tbuckley/cabot-search huggingface dataset:
Inference of Expression-Dependent Negative Selection Based on Polymorphism and Divergence in the Human Genome
Authors: Naoki Osada
Journal: Molecular Biology and Evolution (2007)

There is a mounting evidence for the correlation between the gene expression pattern and sequence divergence. However, little is known about the relationship between the gene expression pattern and polymorphism. We compiled the gene expression, polymorphism, and divergence data from the public databases of the human genome. The ratios of nonsynonymous (A) to synonymous (S) substitutions in polymorphism and divergence in the human genome were strongly influenced by the expression pattern and breadth of genes and showed strong correlations. Among the tissues we analyzed, the brain-expressed genes have the smallest and the liver-expressed genes have the largest proportion of amino acid changes both in polymorphism and divergence. The analysis implies that negative selection is the primary factor affecting expression-dependent gene evolution and the prevalent but nonuniform distribution of slightly deleterious mutations in the genome. Although the genes under relaxed negative selection evolved faster than the other genes, these genes are even more liable to slightly deleterious mutations in the population. On the other hand, nonneutral mutations in the highly conservative genes, such as brain-expressed and housekeeping genes, are largely deleterious and eliminated before they enter the population.
Association of angiotensinogen m235t and a(-6)g gene polymorphisms with coronary heart disease with independence of essential hypertension: the procagene study
Authors: José C Rodrı́guez-Pérez, Francisco Rodrı́guez-Esparragón, Octavio Hernández-Perera, Aránzazu Anabitarte, Antonio Losada, Alfonso Medina, Enrique Hernández, Dolores Fiuza, Octavio Avalos, Carla Yunis, Carlos M Ferrario
Journal: Journal of the American College of Cardiology (2001)
Quantitative rotational thallium-201 tomography for identifying and localizing coronary artery disease.
Authors: E E DePasquale, A C Nody, E G DePuey, E V Garcia, G Pilcher, C Bredlau, G Roubin, A Gober, A Gruentzig, P D'Amato
Journal: Circulation (1988)

The purpose of this study was to develop and validate a method for quantifying the uptake, redistribution, and washout of thallium-201 (201Tl) obtained with rotational tomography. This method generates maximum count circumferential profiles of the short-axis slices of the left ventricle, translates them into polar coordinate profiles, and displays them as a bullseye plot, which consists of a series of concentric circles with the apex at the center and the base at the periphery. Normal limits were established for the distribution of 201Tl in 36 patients with a low (less than 5%) probability of coronary artery disease (CAD). Forty-five patients who had undergone coronary angiography were used as a pilot group to define criteria for the identification and localization of perfusion defects. The best agreement with the results of angiography was found when abnormal regions of the bullseye were defined as contiguous defects over 2.5 SDs below normal. These criteria were applied prospectively to 210 points (179 points with greater than 50% diameter stenosis and 31 with less than 50%). Visual, quantitative, and combined visual and quantitative analysis were compared for overall detection of disease and for detection of individual vessel involvement. The overall sensitivity for detection of disease by these methods was 97%, 95%, and 95%, respectively. The specificities were 68%, 74%, and 71% respectively. The sensitivity for detection of individual vessel involvement with the bullseye alone was 78% for the left anterior descending artery (LAD), 89% for the right coronary artery (RCA), and 65% for the left circumflex (LCx). For visual analysis, the results were 70%, 88%, and 50%, respectively, while the use of visual and quantitative analysis combined identified 75% of LAD, 87% of RCA, and 55% of LCx lesions. We conclude that quantitative analysis of rotational 201Tl tomographic images is a highly accurate technique for determining the presence and location of CAD.
Modelling cost effectiveness of meningococcal serogroup C conjugate vaccination campaign in England and Wales
Authors: C. L Trotter
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To assess the cost effectiveness of a meningococcal serogroup C conjugate vaccination campaign in 0-17 year olds. <b>Design:</b> Cost effectiveness analysis from the perspective of the healthcare provider. <b>Setting:</b> England and Wales. <b>Main outcome measure:</b> Cost per life year saved. <b>Results:</b> In 1998-9, immediately before the introduction of meningococcal C vaccination, the burden of serogroup C disease was considerable, with an estimated 1137 cases in people aged 0-17 years and at least 72 deaths. The vaccination campaign is estimated to have cost between £126m ($180m, €207m) and £241m ($343m, €395m), depending on the price of the vaccine. Under base case assumptions the cost per life year saved from the vaccination campaign is estimated to be £6259. School based vaccination was more cost effective than general practice based vaccination because of lower delivery costs. Immunisation of infants aged under 1 year was the least cost effective component of the campaign because, although this maximises the life years gained, the three dose schedule required is more expensive than other methods of delivery. Estimates of the cost per life year saved were sensitive to assumptions on the future incidence of disease and the case fatality ratio. <b>Conclusions:</b> Meningococcal C vaccination is likely to be more cost effective in all age groups when the incidence of disease is high. It is also more cost effective when given to children aged 1-4 (by general practitioners) and to children and young people aged 5-17 years at school than when administered to infants under 12 months of age or young people aged 16-17 years who are not at school. <h3>What is already known on this topic</h3> The burden of group C meningococcal disease in England and Wales in the late 1990s was considerable In November 1999 the United Kingdom was the first country to introduce mass vaccination against group C meningococcal disease There are no published economic evaluations of the vaccination campaign <h3>What this study adds</h3> This economic evaluation supports the introduction of the meningococcal C vaccine School based vaccination is more cost effective than routine vaccination of infants because delivery costs are lower and fewer doses are required
Receptor Depletion in Diabetes Mellitus: Correction with Therapy
Authors: R P Eaton, R Galagan, E Kaufman, R C Allen, Linda Russell, Frank Miller
Journal: Diabetes Care (1981)

This report describes two patients with diabetes mellitus, presenting with insulin resistance and depression of erythrocyte insulin receptor binding to less than one-third of normal. Scatchard analysis of the data was consistent with a depletion in insulin receptors in these poorly controlled diabetic patients. Therapy with tolbutamide and reduced insulin administration resulted in restoration of erythrocyte receptor binding, clinical resolution of the insulin resistance, and amelioration of hyperglycemia. These data suggest a role for transient depletion and/or dysfunction of cellular receptors of insulin activity in the evolution of insulin resistance in diabetes.
Hypoxic encephalopathy after near-drowning studied by quantitative 1H-magnetic resonance spectroscopy.
Authors: R Kreis, E Arcinue, T Ernst, T K Shonk, R Flores, B D Ross
Journal: Journal of Clinical Investigation (1996)

Early prediction of outcome after global hypoxia of the brain requires accurate determination of the nature and extent of neurological injury and is cardinal for patient management. Cerebral metabolites of gray and white matter were determined sequentially after near-drowning using quantitative 1H nuclear magnetic resonance spectroscopy (MRS) in 16 children. Significant metabolite abnormalities were demonstrated in all patients compared with their age-matched normal controls. Severity of brain damage was quantified from metabolite concentrations and ratios. Loss of N-acetylaspartate, a putative neuronal marker, from gray matter preceded that observed in white matter and was more severe. Total creatine decreased, while lactate and glutamine/glutamate concentrations increased. Changes progressed with time after injury. A spectroscopic prognosis index distinguished between good outcome (n = 5) and poor outcome (n = 11) with one false negative (bad outcome after borderline MRS result) and no false positive results (100% specificity). The distinction was made with 90% sensitivity early (after 48 h) and became 100% later (by days 3 and 4). This compared with 50-75% specificity and 70-100% sensitivity based upon single clinical criteria. MRS performed sequentially in occipital gray matter provides useful objective information which can significantly enhance the ability to establish prognosis after near-drowning.
Continuous Therapy With Certolizumab Pegol Maintains Remission of Patients With Crohn's Disease for up to 18 Months
Authors: Gary R. Lichtenstein, Ole Ø. Thomsen, Stefan Schreiber, Ian C. Lawrance, Stephen B. Hanauer, Ralph Bloomfield, William J. Sandborn
Journal: Clinical Gastroenterology and Hepatology (2010)
Helical Fracture-Reply
Authors: Otto E. Aufranc
Journal: JAMA (1961)

<h3>To the Editor:—</h3> At Dr. Gillies' implied suggestion, I have had another "glance at Webster," (unabridged—1958) and am more impressed than ever with the affluence or richness of the English language. Without compromising, I can readily agree with Dr. Eloesser and his spiral fracture, and Dr. Gillies, and his preference for helical. At the same time I can take a little measure of content from the word oblique as it describes the 3 dimensional muscles of the eye and abdomen. I have studied the words helical and spiral and I can interpret each to mean the same thing. Both words seem to agree with one another and each word gives the other as its meaning. A spiral or helical plane reaches or approaches a center, or will rise or fall above it, or even ascend or descend in the shape of either. There may be more dignity in describing a
Differential Effects of Nifedipine and Co-Amilozide on the Progression of Early Carotid Wall Changes
Authors: Alain Simon, Jérome Gariépy, Dominique Moyse, Jaime Levenson
Journal: Circulation (2001)

Common carotid artery intima-media thickness (IMT) progression was compared between 4 years of treatment with nifedipine and diuretic.This study, ancillary to the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), involved nifedipine 30 mg or co-amilozide (hydrochlorothiazide 25 mg and amiloride 2.5 mg) with optional subsequent titration. Among 439 randomized hypertensive patients, 324 had >/=1 year of follow-up (intent-to-treat group), and 242 completed follow-up (until-end-of-study group). Ultrasonography was performed at baseline, 4 months later, and then every year. Central computerized reading provided far-wall IMT, diameter, and cross-sectional area IMT (CSA-IMT). The primary outcome was IMT progression rate (slope of IMT-time regression). Secondary outcomes were changes from baseline (Delta) in IMT, diameter, and CSA-IMT. In the until-end-of-study population, between-treatment differences existed in IMT progression rate (P=0.002), Delta IMT (P=0.001), and Delta CSA-IMT (P=0.006), because IMT progressed on co-amilozide but not on nifedipine. In the intent-to-treat population, treatment differences existed in Delta IMT (P=0.004) and Delta CSA-IMT (P=0.04) but not in IMT progression rate (P=0.09). Patients with >/=2, 3, or 4 years of follow-up showed treatment differences in IMT progression rate (P=0.04, 0.004, 0.007, respectively), Delta IMT (P=0.005, 0.001, 0.005), and Delta CSA-IMT (P=0.025, 0.013, 0.015). Diameter decreased more on co-amilozide than on nifedipine in the intent-to-treat population (P<0.05), whereas blood pressure decreased similarly on both treatments.A difference in early carotid wall changes is shown between 2 equally effective antihypertensive treatments.
On the Death of House Officers
Authors: Faith Fitzgerald, T. Jock Murray
Journal: Annals of Internal Medicine (1998)

Perspectives1 June 1998On the Death of House OfficersFaith Fitzgerald, MD and T. Jock Murray, MDFaith Fitzgerald, MD and T. Jock Murray, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-11-199806010-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail [On receiving Lawrence Smith's account of the death of a resident, we invited other medical educators to reflect on such events. Drs. Fitzgerald and Murray wrote the following separate perspectives in response. -The Editor]Dr. Fitzgerald: In the second month of his internship, having for half that time been at home on medical leave under therapy for depression, my intern Jeff cut his throat from ear to ear.I had not known him well. At the welcoming party for new housestaff in my backyard, he appeared cheerful and interactive. Three weeks later, a perceptive chief resident brought Jeff to my ... Author, Article, and Disclosure InformationAffiliations: Current Author Addresses: Dr. Fitzgerald: Department of Medicine, University of California, Davis, School of Medicine, PO Box 179002, Sacramento, CA 95817. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Death of House Officers Faith T. Fitzgerald The Death of House Officers Chi-yuan Hsu The Death of House Officers Andrew Naidech Cyclophosphamide-Associated Uroepithelial Toxicity Ronnier J. Aviles , Stacey A. Vlahakis , and Peter L. Elkin CD123 hiDendritic Cell Lymphoma: An Unusual Case of Non-Hodgkin Lymphoma Paulo Lúcio , Antonio Parreira , and Alberto Orfao Quotations on the Wall J. Willis Hurst Metrics Cited ByThomas John (Jock) Murray, OC, MD, FRCP(C), MACP, LLD(Hon), DSC(Hon), FRCP(Lon): A Conversation with the EditorDeath in SpringtimeVictor S. Sloan, MDThe Death of House OfficersChi-yuan Hsu, MDThe Death of House OfficersAndrew Naidech, MD 1 June 1998Volume 128, Issue 11Page: 949-950KeywordsAIDSBeerBehaviorEmotionsHand strengthPharynxResearch laboratoriesShockSuicide Issue Published: 1 June 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Edinburgh Meeting — Accident Services — One for the Road
Authors: John Lister
Journal: New England Journal of Medicine (1959)

BRITISH and Canadian medicine have so much common ancestry traceable to Edinburgh that there could have been no more appropriate place for the medical associations of the two countries to hold their joint scientific meeting this summer.Before the scientific meeting the representative body of the British Medical Association discussed its domestic affairs. Because the problem of the doctor and his pay has not yet been resolved, it had been suggested that the British Medical Association might propose an alternative plan to the National Health Service on a payment-for-service basis. There was little general enthusiasm for the proposition, however, and . . .
Wavelet analysis of heart rate variability preceding ventricular arrhythmias retrieved from implantable cardioverter defibrillators in patients with myocardial infarction
Authors: Haran Burri, Philippe Chevalier, Mohammad Arzi, Paul Rubel, Jocelyne Fayn, Gilbert Kirkorian, Jean-Yves Le Heuzey, Paul Touboul
Journal: Journal of the American College of Cardiology (2003)
Peroperative venography to ensure accurate sapheno-popliteal vein ligation.
Authors: J T Hobbs
Journal: BMJ (1980)

Bone marrow showing lysed nuclear material lying among normal cells.other medication was cimetidine, which she took throughout her stay in hospital.Her total white cell count remained between 0-8 and 1-5 x 109/1 for six days with 0-10 % neutrophils.The total white cell count increased on the seventh day and two weeks after admission was 17-8 x 109/1 with 76 % neutrophils.A skin biopsy showed changes consistent with the diagnosis of scleroderma.Intravenous pyelography, cystoscopy, and retrograde pyelography showed nothing abnormal.Renal arteriography showed reduced cortical blood flow with irregularity and beading of the interlobular, arcuate, and interlobar arteries.A renal biopsy showed changes consistent with malignant scleroderma.The patient remained anuric and was transferred to another renal unit for chronic haemodialysis but died soon after.
Measles outbreak in Greater Manchester, England, October 2012 to September 2013: epidemiology and control
Authors: M Pegorie, K Shankar, W S Welfare, R W Wilson, C Khiroya, G Munslow, D Fiefield, V Bothra, R McCann
Journal: Eurosurveillance (2014)

This paper describes the epidemiology and management of a prolonged outbreak of measles across the 2.7 million conurbation of Greater Manchester in the United Kingdom. Over a period of one year (from October 2012 to September 2013), over a thousand suspected measles cases (n = 1,073) were notified across Greater Manchester; of these, 395 (37%) were laboratory-confirmed, 91 (8%) were classed as probable, 312 (29%) were classed as possible and 275 (26%) excluded. Most confirmed and probable cases occurred in children within two age groups—infants (too young to be eligible for measles-mumps-rubella (MMR) vaccination according to the national immunisation programme) and children aged 10-19 years (low vaccine uptake in this cohort because of unfounded alleged links between the MMR vaccine and autism). During this one year period, there were a series of local outbreaks and many of these occurred within the secondary school setting. A series of public health measures were taken to control this prolonged outbreak: setting up incident management teams to control local outbreaks, a concerted immunisation catch-up campaign (initially local then national) to reduce the pool of children partially or totally unprotected against measles, and the exclusion of close contacts from nurseries and school settings for a period of 10 days following the last exposure to a case of measles.
Abstract A4: Two dimensional chemical interrogation of oncogenic systems and multi-omics integration of signatures reveals novel signaling pathways involved in the pathophysiology of cancer
Authors: Vivek K. Vishnudas, Min Du, Viatscheslav Akmaev, Rangaprasad Sarangarajan, Niven R. Narain
Journal: Cancer Research (2012)

