tbuckley/cabot-search huggingface dataset:
Intervention to Promote Physician Well-being, Job Satisfaction, and Professionalism
Authors: Colin P. West, Liselotte N. Dyrbye, Jeff T. Rabatin, Tim G. Call, John H. Davidson, Adamarie Multari, Susan A. Romanski, Joan M. Henriksen Hellyer, Jeff A. Sloan, Tait D. Shanafelt
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Despite the documented prevalence and clinical ramifications of physician distress, few rigorous studies have tested interventions to address the problem. <h3>Objective</h3> To test the hypothesis that an intervention involving a facilitated physician small-group curriculum would result in improvement in well-being. <h3>Design, Setting, and Participants</h3> Randomized clinical trial of 74 practicing physicians in the Department of Medicine at the Mayo Clinic in Rochester, Minnesota, conducted between September 2010 and June 2012. Additional data were collected on 350 nontrial participants responding to annual surveys timed to coincide with the trial surveys. <h3>Interventions</h3> The intervention involved 19 biweekly facilitated physician discussion groups incorporating elements of mindfulness, reflection, shared experience, and small-group learning for 9 months. Protected time (1 hour of paid time every other week) for participants was provided by the institution. <h3>Main Outcomes and Measures</h3> Meaning in work, empowerment and engagement in work, burnout, symptoms of depression, quality of life, and job satisfaction assessed using validated metrics. <h3>Results</h3> Empowerment and engagement at work increased by 5.3 points in the intervention arm vs a 0.5-point decline in the control arm by 3 months after the study (<i>P</i> = .04), an improvement sustained at 12 months (+5.5 vs +1.3 points;<i>P</i> = .03). Rates of high depersonalization at 3 months had decreased by 15.5% in the intervention arm vs a 0.8% increase in the control arm (<i>P</i> = .004). This difference was also sustained at 12 months (9.6% vs 1.5% decrease;<i>P</i> = .02). No statistically significant differences in stress, symptoms of depression, overall quality of life, or job satisfaction were seen. In additional comparisons including the nontrial physician cohort, the proportion of participants strongly agreeing that their work was meaningful increased 6.3% in the study intervention arm but decreased 6.3% in the study control arm and 13.4% in the nonstudy cohort (<i>P</i> = .04). Rates of depersonalization, emotional exhaustion, and overall burnout decreased substantially in the trial intervention arm, decreased slightly in the trial control arm, and increased in the nontrial cohort (<i>P</i> = .03, .007, and .002 for each outcome, respectively). <h3>Conclusions and Relevance</h3> An intervention for physicians based on a facilitated small-group curriculum improved meaning and engagement in work and reduced depersonalization, with sustained results at 12 months after the study. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01159977
Payment for coroners' postmortem examinations
Authors: Mary N Sheppard
Journal: BMJ (2004)

Editor—Alcolado remembers as a house officer requesting a postmortem examination and being forced to make it a coroner's at the request of a pathologist.1

Firstly, let me make it clear that nobody can force someone to make a death into a coroner's post mortem if a cause of death is established. The doctor simply signs the death certificate to this effect. I know of no pathologist who can bend the ear of the coroner to this extent—rather the opposite. In my experience, cases are often not referred to the coroner that should be, such as postoperative deaths.

Secondly, the idea that the pathologist receives “a substantial payment” for each coroner's post mortem is laughable. I get £78 for each postmortem case I do, and this often involves four to six hours of work because I deal with complex postoperative deaths that usually require detailed examination and histology. The BMA is looking into the fees for coroners' autopsies and campaigning for a substantial increase. The pathologist who forced Alcolado to turn a case into a coroner's post mortem must have been desperate to waste his or her precious time for £78.

Finally, all coroners' cases in my hospital are actively used for teaching and audit purposes.
Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors—Letter
Authors: David C. Binder, Hans Schreiber
Journal: Cancer Research (2014)

There is much effort to develop new therapeutic approaches to rescue dysfunctional T cells in patients with cancer. In the June issue of Cancer Research, Duraiswamy and colleagues demonstrate that a triple therapy consisting of anti-PD-1, anti-CTLA-4, and therapeutic vaccination provides consistent rejection of experimental tumors (1). This triple therapy was better than any single- or double-agent combination.The study by Duraiswamy and colleagues has much translational relevance (1) as new clinical data demonstrate that antagonistic antibodies blocking PD-1 and/or CTLA-4 provide strong responses to some but not all patients (2–4). Interestingly, the limited objective response rate seems to also apply to patients with a presumed preexisting tumor-reactive T-cell response (3, 5). Therefore, the importance of the Duraiswamy study is that it identified an approach that may extend objective response rates to a greater percentage of patients.The study treated mice 3 or 10 days after inoculation of murine colon or murine ovarian cancer cells, respectively (1). At that time, mice still lacked or had barely detectible tumor nodules. However, it takes approximately 14 days and a tumor burden for initially functional tumor-reactive T cells—generated in response to cancer cell inoculation—to become dysfunctional (6, 7). Therefore, it would be important to know whether the approach described by Duraiswamy and colleagues prevented the development of T-cell dysfunction or rescued existent T-cell dysfunction, and how anti-CTLA-4 and PD-1 blockade contributed to the rescue if observed. Using at least 14-day-old tumors exceeding 100 mm3, we found that vaccination with antigen-producing bacteria combined with PD-1 blockade eradicated tumors, but combining anti-CTLA-4 with PD-1 blockade did not improve outcomes (7).Some vaccines may be effective in preventing but not rescuing T-cell dysfunction (8), and preventative approaches may not be effective in treating patients already in a state of T-cell dysfunction. Thus, it would be important to extend experimental studies by Duraiswamy and colleagues by testing the capacity of different types of vaccines and immunoinhibitory pathway blockades to rescue endogenous T cells in unmanipulated long-established experimental tumors.See the Response, p. 633See the Response, p. 635No potential conflicts of interest were disclosed.This research was supported by the NIH grants P01-CA97296, R01-CA22677, and R01-CA37516 to H. Schreiber and the Graduate Training in Growth and Development grant T32 HD009007 to D.C. Binder.
Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.
Authors: J Tamaoki, M Kondo, N Sakai, J Nakata, H Takemura, A Nagai, T Takizawa, K Konno
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.
Suicide in dermatological patients
Authors: J.A. COTTERILL, W.J. CUNLIFFE
Journal: British Journal of Dermatology (1997)

Journal Article Suicide in dermatological patients Get access J.A. COTTERILL, J.A. COTTERILL Lasercare Clinics Ltd, 1 Park View, Harrogate HG1 5LY, U.K., Search for other works by this author on: Oxford Academic Google Scholar W.J. CUNLIFFE W.J. CUNLIFFE The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 2, 1 August 1997, Pages 246–250, https://doi.org/10.1046/j.1365-2133.1997.18131897.x Published: 01 August 1997
Expression of plasminogen activator inhibitors type-1 and type-2 in the mouse lung after administration of crystalline silica
Authors: C Lardot, M Heusterpreute, P Mertens, M Philippe, D Lison
Journal: European Respiratory Journal (1998)

Altered expression of plasminogen activator inhibitors (PAIs) is of potential relevance to the process of lung fibrosis. To clarify the involvement of PAIs in interstitial lung diseases, we examined whether alterations in PAI-1 and PAI-2 were induced in response to a single intratracheal administration of a fibrosing dose of crystalline silica in mice (5 mg x animal(-1)). The time course of changes in PAI activity and PAI-1 protein were characterized in bronchoalveolar lavage fluid (BALF) and changes in PAI-1 and PAI-2 messenger ribonucleic acid (mRNAs) were monitored by reverse transcriptase polymerase chain reaction (RT-PCR) in BALF cells and lung tissue up to the fibrotic stage of the disease. Substantial levels of PAI activity were found in BALF of control animals, whereas no PAI-1 protein was detected. In response to silica treatment, we observed an acute increase of PAI activity and PAI-1 protein levels in BALF (day 1), associated with an induction of PAI-1 and PAI-2 mRNA levels in lung tissue. In alveolar macrophages, silica treatment induced a persistent upregulation of PAI-2 mRNA only. One month after silica treatment, PAI activity was undetectable in BALF while substantial PAI activity was still present in controls. At the same time point, sustained upregulation of PAI-1 and PAI- 2 mRNAs was, however, noted in lung tissue of animals treated with silica. These findings support the possible implication of PAIs in the remodelling process induced by silica in the lung.
Does physical activity reduce seniors' need for healthcare?: a study of 24 281 Canadians
Authors: John C Woolcott, Maureen C Ashe, William C Miller, Peilin Shi, Carlo A Marra
Journal: British Journal of Sports Medicine (2009)

Objectives Physical inactivity has been associated with significant increases in disease morbidity and mortality. This study assessed the association between physical activity and (1) health resource use and (2) health resource use costs. Design and Participants The responses from 24 281 respondents &gt;65 years to the Canadian Community Health Survey Cycle 1.1 were used to find activity levels and determine health resource use and costs. Logistic regression models were used to assess risks of hospitalisation. Results Physical inactivity was associated with statistically significant increases to hospitalisations, lengths of stay and healthcare visits (p&lt;0.01). Average healthcare costs (based on the 2007 value of the Canadian dollar) for the physically inactive were $C1214.15 higher than the healthcare costs of the physically active ($C2005.27 vs $C791.12, p&lt;0.01). Conclusion Among those &gt;65 years, physical activity is strongly associated with reduced health resource use and costs.
Efficacy and Safety of Automatic Remote Monitoring for Implantable Cardioverter-Defibrillator Follow-Up
Authors: Niraj Varma, Andrew E. Epstein, Anand Irimpen, Robert Schweikert, Charles Love
Journal: Circulation (2010)

Monitoring implantable cardiac device function and patient condition is important. The Lumos-T Safely Reduces Routine Office Device Follow-Up (TRUST) trial tested the hypothesis that remote home monitoring with automatic daily surveillance (HM) is safe and effective for implantable cardioverter-defibrillator follow-up for 1 year and enables rapid physician evaluation of significant events.In total, 1339 patients were randomized 2:1 to HM or conventional follow-up. Follow-up checks occurred at 3, 6, 9, 12, and 15 months after implantation. HM was used before office visits at 3 and 15 months in the HM group. At 6, 9, and 12 months, HM only was used but was followed by office visits if necessary. Conventional patients were evaluated with office visits only. Scheduled office visits and unscheduled evaluations, incidence of morbidity, and time elapsed from first event occurrence in each patient to physician evaluation were tracked for each group. HM and conventional patients were similar (age, 63.3+/-12.8 versus 64.0+/-12.1 years; gender, 72.0% versus 73.1% male; New York Heart Association class II, 55.9% versus 60.4%; pathology: left ventricular ejection fraction, 29.0+/-10.7% versus 28.5+/-9.8%; coronary artery disease, 64.8% versus 71.7%; primary prevention indication, 72.2% versus 73.8%; and dual-chamber implants, 57.8% versus 56.6%). HM reduced total in-hospital device evaluations by 45% without affecting morbidity. In the HM group, 85.8% of all 6-, 9-, and 12-month follow-ups were performed remotely only, indicating that HM provided sufficient assessment in the majority. Median time to evaluation was <2 days in the HM group compared with 36 days in the conventional group (P<0.001) for all arrhythmic events.HM is safe and allows more rapid detection of actionable events compared with conventional monitoring in patients with implantable electronic cardiac devices.
Disability and Quality of Life in Social Phobia: Epidemiologic Findings
Authors: Murray B. Stein, Yin M. Kean
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Social phobia in clinical studies is vividly associated with extensive disability and reduced quality of life. It is difficult to obtain a clear portrayal of the impairment associated with social phobia in community samples. Furthermore, it has been unclear in prior studies to what extent indices were attributable to social phobia as opposed to comorbid major depression. The authors examined relevant data from the Ontario Health Survey Mental Health Supplement. METHOD: The Ontario Health Survey Mental Health Supplement, a survey of more than 8,000 residents of Ontario, Canada, aged 15–64, used the University of Michigan Composite International Diagnostic Interview to assign DSM-III-R diagnoses. Several indicators of disability and quality of life were included. The authors compared these indices for persons with and without social phobia and adjusted where indicated for the effects of major depression and relevant sociodemographic factors. RESULTS: Persons with social phobia were impaired on a broad spectrum of measures, ranging from dropping out of school to experiencing disability in one’s main activity. They were also significantly more likely than persons without social phobia to rate themselves as “low functioning” on the Quality of Well-Being Scale and to report dissatisfaction with many aspects of life. Depressive comorbidity seemed to contribute only modestly to these outcomes. CONCLUSIONS: Social phobia can be a serious, disabling anxiety disorder associated with marked reduction in quality of life. Impairment in social phobia is substantial, even in the absence of comorbid major depression.
Comparison of Pax1/9 Locus Reveals 500-Myr-Old Syntenic Block and Evolutionary Conserved Noncoding Regions
Authors: Wei Wang, Jing Zhong, Bing Su, Yan Zhou, Yi-Quan Wang
Journal: Molecular Biology and Evolution (2006)

Identification of conserved genomic regions within and between different genomes is crucial when studying genome evolution. Here, we described regions of strong synteny conservation between vertebrate deuterostomes (tetrapods and teleosts) and invertebrate deuterostomes (amphioxus and sea urchin). The shared gene contents across phylogenetically distant species demonstrate that the conservation of the regions stemmed from an ancestral segment instead of a series of independent convergent events. Comparison of the syntenic regions allows us to postulate the primitive gene organization in the last common ancestor of deuterostomes and the evolutionary events that occurred to the 3 distinct lineages of sea urchin, amphioxus, and vertebrates after their separation. In addition, alignment of the syntenic regions led to the identification of 8 noncoding evolutionarily conserved regions shared between amphioxus and vertebrates. To our knowledge, this is the first report of conserved noncoding sequences shared by vertebrates and nonvertebrates. These noncoding sequences have high possibility of being elements that regulate neighboring genes. They are likely to be a factor in the maintenance of conserved synteny over long phylogenetic distance in different deuterostome lineages.
Macrophage Sphingomyelin Synthase 2 Deficiency Decreases Atherosclerosis in Mice
Authors: Jing Liu, Chongmin Huan, Mahua Chakraborty, Hongqi Zhang, Da Lu, Ming-Shang Kuo, Guoqing Cao, Xian-Cheng Jiang
Journal: Circulation Research (2009)

