Postoperative analgesia for Enhanced recovery in Joint replacement: Audit of a new electronic prescribing order set

Enhanced recovery in joint replacement has been shown to reduce length of inpatient stay, reduce re-admission rates, and can improve early functional recovery. Postoperative analgesia is an important component of the group of interventions required to form a holistic enhanced recovery protocol. The introduction of electronic prescribing provides the opportunity to introduce some standardisation, where clinically appropriate, in the prescription of an evidence based postoperative analgesia protocol. Enhanced recovery following joint replacement has been used at this institution since 2011. An order set for the postoperative analgesia protocol was introduced to the in house electronic prescribing system in August 2014 (JAC Medicines Management; JAC Computer Services Ltd., Basildon, UK). An audit was performed to follow the effect of the new system on compliance with the postoperative analgesia guidelines. Improvements were seen following introduction of the electronic prescribing protocol in all criteria of the guideline with a demonstrated improvement in overall compliance from 0% to 35% in the first loop, with subsequent audit showing further improvement to 59% compliance. Use of an embedded order set within an electronic prescribing system has demonstrated improved compliance with an enhanced recovery protocol. This ensures that the correct evidence based protocol is available to guide the junior clinician at the point of care, when the medication is being prescribed

Investigating controls on salt movement in extensional settings using finite-element modelling

Salt structures present numerous challenges for targeting reservoirs. Salt movement within the subsurface can follow complex pathways, producing deformation patterns in surrounding strata which are often difficult to decipher. Consequently, the relative role of key salt-flow drivers and geological sensitivities on salt-structure evolution are often poorly understood. To address this, we have developed 2D geomechanical models using the finite-element method to simulate salt diapir and pillow development in two extensional tectonic settings. We conducted model sensitivity analyses to examine the influence of geological parameters on field-scale salt structures and their corresponding deformation pattern. Modelled diapirs developing in thin-skinned extensional settings closely resemble published analogue experiments; however, active and passive stages of diapir growth are seldom or never reached, respectively, thus challenging existing ideas that diapir evolution is dominated by passive growth. In all modelled cases, highly strained domains bound the diapir flanks where extensive small-scale faulting and fracturing can be expected. Asymmetrical diapirs are prone to flank collapse and are observed in models with fast extension or sedimentation rates, thin roof sections or salt layers, or initially short or triangular-shaped diapirs. In modelled thick-skinned extensional settings, salt pillows and suprasalt overburden faults can be laterally offset (decoupled) from a reactivating basement fault. This decoupling increases with increased salt-layer thickness, overburden thickness, sedimentation rate and fault angle, and decreased fault slip rates. Contrary to existing consensus, overburden grounding onto the basement fault scarp does not appear to halt development of salt structures above the footwall basement block

The economic burden of cancer in the UK: a study of survivors treated with curative intent.

OBJECTIVE: We aim to describe the economic burden of UK cancer survivorship for breast, colorectal and prostate cancer patients treated with curative intent, 1 year post-diagnosis. METHODS: Patient-level data were collected over a 3-month period 12-15 months post-diagnosis to estimate the monthly societal costs incurred by cancer survivors. Self-reported resource utilisation data were obtained via the electronic Patient-reported Outcomes from Cancer Survivors system and included community-based health and social care, medications, travel costs and informal care. Hospital costs were retrieved through data linkage. Multivariate regression analysis was used to examine cost predictors. RESULTS: Overall, 298 patients were included in the analysis, including 136 breast cancer, 83 colorectal cancer and 79 prostate cancer patients. The average monthly societal cost was $US409 (95$US316-$US502) [mean: £260, 95$US279, 95%CI: $US207-$US351) [mean: £177, 95%CI: £131-£224], patients' out-of-pocket (OOP) expenses (mean: $US40, 95$US15-$US65) [mean: £25, 95$US110, 95%CI: $US57-$US162) [mean: £70, 95%CI: £38-£102]. The distribution of costs was skewed with a small number of patients incurring very high costs. Multivariate analyses showed higher societal costs for breast cancer patients. Significant predictors of OOP costs included age and socioeconomic deprivation. CONCLUSIONS: This study found the economic burden of cancer survivorship is unevenly distributed in the population and that cancer survivors may still incur substantial costs over 1 year post-diagnosis. In addition, this study illustrates the feasibility of using an innovative online data collection platform to collect patient-reported resource utilisation information. Copyright © 2015 John Wiley & Sons, Ltd

Template coexistence in prebiotic vesicle models

The coexistence of distinct templates is a common feature of the diverse proposals advanced to resolve the information crisis of prebiotic evolution. However, achieving robust template coexistence turned out to be such a difficult demand that only a class of models, the so-called package models, seems to have met it so far. Here we apply Wright's Island formulation of group selection to study the conditions for the coexistence of two distinct template types confined in packages (vesicles) of finite capacity. In particular, we show how selection acting at the level of the vesicles can neutralize the pressures towards the fixation of any one of the template types (random drift) and of the type with higher replication rate (deterministic competition). We give emphasis to the role of the distinct generation times of templates and vesicles as yet another obstacle to coexistence.Comment: 7 pages, 8 figure

Identification of the major proteins of an immune modulating fraction from adult Fasciola hepatica released by Nonidet P40

Fasciola hepatica NP-40 released antigens (FhTeg) exhibit potent Th1 immunosuppressive properties in vitro and in vivo. However, the protein composition of this active fraction, responsible for Th1 immune modulatory activity, has yet to be resolved. Therefore, FhTeg, a Nonidet P-40 extract, was subjected to a proteomic analysis in order to identify individual protein components. This was performed using an in house F. hepatica EST database following 2D electrophoresis combined with de novo sequencing based mass spectrometry. The identified proteins, a mixture of excretory/secretory and membrane-associated proteins, are associated with stress response and chaperoning, energy metabolism and cytoskeletal components. The immune modulatory properties of these identified protein(s) is discussed and HSP70 from F. hepatica is highlighted as a potential host immune modulator for future study

Evolutionary game dynamics in phenotype space

Evolutionary dynamics can be studied in well-mixed or structured populations. Population structure typically arises from the heterogeneous distribution of individuals in physical space or on social networks. Here we introduce a new type of space to evolutionary game dynamics: phenotype space. The population is well-mixed in the sense that everyone is equally likely to interact with everyone else, but the behavioral strategies depend on distance in phenotype space. Individuals might behave differently towards those who look similar or dissimilar. Individuals mutate to nearby phenotypes. We study the `phenotypic space walk' of populations. We present analytic calculations that bring together ideas from coalescence theory and evolutionary game dynamics. As a particular example, we investigate the evolution of cooperation in phenotype space. We obtain a precise condition for natural selection to favor cooperators over defectors: for a one-dimensional phenotype space and large population size the critical benefit-to-cost ratio is given by b/c=1+2/sqrt{3}. We derive the fundamental condition for any evolutionary game and explore higher dimensional phenotype spaces.Comment: version 2: minor changes; equivalent to final published versio

The edge of neutral evolution in social dilemmas

The functioning of animal as well as human societies fundamentally relies on cooperation. Yet, defection is often favorable for the selfish individual, and social dilemmas arise. Selection by individuals' fitness, usually the basic driving force of evolution, quickly eliminates cooperators. However, evolution is also governed by fluctuations that can be of greater importance than fitness differences, and can render evolution effectively neutral. Here, we investigate the effects of selection versus fluctuations in social dilemmas. By studying the mean extinction times of cooperators and defectors, a variable sensitive to fluctuations, we are able to identify and quantify an emerging 'edge of neutral evolution' that delineates regimes of neutral and Darwinian evolution. Our results reveal that cooperation is significantly maintained in the neutral regimes. In contrast, the classical predictions of evolutionary game theory, where defectors beat cooperators, are recovered in the Darwinian regimes. Our studies demonstrate that fluctuations can provide a surprisingly simple way to partly resolve social dilemmas. Our methods are generally applicable to estimate the role of random drift in evolutionary dynamics.Comment: 17 pages, 4 figure

Proteomic analysis of embryonic Fasciola hepatica: Characterization and antigenic potential of a developmentally regulated heat shock protein

Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. We report the first post-genomic investigation of cellular proteins expressed by embryonic F. hepatica via two-dimensional electrophoresis, image analysis and tandem mass spectrometry. Antioxidant proteins and protein chaperones are prominently expressed by embryonic F. hepatica. Molecular differences between the egg and other characterized F. hepatica lifecycle stages were noted. Furthermore, proteins expressed within liver fluke eggs differ to those isolated from the well-characterized eggs of the human blood flatworm Schistosoma mansoni were revealed. Plasticity in expression of major proteins, particularly a prominently expressed 65 kDa protein cluster was seen between natural populations of embryonating F. hepatica eggs suggesting that liver fluke embryogenisis is a plastic process. Immunoblotting revealed that the abundant 65 kDa protein cluster is recognised by infection sera from three F. hepatica challenged host species. Mass spectrometry and BLAST analyses demonstrated that the 65 kDa antigen shows homology to egg antigens of other flatworm parasites, and is represented in a F. hepatica EST database constructed from adult fluke transcripts. EST clones encoding the egg antigen were re-sequenced, predicting two forms of the protein. Four clones predict a 312 aa polypeptide, three clones encode a putative 110 amino acid extension at the N-terminus which may be involved in protein secretion, although this extension was not expressed by natively extracted proteins. Consistent expression of alpha crystallin domains confirmed the protein to be a member of the alpha crystallin containing small heat shock protein (AC/sHSP) superfamily. AC/sHSPs are ubiquitous in nature, however, this is the first time a member of this protein superfamily has been described from F. hepatica. The antigenic AC/sHSP was named Fh-HSP35α based on predictions of molecular weight. Production of recombinant Fh-HSP35α reveals considerable mass discrepancy between native and recombinant proteins, although descriptions of other characterized flatworm AC/sHSPs, suggest that the native form is a dimer. Immunoblot analyses confirm that the recombinant protein is recognised by F. hepatica challenged hosts, but does not react with sera from non-infected animals. We discuss the potential of recombinant Fh-HSP35α as an egg-based diagnostic marker for liver fluke infection