An experimental and numerical study on nonlinear impact responses of steel-plated structures in an Arctic environment

Ships and offshore platforms that operate in Arctic regions at low temperatures are likely subjected to impact loads that arise from collisions with icebergs. The aim of this paper was to examine the nonlinear impact response of steel-plated structures in an Arctic environment. In addition to material tensile tests for characterisation of the mechanical properties of polar-class high-tensile steel of grade DH36, an experimental study was undertaken in a dropped-object test facility on steel-plated structure models under impact loads and at low temperatures equivalent to those in Arctic regions. LS-DYNA nonlinear finite element computations were also performed for the corresponding test models. We conclude that nonlinear finite element analyses are useful in the analysis of the nonlinear impact structural responses involving yielding, crushing and brittle fracture at low temperatures as long as the modelling techniques are adequate. The conclusions and insights developed in this paper should be useful in the safety design of ships and offshore platforms intended for operation in Arctic regions

Prognostic value of a modified surprise question designed for use in the emergency department setting.

OBJECTIVE: Few reliable and valid prognostic tools are available to help emergency physicians identify patients who might benefit from early palliative approaches. We sought to determine if responses to a modified version of the surprise question, Would you be surprised if this patient died in the next 30 days could predict in-hospital mortality and resource utilization for hospitalized emergency department patients. METHODS: For this observational study, emergency physicians responded to the modified surprise question with each admission over a five-month study period. Logistic regression analyses were completed and standard test characteristics evaluated. RESULTS: 6,122 visits were evaluated. Emergency physicians responded negatively to the modified surprise question in 918 (15.1%). Test characteristics for in-hospital mortality were: sensitivity 32%, specificity 85%, positive predictive value 6%, negative predictive value 98%. The risk of intensive care unit use (relative risk [RR], 1.87; 95% confidence interval [CI], 1.45 to 2.40), use of \u27comfort measures\u27 orders (RR, 3.43; 95% CI, 2.81 to 4.18), palliative-care consultation (RR, 3.06; 95% CI, 2.62 to 3.56), and in-hospital mortality (RR, 2.18; 95% CI, 1.72 to 2.76) were greater for patients with negative responses. CONCLUSION: The modified surprise question is a simple trigger for palliative care needs, accurately identifying those at greater risk for in-hospital mortality and resource utilization. With a negative predictive value of 98%, affirmative responses to the modified surprise question provide reassurance that in-hospital death is unlikely

Public perceptions of expert disagreement: Bias and incompetence or a complex and random world?

30 page PDFExpert disputes can present laypeople with several challenges including trying to understand why such disputes occur. In an online survey of the U.S. public, we used a psychometric approach to elicit perceptions of expert disputes for 56 forecasts sampled from seven domains (climate change, crime, economics, environment, health, politics, terrorism). People with low education, or with low self-reported knowledge of the topic, were most likely to attribute expert disputes to expert incompetence. People with higher self-reported knowledge tended to attribute disputes to expert bias due to financial or ideological reasons. The more highly educated and cognitively able were most likely to attribute disputes to natural factors, such as the irreducible complexity and randomness of the phenomenon. We highlight several important implications of these results for scientists and risk managers and argue for further research on how people perceive and grapple with expert disputes.We would like to acknowledge the generous support of the National Science Foundation: This material is based upon work supported by NSF under Grant Nos. #1231231 (Robin Gregory, PI; Nathan Dieckmann co-PI) and #0925008 (Nathan Dieckmann, PI) to Decision Research. All views expressed in this paper are those of the authors alone

Trans-dominant cellular inhibition of DC-SIGN-mediated HIV-1 transmission

BACKGROUND: Dendritic cell (DC) transmission of human immunodeficiency virus (HIV) to CD4+ T cells occurs across a point of cell-cell contact referred to as the infectious synapse. The relationship between the infectious synapse and the classically defined immunological synapse is not currently understood. We have recently demonstrated that human B cells expressing exogenous DC-SIGN, DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin, efficiently transmit captured HIV type 1 (HIV-1) to CD4+ T cells. K562, another human cell line of hematopoietic origin that has been extensively used in functional analyses of DC-SIGN and related molecules, lacks the principal molecules involved in the formation of immunological synaptic junctions, namely major histocompatibility complex (MHC) class II molecules and leukocyte function-associated antigen-1 (LFA-1). We thus examined whether K562 erythroleukemic cells could recapitulate efficient DC-SIGN-mediated HIV-1 transmission (DMHT). RESULTS: Here we demonstrate that DMHT requires cell-cell contact. Despite similar expression of functional DC-SIGN, K562/DC-SIGN cells were inefficient in the transmission of HIV-1 to CD4+ T cells when compared with Raji/DC-SIGN cells. Expression of MHC class II molecules or LFA-1 on K562/DC-SIGN cells was insufficient to rescue HIV-1 transmission efficiency. Strikingly, we observed that co-culture of K562 cells with Raji/DC-SIGN cells impaired DMHT to CD4+ T cells. The K562 cell inhibition of transmission was not directly exerted on the CD4+ T cell targets and required contact between K562 and Raji/DC-SIGN cells. CONCLUSIONS: DMHT is cell type dependent and requires cell-cell contact. We also find that the cellular milieu can negatively regulate DC-SIGN transmission of HIV-1 in trans

Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells

The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the anti-apoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent.published_or_final_versio

Regulation of the Cardiac Na+/K+ ATPase by Phospholemman

Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe

Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations

Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies. Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings

Prognostic value of a modified surprise question designed for use in the emergency department setting

Objective Few reliable and valid prognostic tools are available to help emergency physicians identify patients who might benefit from early palliative approaches. We sought to determine if responses to a modified version of the surprise question, “Would you be surprised if this patient died in the next 30 days” could predict in-hospital mortality and resource utilization for hospitalized emergency department patients. Methods For this observational study, emergency physicians responded to the modified surprise question with each admission over a five-month study period. Logistic regression analyses were completed and standard test characteristics evaluated. Results 6,122 visits were evaluated. Emergency physicians responded negatively to the modified surprise question in 918 (15.1%). Test characteristics for in-hospital mortality were: sensitivity 32%, specificity 85%, positive predictive value 6%, negative predictive value 98%. The risk of intensive care unit use (relative risk [RR], 1.87; 95% confidence interval [CI], 1.45 to 2.40), use of ‘comfort measures’ orders (RR, 3.43; 95% CI, 2.81 to 4.18), palliative-care consultation (RR, 3.06; 95% CI, 2.62 to 3.56), and in-hospital mortality (RR, 2.18; 95% CI, 1.72 to 2.76) were greater for patients with negative responses. Conclusion The modified surprise question is a simple trigger for palliative care needs, accurately identifying those at greater risk for in-hospital mortality and resource utilization. With a negative predictive value of 98%, affirmative responses to the modified surprise question provide reassurance that in-hospital death is unlikely

Jejunal perforation caused by a feeding jejunostomy tube: a case report

<p>Abstract</p> <p>Introduction</p> <p>Percutaneous endoscopic gastrostomy and feeding jejunostomy are used for providing long-term nutritional support to patients with neurological disorders. Various mechanical complications of these procedures are described.</p> <p>Case presentation</p> <p>We report a case of a 17-year-old boy with cerebral injury who had a percutaneous endoscopic gastrostomy tube changed to a feeding jejunostomy tube. Twenty-four hours later he developed abdominal pain and became clinically septic. A contrast study through the feeding tube and a subsequent computed tomography scan did not reveal any intra-abdominal pathology. At laparotomy it was discovered that the tip of the feeding tube had perforated through the jejunal wall and was lying outside the lumen. This was successfully treated by re-inserting a feeding jejunostomy tube distally and closure of the perforation and previous FJ site</p> <p>Conclusion</p> <p>We suggest that the threshold for contrast studies and operative intervention should be low in neurologically impaired patients to avoid the delay in treatment of tube-related complications.</p