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1.  Reduced-intensity allografting as first transplantation approach in relapsed/refractory grade 1-2 follicular lymphoma provides improved outcomes in long-term survivors 
Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era.
Adult patients with relapsed/refractory grade 1-2 FL undergoing 1st reduced-intensity allo-HCT or 1st autograft during 2000-2012 were evaluated.
A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger; more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto- vs. allo-HCT groups for non-relapse mortality (NRM) were 5% vs. 26% (p<0.0001); relapse/progression: 54% vs. 20% (p<0.0001); progression-free survival (PFS): 41% vs. 58% (p<0.001) and overall survival (OS): 74% vs. 66% (p=0.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months post-HCT (RR=4.4; p<0.0001), and worse PFS (RR=2.9; p<0.0001) beyond 11 months post HCT. In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.41; p<0.0001), but beyond 24 months with inferior OS (RR=2.2; p=0.006). A landmark analysis of patients alive and progression-free at 2-years post-HCT confirmed these observations, showing no difference in further NRM between both groups, but significantly higher risk of relapse/progression (RR=7.3; p<0.0001) and inferior PFS (RR=3.2; p<0.0001) and OS (RR=2.1; p=0.04) following auto-HCT. The 10-year cumulative incidence of second hematological malignancies following allo- and auto-HCT was 0% and 7%, respectively.
Auto- and RIC-allo-HCT as 1st transplantation approach can provide durable disease control in grade 1-2 FL patients. Continued disease relapse-risk following auto-HCT translates into improved PFS and OS following allo-HCT, in long-term survivors.
PMCID: PMC4639453  PMID: 26253007
grade 1-2 follicular lymphoma; reduced intensity allo-HCT; auto-HCT; long-time survival
2.  Tonic and burst spinal cord stimulation waveforms for the treatment of chronic, intractable pain: study protocol for a randomized controlled trial 
Trials  2016;17:569.
Burst stimulation is a novel form of neurostimulation for the treatment of chronic pain which has demonstrated promise in small uncontrolled studies, but has not yet gained approval for use in the U.S. We report the study methods for an ongoing multicenter, randomized, controlled, cross-over study designed to gain United States Food and Drug Administration (FDA) approval for burst stimulation.
Participants who are candidates for a currently approved neurostimulation device were enrolled and screened. Participants who fail a tonic trial evaluation, have significant depressive symptoms, or evidence lack of compliance with study procedures by failing to complete 7 days of a Pain Diary are excluded. Participants receiving a permanent implant are randomized to receive: (1) 12 weeks of tonic followed by 12 weeks of burst stimulation or (2) 12 weeks of burst stimulation followed by 12 weeks of tonic stimulation. Assessments occur at 6, 12, 18, and 24 weeks. After 24 weeks, participants choose their preferred therapy and are assessed every 6 months for up to 2 years. All patients had the device leads inserted at the site of a successful tonic stimulation trial. Assessments include: a Pain Diary using a Visual Analog Scale (VAS) for overall, trunk, and limb pain, the Beck Depression Inventory, the Pain Catastrophizing Scale, the Oswestry Disability Index, paresthesia, satisfaction, and therapy preference. Reported adverse events are collected throughout the study. The primary endpoint is the noninferiority of burst stimulation compared to tonic measured by the within-subject difference in the mean overall VAS score at the end of each 12-week stimulation period.
This trial represents the largest controlled trial of burst stimulation to date, and is expected to yield important information regarding the safety and efficacy of burst stimulation.
Trial registration, NCT02011893. Registered on 10 December 2013.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1706-5) contains supplementary material, which is available to authorized users.
PMCID: PMC5131423  PMID: 27906080
Neuromodulation; Spinal cord Stimulation; Randomized; Prospective; Comparative efficacy; Burst stimulation; Tonic stimulation
3.  Improvement of Advanced Parkinson’s Disease Manifestations with Deep Brain Stimulation of the Subthalamic Nucleus: A Single Institution Experience 
Brain Sciences  2016;6(4):58.
We present our experience at the University of Illinois at Chicago (UIC) in deep brain stimulation (DBS) of the subthalamic nucleus (STN), describing our surgical technique, and reporting our clinical results, and morbidities. Twenty patients with advanced Parkinson’s disease (PD) who underwent bilateral STN-DBS were studied. Patients were assessed preoperatively and followed up for one year using the Unified Parkinson’s Disease Rating Scale (UPDRS) in “on” and “off” medication and “on” and “off” stimulation conditions. At one-year follow-up, we calculated significant improvement in all the motor aspects of PD (UPDRS III) and in activities of daily living (UPDRS II) in the “off” medication state. The “off” medication UPDRS improved by 49.3%, tremors improved by 81.6%, rigidity improved by 50.0%, and bradykinesia improved by 39.3%. The “off” medication UPDRS II scores improved by 73.8%. The Levodopa equivalent daily dose was reduced by 54.1%. The UPDRS IVa score (dyskinesia) was reduced by 65.1%. The UPDRS IVb score (motor fluctuation) was reduced by 48.6%. Deep brain stimulation of the STN improves the cardinal motor manifestations of the idiopathic PD. It also improves activities of daily living, and reduces medication-induced complications.
PMCID: PMC5187572  PMID: 27983589
subthalamic nucleus; deep brain stimulation; Parkinson’s disease; neuromodulation; clinical outcome
4.  Using “Functional” Target Coordinates of the Subthalamic Nucleus to Assess the Indirect and Direct Methods of the Preoperative Planning: Do the Anatomical and Functional Targets Coincide? 
Brain Sciences  2016;6(4):65.
Objective: To answer the question of whether the anatomical center of the subthalamic nucleus (STN), as calculated indirectly from stereotactic atlases or by direct visualization on magnetic resonance imaging (MRI), corresponds to the best functional target. Since the neighboring red nucleus (RN) is well visualized on MRI, we studied the relationships of the final target to its different borders. Methods: We analyzed the data of 23 PD patients (46 targets) who underwent bilateral frame-based STN deep brain stimulation (DBS) procedure with microelectrode recording guidance. We calculated coordinates of the active contact on DBS electrode on postoperative MRI, which we referred to as the final “functional/optimal” target. The coordinates calculated by the atlas-based “indirect” and “direct” methods, as well as the coordinates of the different RN borders were compared to these final coordinates. Results: The mean ± SD of the final target coordinates was 11.7 ± 1.5 mm lateral (X), 2.4 ± 1.5 mm posterior (Y), and 6.1 ± 1.7 mm inferior to the mid-commissural point (Z). No significant differences were found between the “indirect” X, Z coordinates and those of the final targets. The “indirect” Y coordinate was significantly posterior to Y of the final target, with mean difference of 0.6 mm (p = 0.014). No significant differences were found between the “direct” X, Y, and Z coordinates and those of the final targets. Conclusions: The functional STN target is located in direct proximity to its anatomical center. During preoperative targeting, we recommend using the “direct” method, and taking into consideration the relationships of the final target to the mid-commissural point (MCP) and the different RN borders.
PMCID: PMC5187579  PMID: 28009826
subthalamic nucleus; deep brain stimulation; targeting; Parkinson’s disease; planning
5.  A large‐scale view of Space Technology 5 magnetometer response to solar wind drivers 
In this data report we discuss reprocessing of the Space Technology 5 (ST5) magnetometer database for inclusion in NASA's Coordinated Data Analysis Web (CDAWeb) virtual observatory. The mission consisted of three spacecraft flying in elliptical orbits, from 27 March to 27 June 2006. Reprocessing includes (1) transforming the data into the Modified Apex Coordinate System for projection to a common reference altitude of 110 km, (2) correcting gain jumps, and (3) validating the results. We display the averaged magnetic perturbations as a keogram, which allows direct comparison of the full‐mission data with the solar wind values and geomagnetic indices. With the data referenced to a common altitude, we find the following: (1) Magnetic perturbations that track the passage of corotating interaction regions and high‐speed solar wind; (2) unexpectedly strong dayside perturbations during a solstice magnetospheric sawtooth oscillation interval characterized by a radial interplanetary magnetic field (IMF) component that may have enhanced the accompanying modest southward IMF; and (3) intervals of reduced magnetic perturbations or “calms,” associated with periods of slow solar wind, interspersed among variable‐length episodic enhancements. These calms are most evident when the IMF is northward or projects with a northward component onto the geomagnetic dipole. The reprocessed ST5 data are in very good agreement with magnetic perturbations from the Defense Meteorological Satellite Program (DMSP) spacecraft, which we also map to 110 km. We briefly discuss the methods used to remap the ST5 data and the means of validating the results against DMSP. Our methods form the basis for future intermission comparisons of space‐based magnetometer data.
Key Points
ST5 Magnetic Perturbations Have Been ReprocessedReprocessed data at 100 km compare well to DMSP dataKeogram view of data show response to several solar wind drivers
PMCID: PMC5125408  PMID: 27981071
Space Magnetometers; Field Aligned Currents; High Speed Streams; ST5; Cusp Currents
6.  Transient, small‐scale field‐aligned currents in the plasma sheet boundary layer during storm time substorms 
Geophysical Research Letters  2016;43(10):4841-4849.
We report on field‐aligned current observations by the four Magnetospheric Multiscale (MMS) spacecraft near the plasma sheet boundary layer (PSBL) during two major substorms on 23 June 2015. Small‐scale field‐aligned currents were found embedded in fluctuating PSBL flux tubes near the separatrix region. We resolve, for the first time, short‐lived earthward (downward) intense field‐aligned current sheets with thicknesses of a few tens of kilometers, which are well below the ion scale, on flux tubes moving equatorward/earthward during outward plasma sheet expansion. They coincide with upward field‐aligned electron beams with energies of a few hundred eV. These electrons are most likely due to acceleration associated with a reconnection jet or high‐energy ion beam‐produced disturbances. The observations highlight coupling of multiscale processes in PSBL as a consequence of magnetotail reconnection.
Key Points
Multipoint multiscale observations of field‐aligned currents during storm time substormsSmall‐scale intense field‐aligned currents are found embedded in PSBL flux tubes near separatrix regionField‐aligned low‐energy electron beams correlate with short‐lived localized field‐aligned currents
PMCID: PMC5111425  PMID: 27867235
field‐aligned currents; electron beam; MMS; PSBL
7.  Spin-Hall nano-oscillator with oblique magnetization and Dzyaloshinskii-Moriya interaction as generator of skyrmions and nonreciprocal spin-waves 
Scientific Reports  2016;6:36020.
Spin-Hall oscillators (SHO) are promising sources of spin-wave signals for magnonics applications, and can serve as building blocks for magnonic logic in ultralow power computation devices. Thin magnetic layers used as “free” layers in SHO are in contact with heavy metals having large spin-orbital interaction, and, therefore, could be subject to the spin-Hall effect (SHE) and the interfacial Dzyaloshinskii-Moriya interaction (i-DMI), which may lead to the nonreciprocity of the excited spin waves and other unusual effects. Here, we analytically and micromagnetically study magnetization dynamics excited in an SHO with oblique magnetization when the SHE and i-DMI act simultaneously. Our key results are: (i) excitation of nonreciprocal spin-waves propagating perpendicularly to the in-plane projection of the static magnetization; (ii) skyrmions generation by pure spin-current; (iii) excitation of a new spin-wave mode with a spiral spatial profile originating from a gyrotropic rotation of a dynamical skyrmion. These results demonstrate that SHOs can be used as generators of magnetic skyrmions and different types of propagating spin-waves for magnetic data storage and signal processing applications.
PMCID: PMC5081538  PMID: 27786261
8.  Measurement of transverse forces between the first and second metatarsals: a cadaveric study 
This study was designed to measure transverse forces between the 1st and 2nd metatarsals after reducing the intermetatarsal angle (IMA) in normal and hallux valgus (HV) feet, during non weight-bearing and weight-bearing phases of gait.
Four cadaver feet, three normal and one with hallux valgus, were used. A new suture button device (CyclaPlex™) composed of screw-type buttons connected with a wire was implanted at the mid-shaft of the 1st and 2nd metatarsals of all the feet. IMA was reduced using a tensioning device to pull the wire which was secured laterally at the 1st metatarsal. The 1st metatarsal was pulled laterally towards the 2nd metatarsal until an IMA of about 6° was achieved. The amount of force applied at this point was registered on the force indicator. Each foot attached to the tensioning device was placed in a special construct loaded with weights equal to the original body weight of the donor and positioned at 15° tilt (simulating propulsion phase of the gait cycle). The intermetatarsal force under load indicated on the tensioning device was recorded.
The average recorded transverse intermetatarsal force was 28.5 N (SD 4.2 N) during non weight-bearing phase; the mean increase in the measured force at weight-bearing and 15° tilt was 6 N (SD 2.6 N).
We measured the transverse forces between the 1st and 2nd metatarsals with the use of a suture button device (CyclaPlex™). The data obtained from the measurements will provide a better understanding of foot biomechanics and may therefore also facilitate the development of new devices designed to decrease IMA in HV surgery.
PMCID: PMC5067892  PMID: 27751169
Hallux valgus; CyclaPlex™; Mini TightRope®; Intermetatarsal forces; Foot osteotomy
9.  Mesenchymal stem cells enhance the oncolytic effect of Newcastle disease virus in glioma cells and glioma stem cells via the secretion of TRAIL 
Newcastle disease virus (NDV) is an avian paramyxovirus, which selectively exerts oncolytic effects in cancer cells. Mesenchymal stem cells (MSCs) have been reported to affect tumor growth and deliver anti-tumor agents to experimental glioblastoma (GBM). Here, we explored the effects of NDV-infected MSCs derived from different sources, on glioma cells and glioma stem cells (GSCs) and the mechanisms involved in their effects.
The glioma cell lines (A172 and U87) and primary GSCs that were generated from GBM tumors were used in this study. MSCs derived from bone marrow, adipose tissue or umbilical cord were infected with NDV (MTH-68/H). The ability of these cells to deliver the virus to glioma cell lines and GSCs and the effects of NDV-infected MSCs on cell death and on the stemness and self-renewal of GSCs were examined. The mechanisms involved in the cytotoxic effects of the NDV-infected MSCs and their influence on the radiation sensitivity of GSCs were examined as well.
NDV induced a dose-dependent cell death in glioma cells and a low level of apoptosis and inhibition of self-renewal in GSCs. MSCs derived from bone marrow, adipose and umbilical cord that were infected with NDV delivered the virus to co-cultured glioma cells and GSCs. Conditioned medium of NDV-infected MSCs induced higher level of apoptosis in the tumor cells compared with the apoptosis induced by their direct infection with similar virus titers. These results suggest that factor(s) secreted by the infected MSCs sensitized the glioma cells to the cytotoxic effects of NDV. We identified TRAIL as a mediator of the cytotoxic effects of the infected MSCs and demonstrated that TRAIL synergized with NDV in the induction of cell death in glioma cells and GSCs. Moreover, conditioned medium of infected MSCs enhanced the sensitivity of GSCs to γ-radiation.
NDV-infected umbilical cord-derived MSCs may provide a novel effective therapeutic approach for targeting GSCs and GBM and for sensitizing these tumors to γ-radiation.
PMCID: PMC5057491  PMID: 27724977
Newcastle disease virus (NDV); Glioblastoma (GBM); Glioma stem cells (GSCs); Mesenchymal stem cells (MSCs); TRAIL; γ-radiation; Apoptosis; Self-renewal
10.  Improving Antimicrobial Stewardship by Antibiotic Allergy Delabeling: Evaluation of Knowledge, Attitude, and Practices Throughout the Emerging Infections Network 
Open Forum Infectious Diseases  2016;3(3):ofw153.
Antibiotic allergy testing (AAT) practices of Emerging Infections Network infectious disease physicians were surveyed. Although AAT was perceived to be necessary for removal of inappropriate or unnecessary allergy labels, there was limited access to any form of testing. In this study, we discuss current antibiotic allergy knowledge gaps and the development of AAT practices within antimicrobial stewardship programs, which will potentially improve antimicrobial prescribing.
PMCID: PMC5084721  PMID: 27800527
adverse drug reaction; antibiotic allergy; hypersensitivity; skin prick testing; stewardship; penicillin allergy
11.  Ion‐scale secondary flux ropes generated by magnetopause reconnection as resolved by MMS 
Geophysical Research Letters  2016;43(10):4716-4724.
New Magnetospheric Multiscale (MMS) observations of small‐scale (~7 ion inertial length radius) flux transfer events (FTEs) at the dayside magnetopause are reported. The 10 km MMS tetrahedron size enables their structure and properties to be calculated using a variety of multispacecraft techniques, allowing them to be identified as flux ropes, whose flux content is small (~22 kWb). The current density, calculated using plasma and magnetic field measurements independently, is found to be filamentary. Intercomparison of the plasma moments with electric and magnetic field measurements reveals structured non‐frozen‐in ion behavior. The data are further compared with a particle‐in‐cell simulation. It is concluded that these small‐scale flux ropes, which are not seen to be growing, represent a distinct class of FTE which is generated on the magnetopause by secondary reconnection.
Key Points
Ion‐scale flux ropes are observed during magnetopause reconnectionThe largely force‐free flux ropes exhibit filamentary currents and nonideal ion behaviorSmall flux content and comparison with simulation indicate a secondary reconnection origin
PMCID: PMC5001194  PMID: 27635105
magnetic reconnection; magnetopause; flux rope; secondary island; magnetospheric multiscale
12.  Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers 
Vigorito, Elena | Kuchenbaecker, Karoline B. | Beesley, Jonathan | Adlard, Julian | Agnarsson, Bjarni A. | Andrulis, Irene L. | Arun, Banu K. | Barjhoux, Laure | Belotti, Muriel | Benitez, Javier | Berger, Andreas | Bojesen, Anders | Bonanni, Bernardo | Brewer, Carole | Caldes, Trinidad | Caligo, Maria A. | Campbell, Ian | Chan, Salina B. | Claes, Kathleen B. M. | Cohn, David E. | Cook, Jackie | Daly, Mary B. | Damiola, Francesca | Davidson, Rosemarie | de Pauw, Antoine | Delnatte, Capucine | Diez, Orland | Domchek, Susan M. | Dumont, Martine | Durda, Katarzyna | Dworniczak, Bernd | Easton, Douglas F. | Eccles, Diana | Edwinsdotter Ardnor, Christina | Eeles, Ros | Ejlertsen, Bent | Ellis, Steve | Evans, D. Gareth | Feliubadalo, Lidia | Fostira, Florentia | Foulkes, William D. | Friedman, Eitan | Frost, Debra | Gaddam, Pragna | Ganz, Patricia A. | Garber, Judy | Garcia-Barberan, Vanesa | Gauthier-Villars, Marion | Gehrig, Andrea | Gerdes, Anne-Marie | Giraud, Sophie | Godwin, Andrew K. | Goldgar, David E. | Hake, Christopher R. | Hansen, Thomas V. O. | Healey, Sue | Hodgson, Shirley | Hogervorst, Frans B. L. | Houdayer, Claude | Hulick, Peter J. | Imyanitov, Evgeny N. | Isaacs, Claudine | Izatt, Louise | Izquierdo, Angel | Jacobs, Lauren | Jakubowska, Anna | Janavicius, Ramunas | Jaworska-Bieniek, Katarzyna | Jensen, Uffe Birk | John, Esther M. | Vijai, Joseph | Karlan, Beth Y. | Kast, Karin | Investigators, KConFab | Khan, Sofia | Kwong, Ava | Laitman, Yael | Lester, Jenny | Lesueur, Fabienne | Liljegren, Annelie | Lubinski, Jan | Mai, Phuong L. | Manoukian, Siranoush | Mazoyer, Sylvie | Meindl, Alfons | Mensenkamp, Arjen R. | Montagna, Marco | Nathanson, Katherine L. | Neuhausen, Susan L. | Nevanlinna, Heli | Niederacher, Dieter | Olah, Edith | Olopade, Olufunmilayo I. | Ong, Kai-ren | Osorio, Ana | Park, Sue Kyung | Paulsson-Karlsson, Ylva | Pedersen, Inge Sokilde | Peissel, Bernard | Peterlongo, Paolo | Pfeiler, Georg | Phelan, Catherine M. | Piedmonte, Marion | Poppe, Bruce | Pujana, Miquel Angel | Radice, Paolo | Rennert, Gad | Rodriguez, Gustavo C. | Rookus, Matti A. | Ross, Eric A. | Schmutzler, Rita Katharina | Simard, Jacques | Singer, Christian F. | Slavin, Thomas P. | Soucy, Penny | Southey, Melissa | Steinemann, Doris | Stoppa-Lyonnet, Dominique | Sukiennicki, Grzegorz | Sutter, Christian | Szabo, Csilla I. | Tea, Muy-Kheng | Teixeira, Manuel R. | Teo, Soo-Hwang | Terry, Mary Beth | Thomassen, Mads | Tibiletti, Maria Grazia | Tihomirova, Laima | Tognazzo, Silvia | van Rensburg, Elizabeth J. | Varesco, Liliana | Varon-Mateeva, Raymonda | Vratimos, Athanassios | Weitzel, Jeffrey N. | McGuffog, Lesley | Kirk, Judy | Toland, Amanda Ewart | Hamann, Ute | Lindor, Noralane | Ramus, Susan J. | Greene, Mark H. | Couch, Fergus J. | Offit, Kenneth | Pharoah, Paul D. P. | Chenevix-Trench, Georgia | Antoniou, Antonis C.
PLoS ONE  2016;11(7):e0158801.
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
PMCID: PMC4963094  PMID: 27463617
13.  Measuring Activity Limitation Outcomes in Youth with Spinal Cord Injury 
Spinal cord  2015;54(7):546-552.
Study Design
The Pediatric Spinal Cord Injury Activity Measure (PEDI-SCI AM), which includes calibrated item banks (child and parent versions) for General Mobility, Daily Routines, Wheeled Mobility and Ambulation, can be administered using computerized adaptive tests (CATs) or short forms (SFs). The study objectives are: 1.) examine the psychometric properties of the PEDISCI AM item banks and 10-item CATs); 2.) develop and evaluate the psychometric properties of PEDI-SCI AM SFs.
U.S. Shriners Hospitals for Children (California, Illinois and Pennsylvania).
Calibration data from a convenience sample of 381 children and adolescents with SCI and 322 parents or caregivers were used to examine PEDI-SCI AM item banks, 10-item CATs and SF scores. We calculated group reliability, internal consistency (Cronbach's alpha), and interclass coefficients (ICCs) to assess agreement between 10-item CATs, SFs and item banks. The percent of the sample with highest (ceiling) and lowest (floor) scores was also determined. An expert panel selected items for 14 SFs.
PEDI-SCI item banks, 10-item CATs and SFs demonstrate acceptable group reliability (0.73-0.96) and internal consistency (0.77-0.98). ICC values show strong agreement with item banks for 10-item CATs (0.72-0.99) and SFs. Floor effects are minimal (<15%). Ceiling effects are minimal for children with tetraplegia, but high in children with paraplegia for General Mobility (13.41-26.05%) and Daily Activities (12.99-32.71%).
The PEDI-SCI AM exhibited strong psychometric properties for children with tetraplegia. Replenishment of the General Mobility and Daily Routines item banks is needed to reduce ceiling effects noted for youth with paraplegia.
PMCID: PMC4870166  PMID: 26572606
Spinal Cord Injury; Item Response Theory; Computerized Adaptive Tests; Activity Measure; Pediatrics
14.  Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion—A Potential Mechanism for Dietary Influence on Migraine 
Nutrients  2016;8(7):406.
Calcitonin gene-related peptide (CGRP) is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL) and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 μM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further.
PMCID: PMC4963882  PMID: 27376323
calcitonin gene-related peptide; migraine; food trigger; calcium; grape pomace; ginger; butterbur; petasin
15.  Defining “Protein” Foods 
Nutrition Today  2016;51(3):117-120.
Changing the name of the “protein foods” group on the US Department of Agriculture’s visual food guide, MyPlate, back to the “meat & beans” group would provide important clarification regarding US Department of Agriculture recommendations for a balanced diet. Previous iterations of the food guide named the protein group after its constituent foods (ie, the “meat & beans” group on the 2005 MyPyramid), and the reasons for renaming the entire group with MyPlate are unclear. The exclusion of dairy foods from the “protein foods” group of the 2010 MyPlate illustrates the shortcomings of this group’s name. Dairy foods contain high-quality, affordable protein and constitute a significant portion of the protein intake among the US population but are not listed as “protein foods” on MyPlate. Dairy products and other high-calcium foods do have their own section of MyPlate; however, having this separate group does not mitigate the disingenuousness of having a “protein group” that excludes an important protein source. In addition, because consumers tend to understand food-based terms better than nutrient-based terms, a change to “meat & beans” group would also provide clarification for consumers and for educators regarding the content and role of this group.
PMCID: PMC4890830  PMID: 27340301
16.  Medical Student Mental Health 3.0: Improving Student Wellness Through Curricular Changes 
Academic Medicine  2014;89(4):573-577.
Medical education can have significant negative effects on the well-being of medical students. To date, efforts to improve student mental health have focused largely on improving access to mental health providers, reducing the stigma and other barriers to mental health treatment, and implementing ancillary wellness programs. Still, new and innovative models that build on these efforts by directly addressing the root causes of stress that lie within the curriculum itself are needed to properly promote student wellness. In this article, the authors present a new paradigm for improving medical student mental health, by describing an integrated, multifaceted, preclinical curricular change program implemented through the Office of Curricular Affairs at the Saint Louis University School of Medicine starting in the 2009–2010 academic year. The authors found that significant but efficient changes to course content, contact hours, scheduling, grading, electives, learning communities, and required resilience/mindfulness experiences were associated with significantly lower levels of depression symptoms, anxiety symptoms, and stress, and significantly higher levels of community cohesion, in medical students who participated in the expanded wellness program compared with those who preceded its implementation. The authors discuss the utility and relevance of such curricular changes as an overlooked component of change models for improving medical student mental health.
PMCID: PMC4885556  PMID: 24556765
17.  ‘Not Until I'm Absolutely Half-Dead and Have To:’ Accounting for Non-Use of Antiretroviral Therapy in Semi-Structured Interviews with People Living with HIV in Australia 
AIDS Patient Care and STDs  2015;29(5):267-278.
Current debates regarding the use of antiretroviral therapy (ART) to promote both individual- and population-level health benefits underscore the importance of understanding why a subpopulation of people with diagnosed HIV and access to treatment choose not to use it. Semi-structured interviews were conducted between 2012 and 2014 with 27 people living with HIV in Australia who were not using ART at the time of interview. Analytic triangulation permitted an appreciation of not only the varied personal reasons for non-use of treatment, but also underlying views on HIV treatment, and the ideal conditions imagined necessary for treatment initiation. Policy goals to increase the number of people with HIV using ART must recognize the diverse explanations for non-use of ART, which include concerns about the various impacts of committing to lifelong pharmaceutical treatment use. Our research identified distinctive subgroups among people who are not using antiretroviral therapy, with a range of individual and social needs that may affect treatment decisions. These findings challenge assumptions about treatment non-use in resource-rich settings, revealing persistent consumer fears about the potent and unknown effects of HIV medications that deserve greater recognition in policy debate on treatment uptake.
PMCID: PMC4410544  PMID: 25806574
18.  Development and initial evaluation of the SCI-FI/AT 
To describe the domain structure and calibration of the Spinal Cord Injury Functional Index for samples using Assistive Technology (SCI-FI/AT) and report the initial psychometric properties of each domain.
Cross sectional survey followed by computerized adaptive test (CAT) simulations.
Inpatient and community settings.
A sample of 460 adults with traumatic spinal cord injury (SCI) stratified by level of injury, completeness of injury, and time since injury.
Main outcome measure
Confirmatory factor analysis (CFA) and Item response theory (IRT) analyses identified 4 unidimensional SCI-FI/AT domains: Basic Mobility (41 items) Self-care (71 items), Fine Motor Function (35 items), and Ambulation (29 items). High correlations of full item banks with 10-item simulated CATs indicated high accuracy of each CAT in estimating a person's function, and there was high measurement reliability for the simulated CAT scales compared with the full item bank. SCI-FI/AT item difficulties in the domains of Self-care, Fine Motor Function, and Ambulation were less difficult than the same items in the original SCI-FI item banks.
With the development of the SCI-FI/AT, clinicians and investigators have available multidimensional assessment scales that evaluate function for users of AT to complement the scales available in the original SCI-FI.
PMCID: PMC4445031  PMID: 26010975
Outcome assessment (health care); Psychometrics; Quality of Life; Rehabilitation; Spinal cord injuries
19.  Excitation of propagating spin waves in ferromagnetic nanowires by microwave voltage-controlled magnetic anisotropy 
Scientific Reports  2016;6:25018.
The voltage-controlled magnetic anisotropy (VCMA) effect, which manifests itself as variation of anisotropy of a thin layer of a conductive ferromagnet on a dielectric substrate under the influence of an external electric voltage, can be used for the development of novel information storage and signal processing devices with low power consumption. Here it is demonstrated by micromagnetic simulations that the application of a microwave voltage to a nanosized VCMA gate in an ultrathin ferromagnetic nanowire results in the parametric excitation of a propagating spin wave, which could serve as a carrier of information. The frequency of the excited spin wave is twice smaller than the frequency of the applied voltage while its amplitude is limited by 2 mechanisms: (i) the so-called “phase mechanism” described by the Zakharov-L’vov-Starobinets “S-theory” and (ii) the saturation mechanism associated with the nonlinear frequency shift of the excited spin wave. The developed extension of the “S-theory”, which takes into account the second limitation mechanism, allowed us to estimate theoretically the efficiency of the parametric excitation of spin waves by the VCMA effect.
PMCID: PMC4845021  PMID: 27113392
20.  ICC-dementia (International Centenarian Consortium - dementia): an international consortium to determine the prevalence and incidence of dementia in centenarians across diverse ethnoracial and sociocultural groups 
BMC Neurology  2016;16:52.
Considerable variability exists in international prevalence and incidence estimates of dementia. The accuracy of estimates of dementia in the oldest-old and the controversial question of whether dementia incidence and prevalence decline at very old age will be crucial for better understanding the dynamics between survival to extreme old age and the occurrence and risk for various types of dementia and comorbidities. International Centenarian Consortium – Dementia (ICC-Dementia) seeks to harmonise centenarian and near-centenarian studies internationally to describe the cognitive and functional profiles of exceptionally old individuals, and ascertain the trajectories of decline and thereby the age-standardised prevalence and incidence of dementia in this population. The primary goal of the ICC-Dementia is to establish a large and thorough heterogeneous sample that has the power to answer epidemiological questions that small, separate studies cannot. A secondary aim is to examine cohort-specific effects and differential survivorship into very old age. We hope to lay the foundation for further investigation into risk and protective factors for dementia and healthy exceptional brain ageing in centenarians across diverse ethnoracial and sociocultural groups.
Studies focusing on individuals aged ≥95 years (approximately the oldest 1 percentile for men, oldest 5th percentile for women), with a minimum sample of 80 individuals, including assessment of cognition and functional status, are invited to participate. There are currently seventeen member or potential member studies from Asia, Europe, the Americas, and Oceania. Initial attempts at harmonising key variables are in progress.
General challenges facing large, international consortia like ICC-Dementia include timely and effective communication among member studies, ethical and practical issues relating to human subject studies and data sharing, and the challenges related to data harmonisation. A specific challenge for ICC-Dementia relates to the concept and definition of’abnormal’ in this exceptional group of individuals who are rarely free of physical, sensory and/or cognitive impairments.
PMCID: PMC4839126  PMID: 27098177
Centenarians; Dementia; International; Prevalence; Incidence; Risk factors
22.  HealthMap: a cluster randomised trial of interactive health plans and self-management support to prevent coronary heart disease in people with HIV 
BMC Infectious Diseases  2016;16:114.
The leading causes of morbidity and mortality for people in high-income countries living with HIV are now non-AIDS malignancies, cardiovascular disease and other non-communicable diseases associated with ageing. This protocol describes the trial of HealthMap, a model of care for people with HIV (PWHIV) that includes use of an interactive shared health record and self-management support. The aims of the HealthMap trial are to evaluate engagement of PWHIV and healthcare providers with the model, and its effectiveness for reducing coronary heart disease risk, enhancing self-management, and improving mental health and quality of life of PWHIV.
The study is a two-arm cluster randomised trial involving HIV clinical sites in several states in Australia. Doctors will be randomised to the HealthMap model (immediate arm) or to proceed with usual care (deferred arm). People with HIV whose doctors are randomised to the immediate arm receive 1) new opportunities to discuss their health status and goals with their HIV doctor using a HealthMap shared health record; 2) access to their own health record from home; 3) access to health coaching delivered by telephone and online; and 4) access to a peer moderated online group chat programme. Data will be collected from participating PWHIV (n = 710) at baseline, 6 months, and 12 months and from participating doctors (n = 60) at baseline and 12 months. The control arm will be offered the HealthMap intervention at the end of the trial. The primary study outcomes, measured at 12 months, are 1) 10-year risk of non-fatal acute myocardial infarction or coronary heart disease death as estimated by a Framingham Heart Study risk equation; and 2) Positive and Active Engagement in Life Scale from the Health Education Impact Questionnaire (heiQ).
The study will determine the viability and utility of a novel technology-supported model of care for maintaining the health and wellbeing of people with HIV. If shown to be effective, the HealthMap model may provide a generalisable, scalable and sustainable system for supporting the care needs of people with HIV, addressing issues of equity of access.
Trial registration
Universal Trial Number (UTN) U111111506489; Id NCT02178930 submitted 29 June 2014
PMCID: PMC4779564  PMID: 26945746
Self-management; HIV; Cardiovascular disease; Health plans; Internet; Public health; Health services
23.  Outcomes of unplanned sarcoma excision: impact of residual disease 
Cancer Medicine  2016;5(6):980-988.
This study aimed to compare the oncological results between unplanned excision (UE) and planned excision (PE) of malignant soft tissue tumor and to examine the impact of residual tumor (ReT) after UE. Nonmetastatic soft tissue sarcomas surgically treated in 1996–2012 were included in this study. Disease‐specific survival (DSS), metastasis‐free survival (MFS), and local‐recurrence‐free survival (LRFS) were stratified according to the tumor location and American Joint Committee on Cancer Classification 7th edition stage. Independent prognostic parameters were identified by Cox proportional hazard models. Two‐hundred and ninety PEs and 161 UEs were identified. Significant difference in oncological outcome was observed only for LRFS probability of retroperitoneal sarcomas (5‐year LRFS: 33.0% [UE] vs. 71.0% [PE], P = 0.018). Among the 142 UEs of extremity and trunk, ReT in re‐excision specimen were found in 75 cases (53%). UEs with ReT had significantly lower survival probabilities and a higher amputation rate than UEs without ReT (5‐year DSS: 68.8% vs. 92%, P < 0.001; MFS: 56.1% vs. 90.9%, P < 0.001; LRFS: 75.8% vs. 98.4%, P = <0.001; amputation rate 18.5% vs. 1.8%, P = 0.003). The presence of ReT was an independent poor prognostic predictor for DSS, MFS, and LRFS with hazard ratios of 2.02 (95% confidence interval (CI), 1.25–3.26), 1.62 (95% CI, 1.05–2.51) and 1.94 (95% CI, 1.05–3.59), respectively. Soft tissue sarcomas should be treated in specialized centers and UE should be avoided because of its detrimental effect especially when ReT remains after UE.
PMCID: PMC4924354  PMID: 26929181
Neoplasm staging; prognosis; residual neoplasm; sarcoma mortality; sarcoma surgery; soft tissue sarcoma; treatment outcome
24.  The prevention and management of infections due to multidrug resistant organisms in haematology patients 
Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens.
PMCID: PMC4309626  PMID: 24341410
fluoroquinolone prophylaxis; haematology; healthcare-associated infection; multiresistant gram negatives; vancomycin-resistant enterococci (VRE)
25.  Bile duct reconstruction following laparoscopic cholecystectomy in England 
Surgical Endoscopy  2016;30:3516-3525.
To determine the incidence of bile duct reconstruction (BDR) following laparoscopic cholecystectomy (LC) and to identify associated risk factors.
Major bile duct injury (BDI) requiring reconstruction is a serious complication of cholecystectomy.
All LC and attempted LC operations in England between April 2001 and March 2013 were identified. Patients with malignancy, a stone in bile duct or those who underwent bile duct exploration were excluded. This cohort of patients was followed for 1 year to identify those who underwent BDR as a surrogate marker for major BDI. Logistic regression was used to identify factors associated with the need for reconstruction.
In total, 572,223 LC and attempted LC were performed in England between April 2001 and March 2013. Five hundred (0.09 %) of these patients underwent BDR. The risk of BDR is lower in patient that do not have acute cholecystitis [odds ratio (OR) 0.48 (95 % CI 0.30–0.76)]. The regular use of on-table cholangiography (OTC) [OR 0.69 (0.54–0.88)] and high consultant caseload >80 LC/year [OR 0.56 (0.39–0.54)] reduced the risk of BDR. Patients who underwent BDR were 10 times more likely to die within a year than those who did not require further surgery (6 vs. 0.6 %).
The rate of BDR following laparoscopic cholecystectomy in England is low (0.09 %). The study suggests that OTC should be used more widely and provides further evidence in support of the provision of LC services by specialised teams with an adequate caseload (>80).
PMCID: PMC4956705  PMID: 26830413
Bile duct injury; Bile duct reconstruction; Hospital Episode Statistics data; Laparoscopic cholecystectomy; On-table cholangiography

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