bluuebunny/crossref_metadata_2025 huggingface dataset:
Test Order Does Not Affect Vestibular/Ocular Motor Screening Item Scores in High School Athletes
Authors: D'Amico Nathan R. , Elbin R. J. , Sufrinko Alicia , Schatz Philip , Mucha Anne , Collins Michael W. , Kontos Anthony P.
Published: December 2019

Objective:

To compare VOMS item scores between a fixed and randomized administration order in a sample of nonconcussed high school athletes.

Design:

Post-test only, quasi-experimental design.

Setting:

Local high schools in a mid-west region of the United States.

Patients:

Fifty nonconcussed high school athletes (M = 15.64; SD = 1.12 years) completed the VOMS in a randomized testing order (RANDOM), and 49 (M = 15.64; SD = 1.12 years) completed the VOMS in the fixed testing order (FIXED). The groups were matched on age, sex, learning disorder, attention-deficit/hyperactivity disorder, concussion history, and baseline concussion symptoms.

Interventions:

The Vestibular/Ocular Motor Screening (VOMS) tool comprises pretest symptoms, smooth pursuit (SP), horizontal/vertical saccade (HSAC/VSAC), average near-point of convergence (NPC) distance, convergence symptoms, horizontal/vertical vestibular ocular reflex (HVOR/VVOR), and visual motion sensitivity (VMS).

Main Outcome Measures:

Mann–Whitney U tests were performed to examine differences between FIXED and RANDOM groups on VOMS items. RANDOM scores were rearranged in order of administration and combined with the FIXED group scores, and a Freidman test was performed for repeated measures.

Results:

There were no significant differences between FIXED and RANDOM groups on VOMS pretest symptoms (U = 1171, P = 0.57), SP (U = 1122.5, P = 0.35), HSAC (U = 1128.5, P = 0.44), VSAC (U = 1055.5, P = 0.16), convergence symptoms (U = 1129.0, P = 0.41), average NPC distance (U = 979.0, P = 0.06), HVOR (U = 1085.0, P = 0.25), VVOR (U = 1126.0, P = 0.41), and VMS scores (U = 1101.0, P = 0.32). When VOMS items were rearranged and the sample was combined, there were no differences for repeated measures [χ2 (6) = 9.92, P = 0.13].

Conclusions:

There were no significant differences on VOMS items between FIXED and RANDOM groups for repeated measures. The testing order of VOMS items does not affect VOMS scores in nonconcussed high school athletes.
Assessment of Isometric Knee Flexor Strength Using Hand-Held Dynamometry in High-Level Rugby Players Is Intertester Reliable
Authors: van der Made Anne D. , Paget Liam D. A. , Altink J. Nienke , Reurink Gustaaf , Six Willem R. , Tol Johannes L. , Kerkhoffs Gino M.
Published: December 2019

Objective:

To assess intertester reliability of isometric knee flexor strength testing in high-level rugby players with testers of different physical capacity and different methods of dynamometer fixation.

Design:

Reliability study.

Patients:

Thirty noninjured high-level (Tegner Activity Score ≥9) rugby players, free from hamstring injury in the previous 2 months.

Assessment:

Isometric knee flexor strength (in N) in prone 0/15 degrees (hip/knee flexion) and supine 90/90 degrees position. Tests were performed by 1 female and 2 male testers whose upper-body strength was measured with a 6-repetition maximum bench press test. The prone 0/15 degrees measurement was performed with manual and external belt fixation of the dynamometer.

Main Outcome Measures:

Absolute and relative intertester reliability were calculated using intraclass correlation coefficient (ICC) and minimal detectable change. Paired t-tests were used to identify systematic measurement error between testers and to test for a difference in recorded knee flexor strength between methods of dynamometer fixation.

Methods:

Isometric knee flexor strength was measured in prone 0/15 degrees (hip/knee flexion) and supine 90/90 degrees position.

Results:

Good intertester reliability was found for all pairwise comparisons (ICC 0.80-0.87). MDCs (as percentage of mean strength) ranged from 15.2% to 25.4%. For tester couples where systematic error was identified, Bland–Altman plots and Pearson correlation coefficients demonstrated no statistically significant correlation between mean knee flexor strength and between-tester difference. There was no significant difference in isometric knee flexor strength between manual and belt fixation of the dynamometer.

Conclusions:

In strong high-level rugby players, hand-held dynamometry for isometric knee flexor strength assessment in prone 0/15 degrees and supine 90/90 degrees position is intertester reliable.
PET/computed tomography shows association between subjective pain in knee joints and fluorine-18-fluorodeoxyglucose uptake
Authors: Kamasaki Toshihiko , Mori Keisuke , Taira Yasuyuki , Orita Makiko , Miyamoto Izumi , Usui Toshiya , Chiba Kenya , Kudo Takashi , Takamura Noboru
Published: December 2019

Objective

The aim of this study was to evaluate the capability of fluorine-18-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) in screening for musculoskeletal inflammation and injury in the knee region.

Methods

The study included 12 subjects (6 men and 6 women) who complained of knee pain at rest and 94 controls who did not. Maximum standardized uptake value (SUV)max was calculated for the right and left knees and compared via a 4-point numerical rating scale (NRS) for subjective knee pain. Correlations between SUV values were also evaluated.

Results

SUVmax was significantly higher in knee joints with resting and/or walking pain than in pain-free knee joints. SUVmax in knee joints with walking pain were significantly correlated with NRS category (β = 0.129, P < 0.001).

Conclusion

18F-FDG-PET/CT may be useful in screening for musculoskeletal inflammation and injury in the knee region. As knee pain is common, especially among elderly individuals, we should consider conducting further examinations when 18F-FDG uptake is identified in knee joints.
Development of a Grading Rubric to Assess Learning in Pediatric Physical Therapy Education
Authors: Schreiber Joseph , Gagnon Kendra , Kendall Eydie , LaForme Fiss Alyssa , Rapport Mary Jane , Wynarczuk Kimberly D.
Published: December 2019

The purpose of this perspective article is to describe the development and potential use of a grading rubric to assess pediatric psychomotor and clinical reasoning skills in professional pediatric physical therapist students. Feedback from focus groups made up of pediatric physical therapy educators informed development of the rubric. In addition, preliminary reliability and feasibility of the rubric were evaluated using videotaped student performance on a related pediatric case. Pilot data suggest a range of reliability between slight and moderate across the components of the rubric. Both the case and the rubric are included as appendices, and recommendations are provided for implementation and for future research.
Linear and Nonlinear Measures of Postural Control in a Toddler With Cerebral Palsy: Brief Report
Authors: Pierce Samuel R. , Paremski Athylia C. , Skorup Julie , Stergiou Nicholas , Senderling Benjamin , Prosser Laura A.
Published: December 2019

Purpose:

The purpose of this study was to describe changes in linear and nonlinear measures of postural control along with motor outcomes in a young child with cerebral palsy.

Summary of Key Points:

Posturography in sitting and standing, the Gross Motor Function Measure-66 (GMFM-66), and the Early Clinical Assessment of Balance (ECAB) were performed prior to, during, and after physical therapy. The child demonstrated independent sitting throughout the study and developed independent standing during the study. He made improvements in the GMFM-66 and ECAB throughout the study. Higher average values were found in all linear and nonlinear measures in standing when compared to sitting, which may indicate less predictable movement due to less experience with standing.

Recommendations for Clinical Practice:

Greater variability and lower predictability in postural control likely reflect early stages of skill acquisition. Research is needed to understand the optimal levels of movement variability and predictability.
Use of the Lean Manufacturing Principles to Improve Total Parenteral Nutrition Logistics and Clinical Outcomes in the Neonatal Patient Population
Authors: Mangum Christopher D. , Stanley Andrew J. , Peterson Catherine C. , Biava Laura , Dice James , Khan Jamil , Godambe Sandip A.
Published: December 2019

Introduction:

Total parenteral nutrition (TPN) is one of the most frequently used pharmaceuticals administered to patients in our Neonatal Intensive Care Unit (NICU). Initially, the total interdepartmental processing time (ordering, manufacturing, and delivery between NICU and Pharmacy) averaged 15.2 hours. Inefficiencies in this process only allowed TPN to infuse 8.8 hours on average before labs were collected the next morning. Given the short administration-to-laboratory collection time, we hypothesized that laboratory samples would not adequately reflect the effect of the current TPN infusion. Furthermore, clinicians would be making decisions based on suboptimal data and ultimately nourish this patient population inadequately.

Methods:

The project team and the frontline staff created an efficient process for the manufacture and delivery of TPN. They removed waste in the process associated with manufacturing TPN and created capacity for change upstream (ordering process) and downstream (TPN infusion process) of the internal pharmacy process. The use of selection criteria and new standard operating procedures allowed for controlled PDSA testing of changes on a subset of patients. After we attained proven, sustainable results, we scaled the improvement efforts to the entire NICU patient population.

Results:

After 4 cycles of change, patients now receive TPN on average 14.2 hours before new labs are collected. The interventions over the continuum of this project yielded statistically significant results, increased infusion times to our patients by 61.4% (P < 0.001), improved glucose homeostasis, and decreased average length of stay.

Conclusions:

In conclusion, creating process capacity from incremental changes and iterative PDSA cycles has yielded sustained results.
Economic Benefit of Hand Surgical Efforts in Low- and Middle-Income Countries: A Cost-Benefit Analysis
Authors: Billig Jessica I. , Nasser Jacob S. , Sue Gloria R. , Chang James , Chung Kevin C.
Published: December 2019

Background:

Hand surgeons can alleviate the burden associated with various congenital anomalies, burn sequelae, and trauma that debilitate individuals in low- and middle-income countries. Because few surgeons in these areas have the necessary resources to perform complex hand surgery, surgical trips provide essential surgical care. The authors aimed to determine the economic benefit of hand surgical trips to low- and middle-income countries to comprehensively determine the economic implications of hand surgery trips in low-resource settings.

Methods:

The authors collected data from two major global hand surgery organizations to analyze the economic benefit of hand surgery trips in low- and middle-income countries. The authors used both the human capital approach and the value of a statistical life-year approach to conduct this cost-benefit analysis. To demonstrate the economic gain, the authors subtracted the budgeted cost of each trip from the economic benefit.

Results:

The authors analyzed a total of 15 trips to low- and middle-income countries. The costs of the trips ranged from $3453 to $87,434 (average, $24,869). The total cost for all the surgical trips was $373,040. The authors calculated a net economic benefit of $3,576,845 using the human capital approach and $8,650,745 using the value of a statistical life-year approach.

Conclusions:

The authors found a substantial return on investment using both the human capital approach and the value of a statistical life-year approach. In addition, the authors found that trips emphasizing education had a net economic benefit. Cost-benefit analyses have substantial financial implications and will aid policy makers in developing cost-reduction strategies to promote surgery in low- and middle-income countries.
Secondary Suture Fusion after Primary Correction of Nonsyndromic Craniosynostosis: Recognition of the Problem and Identification of Risk Factors
Authors: Vaca Elbert E. , Sheth Neil , Purnell Chad A. , McGrath Jennifer L. , Gosain Arun K.
Published: December 2019

Background:

Secondary fusion of initially patent cranial sutures after primary correction of nonsyndromic craniosynostosis is rarely reported. This study’s aim is to report the incidence and analyze whether there are variables that may predispose to such fusion.

Methods:

A single-institution, retrospective, case-control study was conducted of all nonsyndromic patients who underwent operative treatment for craniosynostosis from April of 2008 to May of 2017. Patients with less than 1 year of follow-up and/or without a 1-year postoperative computed tomographic scan were excluded. Preoperative, intraoperative, and postoperative variables were analyzed using univariate and multivariate analyses.

Results:

Sixty-six patients were included in the study, with a mean 2.57-year postoperative follow-up. Six patients (8.8 percent) were found to have secondary craniosynostosis, all of whom had fusion of sutures that were initially patent and refusion of the primary pathologic suture(s). Fifty percent of secondary fusions presented as pansynostosis. On univariate analysis, suturectomy with barrel staving (p < 0.01) was significantly associated with secondary suture fusion. On multivariate analysis, bilambdoid suture involvement (p = 0.03) and suturectomy with barrel staving (p = 0.01) were significantly associated with secondary suture fusion.

Conclusions:

Secondary cranial suture fusion may be a relatively common complication after primary craniosynostosis correction. Suturectomy with barrel staving was independently associated with secondary craniosynostosis. Wide surgical separation of the dura from the cranium and osteotomies across patent sutures may predispose to secondary craniosynostosis.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Is There Gender Inequality in Plastic Surgery? Evaluation of Society Leadership and Composition of Editorial Boards
Authors: Chen Kevin , Ha Grace , Schultz Benjamin D. , Zhang Ben , Smith Mark L. , Bradley James P. , Thorne Charles H. , Kasabian Armen K. , Pusic Andrea L. , Tanna Neil
Published: December 2019

Background:

Women now constitute 40.5 percent of integrated plastic surgery residents; however, in 2007, women represented only 11.3 percent of the leadership positions in plastic surgery societies and journal editorial boards. The authors analyzed female representation in these societies and editorial boards over the past 10 years.

Methods:

Names of board members from the major plastic surgery societies (American Society of Plastic Surgeons, The Plastic Surgery Foundation, and American Society for Aesthetic Plastic Surgery, among others) for the past 10 years and the major plastic journals (Plastic and Reconstructive Surgery, Annals of Plastic Surgery, and so on) from the past 5 years were extracted from their websites. The yearly percentage of female plastic surgery residents was obtained from Accreditation Council for Graduate Medical Education published data. The proportions of women in society leadership, editorial boards, and residency were compared with data analyses of time series trend and linear and Auto Regressive Integrated Moving Average time series modeling.

Results:

Over the past 10 years, the percentage of female residents has grown steadily, from 21.84 percent to 37.31 percent. Similarly, female representation in society leadership has grown from 6.78 percent to 20.29 percent. Both growth coefficients were statistically significant and showed no statistical difference between the two. In contrast, editorial board leadership over the past 5 years showed statistically insignificant growth and showed a statistically significant difference when compared to the growth of the percentage of female residents and female representation in society leadership.

Conclusion:

Female representation in plastic surgery society leadership shows promising growth, whereas their representation on editorial boards showed significantly less growth, which may reflect the slower turnover on these boards.
Surgical Strategies for Multicystic Ameloblastoma
Authors: Laino Luigi , Cicciù Marco , Russo Diana , Cervino Gabriele
Published: December 2019

Ameloblastoma is the second most common odontogenic tumor arising in the maxillary bones. The WHO classified ameloblastoma in: solid/multicystic (SMA); unicystic; peripheral and desmoplastic. A conservative or radical approach may be performed for SMA treatment to achieve total excision of the lesion.

In this case report, a 47-year-old woman, presented a deformation of the left mandibular region and paresthesia of the left hemi-labium, at the ortopanoramic x-ray (OPT) a multilocular osteolytic lesion and the rhizalysis of dental elements 3.7, 3.6, 3.5, 3.4 and the inclusion of 3.8 was appreciated; the CT exam showed erosion of the mandibular canal roof and of the vestibular cortex in the mental nerve region. The patient was subjected to the extraction of the elements in rhizalysis and of 3.8 and subsequently to the enucleation of the lesion followed by an extensive peripheral ostectomy performed with a piezoelectric device. The patient underwent to OPT and CT examinations follow-up and after 5 years was subjected to implant surgery, at the same time of the implant's placement, bone biopsies were performed using core drills in order to evaluate the bone histologically. The patient showed complete clinical and radiographic healing; the histological examination demonstrates the formation of lamellar bone.
New Histopathologic Evidence for the Parasympathetic Innervation of the Kidney and the Mechanism of Hypertension Following Subarachnoid Hemorrhage
Authors: Kepoglu Umit , Kanat Ayhan , Aydin Mehmet Dumlu , Akca Nezih , Kazdal Hizir , Zeynal Mete , Kantarci Mecit , Sipal Sare Altas
Published: December 2019

Background:

The Cushing response was first described in 1901. One of its components is elevated systemic blood pressure secondary to raised intracranial pressure. However, controversy still exists in its pathophysiologic mechanism. Hypertension is attributed to sympathetic overactivity and vagotomy increased renal-based hypertension. However, the role of the parasympathetic system in hypertension has not been investigated. This subject was investigated following subarachnoid hemorrhage (SAH).

Methods:

A total of 24 rabbits were used: control group (n = 5), SHAM group (n = 5), and an SAH group (n = 14; bolus injection of blood into the cisterna magna). Blood pressures were examined before, during, and after the experiment. After 3 weeks, animals were decapitated under general anesthesia. Vagal nodose ganglion, axonal degeneration, and renal artery vasospasm (RAV) indexes of all animals were determined histopathologically.

Results:

Significant degenerative changes were detected in the vagal axons and nodose ganglia following SAH in animals with severe hypertension. The mean degenerated neuron density of nodose ganglions, vasospasm index (VSI) values of renal arteries of control, SHAM, and study groups were estimated as 9.0 ± 2.0 mm3, 1.87 ± 0.19; 65.0 ± 12.0 mm3, 1.91 ± 0.34; and 986.0 ± 112.0 mm3, 2.32 ± 0.89, consecutively. Blood pressure was measured as 94.0 ± 10.0 mmHg in control group, 102.0 ± 12.0 mmHg in SHAM; 112.0 ± 14.0 mmHg in middle (n = 9); and >122.0 ± 10.0 mmHg in severe RAV-developed animals (n = 5). Differences VSI values and blood pressure between groups were statistically significant (P < 0.05).

Conclusion:

The degeneration of vagal nodose ganglion has an important role in RAV and the development of RAV and hypertension following SAH.
The Effect of Hyaluronidase on the Fat Graft
Authors: Kim Seung Ki , Yang Jun Young , Kim Chan Woo , Baek Seung Hwa , Kim Uigeon , Hwang Euna
Published: December 2019

Background:

Fat grafting has been widely used for facial rejuvenation and soft tissue reconstruction. However, it is associated with a lower retention rate than expected and complications such as fat necrosis or calcification. Several techniques that may increase the survival rate of fat grafts have been proposed. The techniques that promote the recipient sites vascularity to increase the survival rate of fat grafts include administration of growth factors, platelet- rich plasma, and adipose derived-stem cells or preconditioning of the recipient fat graft site.

Methods:

In this study, the authors evaluated the effect of hyaluronidase on autologous fat graft survival by pretreatment with hyaluronidase at the recipient site by using an animal model. In the experimental group, the recipient site of the fat graft was pretreated with hyaluronidase before fat grafting, whereas the control group was pretreated with normal saline.

Results:

After 8 weeks of fat grafting, the average volume retention was 78.2% in the experimental group and 68.6% in control group. Considerable fibrosis between the fat globules in the control group was confirmed with Masson trichrome staining. CD31 immunofluorescence staining was performed and stained vessels were counted. Counted vessel number was significantly greater in the experimental group than in the control group.

