Anglian Water Services (United Kingdom)

Psoriasis, a chronic inflammatory skin disease, arises from a dysregulated interaction between keratinocytes (KCs) and dendritic cells (DCs). We previously identified Rh family C glycoprotein (RHCG) as a key mediator of KC inflammation and DC activation. Here, we demonstrate that luteolin, a bioactive compound derived from the traditional Chinese formula cooling blood and detoxicating formula (CBDF), directly binds to RHCG, as confirmed by multiple computational methods and in vitro experiments. In vitro, luteolin suppressed RHCG expression in KCs, reducing CXCL14 secretion and subsequent DC activation. Spatial transcriptomics (STs) revealed that luteolin preferentially targets DC-enriched spatial domains and restores desmosomal protein expression (e.g., DSC2), which is dysregulated in psoriasis. In vivo, luteolin ameliorated psoriasis-like inflammation in imiquimod-induced mice, lowering Psoriasis Area and Severity Index (PASI) scores and normalizing pathological markers. Our findings indicate that luteolin disrupts KC-DC communication through multiple modes of action, thereby reversing tissue-level pathology and demonstrating its potential as a targeted therapy for psoriasis.

The management of unstable Weber B ankle fractures presents significant challenges, particularly in patients with osteoporotic bone. Conventional fixation techniques often employ a lag screw to achieve compression at the fracture site. However, in osteoporotic bone, this approach may fail to provide adequate compression and may cause complications such as irritation to surrounding tendons or the distal tibiofibular syndesmosis, sometimes necessitating additional surgery for hardware removal. We describe a novel "seesaw" technique that uses a laterally applied, obliquely oriented locking plate to achieve stable fixation. After initial provisional stabilization with a K wire instead of a lag screw, the distal end of the plate is secured with locking screws. A non-locking screw is then inserted just proximal to the fracture site, serving as a fulcrum. By applying posterior pressure to the plate, a "seesaw" motion is induced, translating the distal fibular fragment anteriorly. This maneuver enables compression across the fracture site and restores anatomic alignment. Final fixation is completed with additional locking screws. Over a three-year period, this technique was employed in more than 50 patients with unstable Weber B fractures. No cases of syndesmotic instability, malalignment, or loss of reduction were observed during the rehabilitation period. This method provides a stable, reproducible alternative to standard fixation techniques and is especially advantageous in osteoporotic bone. It allows for precise anatomic reduction, sustained fracture compression, and early mobilization, potentially reducing complication rates and the need for secondary procedures.

Physics-based hydrodynamic models simulating lake water temperature often face challenges due to sparse observational data and equifinality, where many parameter combinations yield similar goodness-of-fit to observations, complicating calibration. Thi

Abstract Rising sea levels due to climate change are causing increased salinisation of low‐lying coastal and floodplain soils, and the impact of this process on the bioavailability of plant nutrients needs to be understood as mitigation strategies are adapted. Zinc (Zn) is an element of particular importance due to its function as a micronutrient for plants including rice and other staple foods. In the current study, our aim was to investigate the effects of salinisation on zinc adsorption onto soils representing at‐risk coastal and floodplain environments, addressing in particular our knowledge gap concerning the roles that solution chemistry and soil composition play. To this end, we conducted batch adsorption experiments in the laboratory and ran geochemical models in saline solutions up to 0.7 mol L−1 ion strength incorporating both (i) a multi surface model (MSM) for surface reactions containing three phases, that is iron hydroxides, organic matter and phyllosilicate clays, and (ii) aqueous‐phase complexation to dissolved organic and inorganic ligands. Surface reactions were modelled using the diffuse double layer model, the NICA–Donnan model and an ion exchange model using the Gaines–Thomas convention. We combined the experimentally determined mass composition of surface phases with generic modelling parameters taken from the literature. We first show that increasing salinity enhances the formation of aqueous Zn‐chloride complexes in the presence of dissolved organic matter and bicarbonate, thereby decreasing the availability of free Zn2+ and supressing the partitioning of zinc to the adsorbed phase. We demonstrate using batch adsorption experiments with a calcareous hydraquent and a tropaquept, that salinity decreases zinc adsorption strongly in the pH range between 3 and 6. Satisfactory agreement between experiments and model calculations was achieved with root‐mean‐square errors ranging for different salinities between 2.88% and 2.92% for the hydraquent and between 4.59% and 2.74% for the tropaquept soil. Model predictions of adsorption were slightly inferior at low salinity for the hydraquent soil and at high salinity for the tropaquept soil, pointing possibly to an incomplete geochemical model or to a need to parametrise surface adsorption models at higher ionic strengths. Present surface models have been largely parametrised at lower ionic strength. We lastly apply the MSM to examine zinc adsorption in five endoaquepts soils, representing soil series from Bangladesh. We show that increasing salinity decreases zinc adsorption to the soil organic matter and the clay fractions. We conclude from our findings that increased soil salinity due to rising sea levels and climate change will have a significant impact on zinc cycling and possibly other micronutrients in areas where coastal soils and floodplain soils overlap, such as deltas and estuaries. In particular, we predict a decrease in zinc adsorption in acidic to neutral soils. The availability of zinc for biouptake through the roots of crop plants including rice will be significantly disturbed following salinisation, most likely affecting crop production. Our study demonstrates the potential that geochemical modelling combined with experimental data has to improve our capability to assess the effects of salinity due to rising seawater levels in vulnerable regions of the world.

EDITORIAL article Front. Clim., 22 January 2024Sec. Climate and Decision Making Volume 6 - 2024 | https://doi.org/10.3389/fclim.2024.1355110

Abstract Background Helicopter Emergency Medical Services (HEMS) are a limited and expensive resource, and should be intelligently tasked. HEMS dispatch was identified as a key research priority in 2011and 2022, with a call to identify a ‘general set of criteria with the highest discriminating potential’. However, there have been no published data analyses in the subsequent decade that specifically address this priority, and this priority has been reaffirmed in 2022. The objective of this study was to define the dispatch criteria available at the time of the initial emergency call with the greatest HEMS utility using a large, regional, multi-organizational dataset in the UK. Methods This retrospective observational study utilized dispatch data from a regional emergency medical service (EMS) and three HEMS organisations in the East of England, 2016-2019. In a logistic regression model, Advanced Medical Priority Dispatch System (AMPDS) codes with ≥50 HEMS dispatches in the study period were compared with the remainder to identify codes with high-levels of HEMS patient contact and HEMS-level intervention/drug/diagnostic (HLIDD). The primary outcome was to identify AMPDS codes with a >10% HEMS dispatch rate of all EMS taskings that would result in 10-20 high-utility HEMS dispatches per 24-hour period in the East of England. Data were analysed in R, and are reported as number (percentage); significance was p<0.05. Results There were n=25,491 HEMS dispatches (6.4k per year), of which n=23,030 (90.3%) had an associated AMPDS code. n=13,778 (59.8%) of HEMS dispatches resulted in patient contact, and n=8437 (36.6%) had an HLIDD. 43 AMPDS codes had significantly greater rates of patient contact and/or HLIDD compared to the reference group. In an exploratory analysis, a cut-off of ≥70% patient contact rate and/or ≥70% HLIDD (with a >10% HEMS dispatch of all EMS taskings) resulted in 17 taskings per 24-hour period. This definition derived nine AMPDS codes with high HEMS utility. Conclusion We have identified nine ‘golden’ AMPDS codes, available at the time of initial emergency call, that are associated with high-levels of whole-system and HEMS utility in the East of England. We propose that UK EMS should consider immediate HEMS dispatch to these codes.

Germline predisposition to haematological cancers is increasingly being recognised. Widespread adoption of high-throughput and whole genome sequencing is identifying large numbers of causative germline mutations. Constitutional pathogenic variants in six genes (DEAD-box helicase 41 [DDX41], ETS variant transcription factor 6 [ETV6], CCAAT enhancer binding protein alpha [CEBPA], RUNX family transcription factor 1 [RUNX1], ankyrin repeat domain containing 26 [ANKRD26] and GATA binding protein 2 [GATA2]) are particularly significant in increasing the risk of haematological cancers, with variants in some of these genes also associated with non-malignant syndromic features. Allogeneic blood and marrow transplantation (BMT) is central to management in many haematological cancers. Identification of germline variants may have implications for the patient and potential family donors. Beyond selection of an appropriate haematopoietic stem cell donor there may be sensitive issues surrounding identification and counselling of hitherto asymptomatic relatives. If BMT is needed, there is frequently a clinical urgency that demands a rapid integrated multidisciplinary approach to testing and decision making involving haematologists in collaboration with Clinical and Laboratory Geneticists. Here, we present best practice consensus guidelines arrived at following a meeting convened by the UK Cancer Genetics Group (UKCGG), the Cancer Research UK (CRUK) funded CanGene-CanVar research programme (CGCV), NHS England Genomic Laboratory Hub (GLH) Haematological Oncology Malignancies Working Group and the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT).

The role of two- or three-field nodal dissection in the surgical treatment of esophageal and gastroesophageal junction cancer in the minimally invasive era is still controversial. This review aims to clarify the extension of nodal dissection in esophageal and gastroesophageal junctional cancer. A basic evidence-based analysis was designed, and seven research questions were formulated and answered with a narrative review. Reports with little or no data, single cases, small series and review articles were not included. Three-field lymph node dissection improves staging accuracy, enhances locoregional disease control and might improve survival in the group of patients with cervical and upper mediastinal metastatic lymph nodal involvement from middle and proximal-third esophageal cancer.

Abstract This book presents the advancements made in applied metrology in the field of Urban Drainage and Storm water Management over the past two decades in scientific research as well as in practical applications. Given the broadness of this subject (measuring principles, uncertainty in data, data validation, data storage and communication, design, maintenance and management of monitoring networks, technical details of sensor technology), the focus is on water quantity and a sound metrological basis. The book offers common ground for academics and practitioners when setting up monitoring projects in urban drainage and storm water management. This will enable an easier exchange of results so as to allow for a faster scientific progress in the field. A second, but equally important goal, is to allow practitioners access to scientific developments and gained experience when it comes to monitoring urban drainage and storm water systems. In-depth descriptions of international case studies covering all aspects discussed in the book are presented, along with self-training exercises and codes available for readers on a companion website. Numerous detailed examples are given in the book, with corresponding open-source codes and training files available to download here. ISBN: 9781789060102 (Paperback) ISBN: 9781789060119 (eBook)

The aim was to pilot an adapted manualised weight management programme for persons with mild-moderate intellectual disabilities affected by overweight or obesity ('Shape Up-LD'). Adults with intellectual disabilities were enrolled in a 6-month trial (3-month active intervention and 3-month follow-up) and were individually randomised to Shape Up-LD or a usual care control. Feasibility outcomes included recruitment, retention, initial effectiveness and cost. Fifty people were enrolled. Follow-up rates were 78% at 3 months and 74% at 6 months. At 3 and 6 months, controlling for baseline weight, no difference was observed between groups (3 months: β: -0.34, 95% confidence interval [CI]: -2.38, 1.69, 6 months: β: -0.55, 95%CI -4.34, 3.24). It may be possible to carry out a trial of Shape Up-LD, although barriers to recruitment, carer engagement and questionnaire completion need to be addressed, alongside refinements to the intervention.