43 research outputs found

    Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

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    Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH

    Review Section : Nature/Nurture Revisited I

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    Biologically oriented approaches to the study of human conflict have thus far been limited largely to the study of aggression. A sample of the literature on this topic is reviewed, drawing upon four major approaches: comparative psychology, ethology (including some popularized accounts), evolutionary-based theories, and several areas of human physiology. More sophisticated relationships between so-called "innate" and "acquired" determinants of behavior are discussed, along with the proper relevance of animal behavior studies for human behavior. Unless contained in a comprehensive theory which includes social and psychological variables, biolog ically oriented theories (although often valid within their domain) offer at best severely limited and at worst highly misleading explanations of complex social conflicts. The review concludes with a list of several positive contributions of these biological approaches and suggests that social scientists must become more knowledgeable about them.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68270/2/10.1177_002200277401800206.pd

    Dust Devil Sediment Transport: From Lab to Field to Global Impact

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    The impact of dust aerosols on the climate and environment of Earth and Mars is complex and forms a major area of research. A difficulty arises in estimating the contribution of small-scale dust devils to the total dust aerosol. This difficulty is due to uncertainties in the amount of dust lifted by individual dust devils, the frequency of dust devil occurrence, and the lack of statistical generality of individual experiments and observations. In this paper, we review results of observational, laboratory, and modeling studies and provide an overview of dust devil dust transport on various spatio-temporal scales as obtained with the different research approaches. Methods used for the investigation of dust devils on Earth and Mars vary. For example, while the use of imagery for the investigation of dust devil occurrence frequency is common practice for Mars, this is less so the case for Earth. Modeling approaches for Earth and Mars are similar in that they are based on the same underlying theory, but they are applied in different ways. Insights into the benefits and limitations of each approach suggest potential future research focuses, which can further reduce the uncertainty associated with dust devil dust entrainment. The potential impacts of dust devils on the climates of Earth and Mars are discussed on the basis of the presented research results

    National identity predicts public health support during a global pandemic

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    Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

    Variation in neurosurgical management of traumatic brain injury

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    Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

    Introducing user participative design methods to industrial designers

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    Communication between designers and human factors specialists needs to be improved. Over the past few years we have been conducting a range of studies to explore and identify how to improve this communication deficit. A participatory design tool-set was designed to encourage designers and potential end-users of future interactive products to communicate their design intentions and user needs through the use of drawing and placing cards on a table with the use of some limited role-playing. This paper reports on two case studies conducted at two organisations involved in the development of consumer products. Suggestions are provided on how these type of design tools can be improved to increase acceptance by user interface designers

    Feeding Habits and Trophic Morphology of Inshore Lizardfish (Synodus foetens) On the Central Continental Shelf off Veracruz, Gulf of Mexico

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    The inshore lizardfish, Synodus foetens, is one of the most common coastal demersal predators on the continental shelf of the Gulf of Mexico (GOM), but the biology and feeding ecology of this species is virtually unknown. Between November 2001 and January 2003 (10 collections), 603 individuals of S. foetens ranging from 112 to 420 mm standard length (SL) and 13 to 630 g (wet weight) were collected from the continental shelf of Alvarado, Veracruz, Mexico. About 60% of the individuals had empty stomachs with the stomach fullness of the remaining individuals being distributed as follows: 5% full (24.8%), 50-75% full (13.5%), and completely full (1.7%). The mean (+/- SD) wet weight of stomach contents was 12.1 +/- 10.8 g during the rainy season, and 19.0 +/- 13.0 g during the nortes season. Seventeen prey items were identified, with the majority thereof being fish. The most important prey items were Upeneus parrus, Loligo pealei, Engyophrys senta, Trachurus lathami, and Anchoa hepsetus. Seasonal changes in the diet were observed, with U. parrus and L. pealei being the most important prey during the nortes season, whereas E. senta and L. pealei were the main items during the rainy season. Prey size selection was evident among size classes of S. foetens, although no trophic overlap was observed among size classes (C-lk \u3c= 0.004). High trophic level values were determined for all size classes by season (rainy season = 4.67, nortes season = 4.84), and indicated this species belongs to the piscivorous trophic guild that preys upon both demersal and pelagic species
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