Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Optimizing innovation, carbon and health in transport: assessing socially optimal electric mobility and vehicle-to-grid pathways in Denmark

This paper examines the social costs and benefits of potential configurations of electric vehicle deployment, including and excluding vehicle-to-grid. To fully explore the benefits and costs of different electric vehicle pathways, four different scenarios are devised with both today’s and 2030 electricity grid in Denmark. These scenarios combine different levels of electric vehicle implementation and communication ability, i.e. smart charging or full bi-directionality, and then paired with different levels of future renewable energy implementation. Then, the societal costs of all scenarios are calculated, including carbon and health externalities to find the least-cost mix of electric vehicles for society. The most cost-effective penetration of electric vehicles in the near future is found to be 27%, increasing to 75% by 2030. This would equate to a $34 billion reduction to societal costs in 2030, a decrease of 30$1,200 in 2030. However, current vehicle capital cost differences, a lack of willingness to pay for electric vehicles, and consumer discount rates are substantial barriers to electric vehicle deployment in Denmark in the near term

An Image-Free Opto-Mechanical System for Creating Virtual Environments and Imaging Neuronal Activity in Freely Moving Caenorhabditis elegans

Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets

Geophysical monitoring and reactive transport modeling of ureolytically-driven calcium carbonate precipitation

Ureolytically-driven calcium carbonate precipitation is the basis for a promising in-situ remediation method for sequestration of divalent radionuclide and trace metal ions. It has also been proposed for use in geotechnical engineering for soil strengthening applications. Monitoring the occurrence, spatial distribution, and temporal evolution of calcium carbonate precipitation in the subsurface is critical for evaluating the performance of this technology and for developing the predictive models needed for engineering application. In this study, we conducted laboratory column experiments using natural sediment and groundwater to evaluate the utility of geophysical (complex resistivity and seismic) sensing methods, dynamic synchrotron x-ray computed tomography (micro-CT), and reactive transport modeling for tracking ureolytically-driven calcium carbonate precipitation processes under site relevant conditions. Reactive transport modeling with TOUGHREACT successfully simulated the changes of the major chemical components during urea hydrolysis. Even at the relatively low level of urea hydrolysis observed in the experiments, the simulations predicted an enhanced calcium carbonate precipitation rate that was 3-4 times greater than the baseline level. Reactive transport modeling results, geophysical monitoring data and micro-CT imaging correlated well with reaction processes validated by geochemical data. In particular, increases in ionic strength of the pore fluid during urea hydrolysis predicted by geochemical modeling were successfully captured by electrical conductivity measurements and confirmed by geochemical data. The low level of urea hydrolysis and calcium carbonate precipitation suggested by the model and geochemical data was corroborated by minor changes in seismic P-wave velocity measurements and micro-CT imaging; the latter provided direct evidence of sparsely distributed calcium carbonate precipitation. Ion exchange processes promoted through NH4+ production during urea hydrolysis were incorporated in the model and captured critical changes in the major metal species. The electrical phase increases were potentially due to ion exchange processes that modified charge structure at mineral/water interfaces. Our study revealed the potential of geophysical monitoring for geochemical changes during urea hydrolysis and the advantages of combining multiple approaches to understand complex biogeochemical processes in the subsurface

Neurophysiological Defects and Neuronal Gene Deregulation in Drosophila mir-124 Mutants

miR-124 is conserved in sequence and neuronal expression across the animal kingdom and is predicted to have hundreds of mRNA targets. Diverse defects in neural development and function were reported from miR-124 antisense studies in vertebrates, but a nematode knockout of mir-124 surprisingly lacked detectable phenotypes. To provide genetic insight from Drosophila, we deleted its single mir-124 locus and found that it is dispensable for gross aspects of neural specification and differentiation. On the other hand, we detected a variety of mutant phenotypes that were rescuable by a mir-124 genomic transgene, including short lifespan, increased dendrite variation, impaired larval locomotion, and aberrant synaptic release at the NMJ. These phenotypes reflect extensive requirements of miR-124 even under optimal culture conditions. Comparison of the transcriptomes of cells from wild-type and mir-124 mutant animals, purified on the basis of mir-124 promoter activity, revealed broad upregulation of direct miR-124 targets. However, in contrast to the proposed mutual exclusion model for miR-124 function, its functional targets were relatively highly expressed in miR-124–expressing cells and were not enriched in genes annotated with epidermal expression. A notable aspect of the direct miR-124 network was coordinate targeting of five positive components in the retrograde BMP signaling pathway, whose activation in neurons increases synaptic release at the NMJ, similar to mir-124 mutants. Derepression of the direct miR-124 target network also had many secondary effects, including over-activity of other post-transcriptional repressors and a net incomplete transition from a neuroblast to a neuronal gene expression signature. Altogether, these studies demonstrate complex consequences of miR-124 loss on neural gene expression and neurophysiology

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

A review of modelling tools for implementation of the EU Water Framework Directive in handling diffuse water pollution

A numerical catchment-scale model capable of simulating diffuse water pollution is necessary in sustainable environmental management for better implementation of the EU Water Framework Directive. This paper provides critical reviews of most popular and free models for diffuse water modelling, with detailed sources and application potential. Based upon these reviews, further work of selecting and testing the HSPF model was carried out, with a case study in the Upper Bann Catchment, Northern Ireland. The calibrated and validated HSPF model can well represent the characteristics of surface water quantity and quality. Climate change scenario evaluation in 5 years showed that when the annual mean temperature increase 3◦C the mean yearly total runoff volume will decrease by 11.1% and the mean daily river flow 11.4%. If 20% crop and pasture land is converted into forest land in the study area, the mean river concentration of nitrate, nitrite, NH4 and PO4 in 5 years will decrease by 19.4%, 33.3%, 31.3% and 31.3% respectively. When applying filter strip method in 80% crop and pasture land in the area, the reduction of the mean concentration of nitrate, nitrite, NH4 and PO4 in 5 years will be 15.3%, 33.3%, 31.3%, and 5.6% respectively. This study shows that HSPF is a suitable model in handling diffuse source water pollution, which can be introduced into the Programme of Measures in the River Basin Management Plans for better implementation of the EUWFD

SMEs and environmental responsibility: a policy perspective

Environmental policies to promote environmentally-sustainable economic activity have often concentrated on larger firms. However, increasing attention is being paid to the role of SMEs and entrepreneurial actors. In this paper we examine how policy tools are being used to improve the environmental performance of SMEs and to redirect entrepreneurial energies in more environmentally-benign directions. The empirical section adopts a case-based comparative method to examine four instances of policy-making, drawn from different countries and industry sectors. The paper argues that while some interventions have proved effective in their own terms, better integrated approaches are required to address today’s complex and deep-rooted sustainability challenges. The paper identifies several policy implications including the need to: clarify the purpose of any intervention, address potential interactions and trade-offs; select appropriate tools based on informed reviews of the options; remain sensitive to context-specific factors, and to devise effective vehicles for the promotion and governance of entrepreneurial initiatives