tbuckley/cabot-search huggingface dataset:
Public Health, GIS, and the Internet
Authors: Charles M. Croner
Journal: Annual Review of Public Health (2003)

Internet access and use of georeferenced public health information for GIS application will be an important and exciting development for the nation's Department of Health and Human Services and other health agencies in this new millennium. Technological progress toward public health geospatial data integration, analysis, and visualization of space-time events using the Web portends eventual robust use of GIS by public health and other sectors of the economy. Increasing Web resources from distributed spatial data portals and global geospatial libraries, and a growing suite of Web integration tools, will provide new opportunities to advance disease surveillance, control, and prevention, and insure public access and community empowerment in public health decision making. Emerging supercomputing, data mining, compression, and transmission technologies will play increasingly critical roles in national emergency, catastrophic planning and response, and risk management. Web-enabled public health GIS will be guided by Federal Geographic Data Committee spatial metadata, OpenGIS Web interoperability, and GML/XML geospatial Web content standards. Public health will become a responsive and integral part of the National Spatial Data Infrastructure.
GFR Estimation in Adolescents and Young Adults
Authors: Luciano Selistre, Vandréa De Souza, Pierre Cochat, Ivan Carlos Ferreira Antonello, Aoumeur Hadj-Aissa, Bruno Ranchin, Olga Dolomanova, Annie Varennes, Françoise Beyerle, Justine Bacchetta, Laurence Dubourg
Journal: Journal of the American Society of Nephrology (2012)

The performance of creatinine-based equations to obtain the estimated GFR in adolescents and young adults is poorly understood. We assessed creatinine-based GFR estimating equations in a cross-section of 751 adolescents and young adults (1054 measurements), using inulin clearance (measured GFR [mGFR]) as the reference method. We evaluated the following: Cockcroft-Gault, four-variable Modified Diet in Renal Disease, and the Chronic Kidney Disease Epidemiology Collaboration equations for adult participants, as well as the Schwartz 2009 and Schwartz-Lyon equations for pediatric age groups. Participants ranged in age from 10 to 26 years (mean 16.8 years); we divided the population into four groups according to age (10-12 years, 13-17 years, 18-21 years, and 21-25 years). Evaluation of the agreement between these formulas and mGFR (e.g., correlation, Bland-Altman plots, bias, and accuracy) showed that there was a good correlation between mGFR and both pediatric formulas in all age groups, whereas the adult formulas substantially overestimated mGFR. In conclusion, we recommend the use of pediatric equations to estimate GFR from childhood to early adulthood.
Tuberculosis therapy: past, present and future
Authors: M.D. Iseman
Journal: European Respiratory Journal (2002)

The major historical landmarks of tuberculosis (TB) therapy include: the discovery of effective medications (streptomycin and para-aminosalicylic acid) in 1944; the revelation of “triple therapy” (streptomycin, para-aminosalicylic acid and isoniazid) in 1952, which assured cure; recognition in the 1970s that isoniazid and rifampin could reduce the duration of treatment from 18 to 9 months; and the observation in the 1980s that adding pyrazinamide to these drugs allowed cures in only 6 months. To combat noncompliance, intermittent regimens, twice or thrice weekly, have been proven to cure even far-advanced TB in as few as 62–78 encounters over 26 weeks. However, these regimens are not sufficiently short or convenient to facilitate effective treatment in resource-poor countries. Therefore, drug-resistant strains have emerged to threaten TB control in various areas of the world, including India, China, Russia and the former Soviet Union. For these reasons, it is vital that new medications are developed to shorten the duration of therapy, increase the dosing interval of intermittent regimens and replace agents lost to resistance. Other special considerations include identifying optimal therapy for persons with acquired immune deficiency syndrome, particularly noting the problems of drug/drug interactions for those receiving antiretroviral treatment. Finally, the Alchemist's Dream of tuberculosis should be pursued: modulating the immune response to shorten treatment and/or overcome drug resistance.
Simian immunodeficiency virus (SIV)–specific cytotoxic T lymphocytes in gastrointestinal tissues of chronically SIV-infected rhesus monkeys
Authors: Jörn E. Schmitz, Ronald S. Veazey, Marcelo J. Kuroda, Daniel B. Levy, Aruna Seth, Keith G. Mansfield, Christine E. Nickerson, Michelle A. Lifton, Xavier Alvarez, Andrew A. Lackner, Norman L. Letvin
Journal: Blood (2001)
Population control in the small bowel.
Authors: S L Gorbach
Journal: Gut (1967)

Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, is still dependent on cochlear neural output for some time after recovery (up to 6 weeks). We have now studied the capacity of an intrinsic efferent system, i.e., the olivocochlear system, to alter hyperactivity. This system is known to modulate cochlear neural output. Anesthetized guinea pigs were exposed to a loud sound and after 2 or 3 weeks of recovery, single-neuron recordings in inferior colliculus were made to confirm hyperactivity. Olivocochlear axons were electrically stimulated and effects on cochlear neural output and on highly spontaneous neurons in inferior colliculus were assessed. Olivocochlear stimulation suppressed spontaneous hyperactivity in the inferior colliculus. This result is in agreement with our earlier finding that hyperactivity can be modulated by altering cochlear neural output. Interestingly, the central suppression was generally much larger and longer lasting than reported previously for primary afferents. Blockade of the intracochlear effects of olivocochlear system activation eliminated some but not all of the effects observed on spontaneous activity, suggesting also a central component to the effects of stimulation. More research is needed to investigate whether these central effects of olivocochlear efferent stimulation are due to central intrinsic circuitry or to coactivation of central efferent collaterals to the cochlear nucleus.
Preconditioned Endothelial Progenitor Cells Reduce Formation of Melanoma Metastases through SPARC-Driven Cell–Cell Interactions and Endocytosis
Authors: Florence Defresne, Caroline Bouzin, Marie Grandjean, Marc Dieu, Martine Raes, Antonis K. Hatzopoulos, Christian Kupatt, Olivier Feron
Journal: Cancer Research (2011)

Tumor progression is associated with the release of signaling substances from the primary tumor into the bloodstream. Tumor-derived cytokines are known to promote the mobilization and the recruitment of cells from the bone marrow, including endothelial progenitor cells (EPC). Here, we examined whether such paracrine influence could also influence the capacity of EPC to interfere with circulating metastatic cells. We therefore consecutively injected EPC prestimulated by tumor-conditioned medium (EPC-CM) and luciferase-expressing B16 melanoma cells to mice. A net decrease in metastases spreading (vs. nonstimulated EPC) led us to carry out a 2-dimensional difference gel electrophoresis (2D-DIGE) proteomic study to identify possible mediators of EPC-driven protection. Among 33 proteins exhibiting significant changes in expression, secreted protein, acidic and rich in cysteine (SPARC) presented the highest induction after EPC exposure to CM. We then showed that contrary to control EPC, SPARC-silenced EPC were not able to reduce the extent of metastases when injected with B16 melanoma cells. Using adhesion tests and the hanging drop assay, we further documented that cell-cell interactions between EPC-CM and melanoma cells were promoted in a SPARC-dependent manner. This interaction led to the engulfment of melanoma cells by EPC-CM, a process prevented by SPARC silencing and mimicked by recombinant SPARC. Finally, we showed that contrary to melanoma cells, the prometastatic human breast cancer cell line MDA-MB231-D3H2 reduced SPARC expression in human EPC and stimulated metastases spreading. Our findings unravel the influence of tumor cells on EPC phenotypes through a SPARC-driven accentuation of macrophagic capacity associated with limitations to metastatic spread.
Failure of Hemoperfusion in Digoxin Overdose
Authors: Dale A. Rowett
Journal: JAMA (1980)

To the Editor.—  LCDR Sanford E. Warren, MC, USNR, and Darrell D. Fanestil, MD (242:2100, 1979), have questioned the value of hemoperfusion in digoxin overdoses, since serum levels but not tissue stores of digoxin are lowered.  Report of a Case.—  An 82-year-old woman spilled her tablets from a bottle of digoxin in her breakfast cereal. After removing six tablets, she then ate her cereal. Three hours later she had dizziness, vomiting, and atrial fibrillation with a ventricular response of 20 beats per minute. A temporary transvenous pacemaker was inserted. The digoxin level was 11.6 ng/mL, and hemoperfusion was carried out for six hours, using coated activated charcoal (Adsorba 300C). Blood flow rates of 300 mL/min were achieved. Digoxin clearances by hemoperfusion were calculated by the following equation: C=Q B (Ci-Co)/Ci where Q b is the blood flow rate, Ci is the digoxin concentration in the arterial line, and Co is the digoxin
Assessment and management of bipolar disorder: summary of updated NICE guidance
Authors: T. Kendall, R. Morriss, E. Mayo-Wilson, E. Marcus
Journal: BMJ (2014)

Bipolar disorder is a complex, recurrent, and severe mental illness that has an onset typically between 13 and 30 years of age and a lifetime prevalence of 1.4%.1 It is characterised by episodes of mania or hypomania with elation, overactivity, and disinhibited behaviour, as well as episodes of depression with profound loss of interest and motivation, often with milder depressed mood in between episodes. Bipolar disorder is associated with an increased risk of suicide and physical illness, such as ischaemic heart disease, diabetes, chronic obstructive airways disease, pneumonia, and unintentional injury.2 Around two thirds of people with bipolar disorder also experience another mental disorder, usually anxiety disorders, substance misuse disorders, or impulse control disorders.1 The risk of recurrence in the year after a mood episode is especially high (50% in one year and >70% at four years) compared with other psychiatric disorders,3 and this has important implications for the long term management of the disorder. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on assessing and managing bipolar disorder in adults, children, and young people.4 NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Care for adults, children, and young people across all phases of bipolar disorder
Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study
Authors: Josef S Smolen, Jonathan Kay, Eric L Matteson, Robert Landewé, Elizabeth C Hsia, Stephen Xu, Yiying Zhou, Mittie K Doyle
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) inhibitor use. <h3>Methods</h3> Patients (n=461) previously receiving ≥1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint (≥20% improvement in American College of Rheumatology (ACR20) criteria at week 14) findings have been reported for all patients in the trial. Reported herein are further assessments of efficacy/safety among patients receiving golimumab+methotrexate (MTX). <h3>Results</h3> Among efficacy-evaluable patients who received MTX at baseline, more receiving golimumab+MTX (n=201) than placebo+MTX (n=103) achieved ACR20 (40.8% vs 14.6%), ACR50 (20.9% vs 3.9%), and ACR70 (11.4% vs 2.9%) responses at week 24. Among the 137 patients who had received only one prior TNF inhibitor (adalimumab, n=33; etanercept, n=47; and infliximab, n=57), week 24 ACR20 rates were 30.3%, 46.8% and 50.9%, respectively, and thus lowest among those who previously used adalimumab. ACR20 response rates were 44.5% (61/137), 36.2% (17/47) and 23.5% (4/17) among patients who had received one, two or three TNF inhibitors, respectively. Adverse event (AE) rates were comparable across type/number of prior anti-TNF agents, but appeared somewhat higher among patients who discontinued previous TNF inhibitor(s) due to intolerance (37/49, 75.5%) versus lack of efficacy (LOE, 113/191, 59.2%). <h3>Conclusions</h3> Patients with active RA previously treated with ≥1 TNF inhibitor had clinically relevant improvement with golimumab+MTX, which appeared somewhat enhanced among those who received only etanercept or infliximab as their prior TNF inhibitor. Golimumab+MTX safety appeared similar across patients, regardless of TNF inhibitor(s) previously used, with fewer AEs occurring among patients who discontinued prior therapy for LOE.
Difference in pulmonary absorption of inhaled terbutaline in healthy smokers and non-smokers.
Authors: B Schmekel, L Borgstrom, P Wollmer
Journal: Thorax (1991)

Pathophysiological studies have shown that the alveolocapillary transfer of small solutes is much faster in healthy smokers than in non-smokers. The effects of smoking on the pulmonary absorption of inhaled terbutaline were examined in normal subjects. Nine healthy smokers and 13 healthy non-smokers inhaled nebulised terbutaline and dry terbutaline powder on two study days. Plasma concentrations of terbutaline were measured up to 240 minutes after the inhalation. The plasma concentration of terbutaline rose much faster in smokers than in non-smokers, the mean time to peak terbutaline concentration being 17 minutes in the smokers and 50 minutes in the non-smokers. The peak plasma concentration was nearly twice as high in the smokers as in the non-smokers, being 21 mmol/l and 23 mmol/l for the dry powder inhalation and nebuliser respectively in the smokers and 12 mmol/l and 14 mmol/l in the non-smokers. It is concluded that smoking increases the rate of terbutaline absorption and the peak plasma concentration achieved. The rapid pulmonary absorption of terbutaline in smokers may affect the onset of action of the drug and the duration of its therapeutic effects.
Switching to Once-Daily Liraglutide From Twice-Daily Exenatide Further Improves Glycemic Control in Patients With Type 2 Diabetes Using Oral Agents
Authors: John B. Buse, Giorgio Sesti, Wolfgang E. Schmidt, Eduard Montanya, Cheng-Tao Chang, Yizhen Xu, Lawrence Blonde, Julio Rosenstock
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy. RESEARCH DESIGN AND METHODS When added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of β-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 μg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide. RESULTS Switching from exenatide to liraglutide further and significantly reduced A1C (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea. CONCLUSIONS Conversion from exenatide to liraglutide is well tolerated and provides additional glycemic control and cardiometabolic benefits.
Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon
Authors: Giselda Bucca, Emma Laing, Vassilis Mersinias, Nicholas Allenby, Douglas Hurd, Jolyon Holdstock, Volker Brenner, Marcus Harrison, Colin P Smith
Journal: Genome biology (2009)

DNA microarrays are a key resource for global analysis of genome content, gene expression and the distribution of transcription factor binding sites. We describe the development and application of versatile high density ink-jet in situ-synthesized DNA arrays for the G+C rich bacterium Streptomyces coelicolor. High G+C content DNA probes often perform poorly on arrays, yielding either weak hybridization or non-specific signals. Thus, more than one million 60-mer oligonucleotide probes were experimentally tested for sensitivity and specificity to enable selection of optimal probe sets for the genome microarrays. The heat-shock HspR regulatory system of S. coelicolor, a well-characterized repressor with a small number of known targets, was exploited to test and validate the arrays for use in global chromatin immunoprecipitation-on-chip (ChIP-chip) and gene expression analysis. In addition to confirming dnaK, clpB and lon as in vivo targets of HspR, it was revealed, using a novel ChIP-chip data clustering method, that HspR also apparently interacts with ribosomal RNA (rrnD operon) and specific transfer RNA genes (the tRNAGln/tRNAGlu cluster). It is suggested that enhanced synthesis of Glu-tRNAGlu may reflect increased demand for tetrapyrrole biosynthesis following heat-shock. Moreover, it was found that heat-shock-induced genes are significantly enriched for Gln/Glu codons relative to the whole genome, a finding that would be consistent with HspR-mediated control of the tRNA species. This study suggests that HspR fulfils a broader, unprecedented role in adaptation to stresses than previously recognized - influencing expression of key components of the translational apparatus in addition to molecular chaperone and protease-encoding genes. It is envisaged that these experimentally optimized arrays will provide a key resource for systems level studies of Streptomyces biology.
Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes
Authors: Yvette Andersson, Jan Frisell, Maria Sylvan, Jana de Boniface, Leif Bergkvist
Journal: Journal of Clinical Oncology (2010)

Purpose The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Patients and Methods Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Results Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. Conclusion This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.
Learning about genomics and disease from the anucleate human red blood cell
Authors: Edward J. Benz
Journal: Journal of Clinical Investigation (2010)

During the differentiation of an erythrocyte, the developing erythroblast shuts down expression of most of its genes but preserves high levels of expression of certain key genes, such as those encoding hemoglobin and critical membrane proteins. In this issue of the JCI, Gallagher et al. show that a specialized type of DNA sequence element known as an insulator protects the expression of ankyrin, a key membrane protein. In several kindreds, mutations in the insulator led to impaired ankyrin expression and congenital hemolytic anemia. This work provides important insights into ways in which epigenetic changes can alter gene expression and thereby lead to human disease.
A Randomized, Double-Blind, Placebo-Controlled Trial of Omalizumab Combined with Oral Immunotherapy (OIT) in the Treatment of Cow's Milk Allergy (CMA): Safety of Dosing
Authors: Jennifer S. Kim, Robert A. Wood, Robert Lindblad, Sally A. Noone, Melissa N. Paterakis, Alice Henning, Kari C. Nadeau, Kyrsten Spann, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2014)
Proangiogenic Contribution of Adiponectin toward Mammary Tumor Growth <i>In vivo</i>
Authors: Shira Landskroner-Eiger, Binzhi Qian, Eric S. Muise, Andrea R. Nawrocki, Joel P. Berger, Eugene J. Fine, Wade Koba, Yingfeng Deng, Jeffrey W. Pollard, Philipp E. Scherer
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors (“adipokines”) is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design: We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results: Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions: These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic microenvironment.