631 research outputs found

    Molecular cloning of mouse placental lactogen cDNA.

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    Spectropolarimetric measurements of hidden broad lines in nearby megamaser galaxies: a lack of clear evidence for a correlation between black hole masses and virial products

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    High-accuracy black hole (BH) masses require excellent spatial resolution that is only achievable for galaxies within ~100 Mpc using present-day technology. At larger distances, BH masses are often estimated with single-epoch scaling relations for active galactic nuclei. This method requires only luminosity and the velocity dispersion of the broad line region (BLR) to calculate a virial product, and an additional virial factor, ff, to determine BH mass. The accuracy of these single-epoch masses, however, is unknown, and there are few empirical constraints on the variance of ff between objects. We attempt to calibrate single-epoch BH masses using spectropolarimetric measurements of nine megamaser galaxies from which we measure the velocity distribution of the BLR. We do not find strong evidence for a correlation between the virial products used for single-epoch masses and dynamical mass, both for the megamaser sample alone and when combined with dynamical masses from reverberation mapping modeling. Furthermore, we find evidence that the virial parameter ff varies between objects, but we do not find strong evidence for a correlation with other observable parameters such as luminosity or broad line width. Although we cannot definitively rule out the existence of any correlation between dynamical mass and virial product, we find tension between allowed ff values for masers and those widely used in the literature. We conclude that the single-epoch method requires further investigation if it is to be used successfully to infer BH masses.Comment: 27 pages, 16 figures, resubmitted to ApJ after incorporating reviewer's comments. Corrected Figure 8, main results do not chang

    Feasibility of a “Network of Champions” in Implementing a Program to Address Physician Well-being

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    Introduction: Healthcare leaders have been challenged to mitigate burnout and foster well-being among physicians. Professional societies are beginning to address this in a systematic manner. Methods: In 2014, the American College of Physicians (ACP) endeavored to improve well-being for its 160,000 members of internists and trainees through a Well-being Champion (WBC) program based in the majority of its 85 national and international chapters. The program was supported by an evidence-based curriculum, chapter volunteers who served as champions, and in-person and virtual trainings. Training included a 1-2 day program in 2018 and 2019, focused on educating champions on causes of burnout, means of systematically collecting well-being data, and methods for using data for system change to reduce burnout and improve well-being. Results: Training included 158 WBCs in 8 countries. After training, over 90% of champions in both years of the program felt able to articulate the evidence for burnout prevention and suggest interventions, access resources, and administer well-being surveys. While 58% of champions noted high interest in wellness, only 26% had a budget allocated for this, and most budgets were small. Ninety-one percent in both years felt able to analyze survey data and 90% in both years felt able to enhance their own well-being. Eighty-eight to 90% felt able to foster a well-being community and importantly, 85% felt comfortable engaging leadership in this topic. Since 2017, 639 activities were recorded, accounting for 87/158 Champions in 69 Chapters. Annual direct costs varied each year but remained Conclusion: This report describes a model for building regional networks to address physician burnout while promoting well-being and professional fulfillment. After training, champions felt capable of performing key aspects of burnout reduction, including survey administration, data analysis and engaging leadership in systems change. To our knowledge, this is the first model to scale burnout prevention throughout an entire professional society. Using the included program descriptions and curricula, this program may be generalizable for other large professional groups wishing to measure and enhance well-being among their membership

    Which doctors and with what problems contact a specialist service for doctors? A cross sectional investigation

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    Background: In the United Kingdom, specialist treatment and intervention services for doctors are underdeveloped. The MedNet programme, created in 1997 and funded by the London Deanery, aims to fill this gap by providing a self-referral, face-to-face, psychotherapeutic assessment service for doctors in London and South-East England. MedNet was designed to be a low-threshold service, targeting doctors without formal psychiatric problems. The aim of this study was to delineate the characteristics of doctors utilising the service, to describe their psychological morbidity, and to determine if early intervention is achieved. Methods: A cross-sectional study including all consecutive self-referred doctors (n = 121, 50% male) presenting in 2002–2004 was conducted. Measures included standardised and bespoke questionnaires both self-report and clinician completed. The multi-dimensional evaluation included: demographics, CORE (CORE-OM, CORE-Workplace and CORE-A) an instrument designed to evaluate the psychological difficulties of patients referred to outpatient services, Brief Symptom Inventory to quantify caseness and formal psychiatric illness, and Maslach Burnout Inventory. Results: The most prevalent presenting problems included depression, anxiety, interpersonal, self-esteem and work-related issues. However, only 9% of the cohort were identified as severely distressed psychiatrically using this measure. In approximately 50% of the sample, problems first presented in the preceding year. About 25% were on sick leave at the time of consultation, while 50% took little or no leave in the prior 12 months. A total of 42% were considered to be at some risk of suicide, with more than 25% considered to have a moderate to severe risk. There were no significant gender differences in type of morbidity, severity or days off sick. Conclusion: Doctors displayed high levels of distress as reflected in the significant proportion of those who were at some risk of suicide; however, low rates of severe psychiatric illness were detected. These findings suggest that MedNet clients represent both ends of the spectrum of severity, enabling early clinical engagement for a significant proportion of cases that is of importance both in terms of personal health and protecting patient care, and providing a timely intervention for those who are at risk, a group for whom rapid intervention services are in need and an area that requires further investigation in the UK

    Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study

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    Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is approximately 5–10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited 11 patients with established PoTS and 23 age-matched normal controls. Group comparison of gray matter volume revealed diminished gray matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients

    Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

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    Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

    A Proposed Process for Managing the First Amendment Aspects of Campus Hate Speech

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    For public institutions, attempts to regulate hate speech raise substantial legal issues under the First Amendment of the U.S. Constitution. For private institutions, which may not be bound by the First Amendment, attempts to regulate hate speech raise sensitive policy questions concerning the role of free expression on campus. Numerous articles (many of which are listed in the references below) have undertaken substantive analysis of these constitutional issues and policy questions. In contrast, this article explores a preliminary and overarching concern: the process by which a college or university addresses the problem of hate speech, and in particular the process by which the institution manages the First Amendment aspects of the problem. In other words, this article focuses on the decision-making process rather than on the decisions themselves; it is the journey, not the destination, that is of primary concern

    Neurovisceral phenotypes in the expression of psychiatric symptoms

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    This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

    Using the net benefit regression framework to construct cost-effectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope

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    BACKGROUND: Cost-effectiveness acceptability curves (CEACs) describe the probability that a new treatment or intervention is cost-effective. The net benefit regression framework (NBRF) allows cost-effectiveness analysis to be done in a simple regression framework. The objective of the paper is to illustrate how net benefit regression can be used to construct a CEAC. METHODS: One hundred patients referred for ambulatory monitoring with syncope or presyncope were randomized to a one-month external loop recorder (n = 49) or 48-hour Holter monitor (n = 51). The primary endpoint was symptom-rhythm correlation during monitoring. Direct costs were calculated based on the 2003 Ontario Health Insurance Plan (OHIP) fee schedule combined with hospital case costing of labour, materials, service and overhead costs for diagnostic testing and related equipment. RESULTS: In the loop recorder group, 63.27% of patients (31/49) had symptom recurrence and successful activation, compared to 23.53% in the Holter group (12/51). The cost in US dollars for loop recording was 648.50and648.50 and 212.92 for Holter monitoring. The incremental cost-effectiveness ratio (ICER) of the loop recorder was $1,096 per extra successful diagnosis. The probability that the loop recorder was cost-effective compared to the Holter monitor was estimated using net benefit regression and plotted on a CEAC. In a sensitivity analysis, bootstrapping was used to examine the effect of distributional assumptions. CONCLUSION: The NBRF is straightforward to use and interpret. The resulting uncertainty surrounding the regression coefficient relates to the CEAC. When the link from the regression's p-value to the probability of cost-effectiveness is tentative, bootstrapping may be used
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