tbuckley/cabot-search huggingface dataset:
Diabetes Care in Black and White Veterans in the Southeastern U.S.
Authors: Jennifer G. Twombly, Qi Long, Ming Zhu, Peter W.F. Wilson, K.M. Venkat Narayan, Lisa-Ann Fraser, Brian C. Webber, Lawrence S. Phillips
Journal: Diabetes Care (2010)

OBJECTIVE Eliminating health disparities is a national priority, but progress has been difficult because of racial/ethnic differences in insurance coverage and access to health care. We investigated whether there were differences in diabetes care in the Veterans Administration (VA), where health care access should be relatively uniform. RESEARCH DESIGN AND METHODS A1C and plasma glucose were compared before/after diagnosis of diabetes. RESULTS Data were available for 1,456 black and 2,624 white veterans who met criteria for consistent primary care. Over 4–5 years before and after diagnosis, blacks had similar glucose and ∼0.2% higher A1C levels than whites, and A1C differences could be attributed to glucose-independent associations between race and A1C. Blacks and whites also had comparable intervals between diagnostic-level hyperglycemia and diagnosis and between diagnosis and drug initiation. However, A1C was higher in blacks at the time of diagnosis (7.8 vs. 7.1%) and at initiation of pharmacotherapy (8.5 vs. 7.8%) (both P &amp;lt; 0.001). Differences in A1C at diagnosis and drug initiation were too large to be explained by differences in age, sex, BMI, and glucose-independent associations between race and A1C. CONCLUSIONS In the VA, glucose levels are generally comparable in blacks and whites except at the times of diagnosis and initiation of pharmacotherapy, when glucose levels are higher in blacks. While understanding the basis for such residual disparities may be important to improve the health of racial/ethnic minorities in the U.S., a health care system with structure and organization similar to that in the VA may also contribute importantly to relieving disparities in health.
Lack of Evolutionary Conservation at Positions Important for Thermal Stability in the Yeast ODCase Protein
Authors: Agata Jakubowska, Ryszard Korona
Journal: Molecular Biology and Evolution (2009)

Mutations destabilizing the spatial structure of proteins can persist in populations if they are fixed by drift or compensated by other mutations. The prevalence and dynamics of these processes remain largely unrecognized. A suitable target to screen for both deleterious and compensatory mutations is the URA3 gene in yeast. We identified 13 positions in which a single missense substitution causes substantially strong thermal sensitivity. We then applied mild mutagenesis resulting in roughly one base substitution per gene and found that only reversions to an original amino acid can compensate for the thermal instability. However, the 13 positions are not visibly conserved across 53 species of Ascomycota, despite that the gene product is an enzyme of stable function and high efficiency. This shows how much fitness penalties for amino acid substitutions are background dependent, underscoring the role of complex intragenic interactions in the evolution of proteins.
A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for the treatment of tinea capitis
Authors: L.C. Fuller, C.H. Smith, R. Cerio, R.A. Marsden, G. Midgley, A.L. Beard, E.M. Higgins, R.J. Hay
Journal: British Journal of Dermatology (2001)

Journal Article A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for the treatment of tinea capitis Get access L.C. Fuller, L.C. Fuller Department of Dermatology, King's College Hospital, London SE5 9RS, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.H. Smith, C.H. Smith Department of Dermatology, University Hospital Lewisham, London SE13 6LH, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Cerio, R. Cerio Department of Dermatology, The Royal London Hospital, London E1 1BB, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.A. Marsden, R.A. Marsden Department of Dermatology, St George's Hospital, London SW17 0QT, U.K. Search for other works by this author on: Oxford Academic Google Scholar G. Midgley, G. Midgley St John's Institute of Dermatology, Guy's, King's and St Thomas' School of Medicine, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.L. Beard, A.L. Beard Novartis Pharmaceuticals UK Ltd, Camberley, Surrey GU16 5SG, U.K. Search for other works by this author on: Oxford Academic Google Scholar E.M. Higgins, E.M. Higgins Department of Dermatology, King's College Hospital, London SE5 9RS, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.J. Hay R.J. Hay St John's Institute of Dermatology, Guy's, King's and St Thomas' School of Medicine, London SE1 7EH, U.K. Professor R.J.Hay. E‐mail: rod.hay@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 2, 1 February 2001, Pages 321–327, https://doi.org/10.1046/j.1365-2133.2001.04022.x Published: 01 February 2001
Crossing the Quality Chasm in Breast Cancer Care
Authors: Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2004)

Underuse of systemic adjuvant therapies in early-stage breast cancer care is not news.Although diminishing in magnitude, 1 even at the best of centers, some degree of underuse persists. 2Although variations in breast cancer care have been documented for decades, particularly in relation to age, linking these variations to outcomes has been a methodologic challenge.Breast cancer is a relatively rare disease; its outcomes, especially among those with early-stage disease, are relatively low frequency and occur most commonly up to 5 to 10 years after diagnosis.In the United States, at least, complete information on disease characteristics and treatments is difficult to collect, given lack of integrated clinical care and information systems. 3wo recent studies from Canada have overcome many of these methodologic challenges by investigating the impact of adjuvant systemic therapies in women with nodenegative disease cared for in community settings.In the first study, investigators from the British Columbia Cancer Agency report findings from their Breast Cancer Outcomes Database. 4This database includes high-quality demographic, pathologic, staging, treatment, and outcome data for about three fourths of the women diagnosed with breast cancer in British Columbia.More than 1,100 node-negative women not treated with systemic adjuvant therapies who were diagnosed from 1989 through 1991were stratified according to tumor size (Յ 1, 1.1 to 2, and 2.1 to 5 cm) and observed for a median of 10.4 years.Within these tumor size strata, 10-year survival rates for node-negative women were 82%, 75%, and 66%, and overall survival rates were 79%, 78%, and 66%, respectively.Survival was independently associated with tumor size and grade. 4n this issue of the Journal of Clinical Oncology, Hébert-Croteau et al 5 extend these findings by comparing nodenegative women treated and not treated with systemic adjuvant therapies.They took advantage of multiple, highquality linked sources of data in Québec and addressed a central treatment effectiveness question: Do patients for whom treatment guidelines on the basis of randomized clinical trials are followed in clinical practice do better than
Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements.
Authors: D J Sahn, A DeMaria, J Kisslo, A Weyman
Journal: Circulation (1978)

Four hundred M-mode echocardiographic surveys were distributed to determine interobserver variability in M-mode echocardiographic measurements. This was done with a view toward examining the need and determining the criteria for standardization of measurement. Each survey consisted of five M-mode echocardiograms with a calibration marker, measured by the survey participants anonymously. The echoes were judged of adequate quality for measurement of structures. Seventy-six of the 400 (19%) were returned, allowing comparison of interobserver variability as well as examination of the measurement criteria which were used. Mean measurements and percent uncertainty were derived for each structure for each criterion of measurement. For example, for the aorta, 33% of examiners measured the aorta as an outer/inner or leading edge dimension, and 20% measured it as an outer/outer dimension. The percent uncertainty for the measurement (1.97 SD divided by the mean) showed a mean of 13.8% for the 25 packets of five echoes measured using the former criteria and 24.2% using the latter criteria. For ventricular chamber and cavity measurements, almost one-half of the examiners used the peak of the QRS and one-half of the examiners used the onset of the QRS for determining end-diastole. Estimates of the percent of measurement uncertainty for the septum, posterior wall and left ventricular cavity dimension in this study were 10--25%. They were much higher (40--70%) for the right ventricular cavity and right ventricular anterior wall. The survey shows significant interobserver and interlaboratory variation in measurement when examining the same echoes and indicates a need for ongoing education, quality control and standardization of measurement criteria. Recommendations for new criteria for measurement of M-mode echocardiograms are offered.
Risk Stratification for Sudden Cardiac Death
Authors: Jeffrey J. Goldberger, Anirban Basu, Robin Boineau, Alfred E. Buxton, Michael E. Cain, John M. Canty, Peng-Sheng Chen, Sumeet S. Chugh, Otto Costantini, Derek V. Exner, Alan H. Kadish, Byron Lee, Donald Lloyd-Jones, Arthur J. Moss, Robert J. Myerburg, Jeffrey E. Olgin, Rod Passman, William G. Stevenson, Gordon F. Tomaselli, Wojciech Zareba, Douglas P. Zipes, Laurie Zoloth
Journal: Circulation (2014)
Phase II study of the multitargeted antifolate LY231514 (ALIMTA™, MTA, pemetrexed disodium) in patients with advanced pancreatic cancer
Authors: K.D. Miller, J. Picus, C. Blanke, W. John, J. Clark, L.N. Shulman, D. Thornton, E. Rowinsky, P.J. Loehrer
Journal: Annals of Oncology (2000)
'Genomic counseling'? Genetic counseling in the genomic era
Authors: Angus Clarke, Katie Thirlaway
Journal: Genome Medicine (2011)

