bluuebunny/crossref_metadata_2025 huggingface dataset:
Does pre-scanning training improve the image quality of children receiving magnetic resonance imaging?
Authors: Li Jie , Li Qiancheng , Dai Xiuhong , Li Jiong , Zhang Xinxian
Published: January 2019

Background:

Magnetic resonance imaging (MRI) is often used in children for its clear display of body parts. But it is usually hard to acquire high-quality images, for the uncooperative ability of children. It is believed that pre-MRI training could ensure the high quality of images. The current meta-analysis was done to analyze the current evidences in this field.

Methods:

PubMed, Cochrane Library, and Web of Science were systematically searched up to July 2018, for studies assessing the effects of training on pediatric MRI. Data, including image quality, failed scanning rate, and sedation use, were extracted and analyzed using Revman 5.2 software.

Results:

There were 5 studies with 379 subjects in the meta-analysis. Training and control groups were quite comparable when accepted image quality was reviewed (P = .30), but a lower rate of excellent image quality was found in subjects with training (P = .02). The pooling results found no significance between training and control group in sedation use (P = .09) and successful MRI scanning (P = .63).

Conclusions:

It is cautious to conclude that pre-MRI training does not improve the image quality and reduce sedation use among children, for the limited number of studies and sample size. More trials should be encouraged to demonstrate this issue.
Provider Prediction of Disposition for Children With an Acute Exacerbation of Asthma Presenting to the Pediatric Emergency Department
Authors: Caperell Kerry , Pettigrew Justen , Gerughty Andrew , Stevenson Michelle
Published: January 2019

Objective

The aim of this study was to evaluate the accuracy of the initial impression of emergency department providers on the disposition of children with asthma exacerbation.

Methods

We conducted a prospective survey of physicians and other providers in the emergency department of a children's hospital and parents of children presenting with asthma exacerbation. The treating provider completed a survey after finishing the examination and immediately upon exiting the patient's room. Providers predicted the disposition of the child. Additionally, the providers indicated the likelihood of admission using several 10-cm visual analog scales (VASs). Physician accuracy was calculated, and logistic regression models and receiver operator characteristic curves were generated.

Results

Complete data were available for 177 subjects. Medical doctors/nurse practitioners made correct predictions in 129 (79.6%; 95% confidence interval [CI], 73.4–85.8) of 162 encounters. Respiratory therapists were correct in 69 (67.6%; 95% CI, 58.6%–76.7%) of 102 encounters, and parents were correct in 116 (67.4%; 95% CI, 60.4%–74.4%) of 172 encounters. Logistic regression with disposition as the dependent variable revealed that provider VAS for likelihood of admission (odds ratio, 23.717; 95% CI, 9.298–60.495) was associated with admission. A receiver operator characteristic curve generated for actual disposition versus “likelihood of admission” VAS had an area under the curve of 0.856 (95% CI, 0.793–0.919). For admission, a VAS of greater than 7 was 89.9% specific, greater than 7.6 was 92.9% specific, and greater than 8.6 was 96% specific.

Conclusions

Emergency department providers correctly predicted disposition 80% of the time. Providers were particularly likely to correctly predict admission. A VAS score of 7 or greater is nearly 90% specific for admission, with specificity increasing at higher values.
A Finding of Hepatic Abscess in a Teenager Presenting With Abdominal Pain
Authors: Hoffman Jenna W. , Ranasuriya Dunisha
Published: January 2019

Pyogenic hepatic abscess is a rare infection, but it is an important diagnosis to consider because the current mortality is approximately 5%. We present a case of abdominal pain in a 16-year-old male patient whose presentation was initially concerning for appendicitis but was later diagnosed as having a pyogenic hepatic abscess. It is important to direct the patient to the proper treatment including source control with drainage and antibiotics to decrease morbidity and mortality.
Characteristics of Successful Transitions From Inpatient to Outpatient Electroconvulsive Therapy
Authors: LAPID MARIA I. , MCNALLY FORSYTH DIANE , HEGARD TERESA L. , JAZDZEWSKI EMILY A. , CLOBES JANE E. , RYAN DEBRA A. , SOLA CHRISTOPHER , SUTOR BRUCE , KUNG SIMON
Published: January 2019

Objectives:

The purpose of this study was to identify clinical and psychosocial factors involved in transitioning hospitalized patients receiving electroconvulsive therapy (ECT) from the inpatient to the outpatient setting and to propose an algorithm to guide clinicians with this process.

Methods:

A retrospective chart review was completed for adult patients discharged from a psychiatric hospital from 2002 to 2012 who had an acute course of ECT that was initiated in the hospital and completed as an outpatient. We reviewed demographic and clinical information and outcomes, including ECT treatments.

Results:

Among the 277 patients who were identified, the mean age was 52.2 years, 60% were women, and 66% were married. The mean length of hospital stay was 12.9 days, and the mean number of ECT treatments was 4.9 as an inpatient and 3.1 as an outpatient. The most frequent primary diagnosis was depression. Most patients (81%) had a responsible adult at home. Patients had good cognitive functioning at both baseline and discharge, and showed improved functional status at discharge (P<0.001 for change in scores on the Global Assessment of Functioning from admission to discharge).

