The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)

Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable (h2 = 0.21 to 0.57) and highly stable over an individual’s lifespan. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively. This region was adjacent to two candidate loci, Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex, and adult IgE levels and lamb IgA and IgG levels were associated with the major histocompatibility complex (MHC). This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Cocoa agroforest multifunctionality and soil fertility explained by shade tree litter traits

International audienceManipulating plant functional diversity to improve agroecosystem multifunctionality is a central challenge of agricultural systems world-wide. In cocoa agroforestry systems (cAFS), shade trees are used to supply many services to farmers, yet their impact on soil functioning and cocoa yields is likely to vary substantially among tree species. Here we compared the impact of five shade tree species (Canarium schweinfurthii (Canarium), Dacryodes edulis (Safou), Milicia excelsa (Iroko), Ceiba pentandra (Kapok tree), Albizia adianthifolia (Albizia)) and unshaded conditions on the functioning of poor sandy savanna soils within eight cocoa farms in Central Cameroon. We assessed the effects of plant functional traits, leaf litterfall and fine root biomass on a range of soil functions and on cocoa yield. Shade trees generally improved soil pH, NH4+, NO3- and Olsen P content, biomass production of bioassays and soil total C and N content, while leaving cocoa yields unchanged. However, these effects varied largely among species. Improvements of soil functions were low under the two fruit trees (Canarium and Dacryodes), medium under the legume tree Albizia and high under the two timber trees (Milicia and Ceiba). Low litter recalcitrance was most strongly associated with increases in soil fertility indicators such as N and P availability, whereas soil C and N content increased with litter Ca restitution. Synthesis and applications. We demonstrate that cocoa agroforest multifunctionality is substantially influenced by the functional traits of shade tree species. Shade tree species with the most dissimilar traits to cocoa (cocoa showing the lowest leaf litter quality) showed the largest improvement of soil functions. Therefore, selection of shade trees based on their functional traits appears as a promising practice to adequately manage soil functioning. In order to fully assess the beneficial role of shade trees in these agroecosystems. Future research will need to extend this approach to other below-ground traits and other aspects of multifunctionality such as long-term cocoa health and yield

Long-term dynamics of cocoa agroforestry systems established on lands previously occupied by savannah or forests

International audienceCocoa agroforestry systems (cAFS) in Central Cameroon are established on lands which were either forest or savannah. The functioning and ecosystem services (ES) delivery of an agroecosystem can be influenced by past land-use. We hypothesised that savannah-derived cocoa agroforestry systems (S-cAFS) and forest-derived cocoa agroforestry systems (F-cAFS) would (i) progressively drift away from past land-use, and (ii) eventually converge and support comparable levels of ecosystem services. We selected 25 ecosystem attributes directly related to at least one of the following six ecosystem (dis)services (ES): species conservation, carbon storage, crop production, nutrient cycling, soil quality and soil pollution. We followed their temporal evolution in S- and F-cAFS along >70-year chronosequences. Our results showed that the attributes and services studied followed typical temporal trajectories in S- and F-cAFS while generally tending to reach comparable levels on the long run. However, the time needed to do so varied strongly and ranged from 20 to 30 years for perennial species diversity to more than 70 years for C storage or some components of soil quality. The results also demonstrated that S-cAFS could sustainably improve many of the studied attributes and ES. Regarding the attributes related to the cocoa stand, both S- and F-cAFS seemed influenced by their previous land-use up until 15 and 30 years, respectively, after their establishment. With respect to soil quality, nutrient cycling and carbon storage, only S-cAFS could be significantly distinguished from their past land-use, after 15 to 30 years