Reconstruction of contaminant trends in a salt wedge estuary with sediment cores dated using a multiple proxy approach

The Taunton River is a partially mixed tidal estuary in southeastern Massachusetts (USA) which has received significant contaminant inputs, yet little information exists on the history of discharge and the subsequent fate of these contaminants. Three sediment cores taken along a transect were analyzed, reconstructing the spatial and temporal trends of pollution in the estuary. A combination of radiometric dating, contaminant markers, and storm layers from major hurricanes were used to establish age models and sedimentation rates. Age estimates obtained from the different dating methods compared well, establishing an accurate history of contaminant release to the estuary. Polycyclic aromatic hydrocarbons (PAHs) were present in one core at depths corresponding to the early 1860s, earlier than previously established dates of introduction. Temporal and spatial trends of Cr, Cu, Hg and Pb indicated multiple sources of varying input to the river. Polychlorinated biphenyls (PCBs) were present in each of the cores from the 1930s onward, with elevated levels still present in surficial sediments at several sites. A unique organic compound, Topanol, which was produced locally was used as a tracer to track contaminant transport in the river. Tracer data indicates that contaminants are still being transported and deposited to surficial sediments at high concentrations well after their discharge. This reconstruction demonstrates the utility of using multiple dating proxies where often the sole use of radiometric dating techniques is not an option and provides insights into the fate of contaminants discharged decades ago but continue to represent environmental risks

Involvement of p59\u3cem\u3efyn\u3c/em\u3e\u3csup\u3eT\u3c/sup\u3e in Interleukin-5 Receptor Signaling

Previous studies implicate the nonreceptor protein tyrosine kinase (PTK) p59fyn in the propagation of signals from the B cell antigen receptor. To elucidate the functions of this kinase, we examined B cell responsiveness in mice engineered to lack the hematopoietic isoform of p59fyn. Remarkably, antigen receptor signaling was only modestly defective in fynTnull B cells. In contrast, signaling from the interleukin (IL)-5 receptor which ordinarily provides a comitogenic stimulus with antiimmunoglobulin, was completely blocked. Our results document the importance of p59fynT in IL-5 responses in B cells, and they support a general model for cytokine receptor signal transduction involving the simultaneous recruitment of at least three families of PTK

A point mutation in the murine Hem1 gene reveals an essential role for Hematopoietic Protein 1 in lymphopoiesis and innate immunity

Hem1 (Hematopoietic protein 1) is a hematopoietic cell-specific member of the Hem family of cytoplasmic adaptor proteins. Orthologues of Hem1 in Dictyostelium discoideum, Drosophila melanogaster, and Caenorhabditis elegans are essential for cytoskeletal reorganization, embryonic cell migration, and morphogenesis. However, the in vivo functions of mammalian Hem1 are not known. Using a chemical mutagenesis strategy in mice to identify novel genes involved in immune cell functions, we positionally cloned a nonsense mutation in the Hem1 gene. Hem1 deficiency results in defective F-actin polymerization and actin capping in lymphocytes and neutrophils caused by loss of the Rac-controlled actin-regulatory WAVE protein complex. T cell development is disrupted in Hem1-deficient mice at the CD4−CD8− (double negative) to CD4+CD8+ (double positive) cell stages, whereas T cell activation and adhesion are impaired. Hem1-deficient neutrophils fail to migrate in response to chemotactic agents and are deficient in their ability to phagocytose bacteria. Remarkably, some Rac-dependent functions, such as Th1 differentiation and nuclear factor κB (NF-κB)–dependent transcription of proinflammatory cytokines proceed normally in Hem1-deficient mice, whereas the production of Th17 cells are enhanced. These results demonstrate that Hem1 is essential for hematopoietic cell development, function, and homeostasis by controlling a distinct pathway leading to cytoskeletal reorganization, whereas NF-κB–dependent transcription proceeds independently of Hem1 and F-actin polymerization

A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Event shapes in e+e- annihilation and deep inelastic scattering

This article reviews the status of event-shape studies in e+e- annihilation and DIS. It includes discussions of perturbative calculations, of various approaches to modelling hadronisation and of comparisons to data.Comment: Invited topical review for J.Phys.G; 40 pages; revised version corrects some nomenclatur

How can health care organisations make and justify decisions about risk reduction? Lessons from a cross-industry review and a health care stakeholder consensus development process

Interventions to reduce risk often have an associated cost. In UK industries decisions about risk reduction are made and justified within a shared regulatory framework that requires that risk be reduced as low as reasonably practicable. In health care no such regulatory framework exists, and the practice of making decisions about risk reduction is varied and lacks transparency. Can health care organisations learn from relevant industry experiences about making and justifying risk reduction decisions? This paper presents lessons from a qualitative study undertaken with 21 participants from five industries about how such decisions are made and justified in UK industry. Recommendations were developed based on a consensus development exercise undertaken with 20 health care stakeholders. The paper argues that there is a need in health care to develop a regulatory framework and an agreed process for managing explicitly the trade-off between risk reduction and cost. The framework should include guidance about a health care specific notion of acceptable levels of risk, guidance about standardised risk reduction interventions, it should include regulatory incentives for health care organisations to reduce risk, and it should encourage the adoption of an approach for documenting explicitly an organisation’s risk position

Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: protocol for a controlled before and after study

Background Clinical Commissioning Groups (CCGs) are mandated to use research evidence effectively to ensure optimum use of resources by the National Health Service (NHS), both in accelerating innovation and in stopping the use of less effective practices and models of service delivery. We intend to evaluate whether access to a demand-led evidence service improves uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. Methods/design This is a controlled before and after study involving CCGs in the North of England. Participating CCGs will receive one of three interventions to support the use of research evidence in their decision-making: 1) consulting plus responsive push of tailored evidence; 2) consulting plus an unsolicited push of non-tailored evidence; or 3) standard service unsolicited push of non-tailored evidence. Our primary outcome will be changed at 12 months from baseline of a CCGs ability to acquire, assess, adapt and apply research evidence to support decision-making. Secondary outcomes will measure individual clinical leads and managers’ intentions to use research evidence in decision making. Documentary evidence of the use of the outputs of the service will be sought. A process evaluation will evaluate the nature and success of the interactions both within the sites and between commissioners and researchers delivering the service. Discussion The proposed research will generate new knowledge of direct relevance and value to the NHS. The findings will help to clarify which elements of the service are of value in promoting the use of research evidence. Those involved in NHS commissioning will be able to use the results to inform how best to build the infrastructure they need to acquire, assess, adapt and apply research evidence to support decision-making and to fulfil their statutory duties under the Health and Social Care Act

British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials

Testing the Mid-Holocene Relative Sea-Level Highstand Hypothesis in North Wales, United Kingdom

Accurate Holocene relative sea-level curves are vital for modelling future sea-level changes, particularly in regions where relative sea-level changes are dominated by isostatically induced vertical land movements. In North Wales, various glacial isostatic adjustment (GIA) models predict a mid-Holocene relative sea-level highstand between 4 and 6 ka, which is unsubstantiated by any geological sea-level data but affects the ability of geophysical models to model accurately past and future sea levels. Here, we use a newly developed foraminifera-based sea-level transfer function to produce a 3300-year-long late-Holocene relative sea-level reconstruction from a salt marsh in the Malltraeth estuary on the south Anglesey coast in North Wales. This is the longest continuous late-Holocene relative sea-level reconstruction in Northwest Europe. We combine this record with two new late-Holocene sea-level index points (SLIPs) obtained from a freshwater marsh at Rhoscolyn, Anglesey, and with previously published regional SLIPs, to produce a relative sea-level record for North Wales that spans from ca. 13,000 BP to the present. This record leaves no room for a mid-Holocene relative sea-level highstand in the region. We conclude that GIA models that include a mid-Holocene sea-level highstand for North Wales need revision before they are used in the modelling of past and future relative sea-level changes around the British Isles

Identification of the remains of King Richard III

In 2012, a skeleton was excavated at the presumed site of the Grey Friars friary in Leicester, the last-known resting place of King Richard III. Archaeological, osteological and radiocarbon dating data were consistent with th