Rimegepant: first novel oral calcitonin gene-related peptide inhibitor for migraine

Migraine is a neurological condition characterized by intense, debilitating headaches. Symptoms may include nausea, vomiting, numbness or tingling, sensitivity to light and sound. There are multitude of drugs available to treat migraine like triptans, non-steroidal anti-inflammatory drugs, ergots and opioids. But these drugs are associated with adverse effects especially triptans causing cardiovascular effects limiting its use. During last decade, calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for management of migraine. CGRP has been shown to release during episode of migraine attack and it may play a causative role in induction of migraine. Rimegepant is a novel CGRP antagonist has been approved by FDA for treatment of acute migraine. Rimegepant is a first oral CGRP antagonist compared to other gepants. The oral bioavailability of Rimegepant is 64% and high fat meal can decrease the Cmax, Tmax and area under the curve. This drug is mainly metabolized by CYP3A4 and to lesser extent by CYP2C9. Most common adverse reactions associated with this drug were nausea and urinary tract infection. Clinical trials for Rimegepant have been positive, and results suggest that the drug may be a new safe and effective option for treatment of acute migraine

Aortoesophageal Fistula after Endovascular Aortic Aneurysm Repair of a Mycotic Thoracic Aneurysm

Mycotic aneurysms constitute a small proportion of aortic aneurysms. Endovascular repair of mycotic aneurysms has been applied with good short-term and midterm results. However, the uncommon aortoenteric fistula formation remains a potentially fatal complication when repairing such infective aneurysms. We present the case of an 80-year-old woman with thoracic and abdominal aortic mycotic aneurysms, which were successfully treated with endografting. However, the patient presented 3 months later with upper gastrointestinal bleeding secondary to erosion of the thoracic graft into the oesophagus. The patient was treated conservatively due to the high risk of surgical repair. There is currently little exposure to the management of mycotic aortic aneurysms. If suspected, imaging of the entire vasculature will aid initial diagnosis and highlight the extent of the disease process, allowing for efficient management. Aortic endografting for mycotic thoracic aneurysms is a high-risk procedure yet is still an appropriate intervention. Aortoenteric fistulae pose a rare but severe complication of aortic endografting in this setting

Conformal Prediction with Large Language Models for Multi-Choice Question Answering

As large language models continue to be widely developed, robust uncertainty quantification techniques will become crucial for their safe deployment in high-stakes scenarios. In this work, we explore how conformal prediction can be used to provide uncertainty quantification in language models for the specific task of multiple-choice question-answering. We find that the uncertainty estimates from conformal prediction are tightly correlated with prediction accuracy. This observation can be useful for downstream applications such as selective classification and filtering out low-quality predictions. We also investigate the exchangeability assumption required by conformal prediction to out-of-subject questions, which may be a more realistic scenario for many practical applications. Our work contributes towards more trustworthy and reliable usage of large language models in safety-critical situations, where robust guarantees of error rate are required.Comment: 10 page

Eggs for Improving Nutrition, cognitive development and reducing linear growth retardation among Infants and young Children (ENRICH) : Protocol of an egg supplementation trial among children aged 9-18 months in Hyderabad, India

SKB, SRC and BK: conceptualised, designed the study and wrote first draft. LFA, TD, DPP, MC, KS and PA: developed detailed protocols, planned data collection, critical input to manuscript. RM, HD-K, CH, SFR, RPullakhandam, RPalika, RRK, RNK, MLJ and PH: concept, design, critical inputs to manuscript.Peer reviewe

Investor Sentiment for Real Assets: The Case of Dry Bulk Shipping Market*

We investigate the role of sentiment and its implications for real assets. Using shipping sentiment proxies that capture market expectations, valuation, and liquidity, we construct sentiment indices for the dry bulk shipping market. Evidence suggests that sentiment affects the monthly returns of real assets. The empirical findings also show that market sentiment serves as a contrarian indicator for future cycle phases in all sectors. Furthermore, a sentiment-based trading simulation exercise on the sale and purchase of vessels shows that investors can benefit from higher returns compared to the buy-and-hold benchmark, while partially offsetting the highly volatile nature of the shipping industry

Eggs for Improving Nutrition, cognitive development and reducing linear growth retardation among Infants and young Children (ENRICH): protocol of an egg supplementation trial among children aged 9-18 months in Hyderabad, India.

INTRODUCTION: Evidence on the impact of nutrient-rich animal source foods such as eggs for improving child growth and cognition is inconsistent. This study aims to examine the impact of an egg intervention in children, along with behaviour change communication (BCC) to the mother, on linear growth and cognition, and nutritional status in children aged 9-18 months. METHODS AND ANALYSIS: A 9-month open-labelled randomised controlled trial will be conducted in three urban slums in Hyderabad, India, as a substudy of an observational cohort study (n=350) following pregnant women and their children until 18 months of age in a population at risk of stunting. The children born to women enrolled during the third trimester of pregnancy will be block randomised in a 1:4 ratio into the intervention (n=70) and control (n=280) groups. Children in the intervention group will be supplemented with one egg per day starting from 9 months until 18 months of age. BCC designed to enhance adherence to the intervention will be used. The control group will be a part of the observational cohort and will not receive any intervention from the study team. The primary outcome will be length-for-age z-scores, and the secondary outcomes will include cognition, blood biomarkers of nutritional status including fatty acid profile and epigenetic signatures linked with linear growth and cognition. Multivariate intention-to-treat analyses will be conducted to assess the effect of the intervention. ETHICS AND DISSEMINATION: The study is approved by the Institutional ethics committees of ICMR-National Institute of Nutrition, Hyderabad, India and London School of Hygiene and Tropical Medicine, UK. The results will be published in peer-reviewed journals and disseminated to policy-makers. Findings will also be shared with study participants and community leaders. TRIAL REGISTRATION NUMBER: CTRI/2021/11/038208

Venture Capitalists' Decision to Withdraw: The Role of Portfolio Configuration From a Real Options Lens

This is the author's final draft. The publisher's official version is available from: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=2036399.When does a venture capital firm withdraw from an investment project prior to its completion? This study offers a real options view on this decision by examining the contingent effects of portfolio configuration. We explore how project withdrawal can be influenced by two distinct dimensions of portfolio configuration, portfolio focus in a strategic domain and portfolio diversity across multiple domains. The empirical analysis shows that while portfolio focus weakens the negative effect of industry-level uncertainty on a venture capitalist’s propensity to withdraw from a project, portfolio diversity strengthens the effect of uncertainty. This study informs current research on the boundary of real options theory and sheds light on the behavior of venture capitalists in financing entrepreneurship

Anthropometric, biochemical, dietary, morbidity and well-being assessments in women and children in Indonesia, India and Senegal : A UKRI GCRF Action Against Stunting Hub protocol paper

HD-K and EF were responsible for the overall design, training and overseeing implementation of the research. UF, MKH, BK, BF, RM, RPullakhandam, RPalika, TD, SFR, SD, RPradeilles, SA, AW, JPW, PH and CH were involved in its design. UF, MKH, BK, BF, DY, DS, NLZ, TCA, RM, RPullakhandam, RPalika, TD, SFR, SKB KS, DPP, DY, SD, PL-S, BD, PM, SF, ID, AD, TDVI, FT, AD, SS, BMK and DTT implemented the research. HD-K and EF wrote the manuscript. All authors read, provided comments on and approved the final version of the manuscript.Peer reviewe

Linking operations, marketing and environmental capabilities and diversification to hotel performance: a data envelopment analysis approach

This study examines the impacts of marketing capability, operations capability, environmental capability and diversification strategy on performance of hotel industry in the UK. We conceptualize these impacts by drawing on the resource-based-view of a firm as the theoretical underpinning. We use the financial archival data and information obtained from websites. We use content analysis, regression analysis and Data Envelopment Analysis (DEA). Our results show that operations capability and environmental capability have significant positive effects on performance, marketing capability has a significant negative impact but diversification strategy does not impact on performance. Additionally, there is no evidence of the moderating effects of efficiency on these impacts. Our study suggests that hotel industry in the UK ought to focus on developing operations and environmental capabilities especially by exploiting the synergies between them but reduce excessive reliance on marketing. This paper makes two important contributions to the literature. First, it applies a framework linking the three capabilities (operations, marketing and environment) and diversification to the specific case of the hotel industry. Second, unlike similar previous studies, ours is the first to incorporate environmental capabilities in the analysis