The development of a wind tunnel DAQ system by using Labview tools

This paper presents the experimental three-year learning activity developed by a group of teachers in a wind tunnel facility. The authors, leading a team of students, carried out a project consisting of the design, assembly and testing of a wind tunnel. The project included all stages of the process from its initial specifications to its final quality flow assessments, going through the calculation of each element, and the building of the whole wind tunnel. The group of (final year) students was responsible for the whole wind tunnel project as a part of their bachelor degree project. The paper focuses on the development of wind tunnel data acquisition software. This automatic tool is essential to improve the automation of the data acquisition of the wind tunnel facility systems, in particular for a 6DOF multi-axis force/torque sensor. This work can be considered as a typical example of real engineering practice: a set of specifications that has to be modified due to the constraints imposed throughout the project, in order to obtain the final resul

Developing models for future real-time platforms: Virtual simulation and design of new components and systems for aircraft and remotely piloted aircraft systems

In the development of electrified and other vehicle systems, the modelling and simulation of the vehicle is very important. With these tools the preliminary design, as well as later detailed studies of the systems developed, allow engineers to spend less time on each phase of their projects or address them with an integrated approach. In addition, this integrated approach provides the possibility of building hardware-in-the loop models with all the components required. This vehicle modelling and simulation has gained more interest with the increasing use of a wide variety of RPAS, ranging from light weight micro aircraft to large vehicles of various tons. For this reason, the previously-described building tools are the final objective of the developing models to be used in real-time platform projects. The first step presented in this paper is to build a simulator that reproduces the behaviour of a selected aircraft and validate it. This paper presents the study of the performances and behaviour of an OPV used to validate the simulator developed later. At the end, some preliminary tests and estimations of the performances for the selected OPV with an electric motor are presented

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Flow study over bluff bodies based on visualization technique

Flow visualization is a very important part of the study of fluid dynamics processes analyzed in many fields of physics and engineering. The present study explores flow visualization experiment technique applied to blunt shaped bluff bodies placed inside towing tank. Vortex shedding in circular cylinders has been studied in depth, being able to visualize the classical von Kármán vortex street. Moreover, the vortex shedding in cylinders of square section has been studied so that the differences between bodies with different section can be compared. A comparison between theoretical and experimental values of vortex shedding frequencies has been obtained; a high correlation with them shows the appropriate experimental procedure. Finally, this paper tries to advocate the use of the towing tank technique as a method to support the theoretical lectures related with some fluid mechanics concepts quite difficult to understand

Risk Assessment of the Lead intake by consumption of red deer and wild boar meat in Southern Spain

International audienceThe presence of heavy metals in big game meat may pose a risk to human health. The main objective of this work was to carry out a risk assessment study (using a probabilistic and point-estimate approach) of lead intake by consumption of red deer and wild boar meat in Southern Spain based on Spanish data collected in the period 2002-2006. In general, the concentration levels found for wild boar meat (mean= 1291 µg/Kg) were much higher than those observed in red deer meat (mean=326 µg/Kg). The results from a point-estimate risk assessment showed that the estimated average intake of lead among different exposure scenarios varied from 0.1 to 6.5 and from 0.3 to 38 µg/Kg/week for red deer and wild boar meat, respectively; and from 0.3 to 35 µg/Kg/week for individuals consuming both red deer and wild boar meat, and that estimated intake of lead by consumption of big game meat differed significantly between hunters and non-hunters, it being higher for hunters. Besides this, results from the probabilistic risk assessment study corroborated that risk is greater in hunter populations, reaching a maximum in individuals consuming only wild boar and both types of meat, with 0.4 and 0.2 % population above the PTWI (Provisional Tolerable Weekly Intake), respectively. Likewise, the hunter populations consuming wild boar and both types of big game meat (red deer and wild boar meat) were exposed to the maximum Pb level (56 μg/Kg/week) which corresponded to 224 % PTWI, approximately. Further data and studies will be needed to give a complete risk estimation in which it will be crucial to consider the contribution to the Pb intake level of other foods in the diet of both population groups

IgA Nephropathy in Elderly Patients.

Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3

IgA Nephropathy in Elderly Patients

Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics