bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese student writers’ perspectives on anonymous peer review
Authors: Kim Sugene
Published: February 2019

This article explores Japanese EFL learners’ perceptions of face-to-face vs. anonymous peer review in a writing classroom. Albeit few in number, some studies claim that Asian students exhibit difficulty in providing negative feedback because they tend to be hesitant for cultural reasons to criticize others’ work. To verify and extend such observations, this study collected data from 64 Japanese college students regarding their experiences and perspectives after they performed peer review in both conditions. Analysis of the data collected through a survey and semi-structured interviews did not support the previously held views that learners from non-Western cultural backgrounds are predisposed to be reluctant peer reviewers. Further, the findings indicated that Japanese EFL learners’ preference for a specific peer-review mode interacts closely with various factors. Possible pedagogical implications are discussed in relation to ways to better implement peer-review sessions.
Development and usability testing of an audit and feedback tool for anesthesiologists
Authors: Barbeito Atilio , Segall Noa
Published: February 2019

Background

We describe the creation and evaluation of a personal audit and feedback (A&F) tool for anesthesiologists.

Methods

A survey aimed at capturing barriers for personal improvement efforts and feedback preferences was administered to attending anesthesiologists. The results informed the design and implementation of 4 dashboards that display information on individual practice characteristics as well as comparative performance on several quality metrics. The dashboards’ usability was then tested using the human-centered design framework.

Results

Anesthesiologists listed lack of information on current practice as the main barrier for improvement. Regarding usability, participants gave the dashboards an average score of 3.8 (scale 1–5) on consistency, learnability, and information organization, and performed the assigned tasks well, with an average score of 89% (range 79–100%).

Conclusions

We describe the design, implementation, and usability testing of an innovative tool that utilizes data derived from the electronic health record (EHR) system to provide A&F to anesthesiology providers.
NUMB regulates the endocytosis and activity of the anaplastic lymphoma kinase in an isoform-specific manner
Authors: Wei Ran , Liu Xuguang , Voss Courtney , Qin Wentao , Dagnino Lina , Li Lei , Vigny Marc , Li Shawn Shun-Cheng
Published: February 2019

NUMB is an evolutionarily conserved protein that plays an important role in cell adhesion, migration, polarity, and cell fate determination. It has also been shown to play a role in the pathogenesis of certain cancers, although it remains controversial whether NUMB functions as an oncoprotein or tumor suppressor. Here, we show that NUMB binds to anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase aberrantly activated in several forms of cancer, and this interaction regulates the endocytosis and activity of ALK. Intriguingly, the function of the NUMB–ALK interaction is isoform-dependent. While both p66-NUMB and p72-NUMB isoforms are capable of mediating the endocytosis of ALK, the former directs ALK to the lysosomal degradation pathway, thus decreasing the overall ALK level and the downstream MAP kinase signal. In contrast, the p72-NUMB isoform promotes ALK recycling back to the plasma membrane, thereby maintaining the kinase in its active state. Our work sheds light on the controversial role of different isoforms of NUMB in tumorigenesis and provides mechanistic insight into ALK regulation.
Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus
Authors: Schiff David , Van den Bent Martin , Vogelbaum Michael A , Wick Wolfgang , Miller C Ryan , Taphoorn Martin , Pope Whitney , Brown Paul D , Platten Michael , Jalali Rakesh , Armstrong Terri , Wen Patrick Y
Published: February 2019

The finding that most grades II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and deletional analysis of cyclin-dependent kinase inhibitor 2A and 2B. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing, and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein.
Urgent Middle Cerebral Artery Embolectomy of Calcified Embolus After Intravenous Thrombolysis: 2-Dimensional Operative Video
Authors: Fiedler Jiri , Ostry Svatopluk , Bombic Martin , Sterba Ludek , Kostal Petr
Published: February 2019

This video shows an urgent microsurgical embolectomy of the inferior division of the left middle cerebral artery in a patient treated by intravenous thrombolysis (IVT). Patient was eligible for endovascular mechanical thrombectomy
1
; however, the interventional radiologist was not comfortable performing the procedure given prior unsuccessful attempts to remove a calcified cerebral embolus.
2
A 75-yr-old female presented with an acute ischemic stroke with isolated aphasia (NIHSS 9). Using the drip-and-ship concept, IVT (0.9 mg/kg rt-PA) was administered in a regional hospital. Fifty-five minutes after a complete recovery following IVT, multiple transient ischemic attacks of aphasia were observed. While the patient was a candidate for mechanical thrombectomy based on CT perfusion imaging, given the unsuccessful reports in the literature and the interventional radiologist's experience, the decision was made to offer microsurgical embolectomy of the calcified cerebral embolus.
3
Informed consent for the procedure was obtained directly from the patient. Calcified, crumbly embolus was removed from a 5 mm longitudinal arteriotomy. The arteriotomy was sutured with interrupted 10-0 suture. Initial flow after the embolectomy was 6.5 mL/min. Upon inspection, a distal kink was found in the M2 and after repositioning, flow improved to 35 mL/min.

Postoperative CT angiography documented complete recanalization. The clinical findings completely resolved (NIHSS 0) within 12 hr and remained unchanged at 3 mo and 1 yr.

Informed consent was obtained from the patient for use of media for educational and publication purposes.
Reliability and Validity of Measurement Tools for Residual Limb Volume in People With Limb Amputations: A Systematic Review
Authors: Armitage Lucy , Kark Lauren , Czerniec Sharon , Kwah Li Khim
Published: February 2019

Background

Measurements of residual limb volume often guide decisions on the type and timing of prosthetic prescription. To help inform these decisions, it is important that clinicians use measurement tools that are reliable and valid.

Purpose

The aim of this systematic review was to investigate the reliability and validity of measurement tools for residual limb volume in people with limb amputations.

Data Sources

A comprehensive search on MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science was performed on July 11, 2016.

Study Selection

Studies were included if they examined the reliability or validity of measurement tools for residual limb volume, were conducted on humans, and were published in English.

Data Extraction

Data were extracted from 11 reliability and 4 validity studies and included study characteristics, volumetric estimates, and reliability and validity estimates. The quality of the studies was also rated.

Data Synthesis

Data from 2 studies (38 participants) indicated good to excellent intrarater (intraclass correlation coefficient [ICC] ≥0.88) and interrater (ICC ≥0.88) reliability and high between-session reliability (coefficient of variation [CV] = 10%) for water displacement volumetry. One study (28 participants) reported excellent intrarater and interrater reliability (ICC ≥0.93) for the circumferential method, and data from 2 studies (19 participants) indicated high between-session reliability for the optical surface scanner (CV ≤9.8%). Three studies (26 participants) indicated good to excellent between-session reliability results for computed tomography (CV = 9.2%–10.9%). One study (7 participants) showed moderate within-session reliability (CV = 50%). Using water displacement volumetry as the gold standard, 2 studies (79 participants) indicated excellent validity for the circumferential method ( r ≥0.92; ICC ≥0.92). All studies reporting measures of reliability or validity were performed with people who had transtibial amputations.

Limitations

Only studies published in English and in which water displacement volumetry was used as the gold standard were included in this review. The reliability and validity of the quality rating scale used in this review have not been tested.

Conclusions

On the basis of a limited number of moderate- to high-quality studies with small sample sizes, circumferential and water displacement methods were found to be reliable, and the circumferential method was found to be valid in people with transtibial amputations. There are inadequate data for drawing conclusions about volume measurement methods in people with other types of limb amputations.
Federalism and Public Opinion on Healthcare: The Design of the Affordable Care Act’s Insurance Exchanges and User Experience with the Exchanges
Authors: Liebertz Scott , Bunch Jaclyn , Shaw Thomas
Published: February 2019

Using original survey data and the 2016 American National Election Study (ANES), we examine the effects of healthcare exchange type and user experience on individuals’ support for the Affordable Care Act (ACA). States are divided into three different types of ACA exchange implementation regimes: state-run exchanges, federally operated exchanges, and mixed state-federal exchanges. We hypothesize that individuals in states running their own exchanges will demonstrate greater support for the ACA and individuals with experience using the exchanges will exhibit greater levels of support for the ACA. Results from a survey conducted in 2016 in Alabama (a federal exchange), Kentucky (a state exchange at the time), and Arkansas (a mixed state-federal exchange) support these hypotheses. These findings are also confirmed using national data from the ANES. We therefore provide evidence that local control over healthcare implementation leads to better outcomes in terms of citizen satisfaction and that citizens who have experience with exchanges established by the ACA are more likely to feel positively about the law.
Cross-validation of transtheoretical model smoking cessation measures in Chicago WIHS women smokers with and at risk for HIV
Authors: Redding Colleen A , Goldberg David , Weber Kathleen M , Yin Hui-Qing , Paiva Andrea L , Burke-Miller Jane , Cohen Mardge H , Rossi Joseph S
Published: February 2019

People with and at risk for HIV have high rates of smoking, increasing their morbidity and mortality. Effective cessation interventions are needed for this group. Transtheoretical model (TTM)-tailored interventions have demonstrated efficacy, but measures need cross-validation in this population. TTM cessation measures were evaluated in women smokers with and at risk for HIV (N = 111) from Chicago Women’s Interagency HIV Study (WIHS). Confirmatory factor analyses evaluated measurement models. MANOVAs examined relationships between constructs and stage subgroups. For decisional balance, the two-factor uncorrelated model was best (χ2(20) = 13.96; comparative fit index [CFI], 1.0; root mean square error of approximation [RMSEA] = .00), with good (pros α = .78) and fair (cons α = .55) four-item alphas. The one-factor temptations model (α = .90) showed reasonable fit (χ2(18) = 80.22; CFI = .89; RMSEA = .177). Processes of change subscales had fair to good two-item alphas (α = .49–.77) and fit a 10-factor fully correlated model (χ2(125) = 222.72; CFI = .88; RMSEA = .084). MANOVAs by stage of change replicated expected patterns for the pros, overall temptations, and two process subscales with medium-sized effects (η2 = .06–.18). Contrary to expectations, no differences by stage were found for cons or temptation negative affect subscales. The structures of these TTM measures replicated with good internal and external validity, except for the cons, which needs refinement. Negative affect temptations was structurally sound, but did not vary by stage group potentially reflecting this sample’s moderate depression levels and/or their reliance on smoking to deal with negative affect. Results support the use of most TTM measures in research and tailored interventions to increase smoking cessation among women smokers with and at risk for HIV and highlight the importance of managing negative affect in cessation materials targeting this group.
Mapping behavior change techniques to characterize a social cognitive theory informed physical activity intervention for adults at risk of type 2 diabetes mellitus
Authors: Bourne Jessica E , Ivanova Elena , Gainforth Heather L , Jung Mary E
Published: February 2019

