888 research outputs found

    Illusions of gunk

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    The possibility of gunk has been used to argue against mereological nihilism. This paper explores two responses on the part of the microphysical mereological nihilist: (1) the contingency defence, which maintains that nihilism is true of the actual world; but that at other worlds, composition occurs; (2) the impossibility defence, which maintains that nihilism is necessary true, and so gunk worlds are impossible. The former is argued to be ultimately unstable; the latter faces the explanatorily burden of explaining the illusion that gunk is possible. It is argued that we can discharge this burden by focussing on the contingency of the microphysicalist aspect of microphysical mereological nihilism. The upshot is that gunk-based arguments against microphysical mereological nihilism can be resisted

    Collaborations in Liberal Arts Colleges in Support of Digital Humanities

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    The field of digital humanities has been rapidly expanding over the course of the last decade. As such, academic institutions have been working to identify ways of supporting these new endeavors in a time of economic struggles. The Digital Humanities Initiative (DHi) at Hamilton College was conceived as one possible model of supporting digital humanities scholarship at a liberal arts institution. The DHi model relies heavily on collaboration among different teams in the Library and Information Technology Services across campus, and with institutions across the United States. DHi also has international partnerships that promote its goals in research, learning, and public humanities. This chapter will describe the various collaborations of DHi and offer suggestions for how others can implement similar support models at their institutions

    A Review of the Dose Justification of Phase 3 Trials to Regulatory Authorities for Drugs Intended for the Treatment of Type 2 Diabetes in Europe

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    Aims: Cardiovascular outcome trials with anti-diabetic drugs suggest that additional cardiovascular benefit can be achieved independent of improving glycaemic control. Nonetheless, dose selection of anti-diabetic drugs is typically based solely on glycaemic effects. We evaluated whether off-target drug effects are currently considered for dose justification to regulatory agencies. Methods: In the European Union, anti-diabetic drugs are registered by the European Medicines Agency. We extracted available information regarding dose selection from public assessment reports and marketing application dossiers. Descriptive statistics were used to summarise the extracted information. Results: In total, 14 drugs of three drug classes were included; sodium-glucose co-transporter-2 inhibitors (n = 4), dipeptidyl peptidase-4 inhibitors (n = 4) and glucagon-like peptide-1 receptor agonists (n = 6). For these drugs, 21 dose-finding trials were submitted including results of multiple off-target effects, of which body weight (n = 18) and low-density lipoprotein cholesterol (n = 14) were most frequently reported. Dose-response curves for off-target effects appeared to be different compared to the glycaemic dose-response curve. Glycated hemoglobin (100%) and fasting plasma glucose (42.9%), were used most frequently for the dose justification, but generally off-target effects (<25%) were not. Conclusions: Dose justification to regulatory authorities was mainly based on glycaemic effects. The dose-response relationship for the off-target effects did not necessarily follow the dose-response relationship of the on-target effects suggesting that selection of the optimal anti-diabetic dose could benefit from including off-target effects in the dose selection process as well

    F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection

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    Contains fulltext : 88623.pdf (publisher's version ) (Closed access)PURPOSE: To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS: FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS: Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS: FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues.01 maart 201

    Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium

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    Background: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. Objectives: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. Methods: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). Results: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100 pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. Discussion and conclusion: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure

    Education for the anthropocene : planetary health, sustainable health care, and the health workforce

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    Over the past few centuries, human activity has wrought dramatic changes in the natural systems that support human life. Planetary health is a useful concept for health profession education (HPE) teaching and practice because it situates health within a broader understanding of the interdependent socio-ecological drivers of human and planetary health. It facilitates novel ways of protecting both population health and the natural environment on which human health and wellbeing depends. This paper focuses on the climate crisis as an example of the relationship between environmental change, healthcare, and education. We analyze how HPE can help decarbonize the healthcare sector to address both climate change and inequity in health outcomes. Based on the healthcare practitioner’s mandate of beneficence, we propose simple learning objectives to equip HPE graduates with the knowledge, skills, and values to create a sustainable health system, using carbon emission reductions as an example. These learning objectives can be integrated into HPE without adding unduly to the curriculum load

    Measuring centimeter-scale sand ripples using multibeam echosounder backscatter data from the Brown Bank area of the Dutch continental shelf

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    Backscatter data from multibeam echosounders are commonly used to classify seafloor sediment composition. Previously, it was found that the survey azimuth affects backscatter when small organized seafloor structures, such as sand ripples, are present. These sand ripples are too small to be detected in the multibeam bathymetry. Here, we show that such azimuth effects are time dependent and are useful to examine the orientation of sand ripples in relation to the flow direction of the tide. To this end, multibeam echosounder data at four different frequencies were gathered from the area of the Brown Bank in the North Sea. The acoustic results were compared to video and tide-flow data for validation. The sand ripples affected the backscatter at all frequencies, but for the lowest frequencies the effect was spread over more beam angles. Using the acoustic data made it possible to deduce the orientations of the sand ripples over areas of multiple square kilometers. We found that the top centimeter(s) of the seafloor undergoes a complete transformation every six hours, as the orientation of the sand ripples changes with the changing tide. Our methodology allows for morphology change detection at larger scales and higher resolutions than previously achieved

    Subbarrel patterns in somatosensory cortical barrels can emerge from local dynamic instabilities

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    Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In the rodent somatosensory cortex, groups of neurons called "barrels" correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. Here we demonstrate that similar patterns can be simulated by means of local growth-promoting and growth-retarding interactions within the circular domains of single barrels. The model correctly predicts that larger barrels contain more spatially complex subbarrel patterns, suggesting that the development of barrels and of the patterns within them may be understood in terms of some relatively simple dynamic processes. We also simulate the full nonlinear equations to demonstrate the predictive value of our linear analysis. Finally, we show that the pattern formation is robust with respect to the geometry of the barrel by simulating patterns on a realistically shaped barrel domain. This work shows how simple pattern forming mechanisms can explain neural wiring both qualitatively and quantitatively even in complex and irregular domains. © 2009 Ermentrout et al
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