tbuckley/cabot-search huggingface dataset:
The Bell Jar
Authors: Iain McClure
Journal: BMJ (2007)

Chiefly celebrated for her “confessional poetry,” Sylvia Plath (1932-1963) was also ambitious to break new ground with prose. Poignantly, The Bell Jar, published under a pseudonym a month before her death, was her only attempt at the novel form. One of the compelling aspects of this increasingly respected novel is the degree of connection between the troubled life of its heroine, Esther Greenwood, and Plath herself. Inevitably, as we encounter Esther's subtle mental breakdown and successive suicide attempts, we are drawn further into the now almost mythic events of Plath's short life. Despite the inevitable curiosity about the autobiographical content, The Bell Jar is of lasting importance for further reasons.

First and foremost is its subject matter, which has increasing relevance 40 years on. The book examines a contemporary concern—how is it that privileged and educated young people (especially young women) increasingly turn to varied kinds of self harm, as a way of coping and escape? Plath was one of the first writers to explore this area, and her description of Esther's escalating suicidality is all the more realistic for being described so matter of factly.

Various themes spin out from this central idea, such as the restricted role of women in 1950s America, an emerging feminist viewpoint, and personal renewal through struggle.

Esther's development of psychotic depression is Plath's interpretation of the classic “rite of passage” journey. The bell jar of confusion that descends on Esther hampers her personal progress, yet it protects her from being overwhelmed by a highly competitive social world. Plath ushers us into the clinic of the subtly monstrous psychiatrist, Dr Gordon, and exposes us to the stunning brutality of Esther's unanaesthetised electroconvulsive therapy. Psychiatry is redeemed when Esther is renewed under the care of a female consultant, Dr Nolan, who represents what Esther aspires for herself—independence and social respect as a professional woman.

In describing Esther's recovery, Plath covers an aspect of mental illness that is not sufficiently publicised. Esther has undergone a life changing experience. Plath's novel serves as an important reminder that our stigmatised psychiatric wards, sometimes places of misery and tragedy, can also nurture momentous personal change and a new beginning. As we finish the novel, we are drawn again into the author's own life. Esther's overriding concern, as she faces the grand round that will decide for or against her hospital discharge, is whether the bell jar “with its stifling distortions” might descend again. Tragically (for once, this word is not misplaced), Sylvia Plath did not escape the fate that Esther fears.
British Society for Paediatric Dermatology
Authors: K Aljefri, F Charlton, S Leech, Aem Taylor
Journal: British Journal of Dermatology (2014)

In November 2012, the British Society for Paediatric Dermatology approved a taskforce to establish patterns of usage of propranolol in infantile haemangiomas across the U.K.This was subsequently widened to seven further European countries.Herein, we report the results of this multicentre, retrospective case series.Study data were collected and managed using REDCap (Research Electronic Data Capture) tools.RED-Cap is a secure, web-based application designed to support remote data entry for research studies.Thirty-nine centres from eight European countries entered data on patients with haemangiomas who had been treated with propranolol.Most were dermatology centres, but data from paediatricians and paediatric ophthalmologists were also included.Data from 1116 patients were entered into the database.In total, 93% of lesions treated (n = 1035) were infantile haemangiomas, with segmental haemangiomas, congenital haemangiomas and 'other' accounting for only 7% of lesions (n = 81).Of the infantile haemangiomas, 78% (805) were treated in the rapid growth phase, 21% (217) in the stabilization phase and only 1% (13) in the involution phase.The three most common indications for treatment were a periocular haemangioma with threat to vision (32%, n = 327), risk of cosmetic disfigurement on the face (23%, n = 233) and ulceration (21%, n = 218).The median age at initiation of propranolol was 16 weeks (range 1-396).Propranolol was used as monotherapy in 94% of patients (n = 974), and 13652133, 2014, s1, Downloaded from https://onlinelibrary.wiley.com/
Headliners: Chemical Exposures and Childhood Leukemia: Parental Chemical Exposures and ras Mutations in Children
Authors: Jerry Phelps
Journal: Environmental Health Perspectives (2004)

A variety of carcinogens have been shown to induce ras mutations in animal and human tumor models, and ras proto-oncogene mutations have been implicated in the development of many malignancies including pancreatic and breast cancers. However, few data exist associating parental exposures and ras mutations in their children. Now a team including NIEHS grantee Leslie L. Robison of the University of Minnesota report that parents’ chemical exposures may be associated with distinct ras mutations in their children with acute lymphoblastic leukemia (ALL).

This study used data from a large case–control study of childhood ALL conducted by the Children’s Oncology Group in Southern California. DNA samples from the study children were examined for ras mutations. A total of 127 out of 837 ALL cases exhibited ras mutations in the K- or N-ras genes. Earlier studies have reported a 5–20% frequency of ras mutations among patients with ALL.

A number of parental chemical exposures were associated with significantly increased risks for ras mutation in the children. Use of drugs such as marijuana, LSD, and cocaine was associated with increased risk of N-ras mutation (three-fold higher risk for maternal use and two-fold higher risk for paternal use). Paternal use of amphetamines or diet pills was associated with a four-fold increase in N-ras mutation. Maternal exposure to solvents and plastics during pregnancy raised the risk of K-ras mutation about three-fold and seven-fold, respectively, and maternal exposure to plastics after pregnancy was associated with an eight-fold higher risk. Maternal and paternal exposure to oil and coal products and other hydrocarbons before and during pregnancy was associated with about a two-fold greater risk of N-ras mutation.

In previous studies, parental occupational exposure to hydrocarbons (such as chlorinated solvents, benzene, and paints) has been linked to elevated childhood leukemia risk. The present study has extended these findings to include drugs of abuse and additional chemical exposures, and to link them to ras mutations. The authors conclude that parental exposures to hydrocarbons and mind-altering drugs, chemicals that have been previously suggested to increase the risk of childhood leukemia, are related to specific ras mutations in childhood ALL.
International Fetal Cardiac Intervention Registry
Authors: Anita J. Moon-Grady, Shaine A. Morris, Michael Belfort, Ramen Chmait, Joanna Dangel, Roland Devlieger, Stephen Emery, Michele Frommelt, Alberto Galindo, Sarah Gelehrter, Ulrich Gembruch, Sofia Grinenco, Mounira Habli, Ulrike Herberg, Edgar Jaeggi, Mark Kilby, Eftichia Kontopoulos, Pablo Marantz, Owen Miller, Lucas Otaño, Carlos Pedra, Simone Pedra, Jay Pruetz, Ruben Quintero, Greg Ryan, Gurleen Sharland, John Simpson, Emanuel Vlastos, Wayne Tworetzky, Louise Wilkins-Haug, Dick Oepkes
Journal: Journal of the American College of Cardiology (2015)
Discovery of novel genes for serum urate and low-density lipoprotein cholesterol - Two biomarkers of cardiovascular disease
Authors: S J Newhouse, C Wallace, M Hoti, R J Dobson, M Farrall, M Brown, N J Samani, A Dominiczak, J M Connell, J Webster, M Lathrop, M J Caulfield, P B Munroe
Journal: Circulation Research (2007)
Abstract 14885: Blocking VCAM-1/VLA-4 Axis Ameliorates Inflammation and Fibrosis in Experimental Autoimmune Myocarditis
Authors: Ulrich Grabmaier, Stefan Brunner, Johanna Grabmeier, Gabriela Kania, Urs Eriksson, Nadia Herbach, Rudiger Wanke, Wolfgang-Michael Franz
Journal: Circulation (2012)

Introduction: During inflammation, Vascular Cell Adhesion Molecule-1 (VCAM-1) is strongly upregulatedin the inflamed tissue. VLA-4, an integrin which binds to VCAM-1, is expressed on all subpopulat...
Abstract 950: Should We Measure Intima Media Thickness In Patients With Peripheral Arterial Disease?
Authors: Christine Espinola-Klein, Hans J Rupprecht, Christoph Bickel, Karl Lackner, Savvas Savvidis, Thomas Munzel, Stefan Blankenberg
Journal: Circulation (2008)

Background: Carotid intima-media thickness (IMT) is a marker of early atherosclerosis. Patients with peripheral arterial disease (PAD) have advanced atherosclerosis and a high cardiovascular event rate. The aim of this study was to evaluate, whether measurement of carotid IMT adds prognostic information in PAD patients. Methods: We included 165 patients (mean age 64.5 ± 9 years, 71.5% men) with PAD. In all patients IMT was measured at both common carotid arteries and the mean IMT was used for further evaluation. Carotid IMT of more than 0.9 mm was defined as thickened. After a median follow-up of 6.5 years in total 33 patients (20%) died from cardiovascular causes. Results: Mean IMT was 0.75 ± 0.19 mm and in 30 patients (18.2%) an IMT ≥ 0.9 mm could be detected. Cardiovascular mortality was significantly higher in patients with PAD and IMT ≥ 0.9 mm than in patients with IMT ≥ 0.9 mm (IMT ≥ 0.9 mm = 40.0 % versus IMT &lt; 0.9 mm = 15.6 %; P=0.002, figure ). In a fully adjusted Cox regression analysis (adjusted for age, sex, diabetes, hypertension, high density lipoprotein cholesterol, smoking, body mass index and acute coronary syndrome) a carotid IMT ≥ 0.9 mm could not be identified as an independent predictor for cardiovascular death (Hazard Ratio (95% Confidence Interval) = 2.0 (0.9 – 4.2), P=0.09). Conclusion: Patients with PAD and a carotid IMT ≥ 0.9 mm had a higher cardiovascular mortality than patients with normal IMT. But an increased carotid IMT could not be identified as independent predictor for cardiovascular mortality. Therefore it should be discussed whether IMT measurement adds prognostic impact in patients with PAD. Survival in Accordance to Carotid IMT
Abstract 12192: Myocardial Iron Load in Patients With Beta-Thalassaemia Major is Associated With Global Left Ventricular Mechanical Dyssynchrony
Authors: Yiu-fai Cheung, Xue-cun Liang, Godfrey C Chan, Sophia J Wong, Shau-yin Ha
Journal: Circulation (2010)

Background: Dyssynchronous contraction of the left ventricular (LV) myocardium is increasingly recognized as an important factor that may contribute to global LV systolic dysfunction. This study ai...
Erratum to: Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects
Authors: Thomas-Thi Pluess, Daniel Hayoz, Mette M. Berger, Luc Tappy, Jean-Pierre Revelly, Burkhard Michaeli, Yvon A. Carpentier, René L. Chioléro
Journal: Intensive Care Medicine (2007)
Improved Safety Profile of Novel Adenovirus Based Vectors "Capsid-displaying" Complement Inhibitors: Increased Potential for Cardiovascular Gene Transfer Applications
Authors: Sergey S. Seregin, Zachary C. Hartman, Daniel M. Appledorn, Yasser A. Aldhamen, Nathaniel J. Schuldt, Mathew Bujold, Sarah Godbehere, Andrea Amalfitano
Journal: Circulation (2009)

Adenovirus (Ad) based vectors continue to be the most commonly utilized vector for gene therapy trials, with cardiovascular diseases being a primary target. Despite this, Ad induced innate immune responses limit enthusiasm towards more widespread utilization of Ad vectors. Many of these innate immune responses are initiated by Ad capsid activation of the complement system. In this study we characterized a new class of Ad vector, genetically engineered to “capsid-display” the natural complement inhibitor decay accelerating factor (DAF), in an effort to mitigate/abrogate complement dependent innate immune responses. We found that several dosages of an Ad5-GFP control virus caused acute thrombocytopenia. In contrast, the Ad vector displaying DAF did not induce thrombocytopenia. In fact, platelet counts in Ad5-dDAF injected WT mice were not significantly different from counts obtained from Ad5-GFP injected complement deficient (C3-KO) mice at any time point or dose tested. Next, utilizing quantitative bead array based assays we determined that intravenous injection of Ad5 vectors induce release of sICAM-1 (1.5 fold) and sE-selectin (6 fold). In contrast, Ad5-dDAF injected mice had sICAM-1 and sE-selectin plasma levels identical to those measured in Ad5-GFP injected C3-KO mice, and significantly reduced as compared to Ad5-GFP injected WT mice. Ad5-GFP injected C3-KO mice, as well as WT mice injected with the Ad5-dDAF vector had significantly reduced activation of pro-inflammatory genes in heart tissues as compared to WT mice treated with a conventional Ad vector. We found that Ad5-dDAF induction of TLR9, MyD88 and NFkB was significantly mitigated, indicating reduced inflammation in the heart.  Conclusion: We have developed a viable, highly improved Adenovirus vector that capsid displays the human DAF complement regulator. This novel vector significantly reduced Ad triggered thrombocytopenia, endothelial cells activation and pro-inflammatory gene induction in heart tissues, while preserving transduction efficiency. We believe that DAF displaying Ad vectors may become an important gene transfer platform for a variety of cardiovascular applications.  This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Institutional blind spot around mental health needs of paediatric patients
Authors: Sebastian Kraemer
Journal: BMJ (2015)

“In brief” cites the new Care Quality Commission (CQC) survey of children in hospital: “87% rated their overall experience as seven or above out of 10.”1 This gives a false impression. I hope a more detailed report from The BMJ will follow. In its report, the CQC states “Less than half (49% of parents …
Abstract 165: Trpv1 Agonist Rinvanil Induces Pharmacological Hypothermia and Improves the Outcome of CPR in a Rat VF Model
Authors: Fengqing Song, Keld Fosgerau, Tao Yu, Yinlun Weng, Sungphil Chung, Shijie Sun, Max H Weil, Wanchun Tang
Journal: Circulation (2010)

Therapeutic hypothermia after resuscitation was recommended as a routine management by the AHA. However, the optimal cooling method still remains to be investigated. Studies have demonstrated that TRPV1 agonist increases skin vasodilation and decreases body temperature and reduces metabolism. In this study, we investigated the effects of TRPV1 receptor agonist Rinvanil on the outcome in a rat model of CPR. We hypothesized that Rinvanil could induce hypothermia therefore improve survival. VF was induced electrically in 10 male Sprague-Dawley rats and untreated for 6 mins. CPR was started 6 mins prior to defibrillation. Thirty mins after ROSC, animals were randomized to receive either saline vehicle or Rinvanil infusion. The starting dose of Rinvanil was 2.5 mg/kg/h. Dosage was gradually increased to 15 mg/kg/h over 6 hours. The control animals received the same amount of saline. Temperature and myocardial function were monitored for 6 hours and 7 day survival time was observed. Temperature decreased more than 2.5°C with infusion of Rinvanil (Figure 1). Post resuscitation myocardial function was significantly better in the Rinvanil group than that in vehicle group (P<0.05) (Figure 2). Survival was improved in the Rinvanil group when compared with vehicle group (116±76hours vs 20±13hours, P<0.05). TRPV1 receptor agonist Rinvanil induced hypothermia following ROSC and improved myocardial function as well as survival in this rat model of CPR.

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A Candidate Dengue Vaccine Walks a Tightrope
Authors: Cameron P. Simmons
Journal: New England Journal of Medicine (2015)

The most advanced candidate vaccine against dengue viruses, called CYD-TDV, is progressing toward potential registration and review by the World Health Organization (WHO) in 2016. CYD-TDV is a formulation of four chimeric yellow fever 17D vaccine viruses, each one engineered to express the surface envelope and prM (membrane) proteins from one of the four serotypes of dengue virus. The surface envelope protein is a target of virus-neutralizing antibodies. The safety and efficacy of CYD-TDV after the administration of three doses over a 12-month period was recently measured in two pediatric phase 3 trials in Latin America1 and Southeast Asia.2 The . . .
Stable in vivo expression of glucose-6-phosphate dehydrogenase (G6PD) and rescue of G6PD deficiency in stem cells by gene transfer
Authors: Ana Rovira, Maria De Angioletti, Olga Camacho-Vanegas, Delong Liu, Vittorio Rosti, Humilidad F. Gallardo, Rosario Notaro, Michel Sadelain, Lucio Luzzatto
Journal: Blood (2000)
Abstract 15450: Ets Related Protein 71 Regulates Cardiac Morphogenesis
Authors: Tara L Rasmussen, Junghun Kweon, Anwarul Ferdous, Kathy Bowlin, Naoko Koyano-Nakagawa, Daniel J. Garry
Journal: Circulation (2010)

To decipher the Nkx2-5 mediated transcriptional networks that govern fate decisions in multipotent cardiac progenitor cells, a transcriptome analysis revealed that Ets related protein 71 (ER71) was a downstream target of Nkx2.5 in the developing mouse heart. We further demonstrated that ER71 was essential for development of primitive hematopoiesis, the endothelial/endocardial lineages and cardiac development resulting in early (E8.0-E9.0) embryonic lethality of the ER71 null embryo. Transcriptome analysis of the ER71 null and WT littermate embryos support the hypothesis that lineage specific gene expression associated with the hematopoietic, endothelial/endocardial and cardiovascular lineages are absent or significantly dysregulated in the ER71 null embryo. To examine whether ER71 is a novel marker of a common mesangioblast progenitor population, a 3.9 kb ER71-Cre transgenic animal was engineered and mated with the Rosa lox-stop-lox-LacZ reporter mouse model. We observed that ER71 expressing cells daughter the hematopoietic, endothelial/endocardial and a subset of the myocardial lineages early during development (E9-E11). To complement these fate mapping studies, we generated the 3.9 kb ER71-EYFP transgenic mouse model and utilized FACS analysis to define the population or populations of cells in which ER71 is expressed (E7.5-E9.5). We further crossed the ER71-EYFP reporter into the ER71 null background to determine the stage at which the development of the affected lineages is aborted. Together, these studies support the conclusion that ER71 functions in uncommitted progenitor cells to affect embryonic heart development as well as endothelial and hematopoietic lineage commitments.
Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line
Authors: A Pinto, D Aldinucci, A Gloghini, V Zagonel, M Degan, S Improta, S Juzbasic, M Todesco, V Perin, V Gattei, F Herrmann, HJ Gruss, A Carbone
Journal: Blood (1996)
Abstract 15195: MMP-9 Serum Levels Predict Carotid Artery Plaque Progression in Patients without but Not in Patients with Statin Treatment
Authors: Walter S Speidl, Matthias Hoke, Jasmin Amighi, Wolfgang Mlekusch, Gerald Maurer, Renate Koppensteiner, Erich Minar, Johann Wojta, Martin Schillinger
Journal: Circulation (2011)

Background. Matrix metalloproteinase-9 (MMP-9) is expressed in carotid plaques and can reduced by statin treatment. The aim of our study was to examine whether serum levels of MMP-9 are associated ...
Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Paul W Armstrong, Christopher B Granger, Peter X Adams, Christian Hamm, David Holmes, William W O'Neill, Thomas G Todaro, Alec Vahanian, Frans Van de Werf
Journal: JAMA (2007)

ContextReperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents.ObjectiveTo evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI.Design, Setting, and PatientsThis trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006.InterventionsTwo thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset.Main Outcome MeasuresThe primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90.ResultsNo difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91).ConclusionIn this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.Trial Registrationclinicaltrials.gov Identifier: NCT00091637