Regulation of the JNK3 signaling pathway during islet isolation: JNK3 and c-fos as new markers of islet quality for transplantation.

Stress conditions generated throughout pancreatic islet processing initiate the activation of pro-inflammatory pathways and beta-cell destruction. Our goal is to identify relevant and preferably beta-specific markers to assess the activation of beta-cell stress and apoptotic mechanisms, and therefore the general quality of the islet preparation prior to transplantation. Protein expression and activation were analyzed by Western blotting and kinase assays. ATP measurements were performed by a luminescence-based assay. Oxygen consumption rate (OCR) was measured based on standard protocols using fiber optic sensors. Total RNA was used for gene expression analyzes. Our results indicate that pancreas digestion initiates a potent stress response in the islets by activating two stress kinases, c-Jun N-terminal Kinase (JNK) and p38. JNK1 protein levels remained unchanged between different islet preparations and following culture. In contrast, levels of JNK3 increased after islet culture, but varied markedly, with a subset of preparations bearing low JNK3 expression. The observed changes in JNK3 protein content strongly correlated with OCR measurements as determined by the Spearman's rank correlation coefficient rho [Formula: see text] in the matching islet samples, while inversely correlating with c-fos mRNA expression [Formula: see text]. In conclusion, pancreas digestion recruits JNK and p38 kinases that are known to participate to beta-cell apoptosis. Concomitantly, the islet isolation alters JNK3 and c-fos expression, both strongly correlating with OCR. Thus, a comparative analysis of JNK3 and c-fos expression before and after culture may provide for novel markers to assess islet quality prior to transplantation. JNK3 has the advantage over all other proposed markers to be islet-specific, and thus to provide for a marker independent of non-beta cell contamination

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

A survey of the incidence of the Bromus species as weeds of winter cereals in England, Wales and parts of Scotland

In June 1989, a survey was made of 733 fields of winter cereals, 627 in England and Wales and 106 in Fife and the Lothian regions of Scotland. The occurrence of Bromus species was noted in three areas of each field: the uncropped field margin, the cropped headland and the field centre. Three arbitrarily defined infestation levels were recorded: severe,light and intermediate. The most common species recorded was Bromus sterilis L., which accounted for almost 87% of all sightings. Most of the other occurrences were almost equally distributed between B. hordeaceus L., and B. commutatus Schrad. Two other species were found, on one field each: B. diandrus Roth and B. x pseudothominii Hard. Surveyors were briefed to recognize B. secalinus L, but none was reported. The brome grasses were widespread throughout the surveyed regions. They were most common in the Lothians (81% of surveyed fields) and in the South East (60%) and the South West (52%) of England and least common in the Eng lish West Midlands, Fife and Wales (17%, 15% and 4% of surveyed fields). Distribution was biased towards the uncropped margins and field headlands. In England and Wales, there were 146 fields where Bromus species occurred in the field margins only, 179 in margins and headlands only and 63 with infestations in all three areas. In contrast, there were only 26 fields where they were restricted to the cropped areas. A similar pattern occurred in Scotland. The correlations between incidence of the Bromus species and management practices were much weaker than had been anticipated. The standard advice for control is to plough rather than use non-inversion tillage systems, to delay sowing and to avoid long runs of winter cereals. The conclusion of this survey is that, although these practices may be reducing or preventing increase of these weeds, they are not effective at eliminating infestations

The impact of future socio-economic and climate changes on agricultural land use and the wider environment in East Anglia and North West England using a metamodel system

This paper describes a procedure to use a model interactively to investigate future land use by studying a wide range of scenarios defining climate, technological and socio-economic changes. A full model run of several hours has been replaced by a metamodel version which takes a few seconds, and provides the user with an immediate visual output and with the ability to examine easily which factors have the greatest effect. The Regional Impact Simulator combines a model of agricultural land use choices linked with models of urban growth, flooding risk, water quality and consequences for wildlife to estimate plausible futures of agricultural land on a timescale of 20–50 years. The model examines the East Anglian and North West regions of the United Kingdom at a grid resolution of 5 × 5 km, and for each scenario estimates the most likely cropping and its profitability at each location, and classifies land use as arable, intensive or extensive grassland or abandoned. From a modelling viewpoint the metamodel approach enables iteration. It is thus possible to determine how product prices change so that production meets demand. The results of the study show that in East Anglia cropping remains quite stable over a wide range of scenarios, though grassland is eliminated in scenarios with the 2050s High climate scenario – almost certainly due to the low yield in the drier conditions. In the North West there is a very much greater range of outcomes, though all scenarios suggest a reduction in grassland with the greatest in the 2050s High climate scenario combined with the “Regional Stewardship” (environmental) socio-economic scenario. The effects of the predicted changes in land use on plant species showed suitability for species to vary greatly, particularly between the socio-economic scenarios, due to detrimental effects from increases in nitrogen fertilisation. A complete simulation with the Regional Impact Simulator takes around 15 seconds (computer-dependent), which users who responded felt was adequate or better than adequate. The main areas for future improvement, such as the speed of the system, user interaction and the accuracy and detail of the modelling, are c

A systematic review of cluster randomised trials in residential facilities for older people suggests how to improve quality.

BACKGROUND: Previous reviews of cluster randomised trials have been critical of the quality of the trials reviewed, but none has explored determinants of the quality of these trials in a specific field over an extended period of time. Recent work suggests that correct conduct and reporting of these trials may require more than published guidelines. In this review, our aim was to assess the quality of cluster randomised trials conducted in residential facilities for older people, and to determine whether (1) statistician involvement in the trial and (2) strength of journal endorsement of the Consolidated Standards of Reporting Trials (CONSORT) statement influence quality. METHODS: We systematically identified trials randomising residential facilities for older people, or parts thereof, without language restrictions, up to the end of 2010, using National Library of Medicine (Medline) via PubMed and hand-searching. We based quality assessment criteria largely on the extended CONSORT statement for cluster randomised trials. We assessed statistician involvement based on statistician co-authorship, and strength of journal endorsement of the CONSORT statement from journal websites. RESULTS: 73 trials met our inclusion criteria. Of these, 20 (27%) reported accounting for clustering in sample size calculations and 54 (74%) in the analyses. In 29 trials (40%), methods used to identify/recruit participants were judged by us to have potentially caused bias or reporting was unclear to reach a conclusion. Some elements of quality improved over time but this appeared not to be related to the publication of the extended CONSORT statement for these trials. Trials with statistician/epidemiologist co-authors were more likely to account for clustering in sample size calculations (unadjusted odds ratio 5.4, 95% confidence interval 1.1 to 26.0) and analyses (unadjusted OR 3.2, 1.2 to 8.5). Journal endorsement of the CONSORT statement was not associated with trial quality. CONCLUSIONS: Despite international attempts to improve methods in cluster randomised trials, important quality limitations remain amongst these trials in residential facilities. Statistician involvement on trial teams may be more effective in promoting quality than further journal endorsement of the CONSORT statement. Funding bodies and journals should promote statistician involvement and co-authorship in addition to adherence to CONSORT guidelines

Burial depth and cultivation influence emergence and persistence of Phalaris paradoxa seed in an Australian sub-tropical environment

Emergence and persistence characteristics of Phalaris paradoxa seeds in no- and minimum-till situations and at different burial depths were studied in a sub-tropical environment. Three experiments were carried out using naturally shed seeds. In the first experiment, seedlings emerged from May through to September each year, although the majority of seedlings emerged in July. In the second experiment with greater seed density, cultivation in March of each year stimulated seedling emergence, altered the periodicity of emergence and accelerated the decline of seeds in the seedbank compared with plots that received no cultivation. The majority of seedlings in the cultivated plots emerged in May whereas the majority of seedlings in the undisturbed plots emerged in July. Emergence accounted for only 4-19% of the seedbank in both experiments over 2 years. Seed persistence was short in both field experiments, with less than 1% remaining 2 years after seed shed. In the third experiment, burial depth and soil disturbance significantly influenced seedling emergence and persistence of seed. Seedlings emerged most from seed mixed in the top 10 cm when subjected to annual soil disturbance, and from seed buried at 2.5 and 5.0 cm depths in undisturbed soil. Emergence was least from seed on the soil surface, and buried at 10 and 15 cm depths in undisturbed soil. Seeds persisted longest when shed onto the soil surface and persisted least when the soil was tilled. These results suggest that strategic cultivation may be a useful management tool, as it will alter the periodicity of emergence allowing use of more effective control options and will deplete the soil seedbank more rapidly