The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

The impacts of omnichannel retailing properties on customer experience and brand loyalty: A study in the banking sector

AbstractOmnichannel retailing is regarded as an emerging trend in banking. The purpose of this study is to analyze the potential effects of omnichannel retailing properties on customer experience and brand loyalty; it further explores the moderating role of transaction channels. Its centrality has been focused on omnichannel retailing cues comprising integration quality, perceived fluency, and assurance quality; customer experience is analyzed through hedonic and utilitarian values. This study uses the non-probabilistic sampling technique with approximately 1547 respondents via the self-administered questionnaires. The findings indicate that perceived fluency and assurance quality are proved as the critical components of hedonic and utilitarian experiences. It has been found that increasing integration quality leads to a more positive perception of fluency and enhances omnichannel experience quality by switching various channels. This study validates the importance of hedonic and utilitarian experiences which significantly contribute to constituting brand loyalty between clients and banks in omnichannel retailing. The importance of various channels was affirmed as a significant moderator when indicating the effect of perceived fluency on customer experience via physical channels is stronger than digital channels. Applications and limitations are further discussed

An association between chronic undernutrition and educational test scores in Vietnamese children

OBJECTIVE: To examine the association between results of educational tests and the anthropometric status of schoolchildren. DESIGN: Cross-sectional data collected during the baseline survey of a randomised trial. SETTING: Eighty-one primary schools in three districts of northern Vietnam. SUBJECTS: A total of 3055 schoolchildren enrolled in class 3 and born in 1990. MAIN OUTCOME MEASURES: Tests of mathematics and Vietnamese language developed not to show floor or ceiling effects, and Z-scores of height-for-age, weight-for-age and weight-for-height. RESULTS: After controlling for age, sex, district and school the results of test scores in both mathematics and Vietnamese were significantly negatively correlated with Z-scores of height-for-age (P<0.001) and weight-for-age (P<0.001), but not with weight-for-height (P=0.75). CONCLUSIONS: A cross-sectional negative association was observed in Vietnamese primary school children between indicators of chronic undernutrition and tests of educational achievement. SPONSORSHIP: The study was funded by donors to the Partnership for Child Development including the Rockefeller Foundation and the World Bank

Synthesis of new [γ-(Aryl)pyridino]dibenzo-27,28-diazacrownophanes containing two pyridine rings

In continuation of developing new cytotoxic compounds, six azacrownophanes containing both 2,4,6-triarylpyri-dine and 2,6-bis(phenoxymethyl)pyridine moieties were synthesized successfully by one-step domino-condensation of podand 2,6-bis[(2-acetophenyl)oxymethyl]pyridine, arylaldehydes and ammonium acetate according to the conditions of Hantzsch reactions. The compounds 5a-c were selected for cytotoxicity evaluations against human cell lines (HepG2, Lu1, RD, FL and MCF-7). Compound 5b showing the highest cytotoxicity is interesting for the development of promising anticancer drugs. © ISUCT Publishing

Noise, nonlinearity and seasonality: the epidemics of whooping cough revisited

Understanding the mechanisms that generate oscillations in the incidence of childhood infectious diseases has preoccupied epidemiologists and population ecologists for nearly two centuries. This body of work has generated simple yet powerful explanations for the epidemics of measles and chickenpox, while the dynamics of other infectious diseases, such as whooping cough, have proved more challenging to decipher. A number of authors have, in recent years, proposed that the noisy and somewhat irregular epidemics of whooping cough may arise due to stochasticity and its interaction with nonlinearity in transmission and seasonal variation in contact rates. The reason underlying the susceptibility of whooping cough dynamics to noise and the precise nature of its transient dynamics remain poorly understood. Here we use household data on the incubation period in order to parametrize more realistic distributions of the latent and infectious periods. We demonstrate that previously reported phenomena result from transients following the interaction between the stable annual attractor and unstable multiennial solutions

A trial of Itraconazole or Amphotericin B HIV-associated talaromycosis

Background Talaromyces marneffei infection is a major cause of HIV-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate but it has significant side effects, high cost and limited availability. Itraconazole is orally available, better- tolerated and widely-used in place of amphotericin; however, these two strategies have not been compared in clinical trials. Methods In this open-label non-inferiority trial, we randomly assigned 440 HIV-infected adults with microscopy- or culture-confirmed talaromycosis between October 2012 and December 2015 across Vietnam to receive amphotericin 0.7 mg/kg/day (N=219) or itraconazole 400 mg/kg/day (N=221) for two weeks, followed by itraconazole maintenance therapy in all patients. The primary outcome was mortality by two weeks. Secondary outcomes included mortality by week 24, time to clinical resolution, early fungicidal activity, disease relapse, immune reconstitution inflammatory syndrome (IRIS), and tolerability. Results Mortality by two weeks was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.7 percentage points; non-inferiority P<0.0001); however, mortality risks by week 24 were 11.3% and 21.0%, respectively (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6 percentage points; P=0.006). Amphotericin was associated with significantly faster clinical resolution and fungal clearance, and lower rates of relapse and immune reconstitution inflammatory syndrome (IRIS). Patients on amphotericin experienced more infusion reactions, renal failure, hypokalemia, hypomagnesaemia, and anemia. Conclusions Amphotericin is superior to itraconazole as initial therapy for talaromycosis in terms of six-month mortality, clinical response, and fungicidal activity