Acute mesenteric ischemia and duodenal ulcer perforation: a unique double pathology

Background: Acute mesenteric ischaemia and duodenal perforation are surgical emergencies with serious consequences. Patients presenting with acute mesenteric ischaemia alone face a high mortality rate as high as 60% whereas those presenting with peptic ulcer perforation the mortality rates range from 6-14%. There are very few reported cases of patients presenting with this dual pathology. Case presentation: We report a unique case of a 53 year old Italian lady who presented with acute mesenteric ischaemia and duodenal perforation. This is the first report of massive bowel ischaemia and duodenal perforation with no apparent underlying common pathophysiology leading to this presentation. Conclusion: Early management in the intensive care unit and appropriate surgical intervention maximised the patient’s chances of survival despite the poor prognosis associated with her dual pathology. The rare pathology of the patient described can be explained by two possible hypotheses: peptic ulcer disease causing duodenal ulceration, which precipitated ischaemic infarction of the small bowel. The second hypothesis is the patient developed a stress related ulcer following ischaemic bowel infarction secondary to arterial thrombosis

Governing Uncertainty in a Secular Age: Rationalities of Violence, Theodicy and Torture

This article explores the problem of governing uncertainty in a secular age by focusing on the theological notion of ‘theodicy’ as the underlying rationale for the use of torture in the so-called ‘war on terror’. With God’s departure from the world, the problem of uncertainty acquires new salience as human beings can no longer explain tragic events as part of a transcendent order and must find immanent causes for the ‘evils’ that surround them. Taking a cue from Max Weber, I discuss how the problem of theodicy – how to reconcile the existence of God with the presence of evil in the world – does not disappear in the secular age but is mobilized through a Foucauldian biopolitical logic. Secular theodicy governs uncertainty through the production of economies of knowledge that rationalize processes of criminalization and securitization of entire groups and justify the use of violence. This process is particularly striking when analysing the use of torture in the so-called ‘war on terror’. Through a comparison with medieval practices and focusing on the cases of Guantanamo and Abu Ghraib, the article shows how secular torture is the product of a biopolitical theodicy aimed at governing uncertainty through the construction of the tortured as immanent evils who threaten our ‘good life’ and ‘deserve’ their treatment. Secular theodicy turns torture into an extreme form of governmentality of uncertainty in which the disciplining of conduct becomes the construction of subjectivities based on essentialist, stereotypical and racist – and for these very reasons, reassuring – economies of knowledge

Integrated Ecosystem Assessment: Lake Ontario Water Management

BACKGROUND: Ecosystem management requires organizing, synthesizing, and projecting information at a large scale while simultaneously addressing public interests, dynamic ecological properties, and a continuum of physicochemical conditions. We compared the impacts of seven water level management plans for Lake Ontario on a set of environmental attributes of public relevance. METHODOLOGY AND FINDINGS: Our assessment method was developed with a set of established impact assessment tools (checklists, classifications, matrices, simulations, representative taxa, and performance relations) and the concept of archetypal geomorphic shoreline classes. We considered each environmental attribute and shoreline class in its typical and essential form and predicted how water level change would interact with defining properties. The analysis indicated that about half the shoreline of Lake Ontario is potentially sensitive to water level change with a small portion being highly sensitive. The current water management plan may be best for maintaining the environmental resources. In contrast, a natural water regime plan designed for greatest environmental benefits most often had adverse impacts, impacted most shoreline classes, and the largest portion of the lake coast. Plans that balanced multiple objectives and avoided hydrologic extremes were found to be similar relative to the environment, low on adverse impacts, and had many minor impacts across many shoreline classes. SIGNIFICANCE: The Lake Ontario ecosystem assessment provided information that can inform decisions about water management and the environment. No approach and set of methods will perfectly and unarguably accomplish integrated ecosystem assessment. For managing water levels in Lake Ontario, we found that there are no uniformly good and bad options for environmental conservation. The scientific challenge was selecting a set of tools and practices to present broad, relevant, unbiased, and accessible information to guide decision-making on a set of management options

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Fetal loss and maternal serum levels of 2,2',4,4',5,5'-hexachlorbiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure: a cohort study in Greenland and two European populations

<p>Abstract</p> <p>Background</p> <p>In the present study, the aim is to examine the risk of fetal loss related to environmental 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) or 1,1-dichloro-2,2-bis(<it>p</it>-chlorophenyl)ethylene (p,p'-DDE) exposure.</p> <p>Methods</p> <p>We related LC/MS/MS measurements of CB-153 and p,p'-DDE in serum samples to interview-data on previous fetal loss in populations of pregnant women from Poland, Ukraine and Greenland.</p> <p>Results</p> <p>In total, 1710 women were interviewed, and 678 of these had at least one previous pregnancy. The risk of ever experiencing a fetal loss increased at higher levels of CB-153 and p,p'-DDE exposure, with an adjusted odds ratio (OR) of 2.4; confidence interval (CI) (1.1-5.5) for CB-153>200 ng/g lipid compared to 0-25 ng CB-153/g lipid and OR of 2.5 CI (0.9-6.6) for p,p'-DDE>1500 ng/g lipid compared to 0-250 ng DDE/g lipid. However, no clear dose response associations were observed. The results further suggest that high level of organochlorine serum concentrations may be related to repeated loss.</p> <p>Conclusions</p> <p>The risk of fetal loss may increase at higher levels of CB-153 and p,p'-DDE exposure, although lack of dose response and inconsistencies between countries did not allow for firm conclusions.</p

A small-molecule PI3Kα activator for cardioprotection and neuroregeneration

Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development1,2,3,4,5. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kα isoform, a crucial effector of growth factor signalling. 1938 allosterically activates PI3Kα through a distinct mechanism by enhancing multiple steps of the PI3Kα catalytic cycle and causes both local and global conformational changes in the PI3Kα structure. This compound is selective for PI3Kα over other PI3K isoforms and multiple protein and lipid kinases. It transiently activates PI3K signalling in all rodent and human cells tested, resulting in cellular responses such as proliferation and neurite outgrowth. In rodent models, acute treatment with 1938 provides cardioprotection from ischaemia–reperfusion injury and, after local administration, enhances nerve regeneration following nerve crush. This study identifies a chemical tool to directly probe the PI3Kα signalling pathway and a new approach to modulate PI3K activity, widening the therapeutic potential of targeting these enzymes through short-term activation for tissue protection and regeneration. Our findings illustrate the potential of activating kinases for therapeutic benefit, a currently largely untapped area of drug development