Effects of climatic variability and soil quality on the production of large cardamom in Dhankuta

This research was objectively carried out to assess the current status of large cardamom production, major climatic induced impact on production and challenges faced by farmers of Dhankuta district and soil fertility status. The local farmers were categorized as large, medium and small. The farmers of Majhgaun-4 of Pakhribas municipality and Namjang-6 of Chhattar Jorpati municipality growing large cardamom were selected for this study. The field work was conducted applying stratified random sampling between July to August, 2019.Total 90 questionnaire survey and 2 key informant interview were organized to collect the primary data. Total 20 soil samples were collected from 0-30 cm depth. Besides, monthly data of temperature and rainfall were collected from Department of Hydrology and Meteorology. The result showed that the average household production of large, medium and small farmers of Majhgaun-4 has been decreasing with an average rate of 0.363 ton/ha, 0.088 ton/ha 0.078 ton/ha per year respectively. Mann Kendall’s tau correlation showed that there was a significant relationship of average annual temperature and average temperature of critical season of Pakhribas and Dhankuta station having R values 0.733 and 0.643 respectively. The rainfall in both the station Pakhribas and Dhankuta , was decreasing with the rate of -2.696 and -8.618 mm/year. The relation between average household production and average temperature of critical season of Majhgaun was significant. The soil fertility of Majhgaun was the best. The principal component analysis showed that the highest challenges faced by farmers was disease and followed by drought. This research will be useful for large cardamom experts.Keywords: Climate change, large cardamom, productivity, soil fertility status

Случай раннего выявления метастазов в бедренной кости у больного раком полового члена

Background. Bone metastasis is very common in the advanced stage of numerous carcinomas. In penile carcinoma, lymph nodes metastasis is somehow common but it is very rare reported to be secondary from penile cancer. till the date, there are only few cases of penis carcinoma reported bone metastasis in literature worldwide.Case Presentation. Herein, We presented a 51-year-old Nepalese male with squamous cell carcinoma of penis. computed tomography (ct) scan of the patient revealed that there was carcinoma involving glans penis and precure with bilateral external & internal inguinal lymphadenopathies. After then, the patient was under gone for partial penectomy and bilateral inguinal lymphadenectomy and complete 6-cycle chemotherapy. After one year of treatment, patient developed thigh pain and headache and he advised to have magnetic Resonance imaging (mRi) of brain, 99mTc-MDP whole body bone scan and ct scan of pelvis and thigh. The examination report reveals that there was a sclerotic change in vertex of skull bone and moderate 99mTc-MDP uptake in right proximal shaft of femur just below the neck d/d metastasis. The histopathological examination of the true cut biopsy taken from the lesion of the femur showed metastatic keratinizing squamous cell carcinoma which is rare case of femoral shaft bone metastasis secondary from penile carcinoma. Then patient was sent for surgical reconstruction of femur. Based on the case studies review femur shaft bone metastasis from penile cancer is extremely rare.Conclusion. The best of our knowledge; this is the first early detected bone metastases to shaft of the femur in a patient with penile cancer. early diagnosis helps to radical treatment as well as palliative treatment. surgery is the preferred option of the treatments, especially for metastatic foci in the long bones.Аннотация Метастазы в кости часто встречаются на поздних стадиях разных злокачественных новообразований. Для рака полового члена характерно лимфогенное метастазирование, костные метастазы встречаются очень редко. На данный момент в мировой литературе зарегистрировано лишь несколько случаев рака полового члена с метастазами в кости.Описание клинического случая. Мы представляем описание клинического случая плоскоклеточного рака полового члена у 51-летнего мужчины из Непала. Компьютерная томография (КТ) выявила рак полового члена, локализованный на головке и крайней плоти с двусторонней паховой лимфаденопатией. Пациенту выполнена частичная пенэктомия, двусторонняя паховая лимфаденэктомия, проведено 6 курсов адъювантной химиотерапии. Через один год после завершения лечения у пациента появились боли в бедре и головная боль, рекомендована МРТ головного мозга, сканирование костей скелета с 99mTc-MDP и КТ таза и бедра. Обследование показало наличие склеротических изменений в теменной кости черепа и умеренное накопление 99mTc-MDP в проксимальном отделе правом бедренной кости ниже шейки. Гистологическое исследование биоптата, взятого из очага в бедренной кости, выявило метастаз ороговевающего плоскоклеточного рака, что является редким случаем метастазирования рака полового члена в диафиз бедренной кости. Пациент был направлен на хирургическую реконструкцию бедренной кости. Согласно обзору клинических исследований, метастазы в диафизе бедренной кости при раке полового члена встречаются крайне редко.Заключение. Представлен первый случай раннего выявления костных метастазов в диафизе бедренной кости у пациента с раком полового члена. Ранняя диагностика помогает как радикальному, так и паллиативному лечению. Хирургическое вмешательство является предпочтительным вариантом лечения, особенно при метастатических очагах в длинных костях

Micro Health Project

Community health diagnosis is a comprehensive assessment of health status of the community in relation to its social, physical and biological environment. The purpose of community health diagnosis is to define existing problems, determine available resources and set priorities for planning, implementing and evaluating health action, by and for the community. The community health diagnosis program began on 4th September 2015 and continued till 13th September 2015 in ward no 1 and 5 Rupakot VDC, Kaski, Nepal. The program was organized in following phases: data collection, data analysis, first community presentation, prioritization of need and planning of micro health project (MHP), implementation and evaluation of MHP, and final community presentation. On the basis of the observed and the felt needs of the community, we found the real needs and prioritized them as follows. For community: Proper water purification, information about common diseases, KAP on diseases, knowledge on TB and DOTS. For school-going children: Education on environmental sanitation, education on personal hygiene - teeth brushing and hand washing, adolescent health education. We launched micro health project (MHP) on these topics, conducting school-based as well as community-based programs.  Journal of Gandaki Medical College Vol. 10, No. 1, 2017, Page: 59-6

Probing the low-lying level structure of 94Zr through β¯ decay

223-227Low-lying states of 94Zr are populated following b- decay of 94Y, and the emitted g rays from 94Zr are detected using the 8p spectrometer composed of 20 Compton-suppressed HPGe detectors. High- statistics coincidence data have been used for the placement of very weak decay branches in the level scheme. Combining the results of level lifetimes from a previous experiment and the precisely measured branching ratio values of the weak decay branches from the present experiment, it is possible to extract the B(E2) values for all the possible decay branches from a given level. These values are helpful for proper identification of the collective and non-collective states of 94Zr. The experimental findings have been compared with predictions from shell-model calculations with a limited valence space; however, these calculations are inadequate in reproducing all of the measured spectroscopic quantities

Molecular Epidemiology of HIV-1 Subtypes in India: Origin and Evolutionary History of the Predominant Subtype C

This thesis describes the translational genomics of HIV-1subtype C in India from its origin to therapeutic response with the aim to improve our knowledge for better therapeutic and preventive strategies to combat HIV/AIDS. In a systemic approach, we identified the molecular phylogeny of HIV-1 subtypes circulating in India and the time to most recent common ancestors (tMRCA) of predominant HIV-1 subtype C strains. Additionally, this thesis also studied drug resistance mutations in children, adolescents and adults, the role of host factors in evolution of drug resistance, and population dynamics of viremia and viral co-receptor tropism in perinatal transmission. Finally, the long term therapeutic responses on Indian national first-line antiretroviral therapy were also studied. In Paper I, we reported an increase in the HIV-1 recombinant forms in the HIV-1 epidemiology using a robust subtyping methodology. While the study confirmed HIV- 1 subtype C as a dominant subtype, its origin was dated back to the early 1970s from a single or few genetically related strains from South Africa, whereafter, it has evolved independently. In Paper II, the lethal hypermutations due to the activity of human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (hA3G) was significantly associated with antiretroviral therapy (ART) failure in Indian HIV-1 subtype C patients. The presence of M184I and M230I mutations were observed due to the editing of hA3G in the proviral compartment but stop codons were also found in the open reading frames and the same drug resistance mutations were absent in plasma virus. Therefore, it is unlikely that the viral variants which exhibit hypermutated sequences and M184I and/or M230I will mature and expand in vivo and hence are unlikely to have any clinical significance. The high concordance of drug resistance genotyping in the plasma and proviral compartments in therapy-naïve patients, gives weight to the idea of using whole blood for surveillance of drug resistance mutations which precludes logistic challenges of cold chain transport. In Papers III and IV, we identified a substantial proportion of HIV-1 subtype C perinatally-infected older children who had a high burden of plasma viremia but also had high CD4+ T-cell counts. In addition, older children with HIV-1 subtype C infection presented a high prevalence of predicted X4 and R5/X4 tropic strains which indicates that HIV-1 subtype C strains required longer duration of infection and greater disease progression to co-receptor transition from R5- to X4-tropic strains (IV). Our studies also indicate that transmitted drug resistance is low among Indian HIV-1 infected children, adolescents (III) and adults (II). In Paper V, in a longitudinal cohort study, a good long-term response to the Indian national first-line therapy for a median of nearly four years with 2.8% viral failure, indicating the overall success of the Indian ART program. Our study also showed that three immunologically well patients with virological rebound and major viral drug resistance mutations (M184V, K103N and Y181C) during one study visit had undetectable viral load at their next visit. These findings suggest that use of multiple parameters like patients’ immunological (CD4+ T-cell count), virological (viral load) and drug resistance data should all be used to optimize the treatment switch to second line therapy. In conclusion, this translational genomics study enhances our knowledge about the HIV-1 subtype C strains circulating in India which are genetically distinct from prototype African subtype C strains. Considerably more research using appropriate models need to be performed to understand the phenotypic and biological characteristics of these strains to guide efficient disease intervention and management strategies

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation