tbuckley/cabot-search huggingface dataset:
Intervention epidemiology training: a European perspective
Authors: F van Loock, Mike Rowland, T Grein, A Moren
Journal: Eurosurveillance (2001)

Within the widening European Union, large-scale movements of people, animals and food-products increasingly contribute to the potential for spread of communicable diseases. The EU was given a mandate for public health action only in 1992, under the Treaty of European Union ("Maastricht Treaty"), which was broadened in the 1997 with the Treaty of Amsterdam. While all EU countries have statutory requirements for notifying communicable diseases, national and regional communicable disease surveillance practices vary considerably. The Network Committee (NC) for the Epidemiological Surveillance and Control of Communicable Diseases in the EU was established in 1998 to harmonise these activities.
The Role of the Phorbol Ester Receptor/Protein Kinase C in the Sensitivity of Leukemic Cells to Anthracyclines
Authors: W N Hait, W T DeRosa
Journal: Cancer Communications (1991)

The phorbol ester receptor (PER), which is believed to be identical to protein kinase C (PKC), has been implicated in the control of the sensitivities of tumor cells to certain forms of cancer chemotherapy. We evaluated the effects of regulating the expression of PER/PKC on the sensitivity of the R1B6 subclone of HL-60 human promyelocytic leukemic cells to anthracyclines. This cell line is resistant to the effects of phorbol esters on cellular differentiation by virtue of a down-regulated PER. R1B6 cells were maintained in phorbol 12, 13 dibutyric acid (PDBu). Twenty four to thirty six hours after removal of PDBu from the medium there was a 3-fold increase in the number of receptors compared to baseline values measured by [3H]-PDBu binding and a marked increase in the activity of PKC as measured by calcium-phospholipid dependent incorporation of [32P] into histone. Despite these changes in the number of PER and in the activity of PKC there was no difference in the cellular accumulation of [3H]-daunomycin or in the sensitivity of cells to the toxic effects of doxorubicin. Furthermore, there was no difference between the R1B6 cells and the parental HL-60 line in their intrinsic sensitivities to doxorubicin. These studies demonstrate that alterations in the expression of PER and the activity of PKC alone are not sufficient to influence anthracycline accumulation or toxicity in R1B6 human leukemic cells in contrast to recently reported results using other cell lines.
AB0046 Synovial Fluid from Rheumatoid Arthritis Patients Modulates the Immunophenotype and Viability of Monocytes
Authors: M.S. Chimenti, A. Bergamini, P. Triggianese, E. Baffari, P. Conigliaro, R. Perricone
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Monocytes/macrophages are the major immune cells present in synovial tissue responsible for chronic inflammation and joint destruction in Rheumatoid Arthritis (RA). Several proteins involved in inflammation and immune response have been identified in RA synovial fluid (SF-RA). <h3>Objectives</h3> Aim of this study was to determine the effect of SF-RA patients on surface phenotype, co-stimulatory activity, cytokine production and viability of monocytes. <h3>Methods</h3> Purified monocytes from healthy donors were incubated with individual SF-RA specimens obtained from twelve RA patients with active knee arthritis and then analyzed by flow cytometry for ILT4 (immunoglobulin-like transcript 4) as inhibitory immune receptor, and CD86 expression, co-stimulation ability, TNFα and IL-10 production, and rate of spontaneous apoptosis. Twelve SF from patients with knee osteoarthritis (OA) (SF-OA) were used as control. Experiments were also performed in the presence or absence of LPS or Adalimumab. <h3>Results</h3> Surface expression of ILT4 was reduced and that of CD86 increased in monocytes exposed to SF-RA (Figure 1). A significant indirect correlation was observed between ILT4 and DAS, while a direct correlation for CD86 and DAS. The surface phenotype changes induced by SF-RA were associated with increased ability to co-stimulate CD4+ T cells for IFNγ and TNFα production. TNFα and IL-1β response to LPS was increased in SF-RA monocytes compared with OA controls. Finally, a reduction of spontaneous apoptosis was observed in SF-RA monocytes, which was strongly reduced by the addition of adalimumab (Figure 1F). <h3>Conclusions</h3> ILT4 has been shown to exert a negative influence on the stimulatory capacity of APC. Thus, ILT4 exerts a direct influence on innate effectors or an indirect effect on an adaptive response and may play a potential pathogenetic role in RA. Indeed, changes in the relative balance of activating and inhibitory ILTs in the synovium could lead to inappropriate activity of innate immune agents which may drive T-cell activation. Our findings suggest that soluble mediators in SF-RA could contribute to modulate the local effectiveness of the immune response and inflammation. <h3>Disclosure of Interest</h3> None declared
PTU-216 Three-dimensional volume measurements are more accurate than clinical assessment of response to anti-tnf therapy for crohn’s anal fistulae
Authors: NA Yassin, P Lung, P Bassett, A Gupta, R Phillips, A Hart
Journal: Gut (2015)

<h3>Introduction</h3> The use of anti-TNF therapy for the treatment of fistulising perianal Crohn's disease relies heavily on clinical and radiological assessments in order to assess response. We have shown that a third of patients sustain radiological remission at 3-years follow-up. It is difficult to predict response based on MRI images as they are difficult to interpret. Having a three-dimensional (3-D) fistula model and being able to quantify the changes in the fistula volume would be more beneficial than relying on complex and subjective MRI reports. We aim to use computer software and MRI segmentation to design 3D models of Crohn's anal fistulae, measure baseline and 3 years post-biologics treatment fistula volumes and compare with clinical and MRI healing. <h3>Method</h3> Three-Dimensional fistula models were independently created by the surgeon and radiologist using the previously validated surgical computer software. Thirty-eight patients were selected and volumes were measured at baseline and 3-years post biological therapy. Kappa statistics were used to assess correlation between the healing categories for the three assessment techniques: volume measurements, clinical and MRI healing. Binary logistical regression analysis was used to assess predictors of changes in 3-D anal fistula volumes. <h3>Results</h3> A change in baseline and post-treatment volumes was observed. The three assessment tools were clinical healing, radiological healing and change in 3-D anal fistula volumes. The agreement between each pair of assessment techniques were measured using Kappa values. There was fair agreement between 3-D volumes and MRI healing (K = 0.34; 95% CI = 0.11, 0.57). Poor agreement was noted between 3-D volumes and clinical healing (K = 0.05; 95% CI = -0.15, 0.25) and the agreement was also poor for clinical and MRI healing (K = 0.10; 95% CI = -0.12, 0.32). On binary logistical regressional analysis, the single independent factor predictive of 3-D volume change was the duration of the disease. An increased duration of disease was associated with a reduced likelihood of an improvement in volumes (OR = 0.57; 95% CI = 0.33, 0.9, p = 0.045). Five-year increase in the duration of disease was associated with two-fold decrease in the odds of improvement. <h3>Conclusion</h3> MRI volume measurements of 3D Crohn's fistula models provide an accurate assessment tool. The measurement of perianal fistulae volumes is more is useful than using MRI reports alone as it gives a quantitative measure that can be used to assess the efficacy of therapy. Serial fistula volume measurements should be used for monitoring the response to biological therapy for perianal Crohn's fistula patients. <h3>Disclosure of interest</h3> None Declared.
PWE-424 Medical student–s perceptions of a career in gastroenterology: a peer led study
Authors: L China, A Burn-Murdoch
Journal: Gut (2015)

<h3>Introduction</h3> In an era of declining interest in internal medicine training it is paramount that Gastroenterology continues to attract the highest quality applicants to ensure the continued growth and success of the specialty clinically and academically. With re-structuring of medical training doctors have to make career choices earlier (&lt;16 months post qualifying) therefore the pressure to consider specialty choice has shifted to an undergraduate level. The variation in UK undergraduate Gastroenterology curriculums between medical schools is unknown, leading to possible large variation in student experience. Our aim was to identify current undergraduate perceptions of gastroenterology and motivations for considering a career in the specialty. <h3>Method</h3> This was primarily a qualitative study, with some numerical response, using an online survey to collect data. The total study population were all UK medical students, however contact via medical school emails is restricted. Therefore social media was used to distribute the survey creating a purposive, convenience sample with snowball effect. Peer led research, or ‘research from the inside’, leads to increased response rates and open, honest feedback therefore data was collected by a student. Thematic analysis using NVivo was used to analyse qualitative data. <h3>Results</h3> 94 students responded within a 2 week period from 4 UK medical schools, the majority nearing the end of their degree. Only 63% of student–s perceived they had enough exposure to the specialty. 50% of respondents would not even consider a career in Gastroenterology. Main themes regarding a negative perception of the specialty from thematic analysis were: being a medical SpR, long hours, poor core medical training, too much endoscopy and over subspecialisation. Over 1/3 had a perception that the speciality focussed purely on colonic problems. Of those interested in a career in gastroenterology 38% had been inspired by a role model. Primary themes emerging from positive impressions of the speciality were: patient variation, complex cases and close interaction with other specialties. <h3>Conclusion</h3> A large proportion of this student sample had access to gastroenterology placements although this was often too sub-specialised leading to a warped view of the specialty. Main deterants from considering a career in gastroenterology were a perception of longer hours and not wanting to be a general medical trainee. Surprisingly students are aware of these issues at a very early stage in their career. The largest positive influencing factors are influential role models and adequate exposure to the variety Gastroenterology has to offer. A UK wide assessment of undergraduate Gastroenterology curriculums paired with comprehensive student evaluation is required in order to increase understanding and prevent recruitment issues. <h3>Disclosure of interest</h3> None Declared.
Cervical Osteoarthritis
Authors: Carter R. Rowe
Journal: New England Journal of Medicine (1963)

ARTHRITIS is a term that the medical profession is apt to use too freely. This also applies to "cervical arthritis." A large number of persons at forty or fifty years of age will show some narrowing of the space between the fifth and sixth cervical vertebras, with early or mild irregularities of the anterior borders of the vertebras. These changes may progress very slowly, with little disturbance to the patient. Perhaps the term "arthritis" should not be used in such cases. Instead, this condition may be referred to as "changes," normal for the patient's particular age group. Too often, cases . . .
Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I 1-Hour Algorithm
Authors: Johannes Tobias Neumann, Nils Arne Sörensen, Tjark Schwemer, Francisco Ojeda, Rafael Bourry, Vanessa Sciacca, Sarina Schaefer, Christoph Waldeyer, Christoph Sinning, Thomas Renné, Martin Than, William Parsonage, Karin Wildi, Nataliya Makarova, Renate B. Schnabel, Ulf Landmesser, Christian Mueller, Louise Cullen, Jaimi Greenslade, Tanja Zeller, Stefan Blankenberg, Mahir Karakas, Dirk Westermann
Journal: JAMA Cardiology (2016)

Rapid and accurate diagnosis of acute myocardial infarction (AMI) currently constitutes an unmet need.To test a 1-hour diagnostic algorithm to diagnose AMI using a high-sensitivity troponin I assay with a new cutoff level of 6 ng/L.The Biomarkers in Acute Cardiac Care study is a prospective study that investigated the application of the troponin I assay for the diagnosis of AMI in 1040 patients presenting to the emergency department with acute chest pain from July 19, 2013, to December 31, 2014. Results were validated in 2 independent cohorts of 4009 patients. Final follow-up was completed on July 1, 2015, and data were assessed from July 2 to December 15, 2015.Acute chest pain suggestive of AMI.Accurate diagnosis or exclusion of AMI and 12-month mortality in patients with acute chest pain.Of the 1040 patients included from the study cohort, 673 (64.7%) were male and had a median age of 65 (interquartile range, 52-75) years. With application of a low troponin I cutoff value of 6 ng/L, the rule-out algorithm showed a high negative predictive value of 99.8% (95% CI, 98.6%-100.0%) after 1 hour for non-ST-segment elevation MI type 1. The 1-hour approach was comparable to a 3-hour approach. Similarly, a rule-in algorithm based on troponin I levels provided a high positive predictive value with 82.8% (95% CI, 73.2%-90.0%). Moreover, application of the cutoff of 6 ng/L resulted in lower follow-up mortality (1.0%) compared with the routinely used 99th percentile (3.7%) for this assay. Two independent cohorts further validated the performance of this algorithm with high negative and positive predictive values.Patients with possible AMI can be triaged within 1 hour after admission with no loss of safety compared with a 3-hour approach, when a low and sensitive cutoff is applied. This concept enables safe discharge or rapid treatment initiation after 1 hour.
What really happens to tuberculosis patients classified as lost to follow-up in West Yorkshire?
Authors: M Day, A Middlemiss, J Thorpe, E Okereke
Journal: Eurosurveillance (2012)

Tuberculosis (TB) patients who do not complete treatment pose a potential public health risk. In West Yorkshire, local clinicians suspected that this risk was overestimated by the national Enhanced Tuberculosis Surveillance system. We audited patients who failed to complete treatment and were categorised as lost-to-follow-up (LTFU) between 2004 and 2008, using a combination of hand searching existing records and obtaining additional information from clinicians. In the study period 2,031 TB cases with reported outcome were notified in West Yorkshire, 23% (n=474) did not complete treatment, and 199 (42%) of those were categorised as LTFU 12 months after notification. Of these 199, 49% (n=98) remained LTFU after the audit, 51% (n=101) were re-classified to the following categories: 24% (n=47) transferred abroad, 16% (n=31) recommenced and completed treatment, 6% (n=13) transferred to another clinic in the United Kingdom (UK), and 5% (n=10) died. These patients therefore no-longer posed a public health risk. Further training for clinicians to improve accuracy of outcome reporting has been initiated. Nationally, the collection of treatment outcome data needs to be strengthened and extending the follow-up for treatment outcome monitoring should be considered.
Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease
Authors: Paul M Hassoun, Jerry A Krishnan
Journal: New England Journal of Medicine (2004)

1. Caspi D, Lubart E, Graff E, Habot B, Yaron M, Segal R. The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients. Arthritis Rheum 2000;43:103-8. 2. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895-900. 3. Roubenoff R, Klag MJ, Mead LA, Liang KY, Seidler AJ, Hochberg MC. Incidence and risk factors for gout in white men. JAMA 1991; 266:3004-7. 4. Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H. Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the Normative Aging Study. J Rheumatol 2000;27:1708-12.
Retinal Detachment
Authors: Cassio Lynm
Journal: JAMA (2012)

Mahyar Etminan, PharmD, MSc (epi); Farzin Forooghian, MD, MSc, FRCSC; James M. Brophy, MD, PhD, FRCPC; Steven T. Bird, PharmD; David Maberley, MD, MSc, FRCSC
Photodynamic Therapy for Malignant Biliary Obstruction: A Case Series
Authors: S.  Suzuki, K.  Inaba, Y.  Yokoi, K.  Ohata, S.  Ota, M.  Azuma, T.  Tanaka, H.  Konno, S.  Baba, T.  Hirano, S.  Nakamura
Journal: Endoscopy (2004)

Various treatment modalities such as surgical resection, endoscopic insertion of a metal stent, and radiotherapy have been available for patients with bile duct carcinoma [1]. Elderly patients of more than 70 years of age can destroy their quality of life by selecting an inappropriate treatment for their bile duct carcinoma. Photodynamic therapy, by means of the intravenous administration of hematoporphyrin derivative and subsequent laser exposure, has been used as a local cancer therapy [2] [3] [4]. The continuous wave of the argon dye laser has been generally used in photodynamic therapy, but tissue penetrability decreases with the thermal change in the treated region. In contrast, the pulsed excimer dye laser penetrates more deeply and activates the photosensitizer more efficiently than the argon dye laser, without a thermal effect [4] [5]. Although Takeda and associates, in the Japanese literature, have reported the first application of pulsed excimer dye laser in patients with bile duct carcinoma [6], there is insufficient information on the effect of this laser system in photodynamic therapy for malignant biliary stricture.
Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone
Authors: Lauren A. Lawres, Aprajita Garg, Vidya Kumar, Igor Bruzual, Isaac P. Forquer, Isaline Renard, Azan Z. Virji, Pierre Boulard, Eduardo X. Rodriguez, Alexander J. Allen, Sovitj Pou, Keith W. Wegmann, Rolf W. Winter, Aaron Nilsen, Jialing Mao, Douglas A. Preston, Alexia A. Belperron, Linda K. Bockenstedt, David J. Hinrichs, Michael K. Riscoe, J. Stone Doggett, Choukri Ben Mamoun
Journal: The Journal of Experimental Medicine (2016)

Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti. Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis.
Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases
Authors: Mehtap Bacioglu, Luis F. Maia, Oliver Preische, Juliane Schelle, Anja Apel, Stephan A. Kaeser, Manuel Schweighauser, Timo Eninger, Marius Lambert, Andrea Pilotto, Derya R. Shimshek, Ulf Neumann, Philipp J. Kahle, Matthias Staufenbiel, Manuela Neumann, Walter Maetzler, Jens Kuhle, Mathias Jucker
Journal: Neuron (2016)
Research Uncovers Healthy People With Disease-Causing Mutations
Authors: Tracy Hampton
Journal: JAMA (2016)

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The sex of the psychotherapist
Authors: J O Cavenar, D S Werman
Journal: American Journal of Psychiatry (1983)

The authors note the recent controversy about whether the sex of the psychotherapist is an important factor in the treatment of patients with certain neurotic and personality disturbances and suggest that much of the confusion is because supportive and insight-oriented psychotherapy are not clearly distinguished. After reviewing the relevant literature they present five clinical vignettes which suggest that the sex of the therapist is immaterial in insight-oriented psychotherapy and that attention to defenses, transference, and resistance remains the cornerstone of successful psychotherapy.
Endoscopic submucosal dissection – just add water(jet)?
Authors: Daniel von Renteln
Journal: Endoscopy (2014)

Endoscopic submucosal dissection (ESD) is an exciting technique – it holds the promise of completely removing gastrointestinal cancers using a minimally invasive endoscopic approach. ESD allows for en bloc removal of large (superficial) gastrointestinal lesions while respecting oncological principles. At the same time, the technique is far less invasive than the alternative surgical options. ESD was pioneered in Japan in the 1990s and, since then, has gained recognition worldwide as a treatment option for early gastric, rectal, and esophageal neoplasias. ESD for duodenal and colonic lesions is less frequently performed due to the higher risk of complications such as perforation and bleeding.
Cellular Expression of Antiapoptotic BCL-2 Oncoprotein in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia: A Children's Cancer Group Study
Authors: Fatih M. Uckun, Zhiwen Yang, Harland Sather, Peter Steinherz, James Nachman, Bruce Bostrom, Lisa Crotty, Mireille Sarquis, Onur Ek, Tamer Zeren, David Tubergen, Gregory Reaman, Paul Gaynon
Journal: Blood (1997)