The Impact of Idiosyncratic Risk and Macroeconomic Uncertainty on Firms’ Leverage and Investment: Evidence from the Different Industries of Pakistan

The main purpose of this study is to empirically examine the impact of idiosyncratic risk and macroeconomic uncertainty on firm leverage and investment. The analysis is carried out for a large panel data which is obtained from different industries of Pakistan comprising textile, auto and allied, cement, fuel and energy and sugar over the period of 2008-2018. Our investigation provides evidence that firm use less debt during periods of high risk. It also shows that as macroeconomic uncertainty and idiosyncratic risk increases, firms reduce their degrees of leverage. This study shows that idiosyncratic risk has an indirect and statistically significant effect on the Pakistan target firms’ leverage. However, highly profitable firms’ leverage is more sensitive to macroeconomic uncertainty and less sensitive to idiosyncratic risk. The result related to firm characteristics suggests that the firm specific variables such as firm size, tangibility, debt to asset ratio, growth of sales and cash flow to assets ratio are important in the determination of different firms’ investment. The finding also reveals that firm’s investment is more sensitive during periods of heightened firm idiosyncratic risk.  The outcome of the paper is useful for firms’ investment decision and authorities in designing of effective fiscal and monetary policies

The Impact of Idiosyncratic Risk and Macroeconomic Uncertainty on Firms’ Leverage and Investment: Evidence from the Different Industries of Pakistan

The main purpose of this study is to empirically examine the impact of idiosyncratic risk and macroeconomic uncertainty on firm leverage and investment. The analysis is carried out for a large panel data which is obtained from different industries of Pakistan comprising textile, auto and allied, cement, fuel and energy and sugar over the period of 2008-2018. Our investigation provides evidence that firm use less debt during periods of high risk. It also shows that as macroeconomic uncertainty and idiosyncratic risk increases, firms reduce their degrees of leverage. This study shows that idiosyncratic risk has an indirect and statistically significant effect on the Pakistan target firms’ leverage. However, highly profitable firms’ leverage is more sensitive to macroeconomic uncertainty and less sensitive to idiosyncratic risk. The result related to firm characteristics suggests that the firm specific variables such as firm size, tangibility, debt to asset ratio, growth of sales and cash flow to assets ratio are important in the determination of different firms’ investment. The finding also reveals that firm’s investment is more sensitive during periods of heightened firm idiosyncratic risk.  The outcome of the paper is useful for firms’ investment decision and authorities in designing of effective fiscal and monetary policies

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Authentic assessment in medical education: Exploring AI integration and student-as-partners collaboration

Background: Traditional assessments often lack flexibility, personalized feedback, real-world applicability, and the ability to measure skills beyond rote memorization. These may not adequately accommodate diverse learning styles and preferences, nor do they always foster critical thinking or creativity. The inclusion of Artificial Intelligence (AI), especially Generative Pre-trained Transformers, in medical education marks a significant shift, offering both exciting opportunities and notable challenges for authentic assessment practices. Various fields, including anatomy, physiology, pharmacy, dentistry, and pathology, are anticipated to employ the metaverse for authentic assessments increasingly. This innovative approach will likely enable students to engage in immersive, project-based learning experiences, facilitating interdisciplinary collaboration and providing a platform for real-world application of knowledge and skills.Methods: This commentary paper explores how AI, authentic assessment, and Student-as-Partners (SaP) methodologies can work together to reshape assessment practices in medical education.Results: The paper provides practical insights into effectively utilizing AI tools to create authentic assessments, offering educators actionable guidance to enhance their teaching practices. It also addresses the challenges and ethical considerations inherent in implementing AI-driven assessments, emphasizing the need for responsible and inclusive practices within medical education. Advocating for a collaborative approach between AI and SaP methodologies, the commentary proposes a robust plan to ensure ethical use while upholding academic integrity.Conclusion: Through navigating emerging assessment paradigms and promoting genuine evaluation of medical knowledge and proficiency, this collaborative effort aims to elevate the quality of medical education and better prepare learners for the complexities of clinical practice

Genome-wide analysis reveals the TCP-miR159-miR319 module is crucial for rice (Oryza sativa L.) growth and response to drought and salinity.

The TCP are key plant-specific proteins responsible for regulating various developmental activities. Herein, we retrieved 21 OsTCP genes from the genome database of rice. The bioinformatics analysis, including conserved motif, domain, interactive proteins, gene ontology (GO) analysis, target micro-RNAs (miRNA) prediction, and the physiochemical properties, highlight the key aspects of OsTCP genes in Oryza sativa L. The phylogeny analysis disclosed that OsTCP was further clustered into five clades (Clade I - Clade V) based on the structural similarities and functional diversities. The GO analysis of OsTCP proteins showed they are primarily exercising the rice developmental processes, reproductive stages in particular. The microarray expression analysis showed transcription in twelve rice tissues, and the differential expression pattern of OsTCP genes revealed their possible involvement in auxin-mediated growth and response against salinity and drought. The predicted miRNA that includes miR159 and miR319 families further the engagement of OsTCP genes in the post-translational regulation of rice growth. Owing to the above-mentioned outcomes, we speculate that OsTCP genes in the O. sativa genome play an essential role in growth and development and fine-tuning the immune responses to various environmental stresses, thus providing major indications for further functional studies

Exogenously Applied Trehalose Augments Cadmium Stress Tolerance and Yield of Mung Bean (<i>Vigna radiata</i> L.) Grown in Soil and Hydroponic Systems through Reducing Cd Uptake and Enhancing Photosynthetic Efficiency and Antioxidant Defense Systems

Cadmium (Cd) toxicity is a serious environmental issue causing a significant reduction in crop growth and productivity globally. Trehalose (Tre) has emerged as an important reducing sugar that can reduce the adverse impacts of different abiotic stresses. Therefore, the present investigation was performed to determine the key role of Tre in alleviating Cd stress in the mung bean (Vigna radiata L.) crop. The study was comprised of different treatments of cadmium (0, 10, 20 mg kg−1 soil) and Tre (0, 15 and 30 mM). Cd stress significantly restricted the growth and yield of mung bean. However, Tre supplementation markedly improved growth and yield due to pronounced reductions in Cd uptake and Cd-induced oxidative stress as shown by the lower production of hydrogen peroxide (H2O2), electrolyte leakage (EL) and malondialdehyde (MDA) in Cd-stressed plants as well as by the enhanced activities of antioxidant enzymes (CAT, POD, APX and AsA). Moreover, the ameliorative role of Tre to Cd toxicity was also demonstrated by its ability to enhance chlorophyll contents, total soluble protein (TSP) and free amino acids (FAA). Taken together, Tre supplementation played a key beneficial role in improving Cd stress tolerance and yield traits of mung bean through restricting Cd uptake and enhancing photosynthetic capacity, osmolytes biosynthesis and antioxidant activities