Factors affecting the structure of salmonid epidermis

The recent literature concerning the structure of teleost epidermis is reviewed; particular attention is given to salmonids and epidermal variability and plasticity. A preliminary survey of hatchery-reared and wild 0+ brown trout Salmo trutta L. suggested that quantitative and qualitative variation in epidermal structure are related inter alia to development and disease. A subsequent, temporal investigation of disease-free brown trout revealed a decline in the density of superficial mucous cells and a change in their histochemistry early in development; these findings are discussed in relation to habitat and the functional role of epidermal mucous secretion. Infestations by the ectoparasite Ichtyobodo necator were shown to cause a significant depletion of epidermal mucous cells and an increase in the abundance of a previously undescribed acidophilic cell in 0+ brown trout; these pathogenic effects were found to be reversible by therapeutic formalin administration. The sequential histopathology of costiasis in cultured and wild juvenile brown trout is described. Ichtyobodo infestation stimulated an initial hypersecretion of mucus; as infestation intensified Malpighian cell proliferation occurred, mucous cells disappeared and the density of acidophilic cells continued to increase. In the chronic phase of the disease there was a cycle of epidermal hyperplasia and but by autumn, as infestation became less severe, progressive re-development of a normal epidermal structure took place in surviving fish. Analogous changes in cell composition were observed in fish subjected to formalin prophylaxis, and possible applications to fish farm management are suggested. The contents of a presumed secretory acidophilic cell in brown trout, which was also shown to occur in other salmonid taxa, were found to be granular and proteinaceous. Finally, the possibility that there are non-specific epidermal responses to surface active irritation in teleosts is considered in relation to effects of irritants on epithelial mucosae in higher vertebrates

Ability of verbal autopsy data to detect deaths due to uncontrolled hyperglycaemia:testing existing methods and development and validation of a novel weighted score

Objectives: Verbal autopsy (VA) is a useful tool to ascertain cause of death where no other mechanisms exist. We aimed to assess the utility of VA data to ascertain deaths due to uncontrolled hyperglycaemia and to develop a weighted score (WS) to specifically identify cases. Cases were identified by a study or site physician with training in diabetes. These diagnoses were also compared with diagnoses produced by a standard computer algorithm (InterVA-4). Setting: This study was done using VA data from the Health and Demographic Survey sites in Agincourt in rural South Africa. Validation of the WS was done using VA data from Karonga in Malawi. Participants: All deaths from ages 1 to 49 years between 1992 and 2015 and between 2002 and 2016 from Agincourt and Karonga, respectively. There were 8699 relevant deaths in Agincourt and 1663 in Karonga. Results: Of the Agincourt deaths, there were 77 study physician classified cases and 58 computer algorithm classified cases. Agreement between study physician classified cases and computer algorithm classified cases was poor (Cohen’s kappa 0.14). Our WS produced a receiver operator curve with area under the curve of 0.952 (95% CI 0.920 to 0.985). However, positive predictive value (PPV) was below 50% when the WS was applied to the development set and the score was dominated by the necessity for a premortem diagnosis of diabetes. Independent validation showed the WS performed reasonably against site physician classified cases with sensitivity of 86%, specificity of 99%, PPV of 60% and negative predictive value of 99%. Conclusion: Our results suggest that widely used VA methodologies may be missing deaths due to uncontrolled hyperglycaemia. Our WS may offer improved ability to detect deaths due to uncontrolled hyperglycaemia in large populations studies where no other means exist

Conserved in VivoPhosphorylation of Calnexin at Casein Kinase II Sites as Well as a Protein Kinase C/Proline-directed Kinase Site

Calnexin is a lectin-like chaperone of the endoplasmic reticulum (ER) that couples temporally and spatially N-linked oligosaccharide modifications with the productive folding of newly synthesized glycoproteins. Calnexin was originally identified as a major type I integral membrane protein substrate of kinase(s) associated with the ER. Casein kinase II (CK2) was subsequently identified as an ER-associated kinase responsible for the in vitro phosphorylation of calnexin in microsomes (Ou, W-J., Thomas, D. Y., Bell, A. W., and Bergeron, J. J. M. (1992) J. Biol. Chem. 267, 23789-23796). We now report on the in vivo sites of calnexin phosphorylation. After 32PO4 labeling of HepG2 and Madin-Darby canine kidney cells, immunoprecipitated calnexin was phosphorylated exclusively on serine residues. Using nonradiolabeled cells, we subjected calnexin immunoprecipitates to in gel tryptic digestion followed by nanoelectrospray mass spectrometry employing selective scans specific for detection of phosphorylated fragments. Mass analyses identified three phosphorylated sites in calnexin from either HepG2 or Madin-Darby canine kidney cells. The three sites were localized to the more carboxyl-terminal half of the cytosolic domain: S534DAE (CK2 motif), S544QEE (CK2 motif), and S563PR. We conclude that CK2 is a kinase that phosphorylates calnexin in vivo as well as in microsomes in vitro. Another yet to be identified kinase (protein kinase C and/or proline-directed kinase) is directed toward the most COOH-terminal serine residue. Elucidation of the signaling cascade responsible for calnexin phosphorylation at these sites in vivo may define a novel regulatory function for calnexin in cargo folding and transport to the ER exit sites

Au-Ag template stripped pattern for scanning probe investigations of DNA arrays produced by Dip Pen Nanolithography

We report on DNA arrays produced by Dip Pen Nanolithography (DPN) on a novel Au-Ag micro patterned template stripped surface. DNA arrays have been investigated by atomic force microscopy (AFM) and scanning tunnelling microscopy (STM) showing that the patterned template stripped substrate enables easy retrieval of the DPN-functionalized zone with a standard optical microscope permitting a multi-instrument and multi-technique local detection and analysis. Moreover the smooth surface of the Au squares (abput 5-10 angstrom roughness) allows to be sensitive to the hybridization of the oligonucleotide array with label-free target DNA. Our Au-Ag substrates, combining the retrieving capabilities of the patterned surface with the smoothness of the template stripped technique, are candidates for the investigation of DPN nanostructures and for the development of label free detection methods for DNA nanoarrays based on the use of scanning probes.Comment: Langmuir (accepted

Climate Engineering Responses to Climate Emergencies

Despite efforts to stabilize CO_2 concentrations, it is possible that the climate system could respond abruptly with catastrophic consequences. Intentional intervention in the climate system to avoid or ameliorate such consequences has been proposed as one possible response, should such a scenario arise. In a one-week study, the authors of this report conducted a technical review and evaluation of proposed climate engineering concepts that might serve as a rapid palliative response to such climate emergency scenarios. Because of their potential to induce a prompt (less than one year) global cooling, this study concentrated on Shortwave Climate Engineering (SWCE) methods for moderately reducing the amount of shortwave solar radiation reaching the Earth. The study's main objective was to outline a decade-long agenda of technical research that would maximally reduce the uncertainty surrounding the benefits and risks associated with SWCE. For rigor of technical analysis, the study focused the research agenda on one particular SWCE concept--stratospheric aerosol injection--and in doing so developed several conceptual frameworks and methods valuable for assessing any SWCE proposal.Comment: 66 pp., 5 figs., published by Novim, Santa Barbara, Cal., revised referenc

The Lore of Low Methane Livestock:Co-Producing Technology and Animals for Reduced Climate Change Impact

Methane emissions from sheep and cattle production have gained increasing profile in the context of climate change. Policy and scientific research communities have suggested a number of technological approaches to mitigate these emissions. This paper uses the concept of co-production as an analytical framework to understand farmers’ evaluation of a 'good animal’. It examines how technology and sheep and beef cattle are co-produced in the context of concerns about the climate change impact of methane. Drawing on 42 semi-structured interviews, this paper demonstrates that methane emissions are viewed as a natural and integral part of sheep and beef cattle by farmers, rather than as a pollutant. Sheep and beef cattle farmers in the UK are found to be an extremely heterogeneous group that need to be understood in their specific social, environmental and consumer contexts. Some are more amenable to appropriating methane reducing measures than others, but largely because animals are already co-constructed from the natural and the technical for reasons of increased production efficiency

Cross-scale analysis of social-ecological systems:Policy options appraisal for delivering NetZero and other environmental objectives in Scotland

