tbuckley/cabot-search huggingface dataset:
Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis
Authors: C E Wainwright, M W France, P O'Rourke, S Anuj, T J Kidd, M D Nissen, T P Sloots, C Coulter, Z Ristovski, M Hargreaves, B R Rose, C Harbour, S C Bell, K P Fennelly
Journal: Thorax (2009)

<h3>Background:</h3> <i>Pseudomonas aeruginosa</i> is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing. <h3>Methods:</h3> A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with <i>P aeruginosa</i>. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used. <h3>Results:</h3> <i>P aeruginosa</i> was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. <i>P aeruginosa</i> from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles ⩽3.3 μm aerodynamic diameter. <i>P aeruginosa</i>, <i>Burkholderia cenocepacia</i>, <i>Stenotrophomonas maltophilia</i> and <i>Achromobacter xylosoxidans</i> were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008). <h3>Conclusion:</h3> During coughing, patients with CF produce viable aerosols of <i>P aeruginosa</i> and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.
Effects of Gallbladder Function on Human Bile: Compositional and Structural Changes
Authors: Thomas R. Holzbach
Journal: Hepatology (1984)

Water and electrolyte absorption leading to increased intraluminal concentrations of lipids and other solutes comprise the primary physiologic effect of the gallbladder. The dynamics of enterohepatic circulation can lead to confinement of up to 60% of the bile acid pool within the gallbladder during prolonged fasting. This bile acid sequestration markedly reduces both the bile salt secretory rate and total solute concentration in comparison with the nonfasting state producing hepatic bile that is more than normally dilute especially in comparison with gallbladder bile. These conditions favor formation of small low-density vesicles in hepatic bile which are more buoyant than the concentrated biliary micelles found in anatomically dependent regions of the gallbladder. Vesicle formation in hepatic bile may explain the "stratification" phenomenon often noted within the gallbladder. This observation could be accounted for by inhomogeneous mixing of the dissimilar lipid particles, i.e., vesicles and micelles. If vesicles are present and stratified as presumed, the overall cholesterol transporting capability of the total lipid particles, including these regionalized vesicles, would be considerably enhanced. The net effect of this process would lead to an overestimation of the true degree of metastable cholesterol supersaturation for the biliary micellar system within the gallbladder on the incorrect assumption of homogeneous mixing of lipids.
Half a million hours of rugby football. The injuries.
Authors: J. P. Sparks
Journal: British Journal of Sports Medicine (1981)

In 30 seasons at Rugby School half a million hours of Rugby football have led to 9,885 injuries, an incidence of 197.7 injuries per 10.000 player hours. This incidence is compared with those from other school games, and with those of other series of Rugby football injuries. The injuries are compared regionally with those of other series, and the more important are listed.
INFECTION OF CHIMPANZEES BY HUMAN T-LYMPHOTROPIC RETROVIRUSES IN BRAIN AND OTHER TISSUES FROM AIDS PATIENTS
Authors: D.Carleton Gajdusek, ClarenceJ. Gibbs, Pamela Rodgers-Johnson, HerbertL. Amyx, DavidM. Asher, LeonG. Epstein, PremS. Sarin, RobertC. Gallo, Annette Maluish, LarryO. Arthur, L. Montagnier, Donna Mildvan
Journal: The Lancet (1985)
Construct Validity: Advances in Theory and Methodology
Authors: Milton E. Strauss, Gregory T. Smith
Journal: Annual Review of Clinical Psychology (2008)

Measures of psychological constructs are validated by testing whether they relate to measures of other constructs as specified by theory. Each test of relations between measures reflects on the validity of both the measures and the theory driving the test. Construct validation concerns the simultaneous process of measure and theory validation. In this article, we review the recent history of validation efforts in clinical psychological science that has led to this perspective, and we review the following recent advances in validation theory and methodology of importance for clinical researchers. These are: the emergence of nonjustificationist philosophy of science; an increasing appreciation for theory and the need for informative tests of construct validity; valid construct representation in experimental psychopathology; the need to avoid representing multidimensional constructs with a single score; and the emergence of effective new statistical tools for the evaluation of convergent and discriminant validity.
Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study
Authors: Na Lu, Maureen Dubreuil, Yuqing Zhang, Tuhina Neogi, Sharan K Rai, Alberto Ascherio, Miguel A Hernán, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2015)

