A Doctor\u27s Duty to Disclose Life Expectancy Information to Terminally Ill Patients

It is the purpose of this Note to review and evaluate the benefits to making full disclosure to a terminally ill patient. It is this author\u27s position that a patient\u27s well-being and dignity dictate that the physician be forthright with all information regarding a patient\u27s diagnosis and the range of treatments available, including both active and passive treatments

THE FOUR TRANSACTIONAL DISTANCES OF THE APOCALYPSE: A CRITICAL REALIST CASE STUDY OF HIGHER EDUCATION DURING COVID-19

The purpose of this comparative, longitudinal case study was to explore the distance operations system implemented in U.S. colleges and universities during the COVID-19 pandemic. Embedded in a larger two-year study of distance education in the U.S. before and after the health crisis, this study combined a grounded theory methodology with a critical realist approach to identify the components of the distance operations system and illuminate the generative mechanisms that promote or inhibit effective distance education. Primary data for this study consisted of interviews of faculty, staff, and administration of four higher education institutions at two collection points: first during the spring and summer academic terms of 2020; and second, during or immediately after the fall 2020 academic term. Secondary data included participant-provided and public-facing documents, communications, and artifacts related to the transition to and continuity of distance operations. This study refines the construct of transactional distance (Moore, 1993) and offers a typology of distance in two domains: the physical domain, which includes temporal and transportational distance; and the psychological domain, which includes socio-personal and cognitive distance. This research has the potential to both disturb and inform higher education thought and action regarding the ways distance and distance education have been discussed, researched, and practiced. This study reveals that participants variously acted or reacted to, altered or shaped, and measured or adjudged the effects of distance. Thus, this dissertation argues that distance is a construct that higher education can and should distinguish, control, and wield for its purposes. Findings contribute to what is known about distance education at the macro level of theory and systems (Zawacki-Richter, 2009) and point to a need to evaluate the different types of distance and further explore how and under what circumstances distance may be most effective for any institutional activities

Comparisons of computational methods for differential alternative splicing detection using RNA-seq in plant systems

BackgroundAlternative Splicing (AS) as a post-transcription regulation mechanism is an important application of RNA-seq studies in eukaryotes. A number of software and computational methods have been developed for detecting AS. Most of the methods, however, are designed and tested on animal data, such as human and mouse. Plants genes differ from those of animals in many ways, e.g., the average intron size and preferred AS types. These differences may require different computational approaches and raise questions about their effectiveness on plant data. The goal of this paper is to benchmark existing computational differential splicing (or transcription) detection methods so that biologists can choose the most suitable tools to accomplish their goals. ResultsThis study compares the eight popular public available software packages for differential splicing analysis using both simulated and real Arabidopsis thaliana RNA-seq data. All software are freely available. The study examines the effect of varying AS ratio, read depth, dispersion pattern, AS types, sample sizes and the influence of annotation. Using a real data, the study looks at the consistences between the packages and verifies a subset of the detected AS events using PCR studies. ConclusionsNo single method performs the best in all situations. The accuracy of annotation has a major impact on which method should be chosen for AS analysis. DEXSeq performs well in the simulated data when the AS signal is relative strong and annotation is accurate. Cufflinks achieve a better tradeoff between precision and recall and turns out to be the best one when incomplete annotation is provided. Some methods perform inconsistently for different AS types. Complex AS events that combine several simple AS events impose problems for most methods, especially for MATS. MATS stands out in the analysis of real RNA-seq data when all the AS events being evaluated are simple AS events

The impact of leadership development on GP mental health commissioning.

Purpose This paper aims to explore the learning needs of general practitioners (GPs) involved in commissioning mental health provision in England, and offer an evaluation of a leadership and commissioning skills development programme for Mental Health Commissioners. Design/methodology/approach Retrospective mixed method, including online mixed method survey, rating participants' knowledge, skills, abilities, semi-structured telephone interviews and third-party questionnaires were used. Results were analysed for significant differences using the Wilcoxon Signed Ranks test. Open-ended responses and interview transcripts were analysed thematically. Findings Indicative results showed that participants perceived significant impacts in ability across eight key question groups evaluated. Differences were found between the perceived and observed impact in relation to technical areas covered within the programme which were perceived as the highest scoring impacts by participants. Research limitations/implications The indicative results show a positive impact on practice has been both perceived and observed. Findings illustrate the value of this development programme on both the personal development of GP Mental Health Commissioners and commissioning practice. Although the findings of this evaluation increase understanding in relation to an important and topical area, larger scale, prospective evaluations are required. Impact evaluations could be embedded within future programmes to encourage higher participant and third-party engagement. Future evaluations would benefit from collection and analysis of attendance data. Further research could involve patient, service user and carer perspectives on mental health commissioning. Originality value Results of this evaluation could inform the development of future learning programmes for mental health commissioners as part of a national approach to improve mental health provision

