tbuckley/cabot-search huggingface dataset:
Barriers for mental health services for children and adolescents are too high, finds regulator
Authors: Nigel Hawkes
Journal: BMJ (2018)

Mental health services for children and adolescents in England are not working well, the Care Quality Commission has said in a new report.

Schools, local authorities, and the NHS are not working together as well as they might, and the barriers to getting care are unacceptably high, the report said. “You shouldn’t have to be suicidal to get an appointment” was the succinct summary of one service user quoted.1

Despite recent commitments to better funding and government proposals to establish mental health teams in schools, the report said that these would not be enough to achieve the scale of change needed. It made a series of recommendations, including closer collaboration between agencies, a higher priority for children’s mental health, “innovative approaches based on local need,” better quality data, and the greater …
Non-invasive monitoring of <i>in vivo</i> hydrogel degradation and cartilage regeneration by multiparametric MR imaging
Authors: Zelong Chen, Chenggong Yan, Shina Yan, Qin Liu, Meirong Hou, Yikai Xu, Rui Guo
Journal: Theranostics (2018)

Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering.However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging.Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration.The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro.The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months.Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate.Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro.CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo.The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations.Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration.
Identifying high surgical risk in muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC).
Authors: Kathryn E. Marqueen, Nikhil Waingankar, John Sfakianos, Reza Mehrazin, Scot Anthony Niglio, François Audenet, Rachel Jia, Madhu Mazumdar, Bart Ferket, Matt D. Galsky
Journal: Journal of Clinical Oncology (2018)

460 Background: Although RC is the standard treatment for MIBC, it is associated with non-negligible morbidity and mortality. Given the advanced age and prevalence of comorbidities in MIBC patients, many are suboptimal RC candidates. We sought to develop a prediction rule for determining high surgical risk using routinely available pre-surgical variables. Methods: We identified N=8,634 patients with MIBC (cT2-T4aN0M0) who underwent RC, without perioperative chemotherapy, within the National Cancer Database (2003-2012). Using multi-state modeling, we calculated time spent in 3 health states: hospitalized, discharged and death over 90 days post-RC. Predictors were selected in a stepwise manner. Cross validation was performed leaving one of 6 geographic regions out to assess model performance. Time spent in each state was weighted by utility (0=death, 1=full health) to determine 90d quality-adjusted survival (QAS) as a composite of morbidity and mortality. Results: Median age: 69y (IQR 62-78), mean length of stay: 10±12d, and 90d mortality: 654/8,634 (7.6%). Increasing age, cT stage, Charlson comorbidity index (CCI) and lower hospital RC volume were associated with greater 90d mortality (Table). C-statistics of 0.57-0.73 and calibration slopes of 0.54-1.37 (1=perfect) were sufficient across the regions. Our model predicted 25% of patients had a 90d mortality &gt;10%; observed 90d mortality in this group was 14.0% (95% CI 12.5-15.5). Mean QAS was 63d (range 43-68). Conclusions: We developed a multi-state model to identify high post-RC risk that may ultimately help to identify patients for ‘prehabilitation’ strategies and/or inform standard definitions of ‘cystectomy ineligibility’ for clinical trials. [Table: see text]
Novel phosphorylated TAK1 species with functional impact on NF-κB and β-catenin signaling in human Cutaneous T-cell lymphoma
Authors: Fernando Gallardo, Joan Bertran, Erika López-Arribillaga, Jéssica González, Silvia Menéndez, Ignacio Sánchez, Luis Colomo, Mar Iglesias, Marta Garrido, Luis Francisco Santamaría-Babí, Ferran Torres, Ramon M Pujol, Anna Bigas, Lluís Espinosa
Journal: Leukemia (2018)

Cutaneous T-cell lymphomas (CTCLs) represent different subtypes of lymphoproliferative disorders with no curative therapies for the advanced forms of the disease (namely mycosis fungoides and the leukemic variant, Sézary syndrome). Molecular events leading to CTCL progression are heterogeneous, however recent DNA and RNA sequencing studies highlighted the importance of NF-κB and β-catenin pathways. We here show that the kinase TAK1, known as essential in B-cell lymphoma, is constitutively activated in CTCL cells, but tempered by the MYPT1/PP1 phosphatase complex. Blocking PP1 activity, both pharmacologically and genetically, resulted in TAK1 hyperphosphorylation at residues T344, S389, T444, and T511, which have functional impact on canonical NF-κB signaling. Inhibition of TAK1 precluded NF-κB and β-catenin signaling and induced apoptosis of CTCL cell lines and primary Sézary syndrome cells both in vitro and in vivo. Detection of phosphorylated TAK1 at T444 and T344 is associated with the presence of lymphoma in a set of 60 primary human samples correlating with NF-κB and β-catenin activation. These results identified TAK1 as a potential biomarker and therapeutic target for CTCL therapy.
Doctors reject college’s call for return to longer hours
Authors: Abi Rimmer
Journal: BMJ (2016)

Doctors have raised concerns after the president of the Royal College of Surgeons of England (RCS), Clare Marx, said that the European Working Time Directive prevented junior doctors from gaining enough training time.

Marx told the Telegraph that removing the need to follow European Union working time rules when the United Kingdom leaves the EU would improve patient safety by allowing surgeons to undertake thousands of hours of extra training.1 She said, “Because of the working time regulations it’s been extremely difficult to get surgeons enough training.”

Marx continued, “We have progressively seen doctors anxious because they are not getting enough hours. To get good at …
The effects of electronic cigarette vapour on the lung: direct comparison to tobacco smoke
Authors: Viktorija Reinikovaite, Ivan E. Rodriguez, Vijaya Karoor, Aline Rau, Becky B. Trinh, Frederic W-B. Deleyiannis, Laima Taraseviciene-Stewart
Journal: European Respiratory Journal (2018)

Electronic cigarette (e-cigarette) usage in the USA has drastically increased in the past 5 years due to age restrictions on conventional cigarettes, aggressive marketing and a perception that e-cigarettes are a healthy alternative. E-cigarettes contain nicotine, water, glycerol, propylene glycol and optional flavouring. On inhalation, the device heats the ingredients into a vapour [1]. While tobacco cigarette smoke is known to cause deleterious effects on the cardiovascular system, angiogenesis and skin capillary perfusion by causing direct injury to blood vessel walls, increased platelet aggregation, microvascular thrombosis [2–4] and inflammation [5], the consequences of e-cigarette vapour exposure on the lung are still largely unexplored [6, 7]. Recently, Lerner et al. [8] reported that vapours produced by e-cigarettes and e-cigarette fluids with flavourings induced toxicity, oxidative stress and inflammatory response in human bronchial airway epithelial cells (H292) and fetal lung fibroblasts (HFL1) as well as mouse lung. Garcia-Arcos et al. [9] showed that the aerosolised nicotine-containing e-cigarette fluid increased airway hyperreactivity, distal airspace enlargement, mucin production, and cytokine and protease expression in mice, implying potential dangers of nicotine inhalation during e-cigarette use. The inflammatory response to e-cigarette use involved increased neutrophil activation and mucus production [10], and decreased mucociliary clearance [11]. In human embryonic and mouse neural stem cells, human pulmonary fibroblasts [12], and skin and lung cells [13], cytotoxicity of e-cigarette vapour was correlated with the number and concentration of chemicals used to flavour the fluids. We recently showed in the skin flap survival model in vivo that nicotine-containing e-cigarette vapour is just as harmful to the microcirculation as tobacco cigarette smoke [4]. Electronic cigarettes are as toxic as tobacco cigarettes and can cause significant lung damage <http://ow.ly/qT1l30ig1oR>
Role of smooth muscle cells in coronary artery bypass grafting failure
Authors: Kerry Wadey, Joshua Lopes, Michelle Bendeck, Sarah George
Journal: Cardiovascular Research (2018)

Atherosclerosis is the underlying pathology of many cardiovascular diseases. The formation and rupture of atherosclerotic plaques in the coronary arteries results in angina and myocardial infarction. Venous coronary artery bypass grafts are designed to reduce the consequences of atherosclerosis in the coronary arteries by diverting blood flow around the atherosclerotic plaques. However, vein grafts suffer a high failure rate due to intimal thickening that occurs as a result of vascular cell injury and activation and can act as 'a soil' for subsequent atherosclerotic plaque formation. A clinically-proven method for the reduction of vein graft intimal thickening and subsequent major adverse clinical events is currently not available. Consequently, a greater understanding of the underlying mechanisms of intimal thickening may be beneficial for the design of future therapies for vein graft failure. Vein grafting induces inflammation and endothelial cell damage and dysfunction, that promotes vascular smooth muscle cell (VSMC) migration, and proliferation. Injury to the wall of the vein as a result of grafting leads to the production of chemoattractants, remodelling of the extracellular matrix and cell-cell contacts; which all contribute to the induction of VSMC migration and proliferation. This review focuses on the role of altered behaviour of VSMCs in the vein graft and some of the factors which critically lead to intimal thickening that pre-disposes the vein graft to further atherosclerosis and re-occurrence of symptoms in the patient.
The disruptive doctor
Authors: Marika Davies, Mark Dinwoodie
Journal: BMJ (2015)

<h3>Summary</h3> The future climate will be characterized by an increase in frequency and duration of drought and warming that exacerbates atmospheric evaporative demand. How trees acclimate to long-term soil moisture changes and whether these long-term changes alter trees’ sensitivity to short-term (day to months) variations of vapor pressure deficit (VPD) and soil moisture is largely unknown. Leaf gas exchange measurements were performed within a long-term (17 years) irrigation experiment in a Scots pine-dominated forest in one of Switzerland’s driest areas on trees in naturally dry (control), irrigated, and‘irrigation-stop’ (after 11 years of irrigation) conditions. Seventeen years of irrigation increased photosynthesis (A) and stomatal conductance (g<sub>s</sub>) and reduced the g<sub>s</sub> sensitivity to increasing VPD but not to soil drying. Following irrigation-stop, gas exchange did not decrease immediately, but after three years, had decreased significantly in irrigation-stop trees. Vc<sub>max</sub> and J<sub>max</sub> recovered after five years. These results suggest that long-term release of soil drought reduces the sensitivity to atmospheric evaporative demand and that atmospheric constraints may play an increasingly important role in combination with soil drought. In addition, they suggest that structural adjustments lead to an attenuation of initially strong leaf-level acclimation to strong multiple-year drought.
Immunologic profile and prognostic significance of tumor-infiltrating lymphocytes in renal cell carcinoma.
Authors: Amir Ishaq Khan, Caroline Stewart Jansen, Jennifer Wilkinson Carlisle, Kevin Richard Melnick, Kyu Seo Kim, Fares Hosseinzadeh, Nataliya Prokhnevska, Mehmet Asim Bilen, Viraj A. Master, Haydn T. Kissick
Journal: Journal of Clinical Oncology (2018)

673 Background: Renal cell carcinoma (RCC) has been shown to be a genetically and morphologically heterogeneous cancer. As studies show the significance of tumor-infiltrating lymphocytes (TIL) in cancer, it is critical to examine how the phenotype of TILs manifests in RCC. Such analysis may help explain the role of the immune landscape in developing resistance and its contribution to the high treatment failure observed in immunotherapy for RCC. This study compares the immune phenotype of primary tumors, venous tumor thrombi (VTT), and metastases, as well as multiple sites within primary tumors, and investigates whether inter- and intra-tumoral immune heterogeneity is present in RCC. The association of TIL levels and clinical prognosis will also be assessed and compared with current RCC prognostic scores. Methods: Our cohort included 15 VTT and 6 metastases (3 adrenal, 2 bone, 1 liver) with 20 matched primary tumors, as well as 25 non-metastatic primary tumors. The RCC tissue was collected and digested into single cell suspensions. Suspensions were stained for TIL surface markers and processed using flow cytometry. The data was analyzed to capture %CD8 + and %CD4 + in total tumor. The %CD28 + and %PD1 + of CD8 + cells were measured to describe the co-stimulatory and co-inhibitory receptor expression, respectively. Clinical data was obtained to calculate the Mayo Stage, Size, Grade, and Necrosis (SSIGN) and UCLA Integrated Staging System (UISS) scores for each patient and to evaluate recurrence. Results: Immunologic concordance was observed in all measured parameters (%CD8 + , %CD4 + , %CD28 + , and %PD1 + ) for primary tumors and VTT, for primary tumors and their metastases, and for different sites within 10 primary tumors. In our overall cohort, %CD8 + was found to be inversely associated with recurrence (p = 0.02). Furthermore, %CD8 + was not significantly associated with patient Mayo SSIGN and UISS scores. Conclusions: Despite the genetic and morphologic heterogeneity seen in RCC, immunologic concordance was observed for both inter- and intra-tumoral analysis. The association between %CD8 + and recurrence presents a novel and objective immune-based prognostic factor for RCC, independent of Mayo SSIGN and UISS scores.
Prognostic Value of Right Ventricular Dysfunction on Clinical Outcomes After Transcatheter Aortic Valve Replacement
Authors: Masahiko Asami, Stefan Stortecky, Fabien Praz, Jonas Lanz, Lorenz Räber, Anna Franzone, Raffaele Piccolo, George C.M. Siontis, Dik Heg, Marco Valgimigli, Peter Wenaweser, Eva Roost, Stephan Windecker, Thomas Pilgrim
Journal: JACC. Cardiovascular imaging (2018)
TRENDS AND IMPACT OF PSYCHOSOCIAL FACTORS IN ADULTS WITH CONGENITAL HEART DISEASE IN THE UNITED STATES
Authors: Shanti Patel, Aparna Saha, Priti Poojary, Dishita Pandya, Sumeet Pawar, Jignesh Patel, Kanika Mahajan, Pratik Mondal, Shivkumar Agarwal, Gerald Hollander, Jacob Shani, Stephan Kamholz
Journal: Journal of the American College of Cardiology (2018)
Hand fracture management course
Authors: Tarek Boutefnouchet
Journal: BMJ (2010)

The hand fracture management course is aimed at specialist registrars and specialty trainees in trauma and orthopaedics and plastic surgery. It is also aimed at core trainees who want to pursue a career in trauma and orthopaedics or plastic surgery. The course attracts participants from all over the United Kingdom, ranging from people in basic surgical training to more senior registrars. Most delegates have completed membership of the Royal College of Surgeons and have some experience in trauma and orthopaedics, plastic surgery, or both. Although not mandatory, previous completion of a basic fracture management course would be desirable because participants will have a greater appreciation of the principles taught on the hand fracture management …
Abstract P254: Is Obesity Associated With the Predicted 6-Month Mortality in Patients With Atrial Fibrillation and Acute Coronary Syndrome?
Authors: Roseann Chesler, Daniel Fung, Haroon Kamran, Erdal Cavusoglu, Judith E Mitchell
Journal: Circulation (2018)

Introduction: The blunting of the expected improvement in cardiovascular health over the past decade has been attributed in part to the substantial increase in the prevalence of obesity. Atrial fibrillation and heart failure are among the cardiovascular diseases with increasing incidence in the US. We sought to evaluate the effect of obesity on the predicted 6-month mortality in our patients with atrial fibrillation [AF] and acute coronary syndrome [ACS] utilizing the GRACE score [GS], a validated risk assessment model for predicting death within 6-months of hospital discharge. Methods: Eighty patients, 88% black, 54% female, mean age 68, +/-12, h/o AF admitted with ACS were included. Results: An extraordinarily high prevalence of DM and HTN [46% and 95% respectively] and obesity [46%] were noted. The mean weight: 87 Kg, +/- 23. The mean BMI was 31 kgm 2 , +/-10; median BMI 29 kgm 2 and 25% had a BMI of 35 kgm 2 or greater, (Chart). Seventy-five percent of the cohort had clinical or radiographic evidence of congestion. Ejection fraction: mean 45%, +/-17. B-type natriuretic peptide [BNP] level: mean 765 pg/ml. BNP was significantly and negatively related to obesity [BMI p= 0.0001; r= - 0.422; weight p= 0.001; r= - .359]. This inverse relationship of BNP and obesity was most apparent when comparing the level of BNP in patients who were at or above the median BMI (29.3 kgm 2 ), p= 0.001, (Fig). Although we found a significant direct association of the GS with age [p&lt;0.001; r= .62], troponin [p=0.001; r= .74] and BNP [p= 0.018; r= .41], no independent significant relationship was apparent with obesity [weight p= 0.54; r= -.11, or BMI p= 0.11; r= -.28]. Conclusions: In a traditionally high risk cohort with AF and ACS a high prevalence of obesity was recorded. Clinical or radiographic evidence of congestion was present in the majority. We found no significant link between obesity in this population and the GS—predictor of 6-month mortality. Can this be another cardiovascular paradox? Lengthier outcome studies of larger cohorts are warranted.
Blunted cerebral oxygenation during exercise in women with gestational diabetes mellitus: associations with macrovascular function and cardiovascular risk factors
Authors: Evangelia Kintiraki, Konstantina Dipla, Areti Triantafyllou, Nikolaos Koletsos, Iris Grigoriadou, Pavlos Poulakos, Vasileios Sachpekidis, Ioannis S. Vrabas, Andreas Zafeiridis, Eleni Bili, Stella Douma, Dimitrios G. Goulis
Journal: Metabolism (2018)
Health professionals need more autonomy, says Nuffield Trust
Authors: Matthew Limb
Journal: BMJ (2015)

Transforming the NHS’s future will depend on empowering clinical staff to “do the right thing” and boosting professional autonomy, the Nuffield Trust has said.

Nigel Edwards, chief executive of the trust, told a conference earlier this month that it was time to stop trying to use “micro-incentives” to control the behaviour of clinical professionals. “Policy makers on the whole are not clever enough to do it, the environment is too dynamic, and we should give up on that particular dead end,” he said. “Most of the policy instruments we’ve got are substitutes for the failure of professional leadership.”

Edwards spoke at a seminar on the future of the NHS one year on from the publication of the Five Year Forward View .1 The seminar was held by Westminster Health Forum in London on 20 October.

The debate explored what it would take for the NHS and health professionals to …
ASSOCIATION OF VASCULAR STIFFNESS WITH PREVALENT CARDIOVASCULAR DISEASE IN AFRICAN AMERICANS: THE JACKSON HEART STUDY
Authors: Josiah Moore, Solomon Musani, Floyd Washington, Yuichiro Yano, Keith Cobb, Connie Tsao, Emelia Benjamin, Naomi M. Hamburg, Ramachandran Vasan, Gary Mitchell
Journal: Journal of the American College of Cardiology (2018)
A New Ultrasound Method for Estimating Dynamic Intrinsic Positive Airway Pressure: A Prospective Clinical Trial
Authors: Emanuele Bernardi, Lara Pisani, Luca Fasano, Giuseppe Lauria, Vittoria Comellini, Lorenzo Appendini, Giorgio Conti, Francesco Tosello, Elisa Pizzolato, Stefano Nava
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Glasgow Royal Infirmary otology and audiology course
Authors: Rishi Srivastava, Claudia Nogueira
Journal: BMJ (2012)

The Glasgow Royal Infirmary otology and audiology course is an annual four day programme run by Professor George Browning at Glasgow Royal Infirmary and the Royal Hospital for Sick Children at Yorkhill. The aim of the course is to improve the management of patients with otological symptoms.

When this course first started, it was aimed at ear, nose, and throat (ENT) clinicians at consultant level. This course is now in its 27th year and participants are mainly ENT registrars or middle grade doctors and audiologists at various stages in their careers who want to improve and refresh their knowledge and clinical skills. There are 20 places available on the course, with tuition divided into four groups of five participants. The course is usually …
Abstract 15818: Willingness to Reinitiate Statins by Cardiovascular Disease Risk: Data From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Rikki M Tanner, Monika M Safford, Keri L Monda, Benjamin Taylor, Lisandro D Colantonio, Ricardo Dent, Michael E Farkouh, Paul Muntner, Robert S Rosenson
Journal: Circulation (2016)

Introduction: Statins are an effective therapy to reduce cardiovascular disease (CVD) risk. Studies suggest many people who discontinue statins can be successfully re-challenged and continue therap...
Advanced communication skills training for senior clinicians
Authors: Gopalakrishnan Deivasikamani
Journal: BMJ (2012)

Effective communication skills are important for patient care, and patients and their families value good communication highly. But in practice communication is sometimes poor, leading to frustration, despair, strained doctor-patient relationships, and complaints. So, to improve communication skills a national programme was set up in accordance with the NHS cancer plan (2000), reinforced by the National Institute for Health and Clinical Excellence guidance on supportive and palliative care (2004).

It is a learner centred course for training in advanced communication skills. It includes workshops that entail role play and feedback. The main aim is to improve communication skills and to learn how to be an effective communicator. …
Enhancing training opportunities under the new deal—a trainee's perspective
Authors: Jaspreet Kaur
Journal: BMJ (2005)

The European Working Time Directive (EWTD), a non-negotiable part of health and safety legislation, was implemented in August 2004, and is fixed in law. <i>Harvinder Pal Singh, Raj Parmesaran, Sunil Apsingi</i>, and <i>Jaspreet Kaur</i> discuss how junior doctors have been affected thus far