The personal assessments of the current and expected future state of the environment by 3232 community respondents in 18 nations were investigated at the local, national, and global spatial levels. These assessments were compared to a ranking of each country’s environmental quality by an expert panel. Temporal pessimism (“things will get worse”) was found in the assessments at all three spatial levels. Spatial optimism bias (“things are better here than there”) was found in the assessments of current environmental conditions in 15 of 18 countries, but not in the assessments of the future. All countries except one exhibited temporal pessimism, but significant differences between them were common. Evaluations of current environmental conditions also differed by country. Citizens’ assessments of current conditions, and the degree of comparative optimism, were strongly correlated with the expert panel’s assessments of national environmental quality. Aside from the value of understanding global trends in environmental assessments, the results have important implications for environmental policy and risk management strategies

Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumour cell intrinsic and microenvironmental features underpinning CPI sensitization. Here we collated whole-exome and transcriptomic data for >1000 CPI-treated patients across eight tumor-types, utilizing standardized bioinformatics-workflows and clinical outcome-criteria to validate multivariate predictors of CPI-sensitization. Clonal-TMB was the strongest predictor of CPI response, followed by TMB and CXCL9 expression. Subclonal-TMB, somatic copy alteration burden and HLA-evolutionary divergence failed to attain significance. Discovery analysis identified two additional determinants of CPI-response supported by prior functional evidence: 9q34.3 (TRAF2) loss and CCND1 amplification, both independently validated in >1600 CPI-treated patients. We find evidence for collateral sensitivity, likely mediated through selection for CDKN2A-loss, with 9q34.3 loss as a passenger event leading to CPI-sensitization. Finally, scRNA sequencing of clonal neoantigen-reactive CD8-TILs, combined with bulk RNAseq analysis of CPI responding tumors, identified CCR5 and CXCL13 as T cell-intrinsic mediators of CPI-sensitisation.

A concentric cylinder bioreactor has been developed to culture tissue engineered cartilage constructs under hydrodynamic loading. This bioreactor operates in a low shear stress environment, has a large growth area for construct production, allows for dynamic seeding of constructs, and provides for a uniform loading environment. Porous poly-lactic acid constructs, seeded dynamically in the bioreactor using isolated bovine chondrocytes, were cultured for 4 weeks at three seeding densities (60, 80, 100 x 10(6) cells per bioreactor) and three different shear stresses (imposed at 19, 38, and 76 rpm) to characterize the effect of chondrocyte density and hydrodynamic loading on construct growth. Construct seeding efficiency with chondrocytes is greater than 95% within 24 h. Extensive chondrocyte proliferation and matrix deposition are achieved so that after 28 days in culture, constructs from bioreactors seeded at the highest cell densities contain up to 15 x 10(6) cells, 2 mg GAG, and 3.5 mg collagen per construct and exhibit morphology similar to that of native cartilage. Bioreactors seeded with 60 million chondrocytes do not exhibit robust proliferation or matrix deposition and do not achieve morphology similar to that of native cartilage. In cultures under different steady hydrodynamic loading, the data demonstrate that higher shear stress suppresses matrix GAG deposition and encourages collagen incorporation. In contrast, under dynamic hydrodynamic loading conditions, cartilage constructs exhibit robust matrix collagen and GAG deposition. The data demonstrate that the concentric cylinder bioreactor provides a favorable hydrodynamic environment for cartilage construct growth and differentiation. Notably, construct matrix accumulation can be manipulated by hydrodynamic loading. This bioreactor is useful for fundamental studies of construct growth and to assess the significance of cell density, nutrients, and hydrodynamic loading on cartilage development. In addition, studies of cartilage tissue engineering in the well-characterized, uniform environment of the concentric cylinder bioreactor will develop important knowledge of bioprocessing parameters critical for large-scale production of engineered tissues.

Background:Lung cancer is one of the most aggressive and prevalent type of malignancy causing high morbidity and mortality. Tobacco smoking continues to be the leading cause of lung cancer worldwide. An increasing incidence of lung cancer has been observed in India.Objective:The aim of this study was to evaluate the clinico, a pathological profile of the lung cancer in hilly state of Uttrakhand.Materials and Methods:We performed a retrospective analysis of histopathologically proven cases of bronchogenic carcinoma admitted in our hospital from January 1998 to August 2005.Results:Our study included 203 patients with confirmed cases of lung cancer. Male to female ratio was 8.2:1. The common age group being 40-60 years, 9.86% of the patients were less than 40 years old age. Smoking was found to be the main risk factor in 81.77% patients. The most frequent symptom was cough (72.90%) followed by fever (58.12%). The most common radiological presentation was mess lesion (46.31%). The most common histopathological type was squamous cell carcinoma (SCC) (44.83%) followed by adenocarcinoma (19.78%) and small cell lung carcinoma (SCLC) (16.75%). The majority patients (73.29%) were diagnosed in the later stages of the disease (III B and IV).Conclusion:It was found out that SCC was the most frequent histopathological form. SCLC predominates below 40 year and SCC over 60 years of age. Smoking still remains the major risk factors in pathogenesis of lung cancer.