bluuebunny/crossref_metadata_2025 huggingface dataset:
A-61 The Cattell-Horn-Carroll Model Does Not Outperform a Traditional Neuropsychological Model When Using a Digital Test Battery
Authors: Vermeent S , van Elswijk G , Schmand B , Klaming L , Miller J , Dotsch R
Published: August 2019

Objective

Following recent (meta-)analyses showing that the Cattell-Horn-Carroll (CHC) model outperforms traditional neuropsychological models of cognition, we investigated the relative performance of the traditional neuropsychological model (TNM) of cognitive functioning and the CHC model using the digital Philips IntelliSpace Cognition (ISC) test battery.

Method

The ISC battery consists of 11 conventional cognitive tests, which were administered to 221 healthy participants. We used confirmatory factor analysis (CFA) to map outcome measures to cognitive domains. Both models contained processing speed, working memory, memory, and visuospatial ability. TNM included executive functioning consisting of TMT B, Stroop interference, and Phonetic and Semantic Fluency. In the CHC model, these outcome measures were distributed over processing speed and a word fluency domain. The models’ fit was compared through Vuong test for non-nested models.

Results

Both models were a good fit (TNM: χ2(64) = 91.95, p = .013, CFI = .971, RMSEA = .044; CHC: χ2(64) = 83.66, p = .050, CFI = .979, RMSEA = .037). The Vuong test showed that the models could be significantly distinguished based on the observed data, ω2 = 0.21, p < .001. However, the non-nested likelihood ratio test did not offer evidence that either model was a better fit, z = -0.61, p = .727. The 95% confidence interval of the AIC difference contained zero [-18.60, 35.20].

Conclusions

Recent findings showing that the CHC model outperforms the TNM are not corroborated by our findings. Instead, both models captured the data equally well, suggesting that the two theoretical frameworks are not necessarily mutually exclusive.
A-73 Does Trauma Type Influence the Symptom Profile in Feigned Posttraumatic Stress Disorder (PTSD)?
Authors: Sullivan K , Mullan M
Published: August 2019

Objective

Posttraumatic Stress Disorder (PTSD) is vulnerable to feigning. This presents a major challenge for clinicians who must differentiate between genuine and feigned presentations. Past studies have shown that in genuine PTSD the symptom profiles varies as a function of trauma type. It is not yet clear if this variation also occurs for feigned PTSD.

Method

Sixty participants were each randomly assigned to one of two experimental conditions. Both conditions provided: i) coaching about PTSD and ii) instructions to feign PTSD as if for financial gain. The trigger event in the conditions was either sexual assault (SA) or a motor vehicle collision (MVC), and it was manipulated in a written vignette. Outcomes were assessed via standardized measures for PTSD symptoms (PCL-5) and profile invalidity (Structured Inventory of Malingered Symptomology [SIMS]).

Results

All participants exceeded the PCL-5 and SIMS cut scores, indicating a plausible PTSD symptom profile with over-reported (detectable) symptoms. However, there were no statistically significant group differences on the PCL-5 or SIMS at the overall, subscale, or profile levels (all p’s > 0.05).

Conclusions

Unlike genuine PTSD, in simulated PTSD the symptom profile did not differ by trauma type. The feigned performance was detected on the SIMS which could recommend this test, and this requires further investigation. If understanding of the genuine PTSD profiles for different trauma types is further developed and if our result is replicated, the future use of profile-analyses could assist clinicians when evaluating feigned PTSD.
A-75 Predicting neurocognitive impairment using the Green’s Medical Symptom Validity Test dementia profile formula
Authors: Ringdahl E , Seegmiller R , Aden J , Stephens C
Published: August 2019

Objective

The Green’s Medical Symptom Validity Test (MSVT) is a measure of performance validity and has a formula to help distinguish genuine cognitive impairment from suboptimal engagement. The current study used the MSVT “dementia profile” formula to discriminate patients with no neurocognitive disorder (no NCD), mild neurocognitive disorder (mild NCD), and major neurocognitive disorder (major NCD).

Method

198 patients who were seen for comprehensive outpatient neuropsychological testing and passed all MSVT validity measures were included in the study. Specifically, participants included 103 persons with no NCD, 62 diagnosed with a mild NCD, and 33 with major NCD, who were collectively 58% male, with a mean age of 52-years-old (SD = 16.1) and mean education of 14.5 years (SD = 2.5).

Results

The difference score between easy and hard MSVT subtests predicted group assignment (r = .57, p < .001) and effectively differentiated the three groups (p < .001). Mean difference scores of both groups with diagnosed NCD exceeded recommended criteria suggestive of genuine cognitive impairment, with the differences score of major NCD being greater (p < .01) than the mild NCD. Group differences remained significant (p < .001) after adjusting for the effects of age and education. When the NCD groups were compared to the no diagnosis group, ROC curve analysis produced an AUC of .84, with a sensitivity of .72 and specificity of .83.

Conclusions

Findings from this study validate the established difference score between easy and hard subtests of the MSVT, and suggest that the difference score on a valid MSVT profile yields diagnostically relevant information pertaining to the level of an individual’s neurocognitive impairment.
B-04 Combining tDCS and Cognitive Training for People with Severe Mental Illness: Preliminary Feasibility and Acceptability Findings
Authors: Burton C , Tso I , Hampstead B , Taylor S
Published: August 2019

Objective

Technological advances in neuromodulation and cognitive remediation provide opportunities to develop novel interventions, though a critical first determination is whether such treatments are feasible and acceptable to participants. This study evaluated a combined transcranial direct current stimulation (tDCS) and computerized cognitive training intervention for individuals with severe mental illness; we examined participant recruitment, retention, and adherence to the interventions, along with qualitative feedback.

Method

Participants included adults with schizophrenia-spectrum or bipolar disorder and impaired working memory (performance ≤1 standard deviation below average of healthy individuals on a spatial span or letter-number span test). In this randomized crossover study, all participants received the combined intervention (ten tDCS sessions in the clinic concurrent with cognitive training), and ten hours of at-home training, and completed neuropsychological and clinical assessments at three time points.

Results

To date, thirteen participants provided informed consent. Seven participants were screened out; five exceeded the cognitive cutoff and one did not meet the diagnostic criterion. No remaining participants have withdrawn prior to study completion. Four participants completed all tDCS sessions, and one completed 80%. No tDCS session has been discontinued. At-home training has proven more challenging; only one participant completed all ten hours, and three did not complete any at all. Participant feedback has been positive; all expressed satisfaction with both treatments though some said symptoms or busy schedules interfered with at-home training.

Conclusions

Combining tDCS with computerized cognitive training appears feasible and acceptable. Strategic recruitment efforts to capture those with cognitive impairment appears necessary, as well as troubleshooting barriers to at-home training.
B-08 Cerebral Blood Flow Differences at Baseline Between Cortical Regions in Tic Disorders Population
Authors: McDonald B , Lopez A , Lopez-Palacios D , Golden C , Amen D , Willeumier K , Taylor D
Published: August 2019

Objective

To identify CBF differences between individuals with Tic Disorder and healthy controls.

Methods

The data for this study was acquired from a de-identified archival Single-Photon Emission Computed Tomography (SPECT) database. The sample included a healthy control group (n = 83,age M = 42.02,54.22% female) and a second group included individuals diagnosed with Tic Disorder (n = 177,age M = 33.54,83.05% male). Significant differences were found for gender [χ(2) = 41.16,p < .001] between groups. As a result, ANCOVAs were conducted to measure CBF differences across the brain using SPECT scans between the two groups while controlling for gender.

Results

Results showed significant differences between the two groups and perfusion in 4 brain regions. Hypo-perfusion in the Tic Disorder group was observed in the right basal ganglia [F(1,260) = 30.959,p < .001] and left [F(1,260) = 32.16,p < .001]. Hyper-perfusion was found in the right cerebellum [F(1,260) = 16.63,p < .001], and left [F(1,260) = 22.17,p < .001] in the same group.

Conclusion

Results indicate that individuals with tic disorders have diminished CBF than healthy controls in both sides of the basal ganglia. This contrasts previous studies, which have shown that individuals with tic disorders have more CBF in the basal ganglia. Further research is needed to understand this inconsistency; a possible explanation is that there is an inhibiting effect on the basal ganglia. Increased CBF in both sides of the cerebellum supports previous research as this cortical area has been shown to have connections with the basal ganglia, activating the pathway that trigger the motor tics. Tic disorders are usually associated with other comorbidities therefore the sample may have other diagnoses that affect blood flow. Future research should control for potential comorbidities.
B-12 Cognitive Resilience in MS: Associations with Lesion Volume, Pain, and Smoking Status
Authors: Randolph J , Randolph J , Wishart H
Published: August 2019

Objective

Cognitive dysfunction is common in people with MS (pwMS), but relatively little is known about those with no objective or subjective impairment. We sought to further examine a previously characterized cognitively resilient group of pwMS (MS-RES)—individuals without cognitive impairment, without subjective cognitive complaints, and without informant-reported cognitive difficulties—and considered neuroimaging, pain-related, and smoking correlates in this group.

Method

We derived two groups of pwMS: cognitively resilient (MS-RES; N = 15) and other MS (N = 85). MS groups showed equivalent education, gender, symptom and diagnosis duration, MS subtype, EDSS rating, and reported hours of sleep, and endorsed no more than mild depression. Both MS groups were compared to age- and gender-matched healthy controls (N = 31) on appropriate variables, and MS groups were compared on lesion volume, pain, and smoking variables.

Results

Despite showing intact subjective and objective cognition, the MS-RES group had lesion volume comparable to other MS participants. The MS-RES group also reported less of an impact of pain on overall functioning, recreational activities, and life enjoyment compared to other MS participants (p < .05), and were comparable to healthy controls. There was a trend toward MS-RES participants being less likely to be current smokers than others with MS (p = .09), and MS-RES and healthy controls showed comparable smoking status.

Conclusions

We found that cognitively resilient pwMS have unique clinical features that differentiate them from others with MS despite similar lesion volumes. A more complete understanding of cognitively resilient pwMS may inform interventions that promote MS symptom management and general resilience.
Self-efficacy and Performance Validity Testing in Active Duty Service Members
Authors: Armistead-Jehle P , Grills C
Published: August 2019

Objective

The base rate of performance validity test (PVT) failure in the military has been relatively well established and averages approximately 33% in clinical and 50% in disability samples, respectively. Secondary gain is an omnipresent concern; however, frank malingering may not account for all cases of PVT failure. As a result, other psychological and social factors potentially associated with PVT failure have been suggested and include nocebo effect, diagnosis threat, perceived injustice, and loss aversion. Self-efficacy has been associated with a range of medical and psychological conditions and outcomes. It was hypothesized that self-efficacy would be among the psychosocial factors impacting PVT failure.

Method

A retrospective review of 263 US Service Members administered the MMPI-2-RF and the Medical Symptom Validity Test (MSVT) and/or the Non-Verbal MSVT (NV-MSVT) in the context of neuropsychological assessments was conducted.

Results

Correlations between the MMPI-2-RF Inefficacy sub-scale (NFC) and MSVT and NV-MSVT were not statistically significant (r = -0.10, p = .12 & r = -.04, p = .53, respectively). Moreover, the Inefficacy sub-scale did not significantly differ as a function of PVT performance (non-significant t-tests) and effect sizes were low (Cohen’s d of .22 [MSVT] and .11 [NV-MSVT]).

Conclusions

Contrary to initial expectations, the current data failed to demonstrate a reliable relationship between self-efficacy and PVT performances. While various psychosocial variables have been associated with performance validity testing, it appears that self-efficacy is not.
Digit Span Forward as a Performance Validity Test in Dementia Evaluations: Specificity in Mild Cognitive Impairment, Mild Dementia, and Moderate Dementia
Authors: Clark H , Martin P , Schroeder R
Published: August 2019

Objective

Traditional performance validity tests (PVTs) often yield high false positive rates in dementia evaluations. The current study examined the frequency of extremely low scores (≤ 2 percentile) on WAIS-IV Digit Span Forward (DSF) in older adults with Mild Cognitive Impairment (MCI) or dementia to evaluate its possible utility as a PVT in these populations.

Method

Archival data from outpatient neuropsychological evaluations were analyzed. Individuals who were not diagnosed with a neurocognitive disorder, had missing data, or were believed to be invalidly performing were excluded. Participants (n = 195; mean age = 72.8; mean education = 13.2 years) were classified according to their evaluation diagnosis of MCI (n = 72; mean RBANS Total Score = 86.8) or dementia. Dementia patients were further divided by MoCA score into groups of mild dementia (n = 90; MoCA≥15; mean RBANS Total Score = 71.0) or moderate dementia (n = 33; MoCA < 15; mean RBANS Total Score = 55.9). Frequencies of scaled scores were analyzed to calculate specificity values for each group.

Results

A WAIS-IV DSF scaled score of ≤4 (≤ 2 percentile) resulted in specificity values of 0.99 and 0.94 in MCI and mild dementia, respectively. Conversely, in moderate dementia, ≥0.90 specificity was achieved only when using a more conservative cutoff of ≤2.

Conclusions

Low DSF scaled scores occurred infrequently in MCI and mild dementia, indicating strong specificity and potential utility as a PVT in these populations. However, in moderate dementia, low DSF scores were more common, requiring use of a more stringent cutoff. Future research should examine DSF sensitivity to invalid performance, as well as DSF specificity according to specific etiologies of MCI and dementia.
Does Trauma Influence Post-concussive Symptom Recovery in Youth?
Authors: Tarkenton T , Hynan L , Didehbani N , Silver C , Cullum M
Published: August 2019

Objective

Minimal research has focused on youth concussions acquired in traumatic events versus non-traumatic events, despite overlap between post-concussive and post-traumatic stress symptoms. Youth sustaining a concussion during a motor vehicle accident (MVA) may endorse greater emotional and cognitive symptoms than those with sports-related concussion (SRC). This study’s aim was to compare recovery from concussion due to MVA versus SRC to determine if recovery profiles differ.

Data Selection

Participants aged 7-25 who reported to clinic within 30 days of SRC (n = 329) or MVA-related concussion (n = 67) and endorsed persistent post-concussive symptomatology (>1 month) were selected from the North Texas Concussion Registry (ConTex). Data collected at initial visit and 3-month follow-up included a four-factor symptom checklist (physical, emotional, cognitive, sleep), GAD-7 for anxiety, and PHQ-8 for depression.

Data Synthesis

Repeated measures ANOVA compared longitudinal score differences. MVA and SRC groups significantly improved on all measures at follow up; however, the MVA group reported higher symptomatology on all measures at both visits (ps < .01). For all cognitive and emotional scores, a significant interaction was found (ps < .01), with the MVA group demonstrating greater improvement over 3 months (See Image Attachment).

Conclusions

Mechanism of injury influences post-concussion symptom recovery. Despite greater improvement in cognitive and emotional symptoms between visits, the MVA group endorsed significantly higher post-concussive symptomatology across the recovery period. Perhaps because of trauma related to mechanism of injury, specific differences in cognitive and emotional symptom presentation/recovery profiles were observed. Posttraumatic stress symptom assessment may be useful in examining the influence of potential trauma/reactions on post-concussive symptom recovery.
Subtle Cognitive Decline predicts progression to Mild Cognitive Impairment Above and Beyond Alzheimer’s Disease Risk Factors
Authors: Osuna J , Thomas K , Edmonds E , Bangen K , Weigand A , Wong C , Cooper S , Bondi M
Published: August 2019

Objective

Early identification of those at risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is critical for early intervention. Recent work shows that subtle cognitive decline (SCD), operationally-defined using sensitive neuropsychological scores, predicts progression to MCI/AD and is associated with AD biomarkers. We aimed to determine whether SCD adds unique value in predicting progression to MCI/AD above and beyond other AD risk factors.

Method

547 cognitively unimpaired participants from the Alzheimer’s Disease Neuroimaging Initiative (359 without SCD; 188 with SCD) underwent neuropsychological testing and lumbar puncture. Participants were classified as SCD if they performed >1 SD below the demographically-adjusted mean on 1) two neuropsychological total scores in different cognitive domains, or 2) two memory test process scores (e.g., intrusion errors), or 3) one total score and one process score. Cox regressions examined whether SCD status predicted progression to MCI and AD within 5 years after adjusting for age, education, sex, MMSE, depressive symptoms, ischemia risk, apolipoprotein E genotype, and AD biomarker “positivity” based on the cerebrospinal fluid phosphorylated tau-to-β-amyloid ratio.

Results

SCD status predicted progression to MCI (HR = 2.74, 95% CI = 2.07-3.63, p < .001) and AD (HR = 2.20, 95% CI = 1.04-4.65, p = .04) within 5 years, even after including known AD risk factors in the model.

Conclusion

SCD conveys a 2-3 fold increased risk of progression to MCI/AD and is a unique predictor above and beyond risk factors that are commonly used in preclinical AD research. These findings support our novel SCD criteria as a cost-effective and non-invasive method for identifying those at risk for future cognitive decline.
Effects of Multiple Mild TBIs on Neuropsychological Functioning, Psychiatric Symptoms, and Neurobehavioral/Health-Related Symptoms in Combat-Exposed Veterans
Authors: Merritt V , Jurick S , Crocker L , Hoffman S , Keller A , Jak A
Published: August 2019

Objective

The purpose of this study was to examine the influence of multiple mild traumatic brain injuries (mTBI) on objective neuropsychological functioning and subjective symptom reporting in a sample of combat-exposed Veterans.

Method

Participants included 80 combat-exposed Iraq/Afghanistan Veterans (91.3% male; age: M = 34.33, SD = 6.44) divided into three groups based on mTBI history: 0 mTBIs (n = 33), 1-2 mTBIs (n = 26), and 3+ mTBIs (n = 21). Veterans with mTBI were assessed, on average, 7.5 years following their most recent mTBI. Participants underwent comprehensive neuropsychological testing and completed self-report measures assessing psychiatric and neurobehavioral/health-related symptoms.

Results

ANCOVAs adjusting for level of combat exposure showed no group differences on the memory and attention/executive functioning composite scores (p’s>.05). Additionally, groups did not differ with respect to symptoms of posttraumatic stress and depression (p’s>.05). In contrast, there were significant group differences on all neurobehavioral/health-related symptoms, including post-concussive symptom clusters (p’s < .001-.005), sleep problems (p = .024), pain symptoms (p < .001), and pain catastrophizing (p = .049). In general, Veterans with 3+ mTBIs self-reported the most severe symptoms, followed by Veterans with 1-2 mTBIs and 0 mTBIs.

Conclusions

History of multiple, remote mTBIs is associated with elevated subjective neurobehavioral/health-related symptoms in a dose-dependent fashion, but is not associated with objective neuropsychological functioning or ratings of psychiatric distress in combat-exposed Veterans. These results advance understanding of the long-term consequences of multiple mTBIs in this population and suggest that Veterans with 3 or more mTBIs may especially benefit from (1) early treatments aimed at ameliorating sleep and pain symptoms and (2) therapies that provide tools to temper catastrophic thinking about these symptoms.
PGR - 1 A Pediatric Case Study of Autism Spectrum Disorder Associated with Germinal Matrix-Intraventricular Hemorrhage, Periventricular Leukomalacia, and Cerebral Palsy.
Authors: Smith A , Davis A
Published: August 2019

Objective

Germinal matrix-intraventricular hemorrhage (GMH-IVH) is a serious complication of prematurity that places infants at risk for damage to important white matter pathways which can result in periventricular leukomalacia (PVL) and ultimately cerebral palsy (CP). GMH-IVH also increases the risk of developmental and intellectual disabilities for preterm infants, highlighting the need for early detection and treatment.

Method

This case study presents on the neuropsychological profile of a 4-year-old boy who was born micropremature and had a history of multiple hemorrhages, extensive PVL, and CP in the context of significant developmental and social delays.

Results

Neuropsychological testing revealed severe impairments in intellectual functioning (Stanford Binet-5 FSIQ = 42, Nonverbal IQ = 43, Verbal IQ = 47; Leiter-3 Nonverbal IQ = 41), adaptive skills, language, social cognition, visuomotor abilities, spatial skills, pre-academic skills, and attention/executive functioning. He scored in the significant range on measures specific to Autism Spectrum Disorder (ADOS-2; CARS-2; SCQ) and behavioral-emotional functioning. Lastly, he exhibited intermittent staring behaviors that were concerning for possible seizure activity.

Conclusions

Recommendations were made to increase special education services for the child and to modify his academic goals. Recommendations were also given to aid in treatment planning for his referring neurologist and clinical interventions (e.g., ABA, social work, speech/language, occupational therapy, and physical therapy). This case study demonstrates the need for early neuropsychological detection and treatment for children with complications of prematurity during this important period of brain development, particularly as there are higher rates of autism in this population. Prompt detection leads to earlier treatment and better outcomes.
AGR - 1 The Use of Repeat Neuropsychological Assessment to Guide Treatment of Possible Normal Pressure Hydrocephalus in a Complex Case
Authors: Schneider S , Weiss E
Published: August 2019

Objective

Normal Pressure Hydrocephalus (NPH) is a condition that is characterized by the buildup of cerebrospinal fluid (CSF) in the brain that can cause urinary incontinence, gait disturbance, and cognitive impairment. NPH can be progressive but may be managed or reversed with shunt placement. External Lumbar Drainage (ELD) trials in determining if shunt placement is appropriate are common, but the role of repeat neuropsychological assessments during ELD procedures is not well documented in the literature. Repeat, pre, peri and post- ELD trial, assessment in a complex case of possible NPH is presented.

Method

33-year-old Hispanic English-Speaking female with cognitive/memory complaints following intraventricular hemorrhage (IVH) secondary to vasculopathy was initially seen for post IVH outpatient neuropsychological evaluation. MRI showed enlarged ventricles/communicating hydrocephalus and workup for NPH was initiated. Repeat inpatient evaluations were completed during the ELD trial, with annual outpatient neuropsychological follow-up.

Results

Gait evaluation was inconclusive. Inpatient testing demonstrated minor improvement immediately following ELD opening, but performances were variable across the 4 days of re-evaluation. Shunt placement was rejected due to neuropsychological findings. Outpatient follow-up of patient over several years has demonstrated mild improvement and not evidence of cognitive decline since ELD trial.

Conclusions

Assessment of cognitive functioning in outpatient and inpatient settings before, during, and for several years following ELD testing was beneficial to ascertain the decision not to place a shunt. Repeat neuropsychological assessment in inpatient and outpatient settings provided crucial information for guiding treatment decisions.
AGR - 3 Socially Responsible Neuropsychology (SRN) in Action: Navigating Relevant Socio-Cultural and Educational Factors in Frontotemporal Dementia
Authors: Miranda A , Diaz-Santos M , Suarez P , Cagigas X
Published: August 2019

Objective

Socio-cultural factors obscure diagnostic specificity for neurodegenerative disorders, particularly among minority or foreign-born patients with limited access to education. Our objective with the following case presentation is to illustrate the utility of a Socially Responsible Neuropsychology (SRN) model in guiding clinical practice through the comprehensive incorporation of significant, yet common, socio-cultural factors throughout the neuropsychological assessment.

Method

The present case involved a 79-year-old Spanish-speaking Mexican woman with two years of education, who underwent two serial neuropsychological assessments, as well as, structural/functional neuroimaging to monitor acute onset of telegraphic speech following the kidnapping of her husband. The SRN model guided clinical decision-making in understanding the onset and progression of symptoms within the context of medical-psychiatric comorbidities intertwined with socio-cultural and educational factors.

Results

Mild vascular neurocognitive disorder and complicated grief were the initial diagnostic impressions as supported by structural neuroimaging. Neuropsychological assessment over time, however, revealed progressive global cognitive decline whereas psychiatric symptomatology remained stable. In the presence of equivocal converging evidence from available neuroimaging studies (PET vs MRI), strong suspicion for the language variant of frontotemporal neurocognitive disorder was considered given the onset and progressive decline of expressive/receptive language, executive and memory abilities, and qualitative evidence for progressive behavioral disihibition.

Conclusion

Telegraphic speech in an elderly Latina woman that initially appeared most consistent with vascular neurocognitive disorder in the context of complex trauma with possible conversion disorder, was deemed most consistent with a neurodegenerative process after careful consideration of the time course and evolution of the neurocognitive profile over time within an SRN model.
Hierarchically embedded interaction networks represent a missing link in the study of behavioral and community ecology
Authors: Montiglio P O , Gotanda K M , Kratochwil C F , Laskowski K L , Farine D R
Published: August 2019

Because genes and phenotypes are embedded within individuals, and individuals within populations, interactions within one level of biological organization are inherently linked to interactors at others. Here, we expand the network paradigm to consider that nodes can be embedded within other nodes, and connections (edges) between nodes at one level of organization form “bridges” for connections between nodes embedded within them. Such hierarchically embedded networks highlight two central properties of biological systems: 1) processes occurring across multiple levels of organization shape connections among biological units at any given level of organization and 2) ecological effects occurring at a given level of organization can propagate up or down to additional levels. Explicitly considering the embedded structure of evolutionary and ecological networks can capture otherwise hidden feedbacks and generate new insights into key biological phenomena, ultimately promoting a broader understanding of interactions in evolutionary theory.
Association rule mining to identify transcription factor interactions in genomic regions
Authors: Ceddia Gaia , Martino Liuba Nausicaa , Parodi Alice , Secchi Piercesare , Campaner Stefano , Masseroli Marco
Published: August 2019

Motivation

Genome regulatory networks have different layers and ways to modulate cellular processes, such as cell differentiation, proliferation, and adaptation to external stimuli. Transcription factors and other chromatin-associated proteins act as combinatorial protein complexes that control gene transcription. Thus, identifying functional interaction networks among these proteins is a fundamental task to understand the genome regulation framework.

Results

We developed a novel approach to infer interactions among transcription factors in user-selected genomic regions, by combining the computation of association rules and of a novel Importance Index on ChIP-seq datasets. The hallmark of our method is the definition of the Importance Index, which provides a relevance measure of the interaction among transcription factors found associated in the computed rules. Examples on synthetic data explain the index use and potential. A straightforward pre-processing pipeline enables the easy extraction of input data for our approach from any set of ChIP-seq experiments. Applications on ENCODE ChIP-seq data prove that our approach can reliably detect interactions between transcription factors, including known interactions that validate our approach.

Availability and implementation

A R/Bioconductor package implementing our association rules and Importance Index-based method is available at http://bioconductor.org/packages/release/bioc/html/TFARM.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Function of Amicus Curiae Participation by Legal Scholars: The Al-Bashir Appeal Case at the International Criminal Court as an Illustration
Authors: Mao Xiao
Published: August 2019

In the recent case on non-cooperation of Jordan in the Al-Bashir case, the Appeals Chamber of the International Criminal Court for the first time invited on its initiative amicus curiae submissions by legal scholars. This comment focuses on the role of legal scholars as amici curiae. It argues that based on Martti Koskenniemi’s method on the structure of legal argumentation and analysis of the argumentation structure of several submissions by legal scholars in the Al-Bashir case, the role of legal scholars as amici curiae would better be viewed as grammarians capable of shaping the formulation of arguments of the Court. This view stands contrary to the traditional understanding that the amicus curiae participation can improve the court’s legitimacy by providing a neutral and definite answer to the legal dispute.
Valorization of Red Onion Peels for Quercetin Recovery Using Quercetin-Imprinted Polymer
Authors: Ersoy Şeyda Karaman , Tütem Esma , Başkan Kevser Sözgen , Apak Reşat
Published: August 2019

Quercetin (QC) is one of the most prominent dietary antioxidants present in vegetables/fruits, specifically in onions that rank second in consumption following tomato. QC with proven health benefits is now largely utilized as a nutritional supplement. In this work that aims to isolate QC from red onion peels forming a huge agricultural waste, a QC-molecularly imprinted polymer (QC-MIP) in a molar ratio of 1:4:20 (QC:4-vinylpyridine:ethylene glycol dimethacrylate) was prepared thermally through bulk polymerization. Molecularly imprinted solid phase extraction (MISPE) procedures were applied for the selective pre-concentration and purification of QC from both red onion peel methanolic extract with 58% recovery and from the extract hydrolyzate with 86% recovery. The hydrolysis process increased both the QC amount as expected and the recovery yield due to changing matrix components. The results demonstrated that onion peel can easily and efficiently be converted to a valuable product, QC, using QC-MIP as SPE sorbent.
Pulmonary vein isolation using ablation index vs. CLOSE protocol with a surround flow ablation catheter
Authors: Berte Benjamin , Hilfiker Gabriella , Moccetti Federico , Schefer Thomas , Weberndörfer Vanessa , Cuculi Florim , Toggweiler Stefan , Ruschitzka Frank , Kobza Richard
Published: August 2019

Aims

Pulmonary vein isolation (PVI) using ablation index (AI) incorporates stability, contact force (CF), time, and power. The CLOSE protocol combines AI and ≤6 mm interlesion distance. Safety concerns are raised about surround flow ablation catheters (STSF). To compare safety and effectiveness of an atrial fibrillation (AF) ablation strategy using AI vs. CLOSE protocol using STSF.

Methods and results

First cluster was treated using AI and second cluster using CLOSE. Procedural data, safety, and recurrence of any atrial tachycardia (AT) or AF >30 s were collected prospectively. All Classes 1c and III anti-arrhythmic drugs (AAD) were stopped after the blanking period. In total, all 215 consecutive patients [AI: 121 (paroxysmal: n = 97), CLOSE: n = 94 (paroxysmal: n = 74)] were included. Pulmonary vein isolation was reached in all in similar procedure duration (CLOSE: 107 ± 25 vs. AI: 102 ± 24 min; P = 0.1) and similar radiofrequency time (CLOSE: 36 ± 11 vs. AI: 37 ± 8 min; P = 0.4) but first pass isolation was higher in CLOSE vs. AI [left veins: 90% vs. 80%; P < 0.05 and right veins: 84% vs. 73%; P < 0.05]. Twelve-month off-AAD freedom of AF/AT was higher in CLOSE vs. AI [79% (paroxysmal: 85%) vs. 64% (paroxysmal: 68%); P < 0.05]. Only four patients (2%) without recurrence were on AAD during follow-up. Major complications were similar (CLOSE: 2.1% vs. AI: 2.5%; P = 0.87).

Conclusion

The CLOSE protocol is more effective than a PVI approach solely using AI, especially in paroxysmal AF. In this off-AAD study, 79% of patients were free from AF/AT during 12-month follow-up. The STSF catheter appears to be safe using conventional CLOSE targets.
Contrasting effects of isocitrate dehydrogenase deletion on fluxes through enzymes of central metabolism in Escherichia coli
Authors: El-Mansi Mansi
Published: August 2019

Flux analysis is central to understanding cellular metabolism and successful manipulation of metabolic fluxes in microbial cell-factories. Isocitrate dehydrogenase (ICDH) deletion conferred contrasting effects on fluxes through substrate-level phosphorylation (SLP) reactions. While significantly increasing flux through pyruvate kinase, it diminishes flux through succinyl CoA synthetase and upregulates phosphotransacetylase (PTA) and acetate kinase (AK). In addition to acetate, the ICDH-less strain excretes pyruvate, citrate and isocitrate. While efflux to acetate excretion by the Escherichia coli parental strain and its ICDH-less derivative is a reflection of high throughput of glycolytic intermediates, excretion of pyruvate is a reflection of high throughput via pyruvate kinase. On the other hand, citrate and isocitrate excretion is a reflection of truncating the Krebs cycle at the level of ICDH. Furthermore, another striking finding is the inability of the ICDH-less cultures to utilize acetate as a source of carbon despite the availability of an adequate supply of extracellular glutamate (for biosynthesis) and elevated levels of AK and PTA (for acetate uptake). This striking observation is now explicable in the light of the newly proposed hypothesis that the expression of the ace operon enzymes is controlled in response to a minimum threshold signal (ATP), which could not be achieved in the ICDH-less strain.
Sea Turtle Population Genomic Discovery: Global and Locus-Specific Signatures of Polymorphism, Selection, and Adaptive Potential
Authors: Chow Julie C , Anderson Paul E , Shedlock Andrew M
Published: August 2019

In the era of genomics, single-nucleotide polymorphisms (SNPs) have become a preferred molecular marker to study signatures of selection and population structure and to enable improved population monitoring and conservation of vulnerable populations. We apply a SNP calling pipeline to assess population differentiation, visualize linkage disequilibrium, and identify loci with sex-specific genotypes of 45 loggerhead sea turtles (Caretta caretta) sampled from the southeastern coast of the United States, including 42 individuals experimentally confirmed for gonadal sex. By performing reference-based SNP calling in independent runs of Stacks, 3,901–6,998 SNPs and up to 30 potentially sex-specific genotypes were identified. Up to 68 pairs of loci were found to be in complete linkage disequilibrium, potentially indicating regions of natural selection and adaptive evolution. This study provides a valuable SNP diagnostic workflow and a large body of new biomarkers for guiding targeted studies of sea turtle genome evolution and for managing legally protected nonmodel iconic species that have high economic and ecological importance but limited genomic resources.
Finite-time stabilization of stochastic coupled systems on networks by feedback control and its application
Authors: Wu Yongbao , Li Wenxue , Feng Jiqiang
Published: August 2019

In this paper, the finite-time stabilization of stochastic coupled systems on networks (SCSNs) is studied. Different from previous research methods, the method used in this paper combines Lyapunov method with graph theory, and some novel sufficient conditions are obtained to ensure finite-time stability for SCSNs. Meanwhile, the convergence time is closely related to topological structure in networks. As a practical application in physics, we address a concrete finite-time stabilization problem of stochastic coupled oscillators through our main results. In addition, a numerical example is presented to illustrate the effectiveness and feasibility of the theoretical results.
Vaccine stockouts and vaccination rate: examination of unique administrative data from Nigeria
Authors: Sato Ryoko
Published: August 2019

Background

Universal access to vaccines is crucial in protecting the population from deadly diseases. This study presents the prevalence of vaccine stockouts in Nigeria and examines the correlation between the vaccine stockouts and vaccine take-up.

Methods

We use the unique administrative data of monthly vaccine stockouts at each health facility in Nigeria. To evaluate the correlation between the stockouts and the vaccine take-up, the administrative data were merged with the Nigeria Demographic and Health Survey conducted in 2013. We used logistic regression for the correlational study.

Results

The prevalence of vaccine stockouts in Nigeria is high: 82.7% between 2012 and 2013. We find a negative correlation between vaccine stockouts and vaccine take-up. However, we observe the differential correlational pattern depending on the regional vaccine coverage, which we consider as the proxy of the level of demand for vaccines.

Conclusions

We find that, while vaccine stockouts are correlated with the low vaccine take-up on average, this negative correlation between stockouts and vaccination rate is observed only in regions with low demand for vaccines. Reducing vaccine stockouts in regions with the low vaccination coverage might be an effective way to increase the overall vaccination rate.
Good Vibrations: Consumer Responses to Technology-Mediated Haptic Feedback
Authors: Hadi Rhonda , Valenzuela Ana
Published: August 2019

Individuals often experience incidental device-delivered haptic feedback (e.g., vibrational alerts accompanying messages on mobile phones and wearables), yet almost no research has examined the psychological and behavioral implications of technology-mediated touch on consumers. Drawing from theories in social psychology and computer science, we explore how device-delivered haptic feedback may have the capability to augment consumer responses to certain consumer-directed communications. Across four studies, we find that haptic alerts accompanying messages can improve consumer performance on related tasks and demonstrate that this effect is driven by an increased sense of social presence in what can otherwise feel like an impersonal technological exchange. These findings provide applied value for mobile marketers and gadget designers, and carry important implications for consumer compliance in health and fitness domains.
Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up
Authors: Tomita Yoshihiko , Kondo Tsunenori , Kimura Go , Inoue Takamitsu , Wakumoto Yoshiaki , Yao Masahiro , Sugiyama Takayuki , Oya Mototsugu , Fujii Yasuhisa , Obara Wataru , Motzer Robert J , Uemura Hirotsugu
Published: August 2019

Background

Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients.

Methods

CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-to-treat (ITT) patients and safety (ITT patients).

Results

Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months’ minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19–1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62–2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3–4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%).

Conclusions

Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed.

https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.
Prostate-specific antigen bounce after 125I-brachytherapy for prostate cancer is a favorable prognosticator in patients who are biochemical recurrence-free at 4 years and correlates with testosterone
Authors: Nakai Yasushi , Tanaka Nobumichi , Asakawa Isao , Anai Satoshi , Miyake Makito , Morizawa Yosuke , Hori Shunta , Owari Takuya , Fujii Tomomi , Yamaki Kaori , Hasegawa Masatoshi , Fujimoto Kiyohide
Published: August 2019

Background

Because patients with prostate-specific antigen (PSA) bounce do not experience biochemical recurrence (BCR) until PSA bounce occurs, the period until PSA bounce ends can be considered the so-called lead-time bias. Therefore, we evaluated differences in BCR-free rate in prostate cancer patients who were BCR-free 4 years after 125I-brachytherapy alone. Furthermore, we evaluated predictors for PSA bounce and the correlation between testosterone and PSA bounce.

Methods

From 2004 to 2012, 256 patients with prostate adenocarcinoma underwent 125I-brachytherapy alone. PSA and testosterone levels were monitored prior to 125I-brachytherapy, at 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after 125I-brachytherapy and yearly after 5-year follow-up. PSA bounce was defined as ≥0.2 ng/ml increase above the interval PSA nadir, followed by a decrease to nadir or below.

Results

BCR-free rate in patients with PSA bounce (100% 7-year BCR-free rate) was significantly better (P < 0.044) than that in patients without PSA bounce (95.7% 7-year BCR-free rate) in patients who were BCR-free 4 years after 125I-brachytherapy alone (n = 223). Age was the only predictor (odds ratio: 0.93, 95% confidence interval: 0.88–0.98, P = 0.004) for PSA bounce (n = 177). The testosterone level at PSA bounce was significantly higher (P = 0.036) than that at nadir before PSA bounce (87 cases).

Conclusions

Patients with PSA bounce had good BCR-free rate even in patients who were BCR-free 4 years after 125I-brachytherapy alone. Testosterone levels were higher at PSA bounce; increased testosterone levels may be a cause of PSA bounce.
Giving Useful but Not Well-Understood Ideas Their Due
Authors: Omelianchuk Adam
Published: August 2019

In this paper, I introduce the ideas to be discussed in the articles of this journal with reference to an imaginary case involving a pregnant woman declared dead on the basis of neurological criteria. I highlight the fact that although these ideas have proved useful for advancing certain claims in bioethical debates, their implications are not always well understood and may complicate our arguments. The ideas to be discussed are (1) an ethic internal to the profession of medicine; (2) the difference between killing and letting die; (3) the organism as a whole; and (4) the “lives” and interests of the dead.
Glutathione redox state plays a key role in flower development and pollen vigour
Authors: García-Quirós Estefanía , Alché Juan de Dios , Karpinska Barbara , Foyer Christine H
Published: August 2019

roGFP2 measurements demonstrate that ungerminated Arabidopsis pollen grains are highly oxidized. Glutathione-deficient flowers show increased cellular oxidation with poor pollen germination/tube growth, suggesting that the reduced state underpins growth functions.
Is triose phosphate utilization important for understanding photosynthesis?
Authors: Sharkey Thomas D
Published: August 2019

This article comments on:

Fabre D, Yin X, Dingkuhn M, Clément-Vidal A, Roques S, Rouan L, Soutiras A, Luquet D. 2019. Is triose phosphate utilization involved in the feedback inhibition of photosynthesis in rice under conditions of sink limitation? Journal of Experimental Botany 70, 5773–5785.