tbuckley/cabot-search huggingface dataset:
Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis
Authors: Jessica C. Shearer, Meghan L. Stack, Marcie R. Richmond, Allyson P. Bear, Rana A. Hajjeh, David M. Bishai
Journal: PLoS Medicine (2010)

Background Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance). Methods and Findings Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision. Conclusions This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors. Please see later in the article for the Editors' Summary
Genetic variants in thymic stromal lymphopoietin are associated with atopic dermatitis and eczema herpeticum
Authors: Pei-Song Gao, Nicholas M. Rafaels, Deguang Mu, Tracey Hand, Tanda Murray, Mark Boguniewicz, Tissa Hata, Lynda Schneider, Jon M. Hanifin, Richard L. Gallo, Li Gao, Terri H. Beaty, Lisa A. Beck, Donald Y.M. Leung, Kathleen C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2010)
The effect of ketone bodies on renal ammoniogenesis
Authors: Guy Lemieux, Patrick Vinay, Pierre Robitaille, Gérard E. Plante, Yolande Lussier, Pierre Martin
Journal: Journal of Clinical Investigation (1971)

Infusion of ketone bodies to ammonium chloride-loaded acidotic dogs was found to induce significant reduction in urinary excretion of ammonia. This effect could not be attributed to urinary pH variations. Total ammonia production by the left kidney was measured in 25 animals infused during 90 min with the sodium salt of D,L-β-hydroxybutyric acid adjusted to pH 6.0 or 4.2. Ketonemia averaged 4.5 mM/liter. In all experiments the ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed by 60% or more within 60 min after the onset of infusion. Administration of equimolar quantities of sodium acetoacetate adjusted to pH 6.0 resulted in a 50% decrease in renal ammonia production. Infusion of ketone bodies adjusted to pH 6.0 is usually accompanied by a small increase in extracellular bicarbonate (3.7 mM/liter). However infusion of D,L-sodium lactate or sodium bicarbonate in amounts sufficient to induce a similar rise in plasma bicarbonate resulted in only a slight decrement in ammonia production (15%). The continuous infusion of 5% mannitol alone during 90-150 min failed to influence renal ammoniogenesis. Infusion of pure sodium-free β-hydroxybutyric acid prepared by ion exchange (pH 2.2) resulted in a 50% decrease in renal ammoniogenesis in spite of the fact that both urinary pH and plasma bicarbonate fell significantly. During all experiments where ketones were infused, the renal extraction of glutamine became negligible as the renal glutamine arteriovenous difference was abolished. Renal hemodynamics did not vary significantly. Infusion of β-hydroxybutyrate into the left renal artery resulted in a rapid decrease in ammoniogenesis by the perfused kidney. The present study indicates that ketone bodies exert their inhibitory influence within the renal tubular cell. Since their effect is independent of urinary or systemic acid-base changes, it is suggested that they depress renal ammoniogenesis by preventing the transformation of glutamine and glutamate into α-ketoglutarate in the mitochondria of the renal tubular cell.
Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer--response.
Authors: Robert J. Cardnell, Ying Feng, Lixia Diao, You Hong Fan, Fatemah Masrorpour, Jing Wang, Yuqiao Shen, Gordon B Mills, John D. Minna, John Victor Heymach, Lauren Averett Byers
Journal: Clinical Cancer Research (2014)

Small cell lung carcinoma (SCLC) is an aggressive malignancy affecting nearly 30,000 people annually in the United States. We have previously identified elevated PARP1 levels in SCLC and demonstrated in vitro sensitivity to the PARP inhibitors AZD 2281 and AG014699. Here, we evaluate activity of a novel, potent PARP inhibitor, BMN 673, and identify markers of response as a basis for developing predictive markers for clinical application.Inhibition of SCLC proliferation by BMN 673 was assayed in vitro and effects on tumor growth were measured in SCLC xenograft models. Protein expression and pathway activation was assessed by reverse phase protein array and western blot analysis. PARP inhibition was confirmed using a PAR ELISA.We demonstrate striking, single agent activity of BMN 673 in SCLC cell lines and xenografts, with single agent BMN 673 exhibiting in vivo activity similar to cisplatin. Sensitivity to BMN 673 was associated with elevated baseline expression levels of several DNA repair proteins, whereas greater drug resistance was observed in SCLC models with baseline activation of the PI3K/mTOR pathway. Furthermore, we developed and confirmed these data with a novel "DNA repair score" consisting of a group of 17 DNA repair proteins.Elevated expression of multiple DNA repair proteins, as well as a corresponding "DNA repair protein score," predict response to BMN 673 in in vitro SCLC models. These observations complement recent work in which PI3K inhibition sensitizes breast cancer models to PARP inhibition, suggesting cooperation between DNA repair and PI3K pathways.
Validation of a radiographic scoring system for haemochromatosis arthropathy
Authors: Tomáš Dallos, Enijad Sahinbegovic, Elmar Aigner, Roland Axmann, Maximilian Schöniger-Hekele, Thomas Karonitsch, Tanja Stamm, Martin Farkas, Thomas Karger, Alexander Cavallaro, Ulrich Stölzel, Gernot Keyßer, Christian Datz, Georg Schett, Bernhard Manger, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2010)

