of Culture/Civilization in the Arabic Literary Tradition

Charles Taylor’s contribution to social imaginaries offers an interpretive framework for better understanding modernity as secularity. One of its main aspects is conceiving of human society in linear, homogenous time (secular time). Looking into the Arabic intellectual tradition, I will argue in my paper that Taylor’s framework can help us understand major social and intellectual transformations. The Ottoman and Arabic modernization process during the 19th century has often been understood by focusing on certain core concepts. One of these is tamaddun, usually translated as “civilization.” I will be mostly talking about the works of two “pioneers” of Arab modernity (which is traditionally referred to as an-nahḍa, the so-called Arab Renaissance): the Syrian Fransīs Marrāsh and the Egyptian Rifāʿa aṭ-Ṭahṭāwī. First I will focus on Marrāsh’s didactic novel “The Forest of Truth” (1865), as it offers a complex view of tamaddun, which has sometimes been construed as merely a social and political reform program. The category of "social imaginary,” however, is useful in grasping the wider semantic scope of this concept, which is reading it as a signifier for human history conceived of in secular time, as Taylor defines it. This conceptualization of human history functioning within the immanent frame can also be observed in the introduction to “The Extraction of Pure Gold in the Description of Paris” (1834), a systematic account of a travel experience in France that was written by the other “pioneer,” aṭ-Ṭahṭāwī. Finally, in translating tamaddun as “the modern social imaginary of civilization/culture,” the talk aims to consider this imaginary as a major factor in the emergence of the “secular age.” Furthermore, it suggests the importance of studying (quasi-) literary texts, such as historiographical, geographical, and self-narratives in the Arabic literary tradition, in order to further elaborate continuities and ruptures in social imaginaries.

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban.

Fast adaptive responses in the oral jaw of Lake Victoria cichlids

Rapid morphological changes in response to fluctuating natural environments are a common phenomenon in species that undergo adaptive radiation. The dramatic ecological changes in Lake Victoria provide a unique opportunity to study environmental effects on cichlid morphology. This study shows how four haplochromine cichlids adapted their premaxilla to a changed diet over the past 30 years. Directly after the diet change toward larger and faster prey in the late 1980s, the premaxilla (upper jaw) changed in a way that is in agreement with a more food manipulating feeding style. During the 2000s, two zooplanktivorous species showed a reversal of morphological changes after returning to their original diet, whereas two other species showed no reversal of diet and morphology. These rapid changes indicate a potential for extremely fast adaptive responses to environmental fluctuations, which are likely inflicted by competition release and increase, and might have a bearing on the ability of haplochromines to cope with environmental changes. These responses could be due to rapid genetic change or phenotypic plasticity, for which there is ample evidence in cichlid fish structures associated with food capture and processing. These versatile adaptive responses are likely to have contributed to the fast adaptive radiation of haplochromines.

Biodiversity and Fishery Sustainability in the Lake Victoria Basin: An Unexpected Marriage?

Lake Victoria is Africa’s single most important source of inland fishery production. After it was initially fished down in the first half of the 20th century, Lake Victoria became home to a series of introduced food fishes, culminating in the eventual demographic dominance of the Nile perch, Lates niloticus. Simultaneously with the changes in fish stocks, Lake Victoria experienced dramatic changes in its ecology. The lake fishery during most of the 20th century was a multispecies fishery resting on a diverse lake ecosystem, in which native food fishes were targeted. The lake ended the century with a much more productive fishery, but one in which three species — two of them introduced — made up the majority of the catch. Although many fish stocks in Lake Victoria had declined before the expansion of the Nile perch population, a dramatic increase in the population size of Nile perch in the 1980s roughly coincided with the drastic decline or disappearance of many indigenous species. Now, two decades after the rise of Nile perch in Lake Victoria, this species has shown signs of being overfished, and some of the native species that were in retreat — or even thought extinct — are now reemerging. Data on the resurgence of the indigenous species suggest that heavy fishing of Nile perch may enhance biodiversity; this has spawned renewed interest in management options that promote both fishery sustainability and biodiversity conservation.

