ICRC mouse with congenital mega-esophagus as a model to study esophageal tumorigenesis

ICRC mouse, an inbred strain, developed at the Cancer Research Institute, Bombay, exhibits mega-esophagus with markedly hyperplastic mucosa. Diethylnitrosamine (DEN) when given in drinking water at the dose of 4 mg/kg body weight/day, induced esophageal papillomas consistently in 100% of the animals, in a short period of 12 weeks. Further, tumors were produced, even at a very low cumulative dose of 28 mg/kg body weight. Development of the esophageal papillomas was dose dependent. DEN even induces esophageal tumors transplacentally in the ICRC F1 progeny. Tobacco acts predominantly as a promoter in this system. ICRC mouse thus provides a much needed animal model to study esophageal tumorigenesis, including the two-stage carcino genesis. An interesting feature of the study is that initiation could be induced by exposure to low doses of DEN in the intra-uterine life. Tumors develop in such F1 animals only if they are fed tobacco, a predominant promoter, post-natally

Material Characterization of Carbon Fiber Reinforced Polymer Laminate Using Virtual Fields Method

Material Characterization of Carbon Fiber Reinforced Polymer Laminate Using Virtual Fields Metho

Preliminary estimation of temporal and spatiotemporal dynamic measures of COVID-19 transmission in Thailand

Background As a new emerging infectious disease pandemic, there is an urgent need to understand the dynamics of COVID-19 in each country to inform planning of emergency measures to contain its spread. It is essential that appropriate disease control activities are planned and implemented in a timely manner. Thailand was one of the first countries outside China to be affected with subsequent importation and domestic spread in most provinces in the country. Method A key ingredient to guide planning and implementation of public health measures is a metric of transmissibility which represents the infectiousness of a disease. Ongoing policies can utilize this information to plan appropriately with updated estimates of disease transmissibility. Therefore we present descriptive analyses and preliminary statistical estimation of reproduction numbers over time and space to facilitate disease control activities in Thailand. ResultsThe estimated basic reproduction number for COVID-19 during the study ranged from 2.23–5.90, with a mean of 3.75. We also tracked disease dynamics over time using temporal and spatiotemporal reproduction numbers. The results suggest that the outbreak was under control since the middle of April. After the boxing stadium and entertainment venues, the numbers of new cases had increased and spread across the country. Discussion Although various scenarios about assumptions were explored in this study, the real situation was difficult to determine given the limited data. More thorough mathematical modelling would be helpful to improve the estimation of transmissibility metrics for emergency preparedness as more epidemiological and clinical information about this new infection becomes available. However, the results can be used to guide interventions directly and to help parameterize models to predict the impact of these interventions

Zone Wise Local Characterization of Welds Using Digital Image Correlation: Uniform Stress and Virtual Fields Method

The process of welding is associated with high and varying thermal gradients across the weld, resulting in inhomogeneous material properties surrounding the weldment. A proper understanding of the varying mechanical properties of the weld and surrounding materials is important in designing and modelling of components with weld. In the initial study the characterisation of dierent zones such as fusion zone, heat aected zones and unaected base material of a deposited weld is carried out using uniform stress method (USM) involving digital image correlation (DIC) technique. A methodology using the micrographic observation and image processing is proposed for accurate identication of various weld zones. The response of welded samples in the elastic and plastic region is compared with the virgin sample. Full range stress-strain curves are obtained for each zone using the whole eld strain measurement involving DIC. The parameters investigated are Young's modulus, Poisson's ratio, yield stress, strain hardening exponent and strength coecient. A study regarding the variation of properties with respect to varying weld currents of 100 A, 130 A and 150 A is carried out. The Vickers micro hardness measurement is also conducted to obtain the variation in hardness across weldment. Fusion zone of all the welded samples have reported lower Young's modulus and higher yield strength compared to virgin samples. The Vicker's hardness values obtained for fusion and heat aected zones are in line with the yield stress variation obtained zone wise

Development of temporal modelling for forecasting and prediction of malaria infections using time-series and ARIMAX analyses: A case study in endemic districts of Bhutan

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 Economic Affairs. 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.</p> <p>Results</p> <p>It was found that the ARIMA (p, d, q) (P, D, Q)^smodel (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)¹²and (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. 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 of cases of the previous month was also a significant predictor in one district, whereas no variable could predict malaria cases for two districts.</p> <p>Conclusions</p> <p>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.</p