Conclusions:

Factors such as improved cognitive and functional status from admission to discharge, a medically uncomplicated course, and a responsible adult at home were observed among patients transitioned from inpatient to outpatient ECT. On the basis of these study results, a review of the literature, and clinical experience, an algorithm to assist clinical decisions for ECT transitioning was developed.
Clinical Necessity Guidelines for Psychotherapy, Insurance Medical Necessity and Utilization Review Protocols, and Mental Health Parity
Authors: LAZAR SUSAN G. , BENDAT MEIRAM , GABBARD GLEN , LEVY KENNETH , McWILLIAMS NANCY , PLAKUN ERIC M. , SHEDLER JONATHAN , YEOMANS FRANK
Published: January 2019

The founding members of the Coalition for Psychotherapy Parity present Clinical Necessity Guidelines for Psychotherapy, Insurance Medical Necessity and Utilization Review Protocols, and Mental Health Parity. These guidelines support access to psychotherapy as prescribed by the clinician without arbitrary limitations on duration or frequency. The authors of the guidelines first review the evidence that psychotherapy is effective, cost-effective, and often provides a cost-offset in decreased overall medical expenses, morbidity, mortality, and disability. They highlight the disparity between clinicians’ knowledge of generally accepted standards of care for mental health and substance use disorders and the much more limited “crisis stabilization” focus of many insurance companies. The clinical trials that health insurers cite as justification for authorizing only brief treatment for all patients involve highly selected, atypical populations that are not representative of the general population of patients in need of mental health care, who typically have complex conditions and chronic, recurring symptoms requiring ongoing availability of treatment. The standard for other medical conditions reimbursed by insurance is continuation of effective treatment until meaningful recovery, which is therefore the standard required by the Mental Health Parity and Addiction Equity Act for mental health care. However, insurance companies frequently evade the legal requirement to cover treatment of mental illness at parity with other medical conditions. They do this by applying inaccurate proprietary definitions of medical necessity and imposing utilization review procedures much more restrictively for mental health treatment than for other medical care to block access to ongoing care, thus containing insurance company costs in the short term without consideration of the adverse sequelae of undertreated illness (eg, increased costs of other medical services and increased morbidity, mortality, and costs to society in increased disability). The authors of the guidelines conclude that, given appropriate medical necessity guidelines at parity with other medical care, consistent with provider expertise and a broad range of psychotherapy research, there would be no need or place for utilization review protocols. Individuals and psychotherapy organizations are invited to visit the website psychotherapyparity.org to sign on to the guidelines to indicate agreement and support.
Trauma Does Not Predict Patients’ Experiences With Constant Observation
Authors: KROLL DAVID S. , THOM ROBYN , VAN LUNTEREN JENNIFER , TORETTA CARA , CROWLEY BRITTANY , KNOTTS PAULA , FROMSON JOHN
Published: January 2019

Objective:

Little is known about which patient factors are associated with a positive or negative experience of constant observation (CO) in a general hospital or emergency department. We hypothesized that posttraumatic stress disorder (PTSD) would predict a more negative experience with CO.

Methods:

A survey regarding the positive and negative aspects of being observed by a staff member was administered to 83 patients who were admitted to an inpatient psychiatric unit after experiencing CO; 55 of these patients had a history of trauma and 13 were diagnosed with PTSD. A total score reflecting the overall positive or negative experience of CO was calculated for each survey response. The survey also included 4 follow-up questions regarding the importance of individual observer characteristics (eg, sex), which were scored individually along a Likert scale.

Results:

Neither PTSD, trauma history, nor any other participant characteristic was associated with either a positive or negative overall experience with CO. Female participants were more likely than males to consider the sex and age of their staff observers to be important.

Conclusions:

Neither PTSD nor trauma history predicts a negative or positive experience with CO. A predictive model regarding which patients are likely to experience CO positively or negatively remains to be established.
Treatment of Comorbid Adult Attention-deficit/Hyperactivity Disorder and Generalized Anxiety Disorder: 2 Case Reports
Authors: OLIVA FRANCESCO , CAREZANA CLAUDIO , NIBBIO GABRIELE , BRAMANTE STEFANO , PORTIGLIATTI POMERI ALBERTO , MAINA GIUSEPPE
Published: January 2019

Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with anxiety disorders such as generalized anxiety disorder, but the best approach to treat this comorbidity in adults has yet to be determined, as current evidence on which disorder should be treated first is poor and conflicting. In this report, we present 1 case in which we treated adult ADHD first and 1 case in which we treated generalized anxiety disorder before prescribing any medication for ADHD. More studies are required on this topic, but our results suggest that treating anxiety disorders until a clear reduction of anxiety symptoms is observed, or at least taking a combined treatment approach, is more appropriate than treating adult ADHD alone and waiting for a reduction in anxiety symptoms as a secondary effect.
Drug-drug Interactions in Psychiatric Practice, Part 1: Reasons, Importance, and Strategies to Avoid and Recognize Them
Authors: PRESKORN SHELDON H.
Published: January 2019

This column begins a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. As explained in this column, this topic is important for multiple reasons. First, a large percentage of the population is receiving psychiatric medications. Second, these patients are likely to be on multiple medications which means that they are at risk for an adverse DDI. Third, DDIs may occur but not be recognized even though they have significant health care consequences for the patient. Fourth, these consequences can range from a catastrophic outcome to more everyday clinical problems involving a myriad of presentations as enumerated in this column. Also discussed in this column is the fact that all drugs, including psychiatric medications, interact on the basis of their pharmacodynamics and pharmacokinetics rather than their therapeutic use. Therefore, psychiatric medications may interact with medications prescribed for nonpsychiatric reasons as well as with other psychiatric medications. Tables are included that explain reasons for multiple medication use and principles to follow to minimize the risk of adverse DDIs.
The Developmental Profile Inventory: Constructing a Clinically Useful Self-Report for Levels of Psychodynamic Personality Functioning
Authors: POLAK MARIKE G. , VAN RIEL LAURA , INGENHOVEN THEO J.M. , VAN HENRICUS L.
Published: January 2019

Objective:

The Developmental Profile Inventory (DPI) was constructed to assess psychodynamic personality functioning by self-report.

Method:

On the basis of the frame of reference of the Development Profile interview method, a self-report was developed covering 3 domains, self, interpersonal functioning, and problem-solving strategies, which represent 6 maladaptive and 3 adaptive developmental levels of psychodynamic functioning. The DPI was administered to patients with personality disorders who were receiving psychotherapy (N=179) and to normal controls (N=228).

Results:

The internal reliabilities of the subscales were in general in the fair to good range in the patient sample, (α=0.67 to 0.88, ωh=0.52 to 0.87) and adequate to good in the healthy controls (α=0.71 to 0.91, ωh=0.71 to 0.90). Mean item-rest correlations were adequate (0.30 to 0.50). Test-retest reliability was good (intraclass correlation=0.73 to 0.91). The hypothesized factorial structure of the DPI with 9 subscales organized in 3 clusters was partly confirmed by confirmatory factor analysis χ2/df=2.37, root mean square error of approximation=0.060, root mean residual square=0.078, and comparative fit index=0.630, with each factor showing over 80% standardized loadings >0.30, and at least 75% loadings >0.40. The DPI discriminated patients and healthy controls in a meaningful way. Correlations among the DPI and other self-report measures of global personality pathology and psychological complaints showed satisfactory convergent and discriminant validity.

Conclusions:

The DPI is a promising self-report measure for assessing both adaptive and maladaptive patterns of psychodynamic personality functioning. The appropriate initial psychometric properties justify proceeding with more formal tests of construct validity and predictive performance in broader mental health settings.
Thiamine Prescribing and Wernicke’s Encephalopathy Risk Factors in Patients With Alcohol Use Disorders at a Psychiatric Hospital
Authors: LINDER LAUREN MACLEOD , ROBERT SOPHIE , MULLINAX KRISTEN , HAYES GENEVIEVE
Published: January 2019

Background:

Alcohol use disorder (AUD) is the leading cause of thiamine deficiency and can lead to Wernicke’s encephalopathy (WE). WE has a higher prevalence of development in patients with AUD, and current recommendations emphasize parenteral administration of thiamine. Our objective was to characterize thiamine utilization in patients with AUD who were prescribed thiamine and evaluate if those who received oral thiamine had risk factors for the development of WE.

Methods:

This retrospective chart review enrolled adults admitted to a psychiatric hospital from October 2014 through September 2015 diagnosed with AUD as per the International Classification of Diseases, Ninth Edition (ICD-9). The cohort was divided on the basis of route of thiamine administration (nonparenteral vs. parenteral) and was then screened retrospectively for risk factors for WE. Descriptive data and measures of central tendency were utilized to assess the objectives.

Results:

The majority of patients were white male individuals, with a mean age of 48 years. Of the 226 patients, 201 (89%) were prescribed oral thiamine. Of the first 100 patients who received oral thiamine, 36% had risk factors for WE, with the most common risk factor being malnutrition. A χ2 analysis revealed that WE risk factors did not influence route of thiamine administration (χ2=2.148, df=1, P=0.143). No patients were diagnosed with WE during their admission; however, 8 patients received parenteral thiamine at a treatment dose indicated for WE.

Conclusions:

Parenteral thiamine is underutilized in patients with AUD and risk factors for WE. Education is needed to enhance thiamine prescribing and evaluation of risk factors for WE in this population. A thiamine prescribing protocol has been developed for further thiamine optimization.
PTSD Symptom Severity, but Not Trauma Type, Predicts Mental Health Help-seeking in the Military
Authors: GUINA JEFFREY , NAHHAS RAMZI W. , NGUYEN MINH-TRI , FARNSWORTH SETH
Published: January 2019

Objective:

Although veterans with posttraumatic stress disorder (PTSD) have been reported to have high rates of inadequate treatment, to our knowledge this is the first study to evaluate associations between each individual PTSD symptom and treatment-seeking, and the first PTSD help-seeking study to evaluate variables across all—rather than specific—types of trauma.

Methods:

This case-control study surveyed a consecutive sample of active duty military outpatients with trauma histories (N=211), comparing those attending voluntary mental health services (help-seeking cases, n=128) or mandatory dental services required for all active duty personnel (general military population controls, n=83). We used logistic regression to estimate associations between help-seeking and demographics, PTSD symptoms, trauma type, suicide attempts, substance use problems, and chronic pain, with each variable adjusted for sex, age, and race.

Results:

Significant associations were found between help-seeking and PTSD diagnosis (adjusted odds ratio=4.15,P<0.001) and between help-seeking and severities of PTSD symptoms (total, clusters, all individual symptoms except recklessness; each adjusted odds ratio>1,P<0.05).

Conclusions:

In this clinical sample, a clear positive relationship was found between help-seeking and PTSD symptom severity, but not with trauma type, suicide attempts, substance use problems, or pain, after adjusting for multiple testing. Possible explanations and implications of these findings are discussed.
Drug-Drug Interactions (DDIs) in Psychiatric Practice, Part 2: Strategies to Minimize Adverse Outcomes From Unintended DDIs
Authors: PRESKORN SHELDON H.
Published: January 2019

This column is the second in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first column in this series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs and how to recognize such DDIs, and strategies for avoiding them. This second column in the series discusses strategies for minimizing adverse outcomes from such unintended DDIs. Given the huge and rapidly increasing number of available prescription and over-the-counter medications as well as nutritional supplements, the author recommends that all prescribers develop a personal formulary of ∼30 drugs that they use in everyday practice and with which they are intimately familiar. It is recommended that their knowledge of these drugs include both their generic and brand names (to avoid confusion leading to prescription of the wrong drugs), routinely used doses, pharmacokinetics including half-lives, pharmacodynamics including mechanism(s) of action and binding profile for specific receptors, adverse effect profiles, potential DDIs, and the evolving research literature on these agents. The author stresses the value of establishing a therapeutic alliance involving the patient and the people around him or her (eg, prescribers, family members, pharmacists, nurse practitioners, home health professionals, friends when appropriate) to promote the patient’s understanding of and adherence to treatment. It is also important to establish a therapeutic goal with a specific time expectation (eg, reduction in depressive symptoms within 4 wk), after which the prescriber should discuss adherence with the patient and significant others, consider a dose adjustment, or discontinue the drug after an adequate therapeutic trial or the development of an adverse effect that outweighs any benefit the drug may be having. The author outlines major principles for avoiding adverse DDIs and includes a table of online resources that provide information concerning different types of DDIs. The column ends with a discussion of limitations of currently available drug alert software programs and information on how and where to report adverse drug reactions.
Commentary: Role of the Endogenous Opiate System in Psychiatric Disorders Other Than Addiction
Authors: KAHN DAVID A.
Published: January 2019

Two case reports explore opiate use in relation to 2 different psychiatric disorders. In the first case report, the authors reported the finding that opiate abuse appeared to mitigate premorbid Tourette syndrome in a small series of patients with opiate addiction and that this benefit was maintained with medically supervised opiate agonist therapy. In the second case report, the authors noted a significant correlation between prescription opiate use and delusions of infestation in a large psychodermatology clinic (as well as a separate, stronger correlation with stimulant use). These reports highlight the importance of the opiate system in a range of psychiatric disorders, suggesting that there is much more to learn about the role of the endogenous opiate system in brain functioning, and its potential as a target for therapeutic intervention in psychiatric disorders other than addiction.
Knowledge of the Pharmacology of Antidepressants and Antipsychotics Yields Results Comparable With Pharmacogenetic Testing
Authors: MACALUSO MATTHEW , PRESKORN SHELDON H.
Published: January 2019

Several companies offer pharmacogenetic testing for psychiatry on the basis of the claim that the outcome of drug selection is better when guided by such testing than when such testing is not used. This column examines the results of the GeneSight Psychotropic Test which groups various antidepressants and antipsychotics into 3 bins: green (“use as directed”), yellow (“use with caution”), and red (“use with increased caution and more frequent monitoring”). The authors examined how frequently the same drugs appeared in these different bins in 19 patients. They found that of the 22 antidepressants evaluated, 2 were virtually always (>90%) in the green bin: desvenlafaxine and levomilnacipran; and 8 were almost never (≤10.5%) in the green bin: citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, paroxetine, and sertraline. Of the 16 antipsychotics evaluated, they found that 4 were virtually always (>90%) in the green bin: asenapine, lurasidone, paliperidone, and ziprasidone; and 2 were almost never (≤10.5%) in the green bin: chlorpromazine and thioridazine. What was common among those drugs almost always in the green bin versus those almost never in the green bin were newer versus older marketed drugs and those not dependent versus dependent on oxidative metabolism for their clearance. The authors concluded that the results of this pharmacogenetic testing could be predicted on the basis of knowledge of the pharmacology of the drugs, particularly whether their clearance was dependent on oxidative drug metabolism.
Decreasing Treatment Duration of Electroconvulsive Therapy (ECT) Using Daily Right Unilateral Ultrabrief Instead of Bitemporal ECT
Authors: SHAFI REEM M.A. , KUNG SIMON , JOHNSON EMILY K. , LAPID MARIA I. , RASMUSSEN KEITH G.
Published: January 2019

Objective:

Electroconvulsive therapy (ECT) is an effective treatment for depression, but the standard 2 to 3 times weekly treatment course results in a total treatment duration of >2 weeks. We explored the viability of decreasing treatment duration by using daily right unilateral ultrabrief (RULUB) ECT instead of standard bitemporal (BT) ECT.

Methods:

This study involved a retrospective review of records of inpatients 18 to 64 years of age who were treated between 2012 and 2017 at a large tertiary ECT center. Lead placement/technique, treatment duration (days from first to last ECT), number of ECT treatments, and scores on the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Depression Rating Scale (HamD-24) were collected. Statistical analysis was performed using 1-way analysis of variance and t tests.

Results:

Of 214 patients, 112 started daily RULUB ECT (86 were completers and 26 were eventually switched to BT), and 83 started and completed BT ECT. Daily RULUB completers finished their course of ECT 6.5 days faster than those who received BT ECT (11.7 vs. 18.2 d, P<0.0001), while the number of ECT treatments did not significantly differ between the 2 groups (daily RULUB 8.6 treatments vs. BT 8.3 treatments, P=0.4402). There were no significant differences in the final PHQ-9 or HamD-24 depression scores between the 2 groups. One case of significant cognitive impairment was observed in the daily RULUB group.

Conclusions:

Daily RULUB ECT compared with BT ECT allowed depression to be treated faster and with similar efficacy. Randomized controlled trials, which include the use of formal cognitive and physical side effect measures, are needed to further explore the viability of daily RULUB ECT.
Attraction Versus Action in Pedophilic Desire: The Role of Personality Traits and Childhood Experience
Authors: COHEN LISA J. , NDUKWE NWAYIEZE , SIEGFRIED RACHEL , KOPEYKINA IRINA , YASEEN ZIMRI S. , GALYNKER IGOR
Published: January 2019

Objective:

Comparison of pedophilic individuals who do and do not refrain from sexually engaging with children may offer critically important information regarding the differential contributors to pedophilic attraction versus behavior. This study compared 5 traits that are potentially contributory to pedophilic attraction or behavior in both minor-attracted persons (MAPs) who refrain from sexually engaging with minors (nonacting MAPs) and those who have acted on pedophilic attractions and subsequently entered the criminal justice system (forensic MAPs).

Methods:

Subjects included 195 nonacting MAPs, 50 forensic MAPs, and 60 healthy controls. Data on nonacting MAPs were drawn from an online survey, and data on the other 2 groups were based on prior in-person evaluations. Measures included the Millon Clinical Multiaxial Inventory-II (MCMI-II), Barratt Impulsiveness Scale (BIS-11), the MAP Questionnaire, and the Sexual History Questionnaire (SHQ).

Results:

Both MAP groups scored higher than healthy controls on the domains of socially inhibited personality traits, propensity toward cognitive distortions, and subjects’ own childhood sexual abuse (CSA). Forensic MAPs scored higher than nonacting MAPs on the CSA domain, but the 2 MAP groups differed little on the other 2 domains. Forensic MAPs also scored higher than the other 2 groups on the antisocial domain, whereas nonacting MAPs did not differ from controls on this measure. Nonacting MAPs scored higher than controls on impulsivity.

Conclusions:

Antisocial personality traits may be a primary driver of pedophilic behavior that is unrelated to pedophilic attraction. Socially inhibited personality traits and propensity toward cognitive distortions are associated with pedophilic attraction, although the direction of causation is not clear. CSA seems to increase the risk of both attraction and behavior.
Subdissociative Ketamine Use in the Emergency Department
Authors: Nichols Kayla A. , Paciullo Christopher A.
Published: January 2019

Ketamine is an anesthetic known globally both for its potent dissociative properties and potential for abuse. More recently, ketamine demonstrates utility in a variety of disease states such as treatment-resistant depression, status asthmaticus, and acute agitation. In addition, ketamine has been shown to demonstrate various effects at different doses, which adds to its pharmacological benefit. As these new indications continue to come to light, it is important to stay current with the dosing for these indications as well as the adverse effects associated with ketamine's use. This review highlights the history and mechanism of ketamine as well as addressing the use of the different dosing ranges of ketamine.
Managing Acute Salicylate Toxicity in the Emergency Department
Authors: Bowers Dale , Mason Melissa , Clinkscales Molly
Published: January 2019

Salicylates are among the oldest and most widely used medication to date and are utilized for a variety of purposes including the management of fever, inflammation, pain, and cardiovascular prophylaxis. Reports from U.S. Poison Control Centers indicate that over 40,000 Americans are exposed to salicylate-containing substances annually, and although generally deemed safe, fatal intoxications can occur from a single ingestion. Although some ingestions are intentional, many are not, and are a result of the prevalence of salicylates in a wide array of prescription and over-the-counter substances. Because of the wide range of symptoms associated with toxic overdose, as well as the high rate of mortality and complications associated with these cases, the emergency nurse practitioner should have a systematic approach to diagnosing and treating these patients. This case narrative describes the clinical case of a 22-year-old man who presented to the emergency department after ingesting an unknown amount of a salicylate-containing medication. It demonstrates the difficulty associated with appropriately distinguishing between toxic ingestions, hallmark indicators that can assist in appropriate diagnoses, and key interventions that must be initiated in a timely manner to mitigate negative outcomes. This case also serves as the basis for a review of current practice guidelines, and provides the clinician with tools to ensure evidence-based interventions are not delayed, thus increasing the chance of recovery for this patient population.
The development of spatiotemporal organization of episodic memory in children and its disruption in Williams Syndrome
Authors: Mastrogiuseppe Marilina , Bertelsen Natasha , Francesca Bedeschi Maria , Lee Sang Ah
Published: January 2019

Recent theories of episodic memory propose that the hippocampus provides the spatiotemporal framework for episodic memories. If this is true, does the development of episodic memory depend on the binding of space and time? And does this rely, at least partly, on normal hippocampal function? We investigated the development of episodic memory in children 2–8 years of age (Study 1) and its impairment in Williams Syndrome (Study 2) by implementing a nonverbal object-placement task that dissociates the what, where, and when components of episodic memory. Our results indicate that the binding of space and time in memory emerges first in development around the age of 3 and is impaired in Williams Syndrome. Space-time binding both preceded and predicted success in full episodic memory (what+where+when), and associating objects to spatial location seemed to mediate this developmental process. Importantly, these effects were not explained by improvements in object or location memory.
Multiple sources of Shh are critical for the generation and scaling of ventral spinal cord oligodendrocyte precursor populations
Authors: Starikov Lev , Ghinia-Tegla Miruna , Kottmann Andreas H.
Published: January 2019

Graded Sonic Hedgehog (Shh) signaling emanating from notochord and floorplate patterns the early neural tube. Soon thereafter, Shh signaling strength within the ventricular zone becomes dis-contiguous and discontinuous along the ventral to dorsal axis suggesting a distribution of Shh that cannot be achieved by diffusion alone. Here we discover that sequential activation of Shh expression by ventricular zone derivatives is critical for counteracting a precocious exhaustion of the Olig2 precursor cell population of the pMN domain at the end of motor neuron genesis and during the subsequent phase of ventral oligodendrocyte precursor production. Selective expression of Shh by motor neurons of the lateral motor column at the beginning of oligodendrogenesis ensures a more yielding pMN domain at limb levels compared to thoracic levels. Thus, patterned expression of Shh by ventricular zone derivatives including earlier born neurons contributes to the scaling of the spinal cord along the anterior – posterior axis by regulating the activity of a select ventricular zone precursor domain at later stages of development.
Network Inference with Granger Causality Ensembles on Single-Cell Transcriptomic Data
Authors: Deshpande Atul , Chu Li-Fang , Stewart Ron , Gitter Anthony
Published: January 2019

Advances in single-cell transcriptomics enable measuring the gene expression of individual cells, allowing cells to be ordered by their state in a dynamic biological process. Many algorithms assign ‘pseudotimes’ to each cell, representing the progress along the biological process. Ordering the expression data according to such pseudotimes can be valuable for understanding the underlying regulator-gene interactions in a biological process, such as differentiation. However, the distribution of cells sampled along a transitional process, and hence that of the pseudotimes assigned to them, is not uniform. This prevents using many standard mathematical methods for analyzing the ordered gene expression states. We present Single-cell Inference of Networks using Granger Ensembles (SINGE), an algorithm for gene regulatory network inference from single-cell gene expression data. Given ordered single-cell data, SINGE uses kernel-based Granger Causality regression, which smooths the irregular pseudotimes and missing expression values. It then aggregates the predictions from an ensemble of regression analyses with a modified Borda count to compile a ranked list of candidate interactions between transcriptional regulators and their target genes. In two mouse embryonic stem cell differentiation case studies, SINGE outperforms other contemporary algorithms for gene network reconstruction. However, a more detailed examination reveals caveats about transcriptional network reconstruction with single-cell RNA-seq data. Network inference methods, including SINGE, may have near random performance for predicting the targets of many individual regulators even if the overall performance is good. In addition, including uninformative pseudotime values can hurt the performance of network reconstruction methods. A MATLAB implementation of SINGE is available athttps://github.com/gitter-lab/SINGE.
The lymphoid-associated interleukin 7 receptor (IL-7R) regulates tissue resident macrophage development
Authors: Leung Gabriel A. , Cool Taylor , Valencia Clint H. , Worthington Atesh , Beaudin Anna E. , Forsberg E. Camilla
Published: January 2019