Abstract Oncogenic events involve activation of kinases either in case of direct mutation or as a secondary event as recipients and mediators of oncogenic signals. Kinases transduce signals that lead to cell proliferation or inhibition of programmed cell death by activating transcription factors and inhibiting pro apoptotic molecules. Despite the knowledge and huge market for the kinases as targets, small molecule modulators have failed repeatedly to deliver as cancer therapeutics. Primarily, the failure is thought to stem from the lack of kinase discovery platforms that enable a mechanistic understanding of signaling pathways involving transmembrane and cytoplasmic kinases. The Berg Interrogative Biology® Kinase Discovery Platform offers novel technology driven solutions for understanding of kinases in oncogenesis. The approach is powered by “two-dimensional chemical interrogation” where in vitro cancer and control models were interrogated by a kinase inhibitor (sorafenib) in the first dimension. Overall changes in kinase activity were captured by a second dimension of chemical interrogation employing activity-based kinase enrichment probes. Kinases were identified by LC-MS based mass spectrometry. In addition, changes in phospho proteome in response to kinase inhibitor were captured using a phosphoprotein enrichment method followed by LC-MS for identification of proteins. Finally quantitative changes in total protein expression were obtained. Multi-omics data collated from the above mentioned approach was integrated using an AI-based informatics tool leading to generation of data-driven inference of causal networks representing differential kinase activity driving phosphorylation of proteins that are operational in cancer and not in normal models. The technology platform led to discovery of novel kinases that are mechanistically relevant to pathophysiology of cancer. Citation Format: Vivek K. Vishnudas, Min Du, Viatscheslav Akmaev, Rangaprasad Sarangarajan, Niven R. Narain. Two dimensional chemical interrogation of oncogenic systems and multi-omics integration of signatures reveals novel signaling pathways involved in the pathophysiology of cancer [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A4.
TCT-632 What would an outcomes trial comparing FFR for all lesions versus a hybrid approach (resting index plus selective FFR) look like?
Authors: Nils P. Johnson, Keith G. Oldroyd, Ke Xu, Akiko Maehara, Philippe Genereux, K.L. Gould, Gregg Stone, Allen Jeremias
Journal: Journal of the American College of Cardiology (2013)
THE CHANGING DEFINITION OF CONTRAST INDUCED NEPHROPATHY AND ITS CLINICAL IMPLICATIONS: INSIGHTS FROM THE BLUE CROSS BLUE SHIELD OF MICHIGAN CARDIOVASCULAR CONSORTIUM (BMC2)
Authors: Nicklaus Slocum, Mauro Moscucci, Dean Smith, Herb Aronow, Simon Dixon, David Share, Hitinder S. Gurm
Journal: Journal of the American College of Cardiology (2010)
RECONSTRUCTIVE SURGERY IN WAR TIME
Authors: F. C. KIDNER
Journal: JAMA (1918)

The energy and enthusiasm of Sir Robert Jones are responsible for the establishment in the British Isles of fifteen or twenty large, well equipped orthopedic hospitals for wounded soldiers. Over these, Sir Robert exercises a general supervision, and in them he instructs the various members of the staffs in the details of reconstructive work among the wounded. During the past nine months, it has been my good fortune to be stationed in charge of a service at one of the largest of these centers, that at Shepherd's Bush, London. During that time, I have had an opportunity of seeing and of treating large numbers of patients who, in private life, would be considered permanent cripples, but here, through the stimulating teaching and with the wise help of Sir Robert Jones, are being returned to usefulness. The Shepherd's Bush Hospital has 1,100 beds, and is fully equipped with departments for after-treatment,
Preparative immunotherapy with anti-OX40 and anti-CTLA4 improves the response to chemotherapy
Authors: David J Friedman, Kristina Young, Jason R Baird, Benjamin Cottam, Talicia Savage, Pippa Newell, Melissa Kasiewicz, William Redmond, Brendan Curti, Todd Crocenzi, Michael J Gough, Marka Crittenden
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Recent studies have reported that decreased T cell infiltrate alone, or co-ordinate with increased macrophage infiltrate, correlate with decreased survival in a range of cancers, including patients with pancreatic cancer. Importantly, in mouse models of pancreatic cancer,