The Benefit of Enhanced Contractility in the Infarct Borderzone: A Virtual Experiment

Objectives: Contractile function in the normally perfused infarct borderzone (BZ) is depressed. However, the impact of reduced BZ contractility on left ventricular (LV) pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function. Methods: From a previously reported study, magnetic resonance imaging (MRI) images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal-specific finite element (FE) models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling’s law) and stress in the fiber, cross fiber, and circumferential directions were calculated. Animal-specific FE models were performed for three cases: (a) impaired BZ contractility (INJURED); (b) BZ-contractility fully restored (100% BZ IMPROVEMENT); or (c) BZ-contractility partially restored (50% BZ IMPROVEMENT). Results: 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36 and 26%) increase in stroke volume at LVPED = 20 mmHg (8.0 ml, p < 0.001). Moreover, there were a leftward shift in the end-systolic pressure volume relationship, resulting in a 7 and 5% increase in LVPES at 110 mmHg (7.7 ml, p < 0.005). It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. Conclusion: Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed

Radial turbine sound and noise characterisation with acoustic transfer matrices by means of fast one-dimensional models

This is the author's version of a work that was accepted for publication in International Journal of Engine Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published as https://doi.org/10.1177/1468087419889429.[EN] Estimating correctly the turbine acoustics can be valuable during the engine design stage; in fact, it can lead to a more optimised design of the silencer and aftertreatment, as well as to better prediction of the scavenging effects. However, obtaining the sound and noise emissions of radial turbocharger turbines with low computational costs can be challenging. To consider these effects in a time-efficient manner, the acoustic response of single-entry radial turbines can be characterised by means of acoustic transfer matrices that change with the operating conditions. Exploiting the different time-scales of the acoustic phenomena and the change in the operating point of the turbine, lookup tables of acoustic transfer matrices can be computed. Then, the obtained characterisation can be used in mean-value engine models. This article presents a method for generating these lookup tables by means of fast one-dimensional simulations of thoroughly validated fidelity, in terms of both acoustics and extrapolation capabilities. Due to the inherent behaviour of radial turbines, the number of computations needed to fill the lookup tables is relatively small, so the method can be used as a simple preprocessing phase before mean-value simulation campaigns.Torregrosa, AJ.; García-Cuevas González, LM.; Inhestern, LB.; Soler-Blanco, P. (2021). Radial turbine sound and noise characterisation with acoustic transfer matrices by means of fast one-dimensional models. International Journal of Engine Research. 22(4):1312-1328. https://doi.org/10.1177/1468087419889429S13121328224Broatch, A., Galindo, J., Navarro, R., & García-Tíscar, J. (2014). Methodology for experimental validation of a CFD model for predicting noise generation in centrifugal compressors. International Journal of Heat and Fluid Flow, 50, 134-144. doi:10.1016/j.ijheatfluidflow.2014.06.006Galindo, J., Tiseira, A., Navarro, R., Tarí, D., & Meano, C. M. (2017). Effect of the inlet geometry on performance, surge margin and noise emission of an automotive turbocharger compressor. Applied Thermal Engineering, 110, 875-882. doi:10.1016/j.applthermaleng.2016.08.099Peat, K. S., Torregrosa, A. J., Broatch, A., & Fernández, T. (2006). An investigation into the passive acoustic effect of the turbine in an automotive turbocharger. Journal of Sound and Vibration, 295(1-2), 60-75. doi:10.1016/j.jsv.2005.11.033Torregrosa, A., Galindo, J., Serrano, J. R., & Tiseira, A. (2009). A Procedure for the Unsteady Characterization of Turbochargers in Reciprocating Internal Combustion Engines. Fluid Machinery and Fluid Mechanics, 72-79. doi:10.1007/978-3-540-89749-1_10Torregrosa, A. J., Broatch, A., Navarro, R., & García-Tíscar, J. (2014). Acoustic characterization of automotive turbocompressors. International Journal of Engine Research, 16(1), 31-37. doi:10.1177/1468087414562866Broatch, A., Galindo, J., Navarro, R., García-Tíscar, J., Daglish, A., & Sharma, R. K. (2015). Simulations and measurements of automotive turbocharger compressor whoosh noise. Engineering Applications of Computational Fluid Mechanics, 9(1), 12-20. doi:10.1080/19942060.2015.1004788Broatch, A., Galindo, J., Navarro, R., & García-Tíscar, J. (2016). Numerical and experimental analysis of automotive turbocharger compressor aeroacoustics at different operating conditions. International Journal of Heat and Fluid Flow, 61, 245-255. doi:10.1016/j.ijheatfluidflow.2016.04.003Wallace, F. J., & Adgey, J. (1967). Paper 1: Theoretical Assessment of the Non-Steady Flow Performance of Inward Radial Flow Turbines. Proceedings of the Institution of Mechanical Engineers, Conference Proceedings, 182(8), 22-36. doi:10.1243/pime_conf_1967_182_211_02Piscaglia, F., Onorati, A., Marelli, S., & Capobianco, M. (2018). A detailed one-dimensional model to predict the unsteady behavior of turbocharger turbines for internal combustion engine applications. International Journal of Engine Research, 20(3), 327-349. doi:10.1177/1468087417752525Galindo, J., Fajardo, P., Navarro, R., & García-Cuevas, L. M. (2013). Characterization of a radial turbocharger turbine in pulsating flow by means of CFD and its application to engine modeling. Applied Energy, 103, 116-127. doi:10.1016/j.apenergy.2012.09.013Galindo, J., Tiseira, A., Fajardo, P., & García-Cuevas, L. M. (2014). Development and validation of a radial variable geometry turbine model for transient pulsating flow applications. Energy Conversion and Management, 85, 190-203. doi:10.1016/j.enconman.2014.05.072Avola, C., Copeland, C., Romagnoli, A., Burke, R., & Dimitriou, P. (2017). Attempt to correlate simulations and measurements of turbine performance under pulsating flows for automotive turbochargers. Proceedings of the Institution of Mechanical Engineers, Part D: Journal of Automobile Engineering, 233(2), 174-187. doi:10.1177/0954407017739123Galindo, J., Climent, H., Tiseira, A., & García-Cuevas, L. M. (2016). Effect of the numerical scheme resolution on quasi-2D simulation of an automotive radial turbine under highly pulsating flow. Journal of Computational and Applied Mathematics, 291, 112-126. doi:10.1016/j.cam.2015.02.025Serrano, J. R., Arnau, F. J., García-Cuevas, L. M., Dombrovsky, A., & Tartoussi, H. (2016). Development and validation of a radial turbine efficiency and mass flow model at design and off-design conditions. Energy Conversion and Management, 128, 281-293. doi:10.1016/j.enconman.2016.09.032Galindo, J., Navarro, R., García-Cuevas, L. M., Tarí, D., Tartoussi, H., & Guilain, S. (2018). A zonal approach for estimating pressure ratio at compressor extreme off-design conditions. International Journal of Engine Research, 20(4), 393-404. doi:10.1177/1468087418754899Payri, F., Olmeda, P., Arnau, F. J., Dombrovsky, A., & Smith, L. (2014). External heat losses in small turbochargers: Model and experiments. Energy, 71, 534-546. doi:10.1016/j.energy.2014.04.096Serrano, J. R., Olmeda, P., Arnau, F. J., Dombrovsky, A., & Smith, L. (2015). Turbocharger heat transfer and mechanical losses influence in predicting engines performance by using one-dimensional simulation codes. 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A model of turbocharger radial turbines appropriate to be used in zero- and one-dimensional gas dynamics codes for internal combustion engines modelling. Energy Conversion and Management, 49(12), 3729-3745. doi:10.1016/j.enconman.2008.06.031Serrano, J. R., Tiseira, A., García-Cuevas, L. M., Inhestern, L. B., & Tartoussi, H. (2017). Radial turbine performance measurement under extreme off-design conditions. Energy, 125, 72-84. doi:10.1016/j.energy.2017.02.118Welch, P. (1967). The use of fast Fourier transform for the estimation of power spectra: A method based on time averaging over short, modified periodograms. IEEE Transactions on Audio and Electroacoustics, 15(2), 70-73. doi:10.1109/tau.1967.1161901Serrano, J. R., Arnau, F. J., García-Cuevas, L. M., & Inhestern, L. B. (2019). An innovative losses model for efficiency map fitting of vaneless and variable vaned radial turbines extrapolating towards extreme off-design conditions. 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A mixed methods approach to evaluating community drug distributor performance in the control of neglected tropical diseases

BACKGROUND: Trusted literate, or semi-literate, community drug distributors (CDDs) are the primary implementers in integrated preventive chemotherapy (IPC) programmes for Neglected Tropical Disease (NTD) control. The CDDs are responsible for safely distributing drugs and for galvanising communities to repeatedly, often over many years, receive annual treatment, create and update treatment registers, monitor for side-effects and compile treatment coverage reports. These individuals are 'volunteers' for the programmes and do not receive remuneration for their annual work commitment. METHODS: A mixed methods approach, which included pictorial diaries to prospectively record CDD use of time, structured interviews and focus group discussions, was used to triangulate data on how 58 CDDs allocated their time towards their routine family activities and to NTD Programme activities in Uganda. The opportunity costs of CDD time were valued, performance assessed by determining the relationship between time and programme coverage, and CDD motivation for participating in the programme was explored. RESULTS: Key findings showed approximately 2.5 working weeks (range 0.6-11.4 working weeks) were spent on NTD Programme activities per year. The amount of time on NTD control activities significantly increased between the one and three deliveries that were required within an IPC campaign. CDD time spent on NTD Programme activities significantly reduced time available for subsistence and income generating engagements. As CDDs took more time to complete NTD Programme activities, their treatment performance, in terms of validated coverage, significantly decreased. Motivation for the programme was reported as low and CDDs felt undervalued. CONCLUSIONS: CDDs contribute a considerable amount of opportunity cost to the overall economic cost of the NTD Programme in Uganda due to the commitment of their time. Nevertheless, programme coverage of at least 75 %, as required by the World Health Organisation, is not being achieved and vulnerable individuals may not have access to treatment as a consequence of sub-optimal performance by the CDDs due to workload and programmatic factors

Mio-Pliocene Faunal Exchanges and African Biogeography: The Record of Fossil Bovids

The development of the Ethiopian biogeographic realm since the late Miocene is here explored with the presentation and review of fossil evidence from eastern Africa. Prostrepsiceros cf. vinayaki and an unknown species of possible caprin affinity are described from the hominid-bearing Asa Koma and Kuseralee Members (∼5.7 and ∼5.2 Ma) of the Middle Awash, Ethiopia. The Middle Awash Prostrepsiceros cf. vinayaki constitutes the first record of this taxon from Africa, previously known from the Siwaliks and Arabia. The possible caprin joins a number of isolated records of caprin or caprin-like taxa recorded, but poorly understood, from the late Neogene of Africa. The identification of these two taxa from the Middle Awash prompts an overdue review of fossil bovids from the sub-Saharan African record that demonstrate Eurasian affinities, including the reduncin Kobus porrecticornis, and species of Tragoportax. The fossil bovid record provides evidence for greater biological continuity between Africa and Eurasia in the late Miocene and earliest Pliocene than is found later in time. In contrast, the early Pliocene (after 5 Ma) saw the loss of any significant proportions of Eurasian-related taxa, and the continental dominance of African-endemic taxa and lineages, a pattern that continues today

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

&lt;p&gt;Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.&lt;/p&gt; &lt;p&gt;Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.&lt;/p&gt; &lt;p&gt;Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.&lt;/p&gt; &lt;p&gt;Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.&lt;/p&gt

“Clinical features of women with gout arthritis.” A systematic review

Clinically, gout is generally considered as a preferential male disease. However, it definitely does not occur exclusively in males. Our aim was to assess differences in the clinical features of gout arthritis between female and male patients. Five electronic databases were searched to identify relevant original studies published between 1977 and 2007. The included studies had to focus on adult patients with primary gout arthritis and on sex differences in clinical features. Two reviewers independently assessed eligibility and quality of the studies. Out of 355 articles, 14 were selected. Nine fulfilled the quality and score criteria. We identified the following sex differences in the clinical features of gout in women compared to men: the onset of gout occurs at a higher age, more comorbidity with hypertension or renal insufficiency, more often use of diuretics, less likely to drink alcohol, less often podagra but more often involvement of other joints, less frequent recurrent attacks. We found interesting sex differences regarding the clinical features of patients with gout arthritis. To diagnose gout in women, knowledge of these differences is essential, and more research is needed to understand and explain the differences , especially in the general population

Theoretical study on the electronic, structural, properties and reactivity of a series of mono-, di-, tri- and tetrachlorothiophenes as well as corresponding radical cation forms as monomers for conducting polymers

In this paper, electrical and structural properties of mono-, di-, tri- and tetrachlorothiophenes and their radical cations have been studied using the density functional theory and B3LYP method with 6-311++G** basis set. The effects of the number and position of the substituent of chlorine atoms on the properties of the thiophene ring for all chlorothiophenes and their radical cations have been studied. Vibrational frequencies, nuclear chemical shielding constants, spin-density distribution, size and direction of dipole moment vector, ionization potential, electric polarizabilities and NICS values of these compounds have been calculated as well. The analysis of these data showed that double bonds in 3-chlorothiophene are more delocalized and it is the best possible candidate monomer among all chlorothiophenes for the synthesis of corresponding conducting polymers with modified characteristics

Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT

Background The quality of care for people with dementia in care homes is of concern. Interventions that can improve care outcomes are required. Objective To investigate the clinical effectiveness and cost-effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation and improving care outcomes for people living with dementia in care homes, versus usual care. Design A pragmatic, cluster randomised controlled trial with an open-cohort design, follow-up at 6 and 16 months, integrated cost-effectiveness analysis and process evaluation. Clusters were not blinded to allocation. The primary end point was completed by staff proxy and independent assessors. Setting Stratified randomisation of 50 care homes to the intervention and control groups on a 3 : 2 ratio by type, size, staff exposure to dementia training and recruiting hub. Participants Fifty care homes were randomised (intervention, n = 31; control, n = 19), with 726 residents recruited at baseline and a further 261 recruited after 16 months. Care homes were eligible if they recruited a minimum of 10 residents, were not subject to improvement notices, had not used DCM in the previous 18 months and were not participating in conflicting research. Residents were eligible if they lived there permanently, had a formal diagnosis of dementia or a score of 4+ on the Functional Assessment Staging Test of Alzheimer’s Disease, were proficient in English and were not terminally ill or permanently cared for in bed. All homes were audited on the delivery of dementia and person-centred care awareness training. Those not reaching a minimum standard were provided training ahead of randomisation. Eighteen homes took part in the process evaluation. Intervention Two staff members from each intervention home were trained to use DCM and were asked to carry out three DCM cycles; the first was supported by an external expert. Main outcome measures The primary outcome was agitation (Cohen-Mansfield Agitation Inventory), measured at 16 months. Secondary outcomes included resident behaviours and quality of life. Results There were 675 residents in the final analysis (intervention, n = 388; control, n = 287). There was no evidence of a difference in agitation levels between the treatment arms. The adjusted mean difference in Cohen-Mansfield Agitation Inventory score was –2.11 points, being lower in the intervention group than in the control (95% confidence interval –4.66 to 0.44; p = 0.104; adjusted intracluster correlation coefficient: control = 0, intervention = 0.001). The sensitivity analyses results supported the primary analysis. No differences were detected in any of the secondary outcomes. The health economic analyses indicated that DCM was not cost-effective. Intervention adherence was problematic; only 26% of homes completed more than their first DCM cycle. Impacts, barriers to and facilitators of DCM implementation were identified. Limitations The primary completion of resident outcomes was by staff proxy, owing to self-report difficulties for residents with advanced dementia. Clusters were not blinded to allocation, although supportive analyses suggested that any reporting bias was not clinically important. Conclusions There was no benefit of DCM over control for any outcomes. The implementation of DCM by care home staff was suboptimal compared with the protocol in the majority of homes. Future work Alternative models of DCM implementation should be considered that do not rely solely on leadership by care home staff. Trial registration Current Controlled Trials ISRCTN82288852. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 16. See the NIHR Journals Library website for further project information

Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress

Hsp70 is a highly conserved molecular chaperone critical for the folding of new and denatured proteins. While traditional models state that cells respond to stress by upregulating inducible HSPs, this response is relatively slow and is limited by transcriptional and translational machinery. Recent studies have identified a number of post-translational modifications (PTMs) on Hsp70 that act to fine-tune its function. We utilized mass spectrometry to determine whether yeast Hsp70 (Ssa1) is differentially modified upon heat shock. We uncovered four lysine residues on Ssa1, K86, K185, K354 and K562 that are deacetylated in response to heat shock. Mutation of these sites cause a substantial remodeling of the Hsp70 interaction network of co-chaperone partners and client proteins while preserving essential chaperone function. Acetylation/deacetylation at these residues alter expression of other heat-shock induced chaperones as well as directly influencing Hsf1 activity. Taken together our data suggest that cells may have the ability to respond to heat stress quickly though Hsp70 deacetylation, followed by a slower, more traditional transcriptional response