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Summary: Background and Aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy‐proven cirrhosis in NAFLD. Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB‐4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95–0.97). FIB‐4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84–0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92–0.96), and FIB‐4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87–0.89). Conclusions: This cross‐sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher‐risk patients maintain access to specialty care. [ABSTRACT FROM AUTHOR]

Introduction: Improved outcomes of liver disease in childhood and young adulthood have resulted in an increasing number of young adults (YA) entering adult liver services. The adult hepatologist therefore requires a working knowledge in diseases that arise almost exclusively in children and their complications in adulthood., Aims: To provide adult hepatologists with succinct guidelines on aspects of transitional care in YA relevant to key disease aetiologies encountered in clinical practice., Methods: A systematic literature search was undertaken using the Pubmed, Medline, Web of Knowledge and Cochrane database from 1980 to 2023. MeSH search terms relating to liver diseases ('cholestatic liver diseases', 'biliary atresia', 'metabolic', 'paediatric liver diseases', 'autoimmune liver diseases'), transition to adult care ('transition services', 'young adult services') and adolescent care were used. The quality of evidence and the grading of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system., Results: These guidelines deal with the transition of YA and address key aetiologies for the adult hepatologist under the following headings: (1) Models and provision of care; (2) screening and management of mental health disorders; (3) aetiologies; (4) timing and role of liver transplantation; and (5) sexual health and fertility., Conclusions: These are the first nationally developed guidelines on the transition and management of childhood liver diseases in adulthood. They provide a framework upon which to base clinical care, which we envisage will lead to improved outcomes for YA with chronic liver disease., (© 2024 John Wiley & Sons Ltd.)

Background: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. Methods: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Results and discussion: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. Conclusions: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy and the postpartum period is a difficult time for women living with HIV (WLWH) and postpartum engagement with HIV care is often reduced, with implications for health and well-being. We aimed to explore the postpartum health experiences of WLWH in relation to engagement in HIV care., Methods: The NESTOR (iNvESTigating the pregnancy and pOst-paRtum health experience of women living with HIV) study was a UK based qualitative semi-structured interview study. 61 eligible women were identified. We used a purposive sampling technique to recruit women with differing levels of engagement in HIV care. Interviews were conducted via telephone or video call. Interviews were audio recorded and fully transcribed. We used a thematic approach for data analysis, and two researchers independently coded the data and established the key themes., Results: 11 of 61 (18%) eligible women participated in the interviews, and the three main themes were 'infant feeding decisions', 'managing the risk of mother to child transmission', and 'managing the knowledge of their HIV status'. These themes offer detailed insights into the significant psychological and emotional challenges these women had experienced, and the practical support from healthcare professionals in both HIV and maternity services that had enabled them to navigate those challenges., Discussion: There have been life-changing developments in the treatment and care for people living with HIV. However, even in the U = U (undetectable = untransmittable) era, traditional concerns about breastfeeding, risk of transmission to the infant and stigma continue to shape the postpartum experience of WLWH. As these impact on their emotional and psychological wellbeing, support in these areas needs to be prioritised., (© 2024. The Author(s).)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. Methods: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. Results: Participants aged 59 (51–64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid–base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. Conclusions: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD. [ABSTRACT FROM AUTHOR]

Background and Aims: Programmed cell death 1/programmed cell death‐ligand 1 (PD‐1/PDL‐1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholic steatohepatitis (NASH). Hepatic transcriptome was examined by RNA‐Seq in a subset of NAFLD individuals (n = 121). Transcriptomic and deconvolution analyses were performed to identify biological pathways modulated by the risk allele. Results: The rs13023138 C>G showed the most robust association with HCC in UK Biobank (p = 5.28E‐4, OR = 1.32, 95% CI [1.1, 1.5]). In the liver biopsy cohort, rs13023138 G allele was independently associated with severe steatosis (OR 1.17, 95% CI 1.02‐1.34; p =.01), NASH (OR 1.22, 95% CI 1.09‐1.37; p <.001) and advanced fibrosis (OR 1.26, 95% CI 1.06‐1.50; p =.007). At deconvolution analysis, rs13023138 G>C allele was linked to higher hepatic representation of M1 macrophages, paralleled by upregulation of pathways related to inflammation and higher expression of CXCR6. Conclusions: The PDCD1 rs13023138 G allele was associated with HCC development in the general population and with liver disease severity in patients at high risk of NASH. [ABSTRACT FROM AUTHOR]

The article offers information on the British HIV Association guidelines on the management of opportunistic infection in people living with HIV. Topics include reports that the search questions were set and an independent systematic literature review carried out and the PubMed, Medline, Embase and Cochrane Library databases were searched and the literature reviewed to address each question.

Why are public inquiries appointed and what factors are influential? Research shows that inquiry appointment is driven by issue salience, but how this occurs is unclear. The authors suggest that issue salience is driven by: (1) victim relatability, (2) visibility of failings and (3) perceived blameworthiness. This has three significant implications. First, highly salient issues may lead to the appointment of statutory-type inquiries, which might not be the most appropriate form to effectively address the causes of inequality. Second, if wrongdoing against minorities is not sufficiently relatable (as is often the case), there may be insufficient public salience to drive demands for an inquiry. Finally, inquiries may privilege the investigation of blameworthy behaviour and thereby overlook complex systemic flaws. Public inquiries are important tools for lesson learning in the wake of a crisis or controversy. We claim that 'gold standard' statutory inquiries tend to be appointed only when a crisis has publicly salient (i.e. relatable) victims, is perceived to be a result of systemic failings, and has blameworthy behaviour. It is important to appreciate that many public sector failures—particularly those in which widepsread inequality is a core concern—will often fail this threefold test, and therfore be misleadingly attributed to technical or individualized explanations, or be overlooked by government. [ABSTRACT FROM AUTHOR]

The article reports about the breastfeeding and women living with HIV in the Great Britain and high-income countries. Topics include how the risk of HIV transmission through breastfeeding is lower than demonstrated; and how the mothers who intended to breastfeed but were not able to were shown to have an increased risk of postnatal depression.

Background: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. Methods: A two‐day, face‐to‐face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. Results: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non‐steroid‐based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. Conclusions: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real‐world evidence studies assessing anti‐immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti‐IgE and non‐steroid‐based alternative therapies may delay disease progression, leading to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Recent terrorist attacks in the UK have raised questions over the relationship between Britain's foreign policy and terrorist attacks in the UK. The main arguments made by Labour Party leader Jeremy Corbyn, his critics and the views of those charged with defending the UK from terrorism are summarized. The article argues that the UK government's reasons for denying a relationship between foreign policy and terrorist attacks are because of (1) evidence that Britain's foreign policies have contributed to violent radical extremism and (2) links between some "terrorists", designated jihadist groups and Britain's intelligence services. [ABSTRACT FROM AUTHOR]

Abstracts of presentations made during the international combined meeting of the British Hip Society and the Societa Italiana dell'Anca on November 26-27, 2015 in Milan, Italy are presented including "Registry Data Errors in the National Hip Fracture Database" by Duncan Cundall-Curry et al, "FAI and Lumbar Stiffness" by Alessandra Aprato et al and "Infection and Failure Rates Following Thr in Septic Arthritis: A Case Controlled Study" by Madhavan C. Papanna et al.

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were ‘HBV therapy’, ‘HBV treatment’, ‘VE antiviral effects’, ‘tocopherol antiviral activity’, ‘miRNA antiviral activity’ and ‘VE microRNA’. Reports describing the role of miRNA in the regulation of HBV life cycle, in vitro and in vivo available studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment. [ABSTRACT FROM PUBLISHER]

The sphere of foreign policy provides a hitherto unexplored field for studying the applicability of interpretivist concepts and concerns. Here, a particularly useful topic of analysis is that of discursive strategies; namely, the way in which government figures seek to legitimise and justify their decisions and behaviour. Operating at the intersection between beliefs, traditions and dilemmas, the examination of foreign policy discourse offers key insights into a variety of important issues, including political communication and media management. This article considers these themes by examining the changing form of New Labour's discursive strategy on Britain's role in the war on terror during the period of Tony Blair's premiership from 2001 to mid-2007. Charting the various shifts to have taken place in this discursive landscape, the article analyses the way in which these changes were driven by dilemmas resulting from tensions between practical developments and the discursive claims made about them. This shows how various rationalities within the sphere of British politics were operationalised and sustained, and how numerous 'dilemmas of discourse' were addressed. [ABSTRACT FROM AUTHOR]

Counterterrorism efforts over the past five years have yielded important progress against Al-Qaeda abroad, even with heightened anxiety about the threat of attacks at home. There was certainly no ‘clash of civilizations’; violent Salafism engendered a muscular backlash in Muslim-majority countries, which threatened Al-Qaeda's ability to recruit and even survive. At the same time, the policies of major states became more effective and better aligned. A nascent counterterrorism coalition emerged with unprecedented sharing of intelligence, operations and deradicalization techniques (especially bilaterally). In the face of these developments, a defensive Al-Qaeda scrambled to exploit vulnerabilities so as to regain a mental edge. The result was two tactical setbacks for the allies: first, Al-Qaeda and its associates redoubled their efforts to kill civilians on western soil, focusing particularly on radicalized home grown amateurs; and second, they leaned more heavily on reinvigorated affiliates, some of whom tried to project force beyond their local operating areas for the first time. As a result, terrorist operations in the US and UK were more frequent, unpredictable and unsophisticated, but nonetheless potentially lethal. As the period drew to a close, the crucial question was whether the two western allies could maintain their nerve, luck, skill and sufficient equilibrium to both fend off a domestic attack and plan for an effective strategic response in the event that one occurred. [ABSTRACT FROM AUTHOR]

The UK has a large marine renewable energy resource and has been developing a range of wave and tidal technologies for exploiting it. However, progress on moving to the commercial scale has been slow, in part, it is argued, as a result of the way this area of innovation has been supported by the government. This paper looks at the technologies and how they are being developed in the UK and elsewhere. It notes that, although the UK is still in the lead in terms of novel device development, unless better support is provided, the UK might lose out to device developers from other countries in the race to capture the very large global market that is opening up for the relevant technologies. [ABSTRACT FROM AUTHOR]

This paper is about the politics, planning, and public perceptions associated with offshore wind farms. Although only half the applications for onshore wind farms are successful in England and Wales, the latest round of offshore applications have had far higher rates of consent. But is it simply the case that siting wind farms offshore solves the problems that onshore applications encounter? This paper argues that many of the same problems are experienced by both onshore and offshore wind farms, albeit in slightly different ways; and that these need to be addressed if the promised expansion in offshore wind is to be delivered. This paper draws together the research and evidence relating to onshore and offshore wind developments, exploring this with the emerging research on public perceptions of offshore wind farms, and initial empirical evidence from a proposed wind farm off the coast of North Wales. It concludes with some remarks about the potential for offshore wind around the UK, considers the role of spatial planning, and discusses issues for policy and planning that must be addressed if the Government's ambitious targets are to be achieved. [ABSTRACT FROM AUTHOR]

The article looks at the issue of jihad terrorism in Great Britain. After the July 7 terrorist attack, the government has introduced the controversial Terrorism Act 2005, a legislation to outlaw the glorification of terrorism, legislation that proved very controversial in Parliament. One way of comprehending the target set of the British jihadi is to understand that they are not strategists that is they are not engaged in a campaign of strategic bombing.

Describes several post-medieval archaeological sites in Great Britain and Ireland. All Saints Chapel in Bath; Rainbow Wood Farm in Claverton Down; Masonic Hall in Old Orchard Street.

The links between the drivers of change in farming structures and practices, the adoption of those practices and their environmental impacts are complex, multidimensional and dynamic, generally involving long time lags. We can visualize agriculture as having evolved, so far, through two eras: pre-industrial and industrial. There are signs that we are now moving into a third generation: post-industrial agriculture. This is outlined and illustrated. The thesis is that we are passing the apogee of environmental destructiveness in UK agriculture. The policy changes now in place in the new post-Fischler CAP have the capacity to steer rural land use in a different and preferred direction. Of course, this outcome is not guaranteed. [ABSTRACT FROM AUTHOR]

Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview-based case–control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged ≤75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age- and sex-matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2·51, 95% confidence interval (CI) 1·02–12·01], particularly for woodworm treatment (OR = 5·1, 95% CI 1·5–17·4). This study identified significant risks associated with self-reported exposure to solvents, radiation and pesticides in the workplace. Self-reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature. [ABSTRACT FROM AUTHOR]

Features developments in post-medieval Britain and Ireland in 2002 as of December 2003. Number of trenches excavated in Bath, Crescent Lane; Details of the alterations in the Combe Hay, Watercress Cottage; Standard of the window mullions in West Hill House.

Community work is not easily captured in a diagram, and any attempt to visually represent the complex nature of community development is a ready target for criticism. While the Department for International Development's (DFID) sustainable livelihoods framework can be strung up on the same charges of enticing people into simplicity and rigidity, this paper argues that, used flexibly, it can be an effective tool for organizing and analysing ideas. Using a UK community energy scheme as a case example, it demonstrates how, by stirring in an individual project's needs, a little creativity, and a staunch lack of respect for rigid diagrams, the sustainable livelihoods framework and its accompanying approach can cook up an excellent stock for a community development toolkit. [ABSTRACT FROM AUTHOR]