Cell-mediated immune status in patients with squamous cell carcinoma of the oral cavity

Sixteen untreated patients with squamous cell carcinoma of the oral cavity were tested for in vitro immune status in comparison with the normal healthy donors. The parameters investigated were total leukocyte and lymphocyte counts, percentages and absolute counts of T- and B-cells in circulation, subsets of T-cells identified by the Fc receptors, phytohemagglutinin (PHA), and mixed lymphocyte culture (MLC) responses, natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities, and circulating immune complexes (CICs). Eight of these patients were retested 3 to 6 months after surgery. The results showed that there was an increase in leukocyte and lymphocyte counts, an increase in the percentage and absolute number of B-lymphocytes, an increase in the percentage of T-gamma cells, suboptimal PHA and MLC responses, normal NK and ADCC activities, and increased levels of CICs in untreated oral cancer patients. In the postoperative stage, except for a reduction in leukocyte and lymphocyte counts, other abnormalities remained unchanged. The CICs in treated patients correlated with the tumor load in that in three patients showing recurrence, the CIC level remained elevated, whereas in patients without evidence of the disease the CIC level was either low or comparable to the upper normal limits

Malaria Elimination in the Greater Mekong Subregion: Challenges and Prospects

Malaria is a significant public health problem and impediment to socioeconomic development in countries of the Greater Mekong Subregion (GMS), which comprises Cambodia, China’s Yunnan Province, Lao People’s Democratic Republic, Myanmar, Thailand, and Vietnam. Over the past decade, intensified malaria control has greatly reduced the regional malaria burden. Driven by increasing political commitment, motivated by recent achievements in malaria control, and urged by the imminent threat of emerging artemisinin resistance, the GMS countries have endorsed a regional malaria elimination plan with a goal of eliminating malaria by 2030. However, this ambitious, but laudable, goal faces a daunting array of challenges and requires integrated strategies tailored to the region, which should be based on a mechanistic understanding of the human, parasite, and vector factors sustaining continued malaria transmission along international borders. Malaria epidemiology in the GMS is complex and rapidly evolving. Spatial heterogeneity requires targeted use of the limited resources. Border malaria accounts for continued malaria transmission and represents sources of parasite introduction through porous borders by highly mobile human populations. Asymptomatic infections constitute huge parasite reservoir requiring interventions in time and place to pave the way for malaria elimination. Of the two most predominant malaria parasites, Plasmodium falciparum and P. vivax, the prevalence of the latter is increasing in most member GMS countries. This parasite requires the use of 8-aminoquinoline drugs to prevent relapses from liver hypnozoites, but high prevalence of glucose-6-phosphate dehydrogenase deficiency in the endemic human populations makes it difficult to adopt this treatment regimen. The recent emergence of resistance to artemisinins and partner drugs in P. falciparum has raised both regional and global concerns, and elimination efforts are invariably prioritized against this parasite to avert spread. Moreover, the effectiveness of the two core vector control interventions—insecticide-treated nets and indoor residual spraying—has been declining due to insecticide resistance and increased outdoor biting activity of mosquito vectors. These technical challenges, though varying from country to country, require integrated approaches and better understanding of the malaria epidemiology enabling targeted control of the parasites and vectors. Understanding the mechanism and distribution of drug-resistant parasites will allow effective drug treatment and prevent, or slow down, the spread of drug resistance. Coordination among the GMS countries is essential to prevent parasite reintroduction across the international borders to achieve regional malaria elimination

High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.

57 primary tumour samples from Indian oral cancer patients with a 5-15 year tobacco chewing habit, were examined for mutational activation in codons 12, 13 and 61 of the H-ras, K-ras and N-ras oncogenes. The highly sensitive assay based on specific oligonucleotide hybridisation following in vitro amplification of unique sequences by polymerase chain reaction was employed. Mutations were detected in twenty (35%) of the samples and were restricted to H-ras, codons 12, 13 and 61. Two cases had concurrent mutations in codons 12 and 61. The majority of the mutations were at H-ras 61.2 (Glutamine to Arginine) and H-ras 12.2 (Glycine to Valine). Three of the less frequent mutations are apparently novel. Interestingly, eight of the samples with H-ras mutations also showed loss of wild-type H-ras, as judged by absence of signals for wild-type codons 12 or 61 on dot blots. The specific H-ras mutations in these oral malignancies associated with tobacco chewing, may represent an important example of an environmental carcinogen-induced step, in a pathway leading to malignant transformation