The discovery of a fetal origin for tissue-resident macrophages (trMacs) has inspired an intense search for the mechanisms underlying their development. Here, we performed in vivo lineage tracing of cells with an expression history of IL-7Rα, a marker exclusively associated with the lymphoid lineage in adult hematopoiesis. Surprisingly, we found that IL7R-Cre labeled fetal-derived, adult trMacs. Labeling was almost complete in some tissues and partial in other organs. The putative progenitors of trMacs, yolk sac (YS) erythromyeloid progenitors (EMPs), did not express IL-7R, and YS hematopoiesis was unperturbed in IL-7R-deficient mice. In contrast, tracking of IL-7Rα message levels, surface protein expression, and IL7R-Cre-mediated labeling across fetal development revealed dynamic regulation of IL-7Rα mRNA expression and rapid upregulation of IL-7Rα surface protein upon transition from monocyte to macrophage within fetal tissues. Fetal liver monocyte differentiation in vitro produced IL-7R+ macrophages, supporting a direct progenitor-progeny relationship. Additionally, blockade of IL-7R function during late gestation specifically impaired the establishment of fetal-derived tissue macrophages in vivo. These data provide evidence for a distinct function of IL-7Rα in fetal myelopoiesis and identify IL-7R as a novel regulator of tissue-resident macrophage development.
Global proteomic profiling of primary macrophages duringM. tuberculosisinfection identifies TAX1BP1 as a mediator of autophagy targeting
Authors: Budzik Jonathan M. , Garelis Nick E. , Repasy Teresa , Roberts Allison W. , Popov Lauren M. , Parry Trevor J. , Jiminez-Morales David , Swaney Danielle L. , Johnson Jeffrey R. , Krogan Nevan J. , Cox Jeffery S.
Published: January 2019

Macrophages are highly plastic cells that adopt diverse functional capabilities and play critical roles in immunity, cancer, and tissue homeostasis, but how these different cell fates and activities are triggered in response to their environmental cues is not well understood. We used new proteomic tools to identify protein post-translational modifications (PTMs) that control antibacterial responses of macrophages. Here, we report an unbiased and global analysis of the changes in host protein abundance, phosphorylation, and ubiquitylation, during the first 24-hours ofMycobacterium tuberculosis (Mtb)infection of primary macrophages. We discovered 1379 proteins with changes in their phosphorylation state and 591 proteins with changes in their ubiquitylation in response toMtbinfection. We identified pathways regulated by phosphorylation and ubiquitylation that weren’t reflected by changes in protein abundance, indicating that the activity of these pathways was regulated. These include pathways known to be regulated by ubiquitylation and phosphorylation (e.g.autophagy) as well as pathways that were not known to be regulated duringMtbinfection (e.g. nucleocytoplasmic transport and mRNA metabolism). We identified an enrichment in phosphorylation of autophagy receptors (TAX1BP1, p62, optineurin, BNIP3L), several of which were not previously implicated in the host response toMtbinfection. We found that p62 deficiency blocks ubiquitylation and TAX1BP1 deficiency enhances ubiquitylation, suggesting p62 ubiquitylation acts as an amplification loop by promoting downstream adaptor recruitment and serves as a platform for recruitment of ubiquitin. Our results show that TAX1BP1 mediates clearance of ubiquitylatedMtband targets the bacteria to LC3-positive phagophores. Taken together, our proteomic profiling is likely a valuable resource for initiating mechanistic studies of macrophage biology.
The simulation extrapolation technique meets ecology and evolution: A general and intuitive method to account for measurement error
Authors: Ponzi Erica , Keller Lukas F. , Muff Stefanie
Published: January 2019

Measurement error and other forms of uncertainty are commonplace in ecology and evolution and may bias estimates of parameters of interest. Although a variety of approaches to obtain unbiased estimators are available, these often require that errors are explicitly modeled and that a latent model for the unobserved error-free variable can be specified, which in practice is often difficult.

Here we propose to generalize a heuristic approach to correct for measurement error, denoted as simulation extrapolation (SIMEX), to situations where explicit error modeling fails. We illustrate the application of SIMEX using the example of estimates of quantitative genetic parameters, e. g. inbreeding depression and heritability, in the presence of pedigree errors. Following the original SIMEX idea, the error in the pedigree is progressively increased to determine how the estimated quantities are affected by error. The observed trend is then extrapolated back to a hypothetical error-free pedigree, yielding unbiased estimates of inbreeding depression and heritability. We term this application of the SIMEX idea to pedigrees “PSIMEX”. We tested the method with simulated pedigrees with different pedigree structures and initial error proportions, and with real field data from a free-living population of song sparrows.

The simulation study indicates that the accuracy and precision of the extrapolated error-free estimate for inbreeding depression and heritability are good. In the application to the song sparrow data, the error-corrected results could be validated against the actual values thanks to the availability of both an error-prone and an error-free pedigree, and the results indicate that the PSIMEX estimator is close to the actual value. For easy accessibility of the method, we provide the novel R-package PSIMEX.

By transferring the SIMEX philosophy to error in pedigrees, we have illustrated how this heuristic approach can be generalized to situations where explicit latent models for the unobserved variables or for the error of the variables of interest are difficult to formulate. Thanks to the simplicity of the idea, many other error problems in ecology and evolution might be amenable to SIMEX-like error correction methods.
Invasive Siberian chipmunksEutamias sibiricusin Italy: a socio-ecological analysis indicates that they could, and should, be removed
Authors: Cerri Jacopo , Mori Emiliano , Zozzoli Rudy , Gigliotti Andrea , Chirco Antony , Bertolino Sandro
Published: January 2019

BACKGROUND

Eradication of invasive alien species is a form of pest control linked to biodiversity conservation that usually involves killing animals. Squirrels are prominent among invasive alien species in Italy with four species introduced. Three of them are included within the list of alien species of European concern and their eradication and control is recommended. However, their local control is not an easy task, being highly appreciated by the general public. We propose a socio-ecological approach to evaluate the feasibility of eradicating Siberian chipmunks (Eutamias sibiricus) populations. We performed a structured questionnaire to assess the social perception of invasive Siberian chipmunks in urban parks where they occur and to identify groups of visitors who might oppose eradication. We also carried out geographic profiling to test for the spatial expansion of chipmunk populations.

RESULTS

Overall, park visitors regarded chipmunks positively and appreciated to see them, but human-chipmunk interactions were still rare. We did not identify any group of visitors with a strong attachment to chipmunks, who might oppose future control programs. Geographic profiling showed that chipmunks in Valeggio sul Mincio are starting to expand outside of their introduction site.

CONCLUSIONS

Data from questionnaires show that chipmunks eradication, coupled with adequate communication initiatives, might be feasible. Moreover, geographic profiling indicates that time for a rapid removal is running out. Socio-ecological approaches, combining the analysis of structured questionnaires administered to stakeholders and statistical modeling of pest observations, could be a valuable tool to decide the feasibility and the urgency of invasive pest control.
Macrophage-specific NF-κB activation dynamics can segregate inflammatory bowel disease patients
Authors: Papoutsopoulou Stamatia , Burkitt Michael D. , Bergey François , England Hazel , Hough Rachael , Schmidt Lorraine , Spiller David G , White Michael HR , Paszek Pawel , Jackson Dean A. , Dos Santos Vitor A.P. Martins , Sellge Gernot , Pritchard D. Mark , Campbell Barry J. , Müller Werner , Probert Chris S.
Published: January 2019

The heterogeneous nature of inflammatory bowel disease (IBD) presents challenges, particularly when choosing therapy. Activation of the NF-κB transcription factor is a highly-regulated, dynamic event in IBD pathogenesis. We expressed the human NF-κB/p65 subunit in blood-derived macrophages, using lentivirus. Confocal imaging of p65 activation revealed that a higher proportion of macrophages from Crohn’s patients responded to lipid-A compared to controls. In contrast, cells from ulcerative colitis (UC) patients exhibited a shorter duration of p65 nuclear localisation compared to healthy controls and Crohn’s donors. Using a similar lentivirus approach, NF-κB-regulated luciferase was expressed in patient macrophages, isolated from frozen peripheral blood mononuclear cell samples. Following activation, samples could be segregated into three clusters based on the NF-κB-regulated luciferase response. The majority of UC samples appeared in hypo-responsive cluster 1, with Crohn’s patients representing the majority of hyper-responsive cluster 3. A positive correlation was seen between NF-κB-induced luciferase activity and cytokine levels released to medium from stimulated macrophages, but not in serum or biopsy. Analysis of macrophage cytokine responses and patient metadata revealed a strong correlation between Crohn’s patients who smoked and hyper-activation of p65. Thesein vitrodynamic assays of NF-κB activation in blood-derived macrophages segregate IBD patients into groups with different phenotypes and therefore may help determine response to therapy.

Significance statement

This manuscript describes two dynamic assays of NF-κB activation in blood-derived macrophages that can segregate IBD patients into groups with different phenotypes. For the first time we introduce the use of dynamic measurements of a transcription factor activation as a method to stratify patients and we are confident that our approach will lead in future to early patient stratification and prediction of treatment outcome.
Inability to improve performance with control shows limited access to inner states
Authors: Perquin Marlou Nadine , Yang Jessica , Teufel Christoph , Sumner Petroc , Hedge Craig , Bompas Aline
Published: January 2019

Any repeatedly performed action is characterised by endogenous variability, affecting both speed and accuracy – for a large part presumably caused by fluctuations in underlying brain and body states. The current research questions were: 1) whether such states are accessible to us, and 2) whether we can act upon this information to reduce variability. For example, when playing a game of darts, there is an implicit assumption that people can wait to throw until they are in the ‘right’ perceptual-attentional state. If this is true, taking away the ability to self-pace the game should worsen performance. We first tested precisely this assumption asking participants to play darts in a self-paced and a fixed-paced condition. There was no benefit of self-pacing, showing that participants were unable to use such control to improve their performance and reduce their variability. Next, we replicated these findings in two computer-based tasks, in which participants performed a rapid action-selection and a visual detection task in one self-paced and three forced-paced conditions. Over four different empirical tests, we show that the self-paced condition did not lead to improved performance or reduced variability, nor to reduced temporal dependencies in the reaction time series. Overall, it seems that, if people have any access to their fluctuating performance-relevant inner states, this access is limited and not relevant for upcoming performance.