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Patients with metastatic urothelial carcinoma have a dismal prognosis and few treatment options after first-line chemotherapy. Responses to second-line treatment are uncommon. We assessed nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for safety and activity in patients with metastatic or surgically unresectable urothelial carcinoma whose disease progressed or recurred despite previous treatment with at least one platinum-based chemotherapy regimen. In this multicentre, phase 2, single-arm study, patients aged 18 years or older with metastatic or surgically unresectable locally advanced urothelial carcinoma, measurable disease (according to Response Evaluation Criteria In Solid Tumors v1.1), Eastern Cooperative Oncology Group performance statuses of 0 or 1, and available tumour samples for biomarker analysis received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression and clinical deterioration, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was overall objective response confirmed by blinded independent review committee in all treated patients and by tumour PD-L1 expression (≥5% and ≥1%). This trial is registered with ClinicalTrials.gov, number NCT02387996, and is completed. Follow-up is still ongoing. Between March 9, 2015, and Oct 16, 2015, 270 patients from 63 sites in 11 countries received nivolumab, and 265 were evaluated for activity. Median follow-up for overall survival was 7·00 months (IQR 2·96–8·77). Confirmed objective response was achieved in 52 (19·6%, 95% CI 15·0–24·9) of 265 patients. Confirmed objective response was achieved in 23 (28·4%, 95% CI 18·9–39·5) of the 81 patients with PD-L1 expression of 5% or greater, 29 (23·8%, 95% CI 16·5–32·3) of the 122 patients with PD-L1 expression of 1% or greater, and 23 (16·1%, 95% CI 10·5–23·1) of the 143 patients with PD-L1 expression of less than 1%. Grade 3–4 treatment-related adverse events occurred in 48 (18%) of 270 patients—most commonly grade 3 fatigue and diarrhoea, which each occurred in five patients. Three deaths were attributed to treatment (pneumonitis, acute respiratory failure, and cardiovascular failure). Nivolumab monotherapy provided meaningful clinical benefit, irrespective of PD-L1 expression, and was associated with an acceptable safety profile in previously treated patients with metastatic or surgically unresectable urothelial carcinoma. Bristol-Myers Squibb.

An experimental investigation of natural convection heat transfer to non-Newtonian fluids from isothermal, vertical and horizontal flat plates has been carried out. The apparatus used was similar to that of Saunders (16) and Reilly (14). Three non-Newtonian fluids were used in this work to study the effect of flow behavior index (from 0.2 to 0.67) on the heat transfer coefficients. A correlation of the form [special characters omitted]represents the heat transfer results in a satisfactory manner. Dimensionless parameters generalized to include non-Newtonian effects were used to correlate the experimental data employing the method of least squares and yielded the following empirical equations. [special characters omitted](a) Vertical Plates [special characters omitted](b) Horizontal Plate, Heated face up [special characters omitted](c) Horizontal Plate, Heated face down [special characters omitted] These general expressions are valid only for heat transfer in the laminar flow range.

Coronavirus disease 2019 personal protective equipment has been reported to affect communication in healthcare settings. This study sought to identify those challenges experimentally. Bamford-Kowal-Bench speech discrimination in noise performance of healthcare workers was tested under simulated background noise conditions from a variety of hospital environments. Candidates were assessed for ability to interpret speech with and without personal protective equipment, with both normal speech and raised voice. There was a significant difference in speech discrimination scores between normal and personal protective equipment wearing subjects in operating theatre simulated background noise levels (70 dB). Wearing personal protective equipment can impact communication in healthcare environments. Efforts should be made to remind staff about this burden and to seek alternative communication paradigms, particularly in operating theatre environments.

Low back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP. The clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention. Post-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58). The findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.

Sheath blight caused by necrotrophic fungus Rhizoctonia solani Kühn is one of the most serious diseases of rice. Use of high yielding semi dwarf cultivars with dense planting and high dose of nitrogenous fertilizers accentuates the incidence of sheath blight in rice. Its diverse host range and ability to remain dormant under unfavorable conditions make the pathogen more difficult to manage. As there are no sources of complete resistance, management through chemical control has been the most adopted method for sheath blight management. In this review, we provide an up-to-date comprehensive description of host-pathogen interactions, various control measures such as cultural, chemical, and biological as well as utilizing host plant resistance. The section on utilizing host plant resistance includes identification of resistant sources, mapping QTLs and their validation, identification of candidate gene(s) and their introgression through marker-assisted selection. Advances and prospects of sheath blight management through biotechnological approaches such as overexpression of genes and gene silencing for transgenic development against R. solani are also discussed.

Basmati is a speciality segment in the rice genepool characterised by explicit grain quality. For the want of suitable populations, genome-wide association study (GWAS) in Basmati rice has not been attempted. To address this gap, we have performed a GWAS on a panel of 172 elite Basmati multiparent population comprising of potential restorers and maintainers. Phenotypic data was generated for various agronomic and grain quality traits across seven different environments during two consecutive crop seasons. Based on the observed phenotypic variation, three agronomic traits namely, days to fifty per cent flowering, plant height and panicle length, and three grain quality traits namely, kernel length before cooking, length breadth ratio and kernel length after cooking were subjected to GWAS. Genotyped with 80K SNP array, the population was subjected to principal component analysis to stratify the underlying substructure and subjected to the association analysis using Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model. We identified 32 unique MTAs including 11 robust MTAs for the agronomic traits and 25 unique MTAs including two robust MTAs for the grain quality traits. Six out of 13 robust MTAs were novel. By genome annotation, six candidate genes associated with the robust MTAs were identified. Further analysis of the allelic combinations of the robust MTAs enabled the identification of superior allelic combinations in the population. This information was utilized in selecting 77 elite Basmati rice genotypes from the panel. This is the first ever GWAS study in Basmati rice which could generate valuable information usable for further breeding through marker assisted selection, including enhancing of heterosis.