bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Best Practices in Simulation Debriefing
Authors: Rojas Deborah E. , Parker Carlo Guy , Schams Kristin Anne , McNeill Jeanette A.
Published: October 2018

This article describes how one school of nursing responded to the need to educate faculty in the pedagogy of simulation debriefing and how the International Association for Clinical Simulation and Learning Standard VI was implemented. Thirty faculty received training and were evaluated using the Debriefing Assessment for Simulation in Healthcare tool. Lessons learned and examples of student feedback are shared. Plans for future work are also described.
Using Active Learning to Foster Patient Safety Knowledge, Perceived Skills, and Attitudes in Baccalaureate Nursing Students
Authors: Marchi Nadine M. , Dolansky Mary
Published: October 2018

The purposes of this study were to evaluate safety active learning approaches with baccalaureate nursing students and to examine differences between students with and without nursing assistant experience. The approaches evaluated were patient safety modules, making a safety poster, and planning/attending a safety conference. Using a pretest/posttest design, students’ patient safety knowledge, perceived safety skills, and attitudes were evaluated with the Healthcare Professional Patient Safety Assessment Curriculum Survey (HPPSACS). Findings suggested that employment as a nurse assistant had a significant effect on posttest HPPSACS scores.
A 3D App for Teaching Nursing Students ECG Rhythm Interpretation
Authors: Holthaus Abbey , Wright Vivian H.
Published: October 2018

The purpose of this study was to determine the effectiveness of a three-dimensional application on nursing students’ electrocardiogram (ECG) level of knowledge as evidenced by exam performance. Nurse educators must prepare future nurses to competently identify ECG rhythms. As the current classroom environment often lacks application and practice opportunities, students may struggle with ECG rhythm identification at the bedside. An identical 10-item pretest and posttest was used for this quasiexperimental research study. Dependent t-tests and an independent t-test were used for statistical analysis.
Sitting Time: An Increasing Heath Risk Among Nurse Educators
Authors: Main M. Eve , Garrett-Wright Dawn , Sturgeon Lizbeth P. , Jones M. Susan , Blackburn Donna S.
Published: October 2018

Prolonged sitting time (ST) is a distinct risk factor for early mortality and cardiovascular disease. The purpose of this descriptive correlational study was to examine ST and health of Kentucky nurse educators. The written survey included demographic items, general health items, and ST. Total average ST was 10.8 hours (workdays) and 8 hours (non-workdays). There was no relationship between body mass index and ST; however, the medication used to treat hypertension and hypercholesterolemia was associated with increased ST. Nurse educators are at risk for negative health effects of prolonged ST, and effective interventions are imperative.
Nursing Doctoral Faculty Perceptions Related to the Effect of Increasing Enrollments on Productivity
Authors: Smeltzer Suzanne C. , Sharts-Hopko Nancy C. , Cantrell Mary Ann , Heverly Mary Ann , Jenkinson Amanda
Published: October 2018

Nursing faculty teaching in research and clinical doctoral programs participated in a national survey study to examine the impact of expanded doctoral enrollments on the doctoral faculty’s scholarly productivity. They were invited to respond to an open-ended question soliciting information not already addressed in the survey. Results of the analysis are reported here. Findings corroborated the review of literature and results of the survey and focus groups that provided the basis for the survey’s development. Current workloads may be unsustainable, jeopardizing the profession’s response to Institute of Medicine recommendations.
Exploring Nurse Faculty Incivility and Resonant Leadership
Authors: Casale Katherine R.
Published: October 2018

AIM

The purpose of this quantitative correlational study was to explore the relationship between the frequency of interfaculty incivility among nurses in academia and observed levels of resonant leadership of immediate supervisors.

BACKGROUND

Despite mandates to address incivility in health care, nurse faculty report high levels of horizontal incivility among their peers. No known quantitative research has measured the relationship between nurse faculty-to-faculty incivility and resonant leadership traits of leaders.

METHOD

Nursing faculty from 17 universities (n = 260) were emailed an anonymous link to answer survey questions about horizontal peer incivility and leaders’ management styles.

RESULTS

There was a significant inverse relationship (Pearson’s r, −.560) between the frequency of experienced faculty-to-faculty incivility and the level of observed resonant leadership behaviors of participants’ immediate supervisors.

CONCLUSION

Resonant supervisory behaviors inversely correlated with nurse faculty peer incivility, with potential to impact satisfaction, recruitment, and retention.
Mentoring and Development Resources Available to New Doctorally Prepared Faculty in Nursing
Authors: Agger Charlotte A. , Lynn Mary R. , Oermann Marilyn H.
Published: October 2018

AIM

This study examined faculty mentoring practices and strategies currently in place in nursing programs.

BACKGROUND

Mentoring is a critical component of organizations and can be especially important in times of organizational change. Schools of nursing are experiencing rapid organizational shifts with increases in retirement and the proliferation of Doctor of Nursing Practice-prepared faculty.

METHOD

Deans and department chairs of baccalaureate and higher degree programs across the United States participated in a web-based survey.

RESULTS

Results from the survey suggested that the vast majority of nursing programs had practices and strategies aimed at mentoring faculty that were based on the traditional mentor-protégé approach. Few programs differentiated their mentoring practices depending on the type of doctoral education or anticipated roles of the faculty member.

CONCLUSION

Our research highlights the fact that nursing programs still employ traditional methods of faculty mentoring. Recommendations for nursing programs are discussed.
Effectiveness of Two Varying Levels of Virtual Reality Simulation
Authors: Smith Sherrill J. , Farra Sharon L. , Ulrich Deborah L. , Hodgson Eric , Nicely Stephanie , Mickle Angelia
Published: October 2018

AIM

The aim of the study was to assess two levels of immersive virtual reality simulation (VRS) to teach the skill of decontamination.

BACKGROUND

Little is known about the use of VRS in providing disaster education, including retention.

METHOD

Quasiexperimental design with repeated measures, supplemented by qualitative data, using a convenience sample of senior baccalaureate nursing students (n = 197) from four Midwest campuses was used. Students were randomly assigned to a group (two levels of immersive VRS and a control group) to learn the skill of decontamination. Cognitive learning, performance, and performance time were measured pre/post and at six months.

RESULTS

Outcome measures were significant with immediate postintervention improvements and lower retention scores at six months. No significant differences were noted between groups. Students were satisfied with the VRS but found immersive VRS more interactive.

CONCLUSION

VRS provides another alternative for simulated learning experiences; best practice approaches for its use still need to be explored.
Feasibility and Outcomes Associated With the Use of 2.6-Fr Double-Lumen PICCs in Neonates
Authors: O'Malley Christine , Sriram Sudhir , White Melissa , Polinski Carol , Seng Carolyn , Schreiber Michael D.
Published: October 2018

Background:

Low birth-weight infants' survival continues to improve and there is increased need to provide secure vascular access. This study examines safety of larger peripherally inserted central catheters (PICCs) that offer greater utility.

Purpose:

To determine feasibility of 2.6-French (Fr) double-lumen PICCs in newborns and compare noninfectious complications such as thrombus formation, catheter breakage, infiltration, and accidental dislodgment and central line–associated bloodstream infection (CLABSI) rate with that of newborn infants treated with 1.9-Fr single- and double-lumen PICCs.

Methods:

Infants requiring PICCs were admitted in our 69-bed level IV neonatal intensive care unit from September 2006 to May 2015. Two distinct groups were compared: the 1.9-Fr—(single-lumen [n = 105] and double-lumen [n = 27])—and 2.6-Fr double-lumen PICCs (n = 111). Data obtained included birth weight and weight at insertion, gestational age at birth and corrected gestation age at insertion, indication, catheter days, indication for removal, and complications: noninfectious and infectious. Univariate and multivariate statistical analysis evaluated data.

Results:

There were no differences regarding gestational age at birth and insertion and indications for placement of 2.6-Fr double-lumen (n =111) and 1.9-Fr both single- and double-lumen (n = 132) PICCs. The same was noted between the groups' complications. Noninfectious complications were more common in PICCs with peripheral tip location in all groups.

Implications for Practice:

Consider use of 2.6-Fr PICCs in a neonatal intensive care unit when the utility of blood administration and sampling is required.

Implications for Research:

Examine line migration and CLABSI associated with sampling and blood administration.
Circulating Cell-Free DNA—Diagnostic and Prognostic Applications in Personalized Cancer Therapy
Authors: Oellerich Michael , Schütz Ekkehard , Beck Julia , Walson Philip D.
Published: October 2018

Genomic analyses in oncologic care allow for the development of more precise clinical laboratory tests that will be critical for personalized pharmacotherapy. Traditional biopsy-based approaches are limited by the availability of sequential tissue specimens to detect resistance. Blood-based genomic profiling (“liquid biopsy”) is useful for longitudinal monitoring of tumor genomes and can complement biopsies. Tumor-associated mutations can be identified in cell-free tumor DNA (ctDNA) from patient blood samples and used for monitoring disease activity. The US Food and Drug Administration approved a liquid biopsy test for EGFR-activating mutations in patients with non–small-cell lung cancer as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFR T790M in non–small-cell lung cancer. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAF V600E/V600K in melanoma. Chromosomal aberration pattern analysis by low-coverage whole genome sequencing is a new, broader approach. Genomic imbalances detected in cell-free DNA (cfDNA) can be used to compute a copy number instability (CNI) score. In clinical studies, it was demonstrated that the change in CNI score can serve as an early predictor of therapeutic response to chemotherapy/immunotherapy of many cancer types. In multivariable models, it could be shown that the CNI score was superior to clinical parameters for prediction of overall survival in patients with head and neck cancer. There is emerging evidence for the clinical validity of ctDNA testing regarding identification of candidates for targeted therapies, prediction of therapeutic response, early detection of recurrence, resistance mutation detection, measuring genetic heterogeneity, tumor burden monitoring, and risk stratification. Improvement of sensitivity to detect tumors at very early stages is difficult due to insufficient mutant DNA fraction of ≤0.01%. Further developments will include validation in prospective multicenter interventional outcome studies and the development of digital platforms to integrate diagnostic data.
Unique Primary Care Needs of Transgender and Gender Non-Binary People
Authors: NISLY NICOLE L. , IMBOREK KATHERINE L. , MILLER MICHELLE L. , KALISZEWSKI SUSAN D. , WILLIAMS RACHEL M. , KRASOWSKI MATTHEW D.
Published: October 2018

It is important for the practicing primary care provider to become familiar with the unique health care needs for people who identify as transgender men, transgender women, and non-binary people, who are all within the scope of practice of a general obstetrician-gynecologist and other primary care providers. A review of the unique health needs and essential terminology is presented. This knowledge is a basic foundation to develop a welcoming and inclusive practice for people who are gender nonconforming. This fund of knowledge is essential the practicing primary care providers and support staff.
Differences in Hospitalizations Between Fee-for-Service and Medicare Advantage Beneficiaries
Authors: Ndumele Chima D. , Elliott Marc N. , Haviland Amelia M. , Burkhart Q , Orr Nate , Gaillot Sarah , Cleary Paul D.
Published: October 2018

Background:

Previous studies found lower hospitalization rates for enrollees in Medicare Advantage (MA) plans than for beneficiaries with fee-for-service (FFS) coverage. MA enrollment is increasing, especially for those newly eligible for Medicare, but little is known about how service use in FFS or MA differs for new beneficiaries.

Objective:

To compare differences in rates of hospitalization between MA and FFS.

Research Design:

A retrospective study of hospitalization among FFS and MA respondents to the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) survey. Differences in hospitalization rates were assessed using multivariable logistic regression models that controlled for patient sociodemographic and health characteristics. Models included an interaction between age and coverage type to determine whether patterns of care were distinct for enrollees recently eligible for Medicare.

Study Population:

In total, 259,335 respondents to the 2013 MCAHPS survey.

Results:

In total, 14% of FFS and 12% of MA enrollees had ≥1 hospitalization in the 6 months before survey administration. Models adjusted for enrollee demographics found that MA enrollees had 0.81 the odds of being hospitalized relative to those with FFS coverage (95% confidence interval, 0.78–0.84). Differences between groups were substantially reduced and no longer statistically significant when they were fully adjusted (adjusted odds ratio 1.01, 95% confidence interval, 0.97–1.08). Models with interactions indicated no significant age differences in the MA/FFS hospitalization gap.

Conclusion:

Differences in hospital admissions between those with MA and FFS coverage appear to be primarily related to differences in health status.
Spinal Epidural Bleed in Hemophilia: A Rare Site of Bleeding With Complete Resolution With Nonsurgical Management
Authors: Singh Suvir , Philip Chepsy C. , George Uttam , John Manthanathu J.
Published: October 2018

Hemophilia A is an inherited bleeding disorder, seen in 1 in 10,000 live births. It is characterized by an increased risk of bleeding, especially involving the musculoskeletal system. Central nervous system bleeding, including brain and spinal cord bleed is rare in the absence of overt trauma, seen in <5% patients. Epidural spinal bleeding in hemophilia is even rarer, and described in <20 patients so far in literature. We describe a young boy who presented with a cervical spine epidural bleed, and was managed conservatively without any sequelae. We also look at the controversies and recent evidence weighing surgical and conservative management of such bleeds.
Elements Associated With Early Mortality in Children With B Cell Acute Lymphoblastic Leukemia in Chiapas, Mexico: A Case-control Study
Authors: Lepe-Zuniga Jose L. , Ramirez-Nova Virginia
Published: October 2018

Childhood Lymphoblastic leukemia’s (ALL) early mortality (EM) is an undesirable treatment outcome for a disease for which >90% long term success is achievable. In the Western world EM constitutes no >3%; yet, in Chiapas, Mexico, remains around 15%. With the objective of improving on EM, we determined associated elements in 28 ALL who died within 60 days of arriving at Hospital de Especialidades Pediátricas in Chiapas (HEP), by comparing them to those in 84 controls who lived beyond the first 90 days. χ2, t test, and binary logistic regression (BLR) were used to determine significant individual and multiple variables associated to outcome. On arrival, fever, liver and spleen enlargement, active bleeding, lower albumin, less platelets, higher creatinine, and uric acid, more diploid and less hyperdiploid cases were associated with EM cases. Time to diagnosis, nutritional status, risk group and leukocyte count were not related. Antileukemic treatment approach was similar in both groups. The BLR model including fever, active bleeding, liver enlargement, <10,000 platelets/µL, and >2X upper normal lactic dehydrogenase, determined outcome in 66.7% EM and 90.2% controls. To improve on EM in ALL, patients with characteristics defined here ought to be treated differently at HEP.
Hematologic Manifestations of Nutritional Deficiencies: Early Recognition is Essential to Prevent Serious Complications
Authors: Yu Jennifer C. , Shliakhtsitsava Ksenya , Wang YunZu M. , Paul Megan , Farnaes Lauge , Wong Victor , Kim Jenny , Thornburg Courtney D.
Published: October 2018

Nutritional deficiencies, including deficiencies of vitamin B12, copper, and vitamin C, may result in cytopenias and hematologic symptoms. Early recognition of these deficiencies is imperative for prompt treatment and improvement in hematologic and other manifestations. We describe 5 cases which illustrate the hematologic manifestations of nutritional deficiencies and challenges to initial diagnosis and management. Supplementation of the deficient vitamin or micronutrient in all of these cases resulted in rapid resolution of cytopenias, hemorrhage, and other associated hematologic symptoms. We also review other nutritional deficiencies that manifest with hematologic symptoms and compile recommendations on treatment and expected time to response.
Acceptability and Feasibility of a Disease-specific Patient Portal in Adolescents With Sickle Cell Disease
Authors: Kidwell Katherine M. , Peugh James , Westcott Emilie , Nwankwo Cara , Britto Maria T. , Quinn Charles T. , Crosby Lori E.
Published: October 2018

Objective:

To examine the acceptability, feasibility, and efficacy of a health care portal.

Observations:

Adolescents and young adults with sickle cell disease were taught how to use sickle cell disease conditions page in MyChart and completed questionnaires at baseline, postintervention (T2, 6 wk after baseline) and after 3 months (T3). In total, 44 participants (M age=18.82, SD=2.72) viewed an average of 58.07 pages from T1 to T2. The portal was highly accepted (90.32%). Efficacy data indicated that portal use was associated with improved patient-provider communication.

Conclusions:

Electronic portals are promising tools for improving medical self-management.
Perceptions of an Obstetric Clinical Rotation by Nursing Students Who Are Men
Authors: Mitra Jose Mari Lawrence , Phillips Kenneth D. , Wachs Joy E.
Published: October 2018

Background:

Maternity nursing is perceived as an unwelcoming specialty to many nursing students who are men. The purpose of this qualitative study was to describe the experiences of nursing students who are men at a Southeastern university before, during, and after their obstetric clinical rotations.

Methods:

Students were interviewed individually. The sessions were recorded and transcribed. The transcripts were analyzed individually and collectively by a three-person study team using existential phenomenology.

Results:

Seven nursing students who are men participated. Four major themes were discovered: preconceptions, welcoming, perceived rejection (of and by participants), and maternity unit culture. Students' perceptions appeared to be grounded in their level of comfort with maternity nursing.

Conclusions:

This study adds to the scant amount of information available about experiences of nursing students who are men during their clinical maternity nursing rotation and may help to explain why some men may feel unwelcome in women's health nursing.
Accuracy of Reported Tidal Volume During Neonatal Ventilation With Airway Leak: A Lung Model Study
Authors: Moon Kazue , Takeuchi Muneyuki , Tachibana Kazuya , Mizuguchi Soichi , Hirano Shinya
Published: October 2018

Objectives:

To determine the accuracy of tidal volume reported by neonatal ventilators, with and without leak compensation, in invasive and noninvasive ventilation modes in the presence of airway leak; and, to determine what factors have a significant effect on the accuracy of tidal volume reported by ventilators with leak compensation in the presence of airway leak. We hypothesized that ventilators with a leak compensation function that includes estimation of tidal volume could accurately report tidal volume in the presence of airway leak, but that the accuracy of reported tidal volume may be affected by variables such as the identity of the ventilator, lung mechanics, leak size, positive end-expiratory pressure level, and body size.

Design:

In vitro assessment of ventilator volume delivery was conducted for seven acute care ventilators using a passive lung simulator.

Setting:

Laboratory-based measurements.

Interventions:

The error of reported tidal volume was calculated under three ventilation modes (noninvasive-pressure-control, invasive-pressure-control, and invasive-dual-control ventilation), three models of lung mechanics (normal and restrictive and obstructive lung disease), a range of airway leak values, two positive end-expiratory pressure values, and two body weights for each ventilator. Ventilators with and without leak compensation were studied.

Measurements and Main Results:

In the absence of airway leak, all ventilators reported tidal volume accurately. In the presence of airway leak, the error of reported tidal volume increased for all ventilators without a leak compensation algorithm while ventilators with leak compensation that included estimation of tidal volume accurately reported tidal volume. In the presence of airway leak, clinically significant effects on the error of reported tidal volume by ventilators with leak compensation were associated with the choice of ventilator in all modes and with lung mechanics in invasive ventilation modes.

Conclusions:

Reported tidal volume is affected by the presence of airway leak, but in many ventilators a leak compensation algorithm that includes estimation of tidal volume can correct for the discrepancy between actual and reported tidal volume. However, even in ventilators with leak compensation, choice of ventilator and lung mechanics in invasive ventilation modes have a significant effect on error of reported tidal volume.
Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor as Novel Biomarkers for Poor Outcomes in Children With Severe Sepsis and Septic Shock
Authors: Whitney Jane E. , Silverman Melanie , Norton Jackson S. , Bachur Richard G. , Melendez Elliot
Published: October 2018

Objectives

Vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase (sFLT), are biomarkers of endothelial activation. Vascular endothelial growth factor and sFLT have been associated with sepsis severity among adults, but pediatric data are lacking. The goal of this study was to assess VEGF and sFLT as predictors of outcome for children with sepsis.

Methods

Biomarkers measured for each patient at time of presentation to the emergency department were compared in children with septic shock versus children with sepsis without shock. For children with septic shock, the associations between biomarker levels and clinical outcome measures, including intensive care unit and hospital length of stay, vasoactive inotrope score, and measures of organ dysfunction, were assessed.