Rationale: Sphingomyelin synthase (SMS)2 contributes to de novo sphingomyelin (SM) biosynthesis and plasma membrane SM levels. SMS2 deficiency in macrophages diminishes nuclear factor κB and mitogen-activated protein kinase activation induced by inflammatory stimuli. Objective: The effects of SMS2 deficiency on the development of atherosclerosis are investigated. Methods and Results: We measured cholesterol efflux from macrophages of wild-type (WT) and SMS2 knockout (KO) mice. We transplanted SMS2 KO mouse bone marrow into low-density lipoprotein (LDL) receptor (LDLr) knockout mice (SMS2 −/− →LDLr −/− ), creating a mouse model of SMS2 deficiency in the macrophages. We found that SMS2 deficiency caused significant induction of cholesterol efflux in vitro and in vivo. Moreover, we found that SMS2 KO mice had less interleukin-6 and tumor necrosis factor α in the circulation before and after endotoxin stimulation, compared with controls. More importantly, after 3 months on a western-type diet, SMS2 −/− →LDLr −/− mice showed decreased atherosclerotic lesions in the aortic arch, root (57%, P &lt;0.001), and the entire aorta (42%, P &lt;0.01), compared with WT→LDLr −/− mice. Analysis of plaque morphology revealed that SMS2 −/− →LDLr −/− mice had significantly less necrotic core area (71%, P &lt;0.001), less macrophage content (37%, P &lt;0.01), and more collagen content (35%, P &lt;0.05) in atherosclerotic lesions. We also found that SMS2 −/− →LDLr −/− mice had significantly lower free cholesterol and cholesteryl ester levels in the brachiocephalic artery than WT→LDLr −/− mice (33 and 52%, P &lt;0.01 and P &lt;0.001, respectively). Conclusions: SMS2 deficiency in the macrophages reduces atherosclerosis in mice. Macrophage SMS2 is thus a potential therapeutic target for treatment of this disease.
Serum microRNA Expression in Maternal Blood or in Cord Blood As Biomarkers of Atopic Dermatitis at One Year of Age
Authors: Yuzaburo Inoue, Shingo Ochiai, Akifumi Eguchi, Takeshi Yamamoto, Fumiya Yamaide, Yoshinori Morita, Taiji Nakano, Takayasu Arima, Hiroyuki Kojima, Hiroko Suzuki, Yoshiharu Matsuno, Chisato Mori, Toshitada Takemori, Yoichi Kohno, Naoki Shimojo
Journal: Journal of Allergy and Clinical Immunology (2015)
Response to Letters Regarding Article, “Outcome of Patients With Low-Gradient “Severe” Aortic Stenosis and Preserved Ejection Fraction”
Authors: Nikolaus Jander, Jan Minners, Franz-Josef Neumann, Christa Gohlke-Bärwolf, Ingar Holme, Eva Gerdts, Kurt Boman, Philippe Brudi, John B. Chambers, Kenneth Egstrup, Y. Antero Kesäniemi, William Malbecq, Christoph A. Nienaber, Simon Ray, Anne Rossebø, Terje R. Pedersen, Terje Skjærpe, Ronnie Willenheimer, Kristian Wachtell
Journal: Circulation (2011)
A re-examination of variation associated with environmentally stressed organisms
Authors: E. F. Orlando
Journal: Human Reproduction Update (2001)

Variation is an essential feature of biological systems. Populations adapt to dynamic environments, in part, because of this variation. In this review, we re-examine phenotypic variation, especially in organisms living in polluted environments. A recent goal of ecotoxicology is to understand the sublethal effects of exposure to pollutants, e.g. responses to endocrine-disrupting contaminants. While variation is an inherent quality of organisms, variance is a statistical measure of the variation of a trait. Increased variance has been associated with organisms living at the perimeter of a population's range, introduced into novel environments, or exposed to pollution. Some researchers have proposed increased phenotypic variance in exposed populations as an evolutionary mechanism, and others have suggested its use as a biomarker. While we agree that variance often increases in the exposed population, we also recognize that the opposite phenomenon occurs. That is, variance can decrease from exposure to pollution. Altered variance in the exposed population-leading to heteroscedasticity-could result in erroneous conclusions (Type II errors). We suggest that exposure to endocrine-disrupting contaminants could influence the health of populations in ways that are not always represented by measures of central tendency, and that variance and distribution should also be examined in environmentally stressed wildlife.