Project description:Through a combination of a controlled experiment and a survey, we examine the effect of voting power on shareholders' voting behavior at general meetings. To avoid a selection bias, common in archival voting data, we exogenously manipulate shareholders' power to affect the outcome. Our findings suggest that, when it comes to corporate decisions involving conflicts of interest, voting power nudges shareholders to oppose management and to choose the "right" alternative, that is, vote against a proposal which prima facie does not serve the company's best interest. This effect obtained even when the dissenting vote contravened the choices of all other voters. Furthermore, the drive "to do the right thing" was established as significant, above and beyond the size of the economic stake. We also demonstrate that strategic voting among institutional investors is contingent on voting power: when in a position to affect the outcome of a vote, institutional investors tend to eschew strategic considerations and display fewer consistent patterns in their voting, compared to situations in which their ability to make a difference is limited. In anticipation of a "bad" proposal to be put to vote at the general shareholder meeting, institutional investors prefer to negotiate terms with management beforehand, and vote against it only after such negotiations fail. Our results shed new light on the "behind the scenes" processes in shareholder voting and underscore the importance of institutional investor agency to corporate governance, accountability, and minority shareholder representation.Supplementary informationThe online version contains supplementary material available at 10.1007/s10551-022-05108-y.
Project description:Right ventricular (RV)-pulmonary arterial uncoupling is the consequence of increased afterload and/or decreased RV contractility. However, the combination of arterial elastance (Ea) and end-systolic elastance (Ees)/Ea ratio to assess RV function is unclear. We hypothesized that the combination of both could comprehensively assess RV function and refine risk stratification. The median Ees/Ea ratio (0.80) and Ea (0.59 mmHg/mL) were used to classify 124 patients with advanced heart failure into four groups. RV systolic pressure differential was defined as end-systolic pressure (ESP) minus beginning-systolic pressure (BSP). Patients among different subsets showed dissimilar New York Heart Association functional class (V = 0.303, p = 0.010), distinct tricuspid annular plane systolic excursion/ pulmonary artery systolic pressure (mm/mmHg; 0.65 vs. 0.44 vs. 0.32 vs. 0.26, p < 0.001), and diverse prevalence of pulmonary hypertension (33.3% vs. 35% vs. 90% vs. 97.6%, p < 0.001). By multivariate analysis, Ees/Ea ratio (hazard ratio [HR] 0.225, p = 0.004) and Ea (HR 2.194, p = 0.003) were independently associated with event-free survival. Patients with Ees/Ea ratio greater than or equal to 0.80 and Ea less than 0.59 mmHg/mL had better outcomes (p < 0.05). In patients with Ees/Ea ratio greater than or equal to 0.80, those with Ea greater than or equal to 0.59 mmHg/mL had a higher adverse outcome risk (p < 0.05). Ees/Ea ratio less than or equal to 0.80 was associated with adverse outcomes, even when Ea was less than 0.59 mmHg/mL (p < 0.05). Approximately 86% of patients with ESP-BSP greater than 5 mmHg had an Ees/Ea ratio less than or equal to 0.80 and/or an Ea greater than or equal to 0.59 mmHg/mL (V = 0.336, p = 0.001). Combined use of Ees/Ea ratio and Ea could be a comprehensive approach to assessing RV function and predicting outcomes. An exploratory analysis demonstrated that Ees/Ea ratio and Ea might be roughly estimated based on RV systolic pressure differential.
Project description:Recent updates in the classification of central nervous system (CNS) tumors have increased the need for molecular testing. Assessment of multiple alterations in parallel, complex combinations of gene sequence and chromosomal changes, as well as therapy prediction by identification of actionable mutations are the major challenges. We here report on a customized next generation sequencing (NGS)-based DNA panel assay that combines diagnostic and predictive testing and -as a comprehensive approach- allows for simultaneous single nucleotide variant (SNP) / small insertion/deletion (InDel), copy number variation (CNV) and loss of heterozygosity (LOH) detection. We analyzed formalin-fixed and paraffin-embedded (FFPE) DNA from a total of 104 patients with CNS tumors. After amplicon capture-based library preparation, sequencing was performed on the relatively cost-efficient Illiumina MiniSeq platform and evaluated with freely available bioinformatical tools. 57 genes for exonic SNP/InDel calling (19 of those in intronic regions for CNV analysis), 3 chromosomal arms and 4 entire chromosomes for CNV and LOH analysis were covered. Results were extensively validated. Our approach yielded high accuracy, sensitivity and specificity. It led to refined diagnoses in a relevant number of analyzed cases, reliably enabled complex subclassifications (e.g. for medulloblastomas) and identified actionable targets for clinical use. Thus, our single-platform approach is an efficient and powerful tool to comprehensively support molecular testing in neurooncology. Future functionality is guaranteed as novel upcoming biomarkers can be easily incorporated in a modular panel design.
Project description:The generation of new ideas and scientific hypotheses is often the result of extensive literature and database searches, but, with the growing wealth of public and private knowledge, the process of searching diverse and interconnected data to generate new insights into genes, gene networks, traits and diseases is becoming both more complex and more time-consuming. To guide this technically challenging data integration task and to make gene discovery and hypotheses generation easier for researchers, we have developed a comprehensive software package called KnetMiner which is open-source and containerized for easy use. KnetMiner is an integrated, intelligent, interactive gene and gene network discovery platform that supports scientists explore and understand the biological stories of complex traits and diseases across species. It features fast algorithms for generating rich interactive gene networks and prioritizing candidate genes based on knowledge mining approaches. KnetMiner is used in many plant science institutions and has been adopted by several plant breeding organizations to accelerate gene discovery. The software is generic and customizable and can therefore be readily applied to new species and data types; for example, it has been applied to pest insects and fungal pathogens; and most recently repurposed to support COVID-19 research. Here, we give an overview of the main approaches behind KnetMiner and we report plant-centric case studies for identifying genes, gene networks and trait relationships in Triticum aestivum (bread wheat), as well as, an evidence-based approach to rank candidate genes under a large Arabidopsis thaliana QTL. KnetMiner is available at: https://knetminer.org.
Project description:Incarcerated transgender individuals may need to access physical and mental health services to meet their general and gender-affirming (e.g., hormones, surgery) medical needs while incarcerated.This study sought to examine correctional healthcare providers' knowledge of, attitudes toward, and experiences providing care to transgender inmates.In 2016, 20 correctional healthcare providers (e.g., physicians, social workers, psychologists, mental health counselors) from New England participated in in-depth, semi-structured interviews examining their experiences caring for transgender inmates. The interview guide drew on healthcare-related interviews with recently incarcerated transgender women and key informant interviews with correctional healthcare providers and administrators. Data were analyzed using a modified grounded theory framework and thematic analysis.Findings revealed that transgender inmates do not consistently receive adequate or gender-affirming care while incarcerated. Factors at the structural level (i.e., lack of training, restrictive healthcare policies, limited budget, and an unsupportive prison culture); interpersonal level (i.e., custody staff bias); and individual level (i.e., lack of transgender cultural and clinical competence) impede correctional healthcare providers' ability to provide gender-affirming care to transgender patients. These factors result in negative health consequences for incarcerated transgender patients.Results call for transgender-specific healthcare policy changes and the implementation of transgender competency trainings for both correctional healthcare providers and custody staff (e.g., officers, lieutenants, wardens).
Project description:Despite a strong global commitment, polio eradication efforts continue now more than 30 years after the 1988 World Health Assembly resolution that established the Global Polio Eradication Initiative (GPEI), and 20 years after the original target of the year 2000. Prior health economic analyses estimated incremental net benefits of the GPEI of 40-50 billion in 2008 U.S. dollars (US$2008, equivalent to 48-59 billion US$2019), assuming the achievement of polio eradication by 2012. Given the delays in achieving polio eradication and increased costs, we performed an updated economic analysis of the GPEI using an updated integrated global model, and considering the GPEI trajectory as of the beginning of 2020. Applying similar methods and assuming eradication achievement in 2023, we estimate incremental net benefits of the GPEI of 28 billion US$2019, which falls below the prior estimate. Delays in achieving polio eradication combined with the widescale introduction of relatively expensive inactivated poliovirus vaccine significantly increased the costs of the GPEI and make it less cost-effective, although the GPEI continues to yield expected incremental net benefits at the global level when considered over the time horizon of 1988-2029. The overall health and financial benefits of the GPEI will depend on whether and when the GPEI can achieve its goals, when eradication occurs, the valuation method applied, and the path dependence of the actions taken. Reduced expected incremental net benefits of the GPEI and the substantial economic impacts of the COVID-19 pandemic pose large financial risks for the GPEI.
Project description:In 2015, the World Health Organization (WHO) declared tuberculosis (TB) to be responsible for more deaths than any other single infectious disease. The burden of TB among children has frequently been dismissed as relatively low with resulting deaths contributing very little to global under-five all-cause mortality, although without rigorous estimates of these statistics, the burden of childhood TB was, in reality, unknown. Recent work in the area has resulted in a WHO estimate of 1 million new cases of childhood TB in 2014 resulting in 136,000 deaths. Around 3% of these cases likely have multidrug-resistant TB and at least 40,000 are in HIV-infected children. TB is now thought to be a major or contributory cause of many deaths in children under five years old, despite not being recorded as such, and is likely in the top ten causes of global mortality in this age group. In particular, recent work has shown that TB is an under-lying cause of a substantial proportion of pneumonia deaths in TB-endemic countries. Childhood TB should be given higher priority: we need to identify children at greatest risk of TB disease and death and make more use of tools such as active case-finding and preventive therapy. TB is a preventable and treatable disease from which no child should die.
Project description:There are very few international examples of the successful eradication of bovine tuberculosis (TB, caused by infection with Mycobacterium bovis) from a national cattle population. This paper presents a brief overview of the successful TB eradication programme in Australia from 1970, with primary emphasis on lessons of international relevance that were learned from the Australian experience. The national brucellosis and tuberculosis eradication campaign ran for 27 years from 1970 to 1997 and has been followed by ongoing abattoir surveillance. Rapid progress towards eradication was made in southern Australia, but proved much more challenging in extensive pastoral areas of northern Australia. Declaration of TB freedom was made on December 31, 1997. A range of factors were critical to this success, including a compelling rationale for eradication, an agreed final outcome, industry commitment and financial support, a business model for programme planning, implementation and review, consistent and transparent technical standards underpinned by a strict regulatory regime and applied research, the critical role of abattoir surveillance, effective elimination of residual infection and objective measures of programme progress. Although direct translation of some of these experiences may not be possible, many of the lessons learned from the Australian experience may be relevant to other countries.