Ultrasonic, molecular and mechanical testing diagnostics in natural fibre reinforced, polymer-stabilised earth blocks

The aim of this research study was to evaluate the influence of utilising natural polymers as a form of soil stabilization, in order to assess their potential for use in building applications. Mixtures were stabilized with a natural polymer (alginate) and reinforced with wool fibres in order to improve the overall compressive and flexural strength of a series of composite materials. Ultrasonic pulse velocity (UPV) and mechanical strength testing techniques were then used to measure the porous properties of the manufactured natural polymer-soil composites, which were formed into earth blocks. Mechanical tests were carried out for three different clays which showed that the polymer increased the mechanical resistance of the samples to varying degrees, depending on the plasticity index of each soil. Variation in soil grain size distributions and Atterberg limits were assessed and chemical compositions were studied and compared. X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), and energy dispersive X-ray fluorescence (EDXRF) techniques were all used in conjunction with qualitative identification of the aggregates. Ultrasonic wave propagation was found to be a useful technique for assisting in the determination of soil shrinkage characteristics and fibre-soil adherence capacity and UPV results correlated well with the measured mechanical properties

A combination of SEM and EDX studies on a clay-based natural composite with animal fibre and its mechanical implications

A variety of natural fibres are nowadays being utilized as soil reinforcement. Test results demonstrate the positive effects of adding natural fibres to soils, in that they decrease shrinkage, reduce curing time and enhance compressive, flexural and shear strength if an optimum reinforcement ratio can be utilised. This paper describes a study which uses a Scanning Electron Microscope (SEM) and an Energy Diffraction Analysis of X-rays (EDX) technique on clay-based composites stabilized with natural polymer and fibres. Different dosages of fibres and several types of soils have been used in this study with the aim of determining advantageous properties for building material applications. SEM and EDX test results reveal the degree of bonding between the particles of soil and the natural fibers. This has enabled a better understanding of the micro-morphology of the natural fibers and their effect on the overall composite material structure. Microscopic analysis was combined with mechanical tests to establish the different strength characteristics of every soil

Ultrasonic, molecular and mechanical testing diagnostics in natural fibre reinforced, polymer-stabilised earth blocks

The aim of this research study was to evaluate the influence of utilising natural polymers as a form of soil stabilization, in order to assess their potential for use in building applications. Mixtures were stabilized with a natural polymer (alginate) and reinforced with wool fibres in order to improve the overall compressive and flexural strength of a series of composite materials. Ultrasonic pulse velocity (UPV) and mechanical strength testing techniques were then used to measure the porous properties of the manufactured natural polymer-soil composites, which were formed into earth blocks. Mechanical tests were carried out for three different clays which showed that the polymer increased the mechanical resistance of the samples to varying degrees, depending on the plasticity index of each soil. Variation in soil grain size distributions and Atterberg limits were assessed and chemical compositions were studied and compared. X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), and energy dispersive X-ray fluorescence (EDXRF) techniques were all used in conjunction with qualitative identification of the aggregates. Ultrasonic wave propagation was found to be a useful technique for assisting in the determination of soil shrinkage characteristics and fibre-soil adherence capacity and UPV results correlated well with the measured mechanical properties

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Integrating courtyard microclimate in building performance to mitigate extreme urban heat impacts

Extreme heat events are expected to occur more often as a consequence of climate change. This paper quantifies the impact of urban climate on building performance and evaluates the benefits of specific microclimates, such as inner courtyards, to mitigate extreme heat impacts. A reference case study associated with two outdoor weather conditions, an inner courtyard and a local urban climate, was measured, simulated and validated in TRNSYS. The validated model was then compared to three building models with a single outdoor weather condition associated with the urban climate, weather data from a rural station and a typical year weather file. The models were evaluated in free-running conditions and with air-conditioning systems. The results show how urban climate can increase indoor discomfort hours by 32% in free-running conditions and demonstrate that courtyard microclimate can almost completely mitigate the impact of urban overheating in buildings, eliminating severe indoor discomfort hours by more than 88%. Moreover, the increase in cooling energy demand due to urban climate was reduced by more than 15% in the case of having air-conditioning systems. The findings manifest the importance of accurate weather data for building simulation and demonstrate how multi-nodal outdoor conditions can enable additional strategies to mitigate climate risks, highlighting urban microclimates as a promising strategy to tackle extreme heat events in buildings and cities

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

WOS: 000481590200024PubMed ID: 31427717Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern.Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER) [PI15/01159]; Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); Catalan Association for Rett Syndrome; Fondobiorett; Mi Princesa RettWe thank all patients and their families who contributed to this study. The work was supported by grants from the Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER, PI15/01159); Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); the Catalan Association for Rett Syndrome; Fondobiorett and Mi Princesa Rett

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