Genetic counseling can be seen as the health professional role concerned with the impact of genetic disease and genetic information on individuals and families. It has been predominantly concerned with the human problems arising in the context of single gene disorders, chromosome rearrangements and malformation, including syndromes of neurodevelopmental disturbance and dysmorphic physical features. �ese are the core conditions dealt with in genetic counseling practice on both sides of the North Atlantic, although the scope of genetic counseling does vary between countries so that, for example, North American genetic counselors are often heavily engaged in the offer of routine antenatal screening to pregnant women, whereas this is not standard practice in Europe. As genomic analysis enters clinical medicine [1,2], it is timely to reflect on the impact that this will have on genetic counseling practice [3]. Instead of merely single gene test results, will genetic counselors undertake risk counseling for the common, complex disorders on the basis of pan-genome test results such as genomewide single nucleotide polymorphism (SNP) panels, array comparative genome hybridization studies of copy number variants, exome sequencing or full genome sequence? If they do, what impact will this have on the prevention and treatment of the chronic diseases that seem likely to be the major health problems of the 21st century? For now, no reputable professional - genetic counselor or other clinician - is using SNP array results in relation to complex diseases as the basis of health care interventions or to support recommendations about lifestyle: the validity of such interpretations is insufficiently robust and there has been no demonstration of clinical utility [4,5]. However, once genome sequencing is widely available and readily affordable, many of the obstacles to the demonstration of validity will (eventually) disappear, although it will take time for the clinical research community to develop confidence in the interpretation of the accumulating data. At that point, whenever that comes to pass, will genetic counselors embrace the genomics of complex disease as well as the genetics of Mendelian disease? Our answer is a Yes and a No and a Maybe.
Phase I and Pharmacokinetic Study of Lapatinib in Combination With Capecitabine in Patients With Advanced Solid Malignancies
Authors: Quincy S.C. Chu, Garry Schwartz, Johann de Bono, Deborah A. Smith, Kevin M. Koch, Melissa J. Versola, Lini Pandite, Nikita Arya, Jan Curtright, Ronald A. Fleming, Peter T.C. Ho, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2007)

This phase I trial (EGF10005) assessed the safety, optimally tolerated regimen (OTR), and pharmacokinetics of lapatinib and capecitabine in combination in patients with advanced solid malignancies.Patients with previously treated, advanced solid malignancies were eligible. Cohorts of at least three patients each received once-daily oral lapatinib (continuous) and capecitabine (twice daily for 14 days every 21 days). Doses of lapatinib and capecitabine were escalated based on dose-limiting toxicities in the first treatment cycle until the OTR was reached. Additional patients were treated at the OTR dose level to further evaluate safety and for pharmacokinetic analyses.Forty-five patients were treated in the study. The OTR was determined to be lapatinib 1,250 mg/d plus capecitabine 2,000 mg/m(2)/d. The majority of drug-related adverse events were grade 1 to grade 2 in severity, with few grade 3 and no grade 4 toxicities. The most common drug-related toxicities (> 15% of patients) were diarrhea, nausea, rash, palmar-plantar erythrodysesthesia, mucositis, vomiting, and stomatitis. There were four confirmed responses (one complete response and three partial responses). The pharmacokinetics (area under the curve and maximum concentration) of lapatinib, capecitabine and its metabolites, fluorouracil, and alpha-fluoro-beta-alanine, were not meaningfully altered by coadministration.Lapatinib and capecitabine administered on a 3-week schedule were well tolerated, and no pharmacokinetic interaction was observed. Clinical activity was observed in patients with previously treated, advanced solid malignancies.
Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone
Authors: Bruce H. Costom, Melvin M. Grumbach, Selna L. Kaplan
Journal: Journal of Clinical Investigation (1971)

To test the hypothesis that the primary defect in some patients with idiopathic hypopituitary dwarfism is failure to secrete hypothalamic hypophysiotropic-releasing factors, synthetic thyrotropin-releasing factor (TRF), 500 mug, wa given intravenously, and timed venous samples obtained for determination of the concentration of plasma TSH by radioimmunoassay in three groups of subjects: (a) 11 patients without evidence of endocrine or systemic disease, (group I) (b) 8 with isolated growth hormone deficiency and normal thyroid function, (group II) and (c) 9 patients with idiopathic hypopituitary dwarfism and thyroid-stimulating hormone (TSH) deficiency (group III). The mean fasting plasma TSH value was 4.1 muU/ml in group I, and 3.9 muU/ml in group II; in both groups there was a brisk rise in plasma TSH to peak levels of 12-45 muU/ml at 30-45 min, and a fall toward base line levels at 120 min. All children in group III had basal TSH levels of < 1.5 muU/ml; one failed to respond to TRF; eight exhibited a rise in plasma TSH with peak values comparable with those in groups I and II. In four of eight children in group III who responded to TRF, the TSH response was delayed and the initial rise in plasma TSH was not detectable until 10-60 min. In these four patients, plasma TSH levels continued to rise at 120 min. The mean fasting concentration of plasma thyroxine iodide (T(4)) in subjects with normal thyroid function (groups I and II) was 5.6 mug/100 ml, and the mean plasma T(4) level at 120 min was 6.6 mug/100 ml. This difference between fasting and postTRF plasma T(4) was significant (P < 0.001) by paired analysis. Mean fasting plasma T(4) concentration in group III patients was 1.3 mug/100 ml; after TRF a significant rise in T(4) concentration was not detected in this group. The results indicate that TRF test is useful in distinguishing between primary hypothalamic and pituitary forms of TSH deficiency. In light of the evidence of TRF deficiency in eight of nine patients with idiopathic hypopituitary dwarfism, it seems likely that in these patients, other pituitary hormone deficiencies may be attributable to deficiency of their respective releasing factors.
Safety and Efficacy of a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease, SAR236553/REGN727, in Patients With Primary Hypercholesterolemia Receiving Ongoing Stable Atorvastatin Therapy
Authors: James M. McKenney, Michael J. Koren, Dean J. Kereiakes, Corinne Hanotin, Anne-Catherine Ferrand, Evan A. Stein
Journal: Journal of the American College of Cardiology (2012)
Further evidence on the dangers of exposure to second hand tobacco smoke
Authors: E Cetti
Journal: Thorax (2005)

