Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus

We have investigated the apoptotic levels and expression of the apoptotic inducer Bak in non-melanoma skin cancers. Squamous cell carcinomas of known human papillomavirus status from immunocompetent patients were analysed for the expression of the Bak protein, and the expression profile was compared both to the presence of apoptotic cells and the proliferation marker Ki-67. We demonstrate an inverse correlation between human papillomavirus positivity and Bak expression in squamous cell carcinomas, with concomitantly fewer apoptoic cells being detected in the human papillomavirus positive tumours. Bak expression was not observed in basal cell carcinomas irrespective of human papillomavirus status, suggesting that Bak only plays a role in signalling apoptosis in squamous, but not basal, cell cancers. No differences were observed in the proliferation rates between papillomavirus positive and negative squamous cell tumours. However, a significant decrease in the number of apoptotic cells was observed in human papillomavirus-positive squamous cell carcinomas which suggests that the virus may have significantly altered the relationship between proliferation and apoptosis in a proportion of these tumours

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.

Facies architecture and depositional model for a fine-grained hybrid-energy delta: An example from the Upper Cambrian to Lower Ordovician Barik Formation, Central Oman

Recognizing ancient deltas' depositional architecture is challenging due to the complex interplay of the fluvial, waves, and tidal processes. The integration of field-based sedimentological and trace fossils studies of the Late Cambrian-Early Ordovician Barik Formation in Central Oman allowed better identification of different lithofacies architectures and depositional process signatures. The Barik Formation is a major tight-gas reservoir in the Oman Sedimentary Basins, where it is over 800-m thick. The only outcrop analogue is in the Qarn Mahatta Humaid area, where ca. 50-m thickness of the formation is exposed and extends laterally over 5 km. This study revealed the presence of four lithofacies associations, including (a) mouth bar/shoreface, (b) tidal flat, (c) tidal channel, and (d) delta distributary channels using 12 logged sections. The depositional features identified in the field include tidal, wave/storm, and fluvial. The tidal signatures are represented by mud-drapes, large-scale reactivation surfaces, sigmoidal cross-bedding, and climbing and flaser bedding, predominantly in the mixed mud-sand tidal flats of the lower delta plain and delta distributary channels of the upper to lower delta plains. The wave/storm signatures are represented by wave ripples and small-scale hummocky cross-stratification in the mouth bar/shoreface of the delta front platform. The fluvial and subaerial signatures are represented by the occurrence of the scour surfaces with lag deposits of channel-fill and the development of desiccation mud-cracks. The Barik Formation delta sandstones form amalgamated sheet-like bodies prograding to the north-northeast and deposited along a ramp-type low relief basin. This prograding delta represents a highstand system tract. This study presents an example of the ancient fine-grained hybrid-energy prograding delta, where fluvial processes operated beside the tidal and wave/storm processes over a broad and low relief shelf in a vegetation-free system.This work is supported by His Majesty's Trust Fund Grant # SR/SCI/ETHS/15/01 to Sultan Qaboos University (SQU

Renewable and low-carbon energies as mitigation options of climate change for China

This article discusses how renewable and low-carbon energies can serve as mitigation options of climate change in China’s power sector. Our study is based on scenarios developed in PowerPlan, a bottom-up model simulating a countries’ power sector and its emissions. We first adjusted the model to China’s present-day economy and power sector. We then developed different scenarios based on story lines for possible future developments in China. We simulated China’s carbon-based electricity production system of today and possible future transitions towards a low-carbon system relying on renewable and low-carbon energies. In our analysis, we compare the business-as-usual scenarios with more sustainable energy scenarios. We found that by increasing the share of renewable and nuclear energies to different levels, between 17% and 57% of all CO2 emissions from the power sector could be avoided by 2030 compared to the business-as-usual scenario. We also found that electricity generation costs increase when more sustainable power plants are installed. As a conclusion, China has two options: choosing for high climate change mitigation and high costs or choosing for moderate climate change mitigation and moderate costs. In case high climate change mitigation will be chosen, development assistance is likely to be needed to cover the costs.