As the first Christian emperor of Rome, Constantine the Great has long interested those studying the establishment of Christianity. But Constantine is also notable for his ability to control a ...sprawling empire and effect major changes.The Justice of Constantineexamines Constantine's judicial and administrative legislation and his efforts to maintain control over the imperial bureaucracy, to guarantee the working of Roman justice, and to keep the will of his subjects throughout the Roman Empire.
John Dillon first analyzes the record of Constantine's legislation and its relationship to prior legislation. His initial chapters also serve as an introduction to Roman law and administration in later antiquity. Dillon then considers Constantine's public edicts and internal communications about access to law, trials and procedure, corruption, and punishment for administrative abuses. How imperial officials relied on correspondence with Constantine to resolve legal questions is also considered. A study of Constantine's expedited appellate system, to ensure provincial justice, concludes the book.
Constantine's constitutions reveal much about the Theodosian Code and the laws included in it. Constantine consistently seeks direct sources of reliable information in order to enforce his will. In official correspondence, meanwhile, Constantine strives to maintain control over his officials through punishment; trusted agents; and the cultivation of accountability, rivalry, and suspicion among them.
The introduction of efficacious new hepatitis C virus (HCV) treatments galvanized the World Health Organization to define ambitious targets for eliminating HCV as a public health threat by 2030. ...Formidable obstacles to reaching this goal can best be overcome through a micro-elimination approach, which entails pursuing elimination goals in discrete populations through multi-stakeholder initiatives that tailor interventions to the needs of these populations. Micro-elimination is less daunting, less complex, and less costly than full-scale, country-level initiatives to eliminate HCV, and it can build momentum by producing small victories that inspire more ambitious efforts. The micro-elimination approach encourages stakeholders who are most knowledgeable about specific populations to engage with each other and also promotes the uptake of new models of care. Examples of micro-elimination target populations include medical patients, people who inject drugs, migrants, and prisoners, although candidate populations can be expected to vary greatly in different countries and subnational areas.
Plotin a souvent été décrit comme un philosophe qui aurait eu des visions directes de l’Un et de l’intelligible, dont témoignent le début du traité 6 (IV, 8) et les affirmations de Porphyre dans sa ...Vie de Plotin. L’auteur des Ennéades rejoint donc une longue tradition de mystiques connus pour leur expérience du divin. Mais des études récentes ont montré que ces expériences mystiques pouvaient souvent s’expliquer par des troubles neurologiques. Le but de cet article est de comparer la description plotinienne de l’intelligible avec celle d’une expérience de mort imminente (EMI) vécue par l’auteur Eben Alexander et explicable du point de vue strictement neurologique. De cette façon, nous verrons si nous pouvons approfondir notre connaissance des visions plotiniennes telles qu’elles ont pu être vécu par le philosophe.
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.
Direct-acting antiviral therapy (DAAs) for hepatitis C infection (HCV) have a much smaller burden of treatment than interferon-based regimes, require less monitoring and are very effective. New ...pathways are required to increase access to treatment amongst people prescribed opioid substitution therapy (OST).
An exploratory cluster randomised controlled trial with mixed methods evaluation was undertaken to compare the uptake of dried blood spot testing (DBST) and treatment of people with genotype 1 HCV infection in a conventional service pathway versus a pharmacist-led pathway in a population receiving OST.
Pharmacies randomised to the conventional pathway obtained 58 DBST from 244 patients (24%):15 new reactive tests and 33 new negative tests were identified. Within the pharmacist-led pathway, 94 DBST were obtained from 262 patients (36%): 26 new reactive tests and 54 new negative tests were identified. Participants in the pharmacist-led pathway were more likely to take a DBST (p<0.003). Of participants referred for treatment through the conventional pathway, 4 patients from 15 with new reactive tests (27%) attended clinic for assessment. In the pharmacist-led treatment pathway, 20 patients from 26 with new reactive tests (77%) attended for assessment blood tests. Participants in the pharmacist-led pathway were more likely to proceed through the assessment for treatment (p<0.002). One participant completed treatment through the conventional pathway and three patients completed treatment through the pharmacist-led pathway. The process evaluation identified key themes important to service user completers and staff participants.
The study provides evidence that testing and treatment for HCV in a pharmacist led-pathway is a feasible treatment pathway for people who receive supervised OST consumption through community pharmacies. This feasibility trial therefore provides sufficient confirmation to justify proceeding to a full trial.
Gamma‐Glutamyl Transferase (γGT) is a key transferase involved in the transpeptidation of functional gamma‐glutamyl groups to various receptor moieties. It performs important roles in antioxidant ...defence mechanisms, particularly glutathione recycling, xenobiotic metabolism, but analogously may also have a pro‐oxidant role.
γGT is very sensitive for the diagnosis of liver injury, although it has poor specificity for particular aetiologies. It has been used to reflect temporal changes as a form of monitoring depending on aetiology.
Given its cellular role in antioxidant function, it has been investigated as a surrogate biomarker of oxidative stress. It has also been found to be a predictor of mortality across a spectra of non‐hepatic disease pathologies, from metabolic and cardiovascular risk to chronic kidney disease and neoplasia. Similarly, it also remains of interest to the insurance industry given an apparent ability to predict mortality, in addition to a historical interest from law enforcement as a marker of chronic alcohol ingestion.
Here, we review some of the unique characteristics of this important enzyme, previously considered as a mere specific marker of liver dysfunction, but now with clear extra‐hepatic implications and novel applications and utility.
Direct Acting Antiviral (DAAs) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin, and a much higher efficacy in treating ...hepatitis C (HCV). These characteristics mean that initiating treatment and obtaining a virological cure (Sustained Viral response, SVR) on completion of treatment, in non-specialist environments should be feasible. We investigated the English-language literature evaluating community and primary care-based pathways using DAAs to treat HCV infection.
Databases (Cinahl; Embase; Medline; PsycINFO; PubMed) were searched for studies of treatment with DAAs in non-specialist settings to achieve SVR. Relevant studies were identified including those containing a comparison between a community and specialist services where available. A narrative synthesis and linked meta-analysis were performed on suitable studies with a strength of evidence assessment (GRADE).
Seventeen studies fulfilled the inclusion criteria: five from Australia; two from Canada; two from UK and eight from USA. Seven studies demonstrated use of DAAs in primary care environments; four studies evaluated integrated systems linking specialists with primary care providers; three studies evaluated services in locations providing care to people who inject drugs; two studies evaluated delivery in pharmacies; and one evaluated delivery through telemedicine. Sixteen studies recorded treatment uptake. Patient numbers varied from around 60 participants with pathway studies to several thousand in two large database studies. Most studies recruited less than 500 patients. Five studies reported reduced SVR rates from an intention-to-treat analysis perspective because of loss to follow-up before the final confirmatory SVR test. GRADE assessments were made for uptake of HCV treatment (medium); completion of HCV treatment (low) and achievement of SVR at 12 weeks (medium).
Services sited in community settings are feasible and can deliver increased uptake of treatment. Such clinics are able to demonstrate similar SVR rates to published studies and real-world clinics in secondary care. Stronger study designs are needed to confirm the precision of effect size seen in current studies. Prospero: CRD42017069873.
On the General Science of Mathematics is the third of four surviving works out of ten by Iamblichus (c. 245 CE-early 320s) on the Pythagoreans. He thought the Pythagoreans had treated mathematics as ...essential for drawing the human soul upwards to higher realms described by Plato, and downwards to understand the physical cosmos, the products of arts and crafts and the order required for an ethical life. His Pythagorean treatises use edited quotation to re-tell the history of philosophy, presenting Plato and Aristotle as passing on the ideas invented by Pythagoras and his early followers. Although his quotations tend to come instead from Plato and later Pythagoreanising Platonists, this re-interpretation had a huge impact on the Neoplatonist commentators in Athens. Iamblichus' cleverness, if not to the same extent his re-interpretation, was appreciated by the commentators in Alexandria.
Non-alcoholic steatohepatitis (NASH) represents a global health concern. It is characterised by fatty liver, hepatocyte cell death and inflammation, which are associated with lipotoxicity, ...endoplasmic reticulum (ER) stress, mitochondrial dysfunction, iron overload and oxidative stress. NF-E2 p45-related factor 2 (Nrf2) is a transcription factor that combats oxidative stress. Remarkably, Nrf2 is downregulated during the development of NASH, which probably accelerates disease, whereas in pre-clinical studies the upregulation of Nrf2 inhibits NASH. We now review the scientific literature that proposes Nrf2 downregulation during NASH involves its increased ubiquitylation and proteasomal degradation, mediated by Kelch-like ECH-associated protein 1 (Keap1) and/or β-transducin repeat-containing protein (β-TrCP) and/or HMG-CoA reductase degradation protein 1 (Hrd1, also called synoviolin (SYVN1)). Additionally, downregulation of Nrf2-mediated transcription during NASH may involve diminished recruitment of coactivators by Nrf2, due to increased levels of activating transcription factor 3 (ATF3) and nuclear factor-kappaB (NF-κB) p65, or competition for promoter binding due to upregulation of BTB and CNC homology 1 (Bach1). Many processes that downregulate Nrf2 are triggered by transforming growth factor-beta (TGF-β), with oxidative stress amplifying its signalling. Oxidative stress may also increase suppression of Nrf2 by β-TrCP through facilitating formation of the DSGIS-containing phosphodegron in Nrf2 by glycogen synthase kinase-3. In animal models, knockout of Nrf2 increases susceptibility to NASH, while pharmacological activation of Nrf2 by inducing agents that target Keap1 inhibits development of NASH. These inducing agents probably counter Nrf2 downregulation affected by β-TrCP, Hrd1/SYVN1, ATF3, NF-κB p65 and Bach1, by suppressing oxidative stress. Activation of Nrf2 is also likely to inhibit NASH by ameliorating lipotoxicity, inflammation, ER stress and iron overload. Crucially, pharmacological activation of Nrf2 in mice in which NASH has already been established supresses liver steatosis and inflammation. There is therefore compelling evidence that pharmacological activation of Nrf2 provides a comprehensive multipronged strategy to treat NASH.
Thrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating ...thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer.
Between August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7-11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0-3.7%) of controls. Patients <40 years or with pre-existing causes of thrombocytosis were then excluded. Subsequent analysis revealed a 10.8% (6.6-16.3%) incidence of cancer in thrombocytosis patients (n = 176) compared to 2.5% (1.2-4.6%, p = 0.00014) in patients with normal platelet count (PLT) (n = 398). When thrombocytosis is combined with elevated alkaline phosphatase (ALP), there is a positive predictive value (PPV) of 20% for cancer. These rules were subsequently applied to a validation cohort of 71,652 patients, of whom 458 had thrombocytosis and elevated ALP. There was a 30.6% cancer incidence, confirming the strong predictive value of the combined test of PLT and ALP.
These findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated.
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