We experimentally investigate the influence of upstream-edge roundness on the flow around a 5:1 rectangular cylinder. We examine various values of edge curvature radius, ranging from nearly sharp ...edges to r/D=0.1104 at Reynolds number Re=40000, based on the freestream velocity and the crossflow dimension of the cylinder. Additionally, we explore the combined effects of edge roundness and (i) Reynolds number (Re=20000−80000) and (ii) angle of attack (|α|≤2deg). For all examined Re and α, limited sensitivity to upstream-edge rounding is observed up to r/D=0.0360, with results close to those obtained for nominally sharp edges. For r/D≥0.0781, and fixed Re and α=0deg, a noticeable decrease in the size of the mean recirculation region alongside the rectangular cylinder, lr, is observed with increasing r/D. For r/D≥0.0781, the flow features are also sensitive to Re, with a reduction in the length of the mean recirculation with increasing Re. The reduction of lr with increasing r/D and Re is due to the detached shear layer becoming more tilted towards the cylinder. Finally, for r/D≥0.0781, the effect of α, that is the increase of lr on the leeward side surface and the opposite on the windward side, is more important than for small r/D values.
•Experiments have been carried out for a 5:1 rectangular cylinder (BARC benchmark).•Investigation on combined effects of edge curvature radius, Reynolds, and angle of attack.•For curvature radii below r/D=0.0360, the flow features are similar to those of ‘sharp’ edges.•For r/D≥0.0781, the mean lateral recirculation region decreases as r/D increases.•For r/D≥0.0781, the sensitivity to Reynolds and angle of attack is larger.
Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 ...and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51-0.72, P<10(-9)), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58-0.83) with a significant (P=4.94 x 10(-5)) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.
Frontotemporal dementia (FTD) is one of the most important neurodegenerative conditions and Granulin (
GRN
) is one of the major genes associated to the disease. FTD-GRN patients are still orphan for ...any evidence-based target-therapy approach. Interestingly, it has been recently found that alkalizing agents rescued haploinsufficiency in cellular models expressing FTD-
GRN
mutations. We set up a pilot phase II clinical trial in five FTD patients with
GRN
Thr272s(g.1977_1980delCACT) mutation, to determine if amiodarone (200 mg/day) may (1) reverse progranulin deficiency and (2) delay disease progression. Each patient was scheduled for 7 study visits over 12 months period. We assessed GRN levels at baseline and after amiodarone administration during the treatment course. Somatic and neurologic examinations, along with cognitive and behavioral assessment were recorded as well. No significant effect on peripheral GRN levels was observed. In treated FTD, disease course did not differ when compared with a group of untreated FTD-GRN patients. This is the first trial targeting progranulin rescue in FTD-GRN patients using amiodarone. Despite the negative findings, it may be interesting to extend this attempt to a larger sample of subjects and to other alkalizing agents to restore granulin haploinsufficiency.
The aim of this study was to evaluate attitudes and preferences for the clinical management of hypertensive patients with cardiac organ disease, including left ventricular hypertrophy (LVH) and ...coronary artery disease (CAD), in Italy. A predefined 15-item questionnaire was anonymously administered to a large community sample of general practitioners (GPs) and specialised physicians between November 2012 and June 2013. Estimated prevalence of hypertension-related clinical conditions was stratified into four groups (10-20%, 20-40%, 40-50%, >50%); preferences were reported as percentage among valid answers to the survey questionnaire. A total of 1319 physicians (672 males, age 55.0 ± 7.1 years, age of medical activity 27.1 ± 7.6 years), among whom 1264 GPs and 55 specialised physicians, was included. LVH was reported to be the most frequent marker of organ damage by the majority of physicians (73.5%). LV diastolic dysfunction was reported to be relatively frequent (>40%) by more than half of the specialised physicians (58.2%) and less frequent (10-20%) by GPs (49.8%); LV systolic dysfunction, atrial fibrillation and CAD were considered to be less frequent (10-20%) by the majority of physicians (61.3, 71.6 and 53.3%, respectively). Echocardiography was the preferred diagnostic tool used to estimate LVH (76.6%). Tight blood pressure control (130/80 mm Hg) was considered to be the most appropriate by the majority of physicians, both in hypertensive patients with LVH and in those with CAD. With the well-known limitations of a cross-sectional survey, this study provides information on attitudes and preferences for the clinical management of outpatients with hypertension and high CV risk profile in general practice in Italy.
In this paper we study the use of individual blade pitch control as a way to reduce ultimate loads. This load alleviation strategy exploits the fact that cyclic pitching of the blades induces in ...general a reduction of the average loading of a wind turbine, at least for some components as the main bearing, the yaw bearing, or the tower. When ultimate loads are generated during shutdowns, the effect of the use of cyclic pitch results in reduced peak loads. In fact, as the machine starts from a less stressed condition, the response to an extreme gust or other event will result in reduced loading on its components. This form of load mitigation can be seen as a preventative load mitigation strategy: the effect on load reduction is obtained without the need to detect and react to an extreme event, but by simply unloading the machine so that, in case an extreme event happens, the result will be less severe. The effect of peak load mitigation by preventative cyclic pitch is investigated with reference to a multi-MW wind turbine, by using high-fidelity aeroelastic simulations in a variety of operating conditions.
