tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Reduced Ventricular Volumes and Improved Systolic Function With Cardiac Resynchronization Therapy: A Randomized Trial Comparing Simultaneous Biventricular Pacing, Sequential Biventricular Pacing, and Left Ventricular Pacing”
Authors: Rajni K. Rao, Esperanza Viloria, Elyse Foster, Uday N. Kumar, Jill Schafer, David De Lurgio
Journal: Circulation (2008)

We thank Drs Hamilton and Filardo for their interest in our work. 1n a prospective randomized trial in which the same patient is subjected to repeated measurements over time, missing data and repeated measures are known statistical problems for which it is difficult to account.As suggested by Drs Hamilton and Filardo, a longitudinal analysis is the most appropriate model for accounting for missing data. 2 A longitudinal model was used initially to analyze the data, essentially yielded similar clinical results, and did not result in any substantive change to our published conclusions.However, at the suggestion of our reviewers and other readers, we presented the data in a way that is more conventional and easily understood and that facilitates comparison with other trials.To account for repeated measures in the same patient, paired data were used in the published analysis.This should have been more clearly stated in our Methods.We would be happy to provide the data as analyzed by the longitudinal model.With regard to multiplicity, it is correct that additional tests increase the likelihood of type I error.Although it is common practice to provide a comprehensive analysis using the available data, our analysis should be considered exploratory in nature.The limitations of multiple retrospective analyses should have been clearly emphasized; however, the results are valid and are derived from a relatively large trial that directly compared all 3 pacing modalities in a prospective randomized fashion.
Prediction of Coronary Heart Disease in Middle-Aged Adults With Diabetes
Authors: Aaron R. Folsom, Lloyd E Chambless, Bruce B. Duncan, Adam C. Gilbert, James S. Pankow
Journal: Diabetes Care (2003)

OBJECTIVE—To determine the 10-year probability of coronary heart disease (CHD) in diabetic adults and how well basic and novel risk factors predict CHD risk. RESEARCH DESIGN AND METHODS—We measured risk factors in 14,054 participants (1,500 with diabetes) initially free of CHD in the Atherosclerosis Risk in Communities study from 1987 to 1989 and followed them prospectively for CHD incidence through 1998. We used proportional hazards regression models and receiver operating characteristic (ROC) curves for CHD risk prediction. RESULTS—Based on our model using basic risk factors (age, race, total and HDL cholesterol, systolic blood pressure, antihypertensives, and smoking status), ∼61% of diabetic women and 86% of diabetic men had a predicted 10-year CHD probability ≥10%. This CHD risk-prediction model had an area under the ROC curve of 0.72 in diabetic women and 0.67 in diabetic men. Novel risk factors or subclinical disease markers individually added only modest predictivity, but the addition of multiple markers (BMI, waist-to-hip ratio, Keys dietary score, serum albumin and creatinine, factor VIII, white blood cell count, left ventricular hypertrophy determined by electrocardiogram, and carotid intima-media thickness) increased the area under the curve by ∼10%. CONCLUSIONS—Although all diabetic adults are at high risk for CHD, their variation in CHD risk can be predicted moderately well by basic risk factors. No single novel risk marker greatly enhanced absolute CHD risk assessment, but a battery of novel markers did. Our model can provide estimates of CHD risk for the primary prevention of this disease in people with type 2 diabetes.
Lung volumes and flow rates in black and white subjects
Authors: N. L. Lapp, H. E. Amandus, R. Hall, W. K. C. Morgan
Journal: Thorax (1974)

<b>Lapp, N. L., Amandus, H. E., Hall, R., and Morgan, W. K. C. (1974).</b><i>Thorax</i>, <b>29</b>, 185-188. <b>Lung volumes and flow rates in black and white subjects.</b> It has been known for some time that the vital capacity and forced expiratory volume in one second of black subjects are about 12% lower than those of whites of the same age and height. In the present study, total lung capacity and residual volume were also shown to be decreased by about the same percentage. Expiratory flow rates were similarly decreased, but when the difference in lung size was evened out by matching black and white subjects of the same total lung capacity, no significant differences in flow rates were observed.
Muscle dysmorphia: a new syndrome in weightlifters
Authors: P Y L Choi, H G Pope, R Olivardia
Journal: British Journal of Sports Medicine (2002)

