bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Comparison of Multidimensional Clinical Assessment Tools: Sensitivity to Concussion in Student Athletes
Authors: Wilmoth K , Mau K , Guzowski N , Brett B , McCrea M , Nelson L
Published: July 2019

Purpose

Consensus guidelines recommend multidimensional assessment for concussion diagnosis and management. Among cognitive, oculomotor, and postural stability, it remains unclear which modalities perform best in the acute/subacute periods. We conducted a direct comparison to identify those with the strongest sensitivity to sport-related concussion.

Methods

High school and collegiate football players (aged 14–24) completed preseason baseline assessments. Concussed (n=91) and matched non-concussed teammates (n=85) underwent repeat testing at 48 hours, 8 days, and 15 days post-injury. Postconcussive symptoms (SCAT-3 symptom severity), cognition (Standardized Assessment of Concussion, Immediate Post-Concussion and Cognitive Testing, Trail Making Test, Wechsler Adult Intelligence Scale-IV Processing Speed Index), oculomotor functioning (King-Devick Test), and postural stability (Balance Error Scoring System) were compared using Cohen’s d and Receiver Operating Characteristic analyses.

Results

Symptom severity had the greatest sensitivity at 48 hours and 8 days post-injury (Cohen’s d=1.43 and 0.53, AUC=.93 and .63, p<.01). Of the performance-based assessments, BESS was most sensitive to SRC at 48 hours post-injury (Cohen’s d=.74, AUC=.70, p<.01). Oculomotor and cognitive testing via ImPACT, WAIS-IV PSI, and TMT-A were sensitive to a lesser degree (Cohen’s d=.35–.58, p<.05). Verbal memory was the only significant performance-based assessment at days 8 and 15, with small-to-medium effect sizes (Cohen’s d=.37 and .44, p<.05). Other cognitive measures (SAC, TMT-B) were not sensitive to SRC across timepoints (p>.05).

Conclusion

We observed heterogeneity in clinical assessment performance such that the clinical domains strongest in the initial days post-injury (symptom severity, balance) were less sensitive at later follow-up, supporting the potential need for multidimensional assessment.
Examining Changes in Sleep Between Concussed and Healthy Individuals Across Recovery
Authors: Anderson M , Bretzin A C , Petit K M , Tomczyk C P , Savage J L , Covassin T
Published: July 2019

Purpose

To examine changes and the relationship between Pittsburgh Sleep Quality Index (PSQI) scores and the Sport Concussion Assessment Tool–5th Edition (SCAT5) sleep symptom across recovery between concussed and healthy individuals.

Methods

Sixty-eight (18.12±2.6 years; male:n=47, female:n=21; concussed:n=38, healthy:n=30) individuals completed the PSQI and SCAT5 at three times across recovery (≤72 hours of injury, return-to-play (RTP), >one-month after RTP). Two mixed between-within subjects analysis of variance (ANOVAs) evaluated changes in PSQI scores and SCAT5 sleep symptom across recovery between concussed and healthy individuals. Spearman’s rho correlations were used to examine the relationships between the two sleep measures. Significance was set at p≤.05.

Results

There was no significant groupXtime interaction for PSQI scores (Wilks λ=.96, F(2,65)=1.50, p=.23, η2=.04) or SCAT5 sleep symptom (Wilks λ=.93, F(2,65)=2.42, p=.10, η2=.07). There was a significant main effect for time for PSQI scores (Wilks λ=.65, F(2,65)=17.2, p<.001, η2=.35) and SCAT5 sleep symptom (Wilks λ=.88, F(2,65)=4.25, p=.02, η2=.12) with PSQI scores and SCAT5 sleep symptom improving over time. For the SCAT5 sleep symptom there was a significant main effect for group (F(1,66)=13.41, p<.001, η2=.17), with concussed individuals reporting higher SCAT5 sleep symptom (M=0.59, SE=0.1) than healthy controls (M=0.09, SE=0.1). There was no significant correlation between PSQI scores and SCAT5 sleep symptom ≤72 hours (r=.15, p=.36), but there were significant correlations at RTP (r=.38, p=.02) and >one-month (r=.43, p=.01).

Conclusion

Global sleep quality changes throughout recovery and may influence post-concussion outcomes. Utilizing a specialized sleep measure along with sleep-related symptoms may be beneficial to healthcare professionals, specifically during acute concussion management.
Middle School Children with Attention-Deficit/Hyperactivity Disorder Have a Greater Concussion History
Authors: Iverson G L , Kelshaw P M , Cook N E , Caswell S V
Published: July 2019

Purpose

Examine lifetime history of concussions in middle school student athletes who have attention-deficit/hyperactivity disorder (ADHD).

Methods

A sample of 1,037 students from nine middle schools in Virginia, USA (ages 11 to 14, M=12.6, SD=0.93; 45.8% girls) underwent baseline/pre-season assessments during the 2017-2018 academic year and self-reported their health history, including whether or not they had been diagnosed with ADHD and their concussion history. Athletes were divided into two groups, those with ADHD (n=71; 6.8%) and control subjects (n=966). Chi-Square tests were conducted to compare the number of prior concussions in students with and without ADHD.

Results

In the total sample, boys were more likely to report a prior history of concussion than girls [χ2(1) =10.81, p=.001; OR=1.92; 95% CI=1.30-2.85]. The frequency of prior concussion in children with ADHD (23.9%) was twice the frequency of prior concussion among children without ADHD (11.4%) [χ2(1)=9.70, p=.002; OR=2.45; 95% CI=1.37-4.38]. Approximately one in four boys with ADHD (24.5%) and one in five girls with ADHD (22.2%) reported having sustained one or more prior concussions.

Conclusion

ADHD is associated with a greater prevalence of prior concussion in middle school children. Further research is needed to understand the risk of sustaining concussion for young athletes with ADHD, as well as short- and long-term outcomes of concussion among young athletes with ADHD.
Exploring Athletic Trainers' Self-Confidence for Interpreting Results from Concussion Assessments
Authors: D’Amico N R , Covassin T , Murray N , Schatz P , Elbin R J
Published: July 2019

Purpose

To explore athletic trainers' self-confidence for interpreting results from concussion assessments.

Methods

An online survey was administered via the National Athletic Trainers’ Association (NATA) membership listserv to a cross-sectional sample of 10,000 certified athletic trainers (ATCs) employed in high school and collegiate settings. The survey included: 1) ATC demographics (i.e., age, sex, years of experience); 2) ATC concussion management practices (i.e., previous concussion training, continuing education received on concussion, concussion assessments administered); and 3) a 4-point Likert scale (1=no confidence, 4=high confidence) assessing ATC self-confidence for interpreting results from concussion assessments. A total of 725 ATCs completed the survey yielding a response rate of 7.25%; 114 were excluded for missing data and 611 ATCs were included in final analyses. Sample demographics, ATC concussion management practices, and ATC self-confidence scores were examined with demographic statistics (i.e., means, standard deviations, frequencies, percentages) for 16 commonly used concussion assessments.

Results

The sample of ATCs (mean age 38.97±14.89 years) was predominately female (59.2%) and reported an average of 10.08±7.58 years of clinical experience. Clinical examinations (63.2%) and symptom scales (61.4%) were among the most frequent assessments with high ATC self-confidence for interpretation. Vestibular/oculomotor measures (27.2%) and computerized neurocognitive testing (26.2%) were among the most frequent assessments with low ATC self-confidence for interpretation.

Conclusion

Low ATC self-confidence scores for interpreting results from vestibular/oculomotor measures and computerized neurocognitive testing highlight the importance of incorporating a multi-disciplinary team approach and including sport neuropsychologists for the proper management of concussion.
Initial Average Symptom Severity is a Better Predictor of Recovery following Concussion than Total Symptom Burden
Authors: Kowalczyk C L , Holland C L , Collins M W , Kontos A P
Published: July 2019

Purpose

Symptom reports such as the Post-concussion Symptom Scale (PCSS) are common assessments following concussion. Patients with high symptom burden following a concussion take longer to recover. However, two patients could have a symptom burden of 30, which is high, but one patient has endorsed only 6 items for an average severity of 5; whereas, another patient has endorsed 15 items for an average severity of 2. The purpose of this study was to compare the association of different symptom outcomes (i.e., average symptom severity, total symptom severity [i.e., symptom burden] and total number of symptoms) on recovery time.

Methods

Participants included 109 (46-M/64-F) concussed patients aged 13–21 years (15.0±1.7) from a specialty clinic. Participants completed the PCSS and total symptom and average symptom severity scores were then calculated. Recovery time (i.e., date of injury to full medical clearance) was recorded. Pearson product-moment correlations and multiple regression (MR) were used to analyze the data.

Results

The results from the Pearson product-moment correlations indicated that all of the symptom outcomes were correlated. Only the average symptom severity score was correlated (r=.23, p<.05) with recovery time. Results from the MR for recovery time indicated that average symptom severity was associated with a longer recovery time (Beta=.40, t=2.2, p=.03).

Conclusion

Findings indicate that average symptom severity was the best predictors of recovery time, which is in contrast to the literature, and highlights the importance for clinicians to consider average symptom severity in prognosis following concussion.
The Relation Between Cognitive Performance and Symptom Factors Following Concussion
Authors: Whitley E , Gerkin R , Kontos A , Quintana C , Nalepa B , Pardini J
Published: July 2019

Purpose

The purpose of this study was to explore if symptom factors are related to cognitive outcomes. Prior studies have examined the relationship of individual symptoms to cognition. However, the relation between empirically-derived symptom factors and cognitive outcomes has yet to be explored.

Methods

Data were extracted via retrospective chart review of 691 patients (aged 10–24, mean: 14.99±2.63). Participants completed ImPACT and the PCSS within 14 days of injury (mean: 9.27±3.37). Predictors were PCSS factor scores of Cognitive-Fatigue-Migraine (CFM), Affective (AFF), Somatic (SOM), and Sleep (SLP) (Kontos et al., 2012). Outcomes examined were ImPACT composite scores. Univariate analyses were performed and values with p < 0.10 were entered into stepwise linear regression (LR) models. Retained predictors in each LR model had p values <.05.

Results

Verbal memory was predicted by CFM, SOM, age, and gender. Visual memory was predicted by CFM and SOM. Visual motor speed was predicted by age, gender, CFM, SOM, and AFF. Reaction time was best predicted by SOM, CFM, and age. The variance explained was fairly small (0.08 to 0.21). SLP was not a significant predictor in any LR.

Conclusion

CFM and SOM factors were most predictive of lower cognitive performance, similar to prior studies linking dizziness to longer recovery and post-traumatic migraine to worse cognitive performance. These findings underscore the clinical importance of diverse symptom assessment and injury education. Higher CFM and SOM scores may also serve as proxy for injury severity, which we would expect to be associated with worse cognitive performance.
Reliability and Consistency of the Vestibular/Ocular Motor Screening (VOMS) Assessment Near Point of Convergence (NPC) Trials
Authors: Ernst N , Sufrinko A , Collins M , Kontos A
Published: July 2019

Purpose

To examine the reliability of near point of convergence (NPC) across three trials and determine if one trial of NPC is adequate to identify receded NPC post-concussion.

Methods

Participants included 263 concussed patients (64.3% male; age=16.92±3.49 years) evaluated within 21 days of injury. NPC was measured in centimeters from the tip of the nose using a fixation stick and a Gulick anthropometric tape measure. A two-way, mixed effect, absolute agreement intraclass correlation coefficient (ICC 3,1) was conducted to evaluate reliability across the three trials. A chi-square analysis examined consistency of NPC classification (normal/abnormal) on the initial trial compared to average across three trials.

Results

Reliability of the three trials was high (.91 [95%CI, .89–.93]). Agreement between Trial 1 classification and classification based on average of all three trials was high (96.2%). Of the 10 participants who were classified differently for Trial 1 compared to average trials, 8 had borderline (e.g., 4–6 cm) measurements on the first trial.

Conclusion

NPC measurement across trials is reliable for the overall sample, but those who fell well below (i.e. 0–1cm) or well above (>8cm) clinical cutoffs on the first trial were almost always below or above respective cutoffs on the average convergence (>99%). Results suggest it is important to measure NPC across multiple trials for patients with initial borderline measurement.
Preliminary Examinations of Concussion in Older Adults
Authors: Combs J , Puskar A , Blaney N , Collins M , Kontos A
Published: July 2019

Purpose

This study sought to investigate whether concussion in older adults improves through evaluating their performance on the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Vestibular/Ocular-Motor Screen (VOMS) across visits and to describe and better characterize concussion in this at-risk population.

Methods

We conducted a retrospective review of medical records for 69 older adult patients (40 females, 29 males) that presented to a concussion specialty clinic. Participants averaged 64.71 (SD=4.1) years in age and presented within 6-998 days of injury (SD=170.9). Demographics and clinical data were recorded at intake through last appointment. Descriptive analysis, including frequencies, means, and standard deviations were performed as well as paired T-test to compare mean scores for first and last visit. Statistical significance was determined by two-sided p-values <.05.

Results

Twenty out of 69 participants (29%) reported a previous concussion. Concussion symptom severity scores at participants’ first clinic visit averaged 56.19 (SD=26.56) compare with 39.51 (SD=25.53) at their final clinic visit. When comparing ImPACT data, all scores improved comparatively from Visit 1 to Last Visit (P values =0.000-0.014); all VOMS total scores improved as well (P =0.00-0.047). The most frequent primary profile among participants was Vestibular (31.9%).

Conclusion

Older adults diagnosed with concussion showed improvement on ImPACT scores and their symptom severity scores decreased. The most frequent primary concussion profile at initial visit was Vestibular. Further research with this at-risk population is needed.
Variability in ImPACT Baseline Scores in Adolescent Athletes
Authors: Bennett R , Datoc A , Stebbins L , Lashley L , Posey A
Published: July 2019

Purpose

The purpose of this study was to observe the test-retest-reliability of adolescent athlete Baseline ImPACT scores over a one and two-year interval.

Methods

Participants were selected from an archival de-identified sports medicine ImPACT database in Florida. The sample (N=4,044) consisted of primarily male (62.2%), adolescent athletes aged (Mage= 15.45, SD=1.291). Athletes were included in the study if they completed an initial and follow-up baseline ImPACT between 2016 and 2019, and if they had no history of concussion. One-Way ANOVA was conducted to determine the relationship between overall mean composite and total symptom scores between baseline tests.

Results

One-Way ANOVA revealed Verbal Memory (F[2,4041])=16.231, p<.001), Visual Memory (F[2,4041])=23.528, p<.001), and Visual Motor (F[2,4041)=46.111, p<.001) composite scores significantly differed over time. While these results yielded statistical significance over time, further descriptive statistics showed that the mean differences for these composite scores did not fall outside of the ImPACT Reliable Change Index (RCI) criteria.

Conclusion

Assuming no significant physical or cognitive changes between baseline administrations, ImPACT composite and total symptom scores are expected to be consistent over time. Results indicate that ImPACT composite and total symptom scores are reliable in an adolescent sample across one and two-year time periods. Previous literature regarding test-retest reliability of composite and total symptom scores on ImPACT in youth and adolescent athletes has been inconsistent, which has caused researchers and clinicians to question the clinical utility of this assessment. Future research is needed to highlight the utilization of clinical judgement and clarify the psychometric properties of this measure.
Relationships between Head Impacts, Competitive Aggression, and Risk-taking Behavior in Collegiate Ice Hockey Players
Authors: DiFabio M S , Buckley T A
Published: July 2019

Purpose

To examine relationships between head impact kinematics sustained over a season and competitive aggression and self-reported risk-taking behavior in collegiate club ice-hockey athletes.

Methods

Twenty male ice-hockey players (19.9±1.2 y.o, 1.8±0.06 m, 78.5±5.7 kg) completed the Competitive Anger and Aggression Scale (CAAS, Range:0-84) and the Brief Sensation Seeking Scale (BSSS, Range:8-40) during the preseason as measures of competitive aggression and risk-taking behavior with higher/lower reflecting higher/lower aggression and risk taking. Penalty minutes (PM) and games played (GP) were taken from official game records. Head impact kinematics (number of impacts, linear mean, peak, cumulative acceleration) were recorded by tri-axial accelerometers worn during games/practices. Spearman correlation was performed to examine relationships between variables.

Results

The mean number of impacts was 76.6±54.9 (range: 6–171); mean and cumulative acceleration were 36.3±4.2g (range:27.8–42.2g) and 2829.4±2024.9g (range:198.4–6527.2g), respectively. Neither CAAS (mean: 48.7±10.9, range: 24–64) nor BSSS scores (mean: 25.3±4.4, range:15–32) were significantly related to impact kinematics. GP was significantly correlated with number of impacts (r=.63, p=.003) and cumulative linear acceleration (r=.61, p=.004). PM was significantly correlated with number of impacts (r=.52, p=.20) and cumulative linear acceleration (r=.55, p=.13).

Conclusion

There were no relationships between the head impact kinematics and self-reported aggressiveness or risk taking behavior, but more PM was strongly related to higher head impact loads. Considering PM may be useful in aiding to identify athletes who may sustain higher head impact loads, however, self-reports of behavior may not be.
Testing the Hybrid Battery Approach to Evaluating Sports-Related Concussion in the National Hockey League: A Factor Analytic Study
Authors: Echemendia R J , Bruce J M , Thelen J , Hutchison M , Comper P , Meeuwisse W
Published: July 2019

Purpose

Traditional “paper and pencil” neuropsychological tests and computerized test batteries have been employed in the assessment of sports-related concussion (SRC). Each type of test has inherent strengths and weaknesses. The NHL has constructed a “hybrid” battery of tests that uses both traditional and computerized measures in the evaluation of its players suspected of SRC. The purpose of this paper is to use factor analytic techniques to examine the relationships among the measures that comprise this battery.

Methods

Post-injury neuropsychological test data using the hybrid battery were obtained from 343 NHL players following their first concussion while playing in the league. ImPACT was used as the computer test battery. The traditional battery included: Hopkins Verbal Learning Test, Brief Visuospatial Memory Test, Color Trails, PSU Cancellation, Symbol Digits Modalities Test (including incidental memory), and Verbal Fluency.

Results

Five factors were extracted explaining 64.55% of the variance. The factor labels and the measures principally loading on each factor were as follows: Factor 1, Verbal Learning and Memory (HVLT Total and Delayed Recall); Factor 2, Processing Speed (Color Trails A/B, PSU Cancellation, and SDMT-Total); Factor 3, Visual Memory (BVMT- Total and Delayed); Factor 4, Cued Memory (ImPACT-Visual and Verbal Memory Composites); and Factor 5, Reaction Time (ImPACT Reaction Time and Visual Motor Speed composites).

Conclusion

These data underscore the unique contributions of traditional and ImPACT neuropsychological measures to the evaluation SRC in a sample of professional hockey players. It appears that both approaches measure different aspects of cognitive functioning. The next logical step is to use these data in evaluating the diagnostic utility of these measures as part of a combined battery.
The Influence of Hormonal Contraceptives on Baseline ImPACT Performance
Authors: Carrington H W , Broshek D K , Erdman N K , Thompson X D , Walton S R , Resch J E
Published: July 2019

Purpose

Our study examined the influence of hormonal contraceptives (HC) on pre-injury (baseline) ImPACT performance in female collegiate athletes.

Methods

Participants in our cross-sectional study consisted of 304 NCAA Division I female athletes who self-reported taking (HC+ [n=154]) or not taking (HC- [n=154]) HC. HC+ participants were matched to HC- participants for height, weight, sport, and position. HC+ participants had an average age of 19.0±1.33 years, height of 170.5–8.70 cm, and mass of 64.2–10.58 kg. HC- participants had an average age of 19.0±1.24 years, height of 170.3–9.19 cm, and mass of 64.2–9.75 kg. Participants completed ImPACT as part of their preseason baseline assessment. Only participants with valid ImPACT assessments were included in our analyses. Chi-squared (χ2) tests were performed to compare groups in terms of medical history variables. Independent t-tests were used to compare groups in terms of demographic variables, self-reported hours of sleep, and ImPACT (Verbal and Visual Memory, Visual Motor Speed [VMS], Reaction Time [RT], and Total Symptom Severity [TSS]) outcome scores. Analyses were performed with α=0.05.

Results

No differences were observed between groups for demographic variables, hours of sleep, or medical history variables (p<0.05). For VMS, the HC- group (42.9+5.63) scored significantly worse (t[304]=2.17, p=0.03; d=0.25; 95% CI [0.1, 2.7]) than the HC+ group (44.3+5.67). For RT, the HC- group (0.55+0.06) performed significantly slower (t[304]=-2.02, p=0.05; d=0.23; 95% CI [-0.03, -0.0003]) than the HC+ group (0.54+0.05).

Conclusion

Our results suggest HCs may influence ImPACT performance in female collegiate athletes. Clinicians must consider the role of HCs when interpreting ImPACT outcome scores.
PyMethylProcess—convenient high-throughput preprocessing workflow for DNA methylation data
Authors: Levy Joshua J , Titus Alexander J , Salas Lucas A , Christensen Brock C
Published: July 2019

Performing highly parallelized preprocessing of methylation array data using Python can accelerate data preparation for downstream methylation analyses, including large scale production-ready machine learning pipelines. We present a highly reproducible, scalable pipeline (PyMethylProcess) that can be quickly set-up and deployed through Docker and PIP.

Availability and implementation

Project Home Page: https://github.com/Christensen-Lab-Dartmouth/PyMethylProcess. Available on PyPI (pymethylprocess), Docker (joshualevy44/pymethylprocess).

Supplementary information

Supplementary data are available at Bioinformatics online.
Gaussian mixture copulas for high-dimensional clustering and dependency-based subtyping
Authors: Kasa Siva Rajesh , Bhattacharya Sakyajit , Rajan Vaibhav
Published: July 2019

Motivation

The identification of sub-populations of patients with similar characteristics, called patient subtyping, is important for realizing the goals of precision medicine. Accurate subtyping is crucial for tailoring therapeutic strategies that can potentially lead to reduced mortality and morbidity. Model-based clustering, such as Gaussian mixture models, provides a principled and interpretable methodology that is widely used to identify subtypes. However, they impose identical marginal distributions on each variable; such assumptions restrict their modeling flexibility and deteriorates clustering performance.

Results

In this paper, we use the statistical framework of copulas to decouple the modeling of marginals from the dependencies between them. Current copula-based methods cannot scale to high dimensions due to challenges in parameter inference. We develop HD-GMCM, that addresses these challenges and, to our knowledge, is the first copula-based clustering method that can fit high-dimensional data. Our experiments on real high-dimensional gene-expression and clinical datasets show that HD-GMCM outperforms state-of-the-art model-based clustering methods, by virtue of modeling non-Gaussian data and being robust to outliers through the use of Gaussian mixture copulas. We present a case study on lung cancer data from TCGA. Clusters obtained from HD-GMCM can be interpreted based on the dependencies they model, that offers a new way of characterizing subtypes. Empirically, such modeling not only uncovers latent structure that leads to better clustering but also meaningful clinical subtypes in terms of survival rates of patients.

Availability and implementation

An implementation of HD-GMCM in R is available at: https://bitbucket.org/cdal/hdgmcm/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Friend or foe—IDH1 mutations in glioma 10 years on
Authors: Huang L Eric
Published: July 2019

The identification of recurrent point mutations in the isocitrate dehydrogenase 1 (IDH1) gene, albeit in only a small percentage of glioblastomas a decade ago, has transformed our understanding of glioma biology, genomics and metabolism. More than 1000 scientific papers have been published since, propelling bench-to-bedside investigations that have led to drug development and clinical trials. The rapid biomedical advancement has been driven primarily by the realization of a neomorphic activity of IDH1 mutation that produces high levels of (d)-2-hydroxyglutarate, a metabolite believed to promote glioma initiation and progression through epigenetic and metabolic reprogramming. Thus, novel inhibitors of mutant IDH1 have been developed for therapeutic targeting. However, numerous clinical and experimental findings are at odds with this simple concept. By taking into consideration a large body of findings in the literature, this article analyzes how different approaches have led to opposing conclusions and proffers a counterintuitive hypothesis that IDH1 mutation is intrinsically tumor suppressive in glioma but functionally undermined by the glutamate-rich cerebral environment, inactivation of tumor-suppressor genes and IDH1 copy-number alterations. This theory also provides an explanation for some of the most perplexing observations, including the scarcity of proper model systems and the prevalence of IDH1 mutation in glioma.
A Sparse Probabilistic Code Underlies the Limits of Behavioral Discrimination
Authors: Sriram Balaji , Li Lillian , Cruz-Martín Alberto , Ghosh Anirvan
Published: July 2019

The cortical code that underlies perception must enable subjects to perceive the world at time scales relevant for behavior. We find that mice can integrate visual stimuli very quickly (<100 ms) to reach plateau performance in an orientation discrimination task. To define features of cortical activity that underlie performance at these time scales, we measured single-unit responses in the mouse visual cortex at time scales relevant to this task. In contrast to high-contrast stimuli of longer duration, which elicit reliable activity in individual neurons, stimuli at the threshold of perception elicit extremely sparse and unreliable responses in the primary visual cortex such that the activity of individual neurons does not reliably report orientation. Integrating information across neurons, however, quickly improves performance. Using a linear decoding model, we estimate that integrating information over 50–100 neurons is sufficient to account for behavioral performance. Thus, at the limits of visual perception, the visual system integrates information encoded in the probabilistic firing of unreliable single units to generate reliable behavior.
Development and Analytical Validation of the Methodology for Vitamins in Tablets by Ultra-Performance Liquid Chromatography
Authors: d’Oliveira Giulio D C , Chaves Andréa R , Pérez Caridad N
Published: July 2019

In the present study, we developed a reliable and robust chromatographic method for the quantification of multivitamins in tablet samples by ultra-performance liquid chromatography (UPLC) with photodiode array detection. The vitamins nicotinamide, pyridoxine, riboflavin, and thiamin were analyzed and quantified in a total analysis time of 2.5 minutes, using hydrophilic interaction liquid chromatography stationary phase. Tocopherol acetate and cyanocobalamin were analyzed and quantified in a total analysis time of 2.5 minutes, using reversed-phase (RP)-UPLC. The analysis time reported here is lower than that of similar methods reported in the literature for single vitamin determination. The method linearity exhibits a good correlation coefficient (R2 = 0.998) with the relative residual standard deviation in the acceptable limit of 2.0%. The developed methods were validated, and the results demonstrated that the proposed analytical method showed to be selective, sensitive, accurate, and robust for the quantification of evaluated vitamins in multivitamin tablets. The work was fully developed in the quality control laboratory of a pharmaceutical industry in the Agroindustrial District of Anápolis (DAIA, Goiás, Brazil), where the product is manufactured.
Do Enterprise Zones have a role to play in delivering a place-based industrial strategy?
Authors: Hooton Christopher A , Tyler Peter
Published: July 2019

We examine the body of evidence on Enterprise Zone policy with the objective of assessing its role in broader place-based industrial strategy. We conduct an extensive review, consolidate the empirical evidence into one place and examine it according to economic impact by zone type. We identify two gaps in the empirical knowledge that are systematically addressed through new research on several US Enterprise Zones to gain new evidence on their economic additionality. The article concludes by considering other, hitherto poorly explored, pathways by which zones may help an area to adapt to change and embrace longer-term economic futures.
Successful off-pump surgical release for extrinsic compression of outflow graft obstruction of a left ventricular assist device
Authors: Ushijima Tomoki , Tanoue Yoshihisa , Mitsuo Hiroshi , Shiose Akira
Published: July 2019

A 36-year-old woman had received support with the Jarvik 2000 left ventricular assist device for 3 years. Cardiac computed tomography revealed outflow graft obstruction, which appeared as external compression of the outflow graft. The patient underwent surgical release of the obstruction after resternotomy. Yellow sediment had become encrusted in the enclosed space between the covering graft and outflow graft and appeared to have been derived from plasma contents. Successful release of the obstruction was achieved by cutting open the covering graft without cardiopulmonary bypass. Neither pump exchange nor outflow graft exchange was required. This off-pump surgery can be a beneficial procedure in terms of less invasiveness and good curability.
Outcomes of transported and in-house patients on extracorporeal life support: a propensity score-matching study
Authors: Lee Heemoon , Sung Kiick , Suh Gee Young , Chung Chi Ryang , Yang Jeong Hoon , Jeon Kyeongman , Carriere Keumhee Chough , Ahn Joong Hyun , Cho Yang Hyun
Published: July 2019

OBJECTIVES

Patients on extracorporeal life support (ECLS), like other critically ill patients, are transported to other institutions for various reasons. However, little has been reported concerning the characteristics and clinical outcomes of transported patients compared with those of in-house patients.

METHODS

A total of 281 adult patients received ECLS between January 2014 and August 2016. Patients who underwent cannulation at another institution by our team were excluded. Patients were divided into 2 groups: transported group (N = 46) and in-house group (N = 235). All 46 patients were safely transported without serious adverse events. The mean travel distance was 206±140 km, with a mean travel time of 78 ± 57 min. Following propensity score matching, 44 transported patients were matched to 148 in-house patients.

RESULTS

In the matched population, the mean age was 48 ± 13 years in the transported group and 49 ± 17 years in the in-house group (P = 0.70). The ECLS type (venoarterial/venovenous) comprised 35/9 (79.5/20.5%) in the transported group and 119/29 (80.4/19.6%) in the in-house group (P = 0.93). Seventeen (38.6%) extracorporeal cardiopulmonary resuscitations were performed in the transported group and 59 (39.9%) were performed in the in-house group (P = 0.91). The incidence of limb ischaemia and acute kidney injury was higher in the transported group (P = 0.007 and P = 0.001, respectively). However, the rate of survival to discharge did not differ between the groups (63.6% in the transported group vs 64.2% in the in-house group, P = 0.94) and there was no difference in overall mortality (P = 0.99).

CONCLUSIONS

Although transported patients had more complications than in-house ECLS patients, clinical outcomes were comparable in the matched population. Transporting ECLS patients to an experienced centre may be justified based on our experience.
Embodied Art: A Reading of A. S. Byatt’s ‘Body Art’
Authors: Mathews Peter D
Published: July 2019

This article examines the idea of an embodied art in A. S. Byatt’s short story ‘Body Art’. In order to contextualize this concept, the essay begins with a survey of Byatt’s earlier explorations of the link between mind and body, as well as an analysis of the small amount of secondary material relating to ‘Body Art’, a text that has received little critical attention. The article then explores the story’s ties to Dutch vanitas painting, a tradition that is intimately linked to the study of anatomy. The vanitas tradition shows how medicine and art were once a unified field, and explores the consequences of their modern division. This leads to a consideration of the influence of theological debates about mind and body and their effect, in particular, on Renaissance humanist art. The next section examines the shifting meaning of the archival collection, particularly in its significance for modern formations of subjectivity. This idea is particularly important in the context of the story’s allusions to Joseph Beuys, who views the artist’s body as a locus of creativity. Like Beuys, Byatt is interested in art that draws on the imaginative power of religious storytelling and imagery while rejecting its supernatural elements. Byatt draws together all of these elements in her story in order to articulate her vision of an embodied art, one that draws together the conceptual and the physical.
Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis
Authors: Ridker Paul M , MacFadyen Jean G , Thuren Tom , Libby Peter
Published: July 2019

Aims

The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) established that targeting inflammation with interleukin-1β (IL-1β) inhibition can significantly reduce cardiovascular (CV) event rates in the absence of any beneficial effects on cholesterol. Yet, CANTOS participants treated with both high-intensity statins and canakinumab remain at considerable risk for recurrent CV events. Both interleukin-18 (IL-18, which like IL-1β requires the NLRP3 inflammasome for activation) and interleukin-6 (IL-6, a pro-inflammatory cytokine downstream of IL-1) may contribute to the recurrent events that occur even on canakinumab therapy, and thus represent novel targets for treating atherothrombosis.

Methods and results

Plasma samples from 4848 stable post-myocardial infarction patients who were assigned to active IL-1β inhibition or placebo within CANTOS underwent measurement of IL-18 and IL-6 both before and after initiation of canakinumab using validated ELISA. All participants were followed over a median 3.7-year period (maximum 5 years) for recurrent major adverse cardiovascular events (MACE) and for all-cause mortality. Compared to placebo, canakinumab significantly reduced IL-6 levels in a dose-dependent manner yielding placebo-subtracted median percent reductions in IL-6 at 3 months of 24.8%, 36.3%, and 43.2% for the 50, 150, and 300 mg doses, respectively (all P-values <0.001). By contrast, no dose of canakinumab significantly altered IL-18 levels measured at 3 months (all effects <1%, all P-values > 0.05). Yet, despite these differential plasma effects, either baseline and on-treatment levels of IL-18 or IL-6 associated with rates of future CV events. For example, for MACE, each tertile increase in IL-18 measured 3 months after canakinumab initiation associated with a 15% increase in risk [95% confidence interval (CI) 3–29%, P = 0.016], while each tertile increase in IL-6 measured 3 months after canakinumab initiation associated with a 42% increase in risk (95% CI 26–59%, P < 0.0001). Similar effects were observed for MACE-plus, CV death, all-cause mortality, and the for the combination endpoint of all vascular events inclusive of revascularization procedures and hospitalization for congestive heart failure. In baseline as well as on-treatment analyses, risks were highest among those with the highest levels of both IL-18 and IL-6.

Conclusion

There remains substantial residual inflammatory risk related to both IL-18 and IL-6 after IL-1β inhibition with canakinumab These data support further pharmacologic development of therapies for atherothrombosis that target IL-18 or IL-6 signalling, or that can simultaneously inhibit both IL-1β and IL-18 (such as NLRP3 inflammasome inhibitors).

Clinical trial registration

ClinicalTrials.gov NCT01327846.
High penetrance and similar disease progression in probands and in family members with arrhythmogenic cardiomyopathy
Authors: Chivulescu Monica , Lie Øyvind H , Popescu Bogdan A , Skulstad Helge , Edvardsen Thor , Jurcut Ruxandra O , Haugaa Kristina H
Published: July 2019

Aims

We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study.

Methods and results

Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5–9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (−0.6%/year vs. −0.8%/year, P < 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47–182.81, P < 0.01).

Conclusion

More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events.
A non-perturbative method for gravitational potential calculations within heterogeneous and aspherical planets
Authors: Maitra Matthew , Al-Attar David
Published: July 2019

We present a numerically exact method for calculating the internal and external gravitational potential of aspherical and heterogeneous planets. Our approach is based on the transformation of Poisson’s equation into an equivalent equation posed on a spherical computational domain. This new problem is solved in an efficient iterative manner based on a hybrid pseudospectral/spectral element discretization. The main advantage of our method is that its computational cost reflects the planet’s geometric and structural complexity, being in many situations only marginally more expensive than boundary perturbation theory. Several numerical examples are presented to illustrate the method’s efficacy and potential range of applications.
Rotating double-diffusive convection in stably stratified planetary cores
Authors: Monville R , Vidal J , Cébron D , Schaeffer N
Published: July 2019

In planetary fluid cores, the density depends on temperature and chemical composition, which diffuse at very different rates. This leads to various instabilities, bearing the name of double-diffusive convection (DDC). We investigate rotating DDC (RDDC) in fluid spheres. We use the Boussinesq approximation with homogeneous internal thermal and compositional source terms. We focus on the finger regime, in which the thermal gradient is stabilizing whereas the compositional one is destabilizing. First, we perform a global linear stability analysis in spheres. The critical Rayleigh numbers drastically drop for stably stratified fluids, yielding large-scale convective motions where local analyses predict stability. We evidence the inviscid nature of this large-scale double-diffusive instability, enabling the determination of the marginal stability curve at realistic planetary regimes. In particular, we show that in stably stratified spheres, the Rayleigh numbers Ra at the onset evolve like Ra ∼ Ek−1, where Ek is the Ekman number. This differs from rotating convection in unstably stratified spheres, for which Ra ∼ Ek−4/3. The domain of existence of inviscid convection thus increases as Ek−1/3. Secondly, we perform non-linear simulations. We find a transition between two regimes of RDDC, controlled by the strength of the stratification. Furthermore, far from the RDDC onset, we find a dominating equatorially antisymmetric, large-scale zonal flow slightly above the associated linear onset. Unexpectedly, a purely linear mechanism can explain this phenomenon, even far from the instability onset, yielding a symmetry breaking of the non-linear flow at saturation. For even stronger stable stratification, the flow becomes mainly equatorially symmetric and intense zonal jets develop. Finally, we apply our results to the early Earth core. Double diffusion can reduce the critical Rayleigh number by four decades for realistic core conditions. We suggest that the early Earth core was prone to turbulent RDDC, with large-scale zonal flows.
Stir it up: how master-apprentice relationships affect the similarity of product offerings in high-end restaurants
Authors: Castellucci Fabrizio , Slavich Barbara
Published: July 2019

This work explores the determinants of decisions by former apprentices to present product offerings similar to those of their masters. Using a quantitative study of 194 international chefs, this article argues that there is a negative association between the degree to which a master rebels against the rules and conventions of a field and master-apprentice similarity. It also shows that master status and a creative professional’s career stage during an apprenticeship moderate the association between master rebellion and master-apprentice similarity. The work concludes by outlining some implications for the career development and creativity of creative professionals and the emergence of new styles.
Opportunities in Novel Psychotropic Drug Design from Natural Compounds
Authors: Tang Siu Wa , Tang Wayne H
Published: July 2019

Multiple initiatives at the national and international level support natural drug discovery. Psychiatrists and patients are not well informed about natural psychotropics in general. Existing antidepressant and antipsychotic drugs were developed from atropine, a natural product. Subsequent drug developments were largely based on extension and modification of earlier molecular scaffolds. This limits their mechanisms of action to similar neuropathways. Natural psychotropic substances, particularly those with hallucinogenic and psychedelic properties and different chemical structures, may serve as new paths to novel psychotropic drug development.
An Intranasal Exposure Model of Lethal Nipah Virus Infection in African Green Monkeys
Authors: Geisbert Joan B , Borisevich Viktoriya , Prasad Abhishek N , Agans Krystle N , Foster Stephanie L , Deer Daniel J , Cross Robert W , Mire Chad E , Geisbert Thomas W , Fenton Karla A
Published: July 2019

Due to the difficulty in conducting clinical trials for vaccines and treatments against Nipah virus (NiV), licensure will likely require animal models, most importantly non-human primates (NHPs). The NHP models of infection have primarily relied on intratracheal instillation or small particle aerosolization of NiV. However, neither of these routes adequately models natural mucosal exposure to NiV. To develop a more natural NHP model, we challenged African green monkeys with the Bangladesh strain of NiV by the intranasal route using the laryngeal mask airway (LMA) mucosal atomization device (MAD). LMA MAD exposure resulted in uniformly lethal disease that accurately reflected the human condition.
The Fat Body of the Hematophagous Insect, Panstrongylus megistus (Hemiptera: Reduviidae): Histological Features and Participation of the β-Chain of ATP Synthase in the Lipophorin-Mediated Lipid Transfer
Authors: Fruttero Leonardo L , Leyria Jimena , Moyetta Natalia R , Ramos Fabian O , Settembrini Beatriz P , Canavoso Lilián E
Published: July 2019

In insects, lipid transfer to the tissues is mediated by lipophorin, the major circulating lipoprotein, mainly through a nonendocytic pathway involving docking receptors. Currently, the role of such receptors in lipid metabolism remains poorly understood. In this work, we performed a histological characterization of the fat body of the Chagas’ disease vector, Panstrongylus megistus (Burmeister), subjected to different nutritional conditions. In addition, we addressed the role of the β-chain of ATP synthase (β-ATPase) in the process of lipid transfer from lipophorin to the fat body. Fifth-instar nymphs in either fasting or fed condition were employed in the assays. Histological examination revealed that the fat body was composed by diverse trophocyte phenotypes. In the fasting condition, the cells were smaller and presented a homogeneous cytoplasmic content. The fat body of fed insects increased in size mainly due to the enlargement of lipid stores. In this condition, trophocytes contained abundant lipid droplets, and the rough endoplasmic reticulum was highly developed and mitochondria appeared elongated. Immunofluorescence assays showed that the β-ATPase, a putative lipophorin receptor, was located on the surface of fat body cells colocalizing partially with lipophorin, which suggests their interaction. No changes in β-ATPase expression were found in fasting and fed insects. Blocking the lipophorin–β-ATPase interaction impaired the lipophorin-mediated lipid transfer to the fat body. The results showed that the nutritional status of the insect influenced the morphohistological features of the tissue. Besides, these findings suggest that β-ATPase functions as a lipophorin docking receptor in the fat body.