The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological ...characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs’ value as undisturbed reference condition ecosystems.
► A CSA approach could provide cost-effective measures for diffuse P in Ireland. ► However, significant uncertainty remains in delineation of CSAs of P at all scales. ► Pragmatic tools and catchment specific data are required to decrease uncertainty. ► A framework for a CSA approach to the Water Framework Directive is presented. ► The framework is most relevance to the protection of high status waterbodies.
Much is known about electroencephalograph (EEG) patterns during sleep, but until recently, it was difficult to study EEG patterns during conscious, awake behavior. Technological advances such as ...powerful wireless EEG systems have led to a renewed interest in EEG as a clinical and research tool for studying real-time changes in the brain. We report here the first normative study of EEG activity while healthy young adults completed a series of cognitive tests recently published by the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB), a commonly-used standardized measure of cognition primarily used in clinical populations. In this preliminary study using a wireless EEG system, we examined power spectral density (PSD) in four EEG frequency bands. During baseline and cognitive testing, PSD activity for the lower frequency bands (theta and alpha) was greater, relative to the higher frequency bands (beta and gamma), suggesting participants were relaxed and mentally alert. Patterns of alpha desynchronization and synchronization in beta, theta and gamma during the cognitive tests relative to baseline are discussed. Alpha, beta and gamma activity was increased during a memory test compared to two other, less demanding executive function tests. Gamma activity was also inversely correlated with performance on the memory test, consistent with the neural efficiency hypothesis which proposes that better cognitive performance may link with lower cortical energy consumption. In summary, our study suggests that cognitive performance is related to the dynamics of EEG activity in a normative young adult population.
Emerging adults, of whom significant numbers report chronic pain, are characterized as having unique needs and challenges. Psychological/behavioral treatments found to be beneficial for reducing pain ...outcomes in children and adults are understudied in emerging adults. Following a systematic review of the literature, our objective is to report on quantitative studies of psychological/behavioral interventions for chronic pain in emerging adults.
We conducted a search of six databases (Cochrane Central Register of Controlled Trials, Google Scholar, ProQuest, PsycINFO, PubMed, and Web of Science) and reference sections in dissertations and systematic reviews to 4/29/2023. Keywords and phrases were search term combinations of "chronic/persistent pain", "emerging/young adults," and "intervention/treatment" using Boolean logic.
Our review resulted in identifying 37 articles, of which 2 duplicates were removed, and 31 were further excluded by a screening process based on various inclusionary and exclusionary criteria. The search yielded four studies on psychological/behavioral interventions (yoga, acceptance and commitment therapy and relaxation), all of which positively affected the pain experience and/or pain-related outcomes. These studies presented issues in design such as not being blinded or randomized, having a small sample size, and potential confounds that were not reported or examined.
The low number of studies reveals a large gap in the literature and is a call-to-action to further expand our understanding of effective and safer psychological/behavioral therapies for chronic pain in emerging adults. Successful pain management during this developmental phase may help young adults achieve positive trajectories for personal, occupational, relational, and health aspects of their lives.
FAM83B (family with sequence similarity 83, member B) was recently identified as a novel oncogene involved in activating CRAF/MAPK signaling and driving epithelial cell transformation. FAM83B is one ...of eight members of a protein family (FAM83) characterized by a highly conserved domain of unknown function (DUF1669), which is necessary and sufficient to drive transformation. Here, it is demonstrated that additional FAM83 members also exhibit oncogenic properties and have significantly elevated levels of expression in multiple human tumor types using a TissueScan Cancer Survey Panel PCR array and database mining. Furthermore, modeling the observed tumor expression of FAM83A, FAM83C, FAM83D, or FAM83E promoted human mammary epithelial cell (HMEC) transformation, which correlated with the ability of each FAM83 member to bind CRAF (RAF1) and promote CRAF membrane localization. Conversely, ablation of FAM83A or FAM83D from breast cancer cells resulted in diminished MAPK signaling with marked suppression of growth in vitro and tumorigenicity in vivo. Importantly, each FAM83 member was determined to be elevated in at least one of 17 distinct tumor types examined, with FAM83A, FAM83B, and FAM83D most frequently overexpressed in several diverse tissue types. Finally, evidence suggests that elevated expression of FAM83 members is associated with elevated tumor grade and decreased overall survival.
FAM83 proteins represent a novel family of oncogenes suitable for the development of cancer therapies aimed at suppressing MAPK signaling.
Functional relationships between phosphorus (P) discharge and concentration mechanisms were explored using a load apportionment model (LAM) developed for use in a freshwater catchment in Ireland with ...fourteen years of data (1995–2008). The aim of model conceptualisation was to infer changes in point and diffuse sources from catchment P loading during P mitigation, based upon a dataset comprising geospatial and water quality data from a 256
km
2 lake catchment in an intensively farmed drumlin region of the midlands of Ireland. The model was calibrated using river total P (TP), molybdate reactive P (MRP) and runoff data from seven subcatchments. Temporal and spatial heterogeneity of P sources existed within and between subcatchments; these were attributed to differences in agricultural intensity, soil type and anthropogenically-sourced effluent P loading. Catchment rivers were sensitive to flow regime, which can result in eutrophication of rivers during summer and lake enrichment from frequent flood events. For one sewage impacted river, the LAM estimated that point sourced P contributed up to of 90% of annual MRP load delivered during a hydrological year and in this river point P sources dominated flows up to 92% of days. In the other rivers, despite diffuse P forming a majority of the annual P exports, point sources of P dominated flows for up to 64% of a hydrological year. The calibrated model demonstrated that lower P export rates followed specific P mitigation measures. The LAM estimated up to 80% decreases in point MRP load after enhanced P removal at waste water treatments plants in urban subcatchments and the implementation of septic tank and agricultural bye-laws in rural subcatchments. The LAM approach provides a way to assess the long-term effectiveness of further measures to reduce P loadings in EU (International) River Basin Districts and subcatchments.
► Load apportionment models (LAMs) relate phosphorus discharge and concentration. ► LAMs show significant changes of P point and diffuse loadings post P reduction. ► P point sources exist in rural catchments without a WWTP. ► LAMs identify catchments of higher P export risk and sensitive transport pathway. ► Identification of P source magnitude and duration during hydrological year.
Lowland waters in Northern Ireland experience elevated agricultural phosphorus (P) inputs, and in response a variety of control measures targeting farm nutrient management have been implemented. ...Their efficacy in lowering nitrogen (N) and P exports and improving water quality is examined in 40 headwater streams from 1990 to 2009, and to 2014 for 24 of these. Over this period manure production in the study catchments declined by 7%, but regional chemical fertilizer inputs declined by 37% for N and 79% for P, and the regional nutrient surplus was lowered by 18% for N and 49% for P. Diminished pollution by organic wastes meant that 85% of streams exhibited chemistry suitable for salmonids in 2009 compared to 40% in 1990. Flow‐weighted mean concentrations (FWMCs) of nutrients declined between 1990 and 2009, and their correlations with catchment stocking rates became stronger over time. For catchments with manure inputs <16.6 kg P ha−1, total P and nitrate FWMCs declined from 123 ± 19 μg P L−1 and 1.92 ± 0.5 mg N L−1 in 1990 at rates of 2.2 ± 0.5 and 30 ± 10 μg L−1 yr−1, respectively. For catchments with higher manure inputs the respective rates of decline were greater at 5.8 ± 1.0 μg P L−1 yr−1 and 160 ± 20 μg N L−1 yr−1 from 1990 concentrations of 270 ± 25 μg P L−1 and 5.99 ± 0.4 mg N L−1. Although now lower, P concentrations in the more highly stocked catchments still exceed regional nutrient standards so that the identification of further factors impinging on nutrient losses is critical if such standards are to be achieved.
Core Ideas
Amelioration of point source and diffuse agricultural pollution over 20 years.
Reductions to diffuse N export more rapid and pronounced than for P.
Nutrient versus land use intensity correlations stronger after pollution amelioration.
No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely ...high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.
17-β-Estradiol (E2) is a steroid hormone involved in numerous brain functions. E2 regulates synaptic plasticity in part by enhancing NMDA receptor function and spine density in the hippocampus, ...resulting in increased long-term potentiation and facilitation of learning and memory. As the calcium-dependent neutral protease, calpain, is also involved in these processes, we tested whether E2 could activate calpain and examined the functional consequences of E2-mediated calpain activation in hippocampus. Calpain activity was analyzed by a fluorescence resonance energy transfer (FRET)-based assay that allows both quantitative determination and spatial resolution. E2 rapidly activated calpain in cultured cortical and hippocampal neurons, prominently in dendrites and dendritic spines. E2-induced calpain activation was mediated through mitogen-activated protein kinase (MAPK), as it was completely blocked by MEK inhibitors. It was also calcium-independent, as it was still evident in presence of the calcium chelator, BAPTA-AM. Activation of ERα and ERβ receptors by specific agonists stimulated calpain activity. Finally, the rapid E2-mediated increase in excitability in acute hippocampal slices was prevented by a membrane-permeable calpain inhibitor. Furthermore, E2 treatment of acute hippocampal slices resulted in increased actin polymerization and membrane levels of GluR1 but not GluR2/3 subunits of AMPA receptors; both effects were also blocked by a calpain inhibitor. Our results indicate that E2 rapidly stimulates calpain activity through MAP kinase-mediated phosphorylation, resulting in increased membrane levels of AMPA receptors. These effects could be responsible for E2-mediated increase in neuronal excitability and facilitation of cognitive processes.
Differences in contexts (eg, policies, healthcare organisation characteristics) may explain variations in the effects of patient safety practice (PSP) implementations. However, knowledge of which ...contextual features are important determinants of PSP effectiveness is limited and consensus is lacking on a taxonomy of which contexts matter.
Iterative, formal discussions were held with a 22-member technical expert panel composed of experts or leaders in patient safety, healthcare systems, and methods. First, potentially important contextual features were identified, focusing on five PSPs. Then, two surveys were conducted to determine the context likely to influence PSP implementations.
The panel reached a consensus on a taxonomy of four broad domains of contextual features important for PSP implementations: safety culture, teamwork and leadership involvement; structural organisational characteristics (eg, size, organisational complexity or financial status); external factors (eg, financial or performance incentives or PSP regulations); and availability of implementation and management tools (eg, training organisational incentives). Panelists also tended to rate specific patient safety culture, teamwork and leadership contexts as high priority for assessing their effects on PSP implementations, but tended to rate specific organisational characteristic contexts as high priority only for use in PSP evaluations. Panelists appeared split on whether specific external factors and implementation/management tools were important for assessment or only description.
This work can guide research commissioners and evaluators on the contextual features of PSP implementations that are important to report or evaluate. It represents a first step towards developing guidelines on contexts in PSP implementation evaluations. However, the science of context measurement needs maturing.
Hippocampal synaptic structure and function exhibit marked variations during the estrus cycle of female rats. Estradiol activates the mitogen-activated protein (MAP) kinase pathway in numerous cell ...types, and MAP kinase has been shown to play a critical role in the mechanisms underlying synaptic plasticity. Here, we report that endogenous estrogen produces a tonic phosphorylation/activation of extracellular signal-regulated kinase 2 (ERK2)/MAP kinase throughout the female rat brain and an increase in tyrosine phosphorylation of NR2 subunits of N-methyl-D-aspartate (NMDA) receptors. Moreover, cyclic changes in estrogen levels during the estrus cycle of female rats are associated with corresponding changes in the levels of activation of ERK2, the state of tyrosine phosphorylation of NR2 subunits of NMDA receptors, and the magnitude of long-term potentiation in hippocampus. Thus, cyclic changes in female sexual hormones result in marked variations in the state of activation of a major cellular signaling pathway critical for learning and memory and in a cellular model of learning and memory.
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