Public policy confronts complex, contested, wicked problems such as climate and biodiversity crises with challenges of how issues are framed, analysed, codified, and interpreted. Social-ecological systems provide an analytical framework that couples the biosphere and technosphere, recognising biophysical limits and emphasising the importance of critical reflection within policy decision-making. Conducting policy-options appraisals is increasingly seen as a transdisciplinary research-policy endeavour with researchers engaging policy actors in an extended peer community (post-normal science). This paper presents a case study of analysis undertaken with researchers, policy analysts, policy makers and other stakeholders to support decisions on how to implement future agriculture support in Scotland, so that the policy programme better delivers across social, economic and environmental objectives. The key change being considered in the future agricultural support programme is Enhanced Conditionality (EC) where the level of financial support provided to farm-businesses will depend on their undertaking agri-environmental measures that deliver against the key priorities of reducing greenhouse gas emissions and reversing biodiversity losses. The paper outlines the policy context within which the EC options appraisal takes place – highlighting how EC is a crucial component in making the wider suite of policy measures work. The transdisciplinary approach, Quantitative Story Telling (QST) is presented, emerging from decision support, participatory research, and post-normal science for policy domains. The stages of QST highlight the importance of analysis that underpins any quantification (decision on how issues are framed and what it included in the analysis) and the expectation that research outputs with be deliberated on with, and interpreted from, stakeholder perspectives. The project specific analyses are outlined, combining top-down options appraisal of how macro-policy decisions could constrain EC and bottom-up analysis of potential uptake and effectiveness of EC measures, undertaken in inter-disciplinary workshops with domain experts from biodiversity, soils and waters. The paper highlights challenges for implementation and evaluation at meso-scale with interactions between farm-businesses and catchment, landscape and regional objectives. The conclusions of the analysis, in policy terms, are that EC presents an opportunity to significantly realign how agricultural land management is conducted in Scotland, so that it is more effective in delivering climate change and biodiversity objectives, but there are formidable challenges in resolving the policy “sudoku”. Meso-scale issues are likely to mean the need to integrate alternative modelling paradigms such as spatial, empirical agent-based modelling (ABM) into policy option appraisals. By taking multi-scale, social-ecological systems perspectives on EC it has been possible to identify key policy decisions at a range of scales on which the success of EC will depend, to have a realistic understanding of how effective the EC measures might be in heterogenous Scottish environments and what are the likely barriers to uptake. The analysis also highlighted where outcomes of the policy change are likely to be challenging to monitor-evaluate; and where there are dependencies between farm-businesses that mean EC measures need to be supplemented with mechanisms that (1) promote cooperation between land managers and (2) identify and respond to agreed local priorities. The value of the participatory QST process was in making sure the analyses being undertaken were salient and the outputs seen as credible – but the challenges of interpreting necessarily complex outputs remain. The greatest value of QST may be that it provides a structured way to navigate complexity with policy makers rather than seeking to control or eliminate it.</p

Cross-scale analysis of social-ecological systems:Policy options appraisal for delivering NetZero and other environmental objectives in Scotland

Public policy confronts complex, contested, wicked problems such as climate and biodiversity crises with challenges of how issues are framed, analysed, codified, and interpreted. Social-ecological systems provide an analytical framework that couples the biosphere and technosphere, recognising biophysical limits and emphasising the importance of critical reflection within policy decision-making. Conducting policy-options appraisals is increasingly seen as a transdisciplinary research-policy endeavour with researchers engaging policy actors in an extended peer community (post-normal science). This paper presents a case study of analysis undertaken with researchers, policy analysts, policy makers and other stakeholders to support decisions on how to implement future agriculture support in Scotland, so that the policy programme better delivers across social, economic and environmental objectives. The key change being considered in the future agricultural support programme is Enhanced Conditionality (EC) where the level of financial support provided to farm-businesses will depend on their undertaking agri-environmental measures that deliver against the key priorities of reducing greenhouse gas emissions and reversing biodiversity losses. The paper outlines the policy context within which the EC options appraisal takes place – highlighting how EC is a crucial component in making the wider suite of policy measures work. The transdisciplinary approach, Quantitative Story Telling (QST) is presented, emerging from decision support, participatory research, and post-normal science for policy domains. The stages of QST highlight the importance of analysis that underpins any quantification (decision on how issues are framed and what it included in the analysis) and the expectation that research outputs with be deliberated on with, and interpreted from, stakeholder perspectives. The project specific analyses are outlined, combining top-down options appraisal of how macro-policy decisions could constrain EC and bottom-up analysis of potential uptake and effectiveness of EC measures, undertaken in inter-disciplinary workshops with domain experts from biodiversity, soils and waters. The paper highlights challenges for implementation and evaluation at meso-scale with interactions between farm-businesses and catchment, landscape and regional objectives. The conclusions of the analysis, in policy terms, are that EC presents an opportunity to significantly realign how agricultural land management is conducted in Scotland, so that it is more effective in delivering climate change and biodiversity objectives, but there are formidable challenges in resolving the policy “sudoku”. Meso-scale issues are likely to mean the need to integrate alternative modelling paradigms such as spatial, empirical agent-based modelling (ABM) into policy option appraisals. By taking multi-scale, social-ecological systems perspectives on EC it has been possible to identify key policy decisions at a range of scales on which the success of EC will depend, to have a realistic understanding of how effective the EC measures might be in heterogenous Scottish environments and what are the likely barriers to uptake. The analysis also highlighted where outcomes of the policy change are likely to be challenging to monitor-evaluate; and where there are dependencies between farm-businesses that mean EC measures need to be supplemented with mechanisms that (1) promote cooperation between land managers and (2) identify and respond to agreed local priorities. The value of the participatory QST process was in making sure the analyses being undertaken were salient and the outputs seen as credible – but the challenges of interpreting necessarily complex outputs remain. The greatest value of QST may be that it provides a structured way to navigate complexity with policy makers rather than seeking to control or eliminate it.</p

Recent Advances in Combined Modality Therapy

This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy