tbuckley/cabot-search huggingface dataset:
P69 The use of assessment in the delivery of bronchoscopy simulation- Are skills retained at assessment?
Authors: F Chowdhury, S Pathmanathan, I Aslam, J Hogg, J Kastelik
Journal: Thorax (2013)

<h3>Introduction</h3> Bronchoscopy simulation is becoming increasingly used as a tool to improve the confidence and knowledge of trainees, with the intention of increasing the speed of skill acquisition. Although this training has been shown to be effective, little research has been conducted into whether retention of skills occurs. Health Education Yorkshire and The Humber (HEYH) previously designed a mandatory programme to support the education of trainees and this has been extended to involve Anaesthetic trainees who often perform bronchoscopy. <h3>Methods</h3> 8 Respiratory, 8 Anaesthetic and 8 bronchoscopy naive trainees underwent the simulation course. They participated in an assessment two months later. All trainees had access to the simulator to practice in the two-month period. Pre/post course and post assessment Likert scale questionnaires were carried out to assess confidence. Dexterity was assessed with data generated from the Simbionix Simulator including: final navigation scores, bronchial segments identified correctly and number wall hits in the large airways. Knowledge testing was carried out using a preparing the patient metal algorithm taught during the course. The data generated was recorded on an assessment proforma entitled the Basic Bronchoscopy Simulation Assessment Tool (BBSAT). <h3>Results</h3> Statistically significant confidence levels were found in 9 domains in all trainees after the course. Confidence levels fell significantly after assessment in the majority of domains (Table1). Dexterity was retained at assessment, but a small fall in anatomical knowledge was demonstrated in Anaesthetic and Respiratory trainees. MCQ knowledge also showed a general decrease at assessment. The average BBSAT score was 67.2/72 (93%) indicating that all trainees had retained the basic level of skills required to perform bronchoscopy in a simulated environment. <h3>Conclusion</h3> Overall, skills and knowledge are retained to a level required to perform bronchoscopy in a simulated environment, however confidence of trainees is significantly affected at assessment two months later. We propose that trainees are provided with mandatory bronchoscopy simulation training accompanied by assessment to ensure that skills are retained. We believe that basic bronchoscopy should be mastered before diagnostic bronchoscopy is broached; hence the use of a mastery assessment similar to the BBSAT may helpful in guiding simulation-based assessment.
Mitochondrial DNA Length Variation and Heteroplasmy in Natural Populations of the European Sea Bass, Dicentrarchus labrax
Authors: D. Cesaroni, F. Venanzetti, G. Allegrucci, V. Sbordoni
Journal: Molecular Biology and Evolution (1997)

Mitochondrial DNA length variation in Dicentrarchus labrax is the outcome of the simultaneous variation in the copy number of two tandem repeat arrays located in the D-loop region. The repeated sequences, named R17 and R48, are 17 and 48 bp long, respectively. On the basis of 209 individuals collected in eight Mediterranean localities, length variation and its partitioning between the two repeat arrays have been characterized and quantified by means of frequency distributions of repeat copy number and genetic diversity estimates. The median copy numbers are 4 and 11 for the R17 and R48 repeat arrays, respectively. For both repeat arrays, continuity in step variation and the occurrence of both frequent and rare arrangements was observed. More than 50% of the individuals are heteroplasmic for up to four variants. Within populations, heteroplasmy ranges between 33.3% and 70.0% of the individuals. A large proportion of the total gene diversity (29.1%) occurs within individuals and the greatest proportion (66.6%) is found between individuals within populations, while only 4.3% is due to variation between populations. Although the interpopulation component of the diversity is rather low, the significant differentiation of the two Eastern populations from all the other Western samples suggests the occurrence of a phylogeographic component of the genetic divergence between the Mediterranean populations, which is only recognizable on a large geographic scale.
S32 The Relationship Between Exercise Capacity And Inflammatory Markers At Copd Exacerbation
Authors: A. Alahmari, B. Kowlessar, A. Patel, A. Mackay, S. Brill, J. Allinson, R. Singh, J. Wedzicha, G. Donaldson
Journal: Thorax (2014)

<h3>Introduction</h3> Chronic obstructive pulmonary disease (COPD) is characterised by breathlessness, fatigue and reduced daily activity which worsens acutely at exacerbation. A three year observational study has shown a reduction in 6MWT over time that correlates with increase over the same period in plasma Interleukin-6 and C-reactive protein (CRP) levels (Ferrari, Tanni <i>et al</i>. 2013). We therefore investigated whether acute changes in 6MWT at exacerbation were associated with changes in systemic inflammatory markers and the perception of fatigue. <h3>Methods</h3> Forty four patients from the London COPD cohort who had a mean age of (±SD) 71(±7) years; FEV<sub>1 </sub>52(±17)% predicted; male gender 72% and still smoking 30% were asked to performed a 6MWT and completed a FACIT-F questionnaire when stable (baseline) and 3 days after first presenting with the exacerbation. Blood was drawn for assay of CRP and fibrinogen. 6MWT was performed according to ATS protocols. Exacerbations were defined by our usual symptomatic criteria (Seemungal, Donaldson <i>et al</i>. 1998). High scores in the FACIT-F questionnaire indicate low fatigue. Stable COPD was defined as having no exacerbations in the preceding six weeks or subsequent two weeks. Data was analysed by paired t-test, Wilcoxon sign rank test and Spearman correlation. <h3>Results</h3> The 6MWT was significantly lower at 3 day post exacerbation compared to baseline measurements [414(SD±111) vs 359(SD±1222) metres; p ≤ 0.001] and fatigue was worse [37(9.3) vs 35(9.1); p = 0.037]. Inflammatory markers were significantly higher at the exacerbation recovery visit compared to stable state, CRP [median (IQR)] [3.0 (1–8) vs 8.0(3–37) mg/L; p &lt; 0.001] and fibrinogen [3.5 (3–4) vs 4.3 (3–5) g/l; p = 0.003)]. The fall in exercise capacity from baseline to exacerbation recovery visit was positively correlated with greater increases in CRP [rho= -0.41; p = 0.021] (Figure 1A) and in fibrinogen [rho= -0.42, p = 0.025] (Figure 1B). Also, the falls in exercise capacity between baseline and exacerbation were associated with increased in fatigue levels [r = 0.44; p = 0.013] (Figure 1C). <h3>Conclusions</h3> These findings suggest that changes in inflammatory markers and other metabolites in the body at exacerbation altering the perception of fatigue and reducing the patient exercise capacity.
National Schizophrenia Fellowship is highly critical of government's proposals
Authors: R. Moore
Journal: BMJ (1995)

EDITOR,—Nigel Eastman cites the National Schizophrenia Fellowship, representing carers, as the only relevant body not heavily critical of the government's Mental Health (Patients in the Community) Bill.1 It is unfortunate that the fellowship is widely seen to support the bill when in fact it is highly critical of the proposals—in particular, that the bill targets one …
AB0879 Estimation of disease activity of ankylosing spondylitis in real rheumatologic practice in russia:
Authors: E. Volnuhin, E. Galushko, S. Erdes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare various methods of estimation of AS activity in real practice of rheumatologist's in Russia. <h3>Methods</h3> Rheumatologist's from 24 centers of Russia evaluated 330 patients with AS, who visited to their practice during 4 months. The diagnosis was verified by the MNY criteria (1984). X-ray changes of sacroiliac joint were evaluated by two independent experts by blind method. Activity of disease was defined by BASDAI, ASDAS (ESR), physician's global assessment and ESR. <h3>Results</h3> 46% patients have high activity by physician's global assessment, 61% patients - by BASDAI (mean 4,8±2,1); 88% have high and very high activity by ASDAS (ESR) (mean 3,4±1,1); average value of ESR was 33,8±29 mm/h. Russian rheumatologists are guided in clinical practice at an estimation of the disease activity of AS, first of all, on inflammatory markers. Strong correlation has been found between ASDAS and an ESR (r=0,74, by Pirson's method), unlike BASDAI and an ESR (r=0,27); ASDAS was better correlated with physician's global assessment disease activity in comparison with BASDAI (r=0,4). However, number of patients with high activity of AS by BASDAI and ASDAS is rather more. There were the big difference between BASDAI and ASDAS at estimation of high stage of disease activity of AS. <h3>Conclusions</h3> So, we didn't find any preferences at an estimation of disease activity of AS neither by BASDAI nor by ASDAS. It is possible to use for definition of disease activity both of these indexes in clinical practice, and it is more preferable to use ASDAS for the scientific purpose. <h3>Disclosure of Interest</h3> None Declared
Tonsillar Asymmetry from a Parotid Tumor
Authors: Zacharias Vourexakis
Journal: New England Journal of Medicine (2014)

A 28-year-old woman presented with tonsillar asymmetry and a small, painless lump behind the left cheek that had been slowly enlarging over several months. Physical examination revealed displacement of the left tonsil and a firm, immobile mass in the retromandibular region.
S110 Employment histories of people with asthma in the 1958 birth cohort
Authors: R. Ghosh, D. Jarvis, D. Strachan, P. Cullinan
Journal: Thorax (2010)

Reports suggest that people with asthma experience frequent job changes, perhaps to avoid working environments that worsen their asthma. The aim of this analysis is to compare the number of periods of unemployment and jobs from early to mid adult life in people with and without asthma. Due to the differing employment histories of men and women the analyses are presented stratified by sex. <h3>Methods</h3> Participants from the 1958 birth cohort who provided a full occupational history and information on asthma at ages 16 and 42 (n=9856) were included. Employment was defined as a period spent in a job, in child/family care or in full-time education. Unemployment was defined as a period out of employment due to unemployment, sickness/disability or other unspecified reasons. Non-parametric methods were used to determine differences in (1) ever being unemployed (2) number of unemployment periods and (3) number of jobs (all to the age of 42 years) by asthma status (childhood asthma, adult onset asthma and the reporting of ‘ever asthma’ at age 42). <h3>Results</h3> 45.8% of men and 39.5% of women had ever been unemployed by age 42. The median number of jobs by age 42 was 6 (range 1–23) and of unemployment periods was 0 (range 0–15). In women, adult onset asthma and reporting ‘ever asthma’ at 42 were significantly associated with ever being unemployed (p=0.026, p&lt;0.000 respectively), but no associations were seen in men. Childhood asthma and reporting ‘ever asthma’ at 42 were not associated with the number of unemployment periods in either men or women. However, adult onset asthma was associated with increased number of unemployment periods in women (p=0.033), but not men. Differences in number of jobs by asthma status are tabulated. <h3>Conclusions</h3> In a cohort of adults born in 1958, women with adult onset asthma had an increased risk of experiencing unemployment, an increased number of unemployment periods and an increased number of jobs by age 42 years. In men, there was limited evidence that their asthma influenced their employment experience. It is not known whether these associations are seen in more recent cohorts.
Abstract 3140: Analysis of candidate phosphatidylinositol 3’ kinase inhibitor biomarkers in matched synchronous primary and metastatic breast cancer tumors
Authors: Zachary S. Boyd, Carol O'Brien, Jill Spoerke, Sankar Mohan, Ajay Pandita, Jane Fridlyand, Elizabeth Punnoose, Hartmut Koeppen, Lori Friedman, Lukas Amler, Garret Hampton, Mark Lackner
Journal: Cancer Research (2011)

Abstract The class I phosphatidylinositol 3’kinase (PI3K) is activated in a wide variety of human malignancies and inhibitors targeting the PI3K pathway hold great promise in the treatment and management of cancer. Successful development of such inhibitors will be enhanced by identification of responsive patients through the use of predictive biomarkers. Using cell lines and xenograft tumor models to evaluate a collection of putative biomarkers predictive of response to the selective inhibitor GDC-0941 in breast cancer, we have found excellent activity of the PI3K inhibitor GDC-0941 in luminal and HER2 amplified models, and that PIK3CA mutations and HER2 amplification are highly specific biomarkers of response to this agent. PTEN was predictive in some but not all cases, suggesting a need for further biomarkers of response in PTEN-driven disease. Here we report expanded analysis of human breast tumor samples, including matched primary tumor and lymph node metastases from 59 patients, suggesting primary and metastatic sites were generally concordant in terms of status of key biomarkers such as PTEN and PIK3CA, though several notable exceptions were discovered. We also compared PTEN status determined by immunohistochemistry (IHC) with a chromosomal fluorescence in situ hybridization (FISH) assay in a subset of tumors and found evidence for chromosomal deletion of the PTEN locus in several ER+ breast cancers, suggesting that some but not all of the PTEN loss observed in breast occurs at the chromosomal level and that both FISH and IHC may have utility as diagnostic assays. While we report that PIK3CA mutations and PTEN loss have reasonable prevalence to be considered as biomarkers for GDC-0941 in ER+ breast cancer, we have found a number of breast cancer models with no apparent pathway alterations but sensitivity to GDC-0941, indicating the need for additional predictive biomarkers. We identified a collection of genes for which expression levels indicate PI3K pathway activation and correlate with in vitro sensitivity to GDC-0941 as well as apparent prognostic significance in retrospective analysis of breast tumors. We report here expression analysis of these genes across matched primary breast tumors and lymph node metastases. In summary, our data provide strong rationale for developing a selective PI3K inhibitor in the ER+ breast cancer setting, and a framework for clinical implementation of predictive biomarker assays with potential utility in patient selection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3140. doi:10.1158/1538-7445.AM2011-3140
AB0227 Biologic therapy does not increase infection risk scores in a diverse ethnic minority rheumatoid arthritis cohort (emrac)
Authors: G. Kerr, Y. Yazici, C. Swearingen, C. Luo, L. Espinoza, Y. Sherrer, E. Treadwell, A. Mosley-Williams, R. Alamino Perez, Y. Bata, S. Dowell, A. Godoy, M. Paul
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Comorbities, advanced age, and prednisone usage are known risk factors for infection in RA patients who already have compromised immune systems. However, both the infection risk in ethnic minorities with RA and the utility of biologic use as a predictor are unknown. <h3>Objectives</h3> To evaluate infection risk scores (IRS)<sup>1</sup> in a diverse ethnic minority RA cohort, and the effect of biologic therapy. <h3>Methods</h3> Enrolled, consented EMRAC patients were evaluated. IRS measures including socio-demographic (age), previous patient-reported serious infections, extra-articular RA (amyloidosis, Felty's syndrome, vasculitis, pleuritis), RA disease activity-parameters (ESR), prednisone usage, comorbidities (HTN, DM, lipidemia, CVD event), and biologic were abstracted. IRS were estimated using (1) as-published methods, (2) substituting current biologic use for inferred infection risk, and (3) adding current biologic use to published method. Comparisons of IRS risk categories as well as other categorical data was analyzed between ethnic groups using Chi-square test; differences in continuous measures between ethnic groups were estimated using Kruskal-Wallis test. <h3>Results</h3> 468 EMRAC subjects were available for analysis: 393 were female (84%) with mean age of 56.4 years; 183 were Caucasian (39%), 169 were African American (AA) (36%), 79 were Hispanic (17%), and 37 were Other (8%). Comorbidities were reported in 19%, biologic therapy use in 32%, and previous infections in 3%. With previously reported infection, estimated IRS was significantly higher in AAs compared to other ethnic subsets (16% had a 5-10% risk compared to 5%, p=0.001), but was not significant when biologic use was included, either with or without previous infection. <h3>Conclusions</h3> Compared to Caucasians/other ethnic subsets, African American RA patients with previous infections are at increased risk for recurrence. These data suggest a need for increased surveillance for recurrent infections in African American RA patients, and a potential impact on treatment decisions. <h3>References</h3> Crowson, C. Arth. Rheum, 2012. <h3>Acknowledgements</h3> Genentech, Pfizer, Bristol Myers Squibb <h3>Disclosure of Interest</h3> G. Kerr Grant/research support from: EMRAC Group receives unrestricted grant support from Genentech, Pfizer and Bristol Myers Squibb, Y. Yazici: None Declared, C. Swearingen: None Declared, C. Luo: None Declared, L. Espinoza: None Declared, Y. Sherrer: None Declared, E. Treadwell: None Declared, A. Mosley-Williams: None Declared, R. Alamino Perez: None Declared, S. Dowell: None Declared, A. Godoy: None Declared, M. Paul: None Declared
PATHOLOGY OF IN-SSENT CHRONIC TOTAL OCCLUSION: IMPLICATIONS FOR REVASCULARIZATION
Authors: Hiroyoshi Mori, Tobias Koppara, Christoph Lutter, Kazuyuki Yahagi, Emanuel Harari, Robert Kutys, Elena Ladich, Frank Kolodgie, Renu Virmani, Michael Joner
Journal: Journal of the American College of Cardiology (2016)
P4-02-02: The Natural Fetal Estrogen Estetrol (E4), Causes Anti-Estrogenic Effects in Women with Endocrine-Responsive Positive Early Breast Cancer.
Authors: CF Singer, C Natter, S Steurer, M Rudas, F Moinfar, NRCA Appels, M Visser, E Kubista, C Bennink
Journal: Cancer Research (2011)

Abstract Background: Estetrol (E4) is a natural fetal estrogen which exerts estrogenic effects on reproductive organs and on the bone, and effectively reduces menopausal smyptoms. In contrast to other estrogens, however, E4 has estrogen-antagonistic effects on breast cancer cell lines in vitro and in the rat DMBA model, which would make it a suitable Hormone Replacement Therapy (HRT) in breast cancer patients, particularly in women who are being treated with aromatase inhibitors. Patients and Methods: We have investigated the effect of 14 days preoperative treatment with 20 mg E4 per day on tumor proliferation, apoptosis, ER-receptors, PgR receptor and several endocrine parameters in a prospective, randomised, double-blind, placebo-controlled, neo-adjuvant study in 15 pre- and 14 postmenopausal women with estrogen-receptor positive early breast cancer. Results: Estetrol induced a significant increase of SHBG, a significant decrease of FSH in postmenopausal women and no increase of gonadotrophins in premenopausal women. Estetrol had no effect on Ki67 expression and on apoptosis-related Bax and Bcl-2, but the apoptosis index in tumor tissue increased significantly. Systemic IGF-1 levels decreased significantly. Surprisingly the intratumoral epithelial ER-alpha expression decreased significantly, whereas the ER-beta expression showed a trend to increase. Conclusion: Our data suggest that E4 may be suitable and safe for HRT in women with spontaneous or induced menopausal symptoms, since apoptosis increases, IGF-1 decreases and no unfavourable effects are observed on Ki67, Bax and Bcl-2. The decrease of ER-alpha and the increase of ER-beta suggest a mechanism of action, explaining why the natural fetal estrogen E4 has estrogen-antagonistic effects on breast cancer tissue. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-02.
Abstract 440: Wnt signaling regulates neuropilin-2 (NRP2) expression and contributes to cancer cell invasiveness in castration-resistant prostate cancer (CRPC)
Authors: Shuman Liu, Zhengyu Jia, Zheng Sun, Xuesen Li, Yi Guo, Micheal Lilly, Dan Mercola, Bang H. Hoang, Xiaolin Zi
Journal: Cancer Research (2012)

Abstract Progression to CRPC represents a major challenge for treatment of advanced PCa. However, underlying mechanisms of this process remain largely unknown. We found that androgen deprivation in mice bearing PCa patient-derived tumors and in PCa LNCaP cells resulted in increased expression of wnt transcriptional factors: TCF4 and LEF1, as well as c-myc and NRP2. Using GenBank and MatInspector software, we identified five potential binding sites for TCF4 in the 5′ flanking promoter region spanning from –3891 to +108 base pairs of the NRP2 gene. Treatment of LNCaP cells with Wnt3a and Wnt 5a conditioned medium increased NRP2 mRNA expression; and inhibition of Wnt signaling by overexpression of secreted Wnt antagonists (WIF1 and Frzb/sFRP3) in two CRPC cell lines: C4-2B and PC3 down-regulated the expression of NRP2 in both in vitro cell cultures and in in vivo xenograft tumors. Chromatin immunoprecipitation/real-time PCR a! nalysis revealed that both WIF1 and Frzb/sFRP3 expression decreased the in vivo binding of TCF4 and beta-catenin to the NRP2 promoter at five predicted sites. Knock-down of NRP2 by short-hairpin RNA in CRPC cell lines markedly reduced cellular invasiveness and migration capacity. Furthermore, we analyzed gene microarray data sets from the UCI SPECS project. The total of 204 samples from 82 patients include 66 tumors, 65 tumor-adjacent stromas, 28 far stromas and 45 normal prostate samples. The mRNA expression levels of the genes of interest were normalized to the average expression levels of these genes from the normal prostate samples. We showed that the percentage of samples with WIF1 down-regulation progressively increased from far stroma to adjacent stroma and tumors. Strikingly, the levels of NRP2 mRNA are up-regulated in all tested adjacent stroma and most of tumor samples. Furthermore, the expression levels of NRP2 in far and adjacent stroma and tumors are inversely related to WIF1 mRNA levels (correlation coefficients are –0.6918, –0. 2349 and –0.5931; Ps&amp;lt;0.01). For a large series of clinical samples, NRP2 expression appears to be associated with WIF1 down-regulation. These results suggest that NRP2 may be a novel Wnt target gene and contribute to progression of CRPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 440. doi:1538-7445.AM2012-440