A finite difference Poisson solver for irregular geometries

The motivation for this work comes from the development of a 3D quasi-geostrophic Contour Advective Semi-Lagrangian model for vortex interaction in the ocean. The existing code is limited to circular cylindrical geometry and uses polar coordinates. We wish to extend the method to more general cross-sections. The crucial aspect is the solution of the Poisson equation that allows the determination of the stream function from the potential vorticity at each time-step, as this is the part of the algorithm that must be performed on a grid: the advection of potential vorticity contours is fully Lagrangian and hence is easily modified for irregular domains. We develop a 2D algorithm for inverting the Poisson equation for the stream function on an arbitrarily shaped domain, in the special case when the boundary is a streamline, as is the case for our problem. However, the method is also valid for non-zero Dirichlet boundary conditions. The approach uses finite differences with the domain embedded in a rectangular Cartesian grid. We show that the algorithm is second-order accurate and provide several numerical examples

Two opposing hippocampus to prefrontal cortex pathways for the control of approach and avoidance behaviour

The decision to either approach or avoid a potentially threatening environment is thought to rely upon the coordinated activity of heterogeneous neural populations in the hippocampus and prefrontal cortex (PFC). However, how this circuitry is organized to flexibly promote both approach or avoidance at different times has remained elusive. Here, we show that the hippocampal projection to PFC is composed of two parallel circuits located in the superficial or deep pyramidal layers of the CA1/subiculum border. These circuits have unique upstream and downstream connectivity, and are differentially active during approach and avoidance behaviour. The superficial population is preferentially connected to widespread PFC inhibitory interneurons, and its activation promotes exploration; while the deep circuit is connected to PFC pyramidal neurons and fast spiking interneurons, and its activation promotes avoidance. Together this provides a mechanism for regulation of behaviour during approach avoidance conflict: through two specialized, parallel circuits that allow bidirectional hippocampal control of PFC

Detecting contour crossings in contour dynamical and contour-advective semi-Lagrangian simulations

Contour dynamics and contour-advective methods are commonly used numerical techniques for simulating inviscid fluid motions. In these methods the vorticity or potential vorticity of a flow is represented by a series of contours which are advected according to the prevailing velocity field. In some circumstances the contours may cross, eroding the accuracy of the numerical solution and violating the equations of motion. This paper describes an automated method for explicitly revealing such crossings, first considering the case of determining if two contours cross and then later the more general case of determining if and where an arbitrary number of contours cross

the validity of drug effects on proteinuria albuminuria serum creatinine and estimated gfr as surrogate end points for eskd a systematic review

Rationale & Objective Proteinuria, albuminuria, and serum creatinine level are widely used as surrogate end point measures of end-stage kidney disease (ESKD). We evaluated the correlation between antihypertensive drug effects on surrogate renal end points and ESKD. Study Design Systematic review. Setting & Participants Randomized controlled trials of blood pressure–lowering therapy. Selection Criteria for Studies Trials of pharmacological blood pressure–lowering strategies reporting drug effects on albuminuria, proteinuria, or serum creatinine level and ESKD through March 26, 2018. Analytical Approach Bayesian bivariate meta-analysis to calculate correlations between drug effects on surrogate end points and drug effects on ESKD. Risks of bias were adjudicated using the Cochrane tool. Results 22 randomized controlled trials involving 69,642 participants were eligible. Risks of bias in the included trials were frequently unclear due to incomplete reporting. Relative risk for ESKD was statistically significant in 1 of 29 (3.4%) treatment comparisons. There appeared to be little or no correlation between antihypertensive drug effects on serum creatinine level, albuminuria, proteinuria, and the corresponding effects on ESKD. All correlations had wide 95% credible intervals that included the null effect. Limitations Low power due to infrequent outcomes of ESKD and incomplete data reporting in primary trials. Conclusions The association between antihypertensive drug effects on doubling of serum creatinine level and albuminuria or proteinuria with ESKD in treatment trials is not sufficiently certain to enable the confident use of these markers to guide clinical or regulatory decision making

The cessation in pregnancy incentives trial (CPIT): study protocol for a randomized controlled trial

Background: Seventy percent of women in Scotland have at least one baby, making pregnancy an opportunity to help most young women quit smoking before their own health is irreparably compromised. By quitting during pregnancy their infants will be protected from miscarriage and still birth as well as low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. In the UK, the NICE guidelines: 'How to stop smoking in pregnancy and following childbirth' (June 2010) highlighted that little evidence exists in the literature to confirm the efficacy of financial incentives to help pregnant smokers to quit. Its first research recommendation was to determine: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? <p/>Design and Methods: This study is a phase II exploratory individually randomised controlled trial comparing standard care for pregnant smokers with standard care plus the additional offer of financial voucher incentives to engage with specialist cessation services and/or to quit smoking during pregnancy. Participants (n=600) will be pregnant smokers identified at maternity booking who when contacted by specialist cessation services agree to having their details passed to the NHS Smokefree Pregnancy Study Helpline to discuss the trial. The NHS Smokefree Pregnancy Study Helpline will be responsible for telephone consent and follow-up in late pregnancy. The primary outcome will be self reported smoking in late pregnancy verified by cotinine measurement. An economic evaluation will refine cost data collection and assess potential cost-effectiveness while qualitative research interviews with clients and health professionals will assess the level of acceptance of this form of incentive payment. Research questions What is the likely therapeutic efficacy? Are incentives potentially cost-effective? Is individual randomisation an efficient trial design without introducing outcome bias? Can incentives be introduced in a way that is feasible and acceptable? <p/>Discussion: This phase II trial will establish a workable design to reduce the risks associated with a future definitive phase III multicentre randomised controlled trial and establish a framework to assess the costs and benefits of financial incentives to help pregnant smokers to quit