Artificial Intelligence/Operations Research Workshop 2 Report Out

This workshop Report Out focuses on the foundational elements of trustworthy AI and OR technology, and how to ensure all AI and OR systems implement these elements in their system designs. Four sessions on various topics within Trustworthy AI were held, these being Fairness, Explainable AI/Causality, Robustness/Privacy, and Human Alignment and Human-Computer Interaction. Following discussions of each of these topics, workshop participants also brainstormed challenge problems which require the collaboration of AI and OR researchers and will result in the integration of basic techniques from both fields to eventually benefit societal needs

Differentiating normal and problem gambling: a grounded theory approach.

A previous study (Ricketts &amp; Macaskill, 2003) delineated a theory of problem gambling based on the experiences of treatment seeking male gamblers and allowed predictions to be made regarding the processes that differentiate between normal and problem gamblers. These predictions are the focus of the present study, which also utilised a grounded theory approach, but with a sample of male high frequency normal gamblers. The findings suggest that there are common aspects of gambling associated with arousal and a sense of achievement. The use of gambling to manage negative emotional states differentiated normal and problem gambling. Perceived self-efficacy , emotion management skills and perceived likelihood of winning money back were intervening variables differentiating problem and normal gamblers.</p

Tobacco smoking and nicotine dependence in first episode and established psychosis

Aim People with psychotic disorders have increased premature mortality in comparison with the general population, with high rates of cigarette use a contributing factor. We aimed to describe the prevalence of cigarette use and nicotine dependence (ND) in first episode psychosis (FEP), and established psychosis; and to investigate associations between clinical symptoms and ND. Methodology Smoking and clinical data were collected from two cohorts: 181 people with FEP recruited as part of the Physical Health and Substance Use Measures in First Onset Psychosis (PUMP) study and from 432 people with established psychosis recruited as part of the Improving physical health and reducing substance use in psychosis randomised controlled trial (IMPaCT RCT). Results The prevalence of cigarette smoking was 78% in FEP and 62% in established psychosis. Forty nine percent (n=60) of smokers in the FEP cohort and 69% (n=183) of smokers with established psychosis were highly nicotine dependent. Being a highly nicotine dependent smoker was significantly associated with higher PANSS positive symptom scores (F= 5.480 p= 0.004), and with decreased scores on the Rosenberg self-esteem scale (F=3.261, p=0.039) in established psychosis. There was no diagnostic specificity identified in relation to smoking or ND in both groups. Conclusion High rates of cigarette usage and nicotine dependence are problems from the early stages of psychosis. ND is higher in people with established psychosis. Smoking cessation strategies as part of comprehensive management of psychotic disorders at every stage require further development and evaluation

Metabolomics as a Hypothesis-Generating Functional Genomics Tool for the Annotation of Arabidopsis thaliana Genes of “Unknown Function”

Metabolomics is the methodology that identifies and measures global pools of small molecules (of less than about 1,000 Da) of a biological sample, which are collectively called the metabolome. Metabolomics can therefore reveal the metabolic outcome of a genetic or environmental perturbation of a metabolic regulatory network, and thus provide insights into the structure and regulation of that network. Because of the chemical complexity of the metabolome and limitations associated with individual analytical platforms for determining the metabolome, it is currently difficult to capture the complete metabolome of an organism or tissue, which is in contrast to genomics and transcriptomics. This paper describes the analysis of Arabidopsis metabolomics data sets acquired by a consortium that includes five analytical laboratories, bioinformaticists, and biostatisticians, which aims to develop and validate metabolomics as a hypothesis-generating functional genomics tool. The consortium is determining the metabolomes of Arabidopsis T-DNA mutant stocks, grown in standardized controlled environment optimized to minimize environmental impacts on the metabolomes. Metabolomics data were generated with seven analytical platforms, and the combined data is being provided to the research community to formulate initial hypotheses about genes of unknown function (GUFs). A public database (www.PlantMetabolomics.org) has been developed to provide the scientific community with access to the data along with tools to allow for its interactive analysis. Exemplary datasets are discussed to validate the approach, which illustrate how initial hypotheses can be generated from the consortium-produced metabolomics data, integrated with prior knowledge to provide a testable hypothesis concerning the functionality of GUFs

First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade \u3e 1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a Cmax of 1.5 to 7.5 μg/mL (∼3.9–19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (\u3e 9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks