tbuckley/cabot-search huggingface dataset:
Wards will close and services will be cut to achieve 20bn efficiencies, say NHS finance directors
Authors: A. O'Dowd
Journal: BMJ (2011)

<h3>Background/aims</h3> To investigate the factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes. <h3>Methods</h3> Ninety-one eyes of 68 primary open-angle glaucoma patients were enrolled. Only eyes with a minimum of four good quality OCT-A and OCT scans of the optic nerve head acquired at least and with a minimum of 2 years follow-up were included. Area and angular circumference of MvD were analysed on en face images. Univariable and multivariable mixed effects models were constructed to identify the factors contributing to MvD area and angular circumference change over time. <h3>Results</h3> Peripapillary MvD was detected in 53 (58.2%) eyes at baseline and in an additional 17 (18.6%) eyes during follow-up, whereas MvD was not detected in 21 (23.0 %) eyes during the entire follow-up period. In multivariable analysis, worse baseline visual field (VF) mean deviation (MD) (ß=0.27, 95% CI 0.10 to 0.44, p=0.002), greater intraocular pressure (IOP) fluctuations (ß=0.86, 95% CI 0.24 to 1.48, p=0.007), higher peak IOP (ß=0.17, 95% CI −0.01 to 0.35, p=0.067) and greater number of IOP lowering medications (ß=1.36, 95% CI 0.67 to 2.05, p&lt;0.001) were associated with faster MvD area enlargement. Worse baseline VF MD and greater IOP fluctuation were also associated with significantly faster MvD circumferential enlargement in multivariable models. <h3>Conclusion</h3> Greater IOP fluctuation, higher peak IOP, worse baseline VF MD and greater number of glaucoma medications were significantly associated with MvD enlargement in glaucomatous eyes. The identification of factors associated with MvD enlargement may improve our understanding of the role of choroidal vasculature in glaucoma.
Gall stones and mortality: a study of all gall stone related deaths in a single health district.
Authors: P J Godrey, T Bates, M Harrison, M B King, N R Padley
Journal: Gut (1984)

In a prospective study of gall stone related deaths in a single Health District, the biliary tract was examined at necropsy in 1701 cases and 8078 death certificates were searched. Gall stones were identified as the cause of death in only 21 cases (0.26%) but in 291 subjects found to have gall stones or cholecystectomy at necropsy, the mortality was 3.4%. The necropsy prevalence of gall stones in the adult population was 17.1% but nine out of 10 subjects with gall stones had not had a cholecystectomy and women were three times more likely to have had their gall stones removed than men. There were five postoperative deaths (mean age 60 years) with an operative mortality for cholecystectomy in the district of 1.2%. Death due to unoperated gall stones was identified in 16 subjects, most of whom were very elderly women (mean age 81) but carcinoma of the gall bladder was only found in one woman of 90 with gall stones. The prevalence of gall stones rose with age in both sexes but the cholecystectomy rate per head of population at-risk declined sharply in the seventh decade in women and the eighth decade in men. There are a large number of people with unoperated gall stones in the population but gall stone related deaths are very uncommon. The cholecystectomy rate in Britain, however, seems to be rising and it is suggested that if this trend continues there may be an increased number of deaths.
The several Cs of translational clinical research
Authors: David G. Nathan
Journal: Journal of Clinical Investigation (2005)

Perhaps because I am a veteran of the "good old days" (they were really quite bad), young physicians who hope to become clinical investigators often ask me how they might establish their careers. Many are more than a little worried about their futures and often have trouble envisioning a career path that is financially secure for themselves and their families. The grumbling of clinical investigators a few years their senior enhances their angst. So I try to encourage these young physicians because I know the great intellectual (if not monetary) rewards of the field and because I know that the future of medicine absolutely depends on clinical investigators. The following is what I try to say to them.
Relative Respiratory Syncytial Virus Cytopathogenesis in Upper and Lower Respiratory Tract Epithelium
Authors: Hong Guo-Parke, Paul Canning, Isobel Douglas, Rémi Villenave, Liam G. Heaney, Peter V. Coyle, Jeremy D. Lyons, Michael D. Shields, Ultan F. Power
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Respiratory syncytial virus (RSV) is a major pathogen that primarily infects airway epithelium. Most infants suffer mild upper respiratory tract (URT) symptoms, whereas approximately one-third progress to lower respiratory tract (LRT) involvement. Despite the ubiquity of URT infection, little is known about the relative cytopathogenesis of RSV infection in infant URT and LRT.Objectives: This study aimed to compare RSV cytopathogenesis in nasal- and bronchial-derived epithelium from the same individuals using novel models derived from well-differentiated primary pediatric nasal (WD-PNECs) and bronchial epithelial cells (WD-PBECs).Methods: WD-PNECs and WD-PBECs were generated from nasal and bronchial brushes, respectively, and mock-infected or infected with RSV BT2a. RSV tropism, infectivity, cytopathology, growth kinetics, cell sloughing, apoptosis, and cytokine and chemokine responses were determined.Measurements and Main Results: RSV infection in both cultures was restricted to apical ciliated cells and occasional nonciliated cells but not goblet cells. It did not cause gross cytopathology. Infection resulted in apical release of progeny virus, increased apical cell sloughing, apoptosis, and occasional syncytia. RSV growth kinetics and peak titers were higher in WD-PBECs, coincident with higher ciliated cell contents, cell sloughing, and slightly compromised tight junctions. However, proinflammatory chemokine responses were similar for both cultures. Also, lambda IFNs, especially IL-29, were induced by RSV infection.Conclusions: RSV induced remarkably similar, albeit quantitatively lower, cytopathogenesis and proinflammatory responses in WD-PNECs compared with WD-PBECs that reproduce many hallmarks of RSV pathogenesis in infants. WD-PNECs may provide an authentic surrogate model with which to study RSV cytopathogenesis in infant airway epithelium.
Lung volume reduction surgery as an emergency and life-saving procedure
Authors: B Hansson, PG Jorens, P van Schil, W van Kerckhoven, F van den Brande, E Eyskens
Journal: European Respiratory Journal (1997)

Lung volume reduction surgery (LVRS) is emerging as a promising and unique therapeutic option for rigorously selected patients with severe debilitating emphysema. A 51 yr old man with generalized emphysema developed bilateral pneumothoraces during his first holiday abroad. Due to respiratory insufficiency, intubation and mechanical ventilation were necessary. In total, six chest tubes were inserted but massive air leak persisted and his respiratory condition deteriorated due to bronchopneumonia and sepsis. The patient was transferred to Belgium. As a last resort, bilateral LVRS was performed through a median sternotomy. The most diseased areas of the upper lobes containing the air leak were resected bilaterally and a pleurectomy was associated. Three months after operation, there was a remarkable improvement in spirometric values with an increase in forced expiratory volume in one second of almost 100%. The results were sustained after a follow-up of 18 months. In this dramatic case, lung volume reduction surgery proved to be effective, and was even a life saving procedure.
Spheroform: Therapeutic Spheroid‐Forming Nanotextured Surfaces Inspired by Desert Beetle <i>Physosterna cribripes</i>
Authors: Mihyun Lee, Kisuk Yang, Yong Hwa Hwang, Youngro Byun, Dong Yun Lee, Seung‐Woo Cho, Haeshin Lee
Journal: Advanced Healthcare Materials (2014)

An approach is presented to create arrays of quasi-spherical microdroplets by surfaces called "spheroform" inspired by micro-/nanostructures found in the back of the Namib desert beetle. Spheroform is fabricated by microarray formation of catecholamine polymers on the superhydrophobic background. Spheroform is able to precisely control spheroid sizes of therapeutic islet cells and mesenchymal stem cells. The therapeutic spheroids exhibit improved biochemical activities. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Surgical Treatment of Morbid Obesity
Authors: Peter F. Crookes
Journal: Annual Review of Medicine (2006)

Obesity is a major epidemic in developed countries. It induces or exacerbates hypertension, diabetes mellitus, obstructive sleep apnea, dyslipidemia, and many other disease processes, which cumulatively contribute to premature mortality on a scale rivaling that of smoking. At present, bariatric surgery is the only therapeutic modality that can produce sustained weight loss and halt or resolve comorbidities. This success results from the ability to perform the operation reliably, usually laparoscopically, with low mortality. The most commonly performed operation is Roux-en-Y gastric bypass. Other bypasses discussed in this review include biliopancreatic diversion with and without duodenal switch. Purely restrictive operations, especially adjustable gastric banding, have a lower risk but are somewhat less effective. We focus on the more controversial aspects of commonly accepted operations, including patient selection, the spectrum and frequency of complications, and the long-term outcome.
Nutrient-Wide Association Studies
Authors: John P. Forman, Walter C. Willett
Journal: Circulation (2012)

A part from the specific findings of this analysis, the authors encourage the use of what they call a nutrientwide association study, analogous to a genome-wide association study (GWAS), to investigate dietary determinants of health outcomes. 1Similar to the agnostic approach used in a GWAS, the features of their approach include the following:(1) the inclusion of all available nutrient exposures; (2) nonincorporation of previous knowledge; (3) adjustment of statistical tests for multiple comparisons; (4) division of the primary data set into training and test subsets; and (5) the use of a confirmatory data set.The primary objectives are to analyze all of the possible nutrient-disease hypotheses and to avoid false-positive conclusions.
Copenhagen hip and groin outcome score (HAGOS) in male soccer: reference values for hip and groin injury-free players
Authors: Kristian Thorborg, Sonia Branci, Frederik Stensbirk, Jesper Jensen, Per Hölmich
Journal: British Journal of Sports Medicine (2013)

Background/aim Reference values are needed in order to interpret the Copenhagen Hip and Groin Outcome Score (HAGOS) in male soccer players with hip and groin pain. The aim of this study was to establish reference values for HAGOS in hip and groin injury-free male soccer players. Methods We included 444 groin injury-free soccer players from 40 clubs (divisions 1–4) in Eastern Denmark, mean age (SD) 23.6 (4.4), training soccer 3.4 (1) times per week. All players were hip and groin injury-free at the time of inclusion (beginning of season, 2011). Results Of the 444 hip and groin injury-free players, 301 reported no hip and/or groin pain in either the present or the previous season, and 143 reported that they had experienced hip and/or groin pain in the previous season. Players (n=143) with hip and groin pain in the previous season displayed lower scores than players without (n=301), for all HAGOS subscales (p&lt;0.001). Age and playing level were not related to HAGOS. The 95% reference ranges for HAGOS subscales in hip and groin injury-free soccer players, with no pain in the previous or present season (n=301), are: pain: 80.1–100, symptoms: 64.3–100, activities of daily living: 80.3–100, sport and recreational activities: 71.9–100, participation in physical activity: 75–100 and quality of living: 75–100. Conclusions Lower HAGOS subscales are seen in soccer players who have experienced hip and/or groin pain in the previous season, compared with those who have not. Median HAGOS subscale scores in hip and groin injury-free soccer players are in proximity to the maximum score (100 points).
Flt-4–Positive Endothelial Cell Density and Its Clinical Significance in Non–Small Cell Lung Cancer
Authors: Fengshi Chen, Kazumasa Takenaka, Eiji Ogawa, Kazuhiro Yanagihara, Yosuke Otake, Hiromi Wada, Fumihiro Tanaka
Journal: Clinical Cancer Research (2004)

Experimental studies have revealed that fms-like tyrosine kinase (Flt)-4 plays important roles in lymphangiogenesis in malignant tumors, but the clinical significance remains unclear. We assessed Flt-4 expression in tumor cells and in endothelial cells in correlation with clinical outcomes in non-small cell lung cancer (NSCLC).A total of 206 consecutive patients with resected pathological stage I-IIIA NSCLC were reviewed. Expression of Flt-4 was examined immunohistochemically, and Flt-4-positive microvessels were quantitatively evaluated (Flt-4-positive endothelial cell density).There was no significant correlation between Flt-4-positive endothelial cell density and any characteristic of patients including nodal metastases. A significant correlation between Flt-4-positive endothelial cell density and Flt-4 status in tumor cells was documented (P < 0.001), but there was no significant difference in the mean Flt-4-positive endothelial cell density according to vascular endothelial growth factor-C or -D status in tumor cells. The 5-year survival rate for higher Flt-4-positive endothelial cell density tumor (56.4%) was significantly lower than that of lower Flt-4-positive endothelial cell density tumor (69.0%, P = 0.046); the prognostic significance was enhanced in pIIIA-N2 patients (5-year survival rates, 18.8% for higher Flt-4-positive endothelial cell density tumor and 50.0% for lower Flt-4-positive endothelial cell density tumor, respectively; P = 0.012). A multivariate analysis confirmed that higher Flt-4-positive endothelial cell density was a significant and independent prognostic factor (P = 0.019). CD34-positive vessel density or Flt-4 status in tumor cells was not a significant prognostic factor.Flt-4-positive endothelial cell density, not Flt-4 status in tumor cells, was a significant prognostic factor in NSCLC.
Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype.
Authors: J Sprent, M Schaefer, M Hurd, C D Surh, Y Ron
Journal: The Journal of Experimental Medicine (1991)

To seek information on the potential lifespan of normal B and T lymphocytes, lymph node (LN) cells from unprimed mice were transferred to H-2-identical severe combined immunodeficiency (SCID) hosts. At a population level, the donor B and T cells survived for at least 10 mo post-transfer with no reduction in their numbers. In terms of antibody production, LN-injected SCID mice remained responsive to several different antigens and contained unprimed precursors of memory cells for greater than or equal to 6 mo post-transfer. Most of the B and T cells recovered from LN-injected SCID mice expressed the typical virgin phenotype of mature lymphocytes from young mice. These findings suggest that many of the transferred lymphocytes might have remained in interphase as virgin cells from the time of injection. This did not apply to all of the transferred cells, however, because 20-40% of CD4+ cells from long-term SCID hosts displayed a memory phenotype, 7% incorporated 2-bromodeoxyuridine over 5 d, and total numbers of B and T cells increased gradually (twofold) over a 10-mo period. Collectively, the data favor the view that the pool of mature B and T cells in adult mice is largely self sufficient: some of the cells proliferate, presumably in response to environmental antigens, but many mature cells can remain quiescent for prolonged periods. Input of new cells from the primary lymphoid organs continues, but at a much reduced rate relative to young life.
Measurement and analysis of chemically changed mineral fibers after experiments in vitro and in vivo.
Authors: K R Spurny
Journal: Environmental Health Perspectives (1983)

Asbestos, as well as other natural and man-made mineral fibers used for in vitro and in vivo experiments, must be described and defined physically and chemically as exactly as possible before any application. The interactions of fibers with the physical, chemical (air, water, etc.) and biological (cells, tissues, etc.) environments cause important changes in fiber chemistry and crystalline structure. Also, these should be detected as precisely as possible after each experiment. Our recent investigations dealt with the development of a complex analytical system for such measurements and with some applications of these analytical procedures for fibrous material sampled in the environment and from biological materials. Chemical and physical microanalyses of asbestos and glass fibers obtained by environmental sampling (air, water) and from human and animal tissue have shown chemical and crystalline changes in these particles. Scanning electron microscopy, electron microprobe analysis and mass spectrometry analysis were used in these investigations. A partial or total leakage of elements could be observed. The leakage of elements in fibers is of a statistical nature. Some fibers remained chemically unchanged; in some fibers some elements were partially leached; and in some fibers the majority of metallic elements were leached. The potential meaning of this effect is also discussed.
Oxidative modification of low-density lipoproteins by mesangial cells.
Authors: W F Keane, M P O'Donnell, B L Kasiske, Y Kim
Journal: Journal of the American Society of Nephrology (1993)

Because hypercholesterolemia and mesangial cell proliferation may be important in the pathogenesis of glomerulosclerosis, the effects of low-density lipoprotein (LDL) on human mesangial cell proliferation were evaluated. Native LDL (20 to 200 micrograms/mL) caused a dose-dependent increase in (3H)thymidine incorporation and increased mesangial cell numbers over 96 h. The mitogenic effect of LDL was partially blocked by the inhibition of cytochrome P-450, but not by the inhibition of cyclooxygenase or lipoxygenase pathways. Higher LDL concentrations (1,000 to 2,000 micrograms/mL) inhibited (3H)thymidine incorporation and reduced cell numbers, possibly as a result of the oxidative modification of LDL, indicated by an increase in thiobarbituric reactive substances. This peroxidation of LDL involved superoxide, because superoxide dismutase and butylated hydroxytoluene prevented it, whereas hydroxyl radical scavengers were without effect. Native LDL subjected to chemical oxidation by copper sulfate also inhibited mesangial cell proliferation. These results suggest that low concentrations of LDL may stimulate human mesangial cell proliferation, which may, in turn, cause the production of reactive oxygen molecules. Moreover, the oxidative modification of LDL may mediate the toxic effects of high LDL concentrations on human mesangial cells.
Audit of outpatients: entering the loop.
Authors: I K Crombie, H T Davies
Journal: BMJ (1991)

OBJECTIVE--To develop and test a method for routine data collection to observe current practice in outpatient pain clinics. DESIGN--Prospective questionnaire survey completed by consultants on each patient seen during October 1989 to May 1990. SETTING--Outpatient pain clinics of five teaching and five district general hospitals in Scotland and northern England. MAIN OUTCOME MEASURES--Number of new referrals and their source, and characteristics of pain at presentation. RESULTS--4354 forms were completed by 21 consultants over 29 weeks, corresponding to 2241 patients, of whom 981 were new referrals. The proportion of consultations at which new referrals were seen varied among the 10 clinics from 15% to 34%. The difference could not be accounted for by type of hospital. Sources of new referrals varied widely between the clinics (for example, range 22% to 78% for general practitioner referrals), as did new referrals by the type of pain (range 10.8% to 55.2% for low back pain, 10.5% to 32.5% for pain associated with surgery). However, these differences in types of patients seen could not be accounted for by variations in referral patterns among clinics. Problems identified in performing an audit of outpatients included the difficulty of obtaining firm diagnoses, the need for a method to link successive patient contacts, and the complexity of the presenting problem in many patients. CONCLUSIONS--It is possible to collect data for audit routinely in outpatient clinics. Observation of current practice in the clinics suggested possible unmet need or inappropriate management, which may require changes in practice.
Hyperinfectivity: A Critical Element in the Ability of V. cholerae to Cause Epidemics?
Authors: David M Hartley, J. Glenn Morris, David L Smith
Journal: PLoS Medicine (2005)

Cholera is an ancient disease that continues to cause epidemic and pandemic disease despite ongoing efforts to limit its spread. Mathematical models provide one means of assessing the utility of various proposed interventions. However, cholera models that have been developed to date have had limitations, suggesting that there are basic elements of cholera transmission that we still do not understand.