▴ Vineis P, Airoldi L, Veglia F, et al . Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study. BMJ2005;330:277–80 [OpenUrl][1][Abstract/FREE Full Text][2] ▴ McGhee SM, Ho YS, Schooling M, et al . Mortality associated with passive smoking in Hong Kong. BMJ2005;330:287–8 [OpenUrl][3][FREE Full Text][4] Vineis et al report a prospective case-control study examining 123 479 “healthy” never smokers or former smokers. Over 7 years of follow up, cases were defined as “respiratory cancers” or deaths from COPD. Controls were well matched. Information about tobacco smoke exposure and a thorough list of confounders was obtained by questionnaire at recruitment. This strengthens the study by cutting out recall bias. Follow up data were from multiple sources. A subset of subjects and controls were tested for the presence of genetic polymorphisms implicated in carcinogenesis. Exposure to tobacco smoke was associated with increased … [1]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.38327.648472.82%26rft_id%253Dinfo%253Apmid%252F15681570%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=330/7486/277&atom=%2Fthoraxjnl%2F60%2F6%2F473.atom [3]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.38342.706748.47%26rft_id%253Dinfo%253Apmid%252F15677632%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=330/7486/287&atom=%2Fthoraxjnl%2F60%2F6%2F473.atom
Improved Exercise Capacity and Ischemia 6 and 12 Months After Transendocardial Injection of Autologous Bone Marrow Mononuclear Cells for Ischemic Cardiomyopathy
Authors: Emerson C. Perin, Hans F.R. Dohmann, Radovan Borojevic, Suzana A. Silva, Andre L.S. Sousa, Guilherme V. Silva, Claudio T. Mesquita, Luciano Belém, William K. Vaughn, Fernando O.D. Rangel, Joao A.R. Assad, Antonio C. Carvalho, Rodrigo V.C. Branco, Maria I.D. Rossi, Hans J.F. Dohmann, James T. Willerson
Journal: Circulation (2004)

Background— We recently reported the safety and feasibility of autologous bone marrow mononuclear cell (ABMMNC) injection into areas of ischemic myocardium in patients with end-stage ischemic cardiomyopathy. The present study evaluated the safety and efficacy of this therapy at 6- and 12-month follow-up. Methods and Results— Twenty patients with 6- and 12-month follow-up (11 treated subjects; 9 controls) were enrolled in this prospective, nonrandomized, open-label study. Complete clinical and laboratory evaluations as well as exercise stress (ramp treadmill), 2-dimensional Doppler echocardiography, single-photon emission computed tomography (SPECT) perfusion scanning, and 24-hour Holter monitoring were performed at baseline and follow-up. Transendocardial delivery of ABMMNCs was performed with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 mL each. At 6 and 12 months, total reversible defect, as measured by SPECT perfusion scanning, was significantly reduced in the treatment group as compared with the control group. At 12 months, exercise capacity was significantly improved in the treatment group. This improvement correlated well with monocyte, B-cell, hematopoietic progenitor cell, and early hemapoietic progenitor cell phenotypes. Conclusions— The 6- and 12-month follow-up data in this study suggest that transendocardial injection of ABMMNCs in patients with end-stage ischemic heart disease may produce a durable therapeutic effect and improve myocardial perfusion and exercise capacity.
The Big Finger: the second to fourth digit ratio is a predictor of sporting ability in women
Authors: S N Paul, B S Kato, J L Hunkin, S Vivekanandan, T D Spector
Journal: British Journal of Sports Medicine (2006)

The second to fourth finger length ratio (2d:4d) is thought to be related to diverse traits including cognitive ability, disease susceptibility, and sexuality.To examine the relationship between 2d:4d and sports ability in women.Hand radiographs from 607 women (mean age 54 years) were used to estimate 2d:4d. Ranking of sports ability was on a scale (1-5).The highest achieved level of participation in any sport was significantly negatively associated with 2d:4d (b = -4.93, p = 0.01) as was the relationship between 2d:4d and running level (b = -6.81, p = 0.034). Ability in other sports also showed a negative relationship albeit non-significant.These results suggest that a low 2d:4d ratio is related to increased female sports ability. It can be postulated that this ratio may predict potential sports ability. Understanding the mechanisms underpinning this relationship may give important insights into musculoskeletal fitness, health and disease.
Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection
Authors: Peiyuan Lu, Benjamin A. Youngblood, James W. Austin, Ata Ur Rasheed Mohammed, Royce Butler, Rafi Ahmed, Jeremy M. Boss
Journal: The Journal of Experimental Medicine (2014)

Programmed cell death 1 (PD-1) is an inhibitory immune receptor that regulates T cell function, yet the molecular events that control its expression are largely unknown. We show here that B lymphocyte–induced maturation protein 1 (Blimp-1)–deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1.