AUTHOR:e-mail address please Recently more men have reported a desire for larger, more muscular bodies. Muscle dysmorphia (MD) is a new syndrome in which individuals (usually men), although highly muscular, have a pathological belief that they are of very small musculature. As more men are motivated to take up training with weights in order to develop greater musculature, more cases of MD are likely to be encountered. A greater understanding and awareness of the syndrome are therefore needed. Therefore the aim of this study was to investigate perceptions of physical self in male weightlifters, one group with MD (n = 24) and one without (n = 30). Between group comparisons were made using the multidimensional body-self relations questionnaire. The findings confirm the nature of the disorder in that those with MD syndrome have poorer body image and are less happy with their bodies. Moreover, in addition to a desire for greater muscularity, they are very concerned not to gain fat. The results also suggest that future research into perceptions of specific body parts and health is warranted.
Roles of Akt/Pkb and Ikk Complex in Constitutive Induction of Nf–κB in Hepatocellular Carcinomas of Transforming Growth Factor α/C– Myc Transgenic Mice
Authors: Valentina Factor, Aundrea L. Oliver, Ganesh R. Panta, Snorri S. Thorgeirsson, Gail E. Sonenshein, Marcello Arsura
Journal: Hepatology (2001)

NF-kappaB regulates liver cell death during development, regeneration, and neoplastic transformation. For example, we showed that oncogenic Ras- or Raf-mediated transformation of rat liver epithelial cells (RLEs) led to altered NF-kappaB regulation through IKK complex activation, which rendered these cells more resistant to TGF-beta1-induced apoptosis. Thus, based on these findings, we sought to determine whether NF-kappaB could also be involved in tumor growth of liver cells in vivo. Hepatocellular carcinomas (HCCs) derived from bitransgenic mice harboring TGF-alpha and c-myc transgenes targeted specifically to the liver were compared with HCCs from c-myc single transgenic mice. Tumors from bitransgenic mice are characterized by a higher frequency of appearance, lower apoptotic index, and a higher rate of cell proliferation. Here we show that NF-kappaB is activated in HCCs of double TGF-alpha/c-myc transgenic mice, but not of c-myc single transgenic mice, suggesting that TGF-alpha mediates induction of NF-kappaB. Activation of the IKK complex was observed in the HCCs of double TGF-alpha/c-myc transgenic mice, implicating this pathway in NF-kappaB induction. Lastly, activation of the Akt/protein kinase B (PKB), which has recently been implicated in NF-kappaB activation by PDGF, TNF-alpha, and Ras, was also observed. Importantly, human HCC cell lines similarly displayed NF-kappaB activation. Thus, these studies elucidate an anti-apoptotic mechanism by a TGF-alpha-Akt/PKB-IKK pathway, which likely contributes to survival and proliferation, thereby accelerating c-myc-induced liver neoplastic development in vivo.
Spinal injuries in sports in the UK.
Authors: J R Silver
Journal: British Journal of Sports Medicine (1993)

An analysis was made of 150 rugby, trampolining, gymnastics and horse-riding injuries between 1952 and 1985, resulting in severe spinal injury. The individual analyses of the separate sports had been published previously. There are common factors to all these sports. Of those injured 121 had cervical injuries often as a result of participation in sport by young impetuous people, and causes included: inadequate supervision; motivation to attempt tasks beyond their abilities; a mismatch between the abilities of the performer and the task attempted.
Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial
Authors: Jan van Lunzen, Franco Maggiolo, José R Arribas, Aza Rakhmanova, Patrick Yeni, Benjamin Young, Jürgen K Rockstroh, Steve Almond, Ivy Song, Cindy Brothers, Sherene Min
Journal: The Lancet Infectious Diseases (2011)
Emerging Principles Governing the Operation of Neural Networks
Authors: P A Getting
Journal: Annual Review of Neuroscience (1989)

ical, and computational techniques have provided the tools to begin uncovering concepts underlying neural network function. This review is a summary of insights into the organization and operation of neural circuits acquired through application of these techniques to invertebrate and vertebrate systems. This review is not a survey of the vast variety of known neural networks but rather concentrates on emerging concepts applicable to net­ works in general. The first section provides a brief historical perspective. The second and third sections summarize two emerging concepts about the operation and modulation of neural circuits. The first concept is that the operation of a neural network depends upon interactions among mul­ tiple nonlinear processes at the cellular, synaptic, and network levels. The second concept is that modulation of these underlying processes can alter network operation. The final section suggests potentially profitable research directions for the future.
Antibody-dependent and PHA-induced cellular cytotoxicity in rheumatoid arthritis.
Authors: J N Rosenberg, H L Currey
Journal: Annals of the Rheumatic Diseases (1979)

One hundred and thirty nine observations of antibody-dependent cell mediated cytotoxicity (ADCC) were made on 77 with rheumatoid arthritis (RA) and 17 healthy controls. There were no differences in ADCC between these 2 groups or within the RA group with regard to disease activity, duration, seropositivity, or drug treatment. Sixty observations of phytohaemagglutinin induced cytotoxicity were made on 22 patients with RA and 10 healthy controls. Again there were no differences in cytotoxicity between the 2 groups.
A common inversion under selection in Europeans
Authors: Hreinn Stefansson, Agnar Helgason, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Gisli Masson, John Barnard, Adam Baker, Aslaug Jonasdottir, Andres Ingason, Vala G Gudnadottir, Natasa Desnica, Andrew Hicks, Arnaldur Gylfason, Daniel F Gudbjartsson, Gudrun M Jonsdottir, Jesus Sainz, Kari Agnarsson, Birgitta Birgisdottir, Shyamali Ghosh, Adalheidur Olafsdottir, Jean-Baptiste Cazier, Kristleifur Kristjansson, Michael L Frigge, Thorgeir E Thorgeirsson, Jeffrey R Gulcher, Augustine Kong, Kari Stefansson
Journal: Nature Genetics (2005)
Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides.
Authors: D H Carney, R Mann, W R Redin, S D Pernia, D Berry, J P Heggers, P G Hayward, M C Robson, J Christie, C Annable
Journal: Journal of Clinical Investigation (1992)

To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.
Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies
Authors: Gang Wang, Megan L McCain, Luhan Yang, Aibin He, Francesco Silvio Pasqualini, Ashutosh Agarwal, Hongyan Yuan, Dawei Jiang, Donghui Zhang, Lior Zangi, Judith Geva, Amy E Roberts, Qing Ma, Jian Ding, Jinghai Chen, Da-Zhi Wang, Kai Li, Jiwu Wang, Ronald J A Wanders, Wim Kulik, Frédéric M Vaz, Michael A Laflamme, Charles E Murry, Kenneth R Chien, Richard I Kelley, George M Church, Kevin Kit Parker, William T Pu
Journal: Nature Medicine (2014)
Lung Inhomogeneity in Patients with Acute Respiratory Distress Syndrome
Authors: Massimo Cressoni, Paolo Cadringher, Chiara Chiurazzi, Martina Amini, Elisabetta Gallazzi, Antonella Marino, Matteo Brioni, Eleonora Carlesso, Davide Chiumello, Michael Quintel, Guillermo Bugedo, Luciano Gattinoni
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Pressures and volumes needed to induce ventilator-induced lung injury in healthy lungs are far greater than those applied in diseased lungs. A possible explanation may be the presence of local inhomogeneities acting as pressure multipliers (stress raisers).Objectives: To quantify lung inhomogeneities in patients with acute respiratory distress syndrome (ARDS).Methods: Retrospective quantitative analysis of CT scan images of 148 patients with ARDS and 100 control subjects. An ideally homogeneous lung would have the same expansion in all regions; lung expansion was measured by CT scan as gas/tissue ratio and lung inhomogeneities were measured as lung regions with lower gas/tissue ratio than their neighboring lung regions. We defined as the extent of lung inhomogeneities the fraction of the lung showing an inflation ratio greater than 95th percentile of the control group (1.61).Measurements and Main Results: The extent of lung inhomogeneities increased with the severity of ARDS (14 ± 5, 18 ± 8, and 23 ± 10% of lung volume in mild, moderate, and severe ARDS; P < 0.001) and correlated with the physiologic dead space (r2 = 0.34; P < 0.0001). The application of positive end-expiratory pressure reduced the extent of lung inhomogeneities from 18 ± 8 to 12 ± 7% (P < 0.0001) going from 5 to 45 cm H2O airway pressure. Lung inhomogeneities were greater in nonsurvivor patients than in survivor patients (20 ± 9 vs. 17 ± 7% of lung volume; P = 0.01) and were the only CT scan variable independently associated with mortality at backward logistic regression.Conclusions: Lung inhomogeneities are associated with overall disease severity and mortality. Increasing the airway pressures decreased but did not abolish the extent of lung inhomogeneities.
Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators
Authors: T. van der Molen, D. S. Postma, M. O. Turner, B. M. Jong, J. L. Malo, K. Chapman, R. Grossman, C. S. de Graaff, R. A. Riemersma, M. R. Sears
Journal: Thorax (1997)

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.
Modelling the direct costs of chemotherapy-induced neutropenia treatment in Portuguese hospitals clinical practice
Authors: P. Saramago, V. Andreozzi, J. M. Ferreira, J. Félix
Journal: Journal of Clinical Oncology (2007)

17081 Background: Neutropenia (N) and febrile neutropenia (FN) are common adverse effects of chemotherapy, resulting in increased risk of infections and hospitalizations. Both conditions account for substantial health resource utilization (HRU). The objective of this study was to evaluate HRU patterns for patients (PTS) experiencing N or FN in “real world” practice and to model the corresponding HRU cost profiles. Methods: Breast and lung cancer PTS receiving granulocyte colony stimulating factor (GCSF) to treat chemotherapy- induced neutropenia (absolute neutrophil count [ANC] =1500 cell/μL) were selected from 8 Portuguese hospitals. In the absence of a comprehensive database PTS having neutropenia were originally identified from hospital pharmacies GCSF prescription lists; afterwards, HRU frequency (hospitalization, clinical visits, complementary examinations, medication, transfusions) in relation to N or FN (ANC =1000 cell/μL and body temperature= 38.5°C over one hour) was reviewed retrospectively from clinical records. Treatment costs attributed to N/FN were calculated by multiplying HRU frequency by unit costs from the Portuguese Ministry of Health costs database. To account for the skewed nature of the data costs were modelled using generalized linear models with gamma distribution and log link. Results: The study included 50 PTS with breast cancer and 48 with lung cancer. Mean (SD) age was 60.0 (12.5) years and 61.2% were women. Mean (SD) ANC at first N was 724 (433) cell/μL. FN (mean (SD) ANC 440 (370) cell/μL) was developed by 16.5% of PTS. Mean (SD) total cost of N treatment was 922 (1162) € (28% hospitalization, 5% clinical visits, 3% complementary examinations, 54% medication, 10% transfusions). Controlling for PTS clinical and sociodemographic characteristics, total treatment cost were 3.2 (95%CI:1.9–5.2) times higher for PTS with FN (p&lt;0.001) when compared to N PTS, 4.4% (95%CI: 0.1–7.7) greater for every 100 cell/μL decrease in ANC (p=0.03) and 2.5% (95%CI: 1.0–4.1) higher per additional year of age at N or FN diagnosis (p=0.002). Conclusions: Chemotherapy-induced neutropenia direct treatment costs were substantially incremented in febrile patients. [Table: see text]
A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2
Authors: Shinji Hadano, Collette K. Hand, Hitoshi Osuga, Yoshiko Yanagisawa, Asako Otomo, Rebecca S. Devon, Natsuki Miyamoto, Junko Showguchi-Miyata, Yoshinori Okada, Roshni Singaraja, Denise A. Figlewicz, Thomas Kwiatkowski, Betsy A. Hosler, Tally Sagie, Jennifer Skaug, Jamal Nasir, Robert H. Brown, Stephen W. Scherer, Guy A. Rouleau, Michael R. Hayden, Joh-E Ikeda
Journal: Nature Genetics (2001)