bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource
Authors: Goldacre Ben , DeVito Nicholas J , Heneghan Carl , Irving Francis , Bacon Seb , Fleminger Jessica , Curtis Helen 
Published: September 2018

Abstract

Objectives
To ascertain compliance rates with the European Commission’s requirement that all trials on the EU Clinical Trials Register (EUCTR) post results to the registry within 12 months of completion (final compliance date 21 December 2016); to identify features associated with non-compliance; to rank sponsors by compliance; and to build a tool for live ongoing audit of compliance.

Design
Retrospective cohort study.

Setting
EUCTR.

Participants
7274 of 11 531 trials listed as completed on EUCTR and where results could be established as due.

Main outcome measure
Publication of results on EUCTR.

Results

Of 7274 trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%) reported results. Trials with a commercial sponsor were substantially more likely to post results than those with a non-commercial sponsor (68.1%
v
11.0%, adjusted odds ratio 23.2, 95% confidence interval 19.2 to 28.2); as were trials by a sponsor who conducted a large number of trials (77.9%
v
18.4%, adjusted odds ratio 18.4, 15.3 to 22.1). More recent trials were more likely to report results (per year odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Extensive evidence was found of errors, omissions, and contradictory entries in EUCTR data that prevented ascertainment of compliance for some trials.

Conclusions

Compliance with the European Commission requirement for all trials to post results on to the EUCTR within 12 months of completion has been poor, with half of all trials non-compliant. EU registry data commonly contain inconsistencies that might prevent even regulators assessing compliance. Accessible and timely information on the compliance status of each individual trial and sponsor may help to improve reporting rates.
Intensification of older adults’ outpatient blood pressure treatment at hospital discharge: national retrospective cohort study
Authors: Anderson Timothy S , Wray Charlie M , Jing Bocheng , Fung Kathy , Ngo Sarah , Xu Edison , Shi Ying , Steinman Michael A 
Published: September 2018

AbstractObjectivesTo assess how often older adults admitted to hospital for common non-cardiac conditions were discharged with intensified antihypertensive treatment, and to identify markers of appropriateness for these intensifications.DesignRetrospective cohort study.SettingUS Veterans Administration Health System.ParticipantsPatients aged 65 years or over with hypertension admitted to hospital with non-cardiac conditions between 2011 and 2013.Main outcome measuresIntensification of antihypertensive treatment, defined as receiving a new or higher dose antihypertensive agent at discharge compared with drugs used before admission. Hierarchical logistic regression analyses were used to control for characteristics of patients and hospitals.ResultsAmong 14 915 older adults (median age 76, interquartile range 69-84), 9636 (65%) had well controlled outpatient blood pressure before hospital admission. Overall, 2074 (14%) patients were discharged with intensified antihypertensive treatment, more than half of whom (1082) had well controlled blood pressure before admission. After adjustment for potential confounders, elevated inpatient blood pressure was strongly associated with being discharged on intensified antihypertensive regimens. Among patients with previously well controlled outpatient blood pressure, 8% (95% confidence interval 7% to 9%) of patients without elevated inpatient blood pressure, 24% (21% to 26%) of patients with moderately elevated inpatient blood pressure, and 40% (34% to 46%) of patients with severely elevated inpatient blood pressure were discharged with intensified antihypertensive regimens. No differences were seen in rates of intensification among patients least likely to benefit from tight blood pressure control (limited life expectancy, dementia, or metastatic malignancy), nor in those most likely to benefit (history of myocardial infarction, cerebrovascular disease, or renal disease).ConclusionsOne in seven older adults admitted to hospital for common non-cardiac conditions were discharged with intensified antihypertensive treatment. More than half of intensifications occurred in patients with previously well controlled outpatient blood pressure. More attention is needed to reduce potentially harmful overtreatment of blood pressure as older adults transition from hospital to home.
Use of scratchcards for allocation concealment in a prehospital randomised controlled trial
Authors: Keen Leigh , Bulger Jenna Katherine , Rees Nigel , Snooks Helen , Fegan Greg , Ford Simon , Evans Bridie Angela , Longo Mirella 
Published: September 2018

BackgroundRapid Analgesia for Prehospital Hip Disruption was a small study designed to determine the feasibility of undertaking a randomised controlled trial (RCT) to test the clinical and cost-effectiveness of paramedics administering Fascia Iliaca Compartment Block as early prehospital pain relief to patients with a fractured hip. The objective was to devise a simple and effective method of random allocation concealment suitable for use by paramedics while in the emergency prehospital setting.MethodsScratchcards were produced using scratch-off silver stickers which concealed the trial arm allocation. Paramedics were each allocated a unique range of consecutive numbers, used as both the scratchcard number and the patient’s study ID. The cards were designed to allow the paramedic to write on the incident number, date and signature. A small envelope holding the cards was prepared for each paramedic. The study took place between 28 June 2016 and 31 July 2017 in the Swansea area.ResultsNineteen trial paramedics used 71 scratchcards throughout the study and reported no problems randomly allocating patients using the scratchcards. Five protocol deviations were reported in relation to scratchcard use. On auditing the scratchcards, all unused cards were located, and no evidence of tampering with the silver panel was found.ConclusionParamedics can use scratchcards as a method of randomly allocating patients in trials in prehospital care. In the future, a method that allows only the top card to be selected and a more protective method of storing the cards should be used. Scratchcards can be considered for wider use in RCTs in the emergency prehospital setting.Trial registration numberISRCTN60065373; Post-results.
Digoxin and clinical outcomes in the Global Rheumatic Heart Disease Registry
Authors: Karthikeyan Ganesan , Devasenapathy Niveditha , Zühlke Liesl , Engel Mark Emmanuel , Rangarajan Sumathy , Teo Koon K , Mayosi Bongani M , Yusuf Salim 
Published: September 2018

ObjectiveDigoxin is widely used in patients with rheumatic heart disease (RHD) despite a lack of data on its impact on clinical outcomes. We aimed to determine the association of digoxin use on clinical outcomes in patients with RHD.MethodsWe performed a retrospective analysis of the association of digoxin use with mortality at 2 years in a large RHD registry. Secondary outcomes were recurrent heart failure (HF) and hospitalisation for any cause. We assessed associations using multivariable logistic regression in the entire cohort and in subgroups of patients with atrial fibrillation (AF) and HF. We also estimated average treatment effects from propensity-adjusted analyses using inverse probability treatment weighting.ResultsInformation on digoxin use at baseline was available for 98.7% (3298/3343) of patients. In the overall population, digoxin was significantly associated with mortality (OR 1.63, 95% CI 1.30 to 2.04, p<0.0001) and recurrent HF (OR 1.48, 95% CI 1.07 to 2.04, p=0.019). On propensity-weighted analyses, this effect was markedly attenuated (OR 1.05, 95% CI 1.01 to 1.09, p=0.005). Patients in sinus rhythm without HF had a higher propensity-adjusted odds of death with digoxin use (OR 1.06, 95% CI 1.01 to 1.12, p=0.015), but those with both AF and HF had lower mortality (OR 0.88, 95% CI 0.80 to 0.98, p=0.019).ConclusionDigoxin use is associated with higher mortality in patients with RHD, but this is greatly attenuated on propensity adjustment, indicating the presence of substantial treatment bias. The adjusted estimates may therefore not be reliable, and large randomised trials are needed to determine the true effect of digoxin in patients with RHD.
Organic geochemistry at varying scales: from kilometres to ångstroms
Authors: Walters Clifford C. 
Published: September 2018

Abstract

Petroleum geochemistry has historically relied on the analysis of field samples – source rocks, oils and gases. Data collected for individual samples are considered characteristic of a specific geographical location and geological position that, when aggregated with data from other samples, can be extrapolated to larger scales. These scale-ups may be as small as a few metres, such as a detailed characterization of source rocks penetrated by a single well, to global, such as petroleum systems that now span continents due to plate tectonics. However, a single sample contains a wealth of information at smaller scales.
In situ
analytical techniques have improved significantly over the last decade, allowing us to examine sedimentary rocks at ever higher spatial (areal and temporal) resolution. Mass spectrometric imaging is an emerging, enabling technology that can be performed at
c.
200 µm (matrix-assisted laser desorption) to 50 nm (nanoSIMS) resolution. X-ray microcomputed tomography (µ-CT) is being applied to examine the storage and transport of petroleum in low-permeability shales and carbonates at spatial resolutions as low as
c.
8 µm. Pore architecture in shale, both organic and inorganic, can be modelled from small-angle neutron scattering (SANS) data and imaged directly with helium ion microscopy at
c.
1 nm resolution. Atomic force microscopy (AFM) can now resolve the molecular structure of individual asphaltene molecules. Information obtained with these techniques is now revealing the fundamental nature of geological organic materials, opening the span of petroleum geochemistry from atoms to continents.
Visual information processing in older adults: reaction time and motor unit pool modulation
Authors: Kwon MinHyuk , Christou Evangelos A. 
Published: September 2018

Presently, there is no evidence that magnification of visual feedback has motor implications beyond impairments in force control during a visuomotor task. We hypothesized that magnification of visual feedback would increase visual information processing, alter the muscle activation, and exacerbate the response time in older adults. To test this hypothesis, we examined whether magnification of visual feedback during a reaction time task alters the premotor time and the motor unit pool activation of older adults. Participants responded as fast as possible to a visual stimulus while they maintained a steady ankle dorsiflexion force (15% maximum) either with low-gain or high-gain visual feedback of force. We quantified the following: 1) response time and its components (premotor and motor time), 2) force variability, and 3) motor unit pool activity of the tibialis anterior muscle. Older adults exhibited longer premotor time and greater force variability than young adults. Only in older adults, magnification of visual feedback lengthened the premotor time and exacerbated force variability. The slower premotor time in older adults with high-gain visual feedback was associated with increased force variability and an altered modulation of the motor unit pool. In conclusion, our findings provide novel evidence that magnification of visual feedback also exacerbates premotor time during a reaction time task in older adults, which is correlated with force variability and an altered modulation of motor unit pool. Thus these findings suggest that visual information processing deficiencies in older adults could result in force control and reaction time impairments. NEW & NOTEWORTHY It is unknown whether magnification of visual feedback has motor implications beyond impairments in force control for older adults. We examined whether it impairs reaction time and motor unit pool activation. The findings provide novel evidence that magnification of visual feedback exacerbates reaction time by lengthening premotor time, which implicates time for information processing in older adults, which is correlated with force variability and an altered modulation of motor unit pool.
Effect of cervicolumbar coupling on spinal reflexes during cycling after incomplete spinal cord injury
Authors: Zhou R. , Parhizi B. , Assh J. , Alvarado L. , Ogilvie R. , Chong S. L. , Mushahwar V. K. 
Published: September 2018

Spinal networks in the cervical and lumbar cord are actively coupled during locomotion to coordinate arm and leg activity. The goals of this project were to investigate the intersegmental cervicolumbar connectivity during cycling after incomplete spinal cord injury (iSCI) and to assess the effect of rehabilitation training on improving reflex modulation mediated by cervicolumbar pathways. Two studies were conducted. In the first, 22 neurologically intact (NI) people and 10 people with chronic iSCI were recruited. The change in H-reflex amplitude in flexor carpi radialis (FCR) during leg cycling and H-reflex amplitude in soleus (SOL) during arm cycling were investigated. In the second study, two groups of participants with chronic iSCI underwent 12 wk of cycling training: one performed combined arm and leg cycling (A&L) and the other legs only cycling (Leg). The effect of training paradigm on the amplitude of the SOL H-reflex was assessed. Significant reduction in the amplitude of both FCR and SOL H-reflexes during dynamic cycling of the opposite limbs was found in NI participants but not in participants with iSCI. Nonetheless, there was a significant reduction in the SOL H-reflex during dynamic arm cycling in iSCI participants after training. Substantial improvements in SOL H-reflex properties were found in the A&L group after training. The results demonstrate that cervicolumbar modulation during rhythmic movements is disrupted in people with chronic iSCI; however, this modulation is restored after cycling training. Furthermore, involvement of the arms simultaneously with the legs during training may better regulate the leg spinal reflexes.NEW & NOTEWORTHY This work systematically demonstrates the disruptive effect of incomplete spinal cord injury on cervicolumbar coupling during rhythmic locomotor movements. It also shows that the impaired cervicolumbar coupling could be significantly restored after cycling training. Actively engaging the arms in rehabilitation paradigms for the improvement of walking substantially regulates the excitability of the lumbar spinal networks. The resulting regulation may be better than that obtained by interventions that focus on training of the legs only.
Automatic spike sorting for high-density microelectrode arrays
Authors: Diggelmann Roland , Fiscella Michele , Hierlemann Andreas , Franke Felix 
Published: September 2018

High-density microelectrode arrays can be used to record extracellular action potentials from hundreds to thousands of neurons simultaneously. Efficient spike sorters must be developed to cope with such large data volumes. Most existing spike sorting methods for single electrodes or small multielectrodes, however, suffer from the “curse of dimensionality” and cannot be directly applied to recordings with hundreds of electrodes. This holds particularly true for the standard reference spike sorting algorithm, principal component analysis-based feature extraction, followed by k-means or expectation maximization clustering, against which most spike sorters are evaluated. We present a spike sorting algorithm that circumvents the dimensionality problem by sorting local groups of electrodes independently with classical spike sorting approaches. It is scalable to any number of recording electrodes and well suited for parallel computing. The combination of data prewhitening before the principal component analysis-based extraction and a parameter-free clustering algorithm obviated the need for parameter adjustments. We evaluated its performance using surrogate data in which we systematically varied spike amplitudes and spike rates and that were generated by inserting template spikes into the voltage traces of real recordings. In a direct comparison, our algorithm could compete with existing state-of-the-art spike sorters in terms of sensitivity and precision, while parameter adjustment or manual cluster curation was not required. NEW & NOTEWORTHY We present an automatic spike sorting algorithm that combines three strategies to scale classical spike sorting techniques for high-density microelectrode arrays: 1) splitting the recording electrodes into small groups and sorting them independently; 2) clustering a subset of spikes and classifying the rest to limit computation time; and 3) prewhitening the spike waveforms to enable the use of parameter-free clustering. Finally, we combined these strategies into an automatic spike sorter that is competitive with state-of-the-art spike sorters.
Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy
Authors: Berkeley Robert A. , Steele Lynette P. , Mulder Aat A. , van den Wollenberg Diana J.M. , Kottke Timothy J. , Thompson Jill , Coffey Matthew , Hoeben Rob C. , Vile Richard G. , Melcher Alan , Ilett Elizabeth J. 
Published: September 2018

Abstract
Immunotherapy is showing promise for otherwise incurable cancers. Oncolytic viruses (OVs), developed as direct cytotoxic agents, mediate their antitumor effects via activation of the immune system. However, OVs also stimulate antiviral immune responses, including the induction of OV-neutralizing antibodies. Current dogma suggests that the presence of preexisting antiviral neutralizing antibodies in patients, or their development during viral therapy, is a barrier to systemic OV delivery, rendering repeat systemic treatments ineffective. However, we have found that human monocytes loaded with preformed reovirus–antibody complexes, in which the reovirus is fully neutralized, deliver functional replicative reovirus to tumor cells, resulting in tumor cell infection and lysis. This delivery mechanism is mediated, at least in part, by antibody receptors (in particular FcγRIII) that mediate uptake and internalization of the reovirus/antibody complexes by the monocytes. This finding has implications for oncolytic virotherapy and for the design of clinical OV treatment strategies. Cancer Immunol Res; 6(10); 1161–73. ©2018 AACR.
Beyond Schemata in Collective Improvisation: A Support Tool for Music Interactions
Authors: Kalonaris Stefano 
Published: September 2018

Abstract
This article presents results of experiments undertaken with expert musicians using the author’s original system for systemic improvisation. By promoting the formation of parallel and simultaneous layers of sustained musical relationships, this system facilitates an enhanced focus on local clusters and their development over time. This tool opens a novel perspective on improvised interactions and how they are formed, evaluated, updated, modified and abandoned during a performance, encouraging a critical evaluation of collective schemata.
Simulation of Past Changes in the Austrian Snow Cover 1948–2009
Authors: Marke Thomas , Hanzer Florian , Olefs Marc , Strasser Ulrich 
Published: September 2018

Abstract
A distributed snow model is applied to simulate the spatiotemporal evolution of the Austrian snow cover at 1 km × 1 km spatial and daily temporal resolution for the period 1948–2009. After a comprehensive model validation, changes in snow cover conditions are analyzed for all of Austria as well as for different Austrian subregions and elevation belts focusing on the change in snow cover days (SCDs). The comparison of SCDs for the period 1950–79 to those achieved for 1980–2009 for all of Austria shows a decrease in SCDs with a maximum of &gt;35 SCDs near Villach (Carinthia). The analysis of SCD changes in different subregions of Austria reveals mean changes between −11 and −15 days with highest absolute change in SCDs for southern Austria. Two decrease maxima could be identified in elevations of 500–2000 m MSL (between −13 and −18 SCDs depending on the subregion considered) and above 2500 m MSL (over −20 SCDs in the case of central Austria). The temporal distribution of SCD change in the Austrian subregions is characterized by a reduction of SCDs in midwinter and at the end of winter rather than by fewer SCDs in early winter. With respect to the temporal distribution of SCD change in different elevation belts, changes in elevations below 1000 m MSL are characterized by a distinct reduction of SCDs in January. With increasing elevation the maximum change in SCDs shifts toward the summer season, reaching a maximum decrease in the months of June–August above 2500 m MSL.
Antarctic Thermocline Dynamics along a Narrow Shelf with Easterly Winds
Authors: Hattermann Tore 
Published: September 2018

AbstractDetermining the role of Southern Ocean warm intermediate water for driving melting of the Antarctic ice sheet is a major challenge in assessing future sea level rise. Analysis of 2859 CTD profiles obtained between 1977 and 2016 by ships and instrumented seals at the Weddell Sea continental slope reveals a seasonal rise of the Antarctic Slope Front thermocline by more than 100 m during the summer. The signal at Kapp Norvegia (17°W) corresponds with a seasonal warming downstream at the Filchner Trough (40°W), indicating that a coherent evolution of the slope front along the shelf break regulates the onshore flow of warm deep water. Climatological cross sections of the slope front hydrography show that downwelling of Antarctic Surface Water forms a secondary front above the warm deep water interface during summer. Enhanced baroclinic growth rates at this front suggest that the wind-driven suppression of the thermocline is partially compensated by a shallower eddy overturning cell when surface water is present. A simple model of the Weddell Gyre boundary current reveals that wintertime densification of surface waters is crucial for maintaining the deep thermocline along the eastern Weddell Sea coast. The sensitivity of the warm inflow to the cross-frontal density gradient implies a positive feedback with ice shelf melting that may lead to an abrupt transition into a high melting state once warm water rises over the shelf break depth. Despite its regional focus, this study highlights the role of upper ocean buoyancy fluxes for controlling the thermocline depth along seasonally ice-covered narrow shelf regions with cyclonic along-slope winds.