bluuebunny/crossref_metadata_2025_split huggingface dataset:
First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes—Chapter 4: pre‐clinical efficacy and complication data required to justify a clinical trial
Authors: Cooper David K.C. , Bottino Rita , Gianello Pierre , Graham Melanie , Hawthorne Wayne J. , Kirk Allan D. , Korsgren Olle , Park Chung‐Gyu , Weber Collin 
Published: February 2016

AbstractIn 2009, the International Xenotransplantation Association (IXA) published a consensus document that provided guidelines and “recommendations” (not regulations) for those contemplating clinical trials of porcine islet transplantation. These guidelines included the IXA's opinion on what constituted “rigorous pre‐clinical studies using the most relevant animal models” and were based on “non‐human primate testing.” We now report our discussion following a careful review of the 2009 guidelines as they relate to pre‐clinical testing. In summary, we do not believe there is a need to greatly modify the conclusions and recommendations of the original consensus document. Pre‐clinical studies should be sufficiently rigorous to provide optimism that a clinical trial is likely to be safe and has a realistic chance of success, but need not be so demanding that success might only be achieved by very prolonged experimentation, as this would not be in the interests of patients whose quality of life might benefit immensely from a successful islet xenotransplant. We believe these guidelines will be of benefit to both investigators planning a clinical trial and to institutions and regulatory authorities considering a proposal for a clinical trial. In addition, we suggest consideration should be given to establishing an IXA Clinical Trial Advisory Committee that would be available to advise (but not regulate) researchers considering initiating a clinical trial of xenotransplantation.
Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger
Authors: Rogers Mark W. , Mille Marie‐Laure 
Published: February 2016

AbstractPhysiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk.
image
Bassoon and piccolo regulate ubiquitination and link presynaptic molecular dynamics with activity‐regulated gene expression
Authors: Ivanova Daniela , Dirks Anika , Fejtova Anna 
Published: February 2016

AbstractRelease of neurotransmitter is executed by complex multiprotein machinery, which is assembled around the presynaptic cytomatrix at the active zone. One well‐established function of this proteinaceous scaffold is the spatial organization of synaptic vesicle cluster, the protein complexes that execute membrane fusion and compensatory endocytosis, and the transmembrane molecules important for alignment of pre‐ and postsynaptic structures. The presynaptic cytomatrix proteins function also in processes other than the formation of a static frame for assembly of the release apparatus and synaptic vesicle cycling. They actively contribute to the regulation of multiple steps in this process and are themselves an important subject of regulation during neuronal plasticity. We are only beginning to understand the mechanisms and signalling pathways controlling these regulations. They are mainly dependent on posttranslational modifications, including phosphorylation and small‐molecules conjugation, such as ubiquitination. Ubiquitination of presynaptic proteins might lead to their degradation by proteasomes, but evidence is growing that this modification also affects their function independently of their degradation. Signalling from presynapse to nucleus, which works on a much slower time scale and more globally, emerged as an important mechanism for persistent usage‐dependent and homeostatic neuronal plasticity. Recently, two new functions for the largest presynaptic scaffolding proteins bassoon and piccolo emerged. They were implied (1) in the regulation of specific protein ubiquitination and proteasome‐mediated proteolysis that potentially contributes to short‐term plasticity at the presynapse and (2) in the coupling of activity‐induced molecular rearrangements at the presynapse with reprogramming of expression of neuronal activity‐regulated genes.
image
Steady-State Radiolysis of Supercritical Water: Model Predictions and Validation
Authors: Subramanian V. , Joseph J. M. , Subramanian H. , Noël J. J. , Guzonas D. A. , Wren J. C. 
Published: February 2016

Chemical kinetic models are being developed for the γ-radiolysis of subcritical and supercritical water (SCW) to estimate the concentrations of radiolytically produced oxidants. Many of the physical properties of water change sharply at the critical point. These properties control the chemical stability and transport behavior of the ions and radicals generated by the radiolysis of SCW. The effects of changes in the solvent properties of water on primary radiolytic processes and the subsequent aqueous reaction kinetics can be quite complicated and are not yet well understood. The approach used in this paper was to adapt an existing liquid water radiolysis model (LRM) that has already been validated for lower temperatures and a water vapor radiolysis model (VRM) validated for higher temperatures, but for lower pressures, to calculate radiolysis product speciation under conditions approaching the supercritical state. The results were then extrapolated to the supercritical regime by doing critical analysis of the input parameters. This exercise found that the vapor-like and liquid-like models make similar predictions under some conditions. This paper presents and discusses the LRM and VRM predictions for the concentrations of molecular radiolysis products, H2, O2, and H2O2 at two different irradiation times, 1 s and 1 hr, as a function of temperature ranging from 25°C to 400°C. The model simulation results are then compared with the concentrations of H2, O2, and H2O2 measured as a function of γ-irradiation time at 250°C. Model predictions on the effect of H2 addition on the radiolysis product concentrations at 400°C are presented and compared with the experimental results from the Beloyarsk Nuclear Power Plant (NPP).
Reliability and Validity of a Novel Approach to Measure Hip Rotation
Authors: Aefsky Brett , Fleet Niles , Myers Heather , Butler Robert J. 
Published: February 2016

Context:Currently, hip-rotation range of motion (ROM) is clinically measured in an open kinetic chain in either seated or prone position using passive or active ROM. However, during activities of daily living and during sports participation the hip must be able to rotate in a loaded position, and there is no standard measurement for this.Objective:To determine if a novel method for measuring hip rotation in weight bearing will result in good to very good reliability as demonstrated by an intraclass correlation coefficient (ICC) of >.80 and to investigate if weight-bearing hip measurements will result in significantly reduced hip ROM compared with non-weight-bearing methods.Design:Repeated measures.Setting:Outpatient sports physical therapy clinic.Participants:20 healthy participants (10 men, 10 women) recruited for hip-rotation measurements.Methods:Three trials of both internal and external rotation were measured in sitting, prone, and weight bearing. Two therapists independently measured each participant on the same day. The participants returned the following day to repeat the same measurements with the same 2 therapists.Main Outcome Measures:Degrees of hip internal and external rotation measured in prone, sitting, and loaded positions.Results:In general, the measurement of hip ROM across the different conditions was reliable. The intrarater reliability was .67–.95, while interrater reliability was .59–.96. Interrater reliability was improved when values were averaged across the measures (.75–.97). ICCs for active loaded ROM were .67–.81, while interrater ICCs were .53–.87. In general, prone hip ROM was greater than supine and supine was greater than loaded.Conclusions:Loaded hip rotation can be measured in a clinical setting with moderate to good reliability. The rotation ROM of a loaded hip can be significantly decreased compared with unloaded motion.
Effectiveness of Stretching on Posterior Shoulder Tightness and Glenohumeral Internal-Rotation Deficit: A Systematic Review of Randomized Controlled Trials
Authors: Mine Koya , Nakayama Takashi , Milanese Steve , Grimmer Karen 
Published: February 2016

Context:Posterior shoulder tightness (PST) and glenohumeral internal-rotation deficit (GIRD) can contribute to shoulder pain suffered by athletes engaged in overhead sporting activities. Stretching is a common intervention to resolve PST and GIRD, but it has weak evidence of effectiveness to date.Objective:This systematic review aimed to collect and synthesize effectiveness data from English- and Japanese-language randomized controlled trials (RCTs) investigating stretching interventions for PST and GIRD.Evidence Acquisition:7 English databases and 3 Japanese databases were searched from inception until December 5, 2015. Only English- and Japanese-language RCTs were considered. Risk of bias in the included studies was assessed using the Physiotherapy Evidence Database scale. Data were synthesized qualitatively.Evidence Synthesis:Eight English-language and 2 Japanese-language papers of low to high quality were included. There was moderate evidence for positive immediate and short-term effects of cross-body stretch on PST and GIRD in asymptomatic young subjects. Moderate evidence was found to suggest that active sleeper stretch might not be more effective than no intervention to improve PST and GIRD in the short term.Conclusions:Cross-body stretch can be effective to improve PST and GIRD in asymptomatic young subjects immediately or in the short term. Further study with methodological rigor is necessary to investigate the long-term effectiveness of stretching interventions on PST and GIRD in symptomatic patients.
A Randomized Controlled Trial Comparing Rehabilitation Efficacy in Chronic Ankle Instability
Authors: Wright Cynthia J. , Linens Shelley W. , Cain Mary S. 
Published: February 2016

Context:There is minimal patient-oriented evidence regarding the effectiveness of interventions targeted to reduce symptoms associated with chronic ankle instability (CAI). In addition, clinicians aiming to prioritize care by implementing only the most effective components of a rehabilitative program have very little evidence on comparative efficacy.Objective:To assess the comparative efficacy of 2 common ankle rehabilitation techniques (wobble-board [WB] balance training and ankle strengthening using resistance tubing [RT]) using patient-oriented outcomes.Design:Randomized controlled trial.Setting:Laboratory.Patients:40 patients with CAI randomized into 2 treatment groups: RT and WB. CAI inclusion criteria included a history of an ankle sprain, recurrent “giving way,” and a Cumberland Ankle Instability Tool (CAIT) score ≤25.Interventions:Participants completed 5 clinician-oriented tests (foot-lift test, time-in-balance, Star Excursion Balance Test, figure-of-8 hop, and side-hop) and 5 patient-oriented questionnaires (CAIT, Foot and Ankle Ability Measure [FAAM], Activities of Daily Living [ADL] and FAAM Sport scale, Short-Form 36 [SF-36], and Global Rating of Function [GRF]). After baseline testing, participants completed 12 sessions over 4 wk of graduated WB or RT exercise, then repeated baseline tests.Main Outcome Measures:For each patient- and clinician-oriented test, separate 2 × 2 RMANOVAs analyzed differences between groups over time (alpha set at P = .05).Results:There was a significant interaction between group and time for the FAAM-ADL (P = .04). Specifically, the WB group improved postintervention (P < .001) whereas the RT group remained the same (P = .29). There were no other significant interactions or significant differences between groups (all P > .05). There were significant improvements postintervention for the CAIT, FAAM-Sport, GRF, SF-36, and all 5 clinician-oriented tests (all P < .001).Conclusions:A single-exercise 4-wk intervention can improve patient- and clinician-oriented outcomes in individuals with CAI. Limited evidence indicates that WB training was more effective than RT.Level of Evidence:Therapy, level 1b.
Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
Authors: Lundby-Christensen Louise , Vaag Allan , Tarnow Lise , Almdal Thomas P , Lund Søren S , Wetterslev Jørn , Gluud Christian , Boesgaard Trine W , 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 
Published: February 2016

ObjectiveTo assess the effect of 3 insulin analogue regimens on change 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 8 hospitals in Denmark.Participants and interventionsParticipants with type 2 diabetes (glycated haemoglobin (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m2) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c≤7.0% (≤53 mmol/mol).OutcomesPrimary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes.ResultsCarotid IMT change did not differ between groups (biphasic −0.009 mm (95% CI −0.022 to 0.004), aspart+detemir 0.000 mm (95% CI −0.013 to 0.013), detemir −0.012 mm (95% CI −0.025 to 0.000)). HbA1cwas more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ.ConclusionsCarotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.Trial registration numberNCT00657943.
Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH): protocol for a multicentric prospective observational study
Authors: Gupte Akshay , Padmapriyadarsini Chandrasekaran , Mave Vidya , Kadam Dileep , Suryavanshi Nishi , Shivakumar Shri Vijay Bala Yogendra , Kohli Rewa , Gupte Nikhil , Thiruvengadam Kannan , Kagal Anju , Meshram Sushant , Bharadwaj Renu , Khadse Sandhya , Ramachandran Geetha , Hanna Luke Elizabeth , Pradhan Neeta , Gomathy N S , DeLuca Andrea , Gupta Amita , Swaminathan Soumya 
Published: February 2016

IntroductionTuberculosis disease (TB) remains an important global health threat. An evidence-based response, tailored to local disease epidemiology in high-burden countries, is key to controlling the global TB epidemic. Reliable surrogate biomarkers that predict key active disease and latent TB infection outcomes are vital to advancing clinical research necessary to ‘End TB’. Well executed longitudinal studies strengthening local research capacity for addressing TB research priorities and advancing biomarker discovery are urgently needed.Methods and analysisThe Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH) study conducted in Byramjee Jeejeebhoy Government Medical College (BJGMC), Pune and National Institute for Research in Tuberculosis (NIRT), Chennai, India, will establish and maintain three prospective cohorts: (1) an Active TB Cohort comprising 800 adults with pulmonary TB, 200 adults with extrapulmonary TB and 200 children with TB; (2) a Household Contact Cohort of 3200 adults and children at risk of developing active disease; and (3) a Control Cohort consisting of 300 adults and 200 children with no known exposure to TB. Relevant clinical, sociodemographic and psychosocial data will be collected and a strategic specimen repository established at multiple time points over 24 months of follow-up to measure host and microbial factors associated with (1) TB treatment outcomes; (2) progression from infection to active TB disease; and (3)Mycobacterium tuberculosistransmission among Indian adults and children. We anticipate CTRIUMPH to serve as a research platform necessary to characterise some relevant aspects of the TB epidemic in India, generate evidence to inform local and global TB control strategies and support novel TB biomarker discovery.Ethics and disseminationThis study is approved by the Institutional Review Boards of NIRT, BJGMC and Johns Hopkins University, USA. Study results will be disseminated through peer-reviewed journals and research conferences.FundingNIH/DBT Indo-US Vaccine Action Programme and the Indian Council of Medical Research.
Human factors in prehospital research: lessons from the PARAMEDIC trial
Authors: Pocock Helen , Deakin Charles D , Quinn Tom , Perkins Gavin D , Horton Jessica , Gates Simon 
Published: February 2016

BackgroundThere is an urgent need to develop prehospital research capability in order to improve the care of patients presenting to emergency medical services (EMS). The Prehospital Randomised Assessment of a Mechanical compression Device In Cardiac arrest trial, a pragmatic cluster randomised trial evaluating the LUCAS-2 device, represents the largest randomised controlled trial conducted by UK ambulance services to date. The aim of this study was to identify and analyse factors that may influence paramedic attitudes to, and participation in, clinical trials.MethodsPersonal and organisational experience from this trial was assessed by feedback from a workshop attended by collaborators from participating EMS and a survey of EMS personnel participating in the trial. A work systems model was used to explain the impact of five interwoven themes—person, organisation, tasks, tools & technology and environment—on trial conduct including gathering of high-quality data.ResultsThe challenge of training a geographically diverse EMS workforce required development of multiple educational solutions. In order to operationalise the trial protocol, internal organisational relationships were perceived as essential. Staff perceptions of the normalisation of participation and ownership of the trial influenced protocol compliance rates. Undertaking research was considered less burdensome when additional tasks were minimised and more difficult when equipment was unavailable. The prehospital environment presents practical challenges for undertaking clinical trials, but our experience suggests these are not insurmountable and should not preclude conducting high-quality research in this setting.ConclusionsApplication of a human factors model to the implementation of a clinical trial protocol has improved understanding of the work system, which can inform the future conduct of clinical trials and foster a research culture within UK ambulance services.Trial registration numberISRCTN08233942.
Monitoring an effusive eruption at Piton de la Fournaise using radar and thermal infrared remote sensing data: insights into the October 2010 eruption and its lava flows
Authors: Bato M. G. , Froger J. L. , Harris A. J. L. , Villeneuve N. 
Published: February 2016

Abstract

Accurate and fast delivery of information about recent lava flows is important for near-real-time monitoring of eruptions. Here, we have characterized the October 2010 lava flow at Piton de la Fournaise using various InSAR datasets. We first produced a map of the area covered by the lava flow (i.e. Area
lava
=0.71–0.75 km
2
) using the coherence of two syn-eruptive interferograms. Then we analysed two post-eruptive InSAR datasets (i.e. monostatic and bistatic data). The monostatic database provided us simultaneously with the displacement rates, lava thickness, volume and volume flux. We found that the lava flow was subsiding and moving eastward at maximum rates of 13±0.3 and 4±0.2 cm a
−1
, respectively. Also, it had a mean thickness of
Z
mean
=5.85 m, Vol
DRE
=1.77±0.75×10
6
m
3
(1σ) and MOR=1.25±0.53 m
3
s
−1
. The bistatic database provided us only with the thickness and volume information (i.e.
Z
mean
=6.00 m, Vol
DRE
=1.83±0.65×10
6
m
3
and MOR=1.29±0.46 m
3
s
−1
). Finally, we used a thermal remote sensing technique to verify the InSAR-derived measurements. Results show that the monostatic and bistatic datasets were both well within the range for the DRE volume obtained from MODIS data (2.44–4.40×10
6
m
3
).

Supplementary material:

Tables A1 and A2 give satellite images used in this study. Table A3 gives the parameters used for the calculation of the effusion rates. The figures give the data processing of the post-eruptive radar images. These are available at
https://doi.org/10.6084/m9.figshare.c.2213563