tbuckley/cabot-search huggingface dataset:
The Medical Expert Aid Committee
Authors: J. Brown
Journal: BMJ (1898)

Potted Shiraz grapevines, in a glasshouse, were exposed to two different soil temperatures (13°C and 23°C) to evaluate the effects on vegetative growth and floral development from dormancy to anthesis. Soil temperature had no effect on the time of budbreak, anthesis, or the number of flowers per inflorescence. At anthesis total biomass was similar for both treatments, whereas shoot biomass was greater in the warm soil. From dormancy to anthesis, both root and trunk biomass decreased in the cool soil and only root biomass decreased in the warmer soil, but by twice as much as that in the cool soil. During dormancy to anthesis decreases in total nonstructural carbohydrate accounted for most of the decrease in root biomass. At budbreak, 14 cytokinins representing four recognized classes were present in bleeding sap, with <i>trans</i>-zeatin riboside and isopentenyl adenosine as the dominant forms. Total and active free base cytokinin concentrations were similar for both treatments, while sap from vines in the warm soil had significantly lower concentrations of nucleotide cytokinins. However, delivery of cytokinins was significantly greater in the warm soil treatment. By anthesis, cytokinin concentrations were similar for both treatments, but total cytokinin concentrations in xylem sap had decreased by almost 90% from budbreak. Root-generated cytokinins appear to be associated with the mobilization of the carbohydrate reserves at the end of dormancy and the ensuing shoot growth. Comparison of results with those of previous studies reveals that, because of apical dominance and correlative inhibition, the response to soil temperature in terms of number of buds to break and time of budbreak is conditioned by the number of nodes per cane.
Sensitivity of United States HIV antibody tests for detection of HIV-1 group O infections
Authors: C. Schable, C-P. Pau, D. Hu, T. Dondero, G. Schochetman, H. Jaffe, J.R. George, L. Zekeng, L. Kaptue, J-M. Tsague, L. Gurtler
Journal: The Lancet (1994)
Prediction, inference, and the homunculus
Authors: Horace B. Barlow
Journal: Behavioral and Brain Sciences (1998)

Prediction, like filling-in, is an example of pattern completion and both are likely to involve processes of statistical inference. Furthermore, there is no incompatibility between inference and neural filling-in, for the neural processes may be mediating the inferential processes. The usefulness of the “bridge locus” is defended, and it is also suggested that the interpersonal level needs to be included when considering subjective experience.
Whatever next? Predictive brains, situated agents, and the future of cognitive science
Authors: Andy Clark
Journal: Behavioral and Brain Sciences (2013)

Brains, it has recently been argued, are essentially prediction machines. They are bundles of cells that support perception and action by constantly attempting to match incoming sensory inputs with top-down expectations or predictions. This is achieved using a hierarchical generative model that aims to minimize prediction error within a bidirectional cascade of cortical processing. Such accounts offer a unifying model of perception and action, illuminate the functional role of attention, and may neatly capture the special contribution of cortical processing to adaptive success. This target article critically examines this "hierarchical prediction machine" approach, concluding that it offers the best clue yet to the shape of a unified science of mind and action. Sections 1 and 2 lay out the key elements and implications of the approach. Section 3 explores a variety of pitfalls and challenges, spanning the evidential, the methodological, and the more properly conceptual. The paper ends (sections 4 and 5) by asking how such approaches might impact our more general vision of mind, experience, and agency.
Mouse Paneth cell antimicrobial function is independent of Nod2
Authors: Michael T Shanahan, Ian M Carroll, Emily Grossniklaus, Andrew White, Richard J von Furstenberg, Roshonda Barner, Anthony A Fodor, Susan J Henning, R Balfour Sartor, Ajay S Gulati
Journal: Gut (2013)

<h3>Objective</h3> Although polymorphisms of the <i>NOD2</i> gene predispose to the development of ileal Crohn9s disease, the precise mechanisms of this increased susceptibility remain unclear. Previous work has shown that transcript expression of the Paneth cell (PC) antimicrobial peptides (AMPs) α-defensin 4 and α-defensin-related sequence 10 are selectively decreased in <i>Nod2<sup>−/−</sup></i> mice. However, the specific mouse background used in this previous study is unclear. In light of recent evidence suggesting that mouse strain strongly influences PC antimicrobial activity, we sought to characterise PC AMP function in commercially available <i>Nod2<sup>−/−</sup></i> mice on a C57BL/6 (B6) background. Specifically, we hypothesised that <i>Nod2<sup>−/−</sup></i> B6 mice would display reduced AMP expression and activity. <h3>Design</h3> Wild-type (WT) and <i>Nod2<sup>−/−</sup></i> B6 ileal AMP expression was assessed via real-time PCR, acid urea polyacrylamide gel electrophoresis and mass spectrometry. PCs were enumerated using flow cytometry. Functionally, α-defensin bactericidal activity was evaluated using a gel-overlay antimicrobial assay. Faecal microbial composition was determined using 454-sequencing of the bacterial 16S gene in cohoused WT and <i>Nod2<sup>−/−</sup></i> littermates. <h3>Results</h3> WT and <i>Nod2<sup>−/−</sup></i> B6 mice displayed similar PC AMP expression patterns, equivalent α-defensin profiles, and identical antimicrobial activity against commensal and pathogenic bacterial strains. Furthermore, minimal differences in gut microbial composition were detected between the two cohoused, littermate mouse groups. <h3>Conclusions</h3> Our data reveal that Nod2 does not directly regulate PC antimicrobial activity in B6 mice. Moreover, we demonstrate that previously reported Nod2-dependent influences on gut microbial composition may be overcome by environmental factors, such as cohousing with WT littermates.
A Genomic Approach to Improve Prognosis and Predict Therapeutic Response in Chronic Lymphocytic Leukemia
Authors: Daphne R. Friedman, J. Brice Weinberg, William T. Barry, Barbara K. Goodman, Alicia D. Volkheimer, Karen M. Bond, Youwei Chen, Ning Jiang, Joseph O. Moore, Jon P. Gockerman, Louis F. Diehl, Carlos M. Decastro, Anil Potti, Joseph R. Nevins
Journal: Clinical Cancer Research (2009)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by a variable clinical course. Several parameters have prognostic capabilities but are associated with altered response to therapy in only a small subset of patients.We used gene expression profiling methods to generate predictors of therapy response and prognosis. Genomic signatures that reflect progressive disease and responses to chemotherapy or chemoimmunotherapy were created using cancer cell lines and patient leukemia cell samples. We validated and applied these three signatures to independent clinical data from four cohorts, representing a total of 301 CLL patients.A genomic signature of prognosis created from patient leukemic cell gene expression data coupled with clinical parameters significantly differentiated patients with stable disease from those with progressive disease in the training data set. The progression signature was validated in two independent data sets, showing a capacity to accurately identify patients at risk for progressive disease. In addition, genomic signatures that predict response to chlorambucil or pentostatin, cyclophosphamide, and rituximab were generated and could accurately distinguish responding and nonresponding CLL patients.Thus, microarray analysis of CLL lymphocytes can be used to refine prognosis and predict response to different therapies. These results have implications for standard and investigational therapeutics in CLL patients.
Doctors as performance artists
Authors: M. O'Donnell
Journal: Journal of the Royal Society of Medicine (2005)

My father was a GP in a Yorkshire village and used to take me with him in his car and into patients’ houses when he indulged in that strange habit doctors once had of visiting the sick. That’s when I discovered that, in the presence of patients, he became a performer. Later when I worked briefly as his assistant I saw how he suited his performance to the occasion: most often he would play the kindly, wise, and sympathetic counsellor, sometimes the cheery motivator driving away dull care, sometimes the cool assessor defining decisions his patients needed to make. I also discovered that he had acquired much of his understanding of medicine from his patients, in the way that performers learn from their audience. True, he picked up useful knowledge from books and journals but he screened everything he read through the filter of his own experience. I’ve since met lots of GPs who performed in much the same way and concluded that the empathy they have with their patients is one of the elusive qualities possessed by doctors whom patients feel better for seeing, whatever the treatment they prescribe—doctors whom some call ‘healers’. I’ve also concluded that the source of this empathy—the ability to see the world as it appears in the eyes of their audience—is the same for doctors as it is for the actors and writers with whom I’ve worked in the second phase of my career. For most human actions, I suggest, you can define two reasons: a good reason and a real reason. Performers, be they actors, writers, or doctors, seek out life’s real reasons and, if they’re lucky, discover the person who lurks
A Regional Prospective Study of In-Hospital Mortality Associated With Coronary Artery Bypass Grafting
Authors: Gerald T. O'Connor
Journal: JAMA (1991)

<h3>Objective.</h3> —A prospective regional study was conducted to determine if the observed differences in in-hospital mortality rates associated with coronary artery bypass grafting (CABG) are solely the result of differences in patient case mix. <h3>Design.</h3> —Regional prospective cohort study. Data including patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected. This study presents data for 3055 CABG patients between July 1,1987, and April 15, 1989. <h3>Setting.</h3> —This study includes data from all surgeons performing cardiothoracic surgery in Maine, New Hampshire, and Vermont; the data were collected from five regional medical centers. <h3>Patients.</h3> —Data were collected from all consecutive isolated CABG surgery patients during the study period. <h3>Main Outcome Measures.</h3> —Crude and adjusted in-hospital mortality rates associated with CABG. <h3>Main Results.</h3> —The overall crude in-hospital mortality rate for isolated CABG was 4.3%. The rate varied among centers (range, 3.1% to 6.3%) and among surgeons (range, 1.9% to 9.2%). Predictors of in-hospital mortality included increased age, female gender, small body surface area, greater comorbidity, reoperation, poorer cardiac function as indicated by a lower ejection fraction, increased left ventricular end diastolic pressure, and emergent or urgent surgery. After adjusting for the effects of potentially confounding variables, substantial and statistically significant variability was observed among medical centers (<i>P</i>=.021) and among surgeons (<i>P</i>=.025). <h3>Conclusion.</h3> —We conclude that the observed differences in in-hospital mortality rates among institutions and among surgeons in northern New England are not solely the result of differences in case mix as described by these variables and may reflect differences in currently unknown aspects of patient care. Understanding this variation requires a detailed understanding of the processes of care. (<i>JAMA</i>. 1991;266:803-809)
<i>Rb1</i> Haploinsufficiency Promotes Telomere Attrition and Radiation-Induced Genomic Instability
Authors: Iria Gonzalez-Vasconcellos, Natasa Anastasov, Bahar Sanli-Bonazzi, Olena Klymenko, Michael J. Atkinson, Michael Rosemann
Journal: Cancer Research (2013)

Germline mutations of the retinoblastoma gene (RB1) predispose to both sporadic and radiation-induced osteosarcoma, tumors characterized by high levels of genomic instability, and activation of alternative lengthening of telomeres. Mice with haploinsufficiency of the Rb1 gene in the osteoblastic lineage reiterate the radiation susceptibility to osteosarcoma seen in patients with germline RB1 mutations. We show that the susceptibility is accompanied by an increase in genomic instability, resulting from Rb1-dependent telomere erosion. Radiation exposure did not accelerate the rate of telomere loss but amplified the genomic instability resulting from the dysfunctional telomeres. These findings suggest that telomere maintenance is a noncanonical caretaker function of the retinoblastoma protein, such that its deficiency in cancer may potentiate DNA damage-induced carcinogenesis by promoting formation of chromosomal aberrations, rather than simply by affecting cell-cycle control.
Microwave treatment of serum facilitates detection of hepatitis B virus DNA by the polymerase chain reaction. Results of a study in anti-HBe positive chronic hepatitis B
Authors: Josep Costa, F. Xavier López-Labrador, José M. Sánchez-Tapias, Antoni Mas, Angels Vilella, Eva Olmedo, Josep Vidal, María T. Jimenez de Anta, Joan Rodés
Journal: Journal of Hepatology (1995)
Moderate Alcohol Consumption, Estrogen Replacement Therapy, and Physical Activity Are Associated With Increased Insulin Sensitivity
Authors: Jerry R. Greenfield, Katherine Samaras, Arthur B. Jenkins, Paul J. Kelly, Tim D. Spector, Lesley V. Campbell
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate 1) associations between environmental factors (alcohol consumption, hormone replacement therapy [HRT], and physical activity) and insulin resistance and secretion, independent of genetic influences; 2) the contribution of abdominal adiposity to these relationships; and 3) whether gene-environment interactions mediate these associations. RESEARCH DESIGN AND METHODS—Reported effects of lifestyle factors on insulin resistance and secretion are inconsistent, possibly due to difficulty in dissecting environmental from genetic influences and to confounding by adiposity. We examined these relationships in 798 nondiabetic female twins. Insulin resistance and secretion were estimated by modified homeostasis model assessment (HOMA-R′ and HOMA-β′, respectively). Percent total body fat and percent central abdominal fat (CAF) were measured by dual-energy X-ray absorptiometry. RESULTS—All categories of alcohol consumption were associated with lower insulin levels and HOMA-β′ than abstinence. Only moderate alcohol consumers (11–20 units/week) had lower HOMA-R′ than abstainers (−0.16 ± 0.09 vs. 0.14 ± 0.13 SD, P = 0.048). This difference was attenuated after controlling for percent CAF (P = 0.57), which was lower in moderate drinkers. Controlling for genetic and smoking effects in cotwin case-control analysis, monozygotic pairs discordant for alcohol consumption had greater within-pair differences in HOMA-R′ than concordant pairs (P = 0.02). Postmenopausal women using estrogen-only HRT had lower HOMA-R′ than non–HRT users (−0.33 ± 0.16 vs. 0.17 ± 0.08 SD, P = 0.003), even after controlling for percent CAF. Lower fasting glucose levels and insulin resistance and secretion indexes in physically active subjects were partly explained by lower abdominal adiposity. CONCLUSIONS—Moderate alcohol consumption, estrogen replacement, and physical activity are associated with increased insulin sensitivity in female twins. The favorable effects of moderate alcohol consumption and physical activity on insulin sensitivity are partly mediated by lower abdominal adiposity.
Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension
Authors: S. Minder, M. Fischler, B. Muellhaupt, M.P. Zalunardo, R. Jenni, P-A. Clavien, R. Speich
Journal: European Respiratory Journal (2004)

Portopulmonary hypertension (PPHTN) is associated with poor prognosis and high perioperative mortality after orthotopic liver transplantation. This study documents the first case of a patient with PPHTN who was successfully bridged to orthotopic liver transplantation with i.v. iloprost, a stable prostacyclin analogue. The PPHTN had resolved completely 4 months after successful transplantation. In conclusion, portopulmonary hypertension is a relative contraindication to orthotopic liver transplantation, which should be attempted only if pulmonary haemodynamics improve with prostanoids. In this context, iloprost may be a valuable alternative to epoprostenol.
Intercellular Adhesion Molecule-1–Dependent Neutrophil Adhesion to Endothelial Cells Induces Caveolae-Mediated Pulmonary Vascular Hyperpermeability
Authors: Guochang Hu, Stephen M. Vogel, David E. Schwartz, Asrar B. Malik, Richard D. Minshall
Journal: Circulation Research (2008)

We investigated the role of caveolae in the mechanism of increased pulmonary vascular permeability and edema formation induced by the activation of polymorphonuclear neutrophils (PMNs). We observed that the increase in lung vascular permeability induced by the activation of PMNs required caveolin-1, the caveolae scaffold protein. The permeability increase induced by PMN activation was blocked in caveolin-1 knockout mice and by suppressing caveolin-1 expression in rats. The response was also dependent on Src phosphorylation of caveolin-1 known to activate caveolae-mediated endocytosis in endothelial cells. To address the role of PMN interaction with endothelial cells, we used an intercellular adhesion molecule (ICAM)-1 blocking monoclonal antibody. Preventing the ICAM-1–mediated PMN binding to endothelial cells abrogated Src phosphorylation of caveolin-1, as well as the increase in endothelial permeability. Direct ICAM-1 activation by crosslinking recapitulated these responses, suggesting that ICAM-1 activates caveolin-1 signaling responsible for caveolae-mediated endothelial hyperpermeability. Our results provide support for the novel concept that a large component of pulmonary vascular hyperpermeability induced by activation of PMNs adherent to the vessel wall is dependent on signaling via caveolin-1 and increased caveolae-mediated transcytosis. Thus, it is important to consider the role of the transendothelial vesicular permeability pathway that contributes to edema formation in developing therapeutic interventions against PMN-mediated inflammatory diseases such as acute lung injury.
Fiber Orientation in the Canine Left Ventricle during Diastole and Systole
Authors: DANIEL D. STREETER, HENRY M. SPOTNITZ, DALI P. PATEL, JOHN ROSS, EDMUND H. SONNENBLICK
Journal: Circulation Research (1969)

Fiber orientation across the left ventricular myocardial wall has been studied. Specimens were obtained from 18 dog hearts rapidly fixed in situ in systole, in diastole, and in dilated diastole. Fiber orientation was determined across the free wall at eight sites from a T-shaped specimen by measurements with light microscopy in serial paraffin sections. Results indicate: (1) The wall has a well-ordered distribution of fiber angles varying from about 60° (from the circumferential direction) at the inner surface to about -60° on the outer surface. The greatest change in angle with respect to wall thickness occurs at the two surfaces (endocardial and epicardial). (2) Fiber angles did not change significantly during the transition from diastole to systole, despite a 28% increase in wall thickness (except in the papillary muscle root region). (3) The proportion of fibers lying in the sector of fiber angles oriented circumferentially (0±22.5°) to those oriented longitudinally (67.5 to 90° and -67.5 to -90°) is approximately 10:1. This ratio increases toward the base and diminishes toward the apex of the left ventricle. (4) All fiber angles in the lateral wall of hearts in systole increased through the wall by approximately 7° near the base and 19° near the apex relative to their counterparts in diastole, indicating bending or torsion of the left ventricle during contraction.
Fulminant hepatic failure caused by tuberculosis.
Authors: W Hussain, D Mutimer, R Harrison, S Hubscher, J Neuberger
Journal: Gut (1995)

A 54 year old Asian woman developed fulminant hepatic failure followed by renal failure. Because of a past history of possible tuberculosis, she was given antituberculous drugs. The chest x ray was normal. A transjugular liver biopsy showed caseating necrosis, granulomas, and acid fast bacilli indicative of miliary tuberculosis. Despite full supportive therapy, her condition deteriorated and she died. Postmortem examination showed widespread miliary tuberculosis; culture confirmed the presence of Mycobacterium tuberculosis. Tuberculosis causes fulminant hepatic failure rarely and only three cases have been described. In this, as with the other cases, hyponatraemia and hepatomegaly were features at presentation. This is the first report of treatment being given before death.
Cholinergic control of rabbit tracheal transepithelial potential difference in vivo
Authors: J Tamaoki, A Chiyotani, E Tagaya, H Takemura, K Konno
Journal: European Respiratory Journal (1996)

The aim of the present study was to investigate the role of the autonomic nervous system in the regulation of airway epithelial ion transport in vivo. Rabbits were anaesthetized and mechanically-ventilated through a cannula inserted above the carina. The upper tracheal mucosa was exposed, and the electrical potential difference (PD) between the mucosal surface and the submucosal space was continuously measured by a high-impedance voltmeter under open-circuit conditions. Perfusion of the mucosa with atropine caused a rapid decline in PD from -20.1+/-2.0 to -15.2+/-0.9 mV (p&lt;0.01), whereas phentolamine, propranolol, or the tachykinin antagonist, FK224, had no effect. Cutting both cervical vagus nerves decreased PD to the same degree as did atropine. Exogenously applied acetylcholine increased PD in a dose-dependent manner. Topical application of ipratropium bromide reduced the baseline value PD in a dose-dependent manner. The maximal decrease in PD was 43 +/- 0.3 mV (p&lt;0.01), and the dose required to produce a half-maximal effect was 34 microg. Perfusion with either amiloride, a Na channel blocker, and diphenylamine-2-carboxylate, a Cl channel blocker, decreased the baseline PD, and the subsequent application of ipratropium bromide further decreased the PD in each case. We conclude that a cholinergic neural component may play a role in the generation of tracheal potential difference in vivo, probably involving stimulation by endogenously released acetylcholine of both Cl secretion and Na absorption across the airway epithelium.