Patterns of the Remnant Cichlid Fauna in Southern Lake Victoria. Patrones de la Fauna de Ciclidos Remanentes en el Sur del Lago Victoria

During the years 1984–1987 Lake Victoria in East Africa experienced what is probably the largest mass extinction of contemporary vertebrates. Within a decade about 200 endemic species of haplochromine cichlids disappeared. The extinctions that occurred in the 1980s have been documented predominantly on species of offshore and sub-littoral waters in the Mwanza Gulf of southern Lake Victoria. Although the littoral fauna of southern Lake Victoria had not been examined in detail, their diversity seemed less affected by the changes in the ecosystem. We give results of the first comprehensive inventory of the littoral cichlid fauna in southern Lake Victoria and discuss its conservation status. We also report on new developments in the sub-littoral fauna after 1990. More than 50 littoral and 15 sub-littoral stations were sampled between the years 1991 to 1995. Of the littoral stations, 34 were sampled for the first time. One hundred sixty three species of haplochromines were collected. Of these, 102 species were previously unknown. About two thirds of them live in rocky areas that were sampled for the first time. Littoral rocky habitats harbored the highest diversity. Since 1990, however, 13 more species disappeared from established sampling stations in littoral habitats. Fishing practices, spreading of exotic fishes, water hyacinth, and eutrophication are considered important threats to the littoral fauna. Also in the upper sub-littoral the number of species declined further. On deeper sub-littoral mud bottoms individual and species numbers increased again, although they are nowhere close to those found before the Nile perch (Lates niloticus) upsurge. This fauna differs from the well studied pre-Nile perch fauna. At well-established sampling stations, the sub-littoral zone is dominated by previously unknown species, and some known species have performed dramatic habitat shifts.

The sonic hedgehog signaling pathway and the development of pharyngeal arch Derivatives in Haplochromis piceatus, a Lake Victoria cichlid

Objectives Pharyngeal arches develop in the head and neck regions, and give rise to teeth, oral jaws, the hyoid bone, operculum, gills, and pharyngeal jaws in teleosts. In this study, the expression patterns of genes in the sonic hedgehog (shh), wnt, ectodysplasin A (eda), and bone morphogenetic protein (bmp) pathways were investigated in the pharyngeal arches of Haplochromis piceatus, one of the Lake Victoria cichlids. Furthermore, the role of the shh pathway in pharyngeal arch development in H. piceatus larvae was investigated. Methods The expression patterns of lymphocyte enhancer binding factor 1 (lef1), ectodysplasin A receptor (edar), shh, patched 1 (ptch1), bmp4, sp5 transcription factor (sp5), sclerostin domain containing 1a (sostdc1a), and dickkopf 1 (dkk1) were investigated in H. piceatus larvae by in situ hybridization. The role of the shh pathway was investigated through morphological phenotypic characterization after its inhibition. Results We found that lef1, edar, shh, ptch1, bmp4, dkk1, sostdc1a, and sp5 were expressed not only in the teeth, but also in the operculum and gill filaments of H piceatus larvae. After blocking the shh pathway using cyclopamine, we observed ectopic shh expression and the disappearance of ptch1 expression. After six weeks of cyclopamine treatment, an absence of teeth in the oral upper jaws and a poor outgrowth of premaxilla, operculum, and gill filaments in juvenile H. piceatus were observed. Conclusions These results suggest that the shh pathway is important for the development of pharyngeal arch derivatives such as teeth, premaxilla, operculum, and gill filaments in H. piceatus.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS).

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

Tree architecture in a Bornean lowland rain forest: intraspecific and interspecific patterns

Intraspecific and interspecific architectural patterns were studied for eight tree species of a Bornean rain forest. Trees 5--19 m tall in two 4-ha permanent sample plots in primary forest were selected, and three light descriptors and seven architectural traits for each tree were measured. Two general predictions were made: (1) Slow growing individuals (or short ones) encounter lower light, and have flatter crowns, fewer leaf layers, and thinner stems, than do fast growing individuals (or tall ones). (2) Species with higher shade-tolerance receive less light and have flatter crowns, fewer leaf layers, and thinner stems, than do species with lower shade-tolerance. Shade-tolerance is assumed to decrease with maximum growth rate, mortality rate, and adult stature of a species.

O Wee! o wapen! ...

Kurze Komödie, Verdauungsprobleme betreffend ; beteiligte Personen: Diego, Großmeister v. Kastilien, Admiral v. Duynkercken, Pier de Palo, Frans Barbier, Releve Moustache u.A.

Planktonic foraminifera of the Mediterranean Sea

A high-resolution biochronology is presented for the Late Quaternary of the central Mediterranean. In the Late Pleistocene-Holocene successions three assemblage zones are distinguished on the basis of frequency patterns of planktic foraminifera. The age of these zones is determined by Accelerator Mass Spectrometry (AMS)14C dating. The zonal boundaries are dated at 12,700 yr B.P. (the end of Termination Ia) and 9600 yr B.P. (the start of Termination Ib), respectively. The AMS dates show that major changes in the planktic and benthic realms occurred synchronously over wide areas, although records of individual species may show important regional differences. In the studied areas, resedimentation processes revealed by anomalous successions of14C dates, play a far more important role than indicated by the sedimentological and micropaleontological data. Possibly these processes contribute to the very high accumulation rates in the glacial Zone III. Although the AMS technique has increased the accuracy of14C-measurements, admixture of older carbonate may still lead to substantial age differences between areas with different sedimentary regimes.

Analysis of Recent benthic foraminiferal assemblages from the oxygen minimum zone of the Pakistan continental margin

Live (Rose Bengal stained) and dead benthic foraminiferal communities (hard-shelled species only) from the Pakistan continental margin oxygen minimum zone (OMZ) have been studied in order to determine the relation between faunal composition and the oxygenation of bottom waters. During R.R.S. Charles Darwin Cruises 145 and 146 (12 March to May 28 2003), 11 multicores were taken on the continental margin off Karachi, Pakistan. Two transects were sampled, constituting a composite bathymetric profile from 136 m (above the OMZ in spring 2003) down to 1870 m water depth. Cores (surface area 25.5 cm2) were processed as follows: for stations situated above, and in the upper part of the OMZ, sediment slices were taken for the 0-0.5 and 0.5-1 cm intervals, and then in 1 cm intervals down to 10 cm. For the lower part of the OMZ, the second centimetre was also sliced in half-centimetre intervals. Each sample was stored in 10 % borax-buffered formalin for further processing. Onshore, the samples were wet sieved over 63 µm, 150 µm and 300 µm sieves and the residues were stained for one week in ethanol with Rose Bengal. After staining, the residue was washed again. The stained faunas were picked wet in three granulometric fractions (63-150 µm, 150-300 µm and >300 µm), down to 10 cm depth. To gain more insight into the population dynamics we investigated the dead (unstained) foraminifera in the 2-3 cm level for the fractions 150-300 µm and >300 µm. The fractions >300 µm and 150-300 µm show nearly the same faunal distribution and therefore the results are presented here for both fractions combined (i.e. the >150 µm fraction). Live foraminiferal densities show a clear maximum in the first half centimetre of the sediment; only few specimens are found down to 4 cm depth. The faunas exhibit a clear zonation across the Pakistan margin OMZ. Down to 500 m water depth, Uvigerina ex gr. U. semiornata and Bolivina aff. B. dilatata dominate the assemblages. These taxa are largely restricted to the upper cm of the sediment. They are adapted to the very low bottom-water oxygen values (ab. 0.1 ml/l in the OMZ core) and the extremely high input of organic carbon on the upper continental slope. The lower part of the OMZ is characterized by cosmopolitan faunas, containing also some taxa that in other areas have been described in deep infaunal microhabitats.