tbuckley/cabot-search huggingface dataset:
Workload demands in professional multi-stage cycling races of varying duration
Authors: J A Rodríguez-Marroyo, J García-López, C-É Juneau, J G Villa
Journal: British Journal of Sports Medicine (2007)

To analyse and compare the workload exerted by professional cyclists in 5-day, 8-day and 21-day stage races (5-SR, 8-SR, 21-SR).The study subjects were 30 professional cyclists competing in 10 5-SR, 5 8-SR and 5 21-SR. Heart rate (HR) was measured during the races and categorised into three intensity zones: Z1 (below the ventilatory threshold (VT)), Z2 (between VT and the respiratory compensation threshold (RCT)) and Z3 (above RCT). The training impulse (TRIMP) was calculated by multiplying the sum of the time spent in each zone by 1, 2 and 3, respectively. Monotony (average TRIMP/SD) and strain (total TRIMPxmonotony) were also calculated for each race type.The average time spent in Z3 during each stage was significantly (p<0.05) higher for 5-SR ( approximately 31 min) and 8-SR ( approximately 28 min) than for 21-SR ( approximately 14 min). Daily TRIMP values in 5-SR ( approximately 400) and 8-SR ( approximately 395) were also higher than in 21-SR ( approximately 370). Monotony was similar across races ( approximately 3) but strain was about three times higher for 21-SR than for 5-SR and 8-SR.The cyclists' effort by stage was less for 21-SR than for 5-SR and 8-SR. Competition strain and monotony accumulated during longer races influence the choice of strategies adopted by cyclists. It is likely that the intensity of each stage is modulated by total race duration, with longer races averaging the lowest daily workload.
Assessment of a Medication-Based Asthma Index for Population Research
Authors: WENDY J. UNGAR, KENNETH R. CHAPMAN, MARIA T. SANTOS
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Asthma management guidelines recommend the use of preventive medications in sufficient amounts to control asthma symptoms. The validity of a medication use index as a proxy for asthma severity has not been established. We recruited 1,279 Ontario adults with asthma or parents of children with asthma from a community-based surveillance program in 1995–96. Participants completed a telephone questionnaire at baseline, 3 and 6 mo. The questionnaire gathered information about asthma medication use, health care utilization, and symptoms. Asthma was classified as mild in 28%, moderate in 49%, or severe in 23% of patients based on the amount and types of medication used. There were significant differences among groups in health resource use such that adults with higher medication use visited primary care physicians and specialists more frequently, had pulmonary functions tests more frequently, and were admitted to hospital more frequently. The findings among children were similar. There were weak positive correlations between medication use and symptom frequency in adults and children. We conclude that a medication use index may be useful in population-based research where clinical asthma severity data are lacking. Such an index is distinct from but is related to disease control.
Recombinant DNase in cystic fibrosis: a protocol for targeted introduction through n-of-1 trials
Authors: F. G. E. Böllert, J. Y. Paton, T. G. Marshall, J. Calvert, A. P. Greening, J. A. Innes
Journal: European Respiratory Journal (1999)

Nebulized recombinant human deoxyribonuclease (DNase) reduces sputum viscosity and improves lung function in some cystic fibrosis patients, but individual responses are unpredictable.



The aim of this study was to investigate how DNase can be targeted to those cystic fibrosis patients who would benefit most.



The Scottish Cystic Fibrosis Group agreed on a randomized, double-blind, placebo-controlled n-of-1 assessment protocol. Patients underwent a maximum of three 4-week assessment periods (2 weeks saline, 2 weeks DNase each). Measurements performed at hospital (exercise, oximetry and spirometry) and home (symptom scores) were used to derive a scoring system to discriminate maximally between DNase and placebo effects. The data on 89 4-week assessments in 52 patients were reported.



Twenty-four patients have completed the assessment process (12 responders and 12 nonresponders) to date. Forced expiratory volume in one second (FEV1) was the best discriminator of response, rising by >200 mL after DNase in 33 of 89 (37%) assessments compared with 3 of 89 (3%) after saline.



N-of-1 trials, while laborious, permitted genuine treatment effects to be quantified within individuals with confidence, permitting appropriate treatment targeting. This provides a model of how other new expensive therapies may be introduced to maximize patient benefit.
Improved Tumor Targeting by Combined Use of Two Antitenascin Antibodies
Authors: Fiorella Petronzelli, Angela Pelliccia, Anna Maria Anastasi, Valeria D'Alessio, Claudio Albertoni, Antonio Rosi, Barbara Leoni, Clara De Angelis, Giovanni Paganelli, Giovanna Palombo, Maria Dani, Paolo Carminati, Rita De Santis
Journal: Clinical Cancer Research (2005)

In the pretargeted antibody-guided radioimmunotherapy (PAGRIT) system, the combined use of two different antibodies directed against the same tumor antigen could represent a valid approach for improving tumor targeting and therapeutic efficacy. We developed a novel monoclonal antitenascin antibody, ST2485, and studied its biochemical and functional properties by in vitro and in vivo assays. We then investigated the first of the three-step therapy combining ST2485 with another antitenascin antibody, ST2146, previously described, to increase accumulation of biotinylated antibodies at the tumor site.Studies of immunoreactivity, affinity, immunohistochemistry, and biodistribution in xenograft model were carried out on ST2485. Analysis of the ST2485 and ST2146 combination was preliminary carried out by ELISA and BiaCore tests and then by in vivo distribution studies after administration of the radiolabeled biotinylated antibodies, followed by a chase with avidin as clearing agent.ST2485 was found to be a suitable antibody for therapeutic applications. Indeed, for its behavior in all tests, it was comparable with ST2146 and better than BC2, an antibody already used for clinical trials. The additivity of ST2146 and ST2485 in tenascin C binding, shown by in vitro tests, was confirmed by biodistribution studies in a xenograft model where tumor localization of the antibodies was near the sum of each antibody alone, with a tumor-to-blood ratio higher than 24.The results reported in this study suggest that a monoclonal antitenascin antibody mixture can improve tumor targeting. This strategy could represent progress for therapeutic approaches such as PAGRIT.
Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo
Authors: Melissa Swiecki, Yaming Wang, William Vermi, Susan Gilfillan, Robert D. Schreiber, Marco Colonna
Journal: The Journal of Experimental Medicine (2011)

Plasmacytoid dendritic cells (pDCs) specialize in the secretion of type I interferons (IFN-I) and thus are considered critical mediators of antiviral responses. We recently reported that pDCs have a very early but limited and transient capacity to curtail viral infections. Additionally, pDC numbers are not sustained in human infections caused by Hepatitis B or C viruses (HBV and HCV) and HIV. Thus, the numbers and/or function of pDCs appear to be regulated during the course of viral infection. In this study, we show that splenic pDCs are reduced in vivo during several systemic viral infections and after administration of synthetic toll-like receptor ligands. We demonstrate that IFN-I, regardless of the source, contributes to this decline and mediates pDC death via the intrinsic apoptosis pathway. These findings demonstrate a feedback control mechanism by which IFN-I modulates pDC numbers, thus fine-tuning systemic IFN-I response to viruses. IFN-I–mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases.
Following Up Folate and Its Function in Colorectal Carcinogenesis
Authors: R. G. Ziegler
Journal: JNCI Journal of the National Cancer Institute (2012)

given to women with suboptimal micronutrient intake. Because the trial was carried out during the folic acid fortification era and the women volunteering were likely to be health-conscious, with a history of vitamin supplement use, the median intake of folate, B6, and B12 at study entry was relatively high, at 108%, 167%, and 292% of the respective recommended dietary allowances (1). The lack of effect of high-dose folate/B6/B12 supplementation on adenoma risk in a well-nourished population agrees with a recent combined analysis of the three large randomized, placebocontrolled trials of folic acid supplementation, which were carried out in the United States, Canada, the United Kingdom, and Denmark among patients with an adenoma history (2632 men and women) (8). After up to 3.5 years of folic acid use, at 0.5 or 1.0 mg/day, risk of adenoma, or advanced adenoma, was not statistically significantly increased or decreased. Interestingly, folic acid was associated with non-statistically significant reductions in risk among subjects in the two lowest quartiles of circulating folate at study entry. This combined analysis is encouraging, even though more follow-up is needed. The largest of the three trials included had previously reported potentially adverse effects: a statistically nonsignificant increased risk of adenoma, especially advanced adenoma, after 3 and 6–8 years of follow-up (9). Although these randomized trials do suggest that high-dose folic acid is not a promising chemopreventive agent for colorectal cancer, they do not completely resolve the role of folate and other B vitamins in colorectal carcinogenesis. In 2010, in a pooled analysis of 13 prospective studies of folate intake and colon cancer, including 5720 incident cases and up to 7–20 years of follow-up, both dietary folate intake and total folate intake (from diet and supplements) were inversely, although modestly, associated with risk (comparing extreme quintiles, RRs = 0.92, 95% CI = 0.84 to 1.00 and 0.85, 95% CI = 0.77 to 0.95, respectively) (10). The stronger association with total folate intake might be due to an expanded range of intake, enhanced bioavailability of the synthetic folic acid in supplements, or the presence of other B vitamins in the multivitamins that provided most of the supplemental folate. More recently, in analyses of incident colorectal cancer diagnosed in the folic acid fortification era, the American Association of Retired Persons cohort reported a statistically significant 30% reduction in colorectal cancer risk comparing extremes of total folate intake (6484 incident cases) (11); and the Cancer Prevention Study II reported a statistically significant 19% reduction comparing extreme quintiles of total intake (1023 incident cases) (12). Although the strength of these associations with total folate intake
Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula
Authors: Mahesh K. Krishnamoorthy, Rupak K. Banerjee, Yang Wang, Jianhua Zhang, Abhijit Sinha Roy, Saeb F. Khoury, Lois J. Arend, Steve Rudich, Prabir Roy-Chaudhury
Journal: Kidney International (2008)
Psoriatic onycho-pachydermo periostitis: treatment with methotrexate
Authors: A. Bauzá, P. Redondo, D. Aquerreta
Journal: British Journal of Dermatology (2000)

Journal Article Psoriatic onycho‐pachydermo periostitis: treatment with methotrexate Get access A. Bauzá, A. Bauzá Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar P. Redondo, P. Redondo Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar D. Aquerreta D. Aquerreta Radiology, University Clinic of Navarra, School of Medicine, PO Box 4209, 31080 Pamplona, Spain Correspondence: P.Redondo.E‐mail: predondo@unav.es Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 4, 1 October 2000, Pages 901–902, https://doi.org/10.1046/j.1365-2133.2000.03802.x Published: 01 October 2000
UK minister is questioned about recruiting too many GPs
Authors: Adrian O'Dowd
Journal: BMJ (2007)

The government has denied accusations that it allowed a “spectacular failure” in NHS workforce planning to happen. 

In a session of the parliamentary health select committee last week the Department of Health's minister for quality, Philip Hunt, and government officials claimed that problems with workforce levels are set to improve in the next year, despite current cutbacks in staff numbers. 

MPs on the committee tackled Lord Hunt and Department of Health officials on their track record as part of the committee's last session of evidence in its inquiry into workforce planning. 

The committee asked why the staff recruitment …
Letter by Cornet et al Regarding Article, “Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest”
Authors: Alexander D. Cornet, Mike J. Peters, Albertus J. Kooter
Journal: Circulation (2012)

We read with great interest the article by Kilgannon and coworkers 1 demonstrating a dose-dependent linear relationship between supranormal oxygen tension after resuscitation from cardiac arrest and in-hospital death.This observation is important and merits further investigation, but we question the definition of hypoxia.The present study 1 is a secondary analysis of a previously published multicenter cohort study, 2 in which Project IMPACT was analyzed.A total of 6326 patients met the inclusion criteria in both studies.However, in the original analysis, 2 hypoxia was defined as PaO 2 Ͻ60 mm Hg or PaO 2 to fraction of inspired oxygen ratio Ͻ300 mm Hg, rendering 3999 patients hypoxic.In the secondary analysis, hypoxia was defined as PaO 2 Ͻ60 mm Hg or PaO 2 to fraction of inspired oxygen ratio Ͻ200 mm Hg, defining 1867 patients as hypoxic.In other words, 2132 patients were "hypoxic" in the primary analysis but "normoxic" in the secondary analysis.Why did the authors use different definitions of hypoxia?
The central role of the c-Met pathway in rebuilding the liver
Authors: S S Thorgeirsson
Journal: Gut (2012)

In spite of the enormous regenerative capacity of the liver, most dramatically described in the allegory of Prometheus, the effectiveness of cellular treatment for end-stage liver diseases is still limited, with orthotopic liver transplantation being currently the treatment of choice. Nevertheless, long-term success of hepatocyte transplantation for metabolic liver diseases in children has been realised.1–3 In the light of the severe shortage of available donor organs, the application of hepatocyte transplantation for end-stage liver diseases remains an attractive therapeutic option. However, the underlying molecular and cellular mechanisms preventing the effective use of cellular treatment for end-stage liver diseases need to be better understood in order to improve translation of this technique into clinical use.

The work by Kaldenbach et al 4 in the current issue of Gut begins to address these issues by investigating the relevance of hepatocyte growth factor (HGF)/c-Met signalling in vivo for hepatocyte repopulation after transplantation. The authors employed an experimental system that made use of c-Met (loxP/loxP) and hepatocyte-specific conditional c-Met knockout (c-Met−/−) mice as donors and/or recipients for hepatocyte transplantation. Two major findings emerged: (1) c-Met−/− cells did not repopulate the recipient livers after transplantation indicating that c-Met signalling in donor …
Treatment of asthma during pregnancy: more solid evidence needed
Authors: M. Cazzola, M. G. Matera
Journal: Thorax (2008)

In this issue of Thorax , a paper by Tata and colleagues1 assesses the association between maternal asthma and gestational exposure and asthma medications with the risk of congenital malformation in offspring using The Health Improvement Network primary care database ( see page 981 ). Their findings showed that gestational exposure to commonly used asthma medications seems to be safe, although a moderate teratogenic risk of cromones cannot be excluded. This is important information for many doctors, mainly pulmonologists and allergologists involved in the treatment of asthma in pregnant women. It indicates that we can approach the pregnant patient with asthma in the traditional manner, without major concerns and using all the available treatment options with the exclusion of cromones which, in any case, currently represent an unusual therapeutic choice.

The results of this study enable us to reassure our pregnant patients. We have all found that one of the most complicated aspects of the work of a chest physician is to convince a pregnant patient with asthma to adhere to prescribed therapy. Several surveys have shown that women decrease and/or stop asthma medications during early pregnancy, probably because they are concerned about the safety of asthma medications during pregnancy.2–4 Conversely, physicians appear to be reluctant to prescribe asthma medications for pregnant women. A multicentre study found that pregnant women with asthma were significantly less likely to be prescribed corticosteroids in the emergency department: only 44% of pregnant women were treated with corticosteroids compared with 66% of non-pregnant women.5 Those who were admitted to hospital were less likely to be treated with corticosteroids at discharge and were almost three times …
Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis
Authors: Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen Gravallese, Diane Mathis, Christophe Benoist
Journal: The Journal of Experimental Medicine (2002)

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)–α was also required, although seemingly less critically than IL-1, because a proportion of TNF-α–deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFα for bone destruction. The variability in the requirement for TNF-α, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.
T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)-mediated apoptosis of CD4+ T cells from human immunodeficiency virus-infected persons.
Authors: J Estaquier, T Idziorek, W Zou, D Emilie, C M Farber, J M Bourez, J C Ameisen
Journal: The Journal of Experimental Medicine (1995)

Human immunodeficiency virus (HIV) infection leads to a progressive loss of CD4+ T helper (Th) type 1 cell-mediated immunity that is associated with defective in vitro CD4+ T cell proliferation and abnormal T cell death by apoptosis in response to T cell receptor (TCR) stimulation. Quantification of interleukin (IL)-2, interferon gamma, IL-4, IL-5, and IL-10 secretion by immunoassays, and of interferon gamma, IL-4 and IL-10 messenger RNA expression by competitive reverse transcriptase polymerase chain reaction after in vitro stimulation of the TCR revealed a similar Th1 cytokine profile in T cells from HIV-infected persons and from controls. These data indicated that the loss of CD4+ Th1 cell function in HIV-infected persons is not related to a Th1 to Th2 cytokine switch as previously proposed, but to a process of activation-induced death of CD4+ Th1 cells. Despite the absence of elevated levels of Th2 cytokines, apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented in vitro by antibodies to IL-10 or IL-4, two Th2 cytokines that downregulate Th1 cell responses, or by the addition of recombinant IL-12, a cytokine that upregulates Th1 functions. TCR-induced apoptosis of T cell hybridomas and preactivated T cells has been shown to involve the CD95 (Fas/Apo-1) molecule. CD4+ and CD8+ T cells from HIV-infected persons expressed high levels of the CD95 molecule, and, in contrast to T cells from controls, were highly sensitive to antibody-mediated CD95 ligation, which induced apoptosis in a percentage of T cells similar to that induced by TCR stimulation. As TCR-induced apoptosis, CD95-mediated apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented by the addition of recombinant IL-12. Together, these findings suggest that apoptosis of CD4+ T cells from HIV-infected persons involves an abnormal sensitivity to CD95 ligation, and to TCR stimulation in the presence of normal levels of Th2 cytokines. The preventive effect of IL-12 on both mechanisms has potential implications for the design of immunotherapy strategies aimed at the upregulation of CD4+ Th1 cell functions in AIDS.
Natural History of Brugada Syndrome
Authors: Silvia G. Priori, Carlo Napolitano, Maurizio Gasparini, Carlo Pappone, Paolo Della Bella, Umberto Giordano, Raffaella Bloise, Carla Giustetto, Roberto De Nardis, Massimiliano Grillo, Elena Ronchetti, Giovanna Faggiano, Janni Nastoli
Journal: Circulation (2002)

Background — Treatment of patients with Brugada syndrome is complicated by the incomplete information on the natural history of the disease related to the small number of cases reported. Furthermore, the value of programmed electrical stimulation (PES) for risk stratification is highly debated. The objective of this study was to search for novel parameters to identify patients at risk of sudden death. Methods and Results — Clinical data were collected for 200 patients (152 men, 48 women; age, 41±18 years) and stored in a dedicated database. Genetic analysis was performed, and mutations on the SCN5A gene were identified in 28 of 130 probands and in 56 of 121 family members. The life-table method of Kaplan-Meier used to define the cardiac arrest-free interval in patients undergoing PES failed to demonstrate an association between PES inducibility and spontaneous occurrence of ventricular fibrillation. Multivariate Cox regression analysis showed that after adjusting for sex, family history of sudden death, and SCN5A mutations, the combined presence of a spontaneous ST-segment elevation in leads V 1 through V 3 and the history of syncope identifies subjects at risk of cardiac arrest (HR, 6.4; 95% CI, 1.9 to 21; P &lt;0.002). Conclusions — The information on the natural history of patients obtained in this study allowed elaboration of a risk-stratification scheme to quantify the risk for sudden cardiac death and to target the use of the implantable cardioverter-defibrillator.
CULTURAL NUTRITION: ANTHROPOLOGICAL AND GEOGRAPHICAL THEMES
Authors: Louis Evan Grivetti
Journal: Annual Review of Nutrition (1981)

INTRODUCfION   47 CULTURAL NUTRITION: EMERGENCE OF A THEME   49 CULTURAL NUTRITION: RESEARCH APPROACHES   51 Environmentalism   51 Cultural Determinism   51 Cultural Ecology   52 Cultural History   52 Functionalism   52 Regional vs Local Studies   52 CULTURAL NUTRITION: SELECfED TOPICS   53 Evolution and Development of Human Dietaries   53 Religion and Restricted Dietaries   56 World Food Problem: Perspectives and Ethical Considerations   60