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Background: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended. Aim: This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic. Methods: Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance. Results: Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test. Discussion: These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses. Conclusions: Genetic white matter disorders are genetically and phenotypically heterogeneous. Deep phenotyping together with a range of genomic technologies underpin the identification of causes of unclassified white matter disease. A molecular diagnosis is essential for prognostication, appropriate management, and accurate reproductive counseling.

Background The content of the endosperm of the coconut (Cocos nucifera L.) contains “coconut water”. This practically sterile liquid which is prized for its delicate, albeit labile, flavor when fresh, has had a recent dramatic increase in global demand. The organoleptic superiority of water from young coconuts means that degree of maturity at harvesting is the most influential factor in yield and composition. Objective To provide a guide to establishing the authenticity and the potability of samples of coconut water. Method Review and evaluate the literature on the factors that determine the composition and stability of coconut water. Results Data is presented on the variances in natural composition, maturity, processing-induced compositional changes, adulterations, product recalls, classical and instrumental methods of analysis and on the available composition standards of coconut water. Conclusions Advice is provided for official food analysts, and others, on prudent approaches as how to ascertain the authenticity and potability, or otherwise, of coconut water samples.

Background Food fraud is the intentional deception carried out for gain, and is growing. Rice is the most used and the staple cereal for more than half of the world. Because of the scale of the global rice industry, the opportunities for fraud are large, of concern and threat to the economies and health of many. Scope and approach This review ouylines the complexities of the global rice industry and outlines current frauds. Fraudulent actions can be on many levels such as: botanical and geographical origin, adulteration/substitution, ageing, cultivation practices, aroma/flavour and amounts of microelements. To deal with new rice frauds, the range of techniques to detect them is increasing. Key findings and conclusions Current research concerning rice fraud is mainly focussed on rice authenticity testing for botanical/geographical origin or cultivation methods. In the case of Mass Specrometry, more advanced techniques are increasingly applied due to their great untargeted analysis power. Spectroscopic techniques can mainly provide screening, but rapid and non-destructive sample analysis, they are cost effective and once established require little expertise. DNA assays are excellent tools to apply for authenticity testing of botanical origin of rice. There is at present, no single analytical tool capable of providing an answer to all rice authentication problems, thus it is necessary to use several approaches in profiling and identification of possible markers and/or adulterants.

The origin of the method of standard additions (SAM) and of the use of internal standard (IS) in instrumental chemical analysis and their spread into other areas has been reviewed. Recorded applications of IS range from flame spectroscopy in 1877 through multiple techniques to current use in NMR and standard additions with isotopically labelled internal standards in hyphenated techniques. For SAM, applications stemmed from polarography in 1937 and spread to most instrumental methods. Some misconceptions on priorities are corrected.

Background: Recent data show that patients with autoimmune hepatitis have significantly reduced quality of life and that corticosteroids (still central to therapy) carry marked side effects. This study explored the patients’ experience of autoimmune hepatitis and its treatments; aspects that are key to understanding how we can develop safe and effective new approaches to therapy. Methods: An anonymised, internet-based survey was conducted between December 2019 and January 2020. Data were collected about patient demographics, treatments, side effects, impact on day-to-day life, sources of support and attitudes towards autoimmune hepatitis. Semi-structured interviews were then conducted with 13 patients to further explore their support networks, treatment experiences and health priorities. Descriptive and quantitative analyses were undertaken using R and free text responses were subject to thematic analysis. Findings: A total of 270 survey responses were received (median age 55 years and 94% female). Perceived medication side effects were reported by 66% (169/257) and 73% responded negatively about their experience of corticosteroids. The majority (62·3% [(109/175]) would ‘definitely’ or ‘probably’ consider clinical trial participation to improve their care with new and/or improved treatments. Only 18·7% (31/166) reported access to a specialist liver nurse and nearly half were involved in support groups. Data from the interviews and survey suggested that major issues were stigma in liver disease, loss of control and fatigue. Interpretation: This study provides insights into the realities of living with autoimmune hepatitis. There are clear issues with lack of support networks, need for patient empowerment and stigma surrounding liver disease. Patient priorities are better therapies to slow disease progression, avoiding corticosteroids and minimising side effects. The willingness of patients to participate in clinical trials is a positive finding and suggests that trials are achievable provided they have the right design and clinical endpoints. Funding: No funding to declare. Declaration of Interest: Dr Jessica Katharine Dyson has received speaker fees from Dr Falk Pharma and Intercept Pharmaceuticals. MISSING ALL OTHER AUTHORS. Ethical Approval: MISSING

The possibility that prostaglandin E2 (PGE2) has a central action in the fetal lamb arises from studies by Ratter et al. and Robinson. The Prostaglandin E (PGE) release into the fetus may help to preserve fetal growth by decreasing nonessential fetal muscular activity, e.g., fetal breathing movements, thereby sparing glucose. PGE may also maintain a minimum glucose utilization by stimulating insulin release and enhancing pancreatic sensitivity to glucose. PGE2 concentrations in fetal plasma have been shown to increase during late gestation in sheep and this increase parallels the increase in fetal cortisol concentrations. The site of action of PGE2 has also been studied in newborn lambs in which plasma cortisol concentrations increased when PGE2 was infused into the brachiocephalic trunk, but not when infused into the descending aorta. Decreased placental perfusion, caused by placing a clamp on the common iliac artery, results in an increase in fetal cortisol concentrations, which may be secondary to increased fetal PGE2 concentrations.

Methods for the determination of the authenticity of samples of mānuka honey are reviewed. Suggestions are made as to how to authenticate, or otherwise, the label claims for a given sample of mānuka honey.

Methods for the determination of the most commonly found materials used to adulterate coffee as diluents and to establish the geographic and genotypic origin of beans are reviewed. Suggestions are made as to how to start to authenticate, or otherwise, the label claims for a given sample of roast ground coffee.

BACKGROUND Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established. AIM To evaluate the prognostic utility of four biomarkers of basement membrane and interstitial extracellular matrix remodeling in patients with primary sclerosing cholangitis. METHODS Serum samples were available from 138 large-duct primary sclerosing cholangitis patients (of which 102 [74%] with IBD) recruited 2008-2012 and 52 ulcerative colitis patients (controls). The median follow-up time was 2.2 (range 0-4.3) years. Specific biomarkers of type III and V collagen formation (PRO-C3 and PRO-C5, respectively) and type III and IV collagen degradation (C3M and C4M, respectively) were assessed. The Enhanced Liver Fibrosis test, including procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinase-1 and hyaluronic acid was assessed for comparison. RESULTS All markers were elevated in primary sclerosing cholangitis compared to ulcerative colitis patients (P

Over the past twelve years hundreds of official analyses for nitrofuran antibiotic residues in farmed shrimp and prawns have led to product recalls, border rejections, and de-listed suppliers. Positive-release testing regimes have been instigated at huge economic cost. There have been repeated occasions when new scientific information or policy clarification has led to enforcement decisions being seen in a new light and current practice continues to evolve. There remain discrepancies between results found pre-harvest and pre-export in some countries, and results from Border Inspection Posts' analyses when consignments arrive at their destination, despite international harmonisation of test methods and quality criteria. Forensic issues around enforcement decisions following laboratory results for non-compliant consignments containing nitrofurans are summarised herein, including those that have been referred for technical appeal to the UK Government Chemist. Current best practice is collated and specific recommendations and suggestions made for the decision-making process in food safety enforcement. We recommend an approach to semicarbazide analysis from core flesh, removal of ice glaze prior to analysis and that measurement uncertainty is subtracted from the mean result to yield a ‘not less than’ figure used for reporting purposes ‘beyond reasonable doubt’. Research is needed to fill knowledge gaps with regard to sample homogeneity and sampling protocols for nitrofurans in food of animal origin. Sampling should be standardised, as has been established for mycotoxin controls and a modern toxicology risk assessment of nitrofurans and their metabolites in food appears to be warranted.

INFORMATION FROM THE EUCHEMS DIVISION OF ANALYTICAL CHEMISTRY (DAC) THE ROLE OF KNOWLEDGE OF THE HISTORY OF ANALYTICAL CHEMISTRY FOR ACADEMICS AND FOR LAW ENFORCEMENT AUTHORITIES

'Hub-and-spoke' networks may be one solution to reduce the geographical inequality in access to liver transplantation (LT) and the growing demands on, and saturation of, LT centres. It is not clear if such networks improve equity of access, deliver comparable patient outcomes or effect patient satisfaction.Retrospective evaluation of outcomes and patient satisfaction within the Royal Free liver transplant 'hub-and-spoke' network.Patient outcomes in those assessed for LT between September 2011 and 2014 at spoke centres (n = 4) were compared retrospectively with those assessed at the LT hub centre. Patient satisfaction questionnaires were completed and changes in LT referral patterns were explored with data obtained directly from NHS Blood and Transplant (NHSBT).A total of 655 patients (180 spoke; 475 hub) were assessed for LT. Patients referred from spoke centres were more likely to have viral hepatitis as an underlying aetiology (72/180 vs 110/475; P 0.001), or hepatocellular carcinoma (48/180 vs 60/475; P 0.001) as an indication for LT and were more likely to be listed for LT when compared with hub patients (139/180 vs 312/475, P = 0.005). Mortality on the waiting list (9/123 vs 25/269, P = 0.57), waiting time to LT (64-days vs 78-days, P = 0.91) and Model for End-Stage liver disease (MELD)/United Kingdom End-Stage Liver Disease (UKELD) score (P = 0.24/0.26) in listed patients were equivalent as were 1- and 3-year patient and graft survival rates. Patient satisfaction rates were high at both types of centre, with significantly more patients preferring 'locally delivered care' at spoke vs hub (11/50 vs 70/73, P≤0.0001). Since the development of formal hub-and-spoke networks data from NHSBT based on postcode confirmed a significant increase in patients undergoing LT (153%) from spoke centres, whereas numbers assessed and transplanted from the hub centre have remained static.Hub-and-spoke LT networks are effective in offering equivalent clinical outcomes, high patient satisfaction and alleviate clinical pressure on the hub centre. They have to potential to help eliminate the geographical disparity in mortality rates from chronic liver disease.

The history of food adulteration and fraud and attempts at their control from the Middle Ages to date is traced for Belgium and for the UK with special reference to butter and margarine. The development of analytical procedures for the authentication of milk fat is outlined, from those based on the characterisation of fatty acids derived from milk fat in the nineteenth century to chromatographic methods in the next century and the recent rapid spectroscopic approaches. The importance of adequate surveillance programmes to reduce the incidence of food fraud is stressed.