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    A mathematical and numerical model for variable cross-section hull girder with time-varying mass systems applied in marine vessels

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    \ua9 2024 Elsevier LtdFor some types of special-purpose marine vessels, such as dredgers, the variation of mass onboard derived from their working conditions may induce unforeseen loads within a short time, which will lead to unexpected structural responses and fatigue damage. For dredgers, additional loads induced by the mass-variation in their specific working conditions are of significant concern and have not been effectively considered during the design stage. This paper proposes a mathematical and numerical model for structural dynamic analysis of variable cross-section hull girder with time-varying mass characteristics. It leverages the modified Euler-Bernoulli beam theory to accommodate variable mass functions and employs a semi-analytical approach for the analysis of vibration characteristics in the variable cross-section beam. The excitation loads acting on the hull girder are composed of engine loads, propeller loads, and hydrodynamic loads respectively defined in the dynamic model. Furthermore, an improved Kane\u27s dynamic equation is integrated into the mathematical and numerical model, tailored for time-varying mass systems, serving as the primary dynamic solver module. A customized program, written in FORTRAN language, is developed based on the proposed model. In addition, a user-defined case study is given in this paper. The varying wet surface and trim characteristics of the ship hull within a short period are also taken into consideration via dividing wet surface into ten shifting waterlines and loading conditions in variable mass properties. Hydrodynamic analysis results pre-calculated by SESAM are transferred into the program. Finally, dynamic response results including displacement and angular responses of each pre-defined rigid cross-section in the hull girder are generated by the self-developed program, which can be used for further FEA analysis to achieve detailed stress and deformation results. The proposed mathematical and numerical model can be used in the design stage for ships and offshore vessels that have time-varying mass features to evaluate their special structural responses during variable mass operations

    Development of a bespoke finite element wear algorithm to investigate the effect of femoral centre of rotation on the wear evolution in total knee replacements

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    \ua9 2024 Elsevier LtdTotal Knee Replacements (TKRs) are a commonly used treatment to help patients suffering from severely damaged knee joints, which is normally brought on by osteoarthritis. The aim of the surgery is to reduce pain and regain function of the joint, however, some of these implants fail prematurely with implant wear being one of the main factors of failure. Computational analysis is an efficient tool that can provide an in-depth insight on the evolution of wear, before utilising experimental techniques which are time-consuming and costly. In this study, a bespoke finite element (FE) based wear algorithm has been further developed for TKRs and was used to investigate how location of femoral centre of rotation (CoR) affects the evolution of wear at the bearing surfaces. Three locations of femoral CoR have been investigated: international standards (ISO) CoR, being the location defined in ISO 14243-3, distal CoR being the centre of the femoral component\u27s distal radius, and reference CoR being the middle ground between the two. All investigations were setup in accordance with ISO 14243-3 for displacement-controlled wear testing conditions for knee simulators. The wear algorithm extracts contact pressure and sliding distance from the FE analysis to determine wear depth, wear pattern, volumetric wear, and wear rates on the polymeric insert and femoral component\u27s bearing surfaces using Archard\u27s wear law. The polymeric insert volumetric wear rate after 5 million cycles (Mc) for ISO, reference, and distal CoR are 4.37mm3/Mc, 5.40mm3/Mc, and 6.83mm3/Mc respectively. Furthermore, the wear pattern\u27s location on the bearing surfaces is dependent on the femoral CoR, with ISO CoR wear pattern being positioned more posteriorly, distal CoR being more anteriorly, and reference CoR in between ISO and distal. The ISO CoR investigation showed a region of minimal wear between two wear regions at the middle of the femoral component\u27s wear pattern, on both medial and lateral condyles. This region of minimal wear reduces for the reference CoR and further reduces for the distal CoR. After 5 Mc, the average polymeric insert-femoral component contact area changes with femoral CoR, with the average contact area being 66.53mm2, 68.35mm2, and 71.21mm2 for ISO, reference, and distal CoRs respectively, with distal having around 7% more contact area than ISO. The results from this study show that there is a wide range of wear values for different locations of femoral CoR. As such the choice of femoral CoR should be carefully considered when performing any wear investigation to ensure that the CoR location is consistent for all studies being compared

    Impact and cost-effectiveness of scaling up HCV testing and treatment strategies for achieving HCV elimination among people who inject drugs in England: a mathematical modelling study

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    \ua9 2024 The AuthorsBackground: England aims to reach the World Health Organization (WHO) elimination target of decreasing HCV incidence among people who inject drugs (PWID) to <2 per 100 person-years (/100pyrs) by 2030. We assessed what testing and treatment strategies will achieve this target and whether they are cost-effective. Methods: A dynamic deterministic HCV transmission model among PWID was developed for four England regions, utilising data on the scale-up of HCV treatment among PWID in prisons, drug treatment centres (DTC, where opioid agonist therapy is provided), and any other setting (e.g., primary care). The model projected whether the elimination target will be reached with existing testing and treatment initiatives (‘status quo’ model, SQ), or whether improvements are needed from 2024. Cost data was collated through practitioners\u27 interviews and published literature. The mean incremental cost-effectiveness ratio (ICER per quality adjusted life year (QALY) saved, 50-year time horizon; 3.5% discount rate) of SQ (assumes counterfactual of no treatment scale-up post-2015) and improved model (counterfactual: SQ model) was compared to a willingness-to-pay threshold of \ua320,000/QALY saved. Findings: The SQ model projects HCV incidence will decrease by 79.7–98.6% (range of medians) over 2015–2030 to 0.2–2.2/100pyrs, with an ICER of \ua3308–1609/QALY saved across the regions. There is >80% probability of achieving the incidence target in three regions, and 40% probability in the other region. If annual testing in DTC increases to 80% (from 27%) or 75% of people get tested during their prison stay (from 55%) from 2024 in the lower impact region, then their probability increases to >65%, with both strategies being highly cost-effective. Interpretation: Many England regions could reach the WHO HCV elimination target by 2030 under existing testing and treatment pathways. Scaling up of testing in DTC or prisons will help achieve this target and is highly cost-effective. Funding: NIHR

    COLOFIT: Development and Internal-External Validation of Models Using Age, Sex, Faecal Immunochemical and Blood Tests to Optimise Diagnosis of Colorectal Cancer in Symptomatic Patients

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    \ua9 2025 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death. Aim: To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations. Methods: We included all adults (≥ 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT. Predicted 1-year CRC diagnosis were calculated, and externally validated, using Cox proportional hazards modelling with selected multiple fractional polynomial transformations for age, faecal haemoglobin concentration (f-Hb) value, mean corpuscular volume (MCV), platelet count and sex. Results: At a CRC risk threshold of 0.6% (equivalent to f-Hb = 10 μg Hb/g (μg/g)) overall performance of the validated model across age strata using Harrell\u27s C index was ≥ 0.91% (overall C-statistic 93%, 95% CI 92%–95%) with acceptable calibration. Using this model yields similar numbers of detected and missed cancers, but requires ~20% fewer investigations than a f-Hb ≥ 10 μg/g strategy. For approximately 100,000 people per year with symptoms of suspected CRC, we predict it might save > 4500 colonoscopies with no evidence that more cancers would be missed if we used our model compared to using FIT f-Hb ≥ 10 μg/g. Conclusions: Including age, sex, MCV, platelets and f-Hb in a survival analysis model to predict the risk of CRC yields greater diagnostic utility than a simple binary cut off f-Hb ≥ 10 μg/g

    Deep phenotyping of T regulatory cells in psoriatic arthritis highlights targetable mechanisms of disease

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    \ua9 2024 The Authors. Regulatory T cells (Tregs) are immune regulatory T cells that are vital for controlling inflammation. The role of Tregs in inflammatory diseases namely psoriatic arthritis (PsA) is still poorly understood. The underlying reason being a lack of robust unbiased analysis to test the immune regulatory phenotype of human Tregs. Here, we propose that checkpoint receptors can identify functional Tregs in PsA. Using unbiased BD Rhapsody single-cell analysis, we have analyzed the expression pattern of checkpoint receptors in Tregs and found that PsA Tregs are enriched in the expression of CTLA4, TIGIT, PD-1, and GITR while TIM3 was downregulated. Furthermore, PD-1+ Tregs in PsA had an increased type 1 phenotype and expressed the protease asparaginyl endopeptidase. By harnessing the PD-1 signaling pathway and inhibiting asparaginyl endopeptidase, PsA Treg function was significantly enhanced in in vitro suppressor assays. Next, we interrogated the cell interaction pathways of Tregs in PsA and found a diminished crosstalk with circulating osteoclast precursors through the CD244–CD48 coreceptor pathways. Therapeutically, PsA Treg function could be enhanced by modulating PD-1 and osteoclast interactions. Our study suggests that unconventional immune cell crosstalk with Tregs is severely diminished in PsA

    Nonlinear Atmospheric Flow Patterns Confined to Zonal Cloud Bands

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    \ua92024 American Meteorological Society.We derive, at leading order in the thin-shell parameter, a consistent set of nonlinear governing equations for the dynamics of flows confined to a zonal cloud band such as those on Jupiter, in a thin layer near the top of the planetary troposphere. Some exact solutions are provided in the material (Lagrangian) framework. The explicit specification of the individual particle paths enables a detailed study of these flows that model oscillations superimposed on a mean current. This approach is applied to Jupiter’s Great Red Spot and to the filamentary zonal flow at its southern boundary

    Development of a New Score Based on Image Defined Risk Factors to Standardize Surgical Risk in Neuroblastoma Resection - A SIOPEN Collaborative Study

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    \ua9 2024 Elsevier Inc. Background and aims: Image Defined Risk Factors (IDRFs) assess surgical risk in neuroblastoma (NB) and guide neoadjuvant therapy. Despite chemotherapy IDRFs may persist in 70 % of cases. Several studies have suggested that not all IDRFs hold equal significance and that the presence of an IDRF does not inherently signify unresectability. This current study seeks to stratify and assign a score to each IDRF based on its impact on surgical risk. Methods: This collaborative study entailed retrospective collection of patient data from NB operations conducted between 2016 and 2020, together with the computation of a Surgical Complexity Index (SCI) for every patient. The SCI values obtained were correlated with preoperatively identified IDRFs. Mann–Whitney statistical test was employed to assign a relevance score to the association between individual IDRFs and SCI. Results: 14 centers contributed 427 neuroblastoma index cases meeting study inclusion criteria. 303 patients had 1 or more IDRFs. The presence and number of IDRFs in all patients significantly correlated with the SCI value (p < 0.0001). The most frequently encountered IDRF was renal pedicle involvement. There was a significant association observed between clusters of abdominal IDRFs and the occurrence of post-operative complications (p < 0.05), while a weak association link was found with intra-operative complications. A relevance score for individual IDRFs allowed their stratification based on surgical risk. The most relevant IDRFs were extension within two anatomical body compartments, infiltration of the hepato-pancreatic block, encasement of the superior mesenteric artery and coeliac axis, and tumor compressing the trachea. Conclusions: This current study has facilitated the assignment of a relevance score to each IDRF, correlating it with surgical risks. Considering this stratification of surgical risk alongside oncologic risk as defined by the neuroblastoma treatment patient risk grouping should facilitate a more precise definition of surgical objectives and the optimal conditions favoring gross tumor resection. Type of Study: Clinical Research - Study of Diagnostic Test. Level of Evidence: III

    Establishing links between drug registers and essential medicines lists

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    لا يزال الوصول إلى الأدوية الأساسية دون المستوى الأمثل في العديد من الدول. وتشير الدراسات الحديثة التي تفحص تسجيل الأدوية على مستوى الدولة، أن نسبة كبيرة من الأدوية الأساسية ليس لها أي منتجات مقابلة مسجلة للاستخدام على مستوى الدولة، وبالتالي لا يمكن أن تكون متوفرة في جميع الأوقات. وعلى العكس من ذلك، فإن العديد من الأدوية غير الأساسية يتم تسجيلها من جانب السلطات التنظيمية للأسواق المحلية، مما قد يسهل الاستخدام غير المناسب للأدوية ومقاومة مضادات الميكروبات. إن معالجة هذه الفجوة في الصحة العامة تتطلب ربط البيانات الموجودة في سجلات الأدوية الوطنية بقوائم الأدوية الأساسية الوطنية. وسوف يتطلب تحقيق هذا الربط تطوير متغيرات ومعايير بيانات مشتركة لكل من سجلات الأدوية وقوائم الأدوية الأساسية. ومن شأن هذا الربط أن يوفر للجهات التنظيمية للأدوية وواضعي السياسات الصحية، معلومات عن الفجوات في تسجيل الأدوية الأساسية، ويسمح لهم باتخاذ خطوات لإعطاء الأولوية لتسجيل هذه الأدوية. ومن شأن هذا الأسلوب أن يحسن من توفر الأدوية الأساسية لأولويات الصحة العامة، ويحول دون الإفراط في تسجيل الأدوية غير الضرورية.在许多国家,获取基本药物的情况仍然不够理想。最近对国家层面药品登记情况的研究表明,相当一部分基本药物在国家层面的可供使用产品中并没有任何相应登记 记录,因此无法随时提供。相反,监管机构为当地市场登记了许多非必需药物,这可能会导致用药不当的情况加剧和抗菌素耐药性提高。解决这一公共卫生差距问题需要将国家药品登记册的数据与国家基本药物清单关联起来。如要建立此类关联性,需要为药物登记册和基本药物清单制定通用的数据变量和标准。这种关联性有助于药品监管机构和卫生政策制定者及时了解基本药物登记差距相关信息,并确保他们能够采取措施以优先登记这些药物。这一做法有利于根据公共卫生优先级提高基本药物的可用性,并防止非必要药物的过度登记。.(c) 2025 The authors; licensee World Health Organization.Access to essential medicines is still suboptimal in many countries. Recent studies examining the registration of medicines at the country level show that a considerable proportion of essential medicines do not have any corresponding products registered for use at the country level and therefore cannot be available at all times. Conversely, many non-essential medicines are registered by regulatory authorities for local markets, potentially facilitating inappropriate drug use and antimicrobial resistance. Addressing this public health gap requires linking the data on national drug registers with national essential medicines lists. Achieving this linkage will necessitate the development of common data variables and standards for both drug registers and essential medicines lists. This linkage would provide medicines regulators and health policy-makers with information on the gaps in the registration of essential medicines and allow them to take steps to prioritize registration of these medicines. This approach would improve availability of essential medicines for public health priorities and prevent over-registration of unnecessary medicines.L\u27acc\ue8s aux m\ue9dicaments essentiels demeure insuffisant dans de nombreux pays. Des \ue9tudes r\ue9centes consacr\ue9es \ue0 l\u27enregistrement des m\ue9dicaments \ue0 l\u27\ue9chelle du pays montrent qu\u27il n\u27existe aucun produit \ue9quivalent homologu\ue9 sur le territoire pour la plupart de ces m\ue9dicaments, qui ne sont par cons\ue9quent pas disponibles \ue0 tout moment. \uc0 l\u27inverse, de nombreux m\ue9dicaments non essentiels sont homologu\ue9s par les autorit\ue9s de r\ue9glementation pour les march\ue9s locaux, ce qui pourrait favoriser une utilisation inad\ue9quate et une r\ue9sistance aux antimicrobiens. Rem\ue9dier \ue0 ce probl\ue8me de sant\ue9 publique implique la cr\ue9ation de liens entre les donn\ue9es figurant dans les registres nationaux de m\ue9dicaments et les listes nationales de m\ue9dicaments essentiels. Pour \ue9tablir ces liens, il faudra d\ue9velopper des normes et variables de donn\ue9es communes aux registres et aux listes. Les organismes de r\ue9glementation comp\ue9tents ainsi que les responsables de la sant\ue9 pourraient ainsi obtenir des informations concernant les m\ue9dicaments essentiels n\u27ayant pas encore \ue9t\ue9 approuv\ue9s, leur permettant de prendre des mesures visant \ue0 les privil\ue9gier. Une telle approche am\ue9liorerait la disponibilit\ue9 des m\ue9dicaments essentiels pour les priorit\ue9s de sant\ue9 publique, et \ue9viterait l\u27enregistrement abusif de m\ue9dicaments superflus.Во многих странах доступ к основным лекарственным средствам все еще остается неоптимальным. Результаты недавно проведенных исследований, посвященных регистрации лекарственных средств на уровне стран, свидетельствуют о том, что значительная часть основных лекарственных средств не имеет соответствующих препаратов, зарегистрированных для использования на уровне страны, поэтому не может быть доступна на постоянной основе. И наоборот, многие лекарства, не являющиеся жизненно необходимыми, регистрируются регуляторными органами для местных рынков, что потенциально способствует ненадлежащему использованию лекарств и развитию устойчивости к противомикробным препаратам. Для устранения этого пробела в здравоохранении необходимо связать данные национальных реестров лекарственных средств с национальными списками основных лекарственных средств. Для достижения такой взаимосвязи потребуется разработка общих переменных данных и стандартов для реестров лекарственных средств и списков основных лекарственных средств. Такая связь предоставила бы уполномоченным органам и лицам, ответственным за разработку политики в области здравоохранения, информацию о пробелах в регистрации основных лекарственных средств и позволила бы им принять меры по приоритетной регистрации этих лекарственных средств. Такой подход позволит повысить доступность основных лекарственных средств для решения приоритетных задач здравоохранения и предотвратить избыточную регистрацию ненужных лекарственных средств.El acceso a los medicamentos esenciales sigue siendo deficiente en muchos pa\uedses. Estudios recientes que examinan el registro de medicamentos a nivel nacional muestran que un porcentaje considerable de los medicamentos esenciales no tienen ning\ufan producto correspondiente registrado para su uso a nivel nacional y, por lo tanto, no pueden estar disponibles en todo momento. Por otra parte, las autoridades reguladoras registran muchos medicamentos no esenciales para los mercados locales, lo que puede facilitar el uso inadecuado de f\ue1rmacos y la resistencia a los antimicrobianos. Para subsanar esta deficiencia de la sanidad p\ufablica es preciso vincular los datos de los registros nacionales de medicamentos con las listas nacionales de medicamentos esenciales. Lograr esta vinculaci\uf3n exigir\ue1 el desarrollo de variables de datos y est\ue1ndares comunes tanto para los registros de medicamentos como para las listas de medicamentos esenciales. Esta vinculaci\uf3n proporcionar\ueda a los reguladores de medicamentos y a los responsables de elaborar las pol\uedticas sanitarias informaci\uf3n sobre las deficiencias en el registro de medicamentos esenciales y les permitir\ueda tomar medidas para dar prioridad al registro de estos medicamentos. Este planteamiento mejorar\ueda la disponibilidad de medicamentos esenciales para las prioridades de salud p\ufablica y evitar\ueda el registro excesivo de medicamentos innecesarios

    The NANOGrav 15 Yr Data Set: Removing Pulsars One by One from the Pulsar Timing Array

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    \ua9 2025. The Author(s). Published by the American Astronomical Society. Evidence has emerged for a stochastic signal correlated among 67 pulsars within the 15 yr pulsar-timing data set compiled by the NANOGrav collaboration. Similar signals have been found in data from the European, Indian, Parkes, and Chinese pulsar timing arrays. This signal has been interpreted as indicative of the presence of a nanohertz stochastic gravitational-wave background (GWB). To explore the internal consistency of this result, we investigate how the recovered signal strength changes as we remove the pulsars one by one from the data set. We calculate the signal strength using the (noise-marginalized) optimal statistic, a frequentist metric designed to measure the correlated excess power in the residuals of the arrival times of the radio pulses. We identify several features emerging from this analysis that were initially unexpected. The significance of these features, however, can only be assessed by comparing the real data to synthetic data sets. After conducting identical analyses on simulated data sets, we do not find anything inconsistent with the presence of a stochastic GWB in the NANOGrav 15 yr data. The methodologies developed here can offer additional tools for application to future, more sensitive data sets. While this analysis provides an internal consistency check of the NANOGrav results, it does not eliminate the necessity for additional investigations that could identify potential systematics or uncover unmodeled physical phenomena in the data

    Learning by charging: Understanding consumers’ changing attitudes towards vehicle-to-grid

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    \ua9 2024Vehicle-to-grid (V2G) charging, where vehicles can send power to the grid, can provide valuable services to energy systems and network operators. However, social acceptance is an essential and overlooked barrier which must be addressed if V2G is to be successfully deployed. This study investigates the factors that govern attitudes towards V2G, and how electric vehicle (EV) ownership and participation in V2G changes them. For the first time, this includes survey data from users who had experience using a V2G charger, comparing the response of V2G users (n=49) with EV owners (n=520) and non-EV owners (n=1091). We show that time and EV ownership have lowered concerns around range anxiety, and that EV ownership and V2G trial participation leads to a 15%–35% increase in stated willingness to participate in V2G or Smart Charging as compared to a 2013 baseline. Additionally, it is demonstrated that the strongest single predictor for V2G willingness is whether the consumer believes that V2G can contributes to a stable electricity system. These results suggest that education around V2G benefits and allowing consumers to test V2G before committing could be key factors in increasing adoption. We also highlight the importance of data privacy, which for some consumers contributes towards a negative attitude towards V2G. We release the raw survey data and code with this manuscript

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