Transmogrification

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Linear stability of Poiseuille flow over a steady spanwise Stokes layer

The temporal linear stability of plane Poiseuille flow modified by spanwise forcing applied at the walls is considered. The forcing consists of a stationary streamwise distribution of spanwise velocity that generates a steady transversal Stokes layer, known to reduce skin-friction drag in a turbulent flow with little energetic cost. A large numerical study is carried out, where the effects of both the physical and the discretization parameters are thoroughly explored, for three representative subcritical values of the Reynolds number Re. Results show that the spanwise Stokes layer significantly affects the linear stability of the system. For example, at Re=2000 the wall forcing is found to more than double the negative real part of the least-stable eigenvalue, and to decrease by nearly a factor of 4 the maximum transient growth of perturbation energy. These observations are Re dependent and further improve at higher Re. Comments on the physical implications of the obtained results are provided, suggesting that spanwise forcing might be effective to obtain at the same time a delayed transition to turbulence and a reduced turbulent friction

Linear stability of Poiseuille flow over a steady spanwise Stokes layer

The temporal linear stability of plane Poiseuille flow modified by spanwise forcing applied at the walls is considered. The forcing consists of a stationary streamwise distribution of spanwise velocity that generates a steady transversal Stokes layer, known to reduce skin-friction drag in a turbulent flow with little energetic cost. A large numerical study is carried out, where the effects of both the physical and the discretization parameters are thoroughly explored, for three representative subcritical values of the Reynolds number Re. Results show that the spanwise Stokes layer significantly affects the linear stability of the system. For example, at Re=2000 the wall forcing is found to more than double the negative real part of the least-stable eigenvalue, and to decrease by nearly a factor of four the maximum transient growth of perturbation energy. These observations are Re-dependent and further improve at higher $Re$. Comments on the physical implications of the obtained results are provided, suggesting that spanwise forcing might be effective to obtain at the same time a delayed transition to turbulence and a reduced turbulent friction.Comment: Under consideration by PR

Testosterone Therapy in Women With Chronic Heart Failure A Pilot Double-Blind, Randomized, Placebo-Controlled Study

ObjectivesThe primary objective of this study was to assess the effect of a 6-month testosterone supplementation therapy on functional capacity and insulin resistance in female patients with chronic heart failure (CHF).BackgroundPatients with CHF show decreased exercise capacity and insulin sensitivity. Testosterone supplementation improves these variables in men with CHF. No study has evaluated the effects of testosterone supplementation on female patients with CHF.MethodsThirty-six elderly female patients with stable CHF, (ejection fraction 32.9 ± 6) were randomly assigned (2:1 ratio) to receive testosterone transdermal patch (T group, n = 24) or placebo (P group, n = 12), both on top of optimal medical therapy. At baseline and after 6 months, patients underwent 6-min walking test (6MWT), cardiopulmonary exercise test, echocardiogram, quadriceps maximal isometric voluntary contraction, dynamic quadriceps isokinetic strength (peak torque), and insulin resistance assessment by homeostasis model.ResultsDistance walked at 6MWT as well as peak oxygen consumption significantly improved in the T group, whereas they were unchanged in the P group (p < 0.05 for all comparisons). The homeostasis model was significantly reduced in the T group in comparison with the P group (−16.5% vs. +5%, respectively; p < 0.05). Maximal voluntary contraction and peak torque increased significantly in the T group but did not change in the P group. Increase in distance walked at 6MWT was related to the increase in free testosterone levels (r = 0.593, p = 0.01). No significant changes in echocardiographic parameters were observed in either group. No side effects requiring discontinuation of T were detected.ConclusionsTestosterone supplementation improves functional capacity, insulin resistance, and muscle strength in women with advanced CHF. Testosterone seems to be an effective and safe therapy for elderly women with CHF

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A phase 2, randomized, sham-controlled trial

Background -In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%. Methods -REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results -A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions -In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration -URL: http://clinicaltrials.gov. Unique identifier: NCT02600234

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

Background Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. Methods Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13 100 men aged 40-70 and 114 443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. Results A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. Conclusions The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle change

Evolutionary factors affecting the cross-species utility of newly developed microsatellite markers in seabirds

Microsatellite loci are ideal for testing hypotheses relating to genetic segregation at fine spatio-temporal scales. They are also conserved among closely related species, making them potentially useful for clarifying interspecific relationships between recently diverged taxa. However, mutations at primer binding sites may lead to increased non-amplification, or disruptions that may lead to decreased polymorphism in non-target species. Furthermore, high mutation rates and constraints on allele size may also lead, with evolutionary time, to an increase in convergently evolved allele size classes, biasing measures of interspecific genetic differentiation. Here, we used next-generation sequencing to develop microsatellite markers from a shotgun genome sequence of the sub-Antarctic seabird, the thin-billed prion (Pachyptila belcheri), that we tested for cross-species amplification in other Pachyptila and related sub-Antarctic species. We found that heterozygosity decreased and the proportion of non-amplifying loci increased with phylogenetic distance from the target species. Surprisingly, we found that species trees estimated from interspecific FST provided better approximations of mtDNA relationships among the studied species than those estimated using DC, even though FST was more affected by null alleles. We observed a significantly non-linear second order polynomial relationship between microsatellite and mtDNA distances. We propose that the loss of linearity with increasing mtDNA distance stems from an increasing proportion of homoplastic allele size classes that are identical in state, but not identical by descent. Therefore, despite high cross-species amplification success and high polymorphism among the closely related Pachyptila species, we caution against the use of microsatellites in phylogenetic inference among distantly related taxa