Arthropathy is one of the earliest and most common manifestations of hereditary haemochromatosis with a significant impact on quality of life. Although its radiographic features are well known, there is no assessment tool for their evaluation.To develop and validate a novel scoring system for the evaluation of radiographic features of haemochromatosis arthropathy.A dichotomous scoring system assessing four radiographic features of haemochromatosis arthropathy and a 4-grade scale reflecting severity of radiographic change have been developed. Standard radiographs (hand, wrist, knee and ankle) of 170 subjects (116 male, 54 female) with genetically confirmed haemochromatosis and laboratory signs of iron overload were assessed by three readers and construct validity, feasibility and cross-sectional reliability (intrareader and inter-reader) were assessed.Intrareader and inter-reader reliability as assessed by percentage pairwise agreement and Cohen's weighed κ were good to excellent for most features and locations evaluated. Radiographic scores correlated well with clinical parameters (bony swollen joint count, hand function and physician's global health assessment; Pearson's correlation, r²=0.18-0.62, p<0.0001). A complete set of radiographs took 3.4 ± 1.2 (mean ± SD) min to be assessed. An atlas of characteristic radiographic features was compiled.A feasible and reliable radiological assessment tool for the evaluation of haemochromatosis arthropathy has been validated and an atlas of characteristic radiographic features provided.
Pancreatic Ductal Adenocarcinoma Mice Lacking Mucin 1 Have a Profound Defect in Tumor Growth and Metastasis
Authors: Dahlia M. Besmer, Jennifer M. Curry, Lopamudra D. Roy, Teresa L. Tinder, Mahnaz Sahraei, Jorge Schettini, Sun-Il Hwang, Yong Y. Lee, Sandra J. Gendler, Pinku Mukherjee
Journal: Cancer Research (2011)

MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro.
Use of inhaled corticosteroids during pregnancy and risk of pregnancy induced hypertension: nested case-control study
Authors: Marie-Josée Martel, Évelyne Rey, Marie-France Beauchesne, Sylvie Perreault, Geneviève Lefebvre, Amélie Forget, Lucie Blais
Journal: BMJ (2005)

To determine whether the use of inhaled corticosteroids during pregnancy increases the risk of pregnancy induced hypertension and pre-eclampsia among asthmatic women.Nested case-control study.Three administrative health databases from Quebec: RAMQ, MED-ECHO, and Fichier des evenements demographiques.3505 women with asthma, totalling 4593 pregnancies, between 1990 and 2000.Pregnancy induced hypertension and pre-eclampsia.302 cases of pregnancy induced hypertension and 165 cases of pre-eclampsia were identified. Use of inhaled corticosteroids from conception until date of outcome was not associated with an increased risk of pregnancy induced hypertension (adjusted odds ratio 1.02, 95% confidence interval 0.77 to 1.34) or pre-eclampsia (1.06, 0.74 to 1.53). No significant dose-response relation was observed between inhaled corticosteroids and pregnancy induced hypertension or pre-eclampsia. Oral corticosteroids were significantly associated with the risk of pregnancy induced hypertension (adjusted odds ratio 1.57, 1.02 to 2.41), and a trend was seen for pre-eclampsia (1.72, 0.98 to 3.02).No significant increase of the risk of pregnancy induced hypertension or pre-eclampsia was detected among users of inhaled corticosteroids during pregnancy, while markers of uncontrolled and severe asthma were found to significantly increase the risks of pregnancy induced hypertension and pre-eclampsia.
Rapid Identification of Dihydropyrimidine Dehydrogenase Deficiency by Using a Novel 2-13C-Uracil Breath Test
Authors: Lori K. Mattison, Hany Ezzeldin, Mark Carpenter, Anil Modak, Martin R. Johnson, Robert B. Diasio
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Dihydropyrimidine dehydrogenase (DPD)-deficient cancer patients have been shown to develop severe toxicity after administration of 5-fluorouracil. Routine determination of DPD activity is limited by time-consuming and labor-intensive methods. The purpose of this study was to develop a simple and rapid 2-13C-uracil breath test, which could be applied in most clinical settings to detect DPD-deficient cancer patients. Experimental Design: Fifty-eight individuals (50 “normal,” 7 partially, and 1 profoundly DPD-deficient) ingested an aqueous solution of 2-13C-uracil (6 mg/kg). 13CO2 levels were determined in exhaled breath at various time intervals up to 180 min using IR spectroscopy (UBiT-IR300). DPD enzyme activity and DPYD genotype were determined by radioassay and denaturing high-performance liquid chromatography, respectively. Results: The mean (±SE) Cmax, Tmax, δ over baseline values at 50 min (DOB50) and cumulative percentage of 13C dose recovered (PDR) for normal, partially, and profoundly DPD-deficient individuals were 186.4 ± 3.9, 117.1 ± 9.8, and 3.6 DOB; 52 ± 2, 100 ± 18.4, and 120 min; 174.1 ± 4.6, 89.6 ± 11.6, and 0.9 DOB50; and 53.8 ± 1.0, 36.9 ± 2.4, and &amp;lt;1 PDR, respectively. The differences between the normal and DPD-deficient individuals were highly significant (all Ps &amp;lt;0.001). Conclusions: We demonstrated statistically significant differences in the 2-13C-uracil breath test indices (Cmax, Tmax, DOB50, and PDR) among healthy and DPD-deficient individuals. These data suggest that a single time-point determination (50 min) could rapidly identify DPD-deficient individuals with a less costly and time-consuming method that is applicable for most hospitals or physicians’ offices.
A circulating reservoir of pathogenic-like CD4<sup>+</sup>T cells shares a genetic and phenotypic signature with the inflamed synovial micro-environment
Authors: Roberto Spreafico, Maura Rossetti, Jorg van Loosdregt, Carol A Wallace, Margherita Massa, Silvia Magni-Manzoni, Marco Gattorno, Alberto Martini, Daniel J Lovell, Salvatore Albani
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Systemic immunological processes are profoundly shaped by the micro-environments where antigen recognition occurs. Identifying molecular signatures distinctive of such processes is pivotal to understand pathogenic immune responses and manipulate them for therapeutic purposes. Unfortunately, direct investigation of peripheral tissues, enriched in pathogenic T cells, is often impossible or imposingly invasive in humans. Conversely, blood is easily accessible, but pathogenic signatures are diluted systemically as a result of the strict compartmentalisation of immune responses. In this work, we aimed at defining immune mediators shared between the bloodstream and the synovial micro-environment, and relevant for disease activity in autoimmune arthritis. <h3>Methods</h3> CD4<sup>+</sup> T cells from blood and synovium of patients with juvenile idiopathic arthritis (JIA) were immunophenotyped by flow cytometry. The TCR repertoire of a circulating subset showing similarity with the synovium was analysed through next-generation sequencing of TCR β-chain CDR3 to confirm enrichment in synovial clonotypes. Finally, clinical relevance was established by monitoring the size of this subset in the blood of patients with JIA and rheumatoid arthritis (RA). <h3>Results</h3> We identified a small subset of circulating CD4<sup>+</sup> T cells replicating the phenotypical signature of lymphocytes infiltrating the inflamed synovium. These circulating pathogenic-like lymphocytes (CPLs) were enriched in synovial clonotypes and they exhibited strong production of pro-inflammatory cytokines. Importantly, CPLs were expanded in patients with JIA, who did not respond to therapy, and also correlated with disease activity in patients with RA. <h3>Conclusions</h3> CPLs provide an accessible reservoir of pathogenic cells recirculating into the bloodstream and correlating with disease activity, to be exploited for diagnostic and research purposes.
The Fate of Integrated Treatment: Whatever Happened to the Biopsychosocial Psychiatrist?
Authors: Glen O. Gabbard, Jerald Kay
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors suggest that pharmacotherapy and psychotherapy, the major treatment modalities in psychiatry, have become fragmented from one another, creating an artificial separation of the psychosocial and biological domains in psychiatry. METHOD: After a brief discussion of the economic factors influencing this trend, the authors provide a selective overview of recent research. In the absence of systematic empirical data regarding which patients and which conditions might benefit from integrated treatment by one psychiatrist, the authors propose specific clinical situations that call for such integration and also discuss concerns about cost-effectiveness. RESULTS: Recent research suggests that combining psychotherapy and pharmacotherapy may have advantages over either treatment alone in certain clinical situations involving specific disorders. While few of the studies on combined treatment have tested whether a one-person or two-person model of treatment provision is more effective, there are a number of advantages to the one-person treatment model in which a psychiatrist conducts the psychotherapy and prescribes medication for the same patient. CONCLUSIONS: The authors suggest that further research is needed to clarify the optimal situations for the one-person model of integrated treatment and also propose systematic teaching of integrated treatment in all residency training programs.
Predictive factors, microbiology and outcome of patients with parapneumonic effusion
Authors: M. Falguera, J. Carratalà, S. Bielsa, C. García-Vidal, A. Ruiz-González, I. Chica, F. Gudiol, J.M. Porcel
Journal: European Respiratory Journal (2011)

