Reducing MCPA herbicide pollution at catchment scale using an agri-environmental scheme

Publication history: Accepted - 16 May 2022; Published online - 20 May 2022.In river catchments used as drinking water sources, high pesticide concentrations in abstracted waters require an expensive treatment step prior to supply. The acid herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA) is particularly problematic as it is highly mobile in the soil-water environment following application. Here, an agri-environmental scheme (AES) was introduced to a large-scale catchment (384 km2) to potentially reduce the burden of pesticides in the water treatment process. The main measure offered was contractor application of glyphosate by weed wiping as a substitute for boom spraying of MCPA, supported by educational and advisory activities. A combined innovation applied in the assessment was, i) a full before-after-control-impact (BACI) framework over four peak application seasons (April to October 2018 to 2021) where a neighbouring catchment (386 km2) did not have an AES and, ii) an enhanced monitoring approach where river discharge and MCPA concentrations were measured synchronously in each catchment. During peak application periods the sample resolution was every 7 h, and daily during quiescent winter periods. This sampling approach enabled flow- and time-weighted concentrations to be established, and a detailed record of export loads. These loads were up to 0.242 kg km−2 yr−1, and over an order of magnitude higher than previously reported in the literature. Despite this, and accounting for inter-annual and seasonal variations in river discharges, the AES catchment indicated a reduction in both flow- and time-weighted MCPA concentration of up to 21% and 24%, respectively, compared to the control catchment. No pollution swapping was detected. Nevertheless, the percentage of MCPA occurrences above a 0.1 μg L−1 threshold did not reduce and so the need for treatment was not fully resolved. Although the work highlights the advantages of catchment management approaches for pollution reduction in source water catchments, it also indicates that maximising participation will be essential for future AES.This work was carried out as part of Source to Tap (IVA5018), a project supported by the European Union's INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB)

Rivastigmine: an open-label, observational study of safety and effectiveness in treating patients with Alzheimer's disease for up to 5 years

BACKGROUND: Rivastigmine, a butyl- and acetylcholinesterase inhibitor, is approved for symptomatic treatment of Alzheimer's disease (AD). Data supporting the safety and efficacy of second-generation cholinesterase inhibitors, such as rivastigmine, are available for treatment up to 1 year, with limited data up to 2 1/2 years. The purpose of this report is to present safety and effectiveness data for rivastigmine therapy in patients with mild to moderately severe AD receiving treatment for up to 5 years. METHODS: An observational approach was used to study 37 patients with originally mild to moderate AD receiving rivastigmine as a therapy for AD in an open-label extension (ENA713, B352 Study Group, 1998). RESULTS: The initial trial demonstrated rivastigmine was well-tolerated and effective in terms of cognition, global functioning and activities of daily living. In this open label extension, high-dose rivastigmine therapy was safe and well tolerated over a 5-year period. Two thirds of the participants still enrolled at week 234 were in the original high-dose rivastigmine group during the double-blind phase, suggesting that early therapy may confer some benefit in delaying long-term progression of symptoms. CONCLUSIONS: Long-term cholinesterase inhibition therapy with rivastigmine was well tolerated, with no dropouts due to adverse effects past the initial titration period. Early initiation of treatment, with titration to high-dose therapy, may have an advantage in delaying progression of the illness

Biallelic interferon regulatory factor 8 mutation: A complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation

Background: The homozygous K108E mutation of interferon regulatory factor 8 (IRF8) is reported to cause dendritic cell (DC) and monocyte deficiency. However, more widespread immune dysfunction is predicted from the multiple roles ascribed to IRF8 in immune cell development and function. Objective: We sought to describe the effect on hematopoiesis and immunity of the compound heterozygous R83C/R291Q mutation of IRF8, which is present in a patient with recurrent viral infection, granuloproliferation, and intracerebral calcification. Methods: Variant IRF8 alleles were identified by means of exome sequencing, and their function was tested by using reporter assays. The cellular phenotype was studied in detail by using flow cytometry, functional immunologic assay transcriptional profiling, and antigen receptor profiling. Results: Both mutations affected conserved residues, and R291Q is orthologous to R294, which is mutated in the BXH2 IRF8-deficient mouse. R83C showed reduced nuclear translocation, and neither mutant was able to regulate the Ets/IRF composite element or interferon-stimulated response element, whereas R291Q retained BATF/JUN interactions. DC deficiency and monocytopenia were observed in blood, dermis, and lung lavage fluid. Granulocytes were consistently increased, dysplastic, and hypofunctional. Natural killer cell development and maturation were arrested. TH1, TH17, and CD8+ memory T-cell differentiation was significantly reduced, and T cells did not express CXCR3. B-cell development was impaired, with fewer memory cells, reduced class-switching, and lower frequency and complexity of somatic hypermutation. Cell-specific gene expression was widely disturbed in interferon- and IRF8-regulated transcripts. Conclusions: This analysis defines the clinical features of human biallelic IRF8 deficiency, revealing a complex immunodeficiency syndrome caused by DC and monocyte deficiency combined with widespread immune dysregulation

The Making of a Self-Neglect Severity Scale

Research in elder self-neglect has lagged behind that of other forms of mistreatment, despite the fact that self-neglect is the most common allegation reported to Adult Protective Service agencies throughout the US. The lack of a gold-standard to measure self-neglect has hampered efforts to study this phenomenon. Researchers designed the Self-neglect Severity Scale (SSS) based on interviews with Adult Protective Service workers and a national expert panel. The SSS is based on observation and interview and is administered in the home to include an environmental assessment. It was piloted, extensively field tested and then revised. The CREST SSS was developed using survey data and consultation with experts in the field. This instrument utilizes observer ratings, interview responses, and assesses subjects physical and environmental domains. It also assesses functional status as it relates to health and safety issues. After field and pilot testing the SSS was finalized and is currently undergoing reliability and validity testing. The CREST SSS was developed as a state scale to provide a common language for describing cases of self-neglect. It is the first self-neglect severity scale available to researchers. If found to be both reliable and valid it can be used in future intervention studies

Towards resolving the phosphorus chaos created by food systems

© 2019, The Author(s). The chaotic distribution and dispersal of phosphorus (P) used in food systems (defined here as disorderly disruptions to the P cycle) is harming our environment beyond acceptable limits. An analysis of P stores and flows across Europe in 2005 showed that high fertiliser P inputs relative to productive outputs was driving low system P efficiency (38 % overall). Regional P imbalance (P surplus) and system P losses were highly correlated to total system P inputs and animal densities, causing unnecessary P accumulation in soils and rivers. Reducing regional P surpluses to zero increased system P efficiency (+ 16 %) and decreased total P losses by 35 %, but required a reduction in system P inputs of ca. 40 %, largely as fertiliser. We discuss transdisciplinary and transformative solutions that tackle the P chaos by collective stakeholder actions across the entire food value chain. Lowering system P demand and better regional governance of P resources appear necessary for more efficient and sustainable food systems

Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome

The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

Developing institutional capacity for reproductive health in humanitarian settings: A descriptive study

© 2015 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction. Institutions play a central role in advancing the field of reproductive health in humanitarian settings (RHHS), yet little is known about organizational capacity to deliver RHHS and how this has developed over the past decade. This study aimed to document the current institutional experiences and capacities related to RHHS. Materials and Methods. Descriptive study using an online questionnaire tool. Results. Respondents represented 82 institutions from 48 countries, of which two-thirds originated from low-and middle-income countries. RHHS work was found not to be restricted to humanitarian agencies (25%), but was also embraced by development organizations (25%) and institutions with dual humanitarian and development mandates (50%). Agencies reported working with refugees (81%), internally-displaced (87%) and stateless persons (20%), in camp-based settings (78%), and in urban (83%) and rural settings (78%). Sixtyeight percent of represented institutions indicated having an RHHS-related policy, 79% an accountability mechanism including humanitarian work, and 90% formal partnerships with other institutions. Seventy-three percent reported routinely appointing RH focal points to ensure coordination of RHHS implementation. There was reported progress in RHHSrelated disaster risk reduction (DRR), emergency management and coordination, delivery of the Minimum Initial Services Package (MISP) for RH, comprehensive RH services in post-crisis/recovery situations, gender mainstreaming, and community-based programming. Other reported institutional areas of work included capacity development, program delivery, advocacy/policy work, followed by research and donor activities. Except for abortion-related services, respondents cited improved efforts in advocacy, capacity development and technical support in their institutions for RHHS to address clinical services, including maternal and newborn health, sexual violence prevention and response, HIV prevention, management of sexually-transmitted infections, adolescent RH, and family planning. Approximately half of participants reported that their institutions had experienced an increase in dedicated budget and staff for RHHS, a fifth no change, and 1 in 10 a decrease. The Interagency RH Kits were reportedly the most commonly used supplies to support RHHS implementation. Conclusion. The results suggest overall growth in institutional capacity in RHHS over the past decade, indicating that the field has matured and expanded from crisis response to include RHHS into DRR and other elements of the emergency management cycle. It is critical to consolidate the progress to date, address gaps, and sustain momentum

Childhood cancer in the offspring born in 1921–1984 to US radiologic technologists

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921–1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2–1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (⩾82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7–4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure