Estimating the effectiveness and cost-effectiveness of body weight interventions for the prevention of non-communicable disease in local authority areas of England

Background Non-Communicable Diseases related to Body Mass Index (BMI) account for approximately 10% of all disease burden in England. Addressing this burden and its associated health inequalities are major challenges for local and national policymakers, with increasing need to also understand how BMI interventions might affect local areas differently. The aim was set to develop a new local authority-level health model to estimate the disease burden and healthcare cost implications of BMI interventions. Methods Diseases included in the new model were asthma, low back pain, osteoarthritis of the hip, osteoarthritis of the knee, Ischaemic Heart Disease, stroke, hypertensive heart disease, type-2 diabetes mellitus, atrial fibrillation/ flutter, colorectal cancer, breast cancer and oesophageal cancer. Local-level data were estimated via different approaches: adult BMI distributions were produced via individual-level synthetic estimation, child BMI distributions were interpolated from measured BMI and healthcare costs estimated using new high-quality cost collection data. Disease epidemiology was estimated at the Index of Multiple Deprivation quintile level using a Bayesian modelling tool. A scenario on restricting television advertising of unhealthy foods in each of 315 local authorities in England was then used to explore the new model’s capabilities. Findings Patterns to adult and child BMI supported conventional ideas that raised BMI is associated with age and deprivation. Healthcare costs formed very positively skewed distributions without an obvious geographic pattern. Disease epidemiology showed burden was broadly higher in more deprived quintiles. Modelling showed that restricting the advertising of unhealthy foods is likely to benefit more deprived areas more overall, but with overlaps between quintiles of deprivation. It is estimated that 0.0222-0.0521 Quality-Adjusted Life-Years per person could be saved over the lifetime of the 2018 population of children and £11.7-£42.8 per person in healthcare costs. Conclusions This model offers the most local-specific health modelling for BMI interventions in England. Some areas may be harder to reach with a given intervention, creating mismatch between need and ability to intervene

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Quantification of african monsoon runoff during last interglacial sapropel S5

Organic‐rich sapropel layers punctuate the eastern Mediterranean sedimentary sequence, recording deep‐sea anoxic events. The timing of sapropel deposition coincides with precession minima, which are associated with the northward migration of the monsoon rain belt over North Africa. The resultant increase in monsoon precipitation over the Sahara caused an increase in low‐δ 18 O freshwater runoff into eastern Mediterranean surface waters, which is reflected by negative δ 18 O anomalies in the records of planktic foraminiferal calcite. However, despite extensive research on sapropels, the magnitude of monsoon intensification and freshwater runoff, along with its influence on δ 18 O, remains elusive. Here, we present a quantification of African monsoon freshwater runoff into the eastern Mediterranean for the period of deposition of last interglacial sapropel S5 (~128.3–121.5 ka). Our method uses a box model of the Mediterranean Sea, which represents different water masses, and has been calibrated using δ 18 O from planktic foraminiferal species of different depth and seasonal habitats. The model was constrained with existing records of sea level and sea surface temperature then inverted to deconvolve the δ 18 O signal of the surface‐dwelling foraminiferal species Globigerinoides ruber (w) and calculate the freshwater runoff volume. Our calculated African monsoon runoff suggests large increases in freshwater discharge to the eastern Mediterranean (up to ~8.8 times the modern pre‐Aswan Nile discharge). Rapid onset of S5 deposition following the estimated increase in runoff strongly suggests a preconditioning of the eastern Mediterranean for sapropel deposition. Our study also provides insight into the stratification and warming of eastern Mediterranean surface waters during the S5 interval.Australian Research Council | Ref. FL120100050Australian Research Council | Ref. DE190100042Australia-New Zealand IODP Consortium | Ref. LE140100047Australia-New Zealand IODP Consortium | Ref. LE16010006

Discordant inflammatory changes in the apophyseal and sacroiliac joints: serial observations in enthesitis-related arthritis

OBJECTIVE: To determine the extent to which inflammation of the sacroiliac joints (SIJs) and apophyseal joints (AJs) changes concordantly after treatment in enthesitis-related arthritis (ERA). METHODS: A retrospective study was performed with institutional review board approval. 31 young patients with ERA who had been scanned between March 2009 and November 2014 were included. All patients had post-contrast imaging of the SIJs and lumbar spine and short tau inversion-recovery (STIR) images of the SIJs. The severity of sacroiliitis was scored using a modification of an established technique, and inflammation of the AJs was evaluated using a recently described grading system. The changes in SIJ and AJ scores after treatment were classified as either concordant or discordant, and the proportion of scan pairs in these groups was recorded. In addition, the correlation between change in SIJ STIR score (Δnfla) and change in AJ score (ΔAJ) was assessed using Spearman's correlation coefficient. RESULTS: Of a total of 43 scan pairs, the changes in inflammation were concordant in 16 scan pairs and discordant in 27 scan pairs. There was no significant correlation between Δnfla and ΔAJ (R = 0.14, p = 0.37). CONCLUSION: Inflammatory changes in the SIJs and AJs are often discordant. This may be a reason why patients experience ongoing back pain despite apparent improvement in one or the other site. ADVANCES IN KNOWLEDGE: Inflammation may behave differently at different anatomical sites. The SIJs and AJs should both be imaged in patients with ERA with back pain

A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients

<p>Abstract</p> <p>Background</p> <p>The phosphate ester PR-104 is rapidly converted in vivo to the alcohol PR-104A, a nitrogen mustard prodrug that is metabolised to hydroxylamine (PR-104H) and amine (PR-104M) DNA crosslinking agents by one-electron reductases in hypoxic cells and by aldo-keto reductase 1C3 independently of oxygen. In a previous phase I study using a q 3 week schedule of PR-104, the maximum tolerated dose (MTD) was 1100 mg/m²and fatigue, neutropenic fever and infection were dose-limiting. The primary objective of the current study was to determine the dose-limiting toxicity (DLT) and MTD of weekly PR-104.</p> <p>Methods</p> <p>Patients with advanced solid tumours received PR-104 as a 1-hour intravenous infusion on days 1, 8 and 15 every 28 days with assessment of pharmacokinetics on cycle 1 day 1. Twenty-six patients (pts) were enrolled (16 male/10 female; median age 58 yrs, range 30 to 70 yrs) who had received a median of two prior chemotherapy regimens (range, 0 to 3) for melanoma (8 pts), colorectal or anal cancer (3 pts), NSCLC (3 pts), sarcoma (3 pts), glioblastoma (2 pts), salivary gland tumours (2 pts) or other solid tumours (5 pts). PR-104 was administered at 135 mg/m²(3 pts), 270 mg/m²(6 pts), 540 mg/m²(6 pts), 675 mg/m²(7 pts) and 900 mg/m²(4 pts) for a median of two treatment cycles (range, 1 to 7 cycles) and five infusions (range, 1 to 18) per patient.</p> <p>Results</p> <p>Dose-limiting toxicities (DLTs) during cycle one included grade four thrombocytopenia at 540 mg/m²(1 of 6 pts) and grade four thrombocytopenia and neutropenia at 900 mg/m²(2 of 4 pts). At an intermediate dose of 675 mg/m², there were no DLTs among a total of seven patients given 12 treatment cycles but all experienced moderate to severe (grade 2 to 4) haematological toxicity. Thrombocytopenia was delayed in its onset and nadir, and its recovery was protracted and incomplete in many patients. There were no complete or partial tumour responses. PR-104-induced thrombocytopenia and neutropenia correlated with plasma AUC of PR-104, PR-104A and an oxidative semi-mustard metabolite (PR-104S1), but no more strongly than with PR-104 dose-level. There was no significant correlation between plasma AUC for the reduced metabolites and myelotoxicity.</p> <p>Conclusions</p> <p>Thrombocytopenia, and to a lesser extent neutropenia, was the DLT of weekly PR-104. The MTD was 675 mg/m²/week. PR-104 given weekly may be a suitable protocol for further clinical evaluation as a short course of treatment with fractionated radiotherapy or haematopoietic stem cell support, as its duration of dosing is restricted by delayed-onset and protracted thrombocytopenia.</p

Quantification of African Monsoon Runoff During Last Interglacial Sapropel S5

Organic‐rich sapropel layers punctuate the eastern Mediterranean sedimentary sequence,recording deep‐sea anoxic events. The timing of sapropel deposition coincides with precession minima,which are associated with the northward migration of the monsoon rain belt over North Africa. Theresultant increase in monsoon precipitation over the Sahara caused an increase in low‐δ18O freshwaterrunoff into eastern Mediterranean surface waters, which is reflected by negativeδ18O anomalies in therecords of planktic foraminiferal calcite. However, despite extensive research on sapropels, the magnitudeof monsoon intensification and freshwater runoff, along with its influence onδ18O, remains elusive. Here,we present a quantification of African monsoon freshwater runoff into the eastern Mediterranean for theperiod of deposition of last interglacial sapropel S5 (~128.3–121.5 ka). Our method uses a box model of theMediterranean Sea, which represents different water masses, and has been calibrated usingδ18O fromplanktic foraminiferal species of different depth and seasonal habitats. The model was constrained withexisting records of sea level and sea surface temperature then inverted to deconvolve theδ18O signal of thesurface‐dwelling foraminiferal speciesGlobigerinoides ruber(w) and calculate the freshwater runoff volume.Our calculated African monsoon runoff suggests large increases in freshwater discharge to the easternMediterranean (up to ~8.8 times the modern pre‐Aswan Nile discharge). Rapid onset of S5 depositionfollowing the estimated increase in runoff strongly suggests a preconditioning of the eastern Mediterraneanfor sapropel deposition. Our study also provides insight into the stratification and warming of easternMediterranean surface waters during the S5 interval.This work was supported by Australian Research Council (ARC) Australian Laureate Fellowship FL120100050 (E. J. R.) and Discovery Early Career Researcher Award DE190100042 (K. M. G.). G. M. acknowledges support from the University of Vigo program to attract excellent research talent and a generous start‐up package

Practical single-fibre network-oriented quantum key distribution from a compact source of entangled photons in presence of White Rabbit time synchronisation

We demonstrate the feasibility of a network-oriented Quantum Key Distribution (QKD) from affordable components, in the presence of White Rabbit time synchronisation on the same optical fibre. This allows for an optimal usage of resources, where optical networks are tailored for fast and accurate time distribution and lighter QKD systems exploit the network timing for synchronising the operations between distant users

Shoreline modelling on timescales of days to decades

Climate change is resulting in global changes to sea level and wave climates,which in many locations significantly increasethe probability of erosion, floodingand damage to coastal infrastructure and ecosystems.Therefore, there isa pressing societal need to be able to forecast themorphological evolution of our coastlines over a broad range of timescales, spanningdays-to-decades, facilitating more focussed, appropriate,and cost-effective management interventions and data informed planning to support thedevelopment of coastal environments. A wide range of modelling approaches have been used with varying degrees of success to assess both the detailed morphological evolution and/or simplified indicators of coastal erosion/accretion.This paper presents an overview of these modelling approaches, covering the full range of the complexity spectrum, summarising the advantages and disadvantages of eachmethod. A focus is given to reduced-complexity modelling approaches, including models based on equilibrium concepts, which have emerged as a particularly promising methodology for the prediction ofcoastal change over multi-decadal timescales. The advantages of stable, computationally-efficient, reduced-complexity models must be balanced against the requirement for good generality and skill in diverse and complex coastal settings. Significant obstacles are also identified, limiting the generic application of models at regional and global scales. Challenges include: the accurate long-term predictionof model forcing time-series in a changing climate, and accounting for processes that can largely be ignored in the shorter term but increase in importance in the long-term.Further complications include coastal complexities, such asthe accurate assessment of the impacts of headland bypassing. Additional complexities includecomplex structures and geology, mixed grainsize,limited sediment supply, sources and sinks. It is concluded that with present computational resources, data availability limitations and process knowledge gaps, reduced-complexity modelling approaches currently offer the most promising solution to modelling shoreline evolution on daily-to-decadal timescales

Changes in the number of new takeaway food outlets associated with adoption of management zones around schools: A natural experimental evaluation in England

© 2024 The Author(s). Published by Elsevier Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/By the end of 2017, 35 local authorities (LAs) across England had adopted takeaway management zones (or “exclusion zones”) around schools as a means to curb proliferation of new takeaways. In this nationwide, natural experimental study, we evaluated the impact of management zones on takeaway retail, including unintended displacement of takeaways to areas immediately beyond management zones, and impacts on chain fast-food outlets. We used uncontrolled interrupted time series analyses to estimate changes from up to six years pre- and post-adoption of takeaway management zones around schools. We evaluated three outcomes: mean number of new takeaways within management zones (and by three identified sub-types: full management, town centre exempt and time management zones); mean number on the periphery of management zones (i.e. within an additional 100 m of the edge of zones); and presence of new chain fast-food outlets within management zones. For 26 LAs, we observed an overall decrease in the number of new takeaways opening within management zones. Six years post-intervention, we observed 0.83 (95% CI -0.30, −1.03) fewer new outlets opening per LA than would have been expected in absence of the intervention, equivalent to an 81.0% (95% CI -29.1, −100) reduction in the number of new outlets. Cumulatively, 12 (54%) fewer new takeaways opened than would have been expected over the six-year post-intervention period. When stratified by policy type, effects were most prominent for full management zones and town centre exempt zones. Estimates of intervention effects on numbers of new takeaways on the periphery of management zones, and on the presence of new chain fast-food outlets within management zones, did not meet statistical significance. Our findings suggest that management zone policies were able to demonstrably curb the proliferation of new takeaways. Modelling studies are required to measure the possible population health impacts associated with this change.Peer reviewe