bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China
Authors: Chen Jing Jing , Yuan Lin , Huang Zhen , Shi Nian Min , Zhao Yu Liang , Xia Sheng Li , Li Guo Hua , Li Rong Cheng , Li Yan Ping , Yang Shu Yuan , Xia Jie Lai 
Published: October 2016

IntroductionThe invasive pneumococcal diseases (IPDs) caused byStreptococcus pneumoniaepose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7).Methods and analysis1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12–15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed.Ethics and disseminationEthics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance.Trial registration numberNCT02736240.
Venous thromboembolism capture on electronic systems in obstetrics patients at St Thomas' Hospital
Authors: Ahmad Aminah Noor , Byrne Megan Leyla , Imambaccus Nazia , Hubert Dawid , Gateley Anna , Abdullahi Idle Salwa , Lloyd Jilly 
Published: October 2016

Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the UK. Therefore, timely VTE risk assessment is essential in all obstetrics patients. The Commissioning for Quality and Innovation (CQUIN) payment framework set a target for trusts to complete a VTE risk assessment within 24 hours of admission for 95% of patients. A combination of factors, including lack of integration between multiple IT systems, means that this CQUIN target is currently not being met for obstetric patients in the Hospital Birth Centre at Guys and St Thomas' NHS Trust.This project aims to increase staff awareness of this issue and educate them regarding the correct procedure for VTE assessment. Trialled methods included reminders at staff handovers, use of magnets on the patient whiteboard, posters and stickers displayed around the unit and a loyalty card scheme as incentive to complete assessments. Initial average completion rate was 20.7%, which increased to 67.5% after the first plan, do, study, act (PDSA) cycle with a slight drop to 65.7% after the second cycle. Completion rates increased to 92.3% on the last day of the third PDSA cycle. Although we did not reach the 95% target, we have raised awareness of the importance of recording VTE assessment on electronic systems, and hope we have created sustainable change.
Adrenodemedullation activates the Ca2+-dependent proteolysis in soleus muscles from rats exposed to cold
Authors: Manfredi L. H. , Lustrino D. , Machado J. , Silveira W. A. , Zanon N. M. , Navegantes L. C. , Kettelhut I. C. 
Published: October 2016

Previous studies have shown that catecholamines in vivo and in vitro inhibit the activity of Ca2+-dependent proteolysis in skeletal muscles under basal conditions. In the present study we sought to investigate the role of catecholamines in regulating the Ca2+-dependent proteolysis in soleus and extensor digitorum longus (EDL) muscles from rats acutely exposed to cold. Overall proteolysis, the activity of proteolytic systems, protein levels and gene expression of different components of the calpain system were investigated in rats submitted to adrenodemedullation (ADMX) and exposed to cold for 24 h. ADMX drastically reduced plasma epinephrine and promoted an additional increase in the overall proteolysis, which was already increased by cold exposure. The rise in the rate of protein degradation in soleus muscles from adrenodemedullated cold-exposed rats was caused by the high activity of the Ca2+-dependent proteolysis, which was associated with the generation of a 145-kDa cleaved α-fodrin fragment, a typical calpain substrate, and lower protein levels and mRNA expression of calpastatin, the endogenous calpain inhibitor. Unlike that observed for soleus muscles, the cold-induced muscle proteolysis in EDL was not affected by ADMX. In isolated soleus muscle, clenbuterol, a selective β2-adrenoceptor agonist, reduced the basal Ca2+-dependent proteolysis and completely abolished the activation of this pathway by the cholinergic agonist carbachol. These data suggest that catecholamines released from the adrenal medulla inhibit cold-induced protein breakdown in soleus, and this antiproteolytic effect on the Ca2+-dependent proteolytic system is apparently mediated through expression of calpastatin, which leads to suppression of calpain activation. NEW & NOTEWORTHY Although many effects of the sympathetic nervous system on muscle physiology are known, the role of catecholamines in skeletal muscle protein metabolism has been scarcely studied. We suggest that catecholamines released from adrenal medulla may be of particular importance for restraining the activation of the Ca2+-dependent proteolysis in soleus muscles during acute cold exposure. This finding helps us to understand the adaptive changes that occur in skeletal muscle protein metabolism during cold stress.
Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells
Authors: Schaletzki Yvonne , Kromrey Marie-Luise , Bröderdorf Susanne , Hammer Elke , Grube Markus , Hagen Paul , Sucic Sonja , Freissmuth Michael , Völker Uwe , Greinacher Andreas , Rauch Bernhard H. , Kroemer Heyo K. , Jedlitschky Gabriele 
Published: October 2016

SummaryThe multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit β3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knockdown of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leuk aemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.Supplementary Material to this article is available at www.thrombosis-online.com.
A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome
Authors: Pourdjabbar Ali , Hibbert Benjamin , Chong Aun-Yeong , Le May Michel R. , Labinaz Marino , Simard Trevor , Ramirez F. Daniel , Lugomirski Peter , Maze Ronnen , Froeschl Michael , Glover Christopher , Dick Alexander , Marquis Jean-Francois , Bernick Jordan , Wells George , So Derek Y. F. ,   the CAPITAL Investigators
Published: October 2016

SummaryTicagrelor has been endorsed by guidelines as the P2Y12 inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). Blood samples were collected at baseline, 12, 24, 48, 54, 60 and 72 hours (h) for assessment of platelet reactivity. The primary outcome was P2Y12 reactivity units (PRU) at 72 h. Secondary outcomes included: PRUs at each time point, incidence of high on-treatment platelet reactivity (HPR), major adverse cardiac events (MACE) and TIMI bleeding at 30 days. Serial PRUs increased after switching to clopidogrel in both groups. At 72 h, no difference in PRU was observed (165.8 ± 71.0 vs 184.1 ± 67.7, bolus vs no bolus, respectively, p=0.19). At 48 h the PRUs were significantly lower in the bolus arm (114 ± 73.1 vs 165.1 ± 70.5, respectively; p=0.0076) and at 72 h, there was a significant reduction in incidence of HPR (26.7 % vs 56.7 %, p=0.02). No differences in MACE or TIMI bleeding were observed. Although a bolus strategy was not associated with improved platelet inhibition at 72 h; at 48 h, platelet inhibition was superior with reduced incidence of HPR. Larger studies will be required to determine its clinical significance. Until then, decision for giving a bolus of clopidogrel at the time of a switch may in part be dependent on the indication for switching, especially if there are concerns for bleeding risk.Supplementary Material to this article is available online at www.thrombosis-online.com.
Monitoring of coagulation factor therapy in patients with von Willebrand disease type 3 using a microchip flow chamber system
Authors: Holmström Margareta , Schmidt David E. , Hosokawa Kazuya , Blombäck Margareta , Hjemdahl Paul , Ågren Anna 
Published: October 2016

SummaryPatients with type 3 von Willebrand disease (VWD-3) have no measurable levels of VW factor (VWF) and usually require treatment with VWF-FVIII concentrate to prevent and/or stop bleeding. Even though the patients are treated prophylactically, they may experience bleeding symptoms. The aim of this study was to evaluate the effect of VWF-FVIII concentrate treatment in VWD-3 patients with the Total Thrombus Analysis System (T-TAS®), which measures thrombus formation under flow conditions. Coagulation profiles of 10 VWD-3 patients were analysed using T-TAS before and 30 minutes after VWF-FVIII concentrate (Haemate®) injection. Results were compared to VWF- and FVIII activity in plasma, and results with thromboelastometry and ris-tocetin-activated platelet impedance aggregometry (Multiplate®) in whole blood. For comparison, 10 healthy controls were also analysed with T-TAS. A median dose of 27 (range 15–35) IU/kg of VWF-FVIII concentrate increased VWF- and FVIII activity as expected. T-TAS thrombus formation was enhanced when a tissue factor/collagen-coated flow chamber was used at low shear, but treatment effects at high shear using a collagen-coated flow chamber were minimal. Whole blood coagulation assessed by thromboelastometry was normal and did not change (p > 0.05) but ristocetin-induced platelet aggregation improved (p < 0.001). In conclusion, T-TAS detects effects of VWF-FVIII concentrate treatment on coagulation-dependent thrombus formation at low shear, but minor effects are observed on platelet-dependent thrombus formation at high shear. The poor prediction of bleeding by conventional laboratory monitoring in VWD-3 patients might be related to insufficient restoration of platelet-dependent thrombus formation.
Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest
Authors: Reynolds Joshua C. , Grunau Brian E. , Rittenberger Jon C. , Sawyer Kelly N. , Kurz Michael C. , Callaway Clifton W. 
Published: October 2016

Background:
Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest, and case features justifying longer or shorter durations are ill defined. We estimated the impact of resuscitation duration on the probability of favorable functional outcome in out-of-hospital cardiac arrest using a large, multicenter cohort.

Methods:
This was a secondary analysis of a North American, single-blind, multicenter, cluster-randomized, clinical trial (ROC-PRIMED [Resuscitation Outcomes Consortium Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed]) of consecutive adults with nontraumatic, emergency medical services–treated out-of-hospital cardiac arrest. Primary exposure was duration of resuscitation in minutes (onset of professional resuscitation to return of spontaneous circulation [ROSC] or termination of resuscitation). Primary outcome was survival to hospital discharge with favorable outcome (modified Rankin scale [mRS] score of 0–3). Subjects were additionally classified as survival with unfavorable outcome (mRS score of 4–5), ROSC without survival (mRS score of 6), or without ROSC. Subject accrual was plotted as a function of resuscitation duration, and the dynamic probability of favorable outcome at discharge was estimated for the whole cohort and subgroups. Adjusted logistic regression models tested the association between resuscitation duration and survival with favorable outcome.

Results:

The primary cohort included 11 368 subjects (median age, 69 years [interquartile range, 56–81 years]; 7121 men [62.6%]). Of these, 4023 (35.4%) achieved ROSC, 1232 (10.8%) survived to hospital discharge, and 905 (8.0%) had an mRS score of 0 to 3 at discharge. Distribution of cardiopulmonary resuscitation duration differed by outcome (
P
<0.00001). For cardiopulmonary resuscitation duration up to 37.0 minutes (95% confidence interval, 34.9–40.9 minutes), 99% with an eventual mRS score of 0 to 3 at discharge achieved ROSC. The dynamic probability of an mRS score of 0 to 3 at discharge declined over elapsed resuscitation duration, but subjects with initial shockable cardiac rhythm, witnessed cardiac arrest, and bystander cardiopulmonary resuscitation were more likely to survive with favorable outcome after prolonged efforts (30–40 minutes). After adjustment for prehospital (odds ratio, 0.93; 95% confidence interval, 0.92–0.95) and inpatient (odds ratio, 0.97; 95% confidence interval, 0.95–0.99) covariates, resuscitation duration was associated with survival to discharge with an mRS score of 0 to 3.

Conclusions:
Shorter resuscitation duration was associated with likelihood of favorable outcome at hospital discharge. Subjects with favorable case features were more likely to survive prolonged resuscitation up to 47 minutes.

Clinical Trial Registration:

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00394706.
Assessment of the Energy Balance Closure under Advective Conditions and Its Impact Using Remote Sensing Data
Authors: Xu Ziwei , Ma Yanfei , Liu Shaomin , Shi Wenjiao , Wang Jiemin 
Published: October 2016

AbstractA unique and intensive flux observation matrix was established during May to September of 2012 in an oasis–desert area located in the middle reaches of the Heihe River basin, China. The flux observation matrix included 22 eddy covariance systems belonging to the first thematic experiment of the Heihe Watershed Allied Telemetry Experimental Research (HiWATER) project. The energy balance closure ratio (EBR) was assessed and possible mechanisms were investigated using remote sensing data. The results showed that 1) the EBR was in the range of 0.78–1.04 at all sites with an average EBR of 0.92, and 2) the calculated daily EBR exhibited better performance than the 30-min averages. 3) The heat storage cannot be ignored during the crop growing season. An improvement of approximately 6% in the total closure was found after considering the heat storage terms (canopy and photosynthesis storage) in the energy budget at the maize surface, and the canopy and photosynthesis showed approximately equal contributions of 3% for each storage term. The results also showed that 4) the land heterogeneous surface had a significant effect on the EBR. The EBR decreased with land surface heterogeneity increasing (taking the standard deviation of the surface temperature in the eddy covariance system source area as an index). The EBR also decreased when irrigation occurred and increased after irrigation was completed. The advection or secondary circulation broke the closed system of the energy balance given the phenomenon of EBR increasing when the advection or secondary circulation occurred.
ENSO in the CMIP5 Simulations: Life Cycles, Diversity, and Responses to Climate Change
Authors: Chen Chen , Cane Mark A. , Wittenberg Andrew T. , Chen Dake 
Published: October 2016

