Adjuvant Hormonal Therapy in Postmenopausal Women with Breast Cancer: Physician\u27s Choices

The choice of adjuvant hormonal therapy in postmenopausal women with hormone receptor positive breast cancer has remained a matter of controversy and debate. The variety of agents is available, with each claiming to be superior. This clinical survey was undertaken to get an impression of the physician\u27s first choice of therapy in an attempt to find out what questions still need to be answered in the making of standard of care. A web-based clinical survey was sent to the cancer physicians around the world, and 182 physicians responded to the survey. Most were medical oncologists in a tertiary care hospital. 36.3% preferred Anastrozole, 35.2% Tamoxifen, and 22.2% Letrozole as their first choice. Data support (67.8%) and safety concerns (30%) were given as the main reasons for the choice, 63.7% switched their therapy, and 24% had to switch because of side effects. 73.6% used 5 years of adjuvant hormonal therapy, 6.6% for 7 years, and 4.4% for 10 years. 61.5% follow their patients 3 times monthly, and 73.2% used laboratory and radiological assessment at each followup. Conclusion. Physicians show disagreement over the choice and duration of hormonal therapy in this patient population. Clinical trials leading to firm recommendations to set standards from which patients benefit the most are needed

India – Pakistan CBMs since 1947 A Critical Analysis

India and Pakistan have been locked into adversarial relations since 1947. The major conflict between the two countries is the territorial status of Kashmir including several sidelining issues that further deteriorated the bilateral relations. The two countries have been part of several pacts, peace initiatives to manage and resolve their conflict, however, none of the peace efforts could bring them nearer to final settlement. Regional and international developments also impacted relations between India and Pakistan and both were part of various international alliances in cold war era. In post cold war times, the two countries acquired nuclear weapons in May 1998 and since then Kashmir was declared as nuclear flash point. It is therefore needed to encourage India and Pakistan to seek common grounds for better peace prospects in the region. The paper caters a historical survey as well as analysis on India – Pakistan confidence building measures (CBMs) and also suggests future prospects for peaceful co-existence. It also outlines why few agreements could not save the two countries for preceding acrimony and did not serve the purpose of resolving Kashmir conflict once for all

Impact of Foreign Remittances on Financial Development of Pakistan

This research investigates the impact of remittances on financial development of Pakistan. Overseas remittances have positive and major relation with GDP of Pakistan at the same time as inflation and exchange rate has unconstructive effect on economic growth. The multiple regression investigation is used to identify the relationship between the dependent and independent variables. In this study, we considered economic growth as the dependent variable. For independent variables worker’s remittances, foreign direct investment, inflation, and exchange rate and agriculture growth

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

BackgroundThe safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.MethodsPANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.FindingsBetween Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.InterpretationMolnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

RAMIFICATIONS OF GOVERNANCE INFRASTRUCTURE AND FDI FLUX IN PAKISTAN: Khawaja Asif Mehmood, Syeda Azra Batool, Maria Ishtiaq

The prominence of Foreign Direct Investment (FDI) to Pakistan is due to its positive macroeconomic fallouts. The factors that maneuver as impediment towards FDI are socioeconomic in nature. To deliberate such factors, this study is distinctive in context of incorporating governance infrastructure such as; political stability, quality of governance, and control of corruption for the period of 1980-2018. Autoregressive Distributed Lag was used to estimate the coefficient in varied time horizon. Findings concluded governance infrastructure to be significantly and positively affecting the flow of FDI. Thus, better handling of the same is essential so that the macroeconomic goals that are hindered due to lack of capital be fulfilled in ready course of time

Assessment of Safety Culture and Maturity in Mining Environments: Case of Njuli Quarry

Due to an ever increasing concern for safety at most mines in Malawi, this paper aimed at assessing the safety culture and maturity in mining environments by applying the Safety Culture Maturity Model (SCMM). The SCMM is a practical and reliable diagnostic tool to use in the context of Malawian mining environments because it emphasizes the importance of employee involvement in assessing and improving safety culture. Njuli quarry is used as a case study due to its adoption of modern mining technologies and long existence in the mining industry. The methods used to assess the level of maturity of safety culture comprised questionnaires, interviews and behavioral observations. To test the reliability of the questionnaire, the respondents were interviewed using the same questions and comparing the results. There was good reliability of the measures used since the correlation coefficients between questionnaire and interview ranged from r = 0.9 to 1. The results demonstrate that Njuli quarry has more characteristics of the Managing Level 2 or Developing Stage with percentages ranging 55% - 60% followed by the Emerging Level 1 ranging 33% - 36%. The Involving Level 3 ranged 4% - 10% showing improvement in some items of the dimensions of the safety framework. The company had the lowest percentages of 0% - 2% in Cooperating Level 4, and 0% - 1% in Continually Improving Level 5. This was expected because most mining companies in Malawi focus on maximizing production regardless of the safety implications, and also employees do not take safety issues seriously despite minor accidents and near misses. Therefore, the company should carry out safety trainings, set up a safety department, provide PPE to employees, and introduce rewards for best safety performance. Present study has added new knowledge on levels of maturity of safety culture in Malawi’s mining environments which will influence the Department of Mines in policy development, site safety inspections and safety audits