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Perfusate Proteomes Provide Biological Insight Into Oxygenated Versus Standard Hypothermic Machine Perfusion in Kidney Transplantation
No full textNoObjective:
To provide mechanistic insight into key biological alterations in donation after circulatory death kidneys during continuous pefusion we performed mass spectrometry profiling of perfusate samples collected during a phase 3 randomized double-blind paired clinical trial of hypothermic machine perfusion with and without oxygen (COMPARE).
Background:
Despite the clinical benefits of novel perfusion technologies aiming to better preserve donor organs, biological processes that may be altered during perfusion have remained largely unexplored. The collection of serial perfusate samples during the COMPARE clinical trial provided a unique resource to study perfusate proteomic profiles, with the hypothesis that in-depth profiling may reveal biologically meaningful information on how donor kidneys benefit from this intervention.
Methods:
Multiplexed liquid chromatography-tandem mass spectrometry was used to obtain a proteome profile of 210 perfusate samples. Partial least squares discriminant analysis and multivariate analysis involving clinical and perfusion parameters were used to identify associations between profiles and clinical outcomes.
Results:
Identification and quantitation of 1716 proteins indicated that proteins released during perfusion originate from the kidney tissue and blood, with blood-based proteins being the majority. Data show that the overall hypothermic machine perfusion duration is associated with increasing levels of a subgroup of proteins. Notably, high-density lipoprotein and complement cascade proteins are associated with 12-month outcomes, and blood-derived proteins are enriched in the perfusate of kidneys that developed acute rejection.
Conclusions:
Perfusate profiling by mass spectrometry was informative and revealed proteomic changes that are biologically meaningful and, in part, explain the clinical observations of the COMPARE trial
Cryptocurrency Risk and Governance Challenges
No full textNoThis book provides an interdisciplinary critical perspective regarding risk, uncertainty, and governance challenges of cryptocurrencies. It considers the perspectives of several disciplines including accounting, cybersecurity, cyberlaw, economics, ethics, finance, financial regulation, shariah (Islamic) law and technology. Distinguished from other books on similar topic, our in-depth analysis and critical discourse on cryptocurrency risk categories are supplemented by research evidence gathered from surveys and interviews with stakeholders. The inclusion of an Islamic insight matters given mixed views at present regarding the permissibility of cryptocurrencies albeit some countries have imposed somewhat restricted function of cryptocurrencies for non-religious reasons. It is envisaged that this book will help enlighten stakeholders on this aspect of uncertainty and inspire fit and proper governance strategies for the public interest
Strategic workforce planning in health and social care - an international perspective: A scoping review
Get PDFYesEffective strategic workforce planning for integrated and co-ordinated health and social care is essential if future services are to be resourced such that skill mix, clinical practice and productivity meet population health and social care needs in timely, safe and accessible ways globally.
This review presents international literature to illustrate how strategic workforce planning in health and social care has been undertaken around the world with examples of planning frameworks, models and modelling approaches.
The databases Business Source Premier, CINAHL, Embase, Health Management Information Consortium, Medline and Scopus were searched for full texts, from 2005 to 2022, detailing empirical research, models or methodologies to explain how strategic workforce planning (with at least one-year horizon) in health and/or social care has been undertaken, yielding ultimately 101 included references.
The supply/demand of differentiated medical workforce was discussed in 25 references. Nursing and midwifery were characterised as undifferentiated labour, requiring urgent growth to meet demand. Unregistered workers were poorly represented as was the social care workforce. One reference considered planning for heath and social care workers. Workforce modelling was illustrated in 66 references with predilection for quantifiable projections. Increasingly needs-based approaches were called for to better consider demography and epidemiological impacts.
This review’s findings advocate for whole-system needs-based approaches that consider the ecology of co-produced health and social care workforce.Claire Sutton and Julie Prowse are seconded (from February 2022 to March 2023) to the Workforce Observatory, the University of Bradford, West Yorkshire. Their research posts at the Workforce Observatory are funded by Health Education England
Analytical Reliability-based Investment and Operation Model for Post-Failure Network Reconfiguration
Get PDFYesElectricity providers aims to deliver uninterrupted
electrical services to their customers at minimum cost while
providing a satisfactory quality service. Therefore, the power
system reliability is essential in power distribution network
planning, design, and operation. This paper proposes a novel
mathematical model to improve the reliability of reconfigurable
distribution networks via investing and operating tie-lines. While
the failure is being repaired, tie-lines allow the network operator
to transfer loads from failed zones to healthy zones. Constructing
new tie-lines could improve the network’s flexibility, aiming to
reduce the cost of expected energy not supplied (EENS). The
objective function of the proposed method is a trade-off between
the investment cost of tie-lines construction in the planning stage,
the cost of tie-lines operation (e.g., opening/closing), and the cost of
EENS in the operational stage. The model simultaneously
evaluates the best combination of investments and network
configuration for each contingency while considering network
constraints. A multistage mathematical model is developed as
mixed-integer linear programming (MILP) to overcome the
computational complexity and maintain solver traceability for
utility-scale realistic networks. The model can handle the network
reconfiguration (NR) considering N-x contingency analysis in the
operation stage while deciding the investment in tie-lines in the
planning stage. The optimal investment and operation in tie-lines,
according to numerical results, can reduce the cost of the
Distribution System (DS) while responding with contingencies by
51 to 70%
Analysing product attributes of refurbished laptops based on customer reviews and ratings: machine learning approach to circular consumption
No full textYesReviews and ratings of consumers towards a product impact consumer decision-making and their perceptions. Such information is key in measuring consumer satisfaction and net promoter scores. However, when the reviewed products are refurbished, consumer reviews become more important because information influences consumer behaviour and attitude toward looped products. This research explores the decision-influencing attributes of consumers while purchasing refurbished goods using quantitative and qualitative methods. Online after-sales 1986 laptop customers’ review and rating data in the public domain were analysed to reveal the decision-influencing attributes and their impact on potential consumers. The study envisions assisting the operations of sellers in the refurbished market by strengthening their businesses' value proposition and stimulating reverse logistics entrepreneurs to use the opportunity. Review data containing lifecycle valuation of old laptops induced feature extraction by machine learning applications. It is beneficial to sellers in the refurbished product segment. It provides information to strengthen their value proposition and is informative to entrepreneurs wanting to enter the segment. Based on the text analysis of consumer reviews, the study's results show that price, brand, design, performance, services, and utility influence consumers. The frequency analysis technique was used to extract attributes, followed by content analysis and feature selection using SHapley Additive exPlanations (SHAP) for exploring correlations between features and star ratings. Lastly, multinomial logistic regression was used to validate the generated model. The results show that brand, design, price, and utility are the most prominent attributes influencing consumers' decision-making with positive sentiments. In contrast, performance and services often generate neutral and negative sentiments
Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans
Get PDFYesLiving longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H2S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2S (NaGYY4137, 100 µM and 100 nM) and mtH2S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2S donor-mediated health span. Developmentally administered mtH2S (100 nM) improved life/health span vs. equivalent untargeted H2S doses. mtH2S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2S metabolism enzymes and FoxO/daf-16 prevented the positive health span effects of mtH2S, whereas DCAF11/wdr-23 - Nrf2/skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2S treatments. Adult mtH2S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6/elt-3 transcription factor circuit. H2S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2S is a potential healthy aging therapeutic.A.R.V., M.W., and T.E. were supported by the US Army Research Office (W911NF-19-1-0235). L.S., M.W., and T.E. were supported by the United Mitochondrial Disease Foundation (PI-19-0985). L.S. was also supported by the University of Exeter Jubilee Scholarship. M.C., N.J.S., and T.E. were supported by the UK Space Agency (ST/R005737/1). N.J.S. and T.E. were supported by BBSRC (BB/N015894/1). S.A.V. was supported by NASA (NNX15AL16G). N.J.S. was supported by grants from NASA [NSSC22K0250; NSSC22K0278] and acknowledges the support of the Osteopathic Heritage Foundation through funding for the Osteopathic Heritage Foundation Ralph S. Licklider, D.O., Research Endowment in the Heritage College of Osteopathic Medicine
Acquisition time in laser inter-satellite link under satellite vibrations
Get PDFYesPointing, acquisition, and tracking (PAT) is a major technical challenge of laser inter-satellite links (ISLs). For the fast establishment of laser link and the maximization of communication time, it is of importance to minimize the acquisition time. Satellite vibrations affect the PAT procedure adversely, and thus serve to increase the acquisition time. In this paper, we investigate through theoretical analysis the average acquisition time of laser ISLs in the presence of satellite vibrations. The analytic expression about the time taken from the beginning of spiral scan to the acquisition of the scan beam is provided in the presence of the pointing errors caused by vibrations. We also derive the optimum beam divergence angle for the acquisition time. The analyses are validated by Monte-Carlo computer simulations and a proof-of-concept experiment. The results show that the acquisition time can be minimized by adjusting the beam divergence angle adaptively to the link conditions.Grant-in-aid of Hanwha System
Specific transport of temozolomide does not override DNA repair-mediated chemoresistance
No full textYesTemozolomide (TMZ) a DNA alkylating agent, is the standard-of-care for brain tumors, such as glioblastoma multiforme (GBM). Although the physicochemical and pharmacokinetic properties of TMZ, such as chemical stability and the ability to cross the blood-brain barrier (BBB), have been questioned in the past, the acquired chemoresistance has been the main limiting factor of long-term clinical use of TMZ. In the present study, an L-type amino acid transporter 1 (LAT1)-utilizing prodrug of TMZ (TMZ-AA, 6) was prepared and studied for its cellular accumulation and cytotoxic properties in human squamous cell carcinoma, UT-SCC-28 and UT-SCC-42B cells, and TMZ-sensitive human glioma, U-87MG cells that expressed functional LAT1. TMZ-AA 6 accumulated more effectively than TMZ itself into those cancer cells that expressed LAT1 (UT-SCC-42B). However, this did not correlate with decreased viability of treated cells. Indeed, TMZ-AA 6, similarly to TMZ itself, required adjuvant inhibitor(s) of DNA-repair systems, O6-methylguanine-DNA methyl transferase (MGMT) and base excision repair (BER), as well as active DNA mismatch repair (MMR), for maximal growth inhibition. The present study shows that improving the delivery of this widely-used methylating agent is not the main barrier to improved chemotherapy, although utilizing a specific transporter overexpressed at the BBB or glioma cells can have targeting advantages. To obtain a more effective anticancer prodrug, the compound design focus should shift to altering the major DNA alkylation site or inhibiting DNA repair systems.Academy of Finland (grants 294227, 294229, 307057, 311939) and Yorkshire Cancer Research (grant number B210
Strategic workforce planning in health and social care - an international perspective: A scoping review
No full textYesEffective strategic workforce planning for integrated and co-ordinated health and social care is essential if future services are to be resourced such that skill mix, clinical practice and productivity meet population health and social care needs in timely, safe and accessible ways globally.
This review presents international literature to illustrate how strategic workforce planning in health and social care has been undertaken around the world with examples of planning frameworks, models and modelling approaches.
The databases Business Source Premier, CINAHL, Embase, Health Management Information Consortium, Medline and Scopus were searched for full texts, from 2005 to 2022, detailing empirical research, models or methodologies to explain how strategic workforce planning (with at least one-year horizon) in health and/or social care has been undertaken, yielding ultimately 101 included references.
The supply/demand of differentiated medical workforce was discussed in 25 references. Nursing and midwifery were characterised as undifferentiated labour, requiring urgent growth to meet demand. Unregistered workers were poorly represented as was the social care workforce. One reference considered planning for heath and social care workers. Workforce modelling was illustrated in 66 references with predilection for quantifiable projections. Increasingly needs-based approaches were called for to better consider demography and epidemiological impacts.
This review’s findings advocate for whole-system needs-based approaches that consider the ecology of co-produced health and social care workforce.Claire Sutton and Julie Prowse are seconded (from February 2022 to March 2023) to the Workforce Observatory, the University of Bradford, West Yorkshire. Their research posts at the Workforce Observatory are funded by Health Education England
A mixed-methods exploration of the potential use of pharmacogenomics with patients and healthcare professionals
No full textThis research explores the potential of pharmacogenomic (PGx)-guided care for older patients in secondary care. Using a mixed methods approach, the study demonstrates the efficacy of PGx-guided care for patients aged 65 and above, identifies behaviour change techniques for healthcare professionals to successfully adopt PGx-guided medicines optimisation, and paves the way for future implementation strategies. The research adopted a convergent parallel design, comprised of a systematic review, secondary data analysis of hospital admissions data for older patients and a qualitative interview study with older patients and healthcare professionals. This research provides a proof-of-concept for the use of PGx testing in medicines optimisation, leading to a potential decrease in hospitalisations. Notably, the research showed that 22% of medicines that older hospitalised patients use are PGx-influenced, and exposure to such medicines can help predict the length of hospital stay, unplanned admission and repeat hospitalisation, especially among highly frail patients. The study identified factors critical for implementing PGx, including knowledge, role identity, optimism, intentions, context, and capability beliefs. It highlighted prioritised change techniques such as information about health consequences, behaviour instruction, social support, and outcome goal review as essential guides for PGx champions driving implementation efforts in hospital settings. These findings significantly enhance the understanding of PGx's role in geriatric medicine, providing strategies to overcome potential barriers and suggesting necessary alterations to facilitate its implementation. The study underscores the potential of PGx-guided care to enhance medicines optimisation for older individuals, offering valuable insights to shape policy, practice, and direct future research in this field