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Background: We evaluated the long-term effect of stereotactic body radiation therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for local therapy or surgery. Methods: Forty-two HCC patients with tumors [less than or equal to] 100 cc and ineligible for local ablation therapy or surgical resection were treated with SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8) and median follow-up duration 28.7 months (8.4-49.1). Results: Complete response (CR) for the in-field lesion was initially achieved in 59.6% and partial response (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18 patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively. Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In-field progression-free survival at 1 and 3 years was 72.0% and 67.5%, respectively. Patients with smaller tumor had better in-field progression-free survival and overall survival rates ([less than]32 cc vs. [greater than or equal to]32 cc, P [less than] 0.05). No major toxicity was encountered but one patient died with extrahepatic metastasis and radiation-induced hepatic failure. Conclusions: SBRT is a promising noninvasive-treatment for small HCC that is ineligible for local treatment or surgical resection.

Background: Malaria still remains a public health problem in some districts of Bhutan despite marked reduction of cases in last few years. To strengthen the country's prevention and control measures, this study was carried out to develop forecasting and prediction models of malaria incidence in the endemic districts of Bhutan using time series and ARIMAX. Methods: This study was carried out retrospectively using the monthly reported malaria cases from the health centres to Vector-borne Disease Control Programme (VDCP) and the meteorological data from Meteorological Unit, Department of Energy, Ministry of Economics. Time series analysis was performed on monthly malaria cases, from 1994 to 2008, in seven malaria endemic districts. The time series models derived from a multiplicative seasonal autoregressive integrated moving average (ARIMA) was deployed to identify the best model using data from 1994 to 2006. The best-fit model was selected for each individual district and for the overall endemic area was developed and the monthly cases from January to December 2009 and 2010 were forecasted. In developing the prediction model, the monthly reported malaria cases and the meteorological factors from 1996 to 2008 of the seven districts were analysed. The method of ARIMAX modelling was employed to determine predictors of malaria of the subsequent month. Results: It was found that the ARIMA (p, d, q) (P, D, Q)s model ( p and P representing the auto regressive and seasonal autoregressive; d and D representing the non-seasonal differences and seasonal differencing; and q and Q the moving average parameters and seasonal moving average parameters, respectively and s representing the length of the seasonal period) for the overall endemic districts was (2,1,1)(0,1,1)12 ; the modelling data from each district revealed two most common ARIMA models including (2,1,1)(0,1,1)12 and (1,1,1)(0,1,1)12. The forecasted monthly malaria cases from January to December 2009 and 2010 varied from 15 to 82 cases in 2009 and 67 to 149 cases in 2010, where population in 2009 was 285,375 and the expected population of 2010 to be 289,085, respectively. The ARIMAX model of monthly cases and climatic factors showed considerable variations among the different districts. In general, the mean maximum temperature lagged at one month was a strong positive predictor of an increased malaria cases for four districts. The monthly number cases of the previous month were also a significant predictor in one district, whereas no variables could predict malaria cases for two districts. Conclusions: The ARIMA models of time-series analysis were useful in forecasting the number of cases in the endemic areas of Bhutan. There was no consistency in the predictors of malaria cases when using ARIMAX model with selected lag times and climatic predictors. The ARIMA forecasting models could be employed for planning and managing malaria prevention and control programme in Bhutan.

Background: Searching a database of protein structures for matches to a query structure, or occurrences of astructural motif, is an important task in structural biology and bioinformatics. While there are many existingmethods for structural similarity searching, faster and more accurate approaches are still required, and fewcurrent methods are capable of substructure (motif) searching. Results: We developed an improved heuristic for tableau-based protein structure and substructure searchingusing simulated annealing, that is as fast or faster, and comparable in accuracy, with some widely used existingmethods. Furthermore, we created a parallel implementation on a modern graphics processing unit (GPU). Conclusions: The GPU implementation achieves up to 34 times speedup over the CPU implementation oftableau-based structure search with simulated annealing, making it one of the fastest available methods. To thebest of our knowledge, this is the first application of a GPU to the protein structural search problem.

Background: The oncogene CDC25B phosphatase plays an important role in cancer cell growth. We have recently reported that patients with esophageal squamous cell carcinoma (ESCC) have significantly higher serum levels of CDC25B autoantibodies (CDC25B-Abs) than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical significance of serum CDC25B-Abs in patients with ESCC. Methods: CDC25B autoantibodies were measured in sera from both 134 patients with primary ESCC and 134 healthy controls using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which anti-CDC25B antibodies bound CDC25B antigen purified from Eca-109 ESCC tumor cells. The clinicopathologic significance of CDC25B serum autoantibodies was compared to that of the tumor markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment antigen 21-1(CYFRA21-1) . Results: Higher levels of CDC25B autoantibodies were present in sera from patients with ESCC (A450=0.917, SD=0.473) than in sera from healthy control subjects (A450=0.378, SD=0.262, P<0.001). The area under the receiver operating characteristic (ROC) curve for CDC25B-Abs was 0.870 (95% CI: 0.835-0.920). The sensitivity and specificity of CDC25B-Abs for detection of ESCC were 56.7% and 91.0%, respectively, when CDC25-Abs-positive samples were defined as those with an A450 greater than the cut-off value of 0.725. Relatively few patients tested positive for the tumor markers CEA, SCC-Ag and CYFRA21-1 (13.4% ,17.2%, and 32.1%, respectively). A significantly higher number of patients with ESCC tested positive for a combination of CEA, SCC, CYFRA21-1 and CDC25B-Abs (64.2%) than for a combination of CEA, SCC-Ag and CYFRA21-1 (41.0%, P<0.001). The concentration of CDC25B autoantibodies in serum was significantly correlated with tumor stage (P<0.001). Although examination of the total patient pool showed no obvious relationship between CDC25B autoantibodies and overall survival, in the subgroup of patients with stage III-IV tumors, the cumulative five-year survival rate of CDC25B-seropositive patients was 6.7%, while that of CDC25B-seronegative patients was 43.4% (P=0.001, log-rank). In the N1 subgroup, the cumulative five-year survival rate of CDC25B-seropositive patients was 13.6%, while that of CDC25B-seronegative patients was 54.5% (P=0.040, log-rank). Conclusions: Detection of serum CDC25B-Abs is superior to detection of the tumor markers CEA, SCC-Ag and CYFRA21-1 for diagnosis of ESCC, and CDC25B-Abs are a potential prognostic serological marker for advanced ESCC.

Background: High fertility among young people aged 15-24 years is a public health concern in Uganda. Unwanted pregnancy, unsafe induced abortions and associated high morbidity and mortality among young women may be attributed to low contraceptive use. This study aims at exploring reasons for low contraceptive use among young people. Methods: In 16 focus group discussions, the views of young people about obstacles and enabling factors to contraceptive use in Mityana and Mubende districts, Uganda were explored. The groups were homogeneously composed by married and unmarried men and women, between the ages of 15-24. The data obtained was analyzed using qualitative content analysis. Results: Young men and women described multiple obstacles to contraceptive use. The obstacles were categorized as misconceptions and fears related to contraception, gender power relations, socio-cultural expectations and contradictions, short term planning, and health service barriers. Additionally, young people recounted several enabling factors that included female strategies to overcome obstacles, changing perceptions to contraceptive use, and changing attitude towards a small family size. Conclusions: Our findings suggest changing perceptions and behavior shift towards contraceptive use and a small family size although obstacles still exist. Personalized strategies to young women and men are needed to motivate and assist young people plan their future families, adopt and sustain use of contraceptives. Reducing obstacles and reinforcing enabling factors through education, culturally sensitive behavior change strategies have the potential to enhance contraceptives use. Alternative models of contraceptive service delivery to young people are proposed.Key words: contraceptive use, young people, fertility, obstacles, enabling factors, Uganda