tbuckley/cabot-search huggingface dataset:
SURG-14. MDA EXPERIENCE OF LANGUAGE MAPPING USING TMS IN BRAIN TUMOR PATIENTS
Authors: Dhiego Chaves De Almeida Bastos, Bhanu Gogia, Sudhakar Tummala, Sherise Ferguson, Frederick F Lang, Ian Mccutcheon, Jeffrey S Weinberg, Jaimie Payne, Katherine Connelly, Sujit S Prabhu
Journal: Neuro-Oncology (2017)

Presurgical use of transcranial magnetic stimulation for speech mapping in patients with brain lesions involving language related areas and compare it to direct cortical stimulation. The TMS presurgical mapping was performed using the Helsinki and Berlin NBS (Navigated Brain Stimulation) Protocol (2016). To interpret the results, video-based off-line review was performed by two independent observers and a speech pathologist. The responses during stimulation were compared to the patient`s baseline. Language disturbances were classified as classical errors (speech arrest/anomia, semantic and performance) and non-classical errors (delays, hesitation, muscle stimulation). The positive points were exported to the navigation system. DCS positive and negative points were acquired by the navigation system. All points from DCS and TMS were then plotted into a cortical parcellation system that divides the lateral surface of the brain in 37 regions. Regions were labeled positive in TMS when they had one classical error or a cluster of non-classical errors, and positive in DCS when they had reproducible errors. Positive and negative regions were compared for TMS and DCS. Twelve patients were prospectively enrolled in this study. The patients were classified according to speech performance issues in 4 categories (normal, minor, major, aphasic), the majority of patients had normal (6) or minor issues (5). 33% had no positive DCS points. When comparing TMS points with DCS, the sensitivity of TMS was 93.75%, specificity was 91.71%, positive predictive value was 83.33% and negative predictive value (NPV) was 93.75. The patients with major speech issues had a sensitivity of 50% and a NPV of only 50%. 5 patients had complete resection and 2 patients had only a biopsy performed. Good overall correlation with TMS and DCS was seen. True negative correlation between TMS and DCS helped surgical resection.
GP leader urges government to step up investment
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Politicians cannot afford to rest on their laurels, despite recent steps to tackle the crisis in general practice, and must invest more in primary care and the wider NHS, England’s GP leader has urged.

In a keynote speech to the conference of England’s local medical committees in London on 10 November, Richard Vautrey, chair of the BMA’s General Practitioners Committee, called on politicians of all parties to support the case for further investment to help build on steps already taken through NHS England’s General Practice Forward View plan.

“We need politicians and policy …
Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts
Authors: Lavinia Paternoster, Olga E.M. Savenije, Jon Heron, David M. Evans, Judith M. Vonk, Bert Brunekreef, Alet H. Wijga, A. John Henderson, Gerard H. Koppelman, Sara J. Brown
Journal: Journal of Allergy and Clinical Immunology (2017)

Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms.We sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts.The presence of AD was examined in 2 birth cohort studies including 9894 children from the United Kingdom (ALSPAC) and 3652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity.Six latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the 2 cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male sex. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognized class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.Six classes based on temporal trajectories of rash were consistently identified in 2 population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.
Abstract 21127: Evaluation of Pulmonary Regurgitation and Aspiration During Cardiopulmonary Resuscitation (cpr): A Crossover Pilot Human Cadaver Study-Preliminary Data
Authors: Kurt Ruetzler, Steve Leung, Mark Chmiela, Barak Cohen, Richard Drake, Nicole Zimmerman, Daniel Sessler
Journal: Circulation (2017)

Introduction: Chest compression and ventilation during CPR may increase risk of regurgitation and aspiration. Pulmonary aspiration is a clinically relevant endpoint as it is associated with significant mortality. There is limited data comparing the impact of continuous and interrupted chest compression during CPR on risk of regurgitation and aspiration. Thus, we aim to obtain a preliminary estimate of incidences of regurgitation and aspiration of continuous versus interrupted chest compression using a cadaver model. Hypothesis: Interrupted chest compression, compared with continuous chest compression during CPR, is associated with a lower risk of regurgitation and aspiration. Methods: In a cross-over design, 10 cadavers (BMI&lt;45 kg/m 2 ) with no airway pathologies were studied. Cadavers were suctioned for pre-existing stomach contents, applied the Lucas CPR board (Physio Control, Redmond, WA) and a King LTS-D supraglottic device was placed. Stomach content was simulated by methylene-blue and barium sulfate for the first and second interventions, respectively. Cadavers were randomized to receive CPR starting with either 1) Continuous compressions (rate of 100/min), while ventilating at rate of 10/min or 2) Interrupted compressions, while ventilating at a rate of 30:2. Each CPR session lasted 14 minutes. Stomach was properly suctioned prior to the next intervention to avoid cross-over contamination. Regurgitation and/or aspiration was assessed by bronchoscopy (methylene blue) and radiography (barium sulfate). Results: The incidence of regurgitation was 100% for continuous chest compression, while that of interrupted chest compression was 70%. The incidence of aspiration of continuous chest compression was 50% while that of interrupted chest compression was 30%. Conclusions: In conclusion, interrupted chest compression was associated with 20% less incidence of aspiration compared to continuous compression during CPR in our cadaver model. Our study is limited by its small size and use of cadavers, but nonetheless estimated incidences of pulmonary aspiration by CPR method to provide insight for future studies.
Existe la necesidad de una producción pública de vacunas a nivel europeo
Authors: D Lévy-Bruhl
Journal: Eurosurveillance (2006)

En esta edicion de Eurosurveillance, Pascale Rouaud y colegas describen un brote prolongado de enfermedades invasivas meningococicas tipo B en el distrito de la Seine-Maritime, al norte de Francia, asociado a la diseminacion local de una cepa clonal de fenotipo B:14:P1.7,16, perteneciente a lo complejo clonal ST32/ET5.
NIMG-74. RADIOMICS OF TUMOR INVASION 2.0: COMBINING MECHANISTIC TUMOR INVASION MODELS WITH MACHINE LEARNING MODELS TO ACCURATELY PREDICT TUMOR INVASION IN HUMAN GLIOBLASTOMA PATIENTS
Authors: Kristin R Swanson, Nathan Gaw, Andrea Hawkins-Daarud, Pamela R Jackson, Kyle W Singleton, Lauren DeGirolamo, Jennifer Eschbacher, Leslie Baxter, Kris Smith, Peter Nakaji, Samuel McGee, Kamala Clark-Swanson, Bernard Bendok, Amylou Dueck, Teresa Wu, Jing Li, Leland Hu
Journal: Neuro-Oncology (2017)

In glioblastoma (GBM), contrast enhanced (CE)-MRI delineates bulk tumor with contrast-enhancement but poorly characterizes invasive tumor in the nonenhancing T2W abnormality. There is extensive literature in both machine-learning (ML) and mechanistic mathematical oncology seeking to accurately predict diffuse tumor invasion from multi-parametric MRI. ML offers strengths of a data-driven iterative approach, while mechanistic (proliferation-invasion, PI) modeling incorporates spatial relationships with expected drop-offs of tumor cell density from central regions of MRI enhancement. In this study, we build and cross-validate a first-of-its-kind hybrid (ML-PI) model. We collected 82 image-guided biopsies from 18 primary GBM patients throughout CE T1W and nonenhancing T2W regions. For each biopsy, we obtained neuropathologist estimates of tumor cell density and spatially matched MRI (CE T1W, T2W) from which we extracted texture features. PI maps of tumor invasion were generated from MRI-based patient-specific estimates of the net rates of invasion and proliferation. Then, the PI maps were incorporated with a ML model that uses texture features to predict cell density to minimize the prediction error on biopsy samples (ML strength) while making sure tumor-wide prediction (biopsied and unbiopsied regions) conformed with glioblastoma biology (PI strength). We optimized this hybrid ML-PI model using leave-one-out-cross-validation, and compared its performance with PI and ML alone. We used Pearson correlation (r) between cross-validated predicted tumor cell density and true tumor cell density. We focused on prediction within the nonenhancing zone (n=32) because accurate estimation of invasive tumor cell density in this zone has important clinical value for radiation and surgical planning. PI-ML showed significantly stronger correlation (r=0.76) compared to PI (r=0.44) and ML (r=0.04) models alone (p value<0.01). We present a first-of-its-kind hybrid model combining mechanistic modeling and machine learning approaches that accurately quantifies tumor cell gradients within the non-enhancing T2W zone of GBM.
GENE-50. GENOMIC PROFILING AND PRECISION MEDICINE IN GLIOBLASTOMA - A PROSPECTIVE STUDY
Authors: Dorte Schou Nørøxe, Jane Skjøth-Rasmussen, Jannick Brennum, Olga Østrup, Savvas Kinalis, Finn Cilius Nielsen, Petra Hamerlik, Hans Skovgaard Poulsen, Ulrik Lassen
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most malignant brain tumor and is extremely heterogenic. To make a molecular tumor profile of newly diagnosed GBM and again in the relapse. If we find possible targets, we will treat accordingly in protocols. Results will be linked to overall survival (OS), progression free survival (PFS) and clinical data. We plan to include 150 newly diagnosed patients and 40 patients from this cohort if second surgery is performed. RNA- and DNA sequencing will be performed with copy number alterations, tumor specific mutations with variance analyses, TERT-promotor mutations, fusion genes and subclass division. Results will be discussed in a multidisciplinary tumor board. From February 2016 - June 2017, 46 newly diagnosed patients have been enrolled of which six have relapsed. All patients had non- mutated IDH-tumors. 10 patients have died with median OS of 6.2 months making these tumors highly aggressive. Five had mesenchymal subtype and nine had non- MGMT methylated tumors. Eight had mutation in the TERT promotor region and none had ATRX mutation. They all had clinical characteristics correlated with poor survival. 22 newly diagnosed patients have had their genomic profile analyzed so far. None have yet been selected for targeted therapy. Mutations in CDKN2A/B, PTEN, EGFR, RB1, TP53 and NF1 were the top 6 mutated genes. CDKN2A/B and PTEN were mutated in 92% and in all samples either one of them was mutated. Subclass variation was equally distributed and subclass shift from proneural to mesenchymal or classical was observed in 2/4 and 1/4 of the analyzed relapse samples. Analysis of molecular aberrations will aid the use of precision medicine in GBM and introduce a more differentiated treatment approach. Genomic profiling will expand the possibility to include GBM patients for targeted therapy and more treatment protocols are warranted.
CD38-NAD+Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response
Authors: Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Megan W. Wyatt, Payal Dhar, Shanmugam Panneer Selvam, Jianing Fu, Jinyu Zhang, Hung Nguyen, Inhong Kang, Kyle Toth, Mazen Al-Homrani, Mahvash Husain, Gyda Beeson, Lauren Ball, Kristi Helke, Shahid Husain, Elizabeth Garrett-Mayer, Gary Hardiman, Meenal Mehrotra, Michael I. Nishimura, Craig C. Beeson, Melanie Gubbels Bupp, Jennifer Wu, Besim Ogretmen, Chrystal M. Paulos, Jeffery Rathmell, Xue-Zhong Yu, Shikhar Mehrotra
Journal: Cell Metabolism (2017)
TNF regulates transcription of NLRP3 inflammasome components and inflammatory molecules in cryopyrinopathies
Authors: Matthew D. McGeough, Alexander Wree, Maria E. Inzaugarat, Ariela Haimovich, Casey D. Johnson, Carla A. Peña, Raphaela Goldbach-Mansky, Lori Broderick, Ariel E. Feldstein, Hal M. Hoffman
Journal: Journal of Clinical Investigation (2017)

The NLRP3 inflammasome is a protein complex responsible for caspase-1–dependent maturation of the proinflammatory cytokines IL-1β and IL-18. Gain-of-function missense mutations in NLRP3 cause the disease spectrum known as the cryopyrin-associated periodic syndromes (CAPS). In this study, we generated Nlrp3-knockin mice on various KO backgrounds including Il1b/Il18-, caspase-1–, caspase-11– (Casp1/11-), and Tnf-deficient strains. The Nlrp3L351P Il1b–/– Il18–/– mutant mice survived and grew normally until adulthood and, at 6 months of age, exhibited marked splenomegaly and leukophilia. Injection of these mice with low-dose LPS resulted in elevated serum TNF levels compared with Nlrp3L351P Casp1/11–/– mice and Il1b–/– Il18–/– littermates. Treatment of Nlrp3A350V mice with the TNF inhibitor etanercept resulted in all pups surviving to adulthood, with normal body and spleen/body weight ratios. Nlrp3A350V Tnf–/– mice showed a similar phenotypic rescue, with marked reductions in serum IL-1β and IL-18, reduced myeloid inflammatory infiltrate in the skin and spleen, and substantial decreases in splenic mRNA expression of both inflammasome components (Nlrp3, Pycard, pro-Casp1) and pro-cytokines (Il1b, Il18). Likewise, we observed a reduction in the expression of both pro-Casp1 and pro-Il1b in cultured Nlrp3A350V Tnf–/– BM-derived DCs. Our data show that TNF is an important transcriptional regulator of NLRP3 inflammasome components in murine inflammasomopathies. Moreover, these results may have therapeutic implications for CAPS patients with partial responses to IL-1–targeted therapies.
EXTH-26. PRMT5 AS A DRUGGABLE TARGET FOR GLIOBLASTOMA THERAPY
Authors: Yeshavanth Kumar Banasavadi-Siddegowda, Alessandra M Welker, Jaime Imitola, Chenglong Li, Jianying Zhang, Christine E Beattie, Robert Baiocchi, Balveen Kaur
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common adult malignant brain tumor. In spite of standard multi modal therapy consisting of surgical resection followed by radiation and concurrent chemotherapy prognosis remains poor. As complexity of tumor heterogeneity is being increasingly recognized as a therapeutic hurdle, the identification of both differentiated and undifferentiated "stem cell like" populations in the tumor highlights the significance of finding novel targets that affect both cell populations. Protein arginine methyltransferase (PRMT5) is one such candidate whose nuclear expression correlates with poor survival and has been reported to be required for survival of differentiated GBM cells and self-renewal of undifferentiated GBM cells. In the current study we screened the specificity and efficacy of four novel PRMT5 inhibitors in the treatment of GBM. Efficacies of these inhibitors were screened using in vitro GBM neurosphere model and in vivo intracranial zebra fish model of glioma. Standard molecular biology methods employed to investigate changes in cell cycle, growth, and senescence. In vitro and In vivo studies revealed that among the four PRMT5 inhibitors, treatment of GBM cells with compound 5 (CMP5) mirrored the effects of PRMT5 knock down wherein it led to apoptosis of differentiated GBM cells, and drove undifferentiated primary patient derived GBM cells into a non replicative senescent state. CONCLULSION: In vivo antitumor efficacy combined with the specificity of CMP5 underscores the importance of developing it for translation.
Il potenziamento della funzione di allerta precoce nella sorveglianza nella Repubblica di Serbia: lezioni apprese dopo un anno di esperienza
Authors: M Valenciano, I Bergeri, D Jankovic, N Milic, M Parlic, D Coulombier
Journal: Eurosurveillance (2004)

La Repubblica di Serbia, con il supporto dell'Organizzazione Mondiale della Sanita (OMS), ha realizzato un sistema di allarme precoce (ALERT) per malattie infettive prioritarie, a complemento di un sistema di sorveglianza che notifica i casi individuali confermati. Qui sono presentati i risultati della sua valutazione, a un anno dalla implementazione del sistema. Il sistema ALERT si basa sulla notifica di 11 sindromi da parte delle strutture assistenziali di base. I data vengono analizzati settimanalmente in ciascun distretto e trasmessi a epidemiologi nazionali. ALERT viene recepito come un sistema semplice e flessibile, con una accettabilita maggiore a livello nazionale che regionale. Alcuni distretti lo percepiscono come un sistema parallelo con scarsa connessione con le misure di controllo. La sensibilita del sistema nel rilevare casi di meningite e stata del 93% e del 37% per i casi di epatite. L'analisi retrospettiva dei dati di ALERT ha permesso di identificare 9 epidemie, 5 delle quali sono state riconosciute da epidemiologi. E' stato il sistema piu tempestivo nello scoprire 4 focolai epidemici identificati da entrambi i sistemi. ALERT e stato utile nell'innescare un'indagine tempestiva e misure di controllo per l'epidemia di hantavirus e salmonellosi e per determinare l'inizio della stagione dell'influenza. Tuttavia, ALERT non ha rilevato cluster di brucellosi e di tularemia identificati da una inspiegabile sindrome febbrile. Questa valutazione ha sottolineato la necessita di avere una visione globale delle attivita di sorveglianza quando si realizzano nuove componenti come ALERT. Mentre le misure di controllo che si basano sulla notifica di casi individuali confermati sono ben comprese e messe in atto, non vengono pienamente capiti l'indagine e il processo di verifica che dovrebbero risultare da un aumento delle sindromi in ALERT. Programmi di training in epidemiologia di campo, quali EPIET, sono quelli piu adatti per operare questo cambio di prospettiva.
NTOX-15. PATIENT PERSPECTIVES ON LUMBAR PUNCTURE
Authors: Yoshie Umemura, Benjamin Weill, Justin Buthorn, Adrienne Boire
Journal: Neuro-Oncology (2017)

To investigate the pre-procedural perceptions and tolerability of lumbar puncture (LP). Novel diagnostic techniques have greatly expanded clinical indications for cerebro-spinal fluid (CSF) sampling, most commonly obtained via LP. Anecdotal evidence suggests that patients perceive LP to be a painful procedure. This study is designed to better understand the perception and experience of LP, to identify potential intervention(s) for improving patient experience. Prospective surveys were conducted in patients (ages 18-99) pre- and post-LP, to obtain exploratory data regarding patient perceptions and actual experience of LP. Pre-and post-LP symptom presence was compared by McNemar’s test, and the severity rated 0 (none) to 10 (the worst imaginable) by Wilcoxon test. This is an interim analysis after the first 38 patients of planned 200. 38 patients completed the surveys during 1/2017-6/2017. Indication for LP was diagnostic (n=30), therapeutic (n=2), or both (n=6) purposes. The indication for LP was correctly identified by 31 patients pre-LP (82%), partially correct in 2 (5%), and incorrect in 5 (13%). Twenty-one (55%) reported anxiety pre-LP. Significantly more patients predicted LP to be painful compared to those who actually found LP to be painful (61% and 29% respectively) (p=0.0075). On 0-10 point scale, patients anticipated significantly greater pain from LP than they reported after the procedure (mean 3.3 and 1.8 respectively, p=0.0066). Patients also reported significantly less nausea after LP (p=0.047). After LP, 29 patients (76%) answered they would repeat LP if recommended by their doctors. In this interim analysis, we observed that although anticipation of pain contributed to pre-procedure anxiety LP was generally well-tolerated. The majority of patients experienced minimal pain. The preliminary results of this study suggest that measures to reduce pre-procedure anxiety may improve the tolerability of LP.
P3.15-008 [F18]PARPi PET as an In Vivo Pharmacodynamic Biomarker of PARP Inhibitor Therapy in Patient-Derived Xenografts of Small Cell Lung Cancer
Authors: B. Lok, J. Laird, B. Carney, S. Kossatz, P. Donabedian, N. Shah, A. Sadique, E. De StanChina, T. Reiner, J. Poirier, C. Rudin
Journal: Journal of Thoracic Oncology (2017)
P1.03-035 Efficacy of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC
Authors: J. Bosch Barrera, E. Sais, S. Verdura, E. Cuyas, D. Roa, A. Hernández, A. Izquierdo, E. Teixidor, W. Carbajal, M. Lopez, J. Brunet, J.A. Menendez
Journal: Journal of Thoracic Oncology (2017)
Emergence d’infections à SARM chez des chevaux dans un hôpital vétérinaire : caractérisation des souches et comparaison avec des souches humaines
Authors: C Cuny, J Kuemmerle, C Stanek, B Willey, B Strommenger, W Witte
Journal: Eurosurveillance (2006)

Les Staphylococcus aureus resistants a la methicilline (SARM) sont devenus un probleme de sante publique emergent dans le monde entier, n’etant plus associes uniquement a des infections nosocomiales. A l’exception de quelques publications recentes d’infections chez des chats, des chiens et des chevaux, les infections a SARM sont rarement decrites chez les animaux de compagnie. L’article suivant decrit les resultats d’infections a SARM chez des chevaux dans un hopital veterinaire universitaire d’Europe centrale.