Order-of-magnitude speedup for steady states and traveling waves via Stokes preconditioning in Channelflow and Openpipeflow

Steady states and traveling waves play a fundamental role in understanding hydrodynamic problems. Even when unstable, these states provide the bifurcation-theoretic explanation for the origin of the observed states. In turbulent wall-bounded shear flows, these states have been hypothesized to be saddle points organizing the trajectories within a chaotic attractor. These states must be computed with Newton's method or one of its generalizations, since time-integration cannot converge to unstable equilibria. The bottleneck is the solution of linear systems involving the Jacobian of the Navier-Stokes or Boussinesq equations. Originally such computations were carried out by constructing and directly inverting the Jacobian, but this is unfeasible for the matrices arising from three-dimensional hydrodynamic configurations in large domains. A popular method is to seek states that are invariant under numerical time integration. Surprisingly, equilibria may also be found by seeking flows that are invariant under a single very large Backwards-Euler Forwards-Euler timestep. We show that this method, called Stokes preconditioning, is 10 to 50 times faster at computing steady states in plane Couette flow and traveling waves in pipe flow. Moreover, it can be carried out using Channelflow (by Gibson) and Openpipeflow (by Willis) without any changes to these popular spectral codes. We explain the convergence rate as a function of the integration period and Reynolds number by computing the full spectra of the operators corresponding to the Jacobians of both methods.Comment: in Computational Modelling of Bifurcations and Instabilities in Fluid Dynamics, ed. Alexander Gelfgat (Springer, 2018

Assessment of Local Public Health Workers' Willingness to Respond to Pandemic Influenza through Application of the Extended Parallel Process Model

Local public health agencies play a central role in response to an influenza pandemic, and understanding the willingness of their employees to report to work is therefore a critically relevant concern for pandemic influenza planning efforts. Witte's Extended Parallel Process Model (EPPM) has been found useful for understanding adaptive behavior in the face of unknown risk, and thus offers a framework for examining scenario-specific willingness to respond among local public health workers. We thus aim to use the EPPM as a lens for examining the influences of perceived threat and efficacy on local public health workers' response willingness to pandemic influenza.We administered an online, EPPM-based survey about attitudes/beliefs toward emergency response (Johns Hopkins approximately Public Health Infrastructure Response Survey Tool), to local public health employees in three states between November 2006-December 2007. A total of 1835 responses were collected for an overall response rate of 83%. With some regional variation, overall 16% of the workers in 2006-7 were not willing to "respond to a pandemic flu emergency regardless of its severity". Local health department employees with a perception of high threat and high efficacy--i.e., those fitting a 'concerned and confident' profile in the EPPM analysis--had the highest declared rates of willingness to respond to an influenza pandemic if required by their agency, which was 31.7 times higher than those fitting a 'low threat/low efficacy' EPPM profile.In the context of pandemic influenza planning, the EPPM provides a useful framework to inform nuanced understanding of baseline levels of--and gaps in--local public health workers' response willingness. Within local health departments, 'concerned and confident' employees are most likely to be willing to respond. This finding may allow public health agencies to design, implement, and evaluate training programs focused on emergency response attitudes in health departments

Amyloid Triggers Extensive Cerebral Angiogenesis Causing Blood Brain Barrier Permeability and Hypervascularity in Alzheimer's Disease

Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the “Vascular hypothesis”, holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes early-onset AD. The expression of tight junction (TJ) proteins, occludin and ZO-1, were examined in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes, was directly linked to an increased microvascular density but not apoptosis, which strongly supports amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration

Central Exercise Action Increases the AMPK and mTOR Response to Leptin

AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability