tbuckley/cabot-search huggingface dataset:
Value of difficult temperament among 7-year-olds in the general population for predicting psychiatric diagnosis at age 12
Authors: M Maziade, P Capéraà, B Laplante, M Boudreault, J Thivierge, R Côté, P Boutin
Journal: American Journal of Psychiatry (1985)

The authors assessed the predictive value of "difficult" temperament, as defined in the New York Longitudinal Study, in 12-year-old children from the general population of Quebec City whose temperaments had been determined to be difficult or easy at age 7. The difficult and easy temperament groups were balanced for age, sex, and socioeconomic status. The authors used many convergent measuring devices and were blind to the temperament scores of the children at age 7. Temperamentally difficult children had more clinical disorders at age 12 that qualified for a DSM-III diagnosis. An association with family dysfunction in terms of behavior control seemed to increase this risk: there was a lower rate of clinical disorders among children in superior functioning families than among those in dysfunctional families.
Phylogenetic analysis of West Nile virus isolated in Italy in 2008
Authors: G Savini, F Monaco, P Calistri, R Lelli
Journal: Eurosurveillance (2008)

In Italy the first occurrence of West Nile virus (WNV) infection was reported in Tuscany region during the late summer of 1998. In August 2008, the WNV infection re-emerged in Italy, in areas surrounding the Po river delta, and involving three regions Lombardy, Emilia Romagna and Veneto. WNV was isolated from blood and organs samples of one horse, one donkey, one pigeon (Columba livia) and three magpies (Pica pica). The phylogenetic analysis of the isolates, conducted on 255 bp in the region coding for the E protein, indicates that these isolates belong to the lineage I among the European strains. According to the analysis, both the 1998 and 2008 Italian strains as well as isolates from Romania, Russia, Senegal and Kenya fell in the same sub-cluster.
Ethics of off-label treatment.
Authors: C D Atkins
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.4.1637 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9552081 Ethics of off-label treatment. C D AtkinsxC D AtkinsSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.4.1637 PDF "Ethics of off-label treatment.." Journal of Clinical Oncology, 16(4), p. 1637© 1998 by American Society of Clinical Oncology
Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy
Authors: Jordi Sanahuja, Núria Alonso, Javier Diez, Emilio Ortega, Esther Rubinat, Alícia Traveset, Núria Alcubierre, Àngels Betriu, Esmeralda Castelblanco, Marta Hernández, Francisco Purroy, Maria Vittoria Arcidiacono, Carmen Jurjo, Elvira Fernández, Manuel Puig-Domingo, Per-Henrik Groop, Dídac Mauricio
Journal: Diabetes Care (2016)

OBJECTIVE We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. RESEARCH DESIGN AND METHODS We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40–75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). RESULTS The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P &amp;lt; 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P &amp;lt; 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P &amp;lt; 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P &amp;lt; 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P &amp;lt; 0.01 for both variables). CONCLUSIONS Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina.
Clinical utility of blood derived gene cluster analysis of neuroendocrine tumors using neoplasia hallmark criteria.
Authors: Mark S. Kidd, Ignat Drozdov, Irvin Mark Modlin
Journal: Journal of Clinical Oncology (2015)

e15193 Background: We developed a multianalyte blood (51 transcript) assay (MAAA) for GEP-NETs with a sensitivity (98%) and specificity (97%). We now explore tissue expression levels to define by cluster analysis, the biological “hallmarks” of NET neoplasia (proliferation, growth factor signaling). We hypothesized that delineation of blood-based functional gene cluster analysis will provide a predictive value to define disease status. Methods: We evaluated expression in 2 NET transcriptome databases (Group 1: n= 15) by GeneProfiler. Group 2 (n= 22 NETs): tissue with matched blood samples were evaluated by qPCR. Group 3 (n= 138): stable disease (SD): n= 94; progressive disease (PD): n= 44. Validation Group 4 included surgical resection (n= 27) and SSA treatment (n= 35). Regulatory network analysis, linear modeling, PCA, and ROC analyses were used to delineate and evaluate neoplasia “hallmarks” and utility of clusters in a test algorithm. Results: Group 1: 45 (92%) genes were elevated in NET transcriptomes. Group 2: 50 genes (98%) were elevated by qPCR (Fold change > 2, p< 0.05). Correlation analysis was highly significant (R2= 0.7, p< 0.0001) between matched blood and tumors (Group 2). Nine hallmark clusters were defined by 30 (58%) genes; seven of which were increased (FC > 2, p< 0.05) in NET tumors and were closely correlated (p< 0.0001) with blood. Individual clusters differentiated SD from PD with AUCs ranging from 0.5-0.7. A combination of SSTRome, proliferome, epigenome exhibited an AUC of 0.81 and including this with the MAAA algorithm – the NETest - resulted in an AUC of 0.92. Using the NETest in group 3, the SD was significantly lower (28.6±2.4%) than in PD (83±3.2%, p< 0.0001). Clinically (group 4), significant reductions in the NETest were noted for SSA treatment (-26%, p< 0.05) and surgery (-51%, p< 0.005). Conclusions: Measurements of circulating transcripts reflect NET tissue values and biologically relevant expression (clusters) differentiate disease. Merging of gene cluster data amplified the blood-algorithm to predict clinical disease status and correlated with treatment. Use of a blood-based predictor of tumor behavior will enable determination of neuroendocrine tumor activity in real time.
Endpiece: Gluttonous friends
Authors: Jeremy Hugh Baron
Journal: BMJ (2005)

Nowadays, however, to what a stage have the evils of ill-health advanced! This is the interest which we pay on pleasures which we have coveted beyond what is reasonable and right. You need not wonder that diseases are beyond counting: count the cooks! All intellectual interests are in abeyance; those who follow culture lecture to empty rooms, in out-of-the-way places. The halls of the professor and the philosopher are deserted; but what a crowd there is in the cafes! How many young fellows beseige the kitchens of their gluttonous friends!
A genomic approach to therapeutic target validation identifies a glucose-lowering <i>GLP1R</i> variant protective for coronary heart disease
Authors: Robert A. Scott, Daniel F. Freitag, Li Li, Audrey Y. Chu, Praveen Surendran, Robin Young, Niels Grarup, Alena Stancáková, Yuning Chen, Tibor V. Varga, Hanieh Yaghootkar, Jian’an Luan, Jing Hua Zhao, Sara M. Willems, Jennifer Wessel, Shuai Wang, Nisa Maruthur, Kyriaki Michailidou, Ailith Pirie, Sven J. van der Lee, Christopher Gillson, Ali Amin Al Olama, Philippe Amouyel, Larraitz Arriola, Dominique Arveiler, Iciar Aviles-Olmos, Beverley Balkau, Aurelio Barricarte, Inês Barroso, Sara Benlloch Garcia, Joshua C. Bis, Stefan Blankenberg, Michael Boehnke, Heiner Boeing, Eric Boerwinkle, Ingrid B. Borecki, Jette Bork-Jensen, Sarah Bowden, Carlos Caldas, Muriel Caslake, L. Adrienne Cupples, Carlos Cruchaga, Jacek Czajkowski, Marcel den Hoed, Janet A. Dunn, Helena M. Earl, Georg B. Ehret, Ele Ferrannini, Jean Ferrieres, Thomas Foltynie, Ian Ford, Nita G. Forouhi, Francesco Gianfagna, Carlos Gonzalez, Sara Grioni, Louise Hiller, Jan-Håkan Jansson, Marit E. Jørgensen, J. Wouter Jukema, Rudolf Kaaks, Frank Kee, Nicola D. Kerrison, Timothy J. Key, Jukka Kontto, Zsofia Kote-Jarai, Aldi T. Kraja, Kari Kuulasmaa, Johanna Kuusisto, Allan Linneberg, Chunyu Liu, Gaëlle Marenne, Karen L. Mohlke, Andrew P. Morris, Kenneth Muir, Martina Müller-Nurasyid, Patricia B. Munroe, Carmen Navarro, Sune F. Nielsen, Peter M. Nilsson, Børge G. Nordestgaard, Chris J. Packard, Domenico Palli, Salvatore Panico, Gina M. Peloso, Markus Perola, Annette Peters, Christopher J. Poole, J. Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Veikko Salomaa, María-José Sánchez, Naveed Sattar, Stephen J. Sharp, Rebecca Sims, Nadia Slimani, Jennifer A. Smith, Deborah J. Thompson, Stella Trompet, Rosario Tumino, Daphne L. van der A, Yvonne T. van der Schouw, Jarmo Virtamo, Mark Walker, Klaudia Walter, Jean E. Abraham, Laufey T. Amundadottir, Jennifer L. Aponte, Adam S. Butterworth, Josée Dupuis, Douglas F. Easton, Rosalind A. Eeles, Jeanette Erdmann, Paul W. Franks, Timothy M. Frayling, Torben Hansen, Joanna M. M. Howson, Torben Jørgensen, Jaspal Kooner, Markku Laakso, Claudia Langenberg, Mark I. McCarthy, James S. Pankow, Oluf Pedersen, Elio Riboli, Jerome I. Rotter, Danish Saleheen, Nilesh J. Samani, Heribert Schunkert, Peter Vollenweider, Stephen O’Rahilly, Panos Deloukas, John Danesh, Mark O. Goodarzi, Sekar Kathiresan, James B. Meigs, Margaret G. Ehm, Nicholas J. Wareham, Dawn M. Waterworth
Journal: Science Translational Medicine (2016)

A missense variant in GLP1R associated with lower fasting glucose levels and protective against T2D is associated with lower risk of coronary heart disease, suggesting that GLP1R agonists are not associated with an unacceptable increase in cardiovascular risk.
Soundings: Missing Christmas
Authors: James Owen Drife
Journal: BMJ (2002)

A month ago the chaplain's secretary phoned. Would I read a lesson on Christmas morning? Normally I agree and wait to see if I am the warm up man with Isaiah chapter 9, or top of the bill with Luke chapter 2. This time I stammered an apology. After an unbroken run since 1971 I would not—barring accidents—be in hospital this Christmas.

Nor would most of my colleagues. In our consultants' dining room there would be mince pies and a dwindling band of doctors—some reminiscing about Christmas Past when the ward sister sipped an unaccustomed sherry and the senior consultant, in a funny hat, carved the turkey. Neither she nor he would have dreamed of taking Christmas off.

My medical generation experienced the end of an era stretching back to Dickens' time, when the festive season lasted only a day or two.

In A Christmas Carol, Fezziwig's clerks worked normally on 24 December. Not until 7 pm did their boss give the signal to roll up the carpet and start the dancing. And they were back in the office on Boxing Day.

Nowadays parties begin in early December, and the 25th is a blessed relief for everyone except the very young.

Our family stoutly maintained the old tradition. From an early age, our children took it for granted that after Santa had called, you went to hospital to show your toys to the midwives. Later, as students home for the holidays, they automatically woke up, programmed to walk the wards.

In recent years skeleton staffs of nurses began to look puzzled by our presence, and patients became fewer and iller. The lord mayor, the Salvation Army band, and our family followed one another around, hoping to find a patient who could speak or a Christmas mum who could smile while holding on to her caesarean stitches.

This year both children spent the winter abroad—trying, perhaps, to let us down gently and break a 26 year habit. My wife and I decided that rather than buy a tiny turkey and one cracker we too would leave town.

The chaplain was understanding. The nurses chided me, not for going, but for returning early and missing a pagan Hogmanay in Edinburgh.

Please, anything is better than that, even Isaiah.
A bridge over troubled waters
Authors: Lucas Campos, Richard T Ambron, John H Martin
Journal: BMJ (2007)

Spinal cord injury interrupts connections between the brain and spinal cord, rather than producing large-scale damage. Reconnecting severed axons with their prior targets is a primary objective of spinal cord repair. Despite progress, this goal will probably not be attained soon because many problems remain to be solved. We discuss an alternative for promoting motor function after spinal damage by bridging the injury. We highlight a novel spinal injury bridge that we have developed to reconnect spinal motor circuits below the injury with the brain. A spinal nerve that exits above the injury is disconnected and inserted into the cord caudal to injury. Motor axons in the inserted nerve regenerate into the cord and synapse on neurons producing a novel circuit to bypass the injury.
PTU-052 Clinical factors predicting outcome for double balloon enteroscopy: experience from a tertiary centre
Authors: D Rattehalli, F Branchi, DS Sanders, R Sidhu
Journal: Gut (2015)

<h3>Introduction</h3> Double balloon enteroscopy (DBE) has revolutionised our ability to manage small bowel pathology, however there is paucity in the literature on factors that influence outcome. Our aim was to evaluate factors that contributed to improving diagnostic yield and subsequent management. <h3>Method</h3> We performed a retrospective review of patients who underwent DBE from July 2006–October 2014. Data was collected on demographics, indications, procedural details, diagnosis and subsequent management. Tolerability scores were assessed using a validated scoring system (1-no discomfort 2- slight discomfort 3-extremely uncomfortable 4–unbearable). <h3>Results</h3> A total of 399 DBE procedures (mean age 56; 50% male; anterograde n = 256, retrograde n = 143) were performed over 124 months. The commonest indication was obscure gastrointestinal bleeding (OGB, n = 201) and suspected Crohn’s disease (n = 122). Capsule endoscopy (CE) was done prior to DBE in 91% of patients. One patient had a small bowel lesion noted on DBE, which was missed on CE. Demand for DBE has risen gradually in tandem with the diagnostic yield (p &lt; 0.0001, r = 0.9). The diagnostic and therapeutic yield across all indications was 49% and 24% respectively. On univariate analysis, cardiovascular co-morbidity was associated with a higher diagnostic yield (60% vs 45%, p = 0.01) and therapeutic yield (43% vs 17%, p &lt; 0.0001), irrespective of age, possibly due to a higher proportion of vascular lesions in this group. On multivariate analysis, transfusion dependence predicted a positive yield (p = 0.04, CI 0.04–0.95). Duration of procedure (p = 0.2), sedation (p = 0.9) and tolerability (p = 0.3) did not make a difference. The median length of small bowel examined was greater for the anterograde route compared to the retrograde route (170 cm vs 100 cm; p &lt; 0.001). The retrograde route took longer (75 mins vs 60 mins; p &lt; 0.001), but was tolerated better (patient score &gt;3 in 14% vs 24%; p = 0.02) and required lower doses of both midazolam (median: 5 mg vs 6 mg; p = 0.001) and fentanyl (median: 62.5 mcg vs 87.5 mcg p = 0.2). Change in management occurred in 41% of procedures and factors associated with this was age &gt;70 years (p = 0.01). Small bowel tumour was diagnosed in 5% (n = 19) of patients, whilst 40% were subsequently treated for Crohn’s disease. The overall complication rate was 1.25% (pancreatitis n = 2, respiratory arrest n = 1, pulmonary oedema n = 1 and NSTEMI n = 1). <h3>Conclusion</h3> Transfusion dependence was associated with a positive diagnostic yield for DBE whilst the elderly were more likely to have a change in management post DBE. Cardiovascular comorbidity also positively influenced the diagnostic and therapeutic yield. Advocating CE as a first line investigation allows better patient selection. DBE remains a useful modality for small bowel pathology. <h3>Disclosure of interest</h3> None Declared.
FRI0005 Combination Blocking of IL-22 and IL-17 During Experimental Arthritis Potently Reduces TH17-Driven Disease Progression
Authors: D.M. Roeleveld, R. Rogier, B. Walgreen, M.M. Helsen, L. van den Bersselaar, W.B. van den Berg, P.M. van der Kraan, M.I. Koenders
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) patients show elevated levels of IL-22 and IL-22-producing T helper cells that correlate to erosive disease, suggesting a role for this cytokine in the pathogenesis of RA. Interestingly, IL-22 is a dual cytokine with pro- and anti-inflammatory properties, and its effects might be regulated by cooperation and crosstalk with IL-17. <h3>Objectives</h3> The purpose of this study was to elucidate the role of IL-22 in the development of a spontaneous model of experimental arthritis by using IL-1Ra knockout mice. Additionally, we aimed to investigate the therapeutic potential of combined IL-22/IL-17 blocking during experimental arthritis. <h3>Methods</h3> IL-1Ra-deficient mice develop spontaneous arthritis due to excess IL-1 signaling, and we previously demonstrated the importance of IL-17 and Th17 cells in this model<sup>1</sup>. To investigate the role of IL-22 in this arthritis model, we compared IL-1Ra<sup>-/-</sup> x IL-22<sup>+/+</sup> mice to IL-1Ra<sup>-/-</sup> mice lacking IL-22 expression. Paw joint swelling was scored weekly, and mice were sacrificed at the age of fifteen weeks. In addition, arthritic IL-1Ra<sup>-/-</sup> x IL-22<sup>-/-</sup> mice were treated with anti-IL-17 antibodies to determine the therapeutic potency of this combined blocking strategy during experimental arthritis. <h3>Results</h3> IL-1Ra<sup>-/-</sup> mice that also lack IL-22 showed strongly reduced arthritis development, reaching a disease incidence of only 54% at the age of 15 weeks compared to 93% in IL-1Ra<sup>-/-</sup> x IL-22<sup>+/+</sup> mice. In addition, arthritis severity of the mice that did develop arthritis was significantly reduced by 30.6% in the absence of IL-22. Interestingly, combined blocking of IL-22 and IL-17 using IL-1Ra<sup>-/-</sup> x IL-22<sup>-/-</sup> mice treated with neutralizing anti-IL-17 antibodies after the onset of arthritis demonstrated clear additive effects compared to blocking these single cytokines alone, thereby potently reducing progression of this Th17-driven arthritis model. <h3>Conclusions</h3> These findings suggest that IL-22 plays an important role both in the initiation and augmentation of Th17-dependent experimental arthritis, and that targeting IL-22, especially in combination with IL-17 therefore seems an interesting, potent strategy in RA treatment. <h3>References</h3> Koenders MI, Devesa I, Marijnissen RJ, Abdollahi-Roodsaz S, Boots AM, Walgreen B, di Padova FE, Nicklin MJ, Joosten LA, van den Berg WB. Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleuking-1 receptor antagonist-deficient mice. Arthritis Rheum. 58(11): 3461-70, 2008. <h3>Disclosure of Interest</h3> None declared
Utilizing information and telehealth technology to enhance clinical ethics education outreach.
Authors: Colleen M. Gallagher, Jessica Anne Moore, Brittany C Campbell
Journal: Journal of Clinical Oncology (2016)

149 Background: Integrated Ethics provides continuing education monthly for physicians, nurses, social workers, and others to enhance knowledge and understanding of ethical challenges associated with patient care and research. These are offered live at the main campus. There are four regional centers within a thirty-five mile radius of the main campus. Participants from those locations used to have to come to the main campus to participate. This project was initiated to help alleviate rising financial costs associated with the online recording/redistributing of continuing education credit presentations, travel expenses for regional center employees, removal of employees for 4+ hours from the regional centers daily clinical operations to attend presentations, and payment to outside institutions to obtain required ethics CME and CEU credits. Methods: Steps included internal and external discussions, establishing the need, tracking current process, determining which resources were needed, and then updating the process and evaluating it. Among the primary elements was the inclusion of nursing leaders, physicians and social workers from the centers. Ethics staff went to each center for discussions which had the added value of building relationships. Telehealth and information technology representatives assisted in developing the possible methods for delivery of the education and provided information about the process and costs of each for evaluation. Of note was the fact that the profession of the attendees was different among the main campus and regional centers. At main campus 58% of the attendees are physicians, at the regional center 66% are nurses. Varying requirements for continuing education in the professions had to be accounted for in the selection of method delivery and accreditation processes. Results: This project saves a minimum of $22,634 annually and participation at the Regional Care Centers increased by 20%. An average of 309 productivity hours are no longer lost at the centers. Conclusions: Understanding and utilizing new technology and consistent personalized communication efforts realized both cost savings and increased participation.