While gout is associated with cardiovascular (CV)-metabolic comorbidities and their sequelae, the antioxidant effects of uric acid may have neuroprotective benefits. We evaluated the potential impact of incident gout on the risk of developing Alzheimer's disease (AD) in a general population context.We conducted an age-matched, sex-matched, entry-time-matched and body mass index (BMI)-matched cohort study using data from The Health Improvement Network, an electronic medical record database representative of the UK general population, from 1 January 1995 to 31 December 2013. Up to five non-gout individuals were matched to each case of incident gout by age, sex, year of enrolment and BMI. We compared incidence rates of AD between the gout and comparison cohorts, excluding individuals with prevalent gout or dementia at baseline. Multivariate hazard ratios (HRs) were calculated, while adjusting for smoking, alcohol use, physician visits, social deprivation index, comorbidities and medication use. We repeated the same analysis among patients with incident osteoarthritis (OA) as a negative control exposure.We identified 309 new cases of AD among 59 224 patients with gout (29% female, mean age 65 years) and 1942 cases among 238 805 in the comparison cohort over a 5-year median follow up (1.0 vs 1.5 per 1000 person-years, respectively). Univariate (age-matched, sex-matched, entry-time-matched and BMI-matched) and multivariate HRs for AD among patients with gout were 0.71 (95% CI 0.62 to 0.80) and 0.76 (95% CI 0.66 to 0.87), respectively. The inverse association persisted among subgroups stratified by sex, age group (<75 and ≥75 years), social deprivation index and history of CV disease. The association between incident OA and the risk of incident AD was null.These findings provide the first general population-based evidence that gout is inversely associated with the risk of developing AD, supporting the purported potential neuroprotective role of uric acid.
Economic evaluation using decision analytical modelling: design, conduct, analysis, and reporting
Authors: S. Petrou, A. Gray
Journal: BMJ (2011)

Evidence relating to healthcare decisions often comes from more than one study. Decision analytical modelling can be used as a basis for economic evaluations in these situations. Economic evaluations are increasingly conducted alongside randomised controlled trials, providing researchers with individual patient data to estimate cost effectiveness.1 However, randomised trials do not always provide a sufficient basis for economic evaluations used to inform regulatory and reimbursement decisions. For example, a single trial might not compare all the available options, provide evidence on all relevant inputs, or be conducted over a long enough time to capture differences in economic outcomes (or even measure those outcomes).2 In addition, reliance on a single trial may mean ignoring evidence from other trials, meta-analyses, and observational studies. Under these circumstances, decision analytical modelling provides an alternative framework for economic evaluation. Decision analytical modelling compares the expected costs and consequences of decision options by synthesising information from multiple sources and applying mathematical techniques, usually with computer software. The aim is to provide decision makers with the best available evidence to reach a decision—for example, should a new drug be adopted? Following on from our article on trial based economic evaluations,1 we outline issues relating to the design, conduct, analysis, and reporting of economic evaluations using decision analytical modelling. #### Glossary of terms
Membrane-Bound Protein Kinase A Inhibits Smooth Muscle Cell Proliferation In Vitro and In Vivo by Amplifying cAMP–Protein Kinase A Signals
Authors: Ciro Indolfi, Eugenio Stabile, Carmela Coppola, Adriana Gallo, Cinzia Perrino, Giovanna Allevato, Luigi Cavuto, Daniele Torella, Emilio Di Lorenzo, Giancarlo Troncone, Antonio Feliciello, Enrico Vittorio Avvedimento, Massimo Chiariello
Journal: Circulation Research (2001)

Abstract —cAMP-dependent protein kinase is anchored to discrete cellular compartments by a family of proteins, the A-kinase anchor proteins (AKAPs). We have investigated in vivo and in vitro the biological effects of the expression of a prototypic member of the family, AKAP75, on smooth muscle cells. In vitro expression of AKAP75 in smooth muscle cells stimulated cAMP-induced transcription, increased the levels of the cyclin-dependent kinase-2 inhibitor p27 kip1 , and reduced cell proliferation. In vivo expression of exogenous AKAP75 in common carotid arteries, subjected to balloon injury, significantly increased the levels of p27 kip1 and inhibited neointimal hyperplasia. Both the effects in smooth muscle cells in vitro and in carotid arteries in vivo were specifically dependent on the amplification of cAMP-dependent protein kinase (PKA) signals by membrane-bound PKA, as indicated by selective loss of the AKAP75 biological effects in mutants defective in the PKA anchor domain or by suppression of AKAP effects by the PKA-specific protein kinase inhibitor. These data indicate that AKAP proteins selectively amplify cAMP-PKA signaling in vitro and in vivo and suggest a possible target for the inhibition of the neointimal hyperplasia after vascular injury.
Cardiac Care for Older Adults
Authors: Daniel E. Forman, Michael W. Rich, Karen P. Alexander, Susan Zieman, Mathew S. Maurer, Samer S. Najjar, Joseph C. Cleveland, Harlan M. Krumholz, Nanette K. Wenger
Journal: Journal of the American College of Cardiology (2011)

Recent decades have witnessed striking growth in the number of older adults both in the United States and throughout much of the world, largely due to improved public health, nutrition, and medical care. Between 2000 and 2030, the proportion of the world's population age 65 years and older is
Correspondence re: S. Heckl et al., Intracellular Visualization of Prostate Cancer Using Magnetic Resonance Imaging. Cancer Res 2003;63:4766–72.
Authors: Eric Wickstrom
Journal: Cancer Research (2004)

LetterMy colleagues and I read with great interest the paper on magneticresonance imaging of MYC mRNA in prostate cancer xenografts (1).This approach has great potential for noninvasive diagnosis of onco-gene expression. We wonder whether some supplementary material isavailable concerning the chemical characterization of the startingmaterials and the oxidation products between the cysteine amidegroups of TQVKIWFQNRRMKQKK-Cys-NH
t(7;12)(q36;p13) and t(7;12)(q32;p13) – translocations involving ETV6 in children 18 months of age or younger with myeloid disorders
Authors: RM Slater, Ev Drunen, WG Kroes, D Olde Weghuis, E van den Berg, EM Smit, A van der Does-van den Berg, E van Wering, K Hählen, AJ Carroll, SC Raimondi, HB Beverloo
Journal: Leukemia (2001)
From Nicotine to Breast Cancer, Implications of Cholinergic Receptor Pathway
Authors: R. I. Linnoila
Journal: JNCI Journal of the National Cancer Institute (2010)

Nicotine is the most important pharmacologically active compound in all forms of tobacco smoke because of its interaction with cholinergic receptors. In the current issue of the Journal, a research article by Lee et al. (1) and a brief communication by Falvella et al. (2) use different approaches to contribute to a better understanding of the roles of nicotine receptors and the biological basis that underlies the environmental and genetic components of smoking-related cancer risk. Two types of acetylcholine receptors (AChRs) exist: the nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs). The nAChRs are ligand-gated ion channels and form pentameric complexes that consist of four related but genetically and immunologically distinct subunits: a, b, g, and d (3). The a9-nAChR, a known homopentamer that plays a central role in coordinating keratinocyte adhesion and motility during wound healing (4), is encoded by a gene (CHRNA9) on human chromosome 4p (5). Lee et al. (1) showed that a9-nAChRs were ubiquitously expressed in many epithelial and cancer cell lines from lung and breast and that most of the same cell lines also expressed a5- and a10-nAChRs. The a9-nAChRs were also present in primary tumors and nonmalignant breast tissue obtained from patients; however, cancers had increased a9-nAChR expression compared with the surrounding
A functional SNP in PSMA6 confers risk of myocardial infarction in the Japanese population
Authors: Kouichi Ozaki, Hiroshi Sato, Aritoshi Iida, Hiroya Mizuno, Takahiro Nakamura, Yoshinari Miyamoto, Atsushi Takahashi, Tatsuhiko Tsunoda, Shiro Ikegawa, Naoyuki Kamatani, Masatsugu Hori, Yusuke Nakamura, Toshihiro Tanaka
Journal: Nature Genetics (2006)
Targeting the insulin-like growth factor receptor and Src signaling network for the treatment of non-small cell lung cancer
Authors: Hye-Young Min, Hye Jeong Yun, Ji-Sun Lee, Hyo-Jong Lee, Jaebeom Cho, Hyun-Ji Jang, Shin-Hyung Park, Diane Liu, Seung-Hyun Oh, J. Jack Lee, Ignacio I. Wistuba, Ho-Young Lee
Journal: Molecular Cancer (2015)

Therapeutic interventions in the insulin-like growth factor receptor (IGF-1R) pathway were expected to provide clinical benefits; however, IGF-1R tyrosine kinase inhibitors (TKIs) have shown limited antitumor efficacy, and the mechanisms conveying resistance to these agents remain elusive.The expression and activation of the IGF-1R and Src were assessed via the analysis of a publicly available dataset, as well as immunohistochemistry, Western blotting, RT-PCR, and in vitro kinase assays. The efficacy of IGF-1R TKIs alone or in combination with Src inhibitors was analyzed using MTT assays, colony formation assays, flow cytometric analysis, and xenograft tumor models.The co-activation of IGF-1R and Src was observed in multiple human NSCLC cell lines as well as in a tissue microarray (n = 353). The IGF-1R and Src proteins mutually phosphorylate on their autophosphorylation sites. In high-pSrc-expressing NSCLC cells, linsitinib treatment initially inactivated the IGF-1R pathway but led a Src-dependent reactivation of downstream effectors. In low-pSrc-expressing NSCLC cells, linsitinib treatment decreased the turnover of the IGF-1R and Src proteins, ultimately amplifying the reciprocal co-activation of IGF-1R and Src. Co-targeting IGF-1R and Src significantly suppressed the proliferation and tumor growth of both high-pSrc-expressing and low-pSrc-expressing NSCLC cells in vitro and in vivo and the growth of patient-derived tissues in vivo.Reciprocal activation between Src and IGF-1R occurs in NSCLC. Src causes IGF-1R TKI resistance by acting as a key downstream modulator of the cross-talk between multiple membrane receptors. Targeting Src is a clinically applicable strategy to overcome resistance to IGF-1R TKIs.
The ‘Best Practice Guide to Conservative Management of Patellofemoral Pain’: incorporating level 1 evidence with expert clinical reasoning
Authors: Christian John Barton, Simon Lack, Steph Hemmings, Saad Tufail, Dylan Morrissey
Journal: British Journal of Sports Medicine (2015)

Patellofemoral pain (PFP) is both chronic and prevalent; it has complex aetiology and many conservative treatment options.Develop a comprehensive contemporary guide to conservative management of PFP outlining key considerations for clinicians to follow.Mixed methods.We synthesised the findings from six high-quality systematic reviews to September 2013 with the opinions of 17 experts obtained via semistructured interviews. Experts had at least 5 years clinical experience with PFP as a specialist focus, were actively involved in PFP research and contributed to specialist international meetings. The interviews covered clinical reasoning, perception of current evidence and research priorities.Multimodal intervention including exercise to strengthen the gluteal and quadriceps musculature, manual therapy and taping possessed the strongest evidence. Evidence also supports use of foot orthoses and acupuncture. Interview transcript analysis identified 23 themes and 58 subthemes. Four key over-arching principles to ensure effective management included-(1) PFP is a multifactorial condition requiring an individually tailored multimodal approach. (2) Immediate pain relief should be a priority to gain patient trust. (3) Patient empowerment by emphasising active over passive interventions is important. (4) Good patient education and activity modification is essential. Future research priorities include identifying risk factors, testing effective prevention, developing education strategies, evaluating the influence of psychosocial factors on treatment outcomes and how to address them, evaluating the efficacy of movement pattern retraining and improving clinicians' assessment skills to facilitate optimal individual prescription.Effective management of PFP requires consideration of a number of proven conservative interventions. An individually tailored multimodal intervention programme including gluteal and quadriceps strengthening, patellar taping and an emphasis on education and activity modification should be prescribed for patients with PFP. We provide a 'Best Practice Guide to Conservative Management of Patellofemoral Pain' outlining key considerations.
Novel Chromosomal Rearrangements and Break Points at the t(6;9) in Salivary Adenoid Cystic Carcinoma: Association with <i>MYB</i>–<i>NFIB</i> Chimeric Fusion, <i>MYB</i> Expression, and Clinical Outcome
Authors: Yoshitsugu Mitani, Pulivarthi H. Rao, P. Andrew Futreal, Dianna B. Roberts, Philip J. Stephens, Yi-Jue Zhao, Li Zhang, Mutsumi Mitani, Randal S. Weber, Scott M. Lippman, Carlos Caulin, Adel K. El-Naggar
Journal: Clinical Cancer Research (2011)

Abstract Objective: To investigate the molecular genetic heterogeneity associated with the t(6:9) in adenoid cystic carcinoma (ACC) and correlate the findings with patient clinical outcome. Experimental Design: Multimolecular and genetic techniques complemented with massive pair-ended sequencing and single-nucleotide polymorphism array analyses were used on tumor specimens from 30 new and 52 previously analyzed fusion transcript–negative ACCs by reverse transcriptase PCR (RT-PCR). MYB mRNA expression level was determined by quantitative RT-PCR. The results of 102 tumors (30 new and 72 previously reported cases) were correlated with the clinicopathologic factors and patients' survival. Results: The FISH analysis showed 34 of 82 (41.5%) fusion-positive tumors and molecular techniques identified fusion transcripts in 21 of the 82 (25.6%) tumors. Detailed FISH analysis of 11 out the 15 tumors with gene fusion without transcript formation showed translocation of NFIB sequences to proximal or distal sites of the MYB gene. Massive pair-end sequencing of a subset of tumors confirmed the proximal translocation to an NFIB sequence and led to the identification of a new fusion gene (NFIB–AIG1) in one of the tumors. Overall, MYB–NFIB gene fusion rate by FISH was in 52.9% whereas fusion transcript forming incidence was 38.2%. Significant statistical association between the 5′ MYB transcript expression and patient survival was found. Conclusions: We conclude that: (i) t(6;9) results in complex genetic and molecular alterations in ACC, (ii) MYB–NFIB gene fusion may not always be associated with chimeric transcript formation, (iii) noncanonical MYB–NFIB gene fusions occur in a subset of tumors, (iv) high MYB expression correlates with worse patient survival. Clin Cancer Res; 17(22); 7003–14. ©2011 AACR.
Wall stress and patterns of hypertrophy in the human left ventricle.
Authors: W Grossman, D Jones, L P McLaurin
Journal: Journal of Clinical Investigation (1975)

It is generally recognized that chronic left ventricular (LV) pressure overload results primarily in wall thickening and concentric hypertrophy, while chronic LV volume overload is characterized by chamber enlargement and an eccentric pattern of hypertrophy. To assess the potential role of the hemodynamic factors which might account for these different patterns of hypertrophy, we measured LV wall stresses throughout the cardiac cycle in 30 patients studied at the time of cardiac catheterization. The study group consisted of 6 subjects with LV pressure overload, 18 with LV volume overload, and 6 with no evidence of heart disease (control). LV pressure, meridional wall stress (sigman), wall thickness (h), and radius (R) were measured in each patient throughout the cardiac cycle. For patients with pressure overload, LV peak systolic and end diastolic pressures were significantly increased (220 plus or minus 6/23 plus or minus 3 mm Hg) compared to control (117 plus or minus 7/10 plus or minus 1 mm Hg, P less than 0.01 for each). However, peak systolic and end diastolic (sigman) were normal (161 plus or minus 24/23 plus or minus 3 times 10-3 dyn/cm-2) compared to control (151 plus or minus 14/17 plus or minus 2 times 10-3 dyn/cm-2, NS), reflecting the fact that the pressure overload was exactly counterbalanced by increased wall thickness (1.5 plus or minus 0.1 cm for pressure overload vs. 0.8 plus or minus 0.1 cm for control, P less than 0.01). For patients with volume overload, peak systolic (sigman) was not significantly different from control, but end diastolic (sigmam) was consistently higher than normal (41 plus or minus 3 times 10-3 dyn/cm-2 for volume overload, 17 plus or minus 2 times 10-3 dyn/cm-2 for control, P less than 0.01). LV pressure overload was associated with concentric hypertrophy, and an increased value for the ratio of wall thickness to radius (h/R ratio). In contrast, LV volume overload was associated with eccentric hypertrophy, and a normal h/R ratio. These data suggest the hypothesis that hypertrophy develops to normalize systolic but not diastolic wall stress. We propose that increased systolic tension development by myocardial fibers results in fiber thickening just sufficient to return the systolic stress (force per unit cross-sectional area) to normal. In contrast, increased resting or diastolic tension appears to result in gradual fiber elongation or lengthening which improves efficiency of the ventricular chamber but cannot normalize the diastolic wall stress.