Environmental Integrity Index Phase I & II (2011-2012) Watershed Summary Report

Waller Creek Working Grou

Concurrent extrahepatic autoimmunity in autoimmune hepatitis: implications for diagnosis, clinical course and long term outcome

Concurrent extrahepatic autoimmune disease (CEHAID) associated with autoimmune hepatitis (AIH) have been incorporated into the diagnostic criteria stipulated by the International Autoimmune Hepatitis Group (IAIHG). Large comprehensive cohort data on the extrahepatic autoimmunity in AIH remain scanty AIM: To systematically assess features and clinical impact of CEHAID on AIH METHODS: Clinical records of 562 patients with AIH from two tertiary centres in the United Kingdom were retrospectively reviewed RESULTS: Prevalence of CEHAID in patients with AIH were 42%. Autoimmune thyroid disease was the commonest CEHAID associated with AIH (101/562, 18%). Autoimmune skin diseases were more prevalent in AIH-2 than AIH-1 (21.9% vs.7%, p=0.009). Personal history of CEHAID was more commonly found in AIH patients with than without first degree family history of CEHAID [(48/86, 55.8% vs 169/446, 37.9%), p=0.002]. AIH patients with CEHAID were more often female [201/236 (85.2%), p=0.008], had higher post-treatment IAIHG score (22 vs. 20, p<0.001), less reactivity to smooth muscle antibodies (49.8% vs 65%, p<0.001), more likely to have mild fibrosis at diagnosis (20.9% vs. 6.5%, p<0.001), less often had ascites (6.3% vs. 13.6%, p=0.008) and coagulopathy (1.18 vs. 1.27, p=0.013) at presentation. Presence of CEHAID, however, did not significantly affect disease progression, prognosis and survival in AIH CONCLUSIONS: Our study confirms the strong association of CEHAID with AIH. Association between personal and familial extrahepatic autoimmunity especially among first degree relatives was evident. Presence of CEHAID may influence clinical phenotype of AIH at presentation but without notable impact on the long term clinical outcome

Exploring changing attitudes to non-invasive liver fibrosis tests in secondary care pathways: comparison of two national surveys

INTRODUCTION: The increasing availability of non-invasive tests (NITs) has created the opportunity to explore their use in improving risk stratification of advanced liver disease. The study aimed to determine the attitudes and practices among UK secondary care specialists, focusing primarily on attitudes to fibrosis assessment and the use of NITs. METHODS: Two web-based surveys were circulated, first between 2014 and 2015 (survey 1), and again in 2021 (survey 2). The surveys were promoted via the British Society of Gastroenterology, the British Association for the Study of the Liver and using Twitter. RESULTS: In survey 1, 215 healthcare professionals (HCPs) completed the online survey. 112 HCPs completed survey 2. 71 acute UK trusts were represented in survey 1 compared with 60 trusts in survey 2. Between the two surveys, the proportion of HCPs performing fibrosis assessment in all or nearly all cases rose from 45.1% to 74.1% (χ2=25.01; p&lt;0.0001). 46.5% (n=33/71) respondents in acute services reported the use of NITs in clinical pathways in survey 1, rising to 70.0% (n=42/60) in survey 2 (χ2=7.35; p=0.007). Availability of tests has increased but is not universal. The proportion reporting availability as a barrier to uptake fell from 57.2% of responses in survey 1 to 38.4% in 2021 χ2=11.01; p=0.0009). CONCLUSION: Between 2014 and 2021, the role of NITs in fibrosis assessment has risen substantially, as has the proportion of clinicians using NITs in clinical pathways to assess risk of liver disease. Poor access to NITs remains the predominant barrier

Rising incidence, progression and changing patterns of liver disease in Wales 1999-2019

BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing. AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services. METHODS The registry is populated by International Classification of Diseases-10 (ICD-10) code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019. Pseudo-anonymised linkage of: (1) Causative diagnoses; (2) Cirrhosis; (3) Portal hypertension; (4) Decompensation; and (5) Liver cancer diagnoses enabled tracking liver disease progression. RESULTS The population of Wales in 2019 was 3.1 million. Between 1999 and 2019 73054 individuals were diagnosed with a hepatic disorder, including 18633 diagnosed with cirrhosis, 10965 with liver decompensation and 2316 with hepatocellular carcinoma (HCC). Over 21 years the incidence of liver diseases increased 3.6 fold, predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease (NAFLD); the leading cause of liver disease from 2014. The incidence of cirrhosis, decompensation, HCC, and allcause mortality tripled. Liver-related mortality doubled. Alcohol-related liver disease (ArLD), autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality. CONCLUSION A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years. Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD. Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality

Does age matter? The impact of rodent age on study outcomes

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6–20 week age range regardless of the biology being studied. The age referred to as ‘adult’ by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans

Guidelines on the management of abnormal liver blood tests

These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.</p

Top research priorities in liver and gallbladder disorders in the UK

OBJECTIVES: There is a mismatch between research questions considered important by patients, carers and healthcare professionals and the research performed in many fields of medicine. The non-alcohol-related liver and gallbladder disorders priority setting partnership was established to identify the top research priorities in the prevention, diagnostic and treatment of gallbladder disorders and liver disorders not covered by the James-Lind Alliance (JLA) alcohol-related liver disease priority setting partnership. DESIGN: The methods broadly followed the principles of the JLA guidebook. The one major deviation from the JLA methodology was the final step of identifying priorities: instead of prioritisation by group discussions at a consensus workshop involving stakeholders, the prioritisation was achieved by a modified Delphi consensus process. RESULTS: A total of 428 unique valid diagnostic or treatment research questions were identified. A literature review established that none of these questions were considered 'answered' that is, high-quality systematic reviews suggest that further research is not required on the topic. The Delphi panel achieved consensus (at least 80% Delphi panel members agreed) that a research question was a top research priority for six questions. Four additional research questions with highest proportion of Delphi panel members ranking the question as highly important were added to constitute the top 10 research priorities. CONCLUSIONS: A priority setting process involving patients, carers and healthcare professionals has been used to identify the top 10priority areas for research related to liver and gallbladder disorders. Basic, translational, clinical and public health research are required to address these uncertainties

ISBS 2018 AUCKLAND CONFERENCE SPRINZ-HPSNZ-AUT MILLENNIUM APPLIED PROGRAMME

An interactive afternoon of sessions delivered by High Performance Sport New Zealand (HPSNZ) and AUT SPRINZ Biomechanists, Performance Analysts and other biomechanics relevant sport facing practitioners. The 11 sessions are at AUT Millennium (AUTM), which is a satellite site of AUT University and the Auckland training hub for many HPSNZ supported sports such as athletics, sailing, and swimming. These sports and others (cycling, rowing, snow sports etc.) will be represented in the line-up. The applied sessions involve practical demonstrations of aspects of analysis and/or tools used to deliver in the field to directly positively impact athletes performances on the world stage. Following these engaging sessions there will be tasting of New Zealand wine, allowing for further discussion and networking. Sir Graeme Avery will be acknowledged for his contribution to sport science. Mike Stanley is AUT Millennium Chief Executive & NZ Olympic Committee President will explain the partners in the facility. AUT Millennium is a charitable trust established to help New Zealanders live longer and healthier lives, and to enjoy and excel in sport through the provision of world-class facilities, services, research and education. Founded in 2002 as Millennium Institute of Sport and Health (MISH) by Sir Stephen Tindall and Sir Graeme Avery as a premium health and fitness facility for both athletes and the public alike. Partnered with AUT University in 2009, forming AUT Millennium, to expand research and education in the sporting sector. Professor Barry Wilson is an Adjunct Professor with SPRINZ at Auckland University of Technology and will be outlining the research and student opportunities. Martin Dowson is the General Manager Athlete Performance Support at High Performance Sport New Zealand and has overall responsibility for the programme. Simon Briscoe, AUT Millennium Applied Session Coordinator, is the head of the Performance and Technique Analysis discipline within HPSNZ. Simon is coordinating the applied sessions along with technical support from Dr Allan Carman, Research Fellow, AUT SPRINZ. Jodi Cossor and Matt Ingram will provide a demonstration of a multidisciplinary approach driven by biomechanical analysis for Paralympic swimmers. Justin Evans and Sarah-Kate Millar will provide a practical session assessing the athletes rowing stroke to assist the coach on technical changes. This session will demonstrate various rowing traits and how the biomechanist and coach can work together to optimise boat speed. Mike Schofield and Kim Hébert-Losier will provide a session looking at shotput and the evidence based approach to coaching. Dr Craig Harrison and Professor John Cronin will provide examples from the AUTM Athlete Development programme. Kim Simperingham and Jamie Douglas who work with high performance rugby athletes will outline sprinting mechanics in practice. Dr Bruce Hamilton, Fiona Mather, Justin Ralph and Rone Thompson will demonstrate the approach of HPSNZ and Cycling NZ performance health teams in the use of some specific tools for prevention of injury and optimisation of performance. Kelly Sheerin, Denny Wells and Associate Professor Thor Besier will provide examples of using IMU and motion capture methods for running and basketball biomechanics research, education and service. Dr Rodrigo Bini and Associate Professor Andrew Kilding will show how linking of biomechanics and physiology improves injury prevention and performance enhancement. Robert Tang, Andre de Jong and Farhan Tinwala discuss select projects developed by Goldmine, HPSNZ’s in-house engineering team, and how these innovations have enabled unprecedented levels of biomechanics feedback. Cameron Ross and Paul McAlpine demonstrate the technology being used at the Snow Sports NZ training centre in Cadrona to enhance load monitoring of athletes. This application allows greater insight into training performances and biomechanical loads than has been previously possible in the training environment. AUT Millennium tour guides are coordinated by Josh McGeown and include Enora Le Flao, Dustin Oranchuk, Erika Ikeda, Jono Neville, Aaron Uthoff, Andrew Pichardo, Farhan Tinwala, Shelley Diewald, Renata Bastos Gottgtroy, Jessica Yeoman, Casey Watkins, Eric Harbour, Anja Zoellner, Alyssa Joy Spence, Victor Lopez Jr, and Albert Chang

Planetary science and exploration in the deep subsurface: results from the MINAR Program, Boulby Mine, UK

The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining