Beyond Empathy – A Glimpse into the Physician-Patient Relationship

During the first surgery I witnessed, I was struck by an immense sense of wonder at the human body. This research effort determines if this awe is shared by physicians currently practicing medicine, if this wonder will fade as part of an everyday landscape, and delves into the different forms the physician-patient relationship can take. Through a textual study of Sherwin Nuland’s The Wisdom of the Body and interviews of four practicing physicians, these topics were explored. It was found that the sense of awe is a shared experience between physicians, shifting from fascination of anatomy and physiology to pathology and treatment. It was concluded that physicians should try to counteract a cultural paternalistic model of medicine and strive for the morally desirable partnership or friendship models. Each of the interviews identified intimacy as setting medicine apart from other professions and the importance of empathy in developing the physician-patient relationship. It is not enough for physicians to understand what their patients are feeling; they must be willing to take on the pain and joy as their own. This research offers both patients and physicians a better understanding of the intimate relationship they forge

The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and primary sclerosing cholangitis

BACKGROUND: In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) fatigue is a major clinical problem. Abnormal amino acid (AA) patterns have been implicated in the development of fatigue in several non-hepatological conditions but for PBC and PSC no data are available. This study aimed to identify abnormalities in AA patterns and to define their relation with fatigue. METHODS: Plasma concentrations of tyrosine, tryptophan, phenylalanine, valine, leucine and isoleucine were determined in plasma of patients with PBC (n = 45), PSC (n = 27), chronic hepatitis C (n = 22) and healthy controls (n = 73). Fatigue and quality of life were quantified using the Fisk fatigue severity scale, a visual analogue scale and the SF-36. RESULTS: Valine, isoleucine, leucine were significantly decreased in PBC and PSC. Tyrosine and phenylalanine were increased (p < 0.0002) and tryptophan decreased (p < 0.0001) in PBC. In PBC, but not in PSC, a significant inverse relation between tyrosine concentrations and fatigue and quality of life was found. Patients without fatigue and with good quality of life had increased tyrosine concentrations compared to fatigued patients. Multivariate analysis indicated that this relation was independent from disease activity or severity or presence of cirrhosis. CONCLUSION: In patients with PBC and PSC, marked abnormalities in plasma AA patterns occur. Normal tyrosine concentrations, compared to increased concentrations, may be associated with fatigue and diminished quality of life

Predictors of Bicuspid Aortic Valve-Associated Aortopathy in Childhood: A Report From the MIBAVA Consortium

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients. METHODS: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity of AS and AI, history of coarctation, and aortic dimensions. Associations were determined using multivariable regression analysis. A subset of patients undergoing aortic interventions (balloon dilation or Ross) were assessed longitudinally. RESULTS: Data were obtained from 2122 patients (68% male; median age 10.2 years). Fifty percent of patients had ascending aorta dilatation. Right and noncoronary cusp fusion, increasing AS and AI, and older age were independently associated with ascending aorta dilatation. A history of coarctation was associated with less ascending aorta dilatation. In patients with neither AS nor AI, 37% had ascending aorta dilatation (4% severe). No complications related to aortic dilatation occurred in this cohort. Aortic CONCLUSIONS: In this large pediatric cohort of patients with BAV, valve morphology, AS, and AI are independently associated with ascending aorta dilatation, suggesting that hemodynamic factors influence aortopathy. However, even in BAVs with no AS or AI, there is significant ascending aorta dilatation independent of valve morphology. Interventions that led to changes in degree of AI and AS did not seem to influence change in aortic dimensions. The current BAV cohort can be used as a reference group for expected changes in aortic dimensions during childhood

Theoretical basis for reducing time-lines to the determination of positive Mycobacterium tuberculosis cultures using thymidylate kinase (TMK) assays

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>culture of pathogens on growth media forms a "pillar" for both infectious disease diagnosis and drug sensitivity profiling. Conventional cultures of <it>Mycobacterium tuberculosis </it>(M.<it>tb</it>) on Lowenstein Jensen (LJ) medium, however, take over two months to yield observable growth, thereby delaying diagnosis and appropriate intervention. Since DNA duplication during interphase precedes microbial division, "para-DNA synthesis assays" could be used to predict impending microbial growth. Mycobacterial thymidylate kinase (TMKmyc) is a phosphotransferase critical for the synthesis of the thymidine triphosphate precursor necessary for M.<it>tb </it>DNA synthesis. Assays based on high-affinity detection of secretory TMKmyc levels in culture using specific antibodies are considered. The aim of this study was to define algorithms for predicting positive TB cultures using antibody-based assays of TMKmyc levels <it>in vitro</it>.</p> <p>Methods and results</p> <p>Systems and chemical biology were used to derive parallel correlation of "M.<it>tb </it>growth curves" with "TMKmyc curves" theoretically in four different scenarios, showing that changes in TMKmyc levels in culture would in each case be predictive of M.<it>tb </it>growth through a simple quadratic curvature, |tmk| = at²+ bt + c, consistent with the "S" pattern of microbial growth curves. Two drug resistance profiling scenarios are offered: isoniazid (INH) resistance and sensitivity. In the INH resistance scenario, it is shown that despite the presence of optimal doses of INH in LJ to stop M.<it>tb </it>proliferation, bacilli grow and the resulting phenotypic growth changes in colonies/units are predictable through the TMKmyc assay. According to our current model, the areas under TMKmyc curves (AUC, calculated as the integral ∫(at²+ bt + c)dt or ~1/3 at³+ 1/2 bt²+ct) could directly reveal the extent of prevailing drug resistance and thereby aid decisions about the usefulness of a resisted drug in devising "salvage combinations" within resource-limited settings, where second line TB chemotherapy options are limited.</p> <p>Conclusion</p> <p>TMKmyc assays may be useful for reducing the time-lines to positive identification of <it>Mycobacterium tuberculosis </it>(M.<it>tb</it>) cultures, thereby accelerating disease diagnosis and drug resistance profiling. Incorporating "chemiluminiscent or fluorescent" strategies may enable "photo-detection of TMKmyc changes" and hence automation of the entire assay.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Fault rotation and core complex formation : significant processes in seafloor formation at slow-spreading mid-ocean ridges (Mid-Atlantic Ridge, 13°–15°N)

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q03003, doi:10.1029/2007GC001699.The region of the Mid-Atlantic Ridge (MAR) between the Fifteen-Twenty and Marathon fracture zones displays the topographic characteristics of prevalent and vigorous tectonic extension. Normal faults show large amounts of rotation, dome-shaped corrugated detachment surfaces (core complexes) intersect the seafloor at the edge of the inner valley floor, and extinct core complexes cover the seafloor off-axis. We have identified 45 potential core complexes in this region whose locations are scattered everywhere along two segments (13° and 15°N segments). Steep outward-facing slopes suggest that the footwalls of many of the normal faults in these two segments have rotated by more than 30°. The rotation occurs very close to the ridge axis (as much as 20° within 5 km of the volcanic axis) and is complete by ∼1 My, producing distinctive linear ridges with roughly symmetrical slopes. This morphology is very different from linear abyssal hill faults formed at the 14°N magmatic segment, which display a smaller amount of rotation (typically <15°). We suggest that the severe rotation of faults is diagnostic of a region undergoing large amounts of tectonic extension on single faults. If faults are long-lived, a dome-shaped corrugated surface develops in front of the ridges and lower crustal and upper mantle rocks are exposed to form a core complex. A single ridge segment can have several active core complexes, some less than 25 km apart that are separated by swales. We present two models for multiple core complex formation: a continuous model in which a single detachment surface extends along axis to include all of the core complexes and swales, and a discontinuous model in which local detachment faults form the core complexes and magmatic spreading forms the intervening swales. Either model can explain the observed morphology.D. Smith and H. Schouten were supported in this work by NSF grant OCE-0649566. J. Escartın was supported by CNRS

Incidence and prevalence of dementia in linked administrative health data in Saskatchewan, Canada: a retrospective cohort study.

Determining the epidemiology of dementia among the population as a whole in specific jurisdictions - including the long-term care population-is essential to providing appropriate care. The objectives of this study were to use linked administrative databases in the province of Saskatchewan to determine the 12-month incidence and prevalence of dementia for the 2012/13 period (1) among individuals aged 45 and older in the province of Saskatchewan, (2) according to age group and sex, and (3) according to diagnosis code and other case definition criteria

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts