Haemodynamic changes in visceral hybrid repairs of type III and type V thoracoabdominal aortic aneurysms

The visceral hybrid procedure combining retrograde visceral bypass grafting and completion endovascular stent grafting is a feasible alternative to conventional open surgical or wholly endovascular repairs of thoracoabdominal aneurysms (TAAA). However, the wide variability in visceral hybrid configurations means that a priori prediction of surgical outcome based on haemodynamic flow profiles such as velocity pattern and wall shear stress post repair remain challenging. We sought to appraise the clinical relevance of computational fluid dynamics (CFD) analyses in the setting of visceral hybrid TAAA repairs. Two patients, one with a type III and the other with a type V TAAA, underwent successful elective and emergency visceral hybrid repairs, respectively. Flow patterns and haemodynamic parameters were analysed using reconstructed pre- and post-operative CT scans. Both type III and type V TAAAs showed highly disturbed flow patterns with varying helicity values preoperatively within their respective aneurysms. Low time-averaged wall shear stress (TAWSS) and high endothelial cell action potential (ECAP) and relative residence time (RRT) associated with thrombogenic susceptibility was observed in the posterior aspect of both TAAAs preoperatively. Despite differing bypass configurations in the elective and emergency repairs, both treatment options appear to improve haemodynamic performance compared to preoperative study. However, we observed reduced TAWSS in the right iliac artery (portending a theoretical risk of future graft and possibly limb thrombosis), after the elective type III visceral hybrid repair, but not the emergency type V repair. We surmise that this difference may be attributed to the higher neo-bifurcation of the aortic stent graft in the type III as compared to the type V repair. Our results demonstrate that CFD can be used in complicated visceral hybrid repair to yield potentially actionable predictive insights with implications on surveillance and enhanced post-operative management, even in patients with complicated geometrical bypass configurations

Grassland plant and invertebrate species richness increases from mowing are mediated by impacts on soil chemistry

Pasture and improved grasslands are commonly managed by a combination of artificial fertilisation and biomass removal, but a deeper understanding of how management options interact over the long-term are required to improve sustainability. Studies of multi-trophic responses to these options can provide important insights for biodiversity and soil management, particularly when they cover long time periods. In this study, we provide a novel perspective on long-term experimental field studies of grassland management by examining the direct and indirect effects of N fertilisation and mowing (with biomass retention and removal) on above-ground biodiversity, below-ground soil chemistry and their interactions. Our experimental treatments were applied annually from 1994 in medium to high soil fertility conditions on a non-native pastoral farm in New Zealand, and analysis of data to 2013 show that in general, plants and soil properties did not respond to N fertiliser treatments. In response to mowing regimes, soil properties exhibited subtle, but annually varying changes mostly related to biomass retention or removal, and plant richness was consistently higher under all mowing treatments. The management regime with the greatest gains in diversity also depended on year of study. We further analysed the indirect effects of mowing treatments on plant and arthropod richness via soil properties using structural equation modelling, and found that the impact of mowing is likely to be mediated by soil chemistry changes. In particular, the direct positive impact of mowing on plant richness may be offset by changes to soil properties, depending on whether biomass is retained or removed. We suggest that management regime effects on soil chemistry may limit plant composition changes to those species able to take advantage of altered conditions. These findings suggest that management to improve grassland diversity and soil conditions should consider the abiotic history and conditions of the site

The effect of C1-esterase inhibitor on systemic inflammation in trauma patients with a femur fracture - The CAESAR study: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Systemic inflammation in response to a femur fracture and the additional fixation is associated with inflammatory complications, such as acute respiratory distress syndrome and multiple organ dysfunction syndrome. The injury itself, but also the additional procedure of femoral fixation induces a release of pro-inflammatory cytokines such as interleukin-6. This results in an aggravation of the initial systemic inflammatory response, and can cause an increased risk for the development of inflammatory complications. Recent studies have shown that administration of the serum protein C1-esterase inhibitor can significantly reduce the release of circulating pro-inflammatory cytokines in response to acute systemic inflammation.</p> <p>Objective</p> <p>Attenuation of the surgery-induced additional systemic inflammatory response by perioperative treatment with C1-esterase inhibitor of trauma patients with a femur fracture.</p> <p>Methods</p> <p>The study is designed as a double-blind randomized placebo-controlled trial. Trauma patients with a femur fracture, Injury Severity Score ≥ 18 and age 18-80 years are included after obtaining informed consent. They are randomized for administration of 200 U/kg C1-esterase inhibitor intravenously or placebo (saline 0.9%) just before the start of the procedure of femoral fixation. The primary endpoint of the study is Δ interleukin-6, measured at t = 0, just before start of the femur fixation surgery and administration of C1-esterase inhibitor, and t = 6, 6 hours after administration of C1-esterase inhibitor and the femur fixation.</p> <p>Conclusion</p> <p>This study intents to identify C1-esterase inhibitor as a safe and potent anti-inflammatory agent, that is capable of suppressing systemic inflammation in trauma patients. This might facilitate early total care procedures by lowering the risk of inflammation in response to the surgical intervention. This could result in increased functional outcomes and reduced health care related costs.</p> <p>Trial registration</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01275976">NCT01275976</a> (January 12th 2011)</p

Inconvenience due to travelers' diarrhea: a prospective follow-up study

<p>Abstract</p> <p>Background</p> <p>Limited data exist documenting the degree to which travelers are inconvenienced by travelers' diarrhea (TD). We performed a prospective follow-up study at the travel clinic of Leiden University Medical Center in The Netherlands to determine the degree of inconvenience and to determine how experiencing TD affects travelers' perception.</p> <p>Methods</p> <p>Healthy adults who intended to travel to the (sub)tropics for less than two months were invited to take part. Participants filled out a web-based questionnaire before departure and after returning home. TD was defined as three or more unformed stools during a 24-hour period.</p> <p>Results</p> <p>390 of 776 Eligible travelers completed both questionnaires. Participants' median age was 31 years and mean travel duration 23 days. Of 160 travelers who contracted TD (incidence proportion 41%, median duration of TD episode 2.5 days) the majority (107/160, 67%) could conduct their activity program as planned despite having diarrhea. However, 21% (33/160) were forced to alter their program and an additional 13% (20/160) were confined to their accommodation for one or more daylight days; 53 travelers (33%) used loperamide and 14 (9%) an antibiotic. Eight travelers (5%) consulted a physician for the diarrheal illness. When asked about the degree of inconvenience brought on by the diarrheal illness, 39% categorized it as minor or none at all, 34% as moderate and 27% as large or severe. In those who regarded the episode of TD a major inconvenience, severity of symptoms was greater and use of treatment and necessity to alter the activity program were more common. Travelers who contracted travelers' diarrhea considered it less of a problem in retrospect than they had thought it would be before departure.</p> <p>Conclusion</p> <p>Conventional definitions of TD encompass many mild cases of TD (in our study at least a third of all cases) for which treatment is unlikely to provide a significant health benefit. By measuring the degree of inconvenience brought on by TD, researchers and policy makers may be able to better distinguish 'significant TD' from mild TD, thus allowing for a more precise estimation of the size of the target population for vaccination or stand-by antibiotic prescription and of the benefit of such measures.</p

Effects of myocardial sheetlet sliding on left ventricular function

Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics

Numerical Investigation of the Performance of Three Hinge Designs of Bileaflet Mechanical Heart Valves

Thromboembolic complications (TECs) of bileaflet mechanical heart valves (BMHVs) are believed to be due to the nonphysiologic mechanical stresses imposed on blood elements by the hinge flows. Relating hinge flow features to design features is, therefore, essential to ultimately design BMHVs with lower TEC rates. This study aims at simulating the pulsatile three-dimensional hinge flows of three BMHVs and estimating the TEC potential associated with each hinge design. Hinge geometries are constructed from micro-computed tomography scans of BMHVs. Simulations are conducted using a Cartesian sharp-interface immersed-boundary methodology combined with a second-order accurate fractional-step method. Leaflet motion and flow boundary conditions are extracted from fluid–structure-interaction simulations of BMHV bulk flow. The numerical results are analyzed using a particle-tracking approach coupled with existing blood damage models. The gap width and, more importantly, the shape of the recess and leaflet are found to impact the flow distribution and TEC potential. Smooth, streamlined surfaces appear to be more favorable than sharp corners or sudden shape transitions. The developed framework will enable pragmatic and cost-efficient preclinical evaluation of BMHV prototypes prior to valve manufacturing. Application to a wide range of hinges with varying design parameters will eventually help in determining the optimal hinge design

Pandemic Influenza (H1N1) 2009 Is Associated with Severe Disease in India

Background: Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. In absence of reliable information on severity of the disease, the nations are unable to decide on the appropriate response against this disease. Methods: Based on the results of laboratory investigations, attendance in outpatient department, hospital admissions and mortality from the cases of influenza like illness from 1 August to 31 October 2009 in Pune urban agglomeration, risk of hospitalization and case fatality ratio were assessed to determine the severity of pandemic H1N1 and seasonal influenza-A infections. Results: Prevalence of pandemic H1N1 as well as seasonal-A cases were high in Pune urban agglomeration during the study period. The cases positive for pandemic H1N1 virus had significantly higher risk of hospitalization than those positive for seasonal influenza-A viruses (OR: 1.7). Of 93 influenza related deaths, 57 and 8 deaths from Pune (urban) and 27 and 1 death from Pune (rural) were from pandemic H1N1 positive and seasonal-A positive cases respectively. The case fatality ratio 0.86 % for pandemic H1N1 was significantly higher than that of seasonal-A (0.13%) and it was in category 3 of the pandemic severity index of CDC, USA. The data on the cumulative fatality of rural and urban Pune revealed that with time the epidemic is spreading to rural areas

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis

Background: Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. Methods: PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin alpha and beta subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. Results: All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin alpha and beta subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Conclusions: Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page