bluuebunny/crossref_metadata_2025_split huggingface dataset:
The calcium–frequency response in the rat ventricular myocyte: an experimental and modelling study
Authors: Gattoni Sara , Røe Åsmund Treu , Frisk Michael , Louch William E. , Niederer Steven A. , Smith Nicolas P. 
Published: February 2016

Key points
In the majority of species, including humans, increased heart rate increases cardiac contractility. This change is known as the force–frequency response (FFR). The majority of mammals have a positive force–frequency relationship (FFR). In rat the FFR is controversial.
We derive a species‐ and temperature‐specific data‐driven model of the rat ventricular myocyte.
As a measure of the FFR, we test the effects of changes in frequency and extracellular calcium on the calcium–frequency response (CFR) in our model and three altered models.
The results show a biphasic peak calcium–frequency response, due to biphasic behaviour of the ryanodine receptor and the combined effect of the rapid calmodulin buffer and the frequency‐dependent increase in diastolic calcium.
Alterations to the model reveal that inclusion of Ca2+/calmodulin‐dependent protein kinase II (CAMKII)‐mediated L‐type channel and transient outward K+ current activity enhances the positive magnitude calcium–frequency response, and the absence of CAMKII‐mediated increase in activity of the sarco/endoplasmic reticulum Ca2+‐ATPase induces a negative magnitude calcium–frequency response.
AbstractAn increase in heart rate affects the strength of cardiac contraction by altering the Ca2+ transient as a response to physiological demands. This is described by the force–frequency response (FFR), a change in developed force with pacing frequency. The majority of mammals, including humans, have a positive FFR, and cardiac contraction strength increases with heart rate. However, the rat and mouse are exceptions, with the majority of studies reporting a negative FFR, while others report either a biphasic or a positive FFR. Understanding the differences in the FFR between humans and rats is fundamental to interpreting rat‐based experimental findings in the context of human physiology. We have developed a novel model of rat ventricular electrophysiology and calcium dynamics, derived predominantly from experimental data recorded under physiological conditions. As a measure of FFR, we tested the effects of changes in stimulation frequency and extracellular calcium concentration on the simulated Ca2+ transient characteristics and showed a biphasic peak calcium–frequency relationship, consistent with recent observations of a shift from negative to positive FFR when approaching the rat physiological frequency range. We tested the hypotheses that (1) inhibition of Ca2+/calmodulin‐dependent protein kinase II (CAMKII)‐mediated increase in sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) activity, (2) CAMKII modulation of SERCA, L‐type channel and transient outward K+ current activity and (3) Na+/K+ pump dynamics play a significant role in the rat FFR. The results reveal a major role for CAMKII modulation of SERCA in the peak Ca2+–frequency response, driven most significantly by the cytosolic calcium buffering system and changes in diastolic Ca2+.
TRICO II Core Inventory Calculation and its Radiological Consequence Analyses
Authors: Muswema J. L. , Ekoko G. B. , Lobo J. K.-K. , Lukanda V. M. , Boafo E. K. 
Published: February 2016

Two severe accident scenarios are investigated in this paper as they have never been considered previously in the safety analysis report (SAR) of the Congo TRIGA Mark II research reactor (TRICO II) in Kinshasa, the Democratic Republic of Congo. The source term is derived from the reactor core after two postulated accidents: (1) a large plane crash with total destruction of the reactor building and (2) full damage of one fuel element while the reactor building remains intact. Total effective dose (TED), after core inventory, and dose profiles to human organs are derived to assess the operational safety of the reactor. Results from the study will be used to upgrade the current SAR of the reactor as the reactor safety and licensing concepts are changing over the years; the knowledge and lessons learned from the past experience are being updated accordingly with the available data. TEDs to workers of the facility show that higher values are obtained at areas near the source term at the time of the plane crash accident, which dies out as quickly as the plume is carried away following predominant meteorological conditions at the site. The situation with one fuel element totally damaged poses no threat as far as radiation protection is concerned and reveals a maximum TED of 1.30×10−7  mSv at 100 m from the reactor core. This shows that the operation of this type of research reactor is reliable and safe.
Oxidation Behavior of Austenitic Stainless Steel 316L and 310S in Air and Supercritical Water
Authors: Nezakat Majid , Akhiani Hamed , Penttilä Sami , Szpunar Jerzy 
Published: February 2016

In this study, we evaluated the oxidation resistance of austenitic stainless steels 316L and 310S in two different environments: air at 600°C and atmospheric pressure and supercritical water at 600°C and pressure of 25 MPa. Results indicated that both alloys showed good oxidation resistance in air by producing a protective oxide layer on their surface. In addition, alloy 310S exhibited lower weight gain during air oxidation compared to alloy 316L due to its higher content of chromium and nickel. Oxidation of alloy 310S in supercritical water was much lower than that of alloy 316L because of the formation of a protective layer of Mn2CrO4 spinel on the surface. No protective scale was formed on the surface of the alloy 316L, as magnetite (Fe3O4) and iron-chromium spinel (FeCr2O4) were the product of oxidation in supercritical water.
Validity of Power Settings of the Wahoo KICKR Power Trainer
Authors: Zadow Emma K. , Kitic Cecilia M. , Wu Sam S.X. , Smith Stuart T. , Fell James W. 
Published: February 2016

Purpose:To assess the validity of power output settings of the Wahoo KICKR Power Trainer (KICKR) using a dynamic calibration rig (CALRIG) over a range of power outputs and cadences.
Methods:Using the KICKR to set power outputs, powers of 100–999 W were assessed at cadences (controlled by the CALRIG) of 80, 90, 100, 110, and 120 rpm.
Results:The KICKR displayed accurate measurements of power of 250–700 W at cadences of 80–120 rpm with a bias of –1.1% (95% limits of agreement [LoA] –3.6% to 1.4%). A larger mean bias in power was observed across the full range of power tested, 100–999 W (4.2%, 95% LoA –20.1% to 28.6%), due to larger biases of 100–200 and 750–999 W (4.5%, 95% LoA –2.3% to 11.3%, and 13.0%, 95% LoA –24.4% to 50.3%), respectively.
Conclusions:Compared with a CALRIG, the KICKR has acceptable accuracy reporting a small mean bias and narrow LoA in the measurement of power output of 250–700 W at cadences of 80–120 rpm. Caution should be applied by coaches and sports scientists when using the KICKR at power outputs of <200 W and >750 W due to the greater variability in recorded power.
Lasting Improvement of Patient-Reported Outcomes 6 Months After Patellofemoral Pain Rehabilitation
Authors: Hamstra-Wright Karrie L. , Aydemir Burcu , Earl-Boehm Jennifer , Bolgla Lori , Emery Carolyn , Ferber Reed 
Published: February 2016

Background/Objective:Hip- and knee-muscle-strengthening programs are effective in improving short-term patient-reported and disease-oriented outcomes in individuals with patellofemoral pain (PFP), but few to no data exist on moderate- to long-term postrehabilitative outcomes. The first purpose of the study was to assess differences in pain, function, strength, and core endurance in individuals with PFP before, after, and 6 mo after successful hip- or knee-muscle-strengthening rehabilitation. The second purpose was to prospectively follow these subjects for PFP recurrence at 6, 12, and 24 mo postrehabilitation.Methods:For 24 mo postrehabilitation, 157 physically active subjects with PFP who reported treatment success were followed. At 6 mo postrehabilitation, pain, function, hip and knee strength, and core endurance were measured. At 6, 12, 18, and 24 mo, PFP recurrence was measured via electronic surveys.Results:Sixty-eight subjects (43%) returned to the laboratory at 6 mo. Regardless of rehabilitation program, subjects experienced significant improvements in pain and function, strength, and core endurance pre- to postrehabilitation and maintained improvements in pain and function 6 mo postrehabilitation (Visual Analog Scale/Pain—pre 5.12 ± 1.33, post 1.28 ± 1.14, 6 mo 1.68 ± 2.16 cm, P < .05; Anterior Knee Pain Scale/Function—pre 76.38 ± 8.42, post 92.77 ± 7.36, 6 mo 90.27 ± 9.46 points, P < .05). Over the 24 mo postrehabilitation, 5.10% of subjects who responded to the surveys reported PFP recurrence.Conclusions:The findings support implementing a hip-or knee-muscle-strengthening program for the treatment of PFP. Both programs improve pain, function, strength, and core endurance in the short term with moderate- and long-term benefits of improved pain and function and low PFP recurrence.
Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus—the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial
Authors: Lundby-Christensen Louise , Tarnow Lise , Boesgaard Trine W , S Lund Søren , Wiinberg Niels , Perrild Hans , Krarup Thure , Snorgaard Ole , Gade-Rasmussen Birthe , Thorsteinsson Birger , Røder Michael , Mathiesen Elisabeth R , Jensen Tonny , Vestergaard Henrik , Hedetoft Christoffer , Breum Leif , Duun Elsebeth , Sneppen Simone B , Pedersen Oluf , Hemmingsen Bianca , Carstensen Bendix , Madsbad Sten , Gluud Christian , Wetterslev Jørn , Vaag Allan , Almdal Thomas P 
Published: February 2016

ObjectiveTo assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes.Design and settingInvestigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design conducted at eight hospitals in Denmark.Participants and interventions412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c≤7.0% (≤53 mmol/mol).OutcomesThe primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes.ResultsChange in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI −0.003 to 0.026), p=0.11). HbA1cwas more reduced in the metformin group (between-group difference −0.42% (95% CI −0.62% to −0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference −2.6 kg (95% CI −3.3 to −1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001).ConclusionsMetformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results.Trial registration numberNCT00657943; Results.
Benefit–risk assessment of HMG-CoA reductase inhibitors (statins): a discrete choice experiment
Authors: Wanishayakorn Tanatape , Sornlertlumvanich Korn , Ngorsuraches Surachat 
Published: February 2016

ObjectivesTo conduct the benefit–risk assessment of 3-hydroxy-3-methyl-glutaryl (HMG) coenzyme A reductase inhibitors (statins) using a discrete choice experiment, based on 3 major stakeholders’ perspectives including patients, experts and policymakers in Thailand.DesignA discrete choice experiment questionnaire survey in three stakeholders’ perspectives.SettingPublic hospitals in Thailand.ParticipantsA total of 353 policymakers, experts and patients.OutcomesStakeholders’ preferences for assessment criteria (stroke reduction, myocardial infarction reduction, myalgia and hepatotoxicity). Statins’ ranking and maximum acceptable risk in all perspectives were also calculated.ResultsFor any perspective, the most and least important criteria were the risk of hepatotoxicity and the benefit of myocardial infarction reduction, respectively. Patients and experts agreed on the order of importance for myalgia and stroke reduction, but policymakers had different order of importance in these criteria. Overall, results showed that the highest and lowest chances of being chosen were atorvastatin and rosuvastatin, respectively. Only patients’ ranking order was different from others. Maximum acceptable risk of hepatotoxicity was lower than that of myalgia, reflecting the greater concern of all perspectives to statin consequence on liver.ConclusionsThe results of benefit–risk assessment from every perspective were somewhat consistent. This study demonstrated the feasibility of applying a discrete choice experiment in the benefit–risk assessment of drugs and encouraged the engagement of multiple stakeholders in the decision-making process.
Development of an optimised 1:1 physiotherapy intervention post first-time lumbar discectomy: a mixed-methods study
Authors: Rushton A , White L , Heap A , Calvert M , Heneghan N , Goodwin P 
Published: February 2016

ObjectivesTo develop an optimised 1:1 physiotherapy intervention that reflects best practice, with flexibility to tailor management to individual patients, thereby ensuring patient-centred practice.DesignMixed-methods combining evidence synthesis, expert review and focus groups.SettingSecondary care involving 5 UK specialist spinal centres.ParticipantsA purposive panel of clinical experts from the 5 spinal centres, comprising spinal surgeons, inpatient and outpatient physiotherapists, provided expert review of the draft intervention. Purposive samples of patients (n=10) and physiotherapists (n=10) (inpatient/outpatient physiotherapists managing patients with lumbar discectomy) were invited to participate in the focus groups at 1 spinal centre.MethodsA draft intervention developed from 2 systematic reviews; a survey of current practice and research related to stratified care was circulated to the panel of clinical experts. Lead physiotherapists collaborated with physiotherapy and surgeon colleagues to provide feedback that informed the intervention presented at 2 focus groups investigating acceptability to patients and physiotherapists. The focus groups were facilitated by an experienced facilitator, recorded in written and tape-recorded forms by an observer. Tape recordings were transcribed verbatim. Data analysis, conducted by 2 independent researchers, employed an iterative and constant comparative process of (1) initial descriptive coding to identify categories and subsequent themes, and (2) deeper, interpretive coding and thematic analysis enabling concepts to emerge and overarching pattern codes to be identified.ResultsThe intervention reflected best available evidence and provided flexibility to ensure patient-centred care. The intervention comprised up to 8 sessions of 1:1 physiotherapy over 8 weeks, starting 4 weeks postsurgery. The intervention was acceptable to patients and physiotherapists.ConclusionsA rigorous process informed an optimised 1:1 physiotherapy intervention post-lumbar discectomy that reflects best practice. The developed intervention was agreed on by the 5 spinal centres for implementation in a randomised controlled trial to evaluate its effectiveness.
Serum erythropoietin and outcome after ischaemic stroke: a prospective study
Authors: Åberg N David , Stanne Tara M , Jood Katarina , Schiöler Linus , Blomstrand Christian , Andreasson Ulf , Blennow Kaj , Zetterberg Henrik , Isgaard Jörgen , Jern Christina , Svensson Johan 
Published: February 2016

ObjectivesErythropoietin (EPO), which is inversely associated with blood haemoglobin (Hb), exerts neuroprotective effects in experimental ischaemic stroke (IS). However, clinical treatment trials have so far been negative. Here, in patients with IS, we analysed whether serum EPO is associated with (1) initial stroke severity, (2) recovery and (3) functional outcome.DesignProspective. Controls available at baseline.SettingA Swedish hospital-initiated study with outpatient follow-up after 3 months.ParticipantsPatients (n=600; 64% males, mean age 56 years, controls n=600) were included from the Sahlgrenska Academy Study on IS (SAHLSIS).Primary and secondary outcome measuresIn addition to EPO and Hb, initial stroke severity was assessed by the Scandinavian Stroke Scale (SSS) and compared with SSS after 3 months (follow-up) as a measure of recovery. Functional outcome was evaluated using the modified Rankin Scale (mRS) at follow-up. Serum EPO and SSS were divided into quintiles in the multivariate regression analyses.ResultsSerum EPO was 21% and 31% higher than in controls at the acute phase of IS and follow-up, respectively. In patients, acute serum EPO was 19.5% higher in severe versus mild IS. The highest acute EPO quintile adjusted for sex, age and Hb was associated with worse stroke severity quintile (OR 1.70, 95% CI 1.00 to 2.87), better stroke recovery quintile (OR 1.93, CI 1.09 to 3.41) and unfavourable mRS 3–6 (OR 2.59, CI 1.15 to 5.80). However, the fourth quintile of EPO increase (from acute to follow-up) was associated with favourable mRS 0–2 (OR 3.42, CI 1.46 to 8.03). Only the last association withstood full adjustment.ConclusionsThe crude associations between EPO and worse stroke severity and outcome lost significance after multivariate modelling. However, in patients in whom EPO increased, the association with favourable outcome remained after adjustment for multiple covariates.
Effect of temperature and precipitation on salmonellosis cases in South-East Queensland, Australia: an observational study
Authors: Stephen Dimity Maree , Barnett Adrian Gerard 
Published: February 2016

ObjectiveFoodborne illnesses in Australia, including salmonellosis, are estimated to cost over $A1.25 billion annually. The weather has been identified as being influential on salmonellosis incidence, as cases increase during summer, however time series modelling of salmonellosis is challenging because outbreaks cause strong autocorrelation. This study assesses whether switching models is an improved method of estimating weather–salmonellosis associations.DesignWe analysed weather and salmonellosis in South-East Queensland between 2004 and 2013 using 2 common regression models and a switching model, each with 21-day lags for temperature and precipitation.ResultsThe switching model best fit the data, as judged by its substantial improvement in deviance information criterion over the regression models, less autocorrelated residuals and control of seasonality. The switching model estimated a 5°C increase in mean temperature and 10 mm precipitation were associated with increases in salmonellosis cases of 45.4% (95% CrI 40.4%, 50.5%) and 24.1% (95% CrI 17.0%, 31.6%), respectively.ConclusionsSwitching models improve on traditional time series models in quantifying weather–salmonellosis associations. A better understanding of how temperature and precipitation influence salmonellosis may identify where interventions can be made to lower the health and economic costs of salmonellosis.
Access to Transplantation and Transplant Outcome Measures (ATTOM): study protocol of a UK wide, in-depth, prospective cohort analysis
Authors: Oniscu Gabriel C , Ravanan Rommel , Wu Diana , Gibbons Andrea , Li Bernadette , Tomson Charles , Forsythe John L , Bradley Clare , Cairns John , Dudley Christopher , Watson Christopher J E , Bolton Eleanor M , Draper Heather , Robb Matthew , Bradbury Lisa , Pruthi Rishi , Metcalfe Wendy , Fogarty Damian , Roderick Paul , Bradley J Andrew 
Published: February 2016

IntroductionThere is significant intercentre variability in access to renal transplantation in the UK due to poorly understood factors. The overarching aims of this study are to improve equity of access to kidney and kidney–pancreas transplantation across the UK and to optimise organ allocation to maximise the benefit and cost-effectiveness of transplantation.Methods and analysis6844 patients aged 18–75 years starting dialysis and/or receiving a transplant together with matched patients active on the transplant list from all 72 UK renal units were recruited between November 2011 and March 2013 and will be followed for at least 3 years. The outcomes of interest include patient survival, access to the transplant list, receipt of a transplant, patient-reported outcome measures (PROMs) including quality of life, treatment satisfaction, well-being and health status on different forms of renal replacement therapy. Sociodemographic and clinical data were prospectively collected from case notes and from interviews with patients and local clinical teams. Qualitative process exploration with clinical staff will help identify unit-specific factors that influence access to renal transplantation. A health economic analysis will explore costs and outcomes associated with alternative approaches to organ allocation. The study will deliver: (1) an understanding of patient and unit-specific factors influencing access to renal transplantation in the UK, informing potential changes to practices and policies to optimise outcomes and reduce intercentre variability; (2) a patient-survival probability model to standardise access to the renal transplant list and (3) an understanding of PROMs and health economic impact of kidney and kidney–pancreas transplantation to inform the development of a more sophisticated and fairer organ allocation algorithm.Ethics and disseminationThe protocol has been independently peer reviewed by National Institute for Health Research (NIHR) and approved by the East of England Research Ethics Committee. The results will be published in peer-reviewed journals and presented at conferences.