771 research outputs found
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)
Mapping the undergraduate dermatology curriculum – a useful tool towards implementation of national recommendations
Despite the high prevalence of skin complaints in primary and secondary care, dermatology undergraduate (UG) education remains inconsistent across medical schools. The British Association of Dermatologists (BAD) published a revised national undergraduate curriculum in 2016 to guide UK medical schools on minimum competencies required in dermatology. A curriculum mapping study was conducted to determine the alignment of the BAD UG curriculum with the dermatology curriculum of the University of Nottingham (UoN) School of Medicine. Of the 70 intended learning outcomes (ILOs) for dermatology in the medical school, 55 (79%) were mapped to the BAD curriculum, 14 (20%) required modifications to align them with the BAD ILOs, 2 BAD outcomes were unspecified in the current curriculum, and 1 outcome overlapped with others and was deemed redundant. Curriculum mapping is a useful tool to standardise local dermatology ILOs to national recommendations and provides transparency to stakeholders for implementation of the dermatology curriculum
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
Variability in the area, energy and time costs of wintering waders responding to disturbance
Birds’ responses to human disturbance are interesting due to their similarities to anti-predator behaviour, and understanding this behaviour has practical applications for conservation management by informing measures such as buffer zones to protect priority species. To understand better the costs of disturbance and whether it will impact on population size, studies should quantify time-related responses as well as the more commonly reported flight initiation distance (FID). Using waders wintering on an estuarine area, we experimentally disturbed foraging birds on the Wash Embayment, UK, by walking towards them and recording their responses (FID, alert time, time spent in flight, time taken to resume feeding, and total feeding time lost). We present data for 10 species of conservation concern: Curlew Numenius arquata, Oystercatcher Haematopus ostralegus, Bar-tailed Godwit Limosa lapponica, Grey Plover Pluvialis squatarola, Redshank Tringa totanus, Knot Calidris canutus, Turnstone Arenaria interpres, Ringed Plover Charadrius hiaticula, Sanderling Calidris alba and Dunlin Calidris alpina. Larger species responded more strongly, response magnitude was greater under milder environmental conditions, and responses varied over both small and large spatial scales. The energetic costs of individual responses, however, were low relative to daily requirements and disturbance events were unlikely to be frequent enough to seriously limit foraging time. We suggest, therefore, that wintering wader populations on the Wash are not currently significantly negatively impacted by human disturbance during the intertidal foraging period. This is also likely to be the case at other estuarine sites with comparable access levels, visitor patterns, invertebrate food availability and environmental conditions
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
Genomewide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices.
OBJECTIVE: To study the difference in gene expression between human papillomavirus (HPV)-positive and HPV-negative oral cavity and oropharyngeal squamous cell carcinoma (OSCC). DESIGN: We used Affymetrix U133 plus 2.0 arrays to examine gene expression profiles of OSCC and normal oral tissue. The HPV DNA was detected using polymerase chain reaction followed by the Roche LINEAR ARRAY HPV Genotyping Test, and the differentially expressed genes were analyzed to examine their potential biological roles using the Ingenuity Pathway Analysis Software, version 5.0. SETTING: Three medical centers affiliated with the University of Washington. PATIENTS: A total of 119 patients with primary OSCC and 35 patients without cancer, all of whom were treated at the setting institutions, provided tissues samples for the study. RESULTS: Human papillomavirus DNA was found in 41 of 119 tumors (34.5%) and 2 of 35 normal tissue samples (5.7%); 39 of the 43 HPV specimens were HPV-16. A higher prevalence of HPV DNA was found in oropharyngeal cancer (23 of 31) than in oral cavity cancer (18 of 88). We found no significant difference in gene expression between HPV-positive and HPV-negative oral cavity cancer but found 446 probe sets (347 known genes) differentially expressed in HPV-positive oropharyngeal cancer than in HPV-negative oropharyngeal cancer. The most prominent functions of these genes are DNA replication, DNA repair, and cell cycling. Some genes differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer (eg, TYMS, STMN1, CCND1, and RBBP4) are involved in chemotherapy or radiation sensitivity. CONCLUSION: These results suggest that differences in the biology of HPV-positive and HPV-negative oropharyngeal cancer may have implications for the management of patients with these different tumors
Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival
<p>Abstract</p> <p>Background</p> <p>Lymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC.</p> <p>Results</p> <p>We performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate < 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with <it>p </it>= 0.044 or 0.011, respectively).</p> <p>Conclusions</p> <p>Genes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.</p
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
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