We aimed to determine the incidence, clinical consequences and microbiological findings related to the presence of pleural effusion in community-acquired pneumonia, and to identify predictive factors for empyema/complicated parapneumonic effusion. We analysed 4,715 consecutive patients with community-acquired pneumonia from two acute care hospitals. Patients were classified into three groups: no pleural effusion, uncomplicated parapneumonic effusion and empyema/complicated parapneumonic effusion. A total of 882 (19%) patients had radiological evidence of pleural fluid, of whom 261 (30%) met criteria for empyema/complicated parapneumonic effusion. The most important event related to the presence of uncomplicated parapneumonic effusion was a longer hospital stay. Relevant clinical and microbiological consequences were associated with empyema/complicated parapneumonic effusion. Five independent baseline characteristics could predict the development of empyema/complicated parapneumonic effusion: age &lt;60 yrs (p=0.012), alcoholism (p=0.002), pleuritic pain (p=0.002), tachycardia &gt;100 beats·min −1 (p=0.006) and leukocytosis &gt;15,000 mm −3 (p&lt;0.001). A higher incidence of anaerobes and Gram-positive cocci was found in this subgroup of patients. We conclude that only the development of empyema/complicated parapneumonic effusion carried relevant consequences; this condition should be suspected in the presence of some baseline characteristics and managed by using antimicrobials active against Gram-positive cocci and anaerobes.
Studies of the rectal mucosa in coeliac sprue: the intraepithelial lymphocyte.
Authors: L L Austin, W O Dobbins
Journal: Gut (1988)

The dynamics of the rectal surface epithelial lymphocyte and leucocyte response to wheat, gluten, and gliadin enema challenges in control individuals and in patients with coeliac sprue in remission is shown. There is a clear increase in intraepithelial lymphocytes and polymorphonuclear (PMN) leucocytes in response to these enemas in coeliac sprue, but not in controls. The peak response was at eight hours and cleared within 24 hours. There was no change in the crypt epithelium. These data add further support to the role of wheat, gluten, and gliadin in the pathogenesis of coeliac sprue, at least in the rectal mucosa.
Gestational Age at Delivery and Special Educational Need: Retrospective Cohort Study of 407,503 Schoolchildren
Authors: Daniel F. MacKay, Gordon C. S. Smith, Richard Dobbie, Jill P. Pell
Journal: PLoS Medicine (2010)

Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation.We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37-39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12-1.20; 33-36 wk adjusted OR 1.53, 95% CI 1.43-1.63; 28-32 wk adjusted OR 2.66, 95% CI 2.38-2.97; 24-27 wk adjusted OR 6.92, 95% CI 5.58-8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37-39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases.Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery.
Cholestasis. Proceedings of the international congress on cholestasis and related disorders, Florence, Italy, 23–26 March 1994. Edited by P. Gentilini, I. M. Arias, N. McIntyre, and J. Rodes, 382 pp. Amsterdam: Elsevier Science, 1994. $200
Authors: Mark B. Sostek
Journal: Hepatology (1995)

both to identify books of hepatological interest and to serve as book reviewers.
(53) Pseudokeloidal scleroderma
Authors: S.M. Burge, P.S. Mortimer, T.J. Ryan
Journal: British Journal of Dermatology (1985)

Journal Article (53) Pseudokeloidal scleroderma Get access S.M. Burge, S.M. Burge The Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar P.S. Mortimer, P.S. Mortimer The Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar T.J. Ryan T.J. Ryan The Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Page 99, https://doi.org/10.1111/j.1365-2133.1985.tb13068.x Published: 01 July 1985