Status of glaciers and climate change of East Karakoram in early twenty-first century.

This study aims to assess the glaciers change status in Shyok basin, East Karakoram in terms of area and mass balance, and to ascertain if glaciers in this part of Karakoram also display similar anomaly like central or western counterparts. The spatio-temporal monitoring of glaciers during the time frame of 24 years (1990/2000/2014) suggests major percentage of stable glaciers and insignificant retreat in the total glaciated area. The percentage of retreating glaciers has increased after year 2000. Area change analysis of glaciers having size >1 km2 (569 glaciers) suggests the number of fluctuated glaciers have substantially increased i.e. overall 56% glaciers remained stable, 35% retreated and 9% advanced during 1990-2014. The geodetic based findings using SRTM-C (2000) and Cartosat-1 (2010/2011/2014) stereo-imageries for 201 glaciers suggest the mass loss at the rate of -0.10 ± 0.07 m w.e. a-1. To better apprehend the status of glaciers changes in the region, climatic studies using in-situ observations as well as reanalysis dataset (ERA-I) were also undertaken of past 30 years. Therefore, this study is also a maiden attempt to ascertain if along with Karakoram anomaly, a climatic anomaly exists in the Eastern parts of Karakoram or not. A long term field collected snow-meteorological data of East Karakoram region suggests overall warming trend in annual temperature and no trend for snowfall during 1985-2015. The statistically significant increased rates of warming and decreased snowfall after year 2000 support the spatial variations in glaciers of East Karakoram and marginal mass loss. The observations of the marginal mass loss along with warming temperatures indicate that no Karakoram or climatic anomaly is existent over the East Karakoram region. Our study further refutes the prevalence of the elevation-dependent warming (EDW) over East Karakoram region vis-à-vis North-West Himalayan ranges. The impact of hiatus in global warming was also not observed over studied region.

Long-term mass balance modelling (1986-2018) and climate sensitivity of Siachen Glacier, East Karakoram.

Located in the eastern lap of the Karakoram Range, the Siachen Glacier is the second longest glacier in the non-polar areas of the world. High altitude, extreme climate and frequent military conflicts on this glacier create antagonistic surroundings for conventional field studies. Although recent advancements in geodetic technique have helped in the estimation of Siachen mass budget (MB), these geodetic estimates have been observed only for short time periods ranging 6 to 10 years. Hence, current study presents a comprehensive assessment of the Siachen long-term MB (32 years) based on temperature index (TI) model. Annual surface MB variability was modelled between 1986 and 2018 by forcing daily air temperature and precipitation from multiple ground stations distributed well across accumulation/ablation zone of the glacier. Mean annual temperature lapse rate (LR) was found midway between dry adiabatic and moist adiabatic LRs. Precipitation gradient (PG) was observed remarkably different below and above 4800 m.a.s.l. glacier altitude. Furthermore, snowmelt factor (SMF) was also estimated using snow thickness and positive degree days (PDDs) information over the glacier surface. Model results showed a nearly balanced condition (- 0.02 ± 0.05 m.w.e./year) during 1986-2006 followed by an accelerated rate of mass loss during 2007-2018 (- 0.11 ± 0.05 m.w.e./year), thus making the overall condition of Siachen MB negative during the period 1986-2018 (- 0.05 ± 0.05 m.w.e./year). Comparison of modelled MB was made with few geodetic studies conducted for the Siachen Glacier at different time scales (mainly after year 2000). Further, the sensitivity of the modelled glacier-wide MB was - 0.24 m.w.e./year for a temperature rise by 1 °C, while the sensitivity towards 10% increase in precipitation was estimated to be + 0.16 m.w.e./year. A relationship of the annual MB with accumulation area ratio (AAR) and equilibrium line altitude (ELA) was also established for Siachen glacier.

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

The importance of the tumor microenvironment in targeted anticancer therapies has been well recognized. Various protein factors participate in the cross-talk between tumor cells and non-malignant cells. Anterior gradient-2 (AGR2) is overexpressed in diverse human adenocarcinomas and it exists in both intracellular and extracellular spaces. Although intracellular AGR2 has been intensively investigated, the function of secreted AGR2, especially its exact mechanism of action is still poorly understood. Here we report that the secreted AGR2 promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts by enhancing the activities of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2). Further study indicated that AGR2 directly binds to these extracellular signaling molecules, and enhances their homodimerization. The extracellular AGR2 activity can be blocked to reduce angiogenesis and inhibit tumor growth in vitro and in vivo by a monoclonal antibody targeting the AGR2 self-dimerization region, and combined treatment with bevacizumab produced maximum inhibition effect. In conclusion, our investigation reveals a mechanism that directly links the secreted AGR2 with extracellular signaling networks, and we propose that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2.

Antibiotic stewardship in a tertiary care hospital of a developing country: establishment of a system and its application in a unit-GASP Initiative.

PURPOSE: Despite the proven benefits of antimicrobial stewardship, models for executing the same in the developing countries are sparse. The present study highlights the approaches undertaken by our group in initiating one such program in a public sector tertiary level health care setting of a developing country. METHODS: The study focussed on development of a system after evaluation of existing issues and case study of implementation of the program in a unit within the hospital. The system building exercise included (1) development of generic data capture form for prospective audit and feedback; (2) development of an electronic system for data capture; (3) identification of key intervention points for strategy decision for stewardship in a particular unit; (4) application of the stewardship method and (5) evaluation of outcomes. RESULTS: A digital system for prospective audit was constructed after a background study. In the study unit, there was a significant decline in double anaerobic coverage. There was a significant decline in the average number of antimicrobials used per patients and a decrease in Defined Daily Dose of designated antimicrobials was noted. Additionally, there was an increase in the use of optimized doses. CONCLUSION: A system for undertaking antimicrobial stewardship with a mechanism for prospective audit was put in place. The system may be adopted by other public sector hospitals of the developing country.

Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Mixed evidence exists regarding the effects of statins among men with prostate cancer. We aimed to determine the association between statin use and clinical outcomes in prostate cancer using systematic review and meta-analysis. METHODS: Original articles published until second week of August 2015 were searched in electronic databases (Medline-Ovid, Pubmed, Scopus, The Cochrane Library, Web of Science, ProQuest) for studies on statin use in prostate cancer. The main clinical outcomes for the review were: biochemical recurrence (BCR), metastases, and all-cause and prostate cancer-specific mortality. Meta-analysis was performed to calculate the pooled hazard ratio (pHR) and their 95% confidence interval (95% CI). Heterogeneity between the studies was examined using I(2) statistics. Meta-regression was performed, wherever significant heterogeneity was found in the meta-analyses, to find factors associated with poor outcomes, and sensitivity analyses were conducted to assess the robustness of findings. The analyses were conducted using RevMan v5.3, STATA v14, and R v3.1.1. RESULTS: Out of the 1002 retrieved citations, 34 observational cohort studies met the inclusion criteria. Statin use was associated with a 21% reduction in the risk of BCR among those treated with radiation therapy (pHR: 0.79, 95% CI: 0.65, 0.95, P-value=0.01, 10 studies, I(2)=54%), whereas it was not associated with the BCR among those treated with radical prostatectomy (pHR: 0.94, 95% CI: 0.81, 1.09, P-value=0.43, 15 studies, I(2)=65%). Statin use was associated with a 22% reduction in the risk of metastases (pHR: 0.78, 95% CI: 0.68, 0.87, P-value<0.001, 6 studies, I(2)=0%), and a 24% reduction in risk of both all-cause mortality (pHR: 0.76, 95% CI: 0.63, 0.91, P-value=0.004, 6 studies, I(2)=71%), and prostate cancer-specific mortality (pHR: 0.76, 95% CI: 0.64, 0.89, P-value=0.0007, 5 studies, I(2)=40%). CONCLUSIONS: Our systematic review found that statin significantly reduced the all-cause and prostate cancer-specific mortality and improved the BCR in certain subgroup of men with prostate cancer. In future, randomized controlled trials should be conducted to establish efficacy of statins among men with prostate cancer.

Health-related quality of life in patients with chronic obstructive pulmonary disease in North India.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major health problem in India and constitutes an important cause of mortality and morbidity. A cross-sectional study was undertaken to assess health-related quality of life (HRQL) and its determinants in patients with COPD from India. MATERIALS AND METHODS: A total of 126 patients (73.81% male) were enrolled using convenient sampling prospectively in this cross-sectional study. Eligible patients were assessed for socioeconomic status, anthropometric measures, COPD severity, dyspnea and health status using the Hindi version of St George's Respiratory Questionnaire (SGRQ). Linear regression model was used to examine the association between risk factors and HRQL score (a higher score indicating poorer HRQL), adjusting for age and sex. RESULTS: The mean total score for SGRQ in the patients was 52.66 ± 12.89, indicating a marked impairment of HRQL. Impairment was associated with the severity of airway obstruction, but within each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, the variation (SD) was wide [stage I: 47.8 ± 12.3 (n = 14); stage II: 49.28 ± 11.69 (n = 47); stage III: 53.47 ± 11.69 (n = 44); stage IV: 61.75 ± 14.14 (n = 21)]. A regression analysis showed that body mass index, forced expiratory volume in 1 s (FEV 1 ), dyspnea grade, and depression were associated with poor HRQL. CONCLUSION: HRQL of COPD patients was significantly impaired across stages. Marked impairment of HRQL was found even in patients with mild disease.

On the patterns of abundance and diversity of macrolichens of Chopta-Tunganath in the Garhwal Himalaya.

A total of 3211 colonies of macrolichens, from twelve 50 m x 10 m plots distributed across four macrohabitat (vegetation) types between 1500 m-3700 m in the Chopta-Tunganath landscape of the Garhwal Himalaya, yielded 13 families with 15 genera and 85 species. Lobaria retigera stood out as a broad-niched generalist species with moderate levels of abundance in all the three major microhabitats, viz. rock, soil and wood across 83% of all the plots sampled, whereas Umbilicaria indica emerged as an abundantly occurring specialist confined to rock substrates. Heterodermia incana and Leptogium javanicum appeared to be rare members of the community as they were encountered only once during the field survey. Woody microhabitats turned out to be richer than rock and soil substrates for macrolichens. Amongst the macrohabitats, middle altitude (2500-2800 m) Quercus forest was richest in species and genera followed by high altitude (2900-3200 m) Rhododendron forest, higher altitude grasslands (3300-3700 m) and then the lower elevation (1500 m) Quercus forest. Species, genus and family level alpha- as well as beta-diversities were significantly correlated with each other, implying that higher taxonomic ranks such as genera may be used as surrogates for species thus facilitating cost- and time-effective periodic monitoring of the biodiversity of macrolichens. Dynamics of the diversity of lichen communities in relation to various forms of environmental disturbance including livestock grazing and tourism as dominant land use activities in the higher Himalaya need further research.

Development and utilization of a drug information system in the Japanese pharmaceutical industry.

Pharmaceutical companies are responsible for providing updated, relevant information on the efficacy, safety and quality of drugs to medical professionals and finally to patients. To fulfill this responsibility, we must always endeavour to collect and evaluate the relevant information. We developed a drug information database system called Advanced Medical Online Network of Daiichi (AMOND) to manage various information generated during development of new products and after launch of the products using the classification format for retrieval. This system has been used for 9 years for the purpose of supporting medical representatives who play a primary role in the drug information services in the pharmaceutical industry. This system is incorporated into an on-line network system, and can be directly accessed by more than 1200 people at 11 branch offices and more than 110 subbranches all over the country. We upgraded this system to AMOND-II to improve the function, including retrieval and output abilities. As a result, utilization by users of this system increased six times. We report on the improved system, AMOND-II and our experience of the system.

The development and practical use of information systems in the pharmaceutical industry.

To provide information on the efficacy, safety, and quality of medicine promptly and accurately, we have developed two databases: a literature database with numerical data, and a Drug Information database. By an easy-to-use, company-wide information network system, over 1,000 medical representatives in more than 80 offices throughout Japan can retrieve information. Information derived from the system is displayed on the terminal and the original documents are automatically output through a facsimile.

Effect of AA-861, a selective 5-lipoxygenase inhibitor, on models of allergy in several species.

The effects of 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861), a selective 5-lipoxygenase inhibitor, on immunological or non-immunological release of slow reacting substance of anaphylaxis (SRS-A) and histamine and its effects on experimental asthma were investigated. AA-861 showed a dose-dependent inhibition of SRS-A release, with no effect on histamine release from passively sensitized guinea pig, monkey (M. irus) and human lung fragments. An analysis of the anaphylactic diffusate from the human lung fragments, using the combined technique of high performance liquid chromatography and radioimmunoassay, revealed that AA-861 markedly suppresses biosynthesis of the leukotrienes. However, this drug inhibits the release of histamine as well as SRS-A from lung fragments of anaphylactic monkey (M. mulatta) and in the Ca ionophore-stimulated rat peritoneal cavity. AA-861 suppressed the anaphylactically-induced airway resistance in mepyramine- and cimetidine-treated guinea pigs. These results suggest that AA-861 may be clinically effective for treating allergy-related asthma by modulating the 5-lipoxygenase pathway and that an inhibitory mechanism of histamine release by AA-861 may be present in some species.