tbuckley/cabot-search huggingface dataset:
Missing Clinical Information During Primary Care Visits
Authors: Peter C. Smith
Journal: JAMA (2005)

ContextThe coordinating function of primary care is information-intensive and may be impeded by missing clinical information. However, missing clinical information has not been explicitly investigated in the primary care setting.ObjectiveTo describe primary care clinicians’ reports of missing clinical information.Design, Setting, and ParticipantsCross-sectional survey conducted in 32 primary care clinics within State Networks of Colorado Ambulatory Practices and Partners (SNOCAP), a consortium of practice-based research networks participating in the Applied Strategies for Improving Patient Safety medical error reporting study. Two hundred fifty-three clinicians were surveyed about 1614 patient visits between May and December 2003. For every visit during 1 half-day session, each clinician completed a questionnaire about patient and visit characteristics and stated whether important clinical information had been missing. Clinician characteristics were also recorded.Main Outcome MeasuresReports of missing clinical information frequency, type, and presumed location; perceived likelihood of adverse effects, delays in care, and additional services; and time spent looking for missing information. Multivariate analysis was conducted to assess the relationship of missing information to patient, visit, or clinician characteristics, adjusting for potential confounders and effects of clustering.ResultsClinicians reported missing clinical information in 13.6% of visits; missing information included laboratory results (6.1% of all visits), letters/dictation (5.4%), radiology results (3.8%), history and physical examination (3.7%), and medications (3.2%). Missing clinical information was frequently reported to be located outside their clinical system but within the United States (52.3%), to be at least somewhat likely to adversely affect patients (44%), and to potentially result in delayed care or additional services (59.5%). Significant time was reportedly spent unsuccessfully searching for missing clinical information (5-10 minutes, 25.6%; &gt;10 minutes, 10.4%). After adjustment, reported missing clinical information was more likely when patients were recent immigrants (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.06-2.99), new patients (OR, 2.39; 95% CI, 1.70-3.35), or had multiple medical problems compared with no problems (1 problem: OR, 1.09; 95% CI, 0.69-1.73; 2-5 problems: OR, 1.87; 95% CI, 1.21-2.89; &gt;5 problems: OR, 2.78; 95% CI, 1.61-4.80). Missing clinical information was less likely in rural practices (OR, 0.52; 95% CI, 0.29-0.92) and when individual clinicians reported having full electronic records (OR, 0.40; 95% CI, 0.17-0.94).ConclusionsPrimary care clinicians report that missing clinical information is common, multifaceted, likely to consume time and other resources, and may adversely affect patients. Additional research on missing information is needed to focus on validating clinicians’ perceptions and on conducting prospective studies of its causes and sequelae.
The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation
Authors: Claude Capron, Yann Lécluse, Anna Lila Kaushik, Adlen Foudi, Catherine Lacout, Dalila Sekkai, Isabelle Godin, Olivier Albagli, Isabelle Poullion, Fedor Svinartchouk, Elisabeth Schanze, William Vainchenker, Fred Sablitzky, Annelise Bennaceur-Griscelli, Dominique Duménil
Journal: Blood (2006)
Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma
Authors: Ranjit K. Dasgupta, Peter J. Adamson, Faith E. Davies, Sara Rollinson, Philippa L. Roddam, A. John Ashcroft, Ann M. Dring, James A. L. Fenton, J. Anthony Child, James M. Allan, Gareth J. Morgan
Journal: Blood (2003)
Serotonin Transporter Polymorphisms in Familial and Idiopathic Pulmonary Arterial Hypertension
Authors: Elisabeth D. Willers, John H. Newman, James E. Loyd, Ivan M. Robbins, Lisa A. Wheeler, Melissa A. Prince, Krista C. Stanton, Joy A. Cogan, James R. Runo, Daniel Byrne, Marc Humbert, Gerald Simonneau, Benjamin Sztrymf, Jane A. Morse, James A. Knowles, Kari E. Roberts, Jude J. McElroy, Robyn J. Barst, John A. Phillips
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Serotonin is a pulmonary vasoconstrictor and smooth muscle cell mitogen. The serotonin transporter (SERT) is abundant in pulmonary vascular smooth muscle. Compared with the short (S) allele, the long (L) SERT promoter allele is associated with increased SERT transcription and more severe pulmonary hypertension in a cohort of patients with chronic obstructive pulmonary disease, and was more prevalent in a cohort with idiopathic pulmonary arterial hypertension (IPAH), compared with control subjects.Objective: We hypothesized that the SERT L allele would associate with an earlier age at diagnosis and/or shorter survival interval in pulmonary arterial hypertension (PAH) than the S allele.Methods: SERT promoters from 166 familial PAH (FPAH), 83 IPAH, and 125 control subjects were sequenced. One hundred twenty-seven of the patients with FPAH had a known mutation in bone morphogenetic protein receptor 2 (BMPR2).Results: The mean age at diagnosis was 35.8 yr in patients with FPAH and 41.1 yr in patients with IPAH (p = 0.02). There were no significant differences in distribution of the LL, LS, or SS genotypes in IPAH, FPAH, or unaffected BMPR2 mutation carriers. In FPAH, the LL genotype was associated with an earlier age at diagnosis (p < 0.02).Conclusions: In patients with IPAH, these SERT genotypes do not correlate with age at diagnosis or survival interval. In patients with FPAH, the LL genotype correlates with an earlier age at diagnosis than SL or SS, although survival among the groups was similar. The correlation of the SERT promoter polymorphism with age at diagnosis in FPAH suggests a possible relationship between the SERT and BMPR2.
Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes.
Authors: M E Medof, T Kinoshita, V Nussenzweig
Journal: The Journal of Experimental Medicine (1984)

Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. Incorporation of DAF into the cell membranes was temperature dependent, took place on pronase- or trypsin-treated erythrocytes, and did not depend on prior deposition of antibody, C1 or C4. Serum lipoproteins (high and low density) effectively inhibited DAF incorporation, but had no effect on the activity of DAF after its association with the cell membrane. The incorporated DAF could not be removed from the red cell surface by repeated washings in the presence of high salt concentration but was solubilized when the stroma were extracted with 0.1% Nonidet P-40. The presence of DAF in the membrane of EA did not affect the deposition of C1 and C4, but as few as 10(2) DAF molecules per cell profoundly inhibited the assembly of C3 and C5 convertases of both the classical and alternative pathways. The DAF inhibitory effect on EAC14 or EAC43 was not overcome by supplying an excess of C2 or factor B, but the alternative pathway C3 convertase could be assembled in the presence of Ni++, or nonphysiological concentrations of Mg++, which enhances the binding affinity of factor B for C3b. The DAF effect on EAC14 or EAC143 was entirely reversed by treating the cells with specific anti-DAF antibodies, showing that DAF did not alter the structure of C4b or C3b. Taken together, the experimental evidence suggests that DAF interacts directly with membrane-bound C3b or C4b and prevents subsequent uptake of C2 and factor B. DAF can function only within the cell membrane. Indeed, the decay dissociation of the C4b2a enzyme on DAF-containing sheep intermediates was not changed by varying the cell concentration. DAF-treated EA had no influence on the decay of nontreated EAC142 present in the same mixture. Moreover, the inhibitory activity of intact human erythrocytes on C4b2a was not blocked by antibodies to DAF, but was abolished by antibodies to the C3b/C4b receptor (CR1). When incorporated into the membrane of rabbit erythrocytes, human DAF inhibited their lysis by human complement. In conclusion, on the basis of these and previous results, it appears that DAF plays a central role in preventing the amplification of the complement cascade on host cell surfaces.(ABSTRACT TRUNCATED AT 400 WORDS)
A SP1/MIZ1/MYCN Repression Complex Recruits HDAC1 at the<i>TRKA</i>and<i>p75NTR</i>Promoters and Affects Neuroblastoma Malignancy by Inhibiting the Cell Response to NGF
Authors: Nunzio Iraci, Daniel Diolaiti, Antonella Papa, Antonio Porro, Emanuele Valli, Samuele Gherardi, Steffi Herold, Martin Eilers, Roberto Bernardoni, Giuliano Della Valle, Giovanni Perini
Journal: Cancer Research (2010)

Neuroblastoma is the most common extracranial solid tumor of childhood. One important factor that predicts a favorable prognosis is the robust expression of the TRKA and p75NTR neurotrophin receptor genes. Interestingly, TRKA and p75NTR expression is often attenuated in aggressive MYCN-amplified tumors, suggesting a causal link between elevated MYCN activity and the transcriptional repression of TRKA and p75NTR, but the precise mechanisms involved are unclear. Here, we show that MYCN acts directly to repress TRKA and p75NTR gene transcription. Specifically, we found that MYCN levels were critical for repression and that MYCN targeted proximal/core promoter regions by forming a repression complex with transcription factors SP1 and MIZ1. When bound to the TRKA and p75NTR promoters, MYCN recruited the histone deacetylase HDAC1 to induce a repressed chromatin state. Forced re-expression of endogenous TRKA and p75NTR with exposure to the HDAC inhibitor TSA sensitized neuroblastoma cells to NGF-mediated apoptosis. By directly connecting MYCN to the repression of TRKA and p75NTR, our findings establish a key pathway of clinical pathogenicity and aggressiveness in neuroblastoma.
International Myeloma Working Group Consensus Statement Regarding the Current Status of Allogeneic Stem-Cell Transplantation for Multiple Myeloma
Authors: Henk Lokhorst, Hermann Einsele, David Vesole, Benedetto Bruno, Jesus San Miguel, Jose A. Pérez-Simon, Nicolaus Kröger, Philippe Moreau, Gosta Gahrton, Cristina Gasparetto, Sergio Giralt, William Bensinger
Journal: Journal of Clinical Oncology (2010)

To define consensus statement regarding allogeneic stem-cell transplantation (Allo-SCT) as a treatment option for multiple myeloma (MM) on behalf of International Myeloma Working Group.In this review, results from prospective and retrospective studies of Allo-SCT in MM are summarized.Although the introduction of reduced-intensity conditioning (RIC) has lowered the high treatment-related mortality associated with myeloablative conditioning, convincing evidence is lacking that Allo-RIC improves the survival compared with autologous stem-cell transplantation.New strategies are necessary to make Allo-SCT safer and more effective for patients with MM. Until this is achieved, Allo-RIC in myeloma should only be recommended in the context of clinical trials.
Molecular Properties and Biological Functions of Microsomal Epoxide Hydrase
Authors: A Y H Lu, G T Miwa
Journal: The Annual Review of Pharmacology and Toxicology (1980)

Many drugs, mutagens, and environmental carcinogens are aromatic or olefinic compounds and are metabolized in mammals by enzymes localized in the endoplasmic reticulum of various tissues (1, 2). Biologically active arene oxides which are formed by the microsomal cytochrome P-450containing monooxygenase system are the initial products from many of these compounds, polycyclic aromatic hydrocarbons being one class that has been extensively investigated (3-7). These reactive epoxides and arene oxides can be hydrated enzymatically via microsomal epoxide hydrase (epoxide hydratase, Ee 4.2.1.63) to chemically less reactive trans-dihy­ drodiols. In addition, arene oxides can undergo nonenzymatic isomeriza­ tion to phenols, be conjugated with glutathione via the enzyme glutathione-S-epoxide transferase, and also react with DNA, RNA, and proteins to form covalently bound products. Since certain of these arene oxides have toxic, mutagenic, and carcinogenic properties, the ability of epoxide hydrase to convert epoxides to dihydrodiols has been recognized as an important metabolic step in the detoxification of .these compounds. However, most recent investigations (8-16) have also '!fuown that the cyto­ chrome P-450 system and epoxide hydrase convert many polycyclic aro­ matic hydrocarbons to more reactive bay region diol epoxide derivatives. Thus, epoxide hydrase plays a central role in both the inactivation of mutagenic and carcinogenic metabolites of polycyclic aromatic hydrocar-
Prejudice is about politics: A collective action perspective
Authors: John Drury
Journal: Behavioral and Brain Sciences (2012)

Abstract In line with Dixon et al.'s argument, I contend that prejudice should be understood in broadly political rather than in narrowly psychological terms. First, what counts as prejudice is a political judgement. Second, studies of collective action demonstrate that it is in “political” struggles, where subordinate groups together oppose dominant groups, that prejudice can be overcome.
Online Tool to Guide Decisions for<i>BRCA1/2</i>Mutation Carriers
Authors: Allison W. Kurian, Diego F. Munoz, Peter Rust, Elizabeth A. Schackmann, Michael Smith, Lauren Clarke, Meredith A. Mills, Sylvia K. Plevritis
Journal: Journal of Clinical Oncology (2012)

Women with BRCA1 or BRCA2 (BRCA1/2) mutations must choose between prophylactic surgeries and screening to manage their high risks of breast and ovarian cancer, comparing options in terms of cancer incidence, survival, and quality of life. A clinical decision tool could guide these complex choices.We built a Monte Carlo model for BRCA1/2 mutation carriers, simulating breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years and prophylactic mastectomy (PM) and/or prophylactic oophorectomy (PO) at various ages. Modeled outcomes were cancer incidence, tumor features that shape treatment recommendations, overall survival, and cause-specific mortality. We adapted the model into an online tool to support shared decision making.We compared strategies on cancer incidence and survival to age 70 years; for example, PO plus PM at age 25 years optimizes both outcomes (incidence, 4% to 11%; survival, 80% to 83%), whereas PO at age 40 years plus MRI screening offers less effective prevention, yet similar survival (incidence, 36% to 57%; survival, 74% to 80%). To characterize patients' treatment and survivorship experiences, we reported the tumor features and treatments associated with risk-reducing interventions; for example, in most BRCA2 mutation carriers (81%), MRI screening diagnoses stage I, hormone receptor-positive breast cancers, which may not require chemotherapy.Cancer risk-reducing options for BRCA1/2 mutation carriers vary in their impact on cancer incidence, recommended treatments, quality of life, and survival. To guide decisions informed by multiple health outcomes, we provide an online tool for joint use by patients with their physicians (http://brcatool.stanford.edu).
Treatment for newly diagnosed hypertension: patterns of prescribing and antihypertensive effectiveness in the UK
Authors: T. Walley, A. K Duggan, A. R Haycox, C. J Niziol
Journal: Journal of the Royal Society of Medicine (2003)

Improved practice in the management of hypertension depends on an understanding of existing patterns of treatment. To describe the management of newly diagnosed hypertension in British general practice and the effectiveness of current prescribing patterns we conducted a retrospective observational study using data from a computerized general practitioner record database (DIN-LINK). 21 024 patients were first treated for newly diagnosed hypertension between January 1993 and December 1997, and were followed for 4 years. Diuretics or beta-blockers were the most widely prescribed first-line treatments, used in 54% of patients. The mean continuation rate for first-line therapy was 69% at 12 months: the continuation rate was highest for angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists. After 12 months of treatment the mean blood pressure reduction was 19/10 mmHg. Blood pressure targets were met in only 14% of patients. After 48 months of treatment 34% of patients had not improved in band of blood pressure severity. Many patients with severe hypertension at 12 months were still being prescribed only one drug. The lack of aggression in antihypertensive treatment, indicated by the low number of agents prescribed and the failure to achieve targets, is disappointing. Prescribing patterns for first-line therapy corresponded to guidelines. Continuation rates on first-line therapy were higher than often reported. The choice of drug for additions to or switches from first-line therapy had no clear pattern. Routinely collected computerized data could be used to support clinical governance activities in primary care.
High-Dose Dexamethasone Accentuates Nuclear Factor- κ B Activation in Endotoxin-Treated Mice
Authors: RUXANA T. SADIKOT, E. DUCO JANSEN, THOMAS R. BLACKWELL, ORNELLA ZOIA, FIONA YULL, JOHN W. CHRISTMAN, TIMOTHY S. BLACKWELL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We examined the effects of dexamethasone treatment on nuclear factor (NF)- κ B activation and lung inflammation in transgenic reporter mice expressing photinus luciferase under the control of an NF- κ B–dependent promoter (HLL mice). In vitro studies with bone marrow and peritoneal macrophages derived from these mice showed that treatment with dexamethasone blocked luciferase induction after treatment with Escherichia coli lipopolysaccharide (LPS); however, treatment of mice with intraperitoneal injection of dexamethasone at doses of 0.3 μ g/g and 1 μ g/g failed to inhibit NF- κ B–dependent luciferase activity in the lungs. Furthermore, intraperitoneal treatment with 10 μ g/g of dexamethasone prior to LPS paradoxically resulted in augmented luciferase activity as compared with that of mice treated with LPS alone. NF- κ B–dependent luciferase expression in the lungs was detected by bioluminescence imaging and by measurement of luciferase activity in homogenized lung tissue. In these studies, there was an excellent correlation between indirect measurement of luciferase activity by bioluminescence in living mice and direct measurement of luciferase activity in lung tissue. Dexamethasone treatment did not affect LPS-induced neutrophilic influx or the concentration of macrophage inflammatory protein-2 in lung lavage fluid. These findings emphasize the potential error of extrapolating in vitro findings to complex in vivo events such as regulation of inflammation.Keywords: NF-κB; endotoxin; bioluminescence; cytokines; inflammation
Country-specific cost-effectiveness of early intervention with budesonide in mild asthma
Authors: M.J. Buxton, S.D. Sullivan, L.F. Andersson, C.J. Lamm, B. Liljas, W.W Busse, S. Pedersen, K.B. Weiss
Journal: European Respiratory Journal (2004)

Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.
Optimally recovering rate variation information from genomes and sequences: pattern filtering
Authors: J. A. Lake
Journal: Molecular Biology and Evolution (1998)

Nucleotide substitution rates vary at different positions within genes and genomes, but rates are difficult to estimate, because they are masked by the stochastic nature of substitutions. In this paper, a linear method, pattern filtering, is described which can optimally separate the signals (related to substitution rates or to other measures of sequence change) from stochastic noise. Pattern filtering promises to be useful in both genomic and molecular evolution studies. In an example using mitochondrial genomes, it is shown that pattern filtering can reveal coding and non-coding regions without the need for prior identification of reading frames or other knowledge of the sequence and promises to be an important tool for genomic analysis. In a second example, it is shown that pattern filtering allows one to classify sites on the basis of an estimator of substitution rates. Using elongation factor EF-1 alpha sequences, it is shown that the fastest sites favor archaea as the sister taxon of eukaryotes, whereas the slower sites support the eocyte prokaryotes as the sister taxon of eukaryotes, suggesting that the former result is an artifact of "long branch attraction."
Design and construction of fascia lata aortic valve prostheses
Authors: K. G. Reid
Journal: Thorax (1970)

Current techniques for constructing fascia lata aortic valves result in a valve in which redundant cusp tissue is inadvertently incorporated in the proximal part of the cusp. This alters the flow character of the valve and produces a significant stenosis. An alternative technique, based on the normal anatomy of the aortic valve, is suggested which eliminates this fault. The technique is simple and can be used at the time of operation.
Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions
Authors: Holger Kohlhammer, Carsten Schwaenen, Swen Wessendorf, Karlheinz Holzmann, Hans A. Kestler, Dirk Kienle, Thomas F. E. Barth, Peter Möller, German Ott, Jörg Kalla, Bernhard Radlwimmer, Armin Pscherer, Stephan Stilgenbauer, Hartmut Döhner, Peter Lichter, Martin Bentz
Journal: Blood (2004)