tbuckley/cabot-search huggingface dataset:
Regulators to take over running of three failing NHS areas in England
Authors: C. White
Journal: BMJ (2015)

Essex, North Cumbria, and North, East, and West Devon will be the first three NHS areas in England to be subject to a new “whole systems, collaborative” approach to rooting out longstanding and entrenched problems in health and care services, NHS England’s chief, Simon Stevens, has announced.

Speaking at the annual conference of the NHS Confederation in Liverpool on 3 June Stevens said that the “success regimes” would tackle problems in localities where repeated remedial action had failed.

“We all know that there are parts of the country in systematic imbalance, in terms of either their quality, or the structure of their services, or their ability to make …
Abstract 3381: Further Reverse Ventricular Remodeling by Dual-site Left Ventricular Pacing in Cardiac Resynchronization Therapy
Authors: Christophe Leclercq, Fredrik Gadler, Wolfgang Kranig, Sue Ellery, Daniel Gras, Arnaud Lazarus, Jacques Clementy, Claude Daubert
Journal: Circulation (2006)

Cardiac Resynchronization Therapy (CRT) is usually achieved by pacing the two ventricles at one site each. Current evidence indicates standard biventricular pacing (SBVP) may fail at providing acce...
A phase II trial of cyclophosphamide, etoposide, and cisplatin with combined chest and brain radiotherapy in limited small-cell lung cancer: a Cancer and Leukemia Group B Study.
Authors: D J Kwiatkowski, K J Propert, R W Carey, N Choi, M Green
Journal: Journal of Clinical Oncology (1987)

Limited-extent small-cell lung carcinoma (SCLC) remains a therapeutic problem with little improvement in complete response (CR) rates and long-term survival in the past 5 years. From June 1984 through January 1985, 56 patients with limited-extent SCLC were enrolled in a Cancer and Leukemia Group B (CALGB) phase II study using five cycles of cyclophosphamide (500 mg/m2 intravenously [IV] day 1), etoposide (80 mg/m2 IV days 1 to 3), and cisplatin (33 mg/m2 IV days 1 to 3) administered at 3-week intervals (CEP), with radiation therapy (50 Gy to chest and 30 Gy to brain) administered concomitant with cycles 4 and 5, followed by three cycles of cyclophosphamide (500 mg/m2 IV day 1), etoposide (80 mg/m2 IV days 1 to 3), and doxorubicin (50 mg/m2 IV day 1). Of 49 patients evaluable for response, the overall response rate was 88%, with 57% CRs. The median overall survival was 14 months; the median duration of CR was 10 months, and nine CRs remain disease free at a median follow-up of 23 months. Toxicity was significant: 56% patients experienced WBC less than 1,000 microL, 32% platelets less than 25,000 microL and 10% hemoglobin less than 7 g/dL. There was one treatment-related septic death. These results are as good as the best previous CALGB study of SCLC, despite a reduction in duration of treatment from 18 to 5 months. We are currently using a variant of this multimodality treatment approach as our standard management for patients with limited-extent SCLC.
Abstract 2917: Assessment of Left Ventricular Rotation and Torsion with Two-dimensional Speckle Tracking Echocardiography
Authors: Hyung-Kwan Kim, Sang-Eun Lee, Jung-Im Shin, Su-Yeon Choi, Jin-Shik Park, Yong-Jin Kim, Byung-Hee Oh, Young-Bae Park, Yun-Shik Choi, Dae-Won Sohn
Journal: Circulation (2006)

Background- Speckle tracking echocardiography(STE) has a unique feature of angle-independency and thus may provide a powerful means of assessing left ventricular torsion (LVtor). The aims of the pr...
Nipple Excised and Areola Retained after Total Mastectomy (NEAT)
Authors: A B Gordon, N Nasiri, G P H Gui, N P M Sacks
Journal: Journal of the Royal Society of Medicine (2001)

The nipple is part of the lactiferous system1 whereas the areola is a form of pigmented skin, anatomically close but functionally different. For mastectomy, common surgical practice varies between complete excision and preservation of the nipple—areola complex. Two examples of these extremes are given, both giving unsatisfactory results, and a third case in which the differences between nipple and areola were exploited in the NEAT procedure—nipple excised and areola retained.
Volatile organic compounds of exhaled breath in lung cancer and lung inflammatory diseases
Authors: Immanuels Taivans, Gunta Strazda, Normunds Jurka, Uldis Kopeika, Ainis Pirtnieks, Liga Balode, Maris Bukovskis, Agnese Kislina, Jevgenija Aprinceva, Liene Logina
Journal: European Respiratory Journal (2013)

Background  The analysis of exhaled breath volatile organic compounds (VOCs) is a non-invasive diagnostic assay that could be applied for diagnosis of lung cancer.  Objective  The aim of our study was to measure the concentration of VOCs patients with lung cancer, COPD, pneumonia and in healthy volunteers.  Methods  Exhaled breath samples of 31 patient with lung cancer, 19 with COPD, 11 with pneumonia and 10 healthy volunteers were collected trough T-shape non-rebreathing valve into Tedlar bag system after 5 min. washout breathing of VOCs free air. VOCs concentration (ppb) was detected in gas chromatography/mass spectrometry and termodesorbtion device.  Results  Concentration of methanol, ethanol, dodecane and tridecane in breath samples of cancer patients was significantly lower than in patients with COPD, pneumonia and control group.  Conclusions  Different VOCs profile can in vivo discriminate patients with lung cancer, healthy patients and patients with inflammatory lung diseases.
Abstract 13583: Pericardial Adiposity Predicts Atrial Fibrillation Recurrence Following Catheter Ablation
Authors: Hany S Abed, Christopher X Wong, Payman Molaee, Darryl p Leong, Anthony J Nelson, Anthony G Brooks, Dennis H Lau, Kurt C Roberts-Thomson, Gary A Wittert, Walter p Abhayaratna, Stephen G Worthley, Prashanthan Sanders
Journal: Circulation (2010)

Introduction: Obesity is recognised as a risk factor for developing atrial fibrillation (AF). Novel predictors of catheter ablation outcomes may improve selection for this invasive therapy. AIM We ...
High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas.
Authors: R L Heideman, E C Douglass, R A Krance, J Fontanesi, J A Langston, R A Sanford, E H Kovnar, J Ochs, J Kuttesch, J J Jenkins
Journal: Journal of Clinical Oncology (1993)

PURPOSE Evaluation of high-dose chemotherapy with autologous bone marrow rescue (ABMR) in pediatric malignant gliomas. PATIENTS AND METHODS Newly diagnosed (n = 11) and recurrent (n = 2) malignant glioma patients received high-dose chemotherapy within 4 weeks of surgery; three had near total and 10 had subtotal resection/biopsy. High-dose thiotepa (300 mg/m2) and cyclophosphamide (2 g/m2) daily for 3 days were followed by ABMR; response was evaluated at day 30. At day 60, patients with at least stable disease received hyperfractionated (n = 9) or conventional external-beam radiotherapy (n = 2) preceded by local radioactive iodine 125 implantation (n = 2) or radiosurgery (n = 1). RESULTS Grade III and IV toxicities after ABMR consisted of mucositis (n = 12), cardiomyopathy (n = 1), acute abdomen (n = 1), pneumonitis (n = 2), and infection (n = 2). One complete and three partial responses were observed; the objective response rate was 31% (95% confidence interval, 9% to 61%). Seven had stable disease, one had disease progression, and one died of toxicity before response evaluation. The median overall and progression-free survival durations after combined modality therapy were 14 months (range, 4 to 30+) and 9 months (range, 0 to 30+), respectively. One patient remains progression-free at 30+ months. Radionecrosis and white matter changes occurred in three patients: one after hyperfractionated irradiation, and two after 125I implants. CONCLUSION For patients with bulky residual disease after surgery, survival with this aggressive chemotherapy and radiation regimen is not better than that reported for conventional treatment regimens.
Molecular memories in the regulation of seasonal flowering: from competence to cessation
Authors: Fabian Bratzel, Franziska Turck
Journal: Genome biology (2015)

Plants commit to flowering based on endogenous and exogenous information that they can remember across mitotic cell divisions. Here, we review how signal perception and epigenetic memory converge at key integrator genes, and we show how variation in their regulatory circuits supports the diversity of plant lifestyles.
Maximum-tolerated doses of ifosfamide, carboplatin, and etoposide given over 6 days followed by autologous stem-cell rescue: toxicity profile.
Authors: K K Fields, G J Elfenbein, H M Lazarus, B W Cooper, J B Perkins, R J Creger, O F Ballester, J H Hiemenz, W E Janssen, P E Zorsky
Journal: Journal of Clinical Oncology (1995)

PURPOSE A phase I dose-escalation study of ifosfamide, carboplatin, and etoposide (ICE) with autologous stem-cell rescue (ASCR) was conducted to determine the maximum-tolerated dose (MTD) of ICE given over 6 days. PATIENTS AND METHODS One hundred fifty-four patients with a variety of poor-prognosis malignancies received escalating doses of ifosfamide 6,000 to 24,000 mg/m2, carboplatin 1,200 to 2,100 mg/m2, and etoposide 1,800 to 3,000 mg/m2 divided over 6 days. Mesna was administered in a dose equal to ifosfamide. ASCR was performed 48 hours after the completion of ICE. The source of stem cells was bone marrow (BM) in patients without BM micrometastases and peripheral-blood stem cells (PBSC) in patients with BM micrometastases. Patients were evaluated for hematologic and nonhematologic toxicities, as well as response to therapy. RESULTS The MTD of the ICE regimen is 20,100 mg/m2 of ifosfamide, 1,800 mg/m2 of carboplatin, and 3,000 mg/m2 of etoposide. The dose-limiting toxicities of ICE were CNS toxicity and acute renal failure. Additionally, reversible elevations of serum creatinine levels were noted in 29% of patients treated at the upper dose levels. Forty-six patients were treated at the MTD. Severe, reversible mucositis and enteritis were the major nonhematologic toxicities seen at the MTD (78% and 33%, respectively). The overall mortality rate was 8% for all dose levels (4% at the MTD). At the MTD, the median times to an absolute neutrophil count &gt; or = 0.5 x 10(9)/L, to a platelet count &gt; or = 20 x 10(9)/L, and to discharge were 18, 22, and 24 days, respectively. The overall response rate was 40% for 77 patients with assessable disease at the time of treatment. CONCLUSION ICE is well tolerated, with acceptable hematopoietic side effects and predictable organ toxicity.
Deluge of responses to India’s draft law delays stricter tobacco controls
Authors: Vidya Krishnan
Journal: BMJ (2015)

Indian government officials have had to delay the introduction to parliament of proposals to strengthen tobacco control legislation after being overwhelmed with responses to a consultation launched in January.1 The amendments to the tobacco control law, which were due to be aired in the parliament’s monsoon session (21 July to 13 August), are now expected to be heard in the winter session (usually the last week in November to mid-December), at the earliest.

The Indian Ministry of Health and Family Welfare received more than 45 000 emails and 100 000 letters in response to proposed changes to tobacco control legislation …
Applying age-adjusted cut offs to exclude thromboembolic disease with a semi-quantitative D-dimer assay can safely exclude VTE
Authors: Rahul Shrimanker, Neena Kalsi, Andrew Stanton
Journal: European Respiratory Journal (2013)

Recent, large cohort studies have shown that using a higher, age-adjusted D-dimer value (with a highly sensitive ELISA assay) can safely exclude venous thromboembolic (VTE) disease in the over 50’s. We investigated if we were able to apply the same principle locally, using a semi-quantitative latex agglutination assay (INNOVANCE d-dimer).  We reviewed the casenotes of patients aged over 50 assessed in our hospital who had a positive d-dimer (>420 µg/L) over a 1 year period (2011) to determine the results of investigation for VTE if performed. We then considered the two proposed age adjusted cut-offs (AAC) - age x 10 µg/L in the over 50’s (AAC1) and an absolute cut-off of >750 µg/L in the over 60’s (AAC2). We determined the frequency of VTE detection in both groups.  Over 1 year 1324 d-dimers were requested in the over 50 age group. 874 were positive (>420 µg/L). 202 patients had a d-dimer within AAC1 - 124 patients had negative investigations for VTE (42 CTPA, 104 leg USS), 1 positive investigation (below knee DVT) and 77 patients not investigated. 232 patients had a d-dimer within AAC2 - 162 had negative investigation for VTE (49 CTPA, 116 leg USS), 1 positive (below knee DVT, same patient as in AAC1) and 69 patients not investigated. Overall therefore applying the age adjusted D-dimer thresholds would have missed 1 VTE event (of arguable significance).  Applying previously validated age-adjusted D-dimer cut-offs appears to be safe with the INNOVANCE D-dimer assay. This has been integrated into practice in our hospital, reducing the burden on radiology and improving length of stay for patients with suspected VTE.
Patient Knowledge of Operative Care
Authors: O A Williams
Journal: Journal of the Royal Society of Medicine (1993)

To investigate knowledge of perioperative events, a questionnaire was administered to 111 elective surgical patients. Six topics were covered: the operation, the anaesthetic, time spent in the operating theatre, amount of post-operative pain, duration of hospital admission and time required to return to normal fitness. Apart from evaluating information-sources for each topic, the questionnaire assessed degree of knowledge and satisfaction with this information, and the relationship of these to anxiety. More than 30% of the patients responded that they had received no information about anaesthesia, time in theatre, return to fitness or pain. For each topic more than 40% desired further information. Nursing staff provided most information, although for the anaesthetic, time in theatre, return to fitness and pain, more than 60% of patients responded that nobody had provided explanation. There was no correlation between knowledge relating to the topics per se and anxiety, but there was a significant correlation between satisfaction with information and anxiety. This survey shows a considerable need for improved information provision, especially for patients in whom anxiety is associated with a desire for further explanation of operative care.
Correction
Authors: Tung-Lung Tsai, Shyue-Yih Chang, Ching-Yin Ho, Yu Ru Kou
Journal: Gut (2007)

The pathogenetic mechanisms of enhanced laryngeal reflex reactivity (ELRR) in patients with extraoesophageal reflux (EOR) are unclear. In a rat EOR model, a laryngeal acid-pepsin insult produces an ELRR that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS).We investigated whether activation of P2X receptors by ATP subsequent to an increase in ROS may induce ELRR in an inflamed larynx that has been insulted by acid-pepsin or H2O2.The larynxes of 184 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity.Laryngeal insult with acid-pepsin or H2O2 produced ELRR with similar characteristics. These two ELRR events were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist (iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate). Laryngeal application of a P2X receptor agonist (alpha,beta-methylene-ATP) also produced ELRR. An insult with either acid-pepsin or H2O2 similarly promoted an increase in the levels of ATP, lipid peroxidation and inflammation in the larynx.Laryngeal insult with acid-pepsin or H2O2 induces inflammation and produces excess ROS in the rat's larynx. The latter may in turn promote the release of ATP to activate P2X receptors resulting in sensitization of capsaicin-sensitive laryngeal afferent fibers and ELRR.
Paclitaxel (P) plus bevacizumab (B) in patients (pts) with chemosensitive relapsed small cell lung cancer (SCLC): A safety, feasibility and efficacy trial from the Hoosier Oncology Group
Authors: S. I. Jalal, S. Bhatia, L. H. Einhorn, R. H. Ansari, N. Bechar, R. Govindan, K. Koneru, P. M. Bedano, J. Wu, N. H. Hanna
Journal: Journal of Clinical Oncology (2008)

19013 Background: Relapsed SCLC is associated with a poor prognosis. Angiogenesis plays an important role in SCLC. Paclitaxel has single agent activity in SCLC. Targeting angiogenesis in combination with chemotherapy is effective against non-small cell lung cancer. This study evaluates the feasibility, toxicity, and efficacy of combining paclitaxel with bevacizumab in relapsed SCLC. Methods: Eligible pts had chemo-sensitive, relapsed SCLC, previously treated with 1–2 chemotherapy regimens (one must be platinum containing), PS 0–1. Chemosensitive disease was defined as relapse≥ 60 days from completion of first line chemotherapy. The primary endpoint was to estimate progression-free survival (PFS) using Kaplan-Meier analysis (5%α, 91%β) requiring 34 pts to demonstrate a PFS ≥ 24 weeks vs. historical control of 14 weeks. Pts received P at 90mg/m2 iv infusion on days 1, 8, and 15 and B at 10mg/kg iv infusion on days 1 and 15. Cycles were repeated every 28 days. After completing at least 4 cycles, pts with non-progressive disease (PD) were allowed to continue B until PD. Results: Eligible, treated pts (n=34) received a median of 2 cycles (range 1- 6). Pt characteristics: M:F 61.8%:38.2%; median age 67 (39–89); ECOG PS 0:1 47%:53%; prior chemotherapy 1 vs. 2: 85.3%: 14.7%. G3/4 toxicities included: 17.6%neutropenia, 26.5%fatigue, 8.8% hyponatremia, 2 pts each with CVA, sensory neuropathy, and hyperglycemia and 1 patient each with MI, infection, proteinuria, and esophageal fistula. 2 pts discontinued therapy due to toxicity, including one pt that died (possible pulmonary embolus). 14 pts (41.2%) required dose modifications, and 14 pts (41.2%) required dose delays. Response data was available for 27 pts. PRs were seen in 3 pts (11.1%), SD in 15 pts (55.5%), and PD in 9 pts (33.3%). Median PFS was 13 weeks and median OS was 21 weeks. Conclusions: P + B is an active regimen, although frequent dose delays and modifications are required with this dose and schedule. Updated PFS and OS data will be available at the ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, sanofi-aventis, Eli Lilly, Genentech, Pfizer Merck
Patrick Offley Porter Newell
Authors: Antonia Newell
Journal: BMJ (2015)

Patrick Offley Porter Newell was born in Singapore but educated at Portora Royal School, Enniskillen, where he excelled in rugby, cricket, and swimming. On leaving school he worked briefly as a journalist for a local paper in Suffolk before being called up into the Essex Regiment. After fracturing his ankle playing rugby the night before embarking for Sierra Leone, …
Selectively Constrained RNA Editing Regulation Crosstalks with piRNA Biogenesis in Primates
Authors: Xin-Zhuang Yang, Jia-Yu Chen, Chu-Jun Liu, Jiguang Peng, Yin Rei Wee, Xiaorui Han, Chenqu Wang, Xiaoming Zhong, Qing Sunny Shen, Hsuan Liu, Huiqing Cao, Xiao-Wei Chen, Bertrand Chin-Ming Tan, Chuan-Yun Li
Journal: Molecular Biology and Evolution (2015)

Although millions of RNA editing events have been reported to modify hereditary information across the primate transcriptome, evidence for their functional significance remains largely elusive, particularly for the vast majority of editing sites in noncoding regions. Here, we report a new mechanism for the functionality of RNA editing—a crosstalk with PIWI-interacting RNA (piRNA) biogenesis. Exploiting rhesus macaque as an emerging model organism closely related to human, in combination with extensive genome and transcriptome sequencing in seven tissues of the same animal, we deciphered accurate RNA editome across both long transcripts and the piRNA species. Superimposing and comparing these two distinct RNA editome profiles revealed 4,170 editing-bearing piRNA variants, or epiRNAs, that primarily derived from edited long transcripts. These epiRNAs represent distinct entities that evidence an intersection between RNA editing regulations and piRNA biogenesis. Population genetics analyses in a macaque population of 31 independent animals further demonstrated that the epiRNA-associated RNA editing is maintained by purifying selection, lending support to the functional significance of this crosstalk in rhesus macaque. Correspondingly, these findings are consistent in human, supporting the conservation of this mechanism during the primate evolution. Overall, our study reports the earliest lines of evidence for a crosstalk between selectively constrained RNA editing regulation and piRNA biogenesis, and further illustrates that such an interaction may contribute substantially to the diversification of the piRNA repertoire in primates.
Pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) with recommendations for its use. Report of the European Respiratory Society Rehabilitation and Chronic Care Scientific Group (S.E.P.C.R. Rehabilitation Working Group)
Authors: CF Donner, P Howard
Journal: European Respiratory Journal (1992)

GPR55 is a G protein-coupled receptor activated by l-α-lysophosphatidylinositol and suggested to have roles in pain signaling, bone morphogenesis, and possibly in vascular endothelial cells. It has affinity for certain cannabinoids (molecules that interact with the cannabinoid CB<sub>1</sub> and CB<sub>2</sub> receptors), but investigation of its functional role in cell-based systems and in tissue has been limited by a lack of selective pharmacological tools. Here, we present our characterization of GPR55 in the yeast <i>Saccharomyces cerevisiae</i> and in human embryonic kidney (HEK293) cells. We describe GSK494581A (1-{2-fluoro-4-[1-(methyloxy)ethyl]phenyl}-4-{[4′-fluoro-4-(methylsulfonyl)-2-biphenylyl]carbonyl}piperazine), a selective small-molecule ligand of GPR55 identified through diversity screening. GSK494581A is one of a series of benzoylpiperazines originally identified and patented as inhibitors of the glycine transporter subtype 1 (GlyT1). The structure–activity relationship between GPR55 and GlyT1 is divergent across this series. The most GPR55-selective example is GSK575594A (3-fluoro-4-(4-{[4′-fluoro-4-(methylsulfonyl)-2-biphenylyl]carbonyl}-1-piperazinyl)aniline), which is approximately 60-fold selective for GPR55 (pEC<sub>50</sub> = 6.8) over GlyT1 (pIC<sub>50</sub> = 5.0). Several exemplars with activity at GPR55 and GlyT1 have been profiled at a broad range of other molecular targets and are inactive at cannabinoid receptors and all other targets tested. The benzoylpiperazine agonists activate human GPR55 but not rodent GPR55, suggesting that the relatively low level of sequence identity between these orthologs (75%) translates to important functional differences in the ligand-binding site.
Junior doctors to ask lawyers if the NHS is in breach of human rights legislation
Authors: J. Wise
Journal: BMJ (2015)

The BMA is to seek legal advice on whether the NHS is in breach of the Human Rights Act if junior doctors are rostered to work when they have already given advance notice of a special event.

Junior doctors have said that their requests for leave to attend “life events” such as weddings or family celebrations are routinely ignored and that they are expected to organise cover themselves.

Junior doctors voted at their annual conference in London on 16 May for advance requests to be honoured, …