tbuckley/cabot-search huggingface dataset:
Interpretation of central and obstructive apnea event type varies widely between scorers: An observational study
Authors: Andrew Thornton, Parmjit Singh, Warren Ruehland, Peter Rochford
Journal: European Respiratory Journal (2011)

Background: Accurate classification of respiratory events in sleep as central or obstructive is critical to determining underlying pathophysiology and treatment.

Aim: To measure agreement in event classification in a group of scorers.

Methods: From June 2009 to Sept 2010, as part of a proficiency testing program within Australian and New Zealand laboratories, 10 studies were distributed. Four studies with AHI>40/hr and >10% of events scored as central or mixed apnea were chosen for analysis. Studies were scored by up to 103 scorers (mean 80) in up to 24 laboratories. Scored studies were compared and events defined as concordant if they overlapped in time. The majority of scorers indicated they used “Chicago” rules.

Results: There was major disagreement between scorers in classification of respiratory events. The figure shows a scatter plot of the percentage of all apnea classified as central or mixed for each scorer and each study. A superimposed box plot shows median, 25th and 10th percentiles.

![Figure][1] 



Discussion: There is an expectation that scorers can accurately distinguish obstructive from central events. This observational study shows that interpretation varies widely. This has important consequences for treatment of individuals and for conduct of research studies. AASM rules may provide more clarity and improve concordance but ongoing training and interlaboratory comparisons are essential.

 [1]: pending:yes
Selecting Anaesthetists: The Use of Psychological Tests and Structured Interviews
Authors: P E Reeve, M D Vickers, J N Horton
Journal: Journal of the Royal Society of Medicine (1993)

To test the predictive validity of a selection system for Senior House Officers (SHOs) and registrars in anaesthetics, 140 doctors short-listed from 635 applications between 1980 and 1987 were assessed by a semi-structured interview assessed and a personality questionnaire (Cattell 16PFQ-form C). The 62 doctors selected were followed up for between 3 and 8 years. Future performance was predicted from the psychological tests and by the interviewers. Academic, clinical, behavioural, and overall performance were used as criteria of outcome. Correlation coefficients between prediction and outcome measures were statistically highly significant (P < 0.01). Using multiple regression, equations could be derived from five of the Cattell personality factors to predict overall performance. Personality measures discriminated significantly between the best and poorest performers. Interview predictions were also statistically significant (P < 0.01). The method provides a blueprint for the effective selection of junior anaesthetists. Wastage in terms of those leaving the specialty was 16%.
In Vitro Properties of Epithelial Cell Lines Established from Human Carcinomas and Nonmalignant Tissue&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: H S Smith
Journal: JNCI Journal of the National Cancer Institute (1979)

A series of 16 epithelial cell lines derived from human carcinomatous and nonmalignant epithelial tissues were characterized for markers known to correlate with neoplasia in various model systems. The goal of these studies was to determine which in vitro transformation properties were relevant to human epithelial malignancy. The parameters tested were 1) colony formation in Methocel and on confluent monolayers of normal human epithelial cells and fibroblasts and 2) tumor induction in immunosuppressed mice. Cell lines derived from normal tissue and nonmalignant tissue peripheral to cancerous lesions were generally negative for these properties, whereas the carcinoma-derived lines varied in their expression (some lines being more abnormal than others). In most cases, the lines derived from metastatic lesions had more abnormal properties than did those derived from primary carcinomas.
Glioblastomas Require Integrin αvβ3/PAK4 Signaling to Escape Senescence
Authors: Aleksandra Franovic, Kathryn C. Elliott, Laetitia Seguin, M. Fernanda Camargo, Sara M. Weis, David A. Cheresh
Journal: Cancer Research (2015)

Abstract Integrin αvβ3 has been implicated as a driver of aggressive and metastatic disease, and is upregulated during glioblastoma progression. Here, we demonstrate that integrin αvβ3 allows glioblastoma cells to counteract senescence through a novel tissue-specific effector mechanism involving recruitment and activation of the cytoskeletal regulatory kinase PAK4. Mechanistically, targeting either αvβ3 or PAK4 led to emergence of a p21-dependent, p53-independent cell senescence phenotype. Notably, glioblastoma cells did not exhibit a similar requirement for either other integrins or additional PAK family members. Moreover, αvβ3/PAK4 dependence was not found to be critical in epithelial cancers. Taken together, our findings established that glioblastomas are selectively addicted to this pathway as a strategy to evade oncogene-induced senescence, with implications that inhibiting the αvβ3–PAK4 signaling axis may offer novel therapeutic opportunities to target this aggressive cancer. Cancer Res; 75(21); 4466–73. ©2015 AACR.
A Phosphonoacetate-Resistant Mutant of Herpesvirus of Turkeys2
Authors: Lucy F. Lee, K. Nazerian, R. L. Witter, Susan S. Leinbach, John A. Boezi
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article A Phosphonoacetate-Resistant Mutant of Herpesvirus of Turkeys Get access Lucy F. Lee, Lucy F. Lee Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Nazerian, K. Nazerian Search for other works by this author on: Oxford Academic PubMed Google Scholar R. L. Witter, R. L. Witter Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan S. Leinbach, Susan S. Leinbach Search for other works by this author on: Oxford Academic PubMed Google Scholar John A. Boezi John A. Boezi Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 5, May 1978, Pages 1141–1146, https://doi.org/10.1093/jnci/60.5.1141 Published: 01 May 1978 Article history Received: 30 August 1977 Accepted: 25 November 1977 Published: 01 May 1978
ENHANCEMENT OF ANTIBODY FORMATION BY WHOLE BODY X-RADIATION
Authors: Frank J. Dixon, Patricia J. McConahey
Journal: The Journal of Experimental Medicine (1963)

Enhancement and acceleration of the antibody response can be achieved in some situations with large, cytotoxic doses of whole body x-radiation given after antigenic stimulation. The timing of radiation is critical and varies with the kind and physical form of the antigen. It is postulated that the x-radiation depletes the cells of the lymphoid tissues just prior to the rapid proliferation of the antigen stimulated cells. In this situation those surviving cells which are stimulated by antigen multiply more rapidly than their non-stimulated counterparts and disproportionately repopulate the depleted lymphoid tissues. Whether the x-radiation produces other effects contributing to the multiplication of the antibody forming cells was not determined. It appears that x-radiation produces its enhancement of antibody formation by means different from those operating in endotoxin and colchicine induced enhancement.
Assessment of hormone receptor status in breast cancer by immunohistochemical and gene expression assays
Authors: Alice Wang, Karen Chew, S. Y. Chang, K. Lau, C. Santini, T. Vess, L. Kam-Morgan, M. Eisenberg, J. Bennington, S. Anderson, J. Sninsky, F. Waldman, J. Hessling
Journal: Clinical Cancer Research (2006)

A10   Accurate measurement of hormone receptor expression is critical for the care of breast cancer patients. Immunohistochemical (IHC) assays are currently the most widely used method for hormone receptor determination. While IHC assays have broad utilization there are concerns regarding standardization of methods and interpretation. We assessed hormone receptor status using contemporary estrogen (ER) and progesterone (PR) receptor IHC assays as well as real-time quantitative RT-PCR assays to measure gene expression (GE) levels of ER, PR and additional mRNAs involved in receptor expression.Tumor specimens from 315 well-characterized, early-stage, node-negative breast cancer patients were examined. Although the patients were diagnosed between 1975 and 1986, IHC assays for ER and PR were performed using current methods in a single laboratory. Tumors with an Allred score >3 were classified as positive; those
Rare diseases bullet 10: Small vessel vasculitis of the lung
Authors: M. I Schwarz
Journal: Thorax (2000)

The small vessel vasculitides of the lungs1-3 (table1) are inflammatory destructive processes that affect the arterioles, venules, and alveolar capillaries located within the interstitial compartment. An intense infiltration of activated neutrophils results in fibrinoid necrosis and dissolution of arteriolar and venular walls, thus compromising the vascular lumen. Accompanying the arteriolitis and venulitis is a distinct interstitial (alveolar wall) component referred to as necrotising pulmonary capillaritis.4-9 Necrotising pulmonary capillaritis can occur in isolation, in the absence of histological evidence of arteriolitis or venulitis. It is recognised by a marked interstitial neutrophilic infiltration and many of these cells are undergoing leucocytoclasis or fragmentation (fig 1). Because these neutrophils are constantly undergoing cell death (apoptosis), pyknotic cells and nuclear fragments (dust) accumulate within the lung parenchyma. The interstitial space becomes broadened by oedema, fibrin, and the neutrophilic infiltrate and eventually undergoes fibrinoid necrosis (fig 2). During this process the integrity of interstitial capillaries is damaged, permitting red blood cells to traverse the now incompetent alveolar capillary basement membranes and freely enter the interstitial compartment and flood alveolar spaces. Clinically this is referred to as diffuse alveolar haemorrhage, and this accompanies most episodes of small vessel vasculitis in the lungs regardless of aetiology. Fibrin and neutrophils also traverse the damaged alveolar capillary basement membranes and enter the alveolar spaces with the red blood cells. Other histological features in the small vessel vasculitides of the lung include arteriolar and capillary thrombosis, organising haemorrhage, epithelial type 2 cell hyperplasia, and eventually the accumulation of free parenchymal haemosiderin and haemosiderin containing macrophages in alveolar spaces (fig 3). With time, and after repeated episodes of diffuse alveolar haemorrhage due to pulmonary capillaritis, both interstitial pulmonary fibrosis and a progressive obstructive lung disease with the physiological and computed tomographic appearance of emphysema have been described.9 …
Why Do Hospital Doctors Wear White Coats?
Authors: R Farraj, J H Baron
Journal: Journal of the Royal Society of Medicine (1991)

Seventy-two per cent of all hospital doctors and medical students wear white coats and most wear them &gt; 75% of the time. White coats are worn chiefly for easy recognition by colleagues and patients, to put items in the pockets and to keep clothes clean. Psychiatrists and paediatricians try to maximize rapport with patients by deliberately not wearing white coats.
Decreased Erythrocyte Survival in Hemoglobin H Disease As a Result of the Abnormal Properties of Hemoglobin H: The Benefit of Splenectomy
Authors: DEMETRIOS A. RIGAS RIGAS, ROBERT D. KOLER, George Cummings, Marie L. Duerst, Donald R. Malm, Katherine Swisher, Patricia Vanbellinghen
Journal: Blood (1961)
Alteration of Skin in Gross Leukemia. V. Refutation of Virus Involvement&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: T Mariani, Y Maruyama
Journal: JNCI Journal of the National Cancer Institute (1974)

Previous findings in the Gross passage A (GPA) virus-(C3H/Bi × DBA/2)F1 mouse system indicated that the tumor cell was more important in the process of syngeneic skin graft rejection than was the GPA virus. To determine the specific involvement of virus in this rejection, purified GPA virus either in a cell-free filtrate from leukemic tissues or in an irradiated cell-free ascites form was directly injected into newly placed grafts. One and a half years after initial grafting and virus injection, skin was exchanged between the treated group and normal animals to ascertain whether antigens had been altered in the skin of the treated group. In all experiments, the skin grafts were accepted without any graft-site tumors developing. Eventually the animals died from disseminated lymphoma. The GPA virus, though definitely leukemogenic, seemed not to influence syngenic skin rejection in this system.
Characterisation of patients with COPD in Scotland
Authors: Jordan Covvey, Blair Johnston, Anne Boyter
Journal: European Respiratory Journal (2012)

Background: Characteristics and prevalence of the COPD population vary across the globe. Inequality in disease burden between the sexes has emerged as an important trend.  Aim: To describe the population diagnosed with COPD in NHS Forth Valley.  Methods: Data were obtained from 46 practices in NHS Forth Valley via an electronic interface with practice clinical software. Microsoft SQL® queries were designed to isolate patient characteristics, including age, sex, smoking status, and FEV1 % predicted. Data were analysed with Minitab® 16 using 2-sample t-tests and binomial proportion confidence intervals.  Results: 4611 patients were prescribed therapy for COPD in 2009; approximately half (48.0%) were men. The mean age of the cohort was higher for men versus women (69.3 ± 10.8 years v. 68.2 ± 11.3 years, p=0.001). Overall COPD prevalence was similar between men and women. Peak prevalence (per 10,000 population) for men was reached at age 80 – 89 years (903.3), but for women occurred earlier at 70 – 79 years (633.8). Compared to men, prevalence rates were significantly higher in women at younger ages (  Conclusions: Despite similar overall prevalence, female COPD patients in NHS Forth Valley are younger with less advanced disease, but higher smoking rates than their male counterparts.
Expression of BCL-2 in primary breast cancer and its correlation with tumour phenotype
Authors: B. Nathan, B. Gusterson, D. Jadayel, M. O'Hare, R. Anbazhagan, H. Jayatilake, S. Ebbs, K. Micklem, K. Price, R. Gelber, R. Reed, H.-J. Senn, A. Goldhirsch, M.J.S. Dyer
Journal: Annals of Oncology (1994)
Adenosine deaminase for diagnosis of pleural tuberculosis in intermediate-low prevalence scenarios
Authors: Alberto Garcia-Zamalloa Osakidetza, Jorge Taboada Osakidetza
Journal: European Respiratory Journal (2013)

OBJECTIVE: To assess the diagnostic value of ADA for pleural TB in intermediate-low prevalence scenarios  METHODS: We reviewed all patients with pleural effusion from January 1998 to December 2011. ADA value and lymphocyte proportion were determined in all samples. We distinguished confirmed and probable TB following international criteria. ADA 40 U/l and LP 50% were defined as cut-off values.  RESULTS: 607 episodes of pleural effusion were analysed, 93 cases (36 confirmed and 57 probable) were tuberculous (15%). Mean ADA value of both groups were 59 and 64 U/l respectively. On the whole period, ADA40 and LP50 showed a sensitivity, specificity, PPV and NPV of 88%, 98%, 89% and 97%. Area under the curve was 0.97 (95% IC 0.95-0.99).Corresponding values of periods 1998-2003 and 2004-2011 are contained in Table 1 and 2.  CONCLUSIONS  ADA remains useful in intermediate-low prevalence scenarios.
Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC).
Authors: Daniel C. Cho, Jeffrey Alan Sosman, Mario Sznol, Michael S. Gordon, Antoine Hollebecque, Omid Hamid, David F. McDermott, Jean-Pierre Delord, Ina Park Rhee, Ahmad Mokatrin, Marcin Kowanetz, Roel Peter Funke, Gregg Daniel Fine, Thomas Powles
Journal: Journal of Clinical Oncology (2013)

4505 Background: Human RCC expresses PD-L1 and has been shown to respond to immune-based therapy. MPDL3280A, a human monoclonal antibody containing an engineered Fc-domain designed to optimize efficacy and safety, targets PD-L1, blocking PD-L1 from binding its receptors, including PD-1 and B7.1. Methods: Pts with mRCC received MPDL3280A administered IV q3w at doses between 3-20 mg/kg in a Phase I expansion study. Pts were treated for up to 1 y. Response was assessed by RECIST v1.1. Results: As of Jan 10, 2013, 53 RCC pts were evaluable for safety and treated at doses of 3 (n=2), 10 (n=12), 15 (n=18) and 20 mg/kg (n=21). These pts had a median age of 62 y (range 33-79 y), 100% were PS 0-1 and all had had prior surgery. 83% of pts had received prior systemic therapy; 38% received immunotherapy, 57% received TKIs and 36% received anti-angiogenic therapy. Pts received treatment with MPDL3280A for a median duration of 190 days (range 21-317). The incidence of G3/4 AEs in RCC pts was 43%, regardless of attribution, with hypophosphatemia, fatigue, dyspnea and hyperglycemia (all 4%) being the most common. 13% of G3/4 AEs were attributable to study drug. 1 case of myasthenia gravis was observed in a pt who was retrospectively found to have anti-acetylcholine receptor antibodies prior to starting therapy. No G3-5 pneumonitis or diarrhea was reported. No treatment-related deaths occurred. 39 RCC pts enrolled prior to Jul 1, 2012, were evaluable for efficacy. RECIST responses, including CR, were observed across dose levels, with all responses ongoing at the time of data cutoff. Some RCC pts experienced prolonged SD prior to experiencing RECIST response. The 24-week PFS was 50%. Analysis of biomarker data from mandatory archival tumors demonstrated a correlation between PD-L1 status and efficacy. In addition, response correlated with low IL-17 expression in tumor tissue. Updated data will be presented. Conclusions: MPDL3280A was well tolerated, with no pneumonitis-related deaths. PD-L1–positive status correlates with response to MPDL3280A. Durable responses have been observed in RCC pts treated with MPDL3280A and further study is warranted. Clinical trial information: NCT01375842.
Karnofsky performance status revisited: reliability, validity, and guidelines.
Authors: C C Schag, R L Heinrich, P A Ganz
Journal: Journal of Clinical Oncology (1984)

Little research has been conducted documenting the reliability and validity of the Karnofsky Performance Status (KPS) scale, and guidelines based on empirical data do not exist to govern its use. Two hundred ninety-three cancer patients completed a questionnaire that assesses their physical and psychosocial difficulties. Physicians rated patients on the KPS and a subsample of 75 patients was used to evaluate interrater reliability. Analyses were conducted to evaluate the interrater reliability and construct validity of the KPS. The KPS was shown to have good reliability and validity. Detailed examination of the reliability data suggested areas in which physicians err in their judgments. Multiple regression techniques were used to empirically identify seven behaviorally based questions that would be helpful in predicting KPS scores. The seven variables included weight loss, weight gain, reduced energy, difficulty walking, driving, grooming, and working part time. An interview approach with behaviorally based guidelines is presented using these variables to obtain relevant data and make more accurate KPS ratings. With the approach suggested and the guidelines presented, oncologists may train themselves to use the KPS in a standard way, which should increase reliability and validity of the KPS and has implications for patients and research studies that use KPS as a stratifying variable.
Sites of extranodal involvement are prognostic in patients with diffuse large B‐cell lymphoma in the rituximab era: An analysis of the Surveillance, Epidemiology and End Results database
Authors: Jorge J. Castillo, Eric S. Winer, Adam J. Olszewski
Journal: American Journal of Hematology (2013)

Approximately a third of the patients with diffuse large B-cell lymphoma present with extranodal involvement. Our study aims to identify primary extranodal sites of disease associated with prognosis in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. A secondary objective is to describe epidemiological and clinical characteristics of patients with extranodal DLBCL. We included adult patients from the Surveillance, Epidemiology and End Results (SEER) database (2004-2009) in whom DLBCL was the first malignancy diagnosed. Extranodal primary sites were divided into 12 groups according to the topography code reported by SEER. Multivariate overall survival (OS) analyses were performed using Cox proportional-hazard regression models adjusted for age, sex, race, and stage. From a total of 25,992 adult DLBCL patients included in our analysis, 32% presented with extranodal primary sites. Gastrointestinal tract (34%), head/neck (H&N; 14%), and skin/soft tissue (11%) were the most common. In comparison with nodal DLBCL, patients with extranodal involvement were older (with exception of skeletal sites) and presented with earlier stages. In the multivariate analysis, sites associated with worse OS rates were gastrointestinal (Hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.15-1.33; P <0.001), pulmonary (HR 1.59, 95% CI 1.38-1.83; P <0.001), and liver/pancreas (HR 1.58, 95% CI 1.35-1.85; P <0.001), whereas H&N was associated with better survival (HR 0.79, 95% CI 0.70-0.89; P <0.001). In this population-based study, primary extranodal sites of involvement are associated with distinct outcomes in patients with DLBCL. Gastrointestinal, pulmonary, and liver/pancreas sites had a significant worse outcome than nodal sites.
Evolution Is an Experiment: Assessing Parallelism in Crop Domestication and Experimental Evolution
Authors: Brandon S. Gaut
Journal: Molecular Biology and Evolution (2015)

In this commentary, I make inferences about the level of repeatability and constraint in the evolutionary process, based on two sets of replicated experiments. The first experiment is crop domestication, which has been replicated across many different species. I focus on results of whole-genome scans for genes selected during domestication and ask whether genes are, in fact, selected in parallel across different domestication events. If genes are selected in parallel, it implies that the number of genetic solutions to the challenge of domestication is constrained. However, I find no evidence for parallel selection events either between species (maize vs. rice) or within species (two domestication events within beans). These results suggest that there are few constraints on genetic adaptation, but conclusions must be tempered by several complicating factors, particularly the lack of explicit design standards for selection screens. The second experiment involves the evolution of Escherichia coli to thermal stress. Unlike domestication, this highly replicated experiment detected a limited set of genes that appear prone to modification during adaptation to thermal stress. However, the number of potentially beneficial mutations within these genes is large, such that adaptation is constrained at the genic level but much less so at the nucleotide level. Based on these two experiments, I make the general conclusion that evolution is remarkably flexible, despite the presence of epistatic interactions that constrain evolutionary trajectories. I also posit that evolution is so rapid that we should establish a Speciation Prize, to be awarded to the first researcher who demonstrates speciation with a sexual organism in the laboratory.