Participatory on-farm evaluation of wheat genotypes

In wheat development programs, the evaluation and identification of superior genotypes  is the first and leading step in a crop improvement program. Coordinated Farmer’s Field Trial (CFFT) was conducted during the three successive wheat growing season of 2010/11, 2011/12 and 2012/13. In CFFT six different wheat genotypes were planted in different outreach sites of research stations of Nepal Agricultural Research Council (NARC) at varying geographical regions. CFFT was conducted according to standard recommended practices of wheat at farmers’ field with different sets of genotypes for Terai and hill. In CFFT for Terai Tar and Lower valley (TTL) under timely sown irrigated (TSI) condition wheat genotype NL 1073 produced the grain yield of 3695 kg/ha and under the timely sown rainfed (TSR) that was 2738 kg/ha in 2010/11. In 2011/12, wheat genotype NL 1073 had the highest recorded grain yield of 3691 kg/ha in mid western region which was followed by check variety Vijay in CFFT-TTL in 2011/12 in the same region. Similarly in 2012/13, check variety Vijay showed the highest grain yield of 3818 kg/ha and 3044 kg/ha followed by NL 1094 (2938 kg/ha and 3468 kg/ha) in TSR and TSI environments, respectively. In CFFT for Mid and High Hill (MHH) WK 1204 had the highest grain yield of 3967 kg/ha in TSI which was followed by NL 1008 with the yield of 3890 in 2010/11. In 2011/12 the highest mean grain yield was observed in WK 1204 (4242 kg/ha) followed by BL 3872 (3922 kg/ha). Similarly, in 2012/13 NL 1008 was the best genotypes on the basis of grain yield (3297 kg/ha) followed by NL 1055 (3131 kg/ha) under CFFT-MHH

Post-implementation Review of the Himalaya Home Care Project for Home Isolated COVID-19 Patients in Nepal

Background: The emergence of coronavirus disease 2019 (COVID-19) has resulted in a pandemic that has significantly impacted healthcare systems at a global level. Health care facilities in Nepal, as in other low- and middle-income countries, have limited resources for the treatment and management of COVID-19 patients. Only critical cases are admitted to the hospital resulting in most patients in home isolation. Methods: Himalaya Home Care (HHC) was initiated to monitor and provide counseling to home isolated COVID-19 patients for disease prevention, control, and treatment. Counselors included one physician and four nurses. Lists of patients were obtained from district and municipal health facilities. HHC counselors called patients to provide basic counseling services. A follow-up check-in phone call was conducted 10 days later. During this second call, patients were asked about their perceptions of the HHC program. Project objects were: (1) To support treatment of home isolated persons with mild to moderate COVID-19, decrease burden of hospitalizations, and decrease risks for disease transmission; and, (2) To improve the health status of marginalized, remote, and vulnerable populations in Nepal during the COVID-19 pandemic. Results: Data from 5823 and 3988 patients from May 2021-February 2022 were entered in initial and follow-up forms on a REDCap database. The majority of patients who received counseling were satisfied. At follow-up, 98.4% of respondents reported that HHC prevented hospitalization, 76.5% reported they could manage their symptoms at home, and 69.5% reported that counseling helped to limit the spread of COVID-19 in their household. Conclusions: Telehealth can be an essential strategy for providing services while keeping patients and health providers safe during the COVID-19 pandemic

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

COVID-19 vaccination up-take in three districts of Nepal

Vaccine hesitancy during the COVID-19 pandemic continues to be an issue in terms of global efforts to decrease transmission rates. Despite high demand for the vaccines in Nepal, the country still contends with challenges related to vaccine accessibility, equitable vaccine distribution, and vaccine hesitancy. Study objectives were to identify: 1) up-take and intention for use of COVID-19 vaccines, 2) factors associated with vaccine up-take, and 3) trusted communication strategies about COVID-19 and the vaccines. A quantitative survey was implemented in August and September 2021 through an initiative at the Nepali Ministry of Health and Population Department of Health Services, Family Welfare Division. Data were collected from 865 respondents in three provinces (Bagmati, Lumbini, and Province 1). Ordinal multivariate logistic regression was utilized to determine relationships between vaccination status and associated factors. Overall, 62% (537) respondents were fully vaccinated and 18% (159) were partially vaccinated. Those respondents with higher education (p \u3c .001) and higher household income (p \u3c .001) were more likely vaccinated. There were also significant differences in vaccine up-take across the three provinces (p \u3c .001). Respondents who were vaccinated were significantly more likely to perceive vaccines as efficacious in terms of preventing COVID-19 (p = .004) and preventing serious outcomes (p = .010). Among both vaccinated and unvaccinated individuals, there was a high level of trust in information about COVID-19 vaccines provided through local health-care workers [e.g. nurses and physicians]. These results are consistent with other findings within the South Asia region. Targeted advocacy and outreach efforts are needed to support ongoing COVID-19 vaccination campaigns throughout Nepal

G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Receptor Stimulation

We examined the role of G proteins in modulating the response of living cells to receptor activation. The response of an effector, phospholipase C-β to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of Gβγ from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating Gβγ, non-translocating Gβγ subunits do not dissociate from the αq subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered αq induced differential responses to receptor activation in cells with or without an endogenous translocation capable γ subunit. G protein heterotrimer dissociation and βγ translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal

Comprehensive insights into Mycobacterium tuberculosis DevR (DosR) regulon activation switch

DevR regulon function is believed to be crucial for the survival of Mycobacterium tuberculosis during dormancy. In this study, we undertook a comprehensive analysis of the DevR regulon. All the regulon promoters were assigned to four classes based on the number of DevR binding sites (Dev boxes). A minimum of two boxes are essential for complete interaction and their tandem arrangement is an architectural hallmark at all promoters. Initial interaction of DevR with the conserved box is essential for its cooperative binding to adjacent sites bearing low to very poor sequence conservation and is the universal mechanism underlying DevR-mediated transcriptional induction. The functional importance of tandem arrangement was established by analyzing promoter variants harboring Dev boxes with altered spacing. Conserved sequence logos were generated from 47 binding sequences which included 24 newly discovered Dev boxes. In each half site of an 18-bp binding motif, G5 and C7 are essential for DevR binding. Finally, we show that DevR regulon induction occurs in a temporal manner and genes that are induced early are also usually powerfully induced. The information theory-based approach along with binding and temporal expression studies provide us with comprehensive insights into the complex pattern of DevR regulon activation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Simultaneous anterior cruciate ligament repair and medial unicompartmental knee replacement

We present the case of a 55-year-old female who sustained avulsion of anterior cruciate ligament (ACL) from its tibial attachment while undergoing unicompartmental knee replacement (UKR). The fibers of ACL were intact. Realizing the paramount importance of ACL in a knee undergoing UKR, we promptly performed a primary repair of the ACL and continued with the surgery in the same sitting. At the latest follow-up, the patient is doing well both clinically and functionally and has no antero-posterior or varus-valgus laxity. We discuss the cause for ACL avulsion during UKR and precautions to avoid it

Role of Macrophage in Tumor Microenvironment: Prospect in Cancer Immunotherapy

Current evidence suggests an increasing role of macrophages in inflammation and tumor progression. Most tumors contain an abundant number of macrophages as a major component of their leukocyte infiltrate, which co-exist with tumor cells at the tumor microenvironment. Upon activation with soluble tumor antigens, macrophages release a distinct repertoire of growth factor, cytokines, chemokines and enzymes that inhibit growth of the tumor. However, the anti-tumor immune response induced by macrophages does not always ensue. Tumor cells themselves are capable of down-regulating macrophage phenotype and functions and anti-tumor immune responses in the tumor-bearing host. The present review aims to elucidate the role of macrophages in tumor growth and progression, invasion, metastasis, and angiogenesis at the site of tumor growth. Moreover, the effect of tumor microenvironment on the phenotype and function of macrophages, which are altered due to the continuous exposure of various soluble and non-soluble tumor promoting factors secreted by tumor cells, and implication of macrophages in cancer immunotherapy have been discussed in detail