Behavior change techniques (BCTs) are used to target theoretical mechanisms of action predicted to bring about behavior change. Reporting BCTs and connecting them to mechanisms of action is critical to understanding intervention processes of change. This article identifies the BCTs associated with an exercise intervention for individuals at risk of type 2 diabetes and determines the extent to which these BCTs target associated mechanisms of action. BCTs were mapped onto social cognitive theory (SCT) and the theoretical domains framework (TDF) using published literature identifying links between BCTs and SCT/TDF and expert consensus. Two coders then used the 93-item BCT taxonomy (BCTTv1) to independently code BCTs within the intervention. The BCTs used in the current intervention enabled identification of the theoretical mechanisms of action targeted in the intervention. More than 70% of the intervention content incorporated at least one BCT. More than 50% of the BCTs used targeted SCT constructs and more than 70% of BCTs used targeted at least one of the 14 TDF domains. Five BCTs did not map onto either SCT or TDF. This research provides a systematic method of linking BCTs to mechanisms of action. This process increases the transparency of intervention content and identification of the mechanisms of action targeted in the current intervention. Reporting interventions in this manner will enable the most potent mechanisms of actions associated with long-term behavior change to be identified and utilized in future work.

Trial Registration: ClinicalTrials.gov # NCT02164474. Registered on June 12, 2014.
Socialist Television Drama, Newspaper Critics and the Battle of Ideas During the Crisis of Britain’s Post-War Settlement
Authors: Fielding Steven
Published: February 2019

Due to the difficult methodological issues it presents, political historians are wary of using television - the most important mass medium of the later twentieth century - as a means of exploring vernacular political thinking. Attempting to show how television audiences were encouraged to think politically, the article outlines a method generated through an engagement with the work of disciplines beyond history, to help political historians more systematically assess the medium's popular impact. The article takes as its case study Britain during the 1970s, one of the most ideologically contested periods in the country's history. It analyses how television critics employed by the Daily Mirror and Daily Express encouraged their millions of readers to respond to the dramas of socialist playwrights Jim Allen and Trevor Griffiths, thereby giving historians an insight into the shape of those conversations spawned by their work, such private dialogues being the place where the full political meaning of television was ultimately created.
Train delay analysis and prediction based on big data fusion
Authors: Wang Pu , Zhang Qing-peng
Published: February 2019

Despite the fact that punctuality is an advantage of rail travel compared with other long-distance transport, train delays often occur. For this study, a three-month dataset of weather, train delay and train schedule records was collected and analysed in order to understand the patterns of train delays and to predict train delay time. We found that in severe weather train delays are determined mainly by the type of bad weather, while in ordinary weather the delays are determined mainly by the historical delay time and delay frequency of trains. Identifying the factors closely correlated with train delays, we developed a machine-learning model to predict the delay time of each train at each station. The prediction model is useful not only for passengers wishing to plan their journeys more reliably, but also for railway operators developing more efficient train schedules and more reasonable pricing plans.
Trichoderma harzianum Improves Defense Against Fusarium oxysporum by Regulating ROS and RNS Metabolism, Redox Balance, and Energy Flow in Cucumber Roots
Authors: Chen Shuang-Chen , Ren Jing-Jing , Zhao Hong-Jiao , Wang Xiang-Li , Wang Tai-Hang , Jin Sun-Da , Wang Zhong-Hong , Li Chong-yang , Liu Ai-Rong , Lin Xiao-Min , Ahammed Golam Jalal
Published: February 2019

Plant survival in the terrestrial ecosystem is influenced by both beneficial and harmful microbes. Trichoderma spp. are a group of filamentous fungi that promote plant growth and resistance to harmful microbes. Previously, we showed that the genus Trichoderma could effectively suppress Fusarium wilt in cucumber. However, the mechanisms that underlie the effects of the genus Trichoderma on plant defense have not been fully substantiated. Two essential metabolic pathways, such as the ascorbate (AsA)-glutathione (GSH) cycle and the oxidative pentose phosphate pathway (OPPP), have been shown to participate in plant tolerance to biotic stressors; nevertheless, the involvement of these pathways in Trichoderma-induced enhanced defense remains elusive. Here, we show that Trichoderma harzianum could alleviate oxidative and nitrostative stress by minimizing reactive oxygen species (ROS; hydrogen peroxide and superoxide) and reactive nitrogen species (nitric oxide [NO]) accumulation, respectively, under Fusarium oxysporum infection in cucumber roots. The genus Trichoderma enhanced antioxidant potential to counterbalance the overproduced ROS and attenuated the transcript and activity of NO synthase and nitrate reductase. The genus Trichoderma also stimulated S-nitrosylated glutathione reductase activity and reduced S-nitrosothiol and S-nitrosylated glutathione content. Furthermore, the genus Trichoderma enhanced AsA and GSH concentrations and activated their biosynthetic enzymes, γ-GCS and l-galactono-1,4-lactone dehydrogenase. Interestingly, the genus Trichoderma alleviated Fusarium-inhibited activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, enzymes involved in the OPPP. Such positive regulation of the key enzymes indicates the adequate maintenance of the AsA-GSH pathway and the OPPP, which potentially contributed to improve redox balance, energy flow, and defense response. Our study advances the current knowledge of Trichoderma-induced enhanced defense against F. oxysporum in cucumber.
Compared Efficacy of Four Preoxygenation Methods for Intubation in the ICU: Retrospective Analysis of McGrath Mac Videolaryngoscope Versus Macintosh Laryngoscope (MACMAN) Trial Data
Authors: Bailly Arthur , Ricard Jean-Damien , Le Thuaut Aurelie , Helms Julie , Kamel Toufik , Mercier Emmanuelle , Lemiale Virginie , Colin Gwenhael , Mira Jean-Paul , Clere-Jehl Raphaël , Messika Jonathan , Dequin Pierre-Francois , Boulain Thierry , Azoulay Elie , Champigneulle Benoit , Reignier Jean , Lascarrou Jean-Baptiste
Published: February 2019

Objectives:

Severe hypoxemia is the most common serious adverse event during endotracheal intubation. Preoxygenation is performed routinely as a preventive measure. The relative efficacy of the various available preoxygenation devices is unclear. Here, our objective was to assess associations between preoxygenation devices and pulse oximetry values during endotracheal intubation.

Design:

Post hoc analysis of data from a multicenter randomized controlled superiority trial (McGrath Mac Videolaryngoscope Versus Macintosh Laryngoscope [MACMAN]) comparing videolaryngoscopy to Macintosh laryngoscopy for endotracheal intubation in critical care.

Setting:

Seven French ICUs.

Patients:

Three-hundred nineteen of the 371 critically ill adults requiring endotracheal intubation who were included in the MACMAN trial.

Interventions:

None.

Measurements and Main Results:

Minimal pulse oximetry value during endotracheal intubation was the primary endpoint. We also sought risk factors for pulse oximetry below 90%. Of 319 patients, 157 (49%) had bag-valve-mask, 71 (22%) noninvasive ventilation, 71 (22%) non-rebreathing mask, and 20 (7%) high-flow nasal oxygen for preoxygenation. Factors independently associated with minimal pulse oximetry value were the Simplified Acute Physiology Score II severity score (p = 0.03), baseline pulse oximetry (p < 0.001), baseline Pao
2/Fio
2 ratio (p = 0.02), and number of laryngoscopies (p = 0.001). The only independent predictors of pulse oximetry less than 90% were baseline pulse oximetry (odds ratio, 0.71; 95% CI, 0.64–0.79; p < 0.001) and preoxygenation device: with bag-valve-mask as the reference, odds ratios were 1.10 (95% CI, 0.25–4.92) with non-rebreathing mask, 0.10 (95% CI, 0.01–0.80) with noninvasive ventilation, and 5.75 (95% CI, 1.15–28.75) with high-flow nasal oxygen.

Conclusions:

Our data suggest that the main determinants of hypoxemia during endotracheal intubation may be related to critical illness severity and to preexisting hypoxemia. The differences across preoxygenation methods suggest that noninvasive ventilation may deserve preference in patients with marked hypoxemia before endotracheal intubation. Ongoing studies will provide further clarification about the optimal preoxygenation method for endotracheal intubation in critically ill patients.
Polyquaternium-1–Associated Dendritiform Keratopathy
Authors: Verkade Angela , Matoba Alice Y.
Published: February 2019

Purpose:

To report a case of polyquaternium-1 (Polyquad, PQ-1)–associated dendritiform keratopathy that developed after exposure to the tear substitute Systane (Alcon Laboratories, Inc, Fort Worth, TX).

Methods:

A retrospective review of the case was performed.

Results:

Dendritiform keratopathy developed in the patient after an increase in the use of topical Systane from 4 times per day to every hour. Keratopathy resolved with discontinuation of Systane.

Conclusions:

Polyquaternium-1–associated dendritiform keratopathy can occur in patients who have previously tolerated the preservative. Because keratopathy seems to have developed and improved because of dose-dependent factors, the mechanism is more likely toxicity than hypersensitivity.
Inferior Quadrant of Tear Film Is More Likely to Break and Breaks Early in Patients With Dry Eyes
Authors: Zhuo Ran , Zhang Bin , Hou Lijie , Shen Meixiao , Lu Fan , Jiang Jun
Published: February 2019

Purpose:

To investigate the temporal and spatial distribution of tear film breakup time via a noninvasive topographer in normal subjects and patients with dry eye disease (DED).

Methods:

A total of 77 subjects were separated into normal and DED groups based on their symptoms and tear film instabilities. In noninvasive evaluation with Oculus Keratograph, the precorneal tear film was recorded and reconstructed into a two-dimensional map that evolved with time. Whether or not each sector broke and the breakup time if it did were recorded. The map was further grouped into 4 quadrants to reveal the spatial variation.

Results:

By the end of recording, the inferior quadrant in DED subjects had a higher number of broken sectors than other quadrants (P< 0.01). Over the recording period, the cumulative percentage of sectors that were broken rose much quicker in the inferior quadrants, and the inferior quadrant is the only quadrant that showed a significant difference between the normal and DED groups (P< 0.01). This difference peaked at 12 seconds and declined after 15 seconds. Receiver operating characteristic curve for each index always showed the largest differential value in the inferior quadrant.

Conclusions:

Tear film breakup is not homogenously distributed, with sectors in the inferior quadrant being more likely to break and to break earlier. Between normal and DED subjects, a significant difference of tear film instability is more likely to be found in the inferior quadrant.
Aspiration of Tri-folded, Endothelium-In Grafts for Descemet Membrane Endothelial Keratoplasty
Authors: Karakus Sezen , Ighani Mehrnaz , Noparat Puntakarn , Tofigh Marjan , Chiang Eric , Barnes Kali , Chen Conan Y. , Liu Tiffany S. , Eghrari Allen O.
Published: February 2019

Purpose:

In Descemet membrane endothelial keratoplasty (DMEK), loading and positioning of tri-folded grafts into a cartridge is generally conducted with forceps or a hook, risking graft tear or trauma. We demonstrate the feasibility of loading tri-folded grafts into a cartridge with no touch to the endothelium required beyond the tri-folding process.

Methods:

A corneoscleral rim with a prestripped DMEK graft is placed into a petri dish. After the graft is tri-folded with forceps and removed from its stromal attachment, the graft is gently wicked into the tip of a saline-filled Alcon B IOL cartridge connected to IV extension tubing and a 3 cc syringe, drawn into the cartridge by positioning it adjacent to the graft tip. The remainder of the graft is aspirated with the addition of saline. The cartridge orientation is reversed for graft injection. In this retrospective analysis, we analyzed surgical videos for preparation times, and assessed postoperative visual acuity, pachymetry, and endothelial cell density.

Results:

Thirteen cases underwent this approach. Median preparation time from stain to cartridge eye contact was 8.5 minutes, and time from graft injection to final centration and bubbling was 2.9 minutes. Corneal thickness decreased from a median of 623 microns preoperatively to 566 μm at 1 month (P = 0.038). Visual acuity improved by 1 month by a median of 0.3 logarithm of the minimum angle of resolution (logMAR) (P = 0.016). Endothelial cell density decreased by 32.4% at 1 month compared with baseline.

Conclusions:

Endothelium-in DMEK grafts may be loaded into a plastic cartridge using a skill set similar to aspiration of a scroll.
Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study
Authors: Harte Steven E. , Schrepf Andrew , Gallop Robert , Kruger Grant H. , Lai Hing Hung Henry , Sutcliffe Siobhan , Halvorson Megan , Ichesco Eric , Naliboff Bruce D. , Afari Niloofar , Harris Richard E. , Farrar John T. , Tu Frank , Landis John Richard , Clauw Daniel J. ,   for the MAPP Research Network
Published: February 2019

Experimental pain sensitivity was assessed in individuals with urologic chronic pelvic pain syndrome (UCPPS) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. A series of computer-controlled pressure stimuli were delivered to the thumbnail bed, an asymptomatic site distant from the area of UCPPS pain that is considered to be indicative of overall body pain threshold. Stimuli were rated according to a standardized magnitude estimation protocol. Pain sensitivity in participants with UCPPS was compared with healthy controls and a mixed pain group composed of individuals with other chronic overlapping pain conditions, including fibromyalgia, chronic fatigue, and irritable bowel syndromes. Data from 6 participating MAPP testing sites were pooled for analysis. Participants with UCPPS (n = 153) exhibited an intermediate pain sensitivity phenotype: they were less sensitive relative to the mixed pain group (n = 35) but significantly more sensitive than healthy controls (n = 100). Increased pain sensitivity in patients with UCPPS was associated with both higher levels of clinical pain severity and more painful body areas outside the pelvic region. Exploratory analyses in participants with UCPPS revealed that pain sensitivity increased during periods of urologic symptom flare and that less pressure pain sensitivity at baseline was associated with a greater likelihood of subsequent genitourinary pain improvement 1 year later. The finding that individuals with UCPPS demonstrate nonpelvic pain hypersensitivity that is related to clinical symptoms suggests that central nervous system mechanisms of pain amplification contribute to UCPPS.
Early Protocolized Versus Usual Care Rehabilitation for Pediatric Neurocritical Care Patients: A Randomized Controlled Trial
Authors: Fink Ericka L. , Beers Sue R. , Houtrow Amy J. , Richichi Rudolph , Burns Cheryl , Doughty Lesley , Ortiz-Aguayo Roberto , Madurski Catherine A. , Valenta Cynthia , Chrisman Maddie , Golightly Lynn , Kiger Michelle , Patrick Cheryl , Treble-Barna Amery , Pollon Dorothy , Smith Craig M. , Kochanek Patrick
Published: February 2019

Objective

s: Few feasibility, safety, and efficacy data exist regarding ICU-based rehabilitative services for children. We hypothesized that early protocolized assessment and therapy would be feasible and safe versus usual care in pediatric neurocritical care patients.

Design:

Randomized controlled trial.

Setting:

Three tertiary care PICUs in the United States.

Patients:

Fifty-eight children between the ages of 3–17 years with new traumatic or nontraumatic brain insult and expected ICU admission greater than 48 hours.

Interventions:

Early protocolized (consultation of physical therapy, occupational therapy, and speech and language therapy within 72 hr ICU admission, n = 26) or usual care (consultation per treating team, n = 32).

Measurements and Main Results:

Primary outcomes were consultation timing, treatment type, and frequency of deferrals and safety events. Secondary outcomes included patient and family functional and quality of life outcomes at 6 months. Comparing early protocolized (n = 26) and usual care groups (n = 32), physical therapy was consulted during the hospital admission in 26 of 26 versus 28 of 32 subjects (p = 0.062) on day 2.4 ± 0.8 versus 7.7 ± 4.8 (p = 0.001); occupational therapy in 26 of 26 versus 23 of 32 (p = 0.003), on day 2.3 ± 0.6 versus 6.9 ± 4.8 (p = 0.001); and speech and language therapy in 26 of 26 versus 17 of 32 (p = 0.011) on day 2.3 ± 0.7 versus 13.0 ± 10.8 (p = 0.026). More children in the early protocolized group had consults and treatments occur in the ICU versus ward for all three services (all p < 0.001). Eleven sessions were discontinued early: nine during physical therapy and two during occupational therapy, none impacting patient outcome. There were no group differences in functional or quality of life outcomes.

Conclusions:

A protocol for early personalized rehabilitation by physical therapy, occupational therapy, and speech and language therapy in pediatric neurocritical care patients could be safely implemented and led to more ICU-based treatment sessions, accelerating the temporal profile and changing composition of interventions versus usual care, but not altering the total dose of rehabilitation.
Cognitive Behavioral Therapy for Chronic Pain—One Therapeutic Approach for the Opioid Epidemic
Authors: MAJEED MUHAMMAD HASSAN , SUDAK DONNA M.
Published: February 2019

Opioids are frequently prescribed for chronic pain. For the past 2 decades, long-term opioid analgesic therapy was considered the cornerstone of effective pain management for chronic nonmalignant conditions, despite a lack of documented effectiveness and safety, with the attendant risk of addiction, overdose, and death. Cognitive behavioral therapy (CBT) may be used effectively to treat chronic pain, either as a stand-alone treatment or with other nonopioid pharmacological treatments. CBT improves pain-related outcomes along with mobility, quality of life, and disability and mood outcomes. Compared with long-term use of opioids, CBT has dramatically lower risks and may therefore be worth pursuing.
Voltage-gated Potassium Channel Antibody Autoimmune Encephalopathy Presenting With Isolated Psychosis in an Adolescent
Authors: PON NATALIE C. , HOUCK KIMBERLY M. , MUSCAL EYAL , IDICULA SINDHU A.
Published: February 2019

Antibody-mediated encephalopathies associated with serum or cerebrospinal fluid antibodies directed against neuronal structures may present with a multitude of neuropsychiatric syndromes. Although some of the antibody-driven conditions are now well recognized in adults (eg, N-methyl-D-aspartate receptor antibody encephalitis), the spectrum of neuropsychiatric manifestations in the pediatric population is less clear. Psychosis, confusion, catatonia, and additional behavioral changes, along with seizures, encephalopathy, and movement disorders, may be initial manifestations or concurrent features in all age groups. Psychosis, when present, is often part of a broader spectrum of neurological and neuropsychiatric symptoms for which the diagnosis of autoimmune encephalitis is considered. The authors present the case of an adolescent with an acute and isolated psychotic presentation of voltage-gated potassium channel antibody encephalitis, further expanding the phenotypic spectrum of this specific antibody-mediated disease and raising the possibility that specific immune-mediated processes may define a biological subgroup of psychoses.
UKAEA capabilities to address the challenges on the path to delivering fusion power
Authors: Chapman I. T. , Morris A. W.
Published: February 2019

Fusion power could be one of very few sustainable options to replace fossil fuels as the world's primary energy source. Fusion offers the potential of predictable, safe power with no carbon emissions and fuel sources lasting for millions of years. However, it is notoriously difficult to achieve in a controlled, steady-state fashion. The most promising path is via magnetic confinement in a device called a tokamak. A magnetic confinement fusion (MCF) power plant requires many different science, technology and engineering challenges to be met simultaneously. This requires an integrated approach from the outset; advances are needed in individual areas but these only bring fusion electricity closer if the other challenges are resolved in harmony. The UK Atomic Energy Authority (UKAEA) has developed a wide range of skills to address many of the challenges and hosts the JET device, presently the only MCF facility capable of operating with both the fusion fuels, deuterium and tritium. Recently, several major new UKAEA facilities have been funded and some have started operation, notably a new spherical tokamak (MAST Upgrade), a major robotics facility (RACE), and a materials research facility (MRF). Most recently, work has started on Hydrogen-3 Advanced Technology (H3AT) for tritium technology and a group of Fusion Technology Facilities.

This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’
Compact steady-state tokamak performance dependence on magnet and core physics limits
Authors: Menard J. E.
Published: February 2019

Compact tokamak fusion reactors using advanced high-temperature superconducting magnets for the toroidal field coils have received considerable recent attention due to the promise of more compact devices and more economical fusion energy development. Facilities with combined fusion nuclear science and Pilot Plant missions to provide both the nuclear environment needed to develop fusion materials and components while also potentially achieving sufficient fusion performance to generate modest net electrical power are considered. The performance of the tokamak fusion system is assessed using a range of core physics and toroidal field magnet performance constraints to better understand which parameters most strongly influence the achievable fusion performance.

This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’.
Shielding materials in the compact spherical tokamak
Authors: Humphry-Baker Samuel A. , Smith George D. W.
Published: February 2019

Neutron shielding materials are a critical area of development for nuclear fusion technology. In the compact spherical tokamak, shielding efficiency improvements are particularly needed because of severe space constraints. The most spatially restricted component is the central column shield. It must protect the superconducting magnets from excessive radiation-induced degradation, but also from associated heating, so that energy consumption of the cryogenic systems is kept to an acceptable level. Recent simulations show that tungsten carbide and its composites form an attractive class of neutron-attenuating materials. In this paper, the key structure–property relationships of these materials are assessed, as they relate to generic materials challenges for plasma-facing materials. We first consider some fundamental materials properties of monolithic tungsten carbide including thermal transport, mechanical properties and plasma interaction. WC is found to have generally favourable properties compared to metallic tungsten shields. We then report progress on the development of a new candidate cermet material, WC-FeCr. Recent results on its accident safety, thermo-mechanical properties, and irradiation behaviour are presented. This review also highlights the need for further study, particularly in the areas of irradiation damage and hydrogen trapping.

This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’.
Phenylobacterium parvum sp. nov., isolated from lake water
Authors: Baek Chaeyun , Shin Su-Kyoung , Yi Hana
Published: February 2019

A Gram-stain-negative, rod-shaped and aerobic bacterium, designated HYN0004T, was isolated from lake water. The strain grew at 15–35 °C and pH 7.0–9.0 on R2A. The isoprenoid quinone was Q10 and major polar lipids were phosphatidylglycerol and one unidentified glycolipid. The genome was 2.83 Mb with a DNA G+C content of 69.9 mol%. 16S rRNA gene sequence analyses revealed that HYN0004T represented a member of the genus

Phenylobacterium

and shared sequence similarities with

Phenylobacterium conjunctum

(97.8 %),

Phenylobacterium koreense

(97.5 %),

Phenylobacterium aquaticum

(97.2 %), and

Phenylobacterium
heamatophilum (97.0 %). In addition to the low sequence similarities, the phylogenetic tree shapes indicated that HYN0004Trepresents an independent species of this genus. The genomic and phenotypic properties, including small genome size, inability to carry out numerous enzymatic reactions and high ratio of C18 : 1ω6c and/or C18 : 1ω7c in fatty acids, verified the differentiation between HYN0004T and related species. Thus, we propose a novel species of the genus

Phenylobacterium
, named as

Phenylobacterium
parvum sp. nov. The type strain is HYN0004T (=KACC 19185T=NBRC 112736T).
Evolution of the nonsense mediated decay (NMD) pathway is associated with decreased cytolytic immune infiltration
Authors: Zhao Boyang , Pritchard Justin R.
Published: February 2019

Background

The somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers.

Methods

Using TCGA datasets, we derived novel patient-level metrics of ‘NMD burden’ and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes.

Results

We find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models.

Conclusions

Our work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.
A new comprehensive Eye-Tracking Test Battery concurrently evaluating the Pupil Labs Glasses and the EyeLink 1000
Authors: Ehinger Benedikt V. , Groß Katharina , Ibs Inga , König Peter
Published: February 2019

Eye-tracking experiments rely heavily on good data quality of eye-trackers. Unfortunately, it is often that only the spatial accuracy and precision values are available from the manufacturers. These two values alone are not sufficient enough to serve as a benchmark for an eye-tracker: Eye-tracking quality deteriorates during an experimental session due to head movements, changing illumination or calibration decay. Additionally, different experimental paradigms require the analysis of different types of eye movements, for instance smooth pursuit movements, blinks or microsaccades, which themselves cannot readily be evaluated by using spatial accuracy or precision alone. To obtain a more comprehensive description of properties, we developed an extensive eye-tracking test battery. In 10 different tasks, we evaluated eye-tracking related measures such as: the decay of accuracy, fixation durations, pupil dilation, smooth pursuit movement, microsaccade detection, blink detection, or the influence of head motion. For some measures, true theoretical values exist. For others, a relative comparison to a gold standard eye-tracker is needed. Therefore, we collected our gaze data simultaneously from a gold standard remote EyeLink 1000 eye-tracker and compared it with the mobile Pupil Labs glasses.

As expected, the average spatial accuracy of 0.57° for the EyeLink 1000 eye-tracker was better than the 0.82° for the Pupil Labs glasses (N=15). Furthermore, we detected less fixations and shorter saccade durations for the Pupil Labs glasses. Similarly, we found fewer microsaccades using the Pupil Labs glasses. The accuracy over time decayed only slightly for the EyeLink 1000, but strongly for the Pupil Labs glasses. Finally we observed that the measured pupil diameters differed between eye-trackers on the individual subject level but not the group level.

To conclude, our eye-tracking test battery offers 10 tasks that allow us to benchmark the many parameters of interest in stereotypical eye-tracking situations, or addresses a common source of confounds in measurement errors (e.g. yaw and roll head movements).

All recorded eye-tracking data (including Pupil Labs’ eye video files), the stimulus code for the test battery and the modular analysis pipeline are available (https://github.com/behinger/etcomp).

BVE, KG, IIandPKconceived the experiment.IIandBVEcreated the experiment and recorded the gaze data.BVEandKGperformed the analysis.BVE, KGandPKreviewed the manuscript critically.
Hypothesis-Testing Improves the Predicted Reliability of Neuroscience Research
Authors: Alger Bradley E.
Published: February 2019

Critics often cite statistical problems as prime contributors to the “reproducibility crisis” of science, expressing great concern about research that bases major conclusions on single p-valued statistical tests. The critics also argue that the predicted reliability of neuroscience research in particular is low because much of the work depends heavily on small experimental sample sizes and, hence, its statistical tests lack adequate “power.”

It isn’t known how common the practice of basing major conclusions on single tests is in neuroscience or how the statistical criticisms affect the validity of conclusions drawn by laboratory research that evaluates hypotheses via multiple tests. I review a sample of neuroscience publications to estimate the prevalence and extensiveness of hypothesis-testing research. I then apply R.A. Fisher’s method for combining test results to show that the practice of testing multiple predictions of hypotheses increases the predicted reliability of neuroscience research.
Systematic mapping of drug metabolism by the human gut microbiome
Authors: Chankhamjon Pranatchareeya , Javdan Bahar , Lopez Jaime , Hull Raphaella , Chatterjee Seema , Donia Mohamed S.
Published: February 2019

The human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities, making it one of nature’s highest density, highest diversity bioreactors. Several drugs have been previously shown to be directly metabolized by the gut microbiome, but the extent of this phenomenon has not been systematically explored. Here, we develop a systematic screen for mapping the ability of the complex human gut microbiome to biochemically transform small molecules (MDM-Screen), and apply it to a library of 575 clinically used oral drugs. We show that 13% of the analyzed drugs, spanning 28 pharmacological classes, are metabolized by a single microbiome sample. In a proof-of-principle example, we show that microbiome-derived metabolism occursin vivo, identify the genes responsible for it, and provide a possible link between its consequences and clinically observed features of drug bioavailability and toxicity. Our findings reveal a previously underappreciated role for the gut microbiome in drug metabolism, and provide a comprehensive framework for characterizing this important class of drug-microbiome interactions.
Extraocular, rod-like photoreceptors in a flatworm express xenopsin photopigment
Authors: Rawlinson Kate A , Lapraz Francois , Girstmair Johannes , Simpson Fraser , Criswell Katharine E. , Terasaki Mark , Ballister Edward R. , Boldogkoi Miklos , McDowell Richard J. , Rodgers Jessica , Hall Brian K , Lucas Robert J. , Telford Maximilian J.
Published: February 2019

Animals detect light using opsin photopigments. One recently classified opsin clade, the xenopsins, found in lophotrochozoans, challenges our views on opsin and photoreceptor evolution. Originally thought to belong to the Gαi-coupled ciliary opsins, xenopsins are now understood to have diverged from ciliary opsins in pre-bilaterian times, but little is known about the cells that deploy these proteins, or if they form a photopigment and drive phototransduction. We characterized xenopsin in a flatworm, Maritigrella crozieri, and found that it is expressed in a larval eyespot, and in an abundant extraocular cell type around the adult brain. These distinct cells house hundreds of cilia in an intra-cellular vacuole (a phaosome). Cellular assays show Mc xenopsin forms a photopigment and couples to Gαi/o in response to light. These findings reveal a novel photoreceptor cell type and opsin/G-protein couple, and highlight the convergent enclosure of photosensitive cilia in flatworm phaosomes and jawed vertebrate rods.