Results

Soluble fms-like tyrosine kinase and VEGF were elevated in children with septic shock (n = 73) compared with those with sepsis (n = 93). Elevated sFLT but not VEGF was associated with longer intensive care unit length of stay (P = 0.003), longer time requiring vasoactive agents (P < 0.001), higher maximum vasoactive inotrope score (P < 0.001), and higher maximum pediatric logistic organ dysfunction score (P < 0.001).

Conclusions

Vascular endothelial growth factor and sFLT measured in the emergency department are elevated in children with septic shock, and elevated sFLT but not VEGF is associated with worse clinical outcomes.
Attitudes and Opinions of Adolescent Females Regarding 2 Methods of Bladder Filling for Transabdominal Ultrasound
Authors: Waterhouse Marie R. , Pham Phung K. , Chang Todd P.
Published: October 2018

Objectives

Adolescent female patients who are not sexually active and who present to a pediatric emergency department with abdominal pain require a full bladder prior to transabdominal ultrasound. Procedures to fill the bladder are largely institution or provider dependent. We examined adolescent females' attitudes and opinions toward 2 common methods of bladder filling, intravenous fluid administration and transurethral Foley catheter placement, by means of a Q-sort study.

Methods

Two convenience samples of adolescent female patients in the pediatric emergency department at an academic children's hospital participated in the study. In part 1, subjects underwent a semistructured interview to elicit their opinions regarding 2 methods of bladder filling: intravenous fluid or transurethral catheter. The summation of subject statements was then narrowed down to a final Q set of 25 statements. In part 2, a second sample of subjects independently arranged this Q set according to their own agreement or disagreement with each statement. Principal components analysis was conducted to examine factors or collections of statements representing a shared viewpoint and to describe commonalities.

Results

Part 1 was completed with 9 subjects, and part 2 with 26 subjects. Factors revealed from the Q-sort data included acceptance of tests deemed medically necessary, desire for parental involvement, and a wish to minimize discomfort. Most adolescents aligned with 1 of these 3 factors.

Conclusions

Adolescent female patients varied in their attitudes and opinions regarding intravenous catheter hydration and Foley catheter placement for transabdominal ultrasound. Knowledge of adolescent viewpoints may help better inform practitioner-patient communication for this procedure.
Intranetwork and Internetwork Effects of Navigated Transcranial Magnetic Stimulation Using Low- and High-Frequency Pulse Application to the Dorsolateral Prefrontal Cortex: A Combined rTMS–fMRI Approach
Authors: Zhang Haosu , Sollmann Nico , Castrillón Gabriel , Kurcyus Katarzyna , Meyer Bernhard , Zimmer Claus , Krieg Sandro M.
Published: October 2018

Purpose:

Although transcranial magnetic stimulation (TMS) is routinely applied in neuroscience and clinical settings, not much is known about its effects on brain networks. Therefore, this pilot study was set up using repetitive navigated transcranial magnetic stimulation (rTMS) combined with resting-state functional MRI (rs-fMRI) to explore frequency-dependent stimulation effects on an intranetwork and internetwork level.

Methods:

Six healthy subjects (median age: 23.5 years) underwent two rTMS sessions (1 and 10 Hz), 7 days apart, and prestimulation and poststimulation rs-fMRI. Repetitive navigated transcranial magnetic stimulation was delivered to the left dorsolateral prefrontal cortex, with the exact stimulation target being determined by independent component analysis. Alterations of functional connectivity strength were evaluated using seed-based correlation analyses within and between the salience network, central executive network, and posterior and anterior default mode network.

Results:

Low-frequency rTMS resulted in significant intranetwork alterations only for the anterior default mode network and primarily within the left hemisphere. In contrast, high-frequency rTMS led to changes within all four networks of interest. Moreover, the posterior and anterior default mode network largely showed opposite effects to rTMS, and the anterior default mode network was rather isolated from the other networks, which was especially true for low-frequency rTMS. Changes in functional connectivity strength because of low-frequency rTMS were even detectable 7 days after stimulation.

Conclusions:

This is one of the first studies using neuronavigated TMS with independent component analysis–based target selection to explore frequency-dependent stimulation effects in a combined rTMS–fMRI approach. Future studies including higher subject numbers may define the underlying mechanisms for the different responses to low- and high-frequency rTMS.
Transient arousal modulations contribute to resting-state functional connectivity changes associated with head motion parameters
Authors: Gu Yameng , Han Feng , Sainburg Lucas E. , Liu Xiao
Published: October 2018

Correlations of resting-state functional magnetic resonance imaging (rsfMRI) signals are being widely used for assessing functional brain connectivity in health and disease. However, an association was recently observed between rsfMRI connectivity modulations and the head motion parameters and regarded as a causal relationship, which has raised serious concerns about the validity of many rsfMRI findings. Here, we studied the origin of this rsfMRI-motion association and its relationship to arousal modulations. By using a template-matching method to locate arousal-related fMRI changes, we showed that the effects of high motion time points on rsfMRI connectivity are largely due to their significant overlap with arousal-affected time points. The finding suggests that the association between rsfMRI connectivity and the head motion parameters arises from their co-modulations at transient arousal modulations, and this information is critical not only for proper interpretation of motion-associated rsfMRI connectivity changes but also for controlling the potential confounding effects of arousal modulation on rsfMRI metrics.
OSCA: a tool for omic-data-based complex trait analysis
Authors: Zhang Futao , Chen Wenhan , Zhu Zhihong , Zhang Qian , Nabais Marta F. , Qi Ting , Deary Ian J. , Wray Naomi R. , Visscher Peter M. , McRae Allan F. , Yang Jian
Published: October 2018

The rapid increase of omic data in the past decades has greatly facilitated the investigation of associations between omic profiles such as DNA methylation (DNAm) and complex traits in large cohorts. Here, we proposed a mixed-linear-model-based method (called MOMENT) that tests for association between a DNAm probe and trait with all other distal probes fitted in multiple random-effect components to account for the effects of unobserved confounders as well as the correlations between distal probes induced by the confounders. We demonstrated by simulations that MOMENT showed a lower false positive rate and more robustness than existing methods. MOMENT has been implemented in a versatile software package (called OSCA) together with a number of other implementations for omic-data-based analysis including the estimation of variance in a trait captured by all measures of multiple omic profiles, omic-data-based quantitative trait locus (xQTL) analysis, and meta-analysis of xQTL data.
Diversification and collapse of a telomere elongation mechanism
Authors: Saint-Leandre Bastien , Nguyen Son C. , Levine Mia T.
Published: October 2018

In virtually all eukaryotes, telomerase counteracts chromosome erosion by adding repetitive sequence to terminal ends.Drosophila melanogasterinstead relies on specialized retrotransposons that insert preferentially at telomeres. This exchange of goods between host and mobile element—wherein the mobile element provides an essential genome service and the host provides a hospitable niche for mobile element propagation—has been called a ‘genomic symbiosis’. However, these telomere-specialized, ‘jockey’ family elements may actually evolve to selfishly over-replicate in the genomes that they ostensibly serve. Under this intra-genomic conflict model, we expect rapid diversification of telomere-specialized retrotransposon lineages and possibly, the breakdown of this tenuous relationship. Here we report data consistent with both predictions. Searching the raw reads of the 15-million-year-old ‘melanogaster species group’, we generatedde novojockey retrotransposon consensus sequences and used phylogenetic tree-building to delineate four distinct telomere-associated lineages. Recurrent gains, losses, and replacements account for this striking retrotransposon lineage diversity. Moreover, an ancestrally telomere-specialized element has ‘escaped,’ residing now throughout the genome ofD. rhopaloa.InD. biarmipes,telomere-specialized elements have disappeared completely.De novoassembly of long-reads and cytogenetics confirmed this species-specific collapse of retrotransposon-dependent telomere elongation. Instead, telomere-restricted satellite DNA and DNA transposon fragments occupy its terminal ends. We infer thatD. biarmipesrelies instead on a recombination-based mechanism conserved from yeast to flies to humans. Combined with previous reports of adaptive evolution at host proteins that regulate telomere length, telomere-associated retrotransposon diversification and disappearance offer compelling evidence that intra-genomic conflict shapes Drosophila telomere evolution.
The Landscape of Parkin Variants Reveals Pathogenic Mechanisms and Therapeutic Targets in Parkinson’s Disease
Authors: Yi Wei , MacDougall Emma J. , Tang Matthew Y. , Krahn Andrea I. , Gan-Or Ziv , Trempe Jean-François , Fon Edward A.
Published: October 2018

Mutations in Parkin (PARK2), which encodes an E3 ubiquitin ligase implicated in mitophagy, are the most common cause of early onset Parkinson’s Disease (PD). Hundreds of naturally occurring Parkin variants have been reported, both in PD patient and population databases. However, the effects of the majority of these variants on the function of Parkin and in PD pathogenesis remains unknown. Here we develop a framework for classification of the pathogenicity of Parkin variants based on the integration of clinical and functional evidence – including measures of mitophagy and protein stability, and predictive structural modeling – and assess 51 naturally occurring Parkin variants accordingly. Surprisingly, only a minority of Parkin variants, even among those previously associated with PD, disrupted Parkin function. Moreover, a few of these naturally occurring Parkin variants actually enhanced mitophagy. Interestingly, impaired mitophagy in several of the most common pathogenic Parkin variants could be rescued both by naturally-occurring (p.V224A) and structure-guided designer (p.W403A; p.F146A) hyperactive Parkin variants. Together, the findings provide a coherent framework to classify Parkin variants based on pathogenicity and suggest that several pathogenic Parkin variants represent promising targets to stratify patients for genotype-specific drug design.
Variation in pigmentation gene expression is associated with distinct aposematic color morphs in the poison frog, Dendrobates auratus
Authors: Stuckert Adam M. M. , Moore Emily , Coyle Kaitlin P. , Davison Ian , MacManes Matthew D. , Roberts Reade , Summers Kyle
Published: October 2018

Color and pattern phenotypes have clear implications for survival and reproduction in many species. However, the mechanisms that produce this coloration are still poorly characterized, especially at the genomic level. Here we have taken a transcriptomics-based approach to elucidate the underlying genetic mechanisms affecting color and pattern in a highly polytypic poison frog. We sequenced RNA from the skin from four different color morphs during the final stage of metamorphosis and assembled a de novo transcriptome. We then investigated differential gene expression, with an emphasis on examining candidate color genes from other taxa. Overall, we found differential expression of a suite of genes that control melanogenesis, melanocyte differentiation, and melanocyte proliferation (e.g., tyrpl, lefl, leol, and mitf) as well as several differentially expressed genes involved in purine synthesis and iridophore development (e.g., arfgapl, arfgap2, airc, and gairt). Our results provide evidence that several gene networks known to affect color and pattern in vertebrates play a role in color and pattern variation in this species of poison frog.
Cold-Induced Thermogenesis Increases Acetylation on the Brown Fat Proteome and Metabolome
Authors: Entwisle Samuel W. , Sanchez-Gurmaches Joan , Lawrence Robert T. , Pedersen David J. , Jung Su Myung , Martin-Perez Miguel , Guilherme Adilson , Czech Michael P. , Guertin David A. , Villen Judit
Published: October 2018

Stimulating brown adipose tissue (BAT) energy expenditure could be a therapy for obesity and related metabolic diseases. Achieving this requires a systems-level understanding of the biochemical underpinnings of thermogenesis. To identify novel metabolic features of active BAT, we measured protein abundance, protein acetylation, and metabolite levels in BAT isolated from mice living in their thermoneutral zone or in colder environments. We find that the enzymes which synthesize lipids from cytosolic acetyl-coA are among the most robustly increased proteins after cold acclimation, consistent with recent studies highlighting the importance of anabolicde novolipogenesis in BAT. In addition, many mitochondrial proteins are hyperacetylated by cold acclimation, including several sites on UCP1, which may have functional relevance. Metabolomics analysis further reveals cold-dependent increases to acetylated carnitine and several amino acids. This BAT multi-omics resource highlights widespread proteomic and metabolic changes linked to acetyl-CoA synthesis and utilization that may be useful in unraveling the remarkable metabolic properties of active BAT.
Evaluation of North American Asian Citrus Psyllid (Hemiptera: Liviidae) Population Genetics using cytochrome P450 melt curve analysis
Authors: Macias-Velasco Juan F. , Brunson Ryan T. , Hunter Wayne B. , Bextine Blake R.
Published: October 2018

The Asian Citrus Psyllid (ACP) (Diaphorina citri) is a Hemipteran which feeds on Citrus and is the principal vector of the pathogenCandidatusLiberibacter asiaticus (Las); the primary causal agent of Huanglongbing (HLB) or citrus greening disease. Currently HLB is the single greatest threat to the American citrus industry. Previous work has shown that that Cytochrome P450 (CYP4) genes are associated with insecticidal resistance to neonicotinoid insecticides. Infection by Las has also been shown to affect the expression of CYP4 genes. In this study the genetic relationships of ACP populations was evaluated using melting curve analysis of CYP4 genes. Principal component analysis shows the presence of two potential haplotypes. The groups identified by principal component analysis are significantly different from each other (P < 0.05) for all CYP4 genes tested. All populations are most likely within 2-3 mutations of each other. The existence of these mutations sheds light on the potential evolution of ACP in North America. Indicating either coevolution with Las or difference in imidacloprid basal selective pressure in the United States and Mexico.
Sparse Recovery Methods for Cell Detection and Layer Estimation
Authors: LaGrow Theodore J. , Moore Michael G. , Prasad Judy A. , Webber Alexis , Davenport Mark A. , Dyer Eva L.
Published: October 2018

Robust methods for characterizing the cellular architecture (cytoarchitecture) of the brain are needed to differentiate brain areas, identify neurological diseases, and model architectural differences across species. Current methods for mapping the cytoarchitecture and, in particular, identifying laminar (layer) divisions in tissue samples require the expertise of trained neuroanatomists to manually annotate the various regions-of-interest and cells within an image. However, as neuroanatomical datasets grow in volume, manual annotations become inefficient, impractical, and risk the potential of biasing results. In this paper, we propose an automated framework for cellular detection and density estimation that enables the detection of laminar divisions within retinal and neocortical histology datasets. Our approach for layer detection uses total variation minimization to find a small number of change points in the density that signify the beginning and end of each layer. We apply these methods to micron-scale histology images from a variety of cortical areas of the mouse brain and retina, as well as synthetic datasets. Our results demonstrate the feasibility of using automation to reveal the cytoarchitecture of neurological samples in high-resolution images.
The RNA-binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria
Authors: Ge Daniel Tianfang , Wang Wei , Tipping Cindy , Gainetdinov Ildar , Weng Zhiping , Zamore Phillip D.
Published: October 2018

PlWI-interacting RNAs (piRNAs) silence transposons inDrosophilaovaries, ensuring female fertility. Two coupled pathways generate germline piRNAs: the ping-pong cycle, in which the PIWI proteins Aubergine and Ago3 increase the abundance of pre-existing piRNAs, and the phased piRNA pathway, which generates strings of tail-to-head piRNAs, one after another. Proteins acting in the ping-pong cycle localize to nuage, whereas phased piRNA production requires Zucchini, an endonuclease on the mitochondrial surface. Here, we report that Armitage (Armi), an RNA-binding ATPase localized to both nuage and mitochondria, links the ping-pong cycle to the phased piRNA pathway. Mutations that block phased piRNA production deplete Armi from nuage. Armi ATPase mutants cannot support phased piRNA production and inappropriately bind mRNA instead of piRNA precursors. We propose that Armi shuttles between nuage and mitochondria, feeding precursor piRNAs generated by Ago3 cleavage into the Zucchini-dependent production of Aubergine- and Piwi-bound piRNAs on the mitochondrial surface.
Sevoflurane Increases Locomotion Activity in Mice
Authors: Ton Hoai , Ton Hoai , Yang Lei
Published: October 2018

Clinical observation shows emergence agitation and hyperactivity during the induction and/or recovery of anesthesia. However, an animal model to illustrate this clinical phenomenon has not been established. We therefore set out to investigate whether sevoflurane, a commonly used anesthetic, could alter locomotion in the mice during the induction and recovery of anesthesia. The activity of mouse was recorded 5 minutes before, during (for 30 minutes) and 40 minutes after the administration of anesthetic sevoflurane [1-, 1.5- and 2-fold minimum alveolar concentration] at 37 oC. The total walking distance and velocity of movement were measured and quantified as the indexes of locomotion. We found that the anesthetic sevoflurane increased the locomotion of the mice during the induction of the anesthesia. During the recovery phase after anesthesia, the mice exhibited increased locomotion for a short period of time (about 5 minutes) and then displayed a sharp decrease in mobility for up to 60 minutes following the end of anesthesia administration. The anesthetic sevoflurane did not significantly alter the food intake and body weight of the mice. Furthermore, we found that Alzheimer’s disease transgenic mice exhibited a greater sevoflurane-induced hyperactivity than the wild-type mice did. Our results showed that inhalation of the anesthetic sevoflurane induced an acute hyperactivity in mice, particularly among Alzheimer’s disease transgenic mice. These findings from the pilot studies established an animal model to promote further studies into postoperative emergence agitation, hyperactivity and the underlying mechanisms of these conditions.
Standardization and validation of a panel of cross-species microsatellites to individually identify the Asiatic wild dog (Cuon alpinus): implications in population estimation and dynamics
Authors: Modi Shrushti , Habib Bilal , Ghaskadbi Pallavi , Nigam Parag , Mondol Samrat
Published: October 2018

Background

The Asiatic wild dog or dhole (Cuon alpinus) is a highly elusive, monophyletic, forest dwelling, social canid distributed across south and Southeast Asia. Severe pressures from habitat loss, prey depletion, disease, human persecution and interspecific competition resulted in global population decline in dholes. Despite a declining population trend, detailed information on population size, ecology, demography and genetics is lacking. Generating reliable information and landscape level for dholes is challenging due to their secretive behaviour and monomorphic physical features. Recent advances in non-invasive DNA-based tools can be used to monitor populations and individuals across large landscapes. In this paper, we describe standardization and validation of faecal DNA-based methods for individual identification of dholes. We tested this method on field-collected dhole faeces in four tiger reserves of the central Indian landscape in the state of Maharashtra, India. Further, we conducted preliminary analyses of dhole population structure and demography in the study area.

Results

We tested a total of 18 cross-species markers and developed a panel of 12 markers for unambiguous individual identification of dholes. This marker panel identified 101 unique individuals from faecal samples collected across our pilot field study area. These loci showed varied level of amplification success (57-88%), polymorphism (3-9 alleles), heterozygosity (0.23-0.63) and produced a cumulative probability of identity(unbiased)and probability of identity(sibs)value of 4.7×10−10and 1.5×10−4, respectively. Our preliminary analyses of population structure indicated four genetic subpopulations in dholes. Qualitative analyses of population demography show signal of population decline.

Conclusion

Our results demonstrated that the selected panel of 12 microsatellite loci can conclusively identify dholes from poor quality, non-invasive biological samples and help in exploring various population parameters. Our methods can be used to estimate dhole populations and assess population trends for this elusive, social carnivore.
A stable, long-term cortical signature underlying consistent behavior
Authors: Gallego Juan A. , Perich Matthew G. , Chowdhury Raeed H. , Solla Sara A. , Miller Lee E.
Published: October 2018

Animals readily execute learned motor behaviors in a consistent manner over long periods of time, yet similarly stable neural correlates remained elusive up to now. How does the cortex achieve this stable control? Using the sensorimotor system as a model of cortical processing, we investigated the hypothesis that the dynamics of neural latent activity, which capture the dominant co-variation patterns within the neural population, are preserved across time. We recorded from populations of neurons in premotor, primary motor, and somatosensory cortices for up to two years as monkeys performed a reaching task. Intriguingly, despite steady turnover in the recorded neurons, the low-dimensional latent dynamics remained stable. Such stability allowed reliable decoding of behavioral features for the entire timespan, while fixed decoders based on the recorded neural activity degraded substantially. We posit that latent cortical dynamics within the manifold are the fundamental and stable building blocks underlying consistent behavioral execution.