Conclusions:

Pretreatment of hyaluronidase on the fat graft recipient site is a good option to enhance the outcome of the fat graft in the clinical setting.
Digital interventions for adolescent and young adult cancer survivors
Authors: Viola Adrienne , Panigrahi Gargi , Devine Katie A.
Published: December 2019

Purpose of review

AYA patients with cancer have a unique set of psychosocial and support needs to compared with their younger and older counterparts. Digital health interventions overcome many of the barriers to AYA participation in behavioral health interventions. Due to the rapid shifts in digital health, it is important to continually assess the state of the field.

Recent findings

There has been a sharp increase in the number of digital health interventions published in the literature. Interventions are using a variety of modalities and targeting many health behaviors and psychosocial outcomes. Most studies are focused on feasibility and acceptability, and use single-arm and prepost methodologies.

Although randomized controlled trials remain an important design for evaluating efficacy of interventions, the field of digital health interventions would benefit from employing alternative methodologies and analytic approaches to develop and optimize digital health interventions aligned with rapidly evolving technology.
Online interventions geared toward increasing resilience and reducing distress in family caregivers
Authors: Shin Ji Youn , Choi Sung Won
Published: December 2019

Purpose of review

Family caregivers of patients with cancer often spend a great deal of effort on physically and emotionally demanding work while taking care of patients. However, the majority of caregivers are not properly equipped for their role as caregivers, which may lead to increased distress in both caregivers and patients. Herein, we reviewed the recent literature (last 3 years) examining online interventions that seek to support caregiver resilience and decrease distress.

Recent findings

Our search identified interventions involving three main themes: informational support, positive activities, and social support. These are mostly in the form of web-based tools and mobile apps targeting both usability and quality of life. Social network services are also considered in this review as a new environment for caregivers to connect with other individuals with lived experience in similar circumstances.

Existing studies on online interventions to support caregivers is still at a formative development stage and pilot tests of feasibility, rather than a substantive body of randomized controlled trials to assess the impact in different user populations, or to determine specific factors that impact caregiver distress level or resilience. More research is needed to further assess the long-term effects of online interventions on caregiver stress and resilience. Also, the role of different types of social network services and new forms of interaction, such as conversational agents, has not yet been fully investigated in caregiver populations. Future research should strive to seek new modes of providing services that may present novel opportunities to enhance caregiver resilience and reduce distress.
Dissociable effects of prediction and integration during language comprehension: evidence from a large-scale study using brain potentials
Authors: Nieuwland Mante S. , Barr Dale J. , Bartolozzi Federica , Busch-Moreno Simon , Darley Emily , Donaldson David I. , Ferguson Heather J. , Fu Xiao , Heyselaar Evelien , Huettig Falk , Matthew Husband E. , Ito Aine , Kazanina Nina , Kogan Vita , Kohút Zdenko , Kulakova Eugenia , Mézière Diane , Politzer-Ahles Stephen , Rousselet Guillaume , Rueschemeyer Shirley-Ann , Segaert Katrien , Tuomainen Jyrki , Von Grebmer Zu Wolfsthurn Sarah
Published: December 2019

Composing sentence meaning is easier for predictable words than for unpredictable words. Are predictable words genuinely predicted, or simply more plausible and therefore easier to integrate with sentence context? We addressed this persistent and fundamental question using data from a recent, large-scale (
n
= 334) replication study, by investigating the effects of word predictability and sentence plausibility on the N400, the brain's electrophysiological index of semantic processing. A spatio-temporally fine-grained mixed-effect multiple regression analysis revealed overlapping effects of predictability and plausibility on the N400, albeit with distinct spatio-temporal profiles. Our results challenge the view that the predictability-dependent N400 reflects the effects of
either
prediction
or
integration, and suggest that semantic facilitation of predictable words arises from a cascade of processes that activate and integrate word meaning with context into a sentence-level meaning.

This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
Tensors and compositionality in neural systems
Authors: Martin Andrea E. , Doumas Leonidas A. A.
Published: December 2019

Neither neurobiological nor process models of meaning composition specify the operator through which constituent parts are bound together into compositional structures. In this paper, we argue that a neurophysiological computation system cannot achieve the compositionality exhibited in human thought and language if it were to rely on a multiplicative operator to perform binding, as the tensor product (TP)-based systems that have been widely adopted in cognitive science, neuroscience and artificial intelligence do. We show via simulation and two behavioural experiments that TPs violate variable-value independence, but human behaviour does not. Specifically, TPs fail to capture that in the statementsfuzzy cactusandfuzzy penguin, both cactus and penguin are predicated byfuzzy(x) and belong to the set of fuzzy things, rendering these arguments similar to each other. Consistent with that thesis, people judged arguments that shared the same role to be similar, even when those arguments themselves (e.g., cacti and penguins) were judged to be dissimilar when in isolation. By contrast, the similarity of the TPs representingfuzzy(cactus) andfuzzy(penguin) was determined by the similarity of the arguments, which in this case approaches zero. Based on these results, we argue that neural systems that use TPs for binding cannot approximate how the human mind and brain represent compositional information during processing. We describe a contrasting binding mechanism that any physiological or artificial neural system could use to maintain independence between a role and its argument, a prerequisite for compositionality and, thus, for instantiating the expressive power of human thought and language in a neural system.

This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
Tools and Resources: Remote, automated and MRI-compatible administration of interoceptive inspiratory resistive loading
Authors: Rieger Sebastian W , Stephan Klaas Enno , Faull Olivia K.
Published: December 2019

Research on how humans perceive sensory inputs from their bodies (‘interoception’) has been rapidly gaining momentum, with interest across a host of disciplines from physiology through to psychiatry. However, studying interoceptive processes is not without significant challenges, and many methods utilised to access internal states have been largely devoted to capturing and relating naturally-occurring variations in interoceptive signals (such as heartbeats) to measures of how the brain processes these signals. An alternative procedure involves the controlled perturbation of specific interoceptive axes. This is challenging because it requires non-invasive interventions that can be repeated many times within a subject and that are potent but safe. Here we present an effective methodology for instigating these perturbations within the breathing domain. We describe a custom-built circuitry that is capable of delivering inspiratory resistive loads automatically and precisely. Importantly, our approach is compatible with magnetic resonance imaging environments, allowing for the administration of complicated experimental designs in neuroimaging as increasingly required within developing fields such as computational psychiatry/psychosomatics. We describe the experimental setup for both the control and monitoring of the inspiratory resistive loads, and demonstrate its possible utilities within different study designs. This methodology represents an important step forward from the previously utilised, manually-controlled resistive loading setups, which present significant experimental burdens with prolonged and/or complicated sequences of breathing stimuli.
Ontario Neurodegenerative Disease Research Initiative (ONDRI): Structural MRI methods & outcome measures
Authors: Ramirez Joel , Holmes Melissa F. , Scott Christopher J.M. , Ozzoude Miracle , Adamo Sabrina , Szilagyi Gregory M. , Goubran Maged , Gao Fuqiang , Arnott Stephen R. , Lawrence-Dewar Jane M. , Beaton Derek , Strother Stephen C. , Munoz Douglas P. , Masellis Mario , Swartz Richard H. , Bartha Robert , Symons Sean , Black Sandra E. ,   the ONDRI Investigators
Published: December 2019

The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 year multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and cerebrovascular disease patients. This heterogeneous cross-section of patients with complex neurodegenerative and neurovascular pathologies pose significant challenges for standard neuroimaging tools. To effectively quantify regional measures of normal and pathological brain tissue volumes, the ONDRI neuroimaging platform implemented a semi-automated MRI processing pipeline that was able to address many of the challenges resulting from this heterogeneity. This paper describes the comprehensive neuroimaging pipeline methods used to generate regional brain tissue volumes & neurovascular markers.
Anti-inflammatory treatment with FTY720 starting after onset of symptoms reverses synaptic and memory deficits in an AD mouse model
Authors: Kartalou Georgia-Ioanna , Pereira Ana Rita Salgueiro , Endres Thomas , Lesnikova Angelina , Casarotto Plinio , Pousinha Paula , Delanoe Kevin , Edelmann Elke , Castrén Eero , Gottmann Kurt , Marie Helene , Lessmann Volkmar
Published: December 2019

Therapeutical approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Repurposing FDA approved drugs like fingolimod (FTY720) for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms. Here, we addressed whether the FDA approved drug fingolimod rescues AD related synaptic deficits and memory dysfunction in an APP/PS1 AD mouse model when medication starts after onset of symptoms (at 5 months). Male mice received intraperitoneal injections of fingolimod for 1-2 months starting at 5-6 months. This treatment rescued spine density as well as long-term potentiation in hippocampal CA1 pyramidal neurons, and ameliorated dysfunctional hippocampus-dependent memory that was observed in untreated APP/PS1 animals at 6-7 months of age. Immunohistochemical analysis with markers of microgliosis (Iba1) and astrogliosis (GFAP) revealed that our fingolimod treatment regime strongly down regulated neuro-inflammation in the hippocampus and cortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and cortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology and related memory performance deficits observed in untreated AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.
Towards a Chimeric Vaccine against Multiple Isolates ofMycobacteroides- An Integrative Approach
Authors: Satyam Rohit , Bhardwaj Tulika , Jha Niraj Kumar
Published: December 2019

Nontuberculous mycobacterial infection (NTM) such as endophthalmitis, dacryocystitis, canaliculitis are pervasive across the globe and are currently managed by antibiotics such as cefoxitin/imipenem and azithromycin/clarithromycin. However, the recent cases of Mycobacteroides developing drug resistance reported along with the improper practice of medicine intrigued us to explore its genomic and proteomic canvas at a global scale. A timely developed vaccine against Mycobacteroides is, therefore, a much requirement. Consequently, we carried out a vivid Genomic study on five recently sequenced strains of Mycobacteroides and explored their Pan-Core genome/ proteome. The promiscuous antigenic proteins were identified via a subtractive proteomics approach that qualified for virulence causation, resistance and essentiality factors for this notorious bacterium. An integrated pipeline was developed for the identification of B Cell, MHC class I, II epitopes. Our final vaccine construct, V6 qualified for all tests such as absence for allergenicity, presence of antigenicity, etc. and contains β defensin adjuvant, linkers, LAMP1 signal peptide, and PADRE (Pan HLA-DR epitopes) amino acid sequence. The vaccine construct, V6 also interacts with a maximum number of MHC molecules, and the TLR4/MD2 complex confirmed by docking and molecular dynamics simulation studies. The knowledge harnessed from the current study can help improve the current treatment regimens and propel further related studies.
Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age
Authors: Schneider Jules , Lewis Penelope A. , Koester Dominik , Born Jan , Ngo Hong-Viet V.
Published: December 2019

Background

Cortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate sleep-dependent memory consolidation. Experiments utilising auditory closed-loop stimulation to enhance these oscillations have shown great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups.

Objective

We examined the possibility of enhancing SOs and performance on different memory tasks in a healthy older population using auditory closed-loop stimulation and contrast effects to a young adult cohort.

Methods

In a within-subject design, subjects (n = 17, 55.7 ± 1.0 years, 9 female) received auditory click stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to those reported previously in a younger cohort (n = 11, 24.2 ± 0.9 years, 8 female).

Results

Overnight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups.

Conclusions

Our findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations.

Highlights

Auditory closed-loop stimulation induced SOs and sleep spindles in older subjects

Stimulation effects were reduced and overall susceptibility diminished with age

Slow oscillation and sleep spindle dynamics deviated from those in younger subjects

Stimulation shows no evidence for memory effect in older subjects
In vivostudies of glucagon secretion by human islets transplanted in mice
Authors: Tellez Krissie , Hang Yan , Gu Xueying , Stein Roland W. , Kim Seung K.
Published: December 2019

Relatively little is known about regulated glucagon secretion by human islet α cells compared to insulin secretion from β cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulin sequences in humans and mice permitin vivostudies of β cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogousin vivomeasures of glucagon output from human α cells. We used CRISPR/Cas9 genome editing to remove glucagon-encoding codons 2-29 in immunocompromised (NSG) mice, preserving production of other proglucagon-derived hormones, like Glucagon-like-peptide 1. TheseNSG-Glucagon knockout (NSG-GKO) mice had phenotypes associated with glucagon signaling deficits, including hypoglycemia, hyperaminoacidemia, hypoinsulinemia, and islet α cell hyperplasia.NSG-GKOhost metabolic and islet phenotypes reverted after human islet transplantation, and human islets retained regulated glucagon and insulin secretion.NSG-GKOmice provide an unprecedented resource to investigate unique, species-specific human α cell regulationin vivo.
Noncoding de novo mutations contribute to autism spectrum disorder via chromatin interactions
Authors: Kim Il Bin , Lee Taeyeop , Lee Junehawk , Kim Jonghun , Lee Hyunseong , Kim Woo Kyeong , Ju Young Seok , Cho Yongseong , Yu Seok Jong , Kim Soon Ae , Oh Miae , Kwak Tae Hwan , Hali Sai , Han Dong Wook , Kim Eunjoon , Choi Jung Kyoon , Yoo Hee Jeong , Lee Jeong Ho
Published: December 2019

Three-dimensional chromatin structures regulate gene expression across genome. The significance of de novo mutations (DNMs) affecting chromatin interactions in autism spectrum disorder (ASD) remains poorly understood. We generated 931 whole-genome sequences for Korean simplex families to detect DNMs and identified target genes dysregulated by noncoding DNMs via long-range chromatin interactions between regulatory elements. Notably, noncoding DNMs that affect chromatin interactions exhibited transcriptional dysregulation implicated in ASD risks. Correspondingly, target genes were significantly involved in histone modification, prenatal brain development, and pregnancy. Both noncoding and coding DNMs collectively contributed to low IQ in ASD. Indeed, noncoding DNMs resulted in alterations, via chromatin interactions, in target gene expression in primitive neural stem cells derived from human induced pluripotent stem cells from an ASD subject. The emerging neurodevelopmental genes, not previously implicated in ASD, include CTNNA2, GRB10, IKZF1, PDE3B, and BACE1. Our results were reproducible in 517 probands from MSSNG cohort. This work demonstrates that noncoding DNMs contribute to ASD via chromatin interactions.
Effect of EBV-Transformation on Oxidative Phosphorylation Physiology in Human Cell lines
Authors: Weinstein Rachel N. , Crawford Douglas L.
Published: December 2019

Abstract

Do the immortalized and cryopreserved white blood cells that are part of the 1,000 Human Genomes Project represent a valuable cellular physiological resource to investigate the importance of genome wide sequence variation? While much research exists on the nucleotide variation in the 1,000 Human Genomes, there are few quantitative measures of these humans’ physiologies. Fortunately, physiological measures can be done on the immortalized and preserved cells from each of the more than 1,000 individuals that are part of Human Genome project. However, these human white blood cells were immortalized by transforming them with the Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines (LCL)). This transformation integrates the viral genome into the human genome and potentially affects important biological differences among individuals. The questions we address here are whether EBV transformations significantly alters the cellular physiology so that 1) replicate transformations within an individual are significantly different, and 2) whether the variance among replicates obscures the variation among individuals. To address these questions, we quantified oxidative phosphorylation (OxPhos) metabolism in LCLs from six individuals with 4 separate and independent EBV-transformations. We examined OxPhos because it is critical for energy production, and mutations in this pathway are responsible for most inborn metabolic diseases. The data presented here demonstrate that there are small but significant effects of EBV-transformations on some OxPhos parameters. In spite of significant variation due to transformations, there is greater and significant variation among individuals in their OxPhos metabolism. Thus, the LCLs from the 1,000 Human Genome project could provide valuable insights into the natural variation of cellular physiology because there is statistically significant variation among individuals when using these EBV-transformed cells.
The transformation effect of R&D subsidies on firm performance
Authors: Wang Fengrong , Li Yafei , Sun Jinping
Published: December 2019

Purpose

The purpose of this paper studies the transformation effect of research and development (R&D) subsidies on firm performance in emerging economies from the perspective of capital and product markets. It also studies the mechanisms behind R&D subsidies’ transformation effect.

Design/methodology/approach

This study mainly explores the transformation effect of government R&D subsidies on corporate performance and its non-linear characteristics using Chinese A-share listed companies’ data from 2008 to 2016. The authors use the instrumental variable method to reduce endogenous problems and conduct a series of robustness tests to support the conclusions. The mechanisms of the transformation effect are explored via mediation effect models. The impact of firm heterogeneities on the transformation effect is also addressed.

Findings

Results indicate that R&D subsidies promote firm performance and experience obvious transformation effects only within a “moderate interval.” R&D subsidies play a vital role in enhancing firm performance mainly via two mechanisms, namely, signal financing and innovation incentives. Further, the transformation effect is much greater in non-state-owned, young and large enterprises.

Originality/value

This paper contributes to understanding how R&D subsidies affect corporate performance from the perspective of capital and product markets by applying the linear and non-linear techniques that can clarify the relationship between the selected variables under study. The findings of this study might be helpful to identify the right directions for the government to implement and promote the R&D subsidy policies more effectively.
Fault-tolerant redundant repairable system with different failures and delays
Authors: Shekhar Chandra , Kumar Amit , Varshney Shreekant , Ammar Sherif I.
Published: December 2019

Purpose

The internet of things and just-in-time are the embryonic model of innovation for the state-of-the-art design of the service system. This paper aims to develop a fault-tolerant machining system with active and standby redundancy. The availability of the fault-tolerant redundant repairable system is a key concern in the successful deployment of the service system.

Design/methodology/approach

In this paper, the authors cogitate a fault-tolerant redundant repairable system of finite working units along with warm standby unit provisioning. Working unit and standby unit are susceptible to random failures, which interrupt the quality-of-service. The system is also prone to common cause failure, which tends its catastrophe. The instantaneous repair of failed unit guarantees the increase in the availability of the unit/system. The time-to-repair by the single service facility for the failed unit follows the arbitrary distribution. For increasing the practicability of the studied model, the authors have also incorporated real-time machining practices such as imperfect coverage of the failure of units, switching failure of standby unit, common cause failure, reboot delay, switch over delay, etc.

Findings

For deriving the explicit expression for steady-state probabilities of the system, the authors use a supplementary variable technique for which the only required input is the Laplace–Stieltjes transform (LST) of the repair time distribution.

Research limitations/implications

For complex and multi-parameters distribution of repair time, derivation of performance measures is not possible. The authors prefer numerical simulation because of its importance in the application for real-time uses.

Practical implications

The stepwise recursive procedure, illustrative examples, and numerical results have been presented for the diverse category of repair time distribution: exponential (M), n-stage Erlang (Ern), deterministic (D), uniform (U(a,b)), n-stage generalized Erlang (GE[n]) and hyperexponential (HE[n]).

Social implications

Concluding remarks and future scopes have also been included. The studied fault-tolerant redundant repairable system is suitable for reliability analysis of a computer system, communication system, manufacturing system, software reliability, service system, etc.

Originality/value

As per the survey in literature, no previous published paper is presented with so wide range of repair time distribution in the machine repair problem. This paper is valuable for system design for reliability analysis of the fault-tolerant redundant repairable.