tbuckley/cabot-search huggingface dataset:
Network Meta-analysis of Margin Threshold for Women With Ductal Carcinoma In Situ
Authors: Shi-Yi Wang, Haitao Chu, Tatyana Shamliyan, Hawre Jalal, Karen M. Kuntz, Robert L. Kane, Beth A. Virnig
Journal: JNCI Journal of the National Cancer Institute (2012)

Negative margins are associated with reduced risk of ipsilateral breast tumor recurrence (IBTR) for women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). However, there is no consensus about the best minimum margin width. We searched the PubMed database for studies of DCIS published in English between January 1970 and July 2010 and examined the relationship between IBTR and margin status after BCS for DCIS. Women with DCIS were stratified into two groups, BCS with or without radiotherapy. We used frequentist and Bayesian approaches to estimate the odds ratios (OR) of IBTR for groups with negative margins and positive margins. We further examined specific margin thresholds using mixed treatment comparisons and meta-regression techniques. All statistical tests were two-sided. We identified 21 studies published in 24 articles. A total of 1066 IBTR events occurred in 7564 patients, including BCS alone (565 IBTR events in 3098 patients) and BCS with radiotherapy (501 IBTR events in 4466 patients). Compared with positive margins, negative margins were associated with reduced risk of IBTR in patients with radiotherapy (OR = 0.46, 95% credible interval [CrI] = 0.35 to 0.59), and in patients without radiotherapy (OR = 0.34, 95% CrI = 0.24 to 0.47). Compared with patients with positive margins, the risk of IBTR for patients with negative margins was smaller (negative margin >0 mm, OR = 0.45, 95% CrI = 0.38 to 0.53; >2 mm, OR = 0.38, 95% CrI = 0.28 to 0.51; >5 mm, OR = 0.55, 95% CrI = 0.15 to 1.30; and >10 mm, OR = 0.17, 95% CrI = 0.12 to 0.24). Compared with a negative margin greater than 2 mm, a negative margin of at least 10 mm was associated with a lower risk of IBTR (OR = 0.46, 95% CrI = 0.29 to 0.69). We found a probability of .96 that a negative margin threshold greater than 10 mm is the best option compared with other margin thresholds. Negative surgical margins should be obtained for DCIS patients after BCS regardless of radiotherapy. Within cosmetic constraint, surgeons should attempt to achieve negative margins as wide as possible in their first attempt. More studies are needed to understand whether margin thresholds greater than 10 mm are warranted.
Imported Measles in the United States
Authors: Robert W. Amier
Journal: JAMA (1982)

In the period 1980-1981, two hundred nine imported measles cases were reported in the United States. These cases represent 1.3% of the total of 16,630 cases of measles reported to the Centers for Disease Control (CDC) during that period. An average of two imported measles cases were reported each week. The travelers with imported measles were United States citizens and foreign nationals who arrived from 47 different countries throughout the world. However, returning United States citizens have accounted for a rising proportion of imported measles cases. Approximately half (49.3%) of the imported cases were reported by four areas: California, New York State exclusive of New York City, New York City, and Florida. Seven measles outbreaks occurring following importations during the two-year period were identified. In addition to 114 imported measles cases reported to the CDC in 1981, 437 measles cases were reported to be caused directly or indirectly by those importations. The actual number of importassociated cases may have been considerably higher. Imported measles and associated cases together accounted for at least 17% (551/3,124) of reported measles cases in 1981. (<i>JAMA</i>1982;248:2129-2133)
Burden of Human Metapneumovirus Infection in Young Children
Authors: Kathryn M. Edwards, Yuwei Zhu, Marie R. Griffin, Geoffrey A. Weinberg, Caroline B. Hall, Peter G. Szilagyi, Mary A. Staat, Marika Iwane, Mila M. Prill, John V. Williams
Journal: New England Journal of Medicine (2013)

The inpatient and outpatient burden of human metapneumovirus (HMPV) infection among young children has not been well established.We conducted prospective, population-based surveillance for acute respiratory illness or fever among inpatient and outpatient children less than 5 years of age in three U.S. counties from 2003 through 2009. Clinical and demographic data were obtained from parents and medical records, HMPV was detected by means of a reverse-transcriptase polymerase-chain-reaction assay, and population-based rates of hospitalization and estimated rates of outpatient visits associated with HMPV infection were determined.HMPV was detected in 200 of 3490 hospitalized children (6%), 222 of 3257 children in outpatient clinics (7%), 224 of 3001 children in the emergency department (7%), and 10 of 770 asymptomatic controls (1%). Overall annual rates of hospitalization associated with HMPV infection were 1 per 1000 children less than 5 years of age, 3 per 1000 infants less than 6 months of age, and 2 per 1000 children 6 to 11 months of age. Children hospitalized with HMPV infection, as compared with those hospitalized without HMPV infection, were older and more likely to receive a diagnosis of pneumonia or asthma, to require supplemental oxygen, and to have a longer stay in the intensive care unit. The estimated annual burden of outpatient visits associated with HMPV infection was 55 clinic visits and 13 emergency department visits per 1000 children. The majority of HMPV-positive inpatient and outpatient children had no underlying medical conditions, although premature birth and asthma were more frequent among hospitalized children with HMPV infection than among those without HMPV infection.HMPV infection is associated with a substantial burden of hospitalizations and outpatient visits among children throughout the first 5 years of life, especially during the first year. Most children with HMPV infection were previously healthy. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.).
A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation
Authors: Mario Iurlaro, Gabriella Ficz, David Oxley, Eun-Ang Raiber, Martin Bachman, Michael J Booth, Simon Andrews, Shankar Balasubramanian, Wolf Reik
Journal: Genome biology (2013)

DNA methylation (5mC) plays important roles in epigenetic regulation of genome function. Recently, TET hydroxylases have been found to oxidise 5mC to hydroxymethylcytosine (5hmC), formylcytosine (5fC) and carboxylcytosine (5caC) in DNA. These derivatives have a role in demethylation of DNA but in addition may have epigenetic signaling functions in their own right. A recent study identified proteins which showed preferential binding to 5-methylcytosine (5mC) and its oxidised forms, where readers for 5mC and 5hmC showed little overlap, and proteins bound to further oxidation forms were enriched for repair proteins and transcription regulators. We extend this study by using promoter sequences as baits and compare protein binding patterns to unmodified or modified cytosine using DNA from mouse embryonic stem cell extracts.
Neurocognitive Outcomes in Young Adults With Early-Onset Type 1 Diabetes
Authors: Trang T. Ly, Mike Anderson, Kaitrin A. McNamara, Elizabeth A. Davis, Timothy W. Jones
Journal: Diabetes Care (2011)

The aim of this study was to reexamine the neurocognitive function of a cohort of young adults with early-onset type 1 diabetes and compare their cognitive function to a matched control group. We also examined whether cognitive function was related to prospectively obtained severe hypoglycemia history, long-term glycemic control, or severe diabetic ketoacidosis.Testing included Wechsler Intelligence Scale for Children and Adults, Wechsler Memory Scale, Cattell Culture Fair Intelligence Test (CCFIT), Wisconsin Card Sorting Test (WCST), youth and adult self-report, and Beck Depression Inventory. We tested 34 control subjects (mean ± SE, age 19.5 ± 0.5 years) and 33 type 1 diabetic subjects (age 19.3 ± 0.5 years, age at type 1 diabetes onset 3.3 ± 0.3 years, A1C from diagnosis 8.7 ± 0.1%, and diabetes duration 16.0 ± 0.5 years).There was no difference in full-scale IQ scores in type 1 diabetic and control subjects (100.7 ± 2.0 vs. 102.5 ± 1.4). There was no difference between groups in memory subtests or in reporting of emotional and behavioral difficulties. The type 1 diabetes group scored lower on the CCFIT for fluid intelligence compared with control subjects (P = 0.028) and also scored lower on WCST with more perseverative errors (P = 0.002) and fewer categories completed (P = 0.022).These data suggest no difference in general intellectual ability, memory, and emotional difficulties in our cohort of young adults with early-onset type 1 diabetes compared with control subjects and no deterioration over time. There were, however, findings to suggest subtle changes leading to poorer performance on complex tasks of executive function.
Abiraterone and Novel Antiandrogens: Overcoming Castration Resistance in Prostate Cancer
Authors: R. Ferraldeschi, C. Pezaro, V. Karavasilis, J. de Bono
Journal: Annual Review of Medicine (2012)

Suppression of gonadal androgens by medical or surgical castration remains the mainstay of treatment for patients with advanced prostate cancer. However, the response to treatment is not durable, and transition to a "castration-resistant" state is invariable. Recent advances in our understanding of the androgen receptor signaling pathway have led to the development of therapeutic strategies to overcome castration resistance. This article reviews current concepts and challenges behind targeting continued androgen receptor signaling in castration-resistant prostate cancer and provides an overview of recently completed and ongoing clinical trials of novel hormonal agents, with a focus on abiraterone acetate and enzalutamide (MDV3100).
Letrozole Compared With Tamoxifen for Elderly Patients With Endocrine-Responsive Early Breast Cancer: The BIG 1-98 Trial
Authors: Diana Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N. Price, Beat Thürlimann, Henning Mouridsen, Louis Mauriac, John F. Forbes, Robert J. Paridaens, Monica Castiglione-Gertsch, Richard D. Gelber, Marco Colleoni, István Láng, Lucia Del Mastro, Laurence Gladieff, Manuela Rabaglio, Ian E. Smith, Jacquie H. Chirgwin, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2008)

To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial.This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295).Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs.Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy.
Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial
Authors: Mats Brune, Sylvie Castaigne, John Catalano, Kurt Gehlsen, Anthony D. Ho, Wolf-Karsten Hofmann, Donna E. Hogge, Bo Nilsson, Reuven Or, Ana I. Romero, Jacob M. Rowe, Bengt Simonsson, Ruth Spearing, Edward A. Stadtmauer, Jeff Szer, Elisabeth Wallhult, Kristoffer Hellstrand
Journal: Blood (2006)
Apoptosis of bronchoalveolar lavage lymphocytes in hypersensitivity pneumonitis
Authors: C. Laflamme, E. Israël-Assayag, Y. Cormier
Journal: European Respiratory Journal (2003)

The aim of this study was to look at the apoptosis of alveolar lymphocytes in hypersensitivity pneumonitis (HP). HP patients and normal unexposed controls were studied. The percentage of apoptotic lymphocytes was significantly lower in HP patients than in normal patients (37.4±3.4 versus 56.5±5.5% for Annexin V and propidium iodine detection methods and 0.4±0.1 versus 1.0±0.2% for dUTP nick end-labelling technique (TUNEL)). The proportion of bronchoalveolar lavage (BAL) lymphocytes positive for Fas antigen was significantly higher in HP patients than in normal subjects (71.7±5.4 versus 50.4±9.0%). However, no significant difference was found in the proportion of BAL lymphocytes positive for Fas ligand (FasL) between the two groups. Soluble Fas (sFas) levels in the BAL fluid of the patients and normals were 80.5±8.5 pg·mL −1 and 23.2±3.1 pg·mL −1 , respectively. A positive correlation was found between the percentage of BAL lymphocytes and the levels of sFas for the total subjects but not within the separate study groups. The intracellular quantity of the inducible anti-apoptotic gene Bcl-xL product was significantly higher in the pulmonary lymphocytes of HP patients than in lymphocytes of the control, while no difference was found for constitutive anti-apoptotic protein (Bcl–2). In conclusion, the apoptosis of pulmonary lymphocytes is lower in hypersensitivity pneumonitis than in normal subjects. This could be explained, at least in part, by an increase of soluble Fas, the anti-apoptic gene, and Bcl-xL.
Proteomic Analysis Identifies Oxidative Stress Induction by Adaphostin
Authors: Luke H. Stockwin, Maja A. Bumke, Sherry X. Yu, Simon P. Webb, Jack R. Collins, Melinda G. Hollingshead, Dianne L. Newton
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Activities distinct from inhibition of Bcr/abl have led to adaphostin (NSC 680410) being described as “a drug in search of a mechanism.” In this study, proteomic analysis of adaphostin-treated myeloid leukemia cell lines was used to further elucidate a mechanism of action. Experimental Design: HL60 and K562 cells treated with adaphostin for 6, 12, or 24 h were analyzed using two-dimensional PAGE. Differentially expressed spots were excised, digested with trypsin, and analyzed by liquid chromatography–tandem mass spectrometry. The contribution of the redox-active hydroquinone group in adaphostin was also examined by carrying out proteomic analysis of HL60 cells treated with a simple hydroquinone (1,4-dihydroxybenzene) or H2O2. Results: Analysis of adaphostin-treated cells identified 49 differentially expressed proteins, the majority being implicated in the response to oxidative stress (e.g., CALM, ERP29, GSTP1, PDIA1) or induction of apoptosis (e.g., LAMA, FLNA, TPR, GDIS). Interestingly, modulation of these proteins was almost fully prevented by inclusion of an antioxidant, N-acetylcysteine. Validation of the proteomic data confirmed GSTP1 as an adaphostin resistance gene. Subsequent analysis of HL60 cells treated with 1,4-dihydroxybenzene or H2O2 showed similar increases in intracellular peroxides and an almost identical proteomic profiles to that of adaphostin treatment. Western blotting of a panel of cell lines identified Cu/Zn superoxide dismutase (SOD) as correlating with adaphostin resistance. The role of SOD as a second adaphostin resistance gene was confirmed by demonstrating that inhibition of SOD using diethyldithiocarbamate increased adaphostin sensitivity, whereas transfection of SOD I attenuated toxicity. Importantly, treatment with 1,4-dihydroxybenzene or H2O2 replicated adaphostin-induced Bcr/abl polypeptide degradation, suggesting that kinase inhibition is a ROS-dependent phenomenon. Conclusion: Adaphostin should be classified as a redox-active–substituted dihydroquinone.
Implementation and evaluation of a two-compartment model for quantification of myocardial perfusion with rubidium-82 and positron emission tomography.
Authors: P Herrero, J Markham, M E Shelton, S R Bergmann
Journal: Circulation Research (1992)

Positron emission tomography offers the ability to noninvasively assess regional myocardial perfusion in absolute terms (i.e., milliliters per gram per minute). Accurate estimates have been difficult to achieve with generator-produced 82Rb because of the complex behavior of this tracer in the myocardium. The aim of the present study was to determine whether regional myocardial blood flow could be assessed quantitatively with 82Rb and positron emission tomography by using a two-compartment kinetic model. Regional perfusion in milliliters per gram per minute was estimated from dynamic tomographic scans after intravenous administration of 82Rb in 18 studies in 13 intact dogs studied without intervention, after 2 and 24 hours of induced ischemia, during reperfusion after transient occlusion, or at rest and after pharmacological hyperemia after induced coronary artery stenosis. Regional flow was estimated along with the forward and backward rates of transport (k1 and k2 [minutes-1]) after the relative volume of distribution of the first compartment was fixed to 0.53 ml/ml and the tomographic parameters, the recovery and spillover fractions, were fixed to averaged values obtained in previous studies. In 36 comparisons, estimates of regional flow with 82Rb correlated well with flow measured with concomitantly administered radiolabeled microspheres (r = 0.91, p less than 0.05) over the flow range from 0.14 to 4.25 ml/g/min. A putative index of viability, k2, increased significantly in regions with severe ischemia. The results suggest that quantification of regional myocardial perfusion is possible in centers using 82Rb for estimates of myocardial perfusion when a physiologically appropriate, two-compartment model is used.
Using information technology to reduce rates of medication errors in hospitals
Authors: D. W Bates
Journal: BMJ (2000)

Data continue to show that medication errors are frequent and that adverse drug events, or injuries due to drugs, occur more often than necessary.1–4 In fact, the frequency and consequences of iatrogenic injuries seems to dwarf the frequency of other types of injuries that have received more public attention, such as aeroplane and automobile crashes.2 A recent meta-analysis reported an overall incidence of 6.7% for serious adverse drug reactions (a term that excludes events associated with errors) in hospitals.4 Between 28% and 56% of adverse drug events are preventable. 3 5–7

Though the reasons this issue has received so little attention are complex, the reasons that medical injuries occur with some frequency are perhaps less so; medicine is more or less a cottage industry, with little standardisation and relatively few safeguards in comparison to, say, manufacturing. In fact, most of the systems in place in medicine were never formally designed, and this holds for the entire process of giving drugs.

#### Summary points

Although information technologies are widely used in hospitals, relatively few data are available regarding their impact on the safety of the process of giving drugs

Exceptions are computerised physician order entry and computerised physician decision support, which have been found to improve drug safety

Other innovations, including using robots to fill prescriptions, bar coding, automateddispensing devices, and computerisation of the medication administration record, though less studied, should all eventually reduce error rates

The medication system of the future will include these and other technologies, all electronically linked

Take, for example, the allergy detection process used in our hospital several years ago, which was similar to that used in most hospitals at the time. Physicians, medical students, and nurses all asked patients what their allergies were. This information was recorded at several sites in …
Viremia is Associated with Sleep Disturbances, Neurocognitive Disorders and Cytokine Dysregulation in Pediatric HIV Infection
Authors: S.B. Foster, M.E. Paul, D.G. Glaze, J.M. Reuben, L.L. Harris, E.N. Cohen, B. Lee, C.A. Kozinetz, H.L. Schwarzwald, M.W. Kline, C.D. Jackson, A.J. Loeb, P.E. Frerking, J.E. Fehlis, P.Y. Brouwers, W.T. Shearer
Journal: Journal of Allergy and Clinical Immunology (2007)

RATIONALE: Despite the effectiveness of intranasal corticosteroids in managing rhinitis, physicians may be reluctant to prescribe them as long-term treatment to children due to concerns of potential systemic effects.The objective of this study was to determine if there is a reduction in 24-hour serum or urine cortisol, indicative of HPA axis suppression, in children treated with FF, a novel, enhanced-affinity corticosteroid.Bioavailability was determined via serial pharmacokinetic sampling.METHODS: Randomized, double-blind, parallel-group, placebo-controlled, 6-week trial assessing the effects of once-daily FFNS 110mcg on 24-hour serum and urine cortisol in PAR subjects 2 to <12 years of age in a controlled, domiciled environment.Endpoints included change from baseline (expressed as a ratio) in serum cortisol (primary) and urinary free cortisol excretion and serial plasma concentrations of FF.Safety was assessed by adverse events, ECGs, and laboratory tests.Treatment compliance was assessed via several means.RESULTS: Geometric mean serum cortisol ratios from baseline at Week 6 were similar for FFNS (0.94) and placebo (0.98).Adjusting for baseline weighted mean and center, FFNS was non-inferior to placebo (treatment ratio 0.97, 95% CI [0.88, 1.07]).No subjects had urinary free cortisol excretion levels below normal range at Week 6. FF levels were generally not quantifiable after 6 weeks dosing.No safety issues were identified.Conventional and novel compliance assessments provided validation of the safety data.CONCLUSIONS: Once-daily FFNS 110mcg was well-tolerated and not associated with HPA axis suppression following 6 weeks of treatment in children aged 2 to <12 years with PAR.
Zea systematics: ribosomal ITS evidence
Authors: E. S. Buckler, T. P. Holtsford
Journal: Molecular Biology and Evolution (1996)

Ribosomal internal transcribed spacer (ITS) sequences were used to evaluate the phylogenetics of Zea and Tripsacum. Maximum likelihood and polymorphism parsimony were used for phylogenetic reconstructions. Zea ITS nucleotide diversity was high compared to other plant species, but approximately equivalent to other maize loci. Coalescence of ITS alleles was rapid relative to other nuclear loci; however, there was still much diversity within populations. Zea and Tripsacum form a clade clearly differentiated from all other Poaceae. Four Zea ITS pseudogenes were identified by phylogenetic position and nucleotide composition. The phylogenetic position of Z. mays ssp. huehuetenangensis was clearly established as basal to the other Z. mays. The ITS phylogeny disfavored a Z. luxurians and Z. diploperennis clade, which conflicted with some previous studies. The introgression of Z. mays alleles into Z. perennis and Z. diploperennis was also established. The ITS data indicated a near contemporary divergence of domesticated maize and its two closest wild relatives.