bluuebunny/crossref_metadata_2025_split huggingface dataset:
Important issues in the justification of a control treatment in paediatric drug trials
Authors: Kelly Lauren E , Davies Elin Haf , Saint-Raymond Agnes , Tomasi Paolo , Offringa Martin 
Published: April 2016

ObjectiveThe value of comparative effectiveness trials in informing clinical and policy decisions depends heavily on the choice of control arm (comparator). Our objective is to identify challenges in comparator reasoning and to determine justification criteria for selecting a control arm in paediatric clinical trials.DesignA literature search was completed to identify existing sources of guidance on comparator selection. Subsequently, we reviewed a randomly selected sample of comparators selected for paediatric investigation plans (PIPs) adopted by the Paediatric Committee of the European Medicines Agency in 2013. We gathered descriptive information and evaluated their review process to identify challenges and compromises between regulators and sponsors with regard to the selection of the comparator. A tool to help investigators justify the selection of active controls and placebo arms was developed using the existing literature and empirical data.ResultsJustifying comparator selection was a challenge in 28% of PIPs. The following challenging paediatric issues in the decision-making process were identified: use of off-label medications as comparators, ethical and safe use of placebo, duration of placebo use, an undefined optimal dosing strategy, lack of age-appropriate safety and efficacy data, and drug dosing not supported by extrapolation of safety/efficacy evidence from other populations.ConclusionsIn order to generate trials that will inform clinical decision-making and support marketing authorisations, researchers must systemically and transparently justify their selection of the comparator arm for their study. This report highlights key areas for justification in the choice of comparator in paediatric clinical trials.
Impact of a Dutch urban regeneration programme on mental health trends: a quasi-experimental study
Authors: Jongeneel-Grimen Birthe , Droomers Mariël , Kramer Daniëlle , Bruggink Jan-Willem , van Oers Hans , Kunst Anton E , Stronks Karien 
Published: April 2016

BackgroundThis paper aims to assess the mental health impact of an urban regeneration programme implemented from 2008 onwards in the 40 most deprived districts in the Netherlands. Interventions varied from improvements in the built environment to activities promoting social cohesion.MethodsWe accessed repeated cross-sectional data from the annual Health Interview Survey, for the period 2004–2011 among adults (n target districts=1445, n rest of the Netherlands=44 795). We used multilevel logistic regression models to compare the development of mental health in the target districts with the rest of the Netherlands and with comparably deprived districts. Results were presented as ‘slope estimates’ with corresponding 95% CIs. Finally, we analysed the trends by gender and by the intensity of the programme.ResultsThe trend change in mental health between the intervention and preintervention period was approximately the same in the target districts as in broadly comparably deprived control districts (Δ slope 0.06 (−0.08 to 0.20)). However, among women, a tendency was found towards more positive trend changes in the target districts compared with control districts (Δ slope 0.17 (−0.01 to 0.34)). Those districts that implemented an intensive programme experienced an improvement in mental health, while residents of the comparably deprived control districts experienced a deterioration, resulting in a statistically significantly more positive trend change between the preintervention and intervention period in those target districts (Δ slope 0.19 (0.01 to 0.38)).ConclusionsImplementing an urban regeneration programme with a wide range of intensive interventions may be effective in promoting good mental health. Further research is required to examine which mix of interventions is needed for the programme to be effective.
Subjective and objective evaluation of image quality in biplane cerebral digital subtraction angiography following significant acquisition dose reduction in a clinical setting
Authors: Honarmand Amir R , Shaibani Ali , Pashaee Tamila , Syed Furqan H , Hurley Michael C , Sammet Christina L , Potts Matthew B , Jahromi Babak S , Ansari Sameer A 
Published: April 2016

ObjectiveDifferent technical and procedural methods have been introduced to develop low radiation dose protocols in neurointerventional examinations. We investigated the feasibility of minimizing radiation exposure dose by simply decreasing the detector dose during cerebral DSA and evaluated the comparative level of image quality using both subjective and objective methods.MethodsIn a prospective study of patients undergoing diagnostic cerebral DSA, randomly selected vertebral arteries (VA) and/or internal carotid arteries and their contralateral equivalent arteries were injected. Detector dose of 3.6 and 1.2 μGy/frame were selected to acquire standard dose (SD) and low dose (LD) images, respectively. Subjective image quality assessment was performed by two neurointerventionalists using a 5 point scale. For objective image quality evaluation, circle of Willis vessels were categorized into conducting, primary, secondary, and side branch vessels. Two blinded observers performed arterial diameter measurements in each category. Only image series obtained from VA injections opacifying the identical posterior intracranial circulation were utilized for objective assessment.ResultsNo significant difference between SD and LD images was observed in subjective and objective image quality assessment in 22 image series obtained from 10 patients. Mean reference air kerma and kerma area product were significantly reduced by 61.28% and 61.24% in the LD protocol, respectively.ConclusionsOur study highlights the necessity for reconsidering radiation dose protocols in neurointerventional procedures, especially at the level of baseline factory settings.
Asymptotic regimes for hadron diffractive scatterings and Coulomb interaction: Arguments for the black disk mode
Authors: Anisovich V. V. , Nikonov V. A. , Nyiri J. 
Published: April 2016

Comparative analysis of the interplay of hadron and Coulomb interactions in [Formula: see text] scattering amplitudes is performed in a broad energy interval, [Formula: see text], for two extreme cases: for the asymptotic interactions of hadrons in black disk and resonant disk modes. The interactions are discussed in terms of the [Formula: see text]-matrix function technique. In the asymptotic regime, the real part of the hadronic amplitude is concentrated in both cases on the boundary of the disks in the impact parameter space but the LHC energy region is not asymptotic for the resonant disk mode that lead to a specific interplay of hadronic and Coulombic amplitudes. For the [Formula: see text] scattering at [Formula: see text] an interplay of the hadron and Coulomb interactions in the resonant disk modes is realized in a shoulder in [Formula: see text] at [Formula: see text]. The absence of such a shoulder in the data at 8 TeV can be considered as an argument against the resonant disk mode.
Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance
Authors: Naito Hisamichi , Wakabayashi Taku , Kidoya Hiroyasu , Muramatsu Fumitaka , Takara Kazuhiro , Eino Daisuke , Yamane Keitaro , Iba Tomohiro , Takakura Nobuyuki 
Published: April 2016

Abstract
Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor–like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo. These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor–like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200–10. ©2016 AACR.
Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma
Authors: Vatolin Sergei , Phillips James G. , Jha Babal K. , Govindgari Shravya , Hu Jennifer , Grabowski Dale , Parker Yvonne , Lindner Daniel J. , Zhong Fei , Distelhorst Clark W. , Smith Mitchell R. , Cotta Claudiu , Xu Yan , Chilakala Sujatha , Kuang Rebecca R. , Tall Samantha , Reu Frederic J. 
Published: April 2016

Abstract
Multiple myeloma cells secrete more disulfide bond–rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell–based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow–sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in active-site CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma. Cancer Res; 76(11); 3340–50. ©2016 AACR.
Transcatheter Myocardial Needle Chemoablation During Real-Time Magnetic Resonance Imaging
Authors: Rogers Toby , Mahapatra Srijoy , Kim Steven , Eckhaus Michael A. , Schenke William H. , Mazal Jonathan R. , Campbell-Washburn Adrienne , Sonmez Merdim , Faranesh Anthony Z. , Ratnayaka Kanishka , Lederman Robert J. 
Published: April 2016

Background—
Radiofrequency ablation for ventricular arrhythmias is limited by inability to visualize tissue destruction, by reversible conduction block resulting from edema surrounding lesions, and by insufficient lesion depth. We hypothesized that transcatheter needle injection of caustic agents doped with gadolinium contrast under real-time magnetic resonance imaging (MRI) could achieve deep, targeted, and irreversible myocardial ablation, which would be immediately visible.

Methods and Results—
Under real-time MRI guidance, ethanol or acetic acid was injected into the myocardium of 8 swine using MRI-conspicuous needle catheters. Chemoablation lesions had identical geometry by in vivo and ex vivo MRI and histopathology, both immediately and after 12 (7–17) days. Ethanol caused stellate lesions with patchy areas of normal myocardium, whereas acetic acid caused homogeneous circumscribed lesions of irreversible necrosis. Ischemic cardiomyopathy was created in 10 additional swine by subselective transcoronary ethanol administration into noncontiguous territories. After 12 (8–15) days, real-time MRI–guided chemoablation—with 2 to 5 injections to create a linear lesion—successfully eliminated the isthmus and local abnormal voltage activities.

Conclusions—
Real-time MRI–guided chemoablation with acetic acid enabled the intended arrhythmic substrate, whether deep or superficial, to be visualized immediately and ablated irreversibly. In an animal model of ischemic cardiomyopathy, obliteration of a conductive isthmus both anatomically and functionally and abolition of local abnormal voltage activities in areas of heterogeneous scar were feasible. This represents the first report of MRI-guided myocardial chemoablation, an approach that could improve the efficacy of arrhythmic substrate ablation in the thick ventricular myocardium.
Evidence for Integrated Visual Face and Body Representations in the Anterior Temporal Lobes
Authors: Harry Bronson B. , Umla-Runge Katja , Lawrence Andrew D. , Graham Kim S. , Downing Paul E. 
Published: April 2016

AbstractResearch on visual face perception has revealed a region in the ventral anterior temporal lobes, often referred to as the anterior temporal face patch (ATFP), which responds strongly to images of faces. To date, the selectivity of the ATFP has been examined by contrasting responses to faces against a small selection of categories. Here, we assess the selectivity of the ATFP in humans with a broad range of visual control stimuli to provide a stronger test of face selectivity in this region. In Experiment 1, participants viewed images from 20 stimulus categories in an event-related fMRI design. Faces evoked more activity than all other 19 categories in the left ATFP. In the right ATFP, equally strong responses were observed for both faces and headless bodies. To pursue this unexpected finding, in Experiment 2, we used multivoxel pattern analysis to examine whether the strong response to face and body stimuli reflects a common coding of both classes or instead overlapping but distinct representations. On a voxel-by-voxel basis, face and whole-body responses were significantly positively correlated in the right ATFP, but face and body-part responses were not. This finding suggests that there is shared neural coding of faces and whole bodies in the right ATFP that does not extend to individual body parts. In contrast, the same approach revealed distinct face and body representations in the right fusiform gyrus. These results are indicative of an increasing convergence of distinct sources of person-related perceptual information proceeding from the posterior to the anterior temporal cortex.
The quality of diagnosis and management of migraine and tension-type headache in three social groups in Russia
Authors: Lebedeva Elena R , Kobzeva Natalia R , Gilev Denis V , Olesen Jes 
Published: April 2016

Background Three successive editions of the International Classification of Headache Disorders and multiple guideline papers on headache care have described evidence based diagnosis and treatment of headache disorders. It remains unknown, however, to which extent this has improved the diagnosis and management of headache. That was the aim of our study in which we also analysed differences between three social groups in Russia. Methods We studied 1042 students (719 females, 323 males, mean age 20.6, age range 17–40), 1075 workers (146 females, 929 males, mean age 40.4, age range 21–67) and 1007 blood donors (484 females, 523 males, mean age 34.1, age range 18–64). We conducted a semi-structured, validated, face-to-face professional interview. Data on prevalence and associated factors have previously been published. A section of the interview focused on previous diagnosis and treatment, the topic of this paper. Results Only 496 of 2110 participants (23%) with headache in Russia had consulted because of headache. Students consulted more frequently (35%), workers and blood donors less often (13% and 14%). Only 12% of the patients with ICHD-3beta diagnosis of migraine and 11.7% with ICHD-3beta diagnosis of tension-type headache (TTH) had previously been correctly diagnosed. Triptans were used by only 6% of migraine patients. Only 0.4% of migraine patients and no TTH patients had received prophylactic treatment. Conclusion Despite existing guidelines about diagnosis and treatment, both remain poor in Russia. According to the literature this is only slightly better in Europe and America. Dissemination of existing knowledge should have higher priority in the future.
Novel Arthroscopic Classification of Osteochondritis Dissecans of the Knee
Authors: Carey James L. , Wall Eric J. , Grimm Nathan L. , Ganley Theodore J. , Edmonds Eric W. , Anderson Allen F. , Polousky John , Murnaghan M. Lucas , Nissen Carl W. , Weiss Jennifer , Lyon Roger M. , Chambers Henry G. ,   The Research in OsteoChondritis of the Knee (ROCK) Group, Wright Rick W. , Heyworth Benton E. , Peterson Lars , Myer Gregory D. , Shea Kevin G. 
Published: April 2016

Background: Several systems have been proposed for classifying osteochondritis dissecans (OCD) of the knee during surgical evaluation. No single classification includes mutually exclusive categories that capture all of the salient features of stability, chondral fissuring, and fragment detachment. Furthermore, no study has assessed the reliability of these classification systems. Purpose: To determine the intra- and interobserver reliability of a novel, comprehensive arthroscopic classification system with mutually exclusive OCD lesion types. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The Research in OsteoChondritis of the Knee (ROCK) study group developed a classification system for arthroscopic evaluation of OCD of the knee that includes 6 arthroscopic categories—3 immobile types and 3 mobile types. To optimize comprehensibility and applicability, each was developed with a memorable name, a brief description, a line diagram corresponding to the archetypal arthroscopic appearance, and an arthroscopic photograph depicting this archetype. Thirty representative arthroscopic videos were evaluated by 10 orthopaedic surgeon raters, who classified each lesion. After 4 weeks, the raters again classified the OCD lesions depicted in the 30 videos in a new, randomly selected order. Reliability was assessed via the intraclass correlation coefficient (ICC). Results: The interobserver reliability of this novel arthroscopy classification was estimated by an ICC of 0.94 (95% CI, 0.91-0.97) for the first round and 0.95 (95% CI, 0.93-0.98) for the second round. According to the standards for the magnitude of the reliability coefficient of Altman, these ICCs indicate that interobserver reliability was very good. The intraobserver reliability was estimated by an ICC of 0.96 (95% CI, 0.95-0.97), which indicates that the intraobserver reliability was similarly very good. Conclusion: The ROCK OCD knee arthroscopy classification system demonstrated excellent intra- and interobserver reliability. In light of this reliability, this classification system may be used clinically and to facilitate future research, including multicenter studies for OCD.
Site and Severity of the Increased Humeral Retroversion in Symptomatic Baseball Players
Authors: Itami Yasuo , Mihata Teruhisa , Shibano Koji , Sugamoto Kazuomi , Neo Masashi 
Published: April 2016

Background: Humeral retroversion in baseball players is greater in the dominant shoulder than in the nondominant shoulder. However, the site and severity of the humeral rotational deformity remain unclear. Purpose: To evaluate the site of side-to-side differences in humeral retroversion in baseball players and the severity of these changes through 3-dimensional computed tomographic (3D CT) bone models. Study Design: Cross-sectional study; Level of evidence, 3. Methods: From 2008 to 2014, we studied 25 baseball players (12 pitchers, 13 fielders) who underwent surgery for throwing-related injuries (shoulder injury, 15 players; elbow injury, 10 players). The mean age (±SD) at the time of surgery was 20.0 ± 5.9 years. A reconstructed 3D CT model of the entire humerus was divided into 15 segments of equal height (overall mean, 21.4 ± 1.0 mm). The side-to-side difference in humeral retroversion in each segment was calculated by superimposing the model of the dominant side over the mirror-image model of the nondominant side. Results: The overall mean increase in humeral retroversion was 13.0° ± 6.2° on the dominant side. Significant side-to-side differences in retroversion were present throughout the humerus. The largest side-to-side difference in humeral retroversion was seen at the insertions of the internal rotator muscles (2.5° ± 4.3°) and around the proximal physis (2.5° ± 1.4°). At the insertions of shoulder capsule and rotator cuff tendons, the superior half of the humeral head was more retroverted than the inferior half ( P < .0001). The side-to-side difference in humeral retroversion was significantly greater in the pitchers (16.2° ± 5.1°) than in the fielders (10.0° ± 5.7°) ( P = .009), particularly at the proximal physis. Conclusion: Baseball players exhibited significant side-to-side differences in humeral retroversion at multiple sites throughout the humerus, including the proximal humerus near the epiphyseal plate and at the insertions of the internal rotator muscles, the middle of the humeral shaft, and the distal third of the humerus. Therefore, the increased humeral retroversion at multiple sites throughout the humerus needs to be considered when we perform physical examinations, provide treatment, or undertake biomechanical studies for any throwing-related injuries.
Safety of Nurse-Led Ambulation for Patients on Venovenous Extracorporeal Membrane Oxygenation
Authors: Boling Bryan , Dennis Donna R. , Tribble Thomas A. , Rajagopalan Navin , Hoopes Charles W. 
Published: April 2016

Purpose: Venovenous extracorporeal membrane oxygenation (VV ECMO) is an effective therapy in patients with acute lung injury and end-stage lung disease. Although immobility increases the risk of complications, ambulation of patients on VV ECMO is not the standard of care in many institutions. Staff concerns for patient safety remain a barrier to ambulation. In this case series, we present our experience utilizing a nurse-driven ambulatory VV ECMO process to safely rehabilitate patients. Methods: We retrospectively reviewed all VV ECMO cases at our institution between January 1, 2011, and November 1, 2013. Inclusion criteria for this study required patients to be cannulated in the right internal jugular vein and ambulated while on VV ECMO. Results: During the period from January 1, 2011, to November 1, 2013, 18 patients (mean age 49 ± 15 years, 12 male) were ambulated while on ECMO. Eight received a transplant and survived to discharge. Of the remaining patients, 4 were successfully weaned from VV ECMO and 6 died following decisions by the family to withdraw care. The mean duration of VV ECMO support was 18 ± 16 days with the maximum duration being 61 days. All patients received physical therapy, range of motion at the bedside, and ambulated in the hospital. There were no patient falls, decannulations, or any other complications related to ambulation. Conclusion: The adoption of a nurse-driven program to ambulate patients on VV ECMO is safe and may reduce other complications associated with immobility.