Smokeless tobacco - a substantial risk for oral potentially malignant disorders in South Asia

Data sources: Medline, the Science Citation Index (SCI) via Web of Science, Scopus, CINAHL, Global Index Medicus, Google Scholar and SLT-related reports of the International Agency for Research on Cancer and the National Cancer Institute of the United States. Study selection: Observational studies on the use of SLT and the risk of developing OPMDs in South Asian Populations. Data extraction and synthesis: Duplicate selection of studies was undertaken with two reviewers undertaking data abstraction and quality assessment independently. Risk and odds ratios were extracted or calculated for studies where possible. Meta odds ratios (mOR) were calculated using a random effects analysis. Results: Fifteen papers reporting 18 studies were included. The majority (12) were from India. All the studies were case-control designs. MOR for any OPMD with the use of any SLT product was 15.5 (95% CI; 9.9–24.2). Risk was higher in women; mOR = 22.2 (95% CI, 9.1–54.1) than men; mOR = 8.7 (95% CI, 2.1–34.8). Betel quid with tobacco carried the highest risk for OPMD, mOR = 16.1 (95% CI, 7.8–33.5). Conclusions: The findings of our study point towards a strong association between some forms of OPMDs and SLT use in South Asia. The risk estimates are high, irrespective of controlling for confounders such as smoking and alcohol or stratification by sex, country or source of controls. There is also an exposure-response relationship between OPMDs and SLT use

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL

Counseling patients about sexual health when considering post-prostatectomy radiation treatment

Prostate cancer is the second most frequently diagnosed cancer in men in the United States. Many men with clinically localized prostate cancer survive for 15 years or more. Although early detection and successful definitive treatments are increasingly common, a debate regarding how aggressively to treat prostate cancer is ongoing because of the effect of aggressive treatment on the quality of life, including sexual functioning. We examined current research on the effect of post-prostatectomy radiation treatment on sexual functioning, and suggest a way in which patient desired outcomes might be taken into consideration while making decisions with regard to the timing of radiation therapy after prostatectomy

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Elevational Distribution and Extinction Risk in Birds

Mountainous regions are hotspots of terrestrial biodiversity. Unlike islands, which have been the focus of extensive research on extinction dynamics, fewer studies have examined mountain ranges even though they face increasing threats from human pressures – notably habitat conversion and climate change. Limits to the taxonomic and geographical extent and resolution of previously available information have precluded an explicit assessment of the relative role of elevational distribution in determining extinction risk. We use a new global species-level avian database to quantify the influence of elevational distribution (range, maximum and midpoint) on extinction risk in birds at the global scale. We also tested this relationship within biogeographic realms, higher taxonomic levels, and across phylogenetic contrasts. Potential confounding variables (i.e. phylogenetic, distributional, morphological, life history and niche breadth) were also tested and controlled for. We show that the three measures of elevational distribution are strong negative predictors of avian extinction risk, with elevational range comparable and complementary to that of geographical range size. Extinction risk was also found to be positively associated with body weight, development and adult survival, but negatively associated with reproduction and niche breadth. The robust and consistent findings from this study demonstrate the importance of elevational distribution as a key driver of variation in extinction dynamics in birds. Our results also highlight elevational distribution as a missing criterion in current schemes for quantifying extinction risk and setting species conservation priorities in birds. Further research is recommended to test for generality across non-avian taxa, which will require an advance in our knowledge of species’ current elevational ranges and increased efforts to digitise and centralise such data

Economic Analysis of Corporate Law

The economic analysis of corporate law applies the concepts and tools of microeconomics to the study of the legal rules, regulations and practices that govern the formation and operation of business corporations, most notably as regards the rights and duties of directors, officers, shareholders, and creditors. The literature has focused mostly on publicly-traded corporations, but the analytical framework extends to the simpler cases of close corporations and limited liability companies and the more complex case of corporate groups. This article outlines the foundations of the economic analysis of corporate law, contrasts the classic approach with more recent functional scholarship, and briefly discusses the law and economics of three specific issues: limited liability, managerial liability, and takeovers