The flow around a triangular prism with moderate aspect ratio placed vertically on a plane is studied numerically using the large-eddy simulation approach. The results are compared with available and ...new experimental data in order to obtain clues on the physical origin of the velocity fluctuations inside and around the wake. Both the numerical and the experimental velocity signals are analysed through time–frequency techniques based on the wavelet and Hilbert transforms in order to characterize the time variation of the amplitude and frequency of the different detectable fluctuating components. It is shown that the numerical simulation, even if relating to a Reynolds number that is one order of magnitude lower than in the experiments, provides values of the rms wake fluctuations that are in good agreement with those obtained from the hot-wire measurements. Furthermore, it allows the shape of the upper near wake to be defined, and gives useful indications on the dynamics of the vorticity structures originating from the free end of the body and on their possible connection with the wake fluctuating flow field.
Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines ...(CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0–40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments.
Metals are suspected of being involved in the pathogenesis of various neurologic diseases. We previously found a complex imbalance in serum chemical elements and oxidative status in patients with ...clinically definite multiple sclerosis (CDMS).
To understand whether this imbalance affects people with clinically isolated syndrome (CIS) and, if so, whether it predicts conversion to CDMS.
We studied 22 chemical elements and the oxidative status in 49 patients with CIS, 49 patients with CDMS, and 49 healthy donors (HD). Univariate and multivariate approaches were used to identify profiles for each group. A logistic regression analysis was used to identify the predictive potential of baseline data (elements, oxidative status, and MRI findings) for conversion to CDMS over 36 months.
Several elements and oxidative status values differed significantly among the 3 groups. Discriminant analysis revealed a major contribution of Ca, Fe, Sn, Zn, serum antioxidant capacity, and serum oxidative status, which resulted in distinct profiles (the prediction of group membership was 96% cross-validated 92% for HD, 92% cross-validated 92% for CDMS, and 90% cross-validated 86% for CIS). A weighted combination of element concentrations and oxidative status values, adjusting for all other predictors, would predict a reduction in the risk of conversion to CDMS within 3 years (odds ratio 0.37; 95% confidence interval 0.18-0.76; p = 0.007), thereby proving more effective than MRI at baseline.
The peculiar imbalance in serum elements and oxidative status that characterizes patients with CIS and may predict conversion to CDMS warrants studies on larger sample sizes.
Large-Eddy Simulations were conducted to investigate accelerated flows around a square cylinder. The study explores flow characteristics for Gaussian-type accelerations of the inflow within the range ...of Reynolds numbers Re=1.720×104 to Re=6.536×104. Three different inflow acceleration intensities within the same range of Re have been considered. For all analyzed acceleration values, time cells with a constant frequency in vortex shedding were identified in agreement with the experimental findings of Brusco et al. (2022a). The temporal behavior of the vorticity field indicates that vortex packets are shed at a constant frequency within these cells. Moving from one cell to another, there is a discontinuity in the vortex-shedding mechanism, leading to an unsteady but more symmetrical wake and a reduction in crossflow-force fluctuations. Subsequently, vortex shedding restarts at a higher frequency. As acceleration intensity increases, the time length of the constant-frequency time cells decreases. A similar behavior of the Strouhal number with the Reynolds number is obtained for all acceleration intensities.
•Large-Eddy Simulations to investigate accelerated flows around a square cylinder.•Time cells with a constant frequency in vortex shedding.•Discontinuities in the vortex-shedding mechanism occur when moving from one cell to another.•Remarkable variation of the vortex-shedding Strouhal number during flow acceleration.•The Strouhal number has a similar behavior with Reynolds for all acceleration intensities.
Background: Compared with quantitative observations, the search for qualitative changes that may characterize the immune response to Epstein–Barr virus (EBV) in multiple sclerosis (MS) has been less ...intense.
Objective: To examine the B-cell epitopes of antibodies against the Epstein–Barr nuclear antigen-1 (EBNA-1) and their relevance for MS, through a study in disease-discordant identical twins.
Methods: We evaluated the antibodies to all unique, maximally overlapping octapeptides of EBNA-1 in 12 pairs of monozygotic (MZ) twins (9 MS-discordant, 3 healthy), 3 non-twin patients and 2 healthy subjects. All except one of the patients were untreated. The EBV serology of these individuals had been assessed in advance using commercially available and in-house enzyme-linked immunosorbent assay (ELISA) kits, including assays for antibodies against select peptides of EBNA-1: EBNA-72 (GAGGGAGAGG) and EBNA-206 (EADYFEYHQEGGPDGE).
Results: The glycine–alanine rich domain of EBNA-1 was immunodominant in all subjects. Compared with healthy individuals, and similarly to what has been described in infectious mononucleosis (IM) patients, affected co-twins and non-twin patients had a significantly increased response to another EBNA-1 epitope (aa. 401–411).
Conclusion: In a study that controls for confounders, our data focus an EBNA-1 specificity that may be associated with MS pathogenesis.
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