AbstractFocusing on ENSO seasonal phase locking, diversity in peak location, and propagation direction, as well as the El Niño–La Niña asymmetry in amplitude, duration, and transition, a set of empirical probabilistic diagnostics (EPD) is introduced to investigate how the ENSO behaviors reflected in SST may change in a warming climate.EPD is first applied to estimate the natural variation of ENSO behaviors. In the observations El Niños and La Niñas mainly propagate westward and peak in boreal winter. El Niños occur more at the eastern Pacific whereas La Niñas prefer the central Pacific. In a preindustrial control simulation of the GFDL CM2.1 model, the El Niño–La Niña asymmetry is substantial. La Niña characteristics generally agree with observations but El Niño’s do not, typically propagating eastward and showing no obvious seasonal phase locking. So an alternative approach is using a stochastically forced simulation of a nonlinear data-driven model, which exhibits reasonably realistic ENSO behaviors and natural variation ranges.EPD is then applied to assess the potential changes of ENSO behaviors in the twenty-first century using CMIP5 models. Other than the increasing SST climatology, projected changes in many aspects of ENSO reflected in SST anomalies are heavily model dependent and generally within the range of natural variation. Shifts favoring eastward-propagating El Niño and La Niña are the most robust. Given various model biases for the twentieth century and lack of sufficient model agreements for the twenty-first-century projection, whether the projected changes for ENSO behaviors would actually take place remains largely uncertain.
Embolization with larger-caliber coils can increase packing density: Evidence from the pilot phase of a randomized trial
Authors: Cloutier Francis , Khoury Naim , Ghostine Jimmy , Farzin Behzad , Kotowski Marc , Weill Alain , Roy Daniel , Raymond Jean 
Published: October 2016

Background and purpose Endovascular coil embolization of cerebral aneurysms is associated with suboptimal angiographic results in up to 20–30% of patients. Coil packing density has been used as an index of the success of the initial procedure. The trial sought to study the effects of using 15-caliber coils, as compared with 10-caliber coils, on packing density. Methods Does Embolization with Larger coils lead to better Treatment of Aneurysms (DELTA) is an investigator-initiated multicenter prospective, randomized, controlled clinical trial. Patients are randomized 1:1 to embolization with either 10-caliber coils exclusively (control group) or the highest safely achievable proportion of 15-caliber coils and 10-caliber coils if necessary (intervention group) in 4–12-mm aneurysms. The endpoint of the pilot phase of the trial was the capacity to increase packing density of the initial procedure, calculated using a mathematical transformation of the dimensions entered into the case report forms. Secondary outcomes included the total number of coils used per aneurysm, total fluoroscopy time, initial angiographic outcomes and any adverse or undesirable event. Results Seventy patients were recruited between June 2014 and November 2015. Compared with 10-caliber coils, the 15-caliber coil group had a higher median packing density (44% vs 24%, p = 0.017). Results of other outcome measures were similar for the two groups. Conclusion Coiling of small and medium aneurysms randomized to 15-caliber coils achieved higher packing densities compared with coiling using 10-caliber coils.
Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care
Authors: Billot Laurent , Lindley Richard I , Harvey Lisa A , Maulik Pallab K , Hackett Maree L , Murthy Gudlavalleti VS , Anderson Craig S , Shamanna Bindiganavale R , Jan Stephen , Walker Marion , Forster Anne , Langhorne Peter , Verma Shweta J , Felix Cynthia , Alim Mohammed , Gandhi Dorcas BC , Pandian Jeyaraj Durai 
Published: October 2016

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.