165 research outputs found

    Evaluating enhanced recovery after surgery: time to cover new ground and discover the missing patient voice

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    Multicomponent peri-operative interventions offer to accelerate patient recovery and improve cost-effectiveness. The recent National Institute of Health Research-commissioned evidence synthesis review by Nunns et al. considers the effectiveness and cost-effectiveness of all types of multicomponent interventions for older adults undergoing elective inpatient surgery. Enhanced recovery programmes (ERPs) were the most commonly evaluated intervention. An association between ERPs and decreased length of stay was observed, whilst complication rates and time to recovery were static or sometimes reduced. Important areas which lack research in the context of ERPs are patient-reported outcome measures, patients with complex needs and assessment of factors pertaining to successful ERP implementation. The next generation of ERP studies should seek to develop our understanding in these key areas

    Precursor-Engineered Volatile Inks Enable Reliable Blade-Coating of Cesium-Formamidinium Perovskites Toward Fully Printed Solar Modules.

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    Reliable fabrication of large-area perovskite films with antisolvent-free printing techniques requires high-volatility solvents, such as 2-methoxyethanol (2ME), to formulate precursor inks. However, the fabrication of high-quality cesium-formamidinium (Cs-FA) perovskites has been hampered using volatile solvents due to their poor coordination with the perovskite precursors. Here, this issue is resolved by re-formulating a 2ME-based Cs0.05FA0.95PbI3 ink using pre-synthesized single crystals as the precursor instead of the conventional mixture of raw powders. The key to obtaining high-quality Cs-FA films lies in the removal of colloidal particles from the ink and hence the suppression of colloid-induced heterogeneous nucleation, which kinetically facilitates the growth of as-formed crystals toward larger grains and improved film crystallinity. Employing the precursor-engineered volatile ink in the vacuum-free, fully printing processing of solar cells (with carbon electrode), a power conversion efficiency (PCE) of 19.3%, a T80 (80% of initial PCE) of 1000 h in ISOS-L-2I (85 °C/1 Sun) aging test and a substantially reduced bill of materials are obtained. The reliable coating methodology ultimately enables the fabrication of carbon-electrode mini solar modules with a stabilized PCE of 16.2% (average 15.6%) representing the record value among the fully printed counterparts and a key milestone toward meeting the objectives for a scalable photovoltaic technology

    Multicomponent hospital-led interventions to reduce hospital stay for older adults following elective surgery: a systematic review

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    BackgroundElective older adult inpatient admissions are increasingly common. Older adults are at an elevated risk of adverse events in hospital, potentially increasing with lengthier hospital stay. Hospital-led organisational strategies may optimise hospital stay for elective older adult inpatients.ObjectivesTo evaluate the effectiveness and cost-effectiveness of hospital-led multicomponent interventions to reduce hospital stay for older adults undergoing elective hospital admissions.Data sourcesSeven bibliographic databases (MEDLINE, MEDLINE In-Process &amp; Other Non-Indexed Citations, EMBASE, Health Management Information Consortium, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine Database) were searched from inception to date of search (August 2017), alongside carrying out of web searches, citation searching, inspecting relevant reviews, consulting stakeholders and contacting authors. This search was duplicated, with an additional cost-filter, to identify cost-effectiveness evidence.Review methodsComparative studies were sought that evaluated the effectiveness or cost-effectiveness of relevant interventions in elective inpatients with a mean or median age of ≥ 60 years. Study selection, data extraction and quality assessment were completed independently by two reviewers. The main outcome was length of stay, but all outcomes were considered. Studies were sorted by procedure, intervention and outcome categories. Where possible, standardised mean differences or odds ratios were calculated. Meta-analysis was performed when multiple randomised controlled trials had the same intervention, treatment procedure, comparator and outcome. Findings were explored using narrative synthesis.FindingsA total of 218 articles were included, with 80 articles from 73 effectiveness studies (n = 26,365 patients) prioritised for synthesis, including 34 randomised controlled trials conducted outside the UK and 39 studies from the UK, of which 12 were randomised controlled trials. Fifteen studies included cost-effectiveness data. The evidence was dominated by enhanced recovery protocols and prehabilitation, implemented to improve recovery from either colorectal surgery or lower limb arthroplasty. Six other surgical categories and four other intervention types were identified. Meta-analysis found that enhanced recovery protocols were associated with 1.5 days’ reduction in hospital stay among patients undergoing colorectal surgery (Cohen’sd = –0.51, 95% confidence interval –0.78 to –0.24;p &lt; 0.001) and with 5 days’ reduction among those undergoing upper abdominal surgery (Cohen’sd = –1.04, 95% confidence interval –1.55 to –0.53;p &lt; 0.001). Evidence from the UK was not pooled (owing to mixed study designs), but it echoed findings from the international literature. Length of stay usually was reduced with intervention or was no different. Other clinical outcomes also improved or were no worse with intervention. Patient-reported outcomes were not frequently reported. Cost and cost-effectiveness evidence came from 15 highly heterogeneous studies and was less conclusive.LimitationsStudies were usually of moderate or weak quality. Some intervention or treatment types were under-reported or absent. The reporting of variance data often precluded secondary analysis.ConclusionsEnhanced recovery and prehabilitation interventions were associated with reduced hospital stay without detriment to other clinical outcomes, particularly for patients undergoing colorectal surgery, lower limb arthroplasty or upper abdominal surgery. The impacts on patient-reported outcomes, health-care costs or additional service use are not well known.Future workFurther studies evaluating of the effectiveness of new enhanced recovery pathways are not required in colorectal surgery or lower limb arthroplasty. However, the applicability of these pathways to other procedures is uncertain. Future studies should evaluate the implementation of interventions to reduce service variation, in-hospital patient-reported outcomes, impacts on health and social care service use, and longer-term patient-reported outcomes.Study registrationThis study is registered as PROSPERO CRD42017080637.FundingThe National Institute for Health Research Health Services and Delivery Research programme.</jats:sec

    Crack-Like Processes Governing the Onset of Frictional Slip

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    We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

    Evaluating enhanced recovery after surgery: time to cover new ground and discover the missing patient voice

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    AbstractMulticomponent peri-operative interventions offer to accelerate patient recovery and improve cost-effectiveness. The recent National Institute of Health Research-commissioned evidence synthesis review by Nunns et al. considers the effectiveness and cost-effectiveness of all types of multicomponent interventions for older adults undergoing elective inpatient surgery. Enhanced recovery programmes (ERPs) were the most commonly evaluated intervention. An association between ERPs and decreased length of stay was observed, whilst complication rates and time to recovery were static or sometimes reduced. Important areas which lack research in the context of ERPs are patient-reported outcome measures, patients with complex needs and assessment of factors pertaining to successful ERP implementation. The next generation of ERP studies should seek to develop our understanding in these key areas.</jats:p

    Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

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    The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

    Visual ecology of aphids – a critical review on the role of colours in host finding

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    We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms. Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region. We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours that are not likely to hold. Finally we also discuss the implications for developing and optimising strategies of aphid control and monitoring

    An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

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    Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways

    Palmitate-Induced β-Cell Dysfunction Is Associated with Excessive NO Production and Is Reversed by Thiazolidinedione-Mediated Inhibition of GPR40 Transduction Mechanisms

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    BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. CONCLUSION: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes
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