121 research outputs found

    Electric and Magnetic fields due to Dirac particles in FRW spacetime

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    Some solutions of the Maxwell equations with Dirac particles for the source in FRW spacetime are discussed. The Green's function of the equation for the radial component of the Maxwell fields, F_{r\eta} and F_{\theta\phi} is solved. Green's function is found to reduce to that of Minkowskian spacetime in the appropriate limit. Also, the Lienard-Wiechert type solution is derived. Also, the solutions with the Dirac particle current is also presented. It is found that the F_{r\eta} is composed of even angular momentum states while the odd states constitue F_{\theta\phi} .Comment: 8 pages including 2 figure

    Why are so many Nepali women killing themselves? A review of key issues

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    Background: For decades the maternal mortality in Nepal was the lead cause of death among women, with great improvements in the maternal mortality ratio in the twentieth century the second most common cause has become more prominent. Suicide is now one of the leading causes of death for women of a reproductive age in Nepal. This scoping review brings together the key available literature to identify the causes of suicide among women in Nepal. Methods: Published and unpublished studies and the grey literature published on women and suicide related to Nepal between 2000 and 2014 were searched and included in this review. Results: This review suggested a number of explanations for the high rate of suicide among women including: partner violence, alcoholism and polygamy, the culture of silence, early age marriage and prolonged child bearing and dependency on men for financial security. Conclusion: This paper highlights some challenges and suggests ways forward in the improvement of mental health in Nepal

    From Rags to Riches: Assessing poverty and vulnerability in urban Nepal

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    Urbanisation brings with it rapid socio-economic change with volatile livelihoods and unstable ownership of assets. Yet, current measures of wealth are based predominantly on static livelihoods found in rural areas. We sought to assess the extent to which seven common measures of wealth appropriately capture vulnerability to poverty in urban areas. We then sought to develop a measure that captures the characteristics of one urban area in Nepal. We collected and analysed data from 1,180 households collected during a survey conducted between November 2017 and January 2018 and designed to be representative of the Kathmandu valley. A separate survey of a sub set of households was conducted using participatory qualitative methods in slum and non-slum neighbourhoods. A series of currently used indices of deprivation were calculated from questionnaire data. We used bivariate statistical methods to examine the association between each index and identify characteristics of poor and non-poor. Qualitative data was used to identify characteristics of poverty from the perspective of urban poor communities which were used to construct an Urban Poverty Index that combined asset and consumption focused context specific measures of poverty that could be proxied by easily measured indicators as assessed through multivariate modelling. We found a strong but not perfect association between each measure of poverty. There was disagreement when comparing the consumption and deprivation index on the classification of 19% of the sample. Choice of short-term monetary and longer-term capital approaches accounted for much of the difference. Those who reported migrating due to economic necessity were most likely to be categorised as poor. A combined index was developed to capture these dimension of poverty and understand urban vulnerability. A second version of the index was constructed that can be computed using a smaller range of variables to identify those in poverty. Current measures may hide important aspects of urban poverty. Those who migrate out of economic necessity are particularly vulnerable. A composite index of socioeconomic status helps to capture the complex nature of economic vulnerability

    When left ventricular failure complicates chronic obstructive pulmonary disease: Hypoxia plays the major role

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    Abstract Introduction: As the chronic obstructive pulmonary disease (COPD) progress, is usually accompanied by involvement of the both left ventricle (LV) and right ventricle (RV), and their systolic and diastolic function. Signs and symptoms of LV failure can be difficult to distinguish from those of COPD. Objective: The study was carried out to determine the prevalence of LV systolic dysfunction in the COPD patients and to assess the possible risk factor behind such development. Material and Methods: It is a prospective study of 60 cases of COPD patients with or without cor-pulmonale attending Manipal Teaching Hospital. Results: The prevalence of LV systolic dysfunction was found to be 26.7%, and the findings directly correlate with the severity of COPD i.e., the more the severity of the lung disease more the probability for the incidence of LV systolic dysfunction. These data are in support of the hypothesis that hypoxia and the excess accumulation of toxic metabolic products like lactic acid, significant right-to-left shunting through the bronchial circulation explains the diminished LV ejection fraction in severe COPD patients. Conclusion: Routine echocardiography investigation of the severe COPD patients is required for assessing the status of LV function and to rule out the possible association of LV systolic dysfunction. Key words: Chronic obstructive pulmonary disease, Cor-pulmonale, Hypoxia, LV systolic dysfunction hronic obstructive pulmonary disease (COPD) is a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema which is progressive and is partially reversible. Right ventricular (RV) hypertrophy and dilatation secondary to pulmonary hypertension caused by COPD (i.e., cor pulmonale) is unrelated to the left side of the heart. With RV pressure overload, the septum tends to be displaced toward the left ventricle (LV) during systole, which causes a distortion of the LV 1 . Since the myocardial fibres of the RV free walls are connected with those of the septum and LV free wall, a pressure increase in the RV is accompanied by changes in the LV systolic function 2 . This might be a partial explanation for the LV involvement in the course of COPD, causing an increased morbidity and mortality of ischemic heart disease and LV dysfunction 3 . Understanding the relationship between RV hypertrophy and LV systolic function in patients with COPD will be helpful for the better patient management. Objective The main objective of this study is to determine the prevalence of LV systolic dysfunction in the COPD patients and to assess the possible risk factor behind such development

    A comprehensive and version-controlled database of glacial lake outburst floods in High Mountain Asia

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    Glacial lake outburst floods (GLOFs) have been intensely investigated in High Mountain Asia (HMA) in recent years and are the most well-known hazard associated with the cryosphere. As glaciers recede and surrounding slopes become increasingly unstable, such events are expected to increase, although current evidence for an increase in events is ambiguous. Many studies have investigated individual events, and while several regional inventories exist, they either do not cover all types of GLOF or are geographically constrained. Further, downstream impacts are rarely discussed. Previous inventories have relied on academic sources and have not been combined with existing inventories of glaciers and lakes. In this study, we present the first comprehensive inventory of GLOFs in HMA, including details on the time of their occurrence, processes of lake formation and drainage involved, and downstream impacts. We document 697 individual GLOFs that occurred between 1833 and 2022. Of these, 23 % were recurring events from just three ephemeral ice-dammed lakes. In combination, the documented events resulted in 6906 fatalities of which 906 can be attributed to 24 individual GLOF events, which is 3 times higher than a previous assessment for the region. The integration of previous inventories of glaciers and lakes within this database will inform future assessments of potential drivers of GLOFs, allowing more robust projections to be developed. The database and future, updated versions are traceable and version-controlled and can be directly incorporated into further analysis. The database is available at https://doi.org/10.5281/zenodo.7271187 (Steiner and Shrestha, 2023), while the code including a development version is available on GitHub.</p

    Monitoring Immune Checkpoint Regulators as Predictive Biomarkers in Hepatocellular Carcinoma

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    The global burden of hepatocellular carcinoma (HCC), one of the frequent causes of cancer-related deaths worldwide, is rapidly increasing partly due to the limited treatment options available for this disease and recurrence due to therapy resistance. Immune checkpoint inhibitors that are proved to be beneficial in the treatment of advanced melanoma and other cancer types are currently in clinical trials in HCC. These ongoing trials are testing the efficacy and safety of a few select checkpoints in HCC. Similar to observations in other cancers, these immune checkpoint blockade treatments as monotherapy may benefit only a fraction of HCC patients. Studies that assess the prevalence and distribution of other immune checkpoints/modulatory molecules in HCC have been limited. Moreover, robust predictors to identify which HCC patients will respond to immunotherapy are currently lacking. The objective of this study is to perform a comprehensive evaluation on different immune modulators as predictive biomarkers to monitor HCC patients at high risk for poor prognosis. We screened publically available HCC patient databases for the expression of previously well described immune checkpoint regulators and evaluated the usefulness of these immune modulators to predict high risk, patient overall survival and recurrence. We also identified the immune modulators that synergized with known immune evasion molecules programmed death receptor ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and correlated with worse patient outcomes. We evaluated the association between the expression of epithelial-to-mesenchymal transition (EMT) markers and PD-L1 in HCC patient tumors. We also examined the relationship of tumor mutational burden with HCC patient survival. Notably, expression of immune modulators B7-H4, PD-L2, TIM-3, and VISTA were independently associated with worse prognosis, while B7-H4, CD73, and VISTA predicted low recurrence-free survival. Moreover, the prognosis of patients expressing high PD-L1 with high B7-H4, TIM-3, VISTA, CD73, and PD-L2 expression was significantly worse. Interestingly, PD-L1 expression in HCC patients in the high-risk group was closely associated with EMT marker expression and prognosticates poor survival. In HCC patients, high tumor mutational burden (TMB) predicted worse patient outcomes than those with low TMB

    The Fusion of CLEC12A and MIR223HG Arises from a trans-Splicing Event in Normal and Transformed Human Cells

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    Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they are also widely detected in normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine the genetic structure and biological roles of CLEC12A-MIR223HG, a novel chimeric transcript produced by the fusion of the cell surface receptor CLEC12A and the miRNA-223 host gene (MIR223HG), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that CLEC12A-MIR223HG is not just expressed in CML, but also in a variety of normal tissues and cell lines. CLEC12A-MIR223HG expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that CLEC12A-MIR223HG is a product of trans-splicing rather than a chromosomal rearrangement and that transcriptional activation of CLEC12A with the CRISPR/Cas9 Synergistic Activation Mediator (SAM) system increases CLEC12A-MIR223HG expression. CLEC12A-MIR223HG translates into a chimeric protein, which largely resembles CLEC12A but harbours an altered C-type lectin domain altering key disulphide bonds. These alterations result in differences in post-translational modifications, cellular localization, and protein–protein interactions. Taken together, our observations support a possible involvement of CLEC12A-MIR223HG in the regulation of CLEC12A function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs

    The Fusion of CLEC12A and MIR223HG Arises from a trans-Splicing Event in Normal and Transformed Human Cells

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    Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they are also widely detected in normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine the genetic structure and biological roles of CLEC12A-MIR223HG, a novel chimeric transcript produced by the fusion of the cell surface receptor CLEC12A and the miRNA-223 host gene (MIR223HG), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that CLEC12A-MIR223HG is not just expressed in CML, but also in a variety of normal tissues and cell lines. CLEC12A-MIR223HG expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that CLEC12A-MIR223HG is a product of trans-splicing rather than a chromosomal rearrangement and that transcriptional activation of CLEC12A with the CRISPR/Cas9 Synergistic Activation Mediator (SAM) system increases CLEC12A-MIR223HG expression. CLEC12A-MIR223HG translates into a chimeric protein, which largely resembles CLEC12A but harbours an altered C-type lectin domain altering key disulphide bonds. These alterations result in differences in post-translational modifications, cellular localization, and protein–protein interactions. Taken together, our observations support a possible involvement of CLEC12A-MIR223HG in the regulation of CLEC12A function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs
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