9 research outputs found
Determinants of high somatic-cell count prevalence in dairy herds practicing teat dipping and dry cow therapy and with no evidence of Streptococcus-agalactiae on repeated bulk tank milk examination
No full textPT: J; CR: 1982, SAS USERS GUIDE STAT BODOH GW, 1976, J DAIRY SCI, V59, P1119 BRAMLEY AJ, 1984, J DAIRY RES, V51, P481 BUSHNELL RB, 1984, 23RD P ANN M NAT MAS, P31 BUSHNELL RB, 1985, 24TH P ANN M NAT MAS, P45 DOHOO IR, 1982, CAN VET J, V23, P119 GALTON DM, 1984, 17TH P ANN C AM ASS, P108 GOODHOPE RG, 1980, CAN J COMP MED, V44, P351 HARVEY WR, 1982, J ANIM SCI, V54, P1067 HOARE RJT, 1979, AUST J DAIRY TECHNOL, V34, P91 HUESTON WD, 1987, PREV VET MED, V4, P447 KIRK JH, 1984, COMP CONT EDUC PRACT, V6, S237 LESLIE KE, 1983, COMPEND CONTIN ED P, V5, S601 LINDSTROM UB, 1983, ACTA AGR SCAND, V33, P389 MEIN GA, 1977, AUST J DAIRY TECHNOL, V32, P81 MINETT FC, 1933, J COMP PATH THERAP, V46, P131 MOXLEY JE, 1978, J DAIRY SCI, V61, P1637 NEWMAN LE, 1973, AM J VET RES, V34, P979 PEARSON JKL, 1972, VET REC, V91, P615 POSTLE DS, 1968, AM J VET RES, V29, P669 POSTLE DS, 1971, J MILK FOOD TECH, V34, P517 SMITH KL, 1983, J DAIRY SCI, V66, P1790 STABLEFORTH AW, 1935, J COMP PATHOL, V48, P300; NR: 23; TC: 11; J9: PREV VET MED; PG: 12; GA: DU955Source type: Electronic(1
Iatrogenic portobiliary fistula complicating endoscopic stenting of a pancreatic cyst, with possible carcinoma: a case report.
No full textMonoclonal Antibodies to Migraine: Witnesses to modern biomedicine, an A-Z
No full textThe History of Modern Biomedicine Research Group hosted its first Witness Seminar, on monoclonal antibodies, in 1993. Since then more than sixty such meetings have been held, the most recent on migraine in 2013. These all sought to go behind-the-scenes of contemporary biomedicine to find out ‘what really happened’. In this, the Group’s twenty-first anniversary year, we are delighted to present our fiftieth Witness Seminar volume Monoclonal Antibodies to Migraine: Witnesses to modern biomedicine, an A–Z. Comprising a series of extracts from previous volumes, contributors include clinicians, scientists, patients and numerous others involved in modern biomedicine, in the UK and beyond. Topics range from ‘age discrimination’ to ‘Zantac’, and feature memories from every decade between the 1930s and the present.The History of Modern Biomedicine Research Group hosted its first Witness Seminar, on monoclonal antibodies, in 1993. Since then more than sixty such meetings have been held, the most recent on migraine in 2013. These all sought to go behind-the-scenes of contemporary biomedicine to find out ‘what really happened’. In this, the Group’s twenty-first anniversary year, we are delighted to present our fiftieth Witness Seminar volume Monoclonal Antibodies to Migraine: Witnesses to modern biomedicine, an A–Z. Comprising a series of extracts from previous volumes, contributors include clinicians, scientists, patients and numerous others involved in modern biomedicine, in the UK and beyond. Topics range from ‘age discrimination’ to ‘Zantac’, and feature memories from every decade between the 1930s and the present.The History of Modern Biomedicine Research Group hosted its first Witness Seminar, on monoclonal antibodies, in 1993. Since then more than sixty such meetings have been held, the most recent on migraine in 2013. These all sought to go behind-the-scenes of contemporary biomedicine to find out ‘what really happened’. In this, the Group’s twenty-first anniversary year, we are delighted to present our fiftieth Witness Seminar volume Monoclonal Antibodies to Migraine: Witnesses to modern biomedicine, an A–Z. Comprising a series of extracts from previous volumes, contributors include clinicians, scientists, patients and numerous others involved in modern biomedicine, in the UK and beyond. Topics range from ‘age discrimination’ to ‘Zantac’, and feature memories from every decade between the 1930s and the present.The History of Modern Biomedicine Research Group hosted its first Witness Seminar, on monoclonal antibodies, in 1993. Since then more than sixty such meetings have been held, the most recent on migraine in 2013. These all sought to go behind-the-scenes of contemporary biomedicine to find out ‘what really happened’. In this, the Group’s twenty-first anniversary year, we are delighted to present our fiftieth Witness Seminar volume Monoclonal Antibodies to Migraine: Witnesses to modern biomedicine, an A–Z. Comprising a series of extracts from previous volumes, contributors include clinicians, scientists, patients and numerous others involved in modern biomedicine, in the UK and beyond. Topics range from ‘age discrimination’ to ‘Zantac’, and feature memories from every decade between the 1930s and the present.The History of Modern Biomedicine Research Group hosted its first Witness Seminar, on monoclonal antibodies, in 1993. Since then more than sixty such meetings have been held, the most recent on migraine in 2013. These all sought to go behind-the-scenes of contemporary biomedicine to find out ‘what really happened’. In this, the Group’s twenty-first anniversary year, we are delighted to present our fiftieth Witness Seminar volume Monoclonal Antibodies to Migraine: Witnesses to modern biomedicine, an A–Z. Comprising a series of extracts from previous volumes, contributors include clinicians, scientists, patients and numerous others involved in modern biomedicine, in the UK and beyond. Topics range from ‘age discrimination’ to ‘Zantac’, and feature memories from every decade between the 1930s and the present.Wellcome Trust
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
No full textPrimary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist
Hetrocyclic methacrylate systems as vehicles for the release of active species.
No full textPhDThe room temperature polymerising heterocyclic polymer system, poly(ethyl
methacrylate)/tetrahydrofurfuryl methacrylate (PEM/THFM) has been shown
previously to be biocompatible and supported tissue repair, specifically for bone
and cartilage, and biologically inert when in contact with the dental pulp. It
proved more effective, than other glassy methacrylates in the release of active
species.
The PEM/THFM system is a rigid material. The aim of this study was to develop
and characterise the use of this system as a flexible patch, for application and
retention to the buccal mucosa, thus facilitating sustained regulated release.
Model species, dextrans, were used to represent macromolecular drugs whereby
the effect of molecular weight could be studied. N-methyl pyrrolidone was added
to the polymer system as a biocompatible plasticiser to enhance molecular
mobility, and hence the transport of species. The effect of the addition of chitosan
was also studied, due to its bioadhesiveness and permeation enhancing ability.
A range of systems was investigated both in terms of water and species release.
The release of the agent was measured by a fluorometer, the leachable
components by HPLC and Confocal microscopy demonstrated the transport of
water and active species through the system. Immunological and viability studies
established whether the leachants or released components of the polymeric
systems had an inflammatory or irritant action on `in vitro' stratified epithelium.
The addition of N-methyl pyrrolidone, dextran and chitosan substantially
increased water uptake, thus affecting the release kinetics. Analysis of the
kinetics of water uptake showed Case I, combination of Case I and Case II, and
Case II kinetics, depending on the systems studied. Dextran release was largely
diffusion controlled, from which diffusion coefficients were calculated; the
amount released varied between the systems studied
Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA response score
No full textBACKGROUND:
Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters.
METHODS:
We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples.
FINDINGS:
2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p<0·0001), higher total bilirubin concentration (p=0·0003), lower aminotransferase concentration (p=0·0012), younger age (p<0·0001), longer interval from diagnosis to the start of UDCA treatment (treatment time lag, p<0·0001), and worsening of alkaline phosphatase concentration from diagnosis (p<0·0001). Based on these variables, we derived a predictive score of UDCA response. In the external validation cohort, 460 patients diagnosed with primary biliary cholangitis were treated with UDCA, with follow-up data until May 31, 2016. In this validation cohort, the area under the receiver operating characteristic curve for the score was 0·83 (95% CI 0·79-0·87). In 20 liver biopsy samples from patients with primary biliary cholangitis, the UDCA response score was associated with ductular reaction (r=-0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present).
INTERPRETATION:
We have derived and externally validated a model based on pretreatment variables that accurately predicts UDCA response. Association with histological features provides face validity. This model provides a basis to explore alternative approaches to treatment stratification in patients with primary biliary cholangitis.
FUNDING:
UK Medical Research Council and University of Milan-Bicocca
Reducing the environmental footprint of gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) position statement
No full textClimate change and the destruction of ecosystems by human activities are among the greatest challenges of the 21st century and require urgent action. Health care activities significantly contribute to the emission of greenhouse gases and waste production, with gastrointestinal (GI) endoscopy being one of the largest contributors. This Position Statement aims to raise awareness of the ecological footprint of GI endoscopy and provides guidance to reduce its environmental impact. The European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) outline suggestions and recommendations for health care providers, patients, governments, and industry. MAIN STATEMENTS 1: GI endoscopy is a resource-intensive activity with a significant yet poorly assessed environmental impact. 2: ESGE-ESGENA recommend adopting immediate actions to reduce the environmental impact of GI endoscopy. 3: ESGE-ESGENA recommend adherence to guidelines and implementation of audit strategies on the appropriateness of GI endoscopy to avoid the environmental impact of unnecessary procedures. 4: ESGE-ESGENA recommend the embedding of reduce, reuse, and recycle programs in the GI endoscopy unit. 5: ESGE-ESGENA suggest that there is an urgent need to reassess and reduce the environmental and economic impact of single-use GI endoscopic devices. 6: ESGE-ESGENA suggest against routine use of single-use GI endoscopes. However, their use could be considered in highly selected patients on a case-by-case basis. 7: ESGE-ESGENA recommend inclusion of sustainability in the training curricula of GI endoscopy and as a quality domain. 8: ESGE-ESGENA recommend conducting high quality research to quantify and minimize the environmental impact of GI endoscopy. 9: ESGE-ESGENA recommend that GI endoscopy companies assess, disclose, and audit the environmental impact of their value chain. 10: ESGE-ESGENA recommend that GI endoscopy should become a net-zero greenhouse gas emissions practice by 2050.status: Publishe
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
No full textBACKGROUND & AIMS: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease.METHODS: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals).RESULTS: Single-marker association analyses found approximately 100 loci displaying P < 5* 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P= 4.80* 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P= 9.93* 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P= 6.2* 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBCcase patients (1.75- and 1.64-fold, respectively).CONCLUSIONS: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus
