bluuebunny/crossref_metadata_2025 huggingface dataset:
LipidFinder on LIPID MAPS: peak filtering, MS searching and statistical analysis for lipidomics
Authors: Fahy Eoin , Alvarez-Jarreta Jorge , Brasher Christopher J , Nguyen An , Hawksworth Jade I , Rodrigues Patricia , Meckelmann Sven , Allen Stuart M , O'Donnell Valerie B
Published: August 2018

We present LipidFinder online, hosted on the LIPID MAPS website, as a liquid chromatography/mass spectrometry (LC/MS) workflow comprising peak filtering, MS searching and statistical analysis components, highly customized for interrogating lipidomic data. The online interface of LipidFinder includes several innovations such as comprehensive parameter tuning, a MS search engine employing in-house customized, curated and computationally generated databases and multiple reporting/display options. A set of integrated statistical analysis tools which enable users to identify those features which are significantly-altered under the selected experimental conditions, thereby greatly reducing the complexity of the peaklist prior to MS searching is included. LipidFinder is presented as a highly flexible, extensible user-friendly online workflow which leverages the lipidomics knowledge base and resources of the LIPID MAPS website, long recognized as a leading global lipidomics portal.

Availability and implementation

LipidFinder on LIPID MAPS is available at: http://www.lipidmaps.org/data/LF.
GlycanAnalyzer: software for automated interpretation of N-glycan profiles after exoglycosidase digestions
Authors: Walsh Ian , Nguyen-Khuong Terry , Wongtrakul-Kish Katherine , Tay Shi Jie , Chew Daniel , José Tasha , Taron Christopher H , Rudd Pauline M
Published: August 2018

Many eukaryotic proteins are modified by N-glycans. Liquid chromatography (ultra-performance –UPLC and high-performance–HPLC) coupled with mass spectrometry (MS) is conventionally used to characterize N-glycan structures. Software can automatically assign glycan structures by matching their observed retention times and masses with standardized values in reference databases. However, more precise confirmation of N-glycan structures can be derived using exoglycosidases, enzymes that remove specific monosaccharides from glycans. Exoglycosidase removal of monosaccharides results in signature peak shifts, in both UPLC and MS1, yielding an effective way to verify N-glycan structure with high detail (down to the position and isomeric linkage of each monosaccharide). Because manual interpretation of exoglycosidase data is complex and time consuming, we developed GlycanAnalyzer, a web application that pattern matches N-glycan peak shifts following exoglycosidase digestion and automates structure assignments. GlycanAnalyzer significantly improves assignment accuracy over other auto-assignment methods on tests with a monoclonal antibody and four glycan standards (100% versus 82% for the next best software). By automating data interpretation, GlycanAnalyzer enables the easier use of exoglycosidases to precisely define N-glycan structure.

Availability and implementation

http://glycananalyzer.neb.com. Datasets available online.

Supplementary information

Supplementary data are available at Bioinformatics online.
KEDDY: a knowledge-based statistical gene set test method to detect differential functional protein–protein interactions
Authors: Jung Sungwon
Published: August 2018

Motivation

Identifying differential patterns between conditions is a popular approach to understanding the discrepancy between different biological contexts. Although many statistical tests were proposed for identifying gene sets with differential patterns based on different definitions of differentiality, few methods were suggested to identify gene sets with differential functional protein networks due to computational complexity.

Results

We propose a method of Knowledge-based Evaluation of Dependency DifferentialitY (KEDDY), which is a statistical test for differential functional protein networks of a set of genes between two conditions with utilizing known functional protein–protein interaction information. Unlike other approaches focused on differential expressions of individual genes or differentiality of individual interactions, KEDDY compares two conditions by evaluating the probability distributions of functional protein networks based on known functional protein–protein interactions. The method has been evaluated and compared with previous methods through simulation studies, where KEDDY achieves significantly improved performance in accuracy and speed than the previous method that does not use prior knowledge and better performance in identifying gene sets with differential interactions than other methods evaluating changes in gene expressions. Applications to cancer data sets show that KEDDY identifies alternative cancer subtype-related differential gene sets compared to other differential expression-based methods, and the results also provide detailed gene regulatory information that drives the differentiality of the gene sets.

Availability and implementation

The Java implementation of KEDDY is freely available to non-commercial users at https://sites.google.com/site/sjunggsm/keddy.

Supplementary information

Supplementary data are available at Bioinformatics online.
Processing of big heterogeneous genomic datasets for tertiary analysis of Next Generation Sequencing data
Authors: Masseroli Marco , Canakoglu Arif , Pinoli Pietro , Kaitoua Abdulrahman , Gulino Andrea , Horlova Olha , Nanni Luca , Bernasconi Anna , Perna Stefano , Stamoulakatou Eirini , Ceri Stefano
Published: August 2018

Motivation

We previously proposed a paradigm shift in genomic data management, based on the Genomic Data Model (GDM) for mediating existing data formats and on the GenoMetric Query Language (GMQL) for supporting, at a high level of abstraction, data extraction and the most common data-driven computations required by tertiary data analysis of Next Generation Sequencing datasets. Here, we present a new GMQL-based system with enhanced accessibility, portability, scalability and performance.

Results

The new system has a well-designed modular architecture featuring: (i) an intermediate representation supporting many different implementations (including Spark, Flink and SciDB); (ii) a high-level technology-independent repository abstraction, supporting different repository technologies (e.g., local file system, Hadoop File System, database or others); (iii) several system interfaces, including a user-friendly Web-based interface, a Web Service interface, and a programmatic interface for Python language. Biological use case examples, using public ENCODE, Roadmap Epigenomics and TCGA datasets, demonstrate the relevance of our work.

Availability and implementation

The GMQL system is freely available for non-commercial use as open source project at: http://www.bioinformatics.deib.polimi.it/GMQLsystem/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Precision Surveillance for Viral Respiratory Pathogens: Virome Capture Sequencing for the Detection and Genomic Characterization of Severe Acute Respiratory Infection in Uganda
Authors: Cummings Matthew J , Tokarz Rafal , Bakamutumaho Barnabas , Kayiwa John , Byaruhanga Timothy , Owor Nicholas , Namagambo Barbara , Wolf Allison , Mathema Barun , Lutwama Julius J , Schluger Neil W , Lipkin W Ian , O’Donnell Max R
Published: August 2018

Background

Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential.

Methods

Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens.

Results

Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses.

Conclusions

Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.
Deployment and Smokeless Tobacco Use Among Active Duty Service Members in the U.S. Military
Authors: Lin Jie , Zhu Kangmin , Soliván-Ortiz Aida M , Larsen Stacy L , Schneid Thomas R , Shriver Craig D , Lee Sukhyung
Published: August 2018

Introduction

The prevalence of smokeless tobacco use among U.S. active duty service members has been much higher than in the U.S. general population. The association between deployment and smokeless tobacco use has not been well studied. We investigated the association between deployment and smokeless tobacco use among U.S. active duty service members. We also evaluated the modification effects from other factors related to smokeless tobacco use on the deployment-smokeless tobacco use association.

Materials and Methods

Eligible active duty service members stationed at two military installations (Fort Bragg, NC, USA and Lackland Air Force Base, TX, USA) were recruited from July 2015 to May 2016. Each participant completed a self-administered questionnaire. Multivariable logistic regression was used to assess the association between deployment and smokeless tobacco use and estimated odds ratio (OR) and 95% confidence interval (CI). Stratified analysis was performed to evaluate modification effects from other commonly known factors related to smokeless tobacco use in military, specifically, cigarette smoking status, use among family members (family history of use), perception of harm, and use among military peers.

Results

Out of 2,465 study participants who completed the questionnaire, 548 were smokeless tobacco users. Service members who had been deployed to a combat zone had 1.39 fold (95% CI = 1.03–1.87) increased odds of using smokeless tobacco than those who never deployed to a combat zone. The odds of smokeless tobacco use among those who had been deployed once, twice, three times and four or more times to a combat zone were 1.27 (95% CI = 0.91–1.78), 1.30 (95% CI = 0.85–1.99), 2.49 (95% CI = 1.45–4.28), and 2.88 (95% CI = 1.71–4.86), respectively, with a significant dose–response trend (p for trend <0.0001). Further, subjects who served in combat units during deployment exhibited more than two-fold increased odds of use as compared with those who had never been deployed (OR = 2.03, 95% CI = 1.41–2.93). In stratified analysis, the association between deployment and smokeless tobacco use was only present among subjects who never smoked cigarettes, those without family history of smokeless tobacco use, and those who had low perception of harm of use.

Conclusions

Military deployment was associated with smokeless tobacco use among active service members. However, the influence of military deployment on smokeless tobacco use was not equally strong on all service members. Subjects who never smoked cigarettes, who had no family history of use and who had low perception of harm were the most susceptible subgroups to deployment-related smokeless tobacco use. This study has implications to identify high-risk subgroups to reduce smokeless tobacco use in the U.S. military.
Flying in Cyberspace: Policing Global Travel Fraud
Authors: Hutchings Alice
Published: August 2018

Airline tickets that have been obtained illicitly represent a truly global crime. The travel industry and law enforcement have been attempting to address travel fraud for some time. Airline tickets can be obtained using various cybercrime methods. They are traded and advertised on online blackmarkets and through fraudulent travel agencies. This research is qualitative in nature, informed by interviews with law enforcement and industry stakeholders, as well as the analysis of a marketplace where fraudulently obtained tickets are traded. This research considers: the nature of the criminal market for fraudulently obtained tickets, the involvement of co-offending and organized crime, the geographic nature of travel fraud, and the ways in which those supplying fraudulently obtained tickets try to avoid detection. Also considered is how the nature of travel fraud has changed over time, ways in which it may continue to change, and the challenges faced by law enforcement.
Precision Physical Therapy: Exercise, the Epigenome, and the Heritability of Environmentally Modified Traits
Authors: Woelfel Jessica R , Dudley-Javoroski Shauna , Shields Richard K
Published: August 2018

One of the newest frontiers of physical therapy is the field of epigenetics, which examines how pervasive environmental factors such as exercise regulate the expression of genes. The epigenome may be one of the most powerful systems through which exercise exerts its beneficial effects on health and longevity. Large epidemiology studies show that individuals who regularly exercise demonstrate a lower “epigenetic age,” experience fewer metabolic diseases, and enjoy greater longevity. However, the dose, mode, intensity, and duration of exercise required to achieve a healthy epigenetic profile is unknown. As experts in exercise prescription, physical therapists are ideally suited to contribute to the discovery of this dose-response relationship. This perspective makes a case for the genesis of “precision physical therapy,” which capitalizes on epigenetic discoveries to optimize exercise-based interventions. Summarized here is the emerging body of knowledge supporting epigenetic adaptations to exercise in humans, including the intriguing possibility that these environmentally modified traits could be passed down to offspring. In the future, it is likely that epigenetic data will enhance our understanding of individual disease risk and individual response to prescribed exercise. The profession of physical therapy must be alert to new epigenetic knowledge that can enhance the specificity and efficacy of movement-based treatments.
How do members of a fire and rescue service perceive expanding their roles to deliver more health care services?
Authors: Byrne-Davis L M T , Marchant D , Bull E R , Gyles D , Dean E , Hart J K
Published: August 2018

Background

Increasingly, public sector workers are being required to expand their roles into public health. Fire and rescue services, as part of the Emergency Medical Response trial, are at the forefront of role expansion, with increasing capacity due to reducing numbers of fires in recent years. Firefighter roles, successfully implemented, include responding to cardiac arrests and conducting checks on health and wellbeing in people’s own homes. In this study, we explored fire service members’ perceptions about this role expansion, to increase understanding of how role expansion can be introduced and supported.

Methods

We interviewed 21 firefighters and team members about their perceptions of new roles. Interviews were conducted, transcribed and thematically analysed until reaching thematic saturation.

Results

Perspectives differed for responding to cardiac arrests and wellbeing checks. Cardiac arrests were seen as aligned with core roles and thus more acceptable. For both types of new role participants wanted more training and opportunities to provide feedback on implementation.

Conclusions

How team members viewed role expansion depended on new role alignment with core role, training and being able to give feedback to management to shape future services.
Nonlinear electro-elastic bodies with residual stresses: spectral formulation
Authors: Shariff M H B M , Bustamante R , Merodio J
Published: August 2018

In the present article, a spectral model is developed for residually stressed electro-elastic bodies. The model uses a total energy function that depends on the right stretch tensor, residual stress tensor and one of the electric variables. Some boundary value results with cylindrical symmetry are given. Results for the inflation of a hollow sphere, where the residual stress is assumed to depend only on the radial position, are also given. The constitutive formulation contains spectral invariants that have an immediate physical interpretation which is useful in a rigorous construction of a specific form of the total energy function via an appropriate experiment
NLRP3 deficiency exacerbates enterovirus infection in mice
Authors: Wang Chen , Fung Gabriel , Deng Haoyu , Jagdeo Julienne , Mohamud Yasir , Xue Yuan Chao , Jan Eric , Hirota Jeremy A. , Luo Honglin
Published: August 2018

The role for the NOD‐like receptor (NLR) P3 inflammasome in enterovirus infection remains controversial. Available data suggest that the NLRP3 inflammasome is protective against enterovirus A71 but detrimental to the host during coxsackievirus B3 (CVB3) infection. CVB3 is a common etiologic agent associated with myocarditis and pancreatitis. Previous findings on the role of NLRP3 in CVB3 were based primarily on indirect evidence. Here, we utilized NLRP3 knockout mice as well as immune and cardiac cells to investigate the direct interplay between CVB3 infection and NLRP3 activation. We demonstrated that NLRP3 knockout mice exhibited more severe disease phenotype after CVB3 infection (significantly higher virus titers), increased myocardial, and pancreatic damage, as well as markedly impaired cardiac function compared to nontransgenic control mice. We further showed that NLRP3 activity was enhanced during early stage of CVB3 infection, as evidenced by increased gene expression and/or secretion of IL‐1β and caspase‐1. Finally, we demonstrated that CVB3 inactivates the NLRP3 inflammasome by degrading NLRP3 and its upstream serine/threonine‐protein kinase receptor‐interacting protein 1/3 via the proteolytic activity of virus‐encoded proteinases. Taken together, our results reveal the functional significance of NLRP3 in host antiviral immunity against CVB3 infection and the mechanisms by which CVB3 has evolved to counteract the host defense response.—Wang, C., Fung, G., Deng, H., Jagdeo, J., Mohamud, Y., Xue, Y. C., Jan, E., Hirota, J. A., Luo, H. NLRP3 deficiency exacerbates enterovirus infection in mice. FASEB J. 33, 942–952 (2019). www.fasebj.org
Alterations in plasma acylcarnitine and amino acid profiles may indicate poor nutrition during the suckling period due to maternal intake of an unbalanced diet and may predict later metabolic dysfunction
Authors: Pomar Catalina A. , Kuda Ondrej , Kopecky Jan , Rombaldova Martina , Castro Heriberto , Picó Catalina , Sánchez Juana , Palou Andreu
Published: August 2018

Plasma profiles of acylcarnitines (ACs) and amino acids (AAs) may have interest as potential biomarkers. Here we analyzed plasma AC and AA profiles in 2 rat models with different metabolic programming outcomes: offspring of dams fed a cafeteria diet during lactation (O‐CAF, with a thin‐outside–fat‐inside phenotype) and the offspring of dams with diet‐induced obesity subjected to dietary normalization before gestation [offspring of postcafeteria dams (O‐PCaf), nonaltered phenotype]. The purpose was to identify early variables that might indicate a propensity for a dysmetabolic state. O‐CAF rats presented higher circulating levels of most of the lipid‐derived ACs and higher hepatic expression of genes related to fatty acid oxidation (Ppara and Cpt1a) than controls [offspring of control dams (O‐C)]. They also exhibited an altered plasma AA profile. These differences were not observed in O‐PCaf animals. A partial least squares‐discriminant analysis score plot of the metabolomics data showed a clear separation between O‐CAF and O‐C animals. The long‐chain ACs (C18, C18:1, C18:2, C16:1, and C16DC) and the AAs glycine, alanine, isoleucine, serine, and proline are the variables mainly influencing this separation. In summary, we have identified a cluster of ACs and AAs whose alterations may indicate poor nutrition during lactation due to maternal unbalanced diet intake and predict the later dysmetabolic phenotype observed in the offspring.—Pomar, C. A., Kuda, O., Kopecky, J., Rombaldova, M., Castro, H., Picó, C., Sánchez, J., Palou, A. Alterations in plasma acylcarnitine and amino acid profiles may indicate poor nutrition during the suckling period due to maternal intake of an unbalanced diet and may predict later metabolic dysfunction. FASEB J. 33, 796–807 (2019). www.fasebj.org
A young testicular microenvironment protects Leydig cells against age‐related dysfunction in a mouse model of premature aging
Authors: Curley Michael , Milne Laura , Smith Sarah , J⊘rgensen Anne , Frederiksen Hanne , Hadoke Patrick , Potter Paul , Smith Lee B.
Published: August 2018

Testicular Leydig cells (LCs) are the primary source of circulating androgen in men. As men age, circulating androgen levels decline. However, whether reduced LC steroidogenesis results from specific effects of aging within LCs or reflects degenerative alterations to the wider supporting microenvironment is unclear; inability to separate intrinsic LC aging from that of the testicular microenvironment in vivo has made this question difficult to address. To resolve this, we generated novel mouse models of premature aging, driven by CDGSH iron sulfur domain 2 (Cisd2) deletion, to separate the effects of cell intrinsic aging from extrinsic effects of aging on LC function. At 6 mo of age, constitutive Cisd2‐deficient mice display signs of premature aging, including testicular atrophy, reduced LC and Sertoli cell (SC) number, decreased circulating testosterone, increased luteinizing hormone/testosterone ratio, and decreased expression of steroidogenic mRNAs, appropriately modeling primary testicular dysfunction observed in aging men. However, mice with Cisd2 deletion (and thus premature aging) restricted to either LCs or SCs were protected against testicular degeneration, demonstrating that age‐related LCs dysfunction cannot be explained by intrinsic aging within either the LC or SC lineages alone. We conclude that age‐related LC dysfunction is largely driven by aging of the supporting testicular microenvironment.—Curley, M., Milne, L., Smith, S., J⊘rgensen, A., Frederiksen, H., Hadoke, P., Potter, P., Smith, L. B. A Young testicular microenvironment protects Leydig cells against age‐related dysfunction in a mouse model of premature aging. FASEB J. 33, 978–995 (2019). www.fasebj.org
Clinical Impact of Corrective Cast Treatment for Early Onset Scoliosis: Is It a Worthwhile Treatment Option to Suppress Scoliosis Progression Before Surgical Intervention?
Authors: Kawakami Noriaki , Koumoto Izumi , Dogaki Yoshihiro , Saito Toshiki , Tauchi Ryoji , Kawakami Kazuki , Suzuki Teppei , Uno Koki
Published: August 2018

Background:

Although corrective cast (CC) has been back in use for the treatment of early onset scoliosis (EOS), no studies have reported how clinically meaningful CC was in comparison with brace-only treatment (BT) in EOS. The aim of this study was to investigate the effect of CC treatment in terms of suppression of scoliosis progression before surgery.

Methods:

This study was designed to conduct a comparison of patients treated at 2 spine institutions differing in treating methods (one: mainly CC with brace, the other: BT). Applying casts were performed without general anesthesia and repeatedly with the interval of 2 to 6 months combined with corrective brace application called alternatively repetitive cast and brace treatment (ARCBT). In total, 58 patients met the following criteria: (1) age at the first visit ≤6 years, (2) scoliosis ≥40 degrees, (3) conservative treatment≥2 years. Patients with congenital scoliosis were excluded in this study. In total, 58 patients were divided into 2 groups; cast/brace group (C/B-G) and BT group (B-G).

Results:

There were no significant differences of diagnosis (P=0.2773), sex (P=0.0670), age at the first visit (P=0.1457), scoliosis magnitude (P=0.1980), and duration for conservative treatment (P=0.2578) between 2 groups. Most of the patients who were treated with ARCBT, were switched to BT due to lower compliance for CC after the age of around 7 years. The progression of scoliosis during ARCBT and BT were 4.4 and 5.8 degree/y, respectively. Those during ARCBT in C/B-G was 2.8 degree/y comparing with 8.4 degree/y after switch to BT after 7 years of age. There was a significant difference between scoliosis progression during ARCBT in C/B-G and that of B-G (P=0.0086).

Conclusions:

This study showed that ARCBT had a significant impact on suppression of scoliosis progression compared with BT in EOS. However, the termination of cast application and the switch to BT may be still a clinical question considering the time to surgical intervention.

Level of Evidence:

Level III—retrospective comparative study.
Increasing Brace Treatment for Pediatric Distal Radius Buckle Fractures: Using Quality Improvement Methodology to Implement Evidence-based Medicine
Authors: Little Kevin J. , Godfrey Jenna , Cornwall Roger , Carr Preston , Dolan Kevin , Balch Samora Julie
Published: August 2018

Background:

Multiple randomized trials have showed equivalent outcomes and improved patient/family satisfaction using a removable brace to treat pediatric distal radius buckle fractures (DRBF). We tested the hypothesis that we could use quality improvement (QI) methodology to increase the proportion of patients with DRBF treated with removable braces at 2 tertiary care orthopaedic clinics from a baseline of 34.8% to 80%.

Methods:

Clinic billing records were reviewed monthly to determine treatment (brace vs. cast) of DRBF and tracked using control charts (p-chart). Balance measures including correct application of the diagnostic criteria and algorithm were monitored. Process measures including the number of follow-up visits, radiographs obtained, and total cost of treatment were collected. Baseline data were obtained over a 3-month period, followed by a 12-month period of interventions using Plan-Do-Study-Act cycles targeting both individuals and groups of providers.

Results:

The proportion of DRBF treated in a brace increased from a combined baseline of 34.8% to a combined 84% at the end of the study period. Following intervention, 83% (15/18) of providers began using braces for a majority of patients (defined as >67%), with only 1 provider continuing to use casts 100% of the time. Patient preference was cited as the most common reason for use of cast treatment. There was a significant decrease in the number of radiographs obtained at 1 of 2 institutions. The charges for brace treatment averaged $630 less per patient than for cast treatment, leading to an estimated medical-cost savings of $205,000 following intervention.

Conclusions:

Implementation of brace treatment for pediatric DRBF using QI methodology resulted in a shift toward brace treatment in the majority of patients, leading to substantial medical and nonmedical cost savings. Although patient preference was cited as the most common reason for persistent cast treatment, the data show the use of cast treatment to be more dependent upon individual provider preference.

Level of Evidence:

Level II—therapeutic.
Differentiation of Deep Venous Thrombosis Among Children With or Without Osteomyelitis
Authors: Ligon John A. , Journeycake Janna M. , Josephs Shellie C. , Tareen Naureen G. , Lindsay Eduardo A. , Copley Lawson A.B.
Published: August 2018

Background:

Children with osteomyelitis are at risk for deep venous thrombosis (DVT). This study evaluates the characteristics of DVT among children to differentiate between those with and without osteomyelitis.

Methods:

Children with DVT of any cause were studied between 2008 and 2016. Children with DVT and osteomyelitis were compared with those with DVT without osteomyelitis. Another comparison cohort included children with osteomyelitis but without DVT. Comorbidities, severity of illness (SOI), and clinical course were compared between cohorts.

Results:

DVT was identified in 224 children, a prevalence of 2.5 per 10,000 children. Among those with DVT, 28 (12.1%) had osteomyelitis. The DVT rate among 466 children with osteomyelitis was 6.0%. Children with osteomyelitis and DVT had greater SOI (9.1 vs. 2.7), bacteremia rate (82.1% vs. 38.4%), methicillin-resistant Staphylococcus aureus rate (89.3% vs. 21.2%), surgeries per child (2.1 vs. 0.7), and intensive care unit admission rate (67.9% vs. 5.9%) than that of children without DVT (P<0.00001). Of 196 children who had DVT without osteomyelitis, 166 (84.7%) had comorbidities including defined hypercoagulability (27 or 13.8%). Children with DVT due to osteomyelitis were without comorbidities or hypercoagulability (P<0.00001). The rate of pulmonary embolism was similar for children with DVT with or without osteomyelitis (3/28, or 10.7% vs. 18/196, or 9.2%).

Conclusions:

Children with DVT and osteomyelitis differ substantially from other children with DVT by the absence of comorbidities or post-thrombotic syndrome. They also differ from children with osteomyelitis without DVT by higher SOI, methicillin-resistant S. aureus rate, and occurrence of intensive care. Awareness of for the characteristics of DVT among children with osteomyelitis will reduce delay to diagnostic ultrasound and improve anticoagulation management which must be carefully coordinated given the high rate of surgery of these children.

Level of Evidence:

Level II—prognostic, retrospective cohort comparison.
Review: Proposed Methods to Improve the Survival of Adipose Tissue in Autologous Fat Grafting
Authors: Landau Mark J. , Birnbaum Zoe E. , Kurtz Lauren G. , Aronowitz Joel A.
Published: August 2018

In 2009, the American Society of Plastic Surgeons Task Force on Autologous Fat Grafting (AFG) determined that autologous fat grafting was a safe procedure with a relatively low rate of complications. This consensus opinion unleashed a wave of popularity as plastic surgeons discovered the procedures' efficacy in a wide variety of cosmetic and reconstructive indications. Frequently reported cosmetic applications include soft-tissue augmentation of breast, buttocks, hips, face, and hands, whereas reconstructive applications include adjunct for breast reconstruction contour problems, plantar fat pad improvement, and correction of various posttraumatic and surgical contour deformities. Recognition of other regenerative effects of fat grafting expanded the use AFG for improvement of hypertrophic scar tissue, postradiation sequelae, lipodystrophy, hyperpigmentation, senile skin changes, and actinic damage. The popularity of AFG is supported by a remarkably low risk of complications, minimal scars, and readily available donor sites. Despite recognition of the advantages of AFG, there still is no consensus regarding optimal techniques of harvest, graft preparation, and injection. Further, the yield of permanent volume falls within a very wide range. In this article, we review the basic science of fat grafting, proposed methods offered to improve engraftment, and reported outcomes of AFG procedures.
Hospital purchasing alliances: Ten years after
Authors: Burns Lawton R. , Briggs Allison D.
Published: August 2018

Background:

Most hospitals outsource supply procurement to purchasing alliances, or group purchasing organizations (GPOs). Despite their early 20th century origin, we lack both national and trend data on alliance utilization, services, and performance. The topic is important as alliances help hospitals control costs, enjoy tailwinds from affiliated regional/local alliances, and face headwinds from hospital self-contracting and criticism of certain business practices.

Purpose:

We compare the utilization, services, and performance of alliances in 2004 and 2014.

Approach:

We analyze alliances using two comparable surveys of hospitals. We use significance tests to assess changes in alliance utilization, services, and performance (e.g., cost savings). We also assess the use of regional/local alliances affiliated with national GPOs.

Results:

Purchasing through national alliances has somewhat diminished. Over 10 years, hospitals have diversified GPO memberships to include regional/local alliances (many affiliated with their national GPO) and engaged in self-contracting. At the same time, hospitals have increased purchases of many categories of supplies/services through national GPOs and endorsed their value-added functions and increasingly important role. Hospitals report greater satisfaction with several GPO functions; performance on most dimensions has not changed.

Conclusions:

National alliances still play important roles that hospitals find valuable.

Practice Implications:

Purchasing alliances continue to play an important role in helping hospitals with both cost savings and new services. Their growing complexity, along with growing use of self-contracting, poses managerial challenges for hospital purchasing staff that may require greater hospital investment.
How to make a job more than just a paycheck: Understanding physician disengagement
Authors: Yanchus Nancy J. , Carameli Kelley A. , Ramsel Dee , Osatuke Katerine
Published: August 2018

Background:

The benefits of physician engagement are numerous, including improved physician recruitment, retention, and leadership development—outcomes associated with substantial costs or potential savings for health care organizations. However, physician disengagement is a serious detriment, associated with poorer quality of patient care and higher turnover of clinical staff. Using a workforce census survey, we examined what makes physicians engaged or disengaged in their work at a large U.S. health care system.

Purpose:

This study expands our understanding of physician engagement and disengagement, states that impact patient care service delivery and care experiences.

Methodology/Approach:

We explain group differences using qualitative survey comments from 142 engaged and disengaged physicians, which we report with illustrative quotes and frequency counts of referenced themes.

Results:

Engaged physicians discussed positive interpersonal relationships as connected with seeing their work as meaningful. Disengaged physicians expressed concerns about out-of-touch executive leadership. Leadership played a role in psychological safety for both engaged and disengaged physicians: It was described as present and positive for the engaged group and absent for the disengaged group.

Conclusion:

There are commonalities and differences in the drivers of physician engagement and disengagement. Our results shed light on why physicians might withdraw from inherently meaningful work. These findings can inform organizational efforts toward decreasing physician disengagement and increasing and maintaining an engaged physician workforce.

Practice Implications:

To reduce physician disengagement, we recommend leadership development around key skills (i.e., visibility, transparency, accessibility). We also suggest that improving supervisors’ (e.g., clinical service chiefs’) knowledge about workflow processes, staffing needs, patient panel sizes, and administrative tasks carried by physicians could better balance physicians’ workload. Finally, human resource systems can help reduce disengagement by adjusting hiring and training processes to mitigate low staffing levels.
Unique Clinical Language Patterns Among Expert Vestibular Providers Can Predict Vestibular Diagnoses
Authors: Luo Jake , Erbe Christy , Friedland David R.
Published: August 2018

Objective:

To identify novel language usage by expert providers predictive of specific vestibular conditions.

Study Design:

Retrospective chart review and natural language processing. Level IV.

Setting:

Tertiary referral center.

Patients:

Patients seen for vestibular complaint.

Intervention(s):

Natural language processing and machine learning analyses of semantic and syntactic patterns in clinical documentation from vestibular patients.

Main Outcome Measure:

Accuracy of Naïve Bayes predictive models correlating language usage with clinical diagnoses.

Results:

Natural language analyses on 866 physician-generated histories from vestibular patients found 3,286 unique examples of language usage of which 614 were used 10 or greater times. The top 15 semantic types represented only 11% of all Unified Medical Language System semantic types but covered 86% of language used in vestibular patient histories. Naïve Bayes machine learning algorithms on a subset of 255 notes representing benign paroxysmal positional vertigo, vestibular migraine, anxiety-related dizziness and central dizziness generated strong predictive models showing an average sensitivity rate of 93.4% and a specificity rate of 98.2%. A binary model for assessing whether a subject had a specific diagnosis or not had an average AUC for the receiver operating characteristic curves of .995 across all conditions.

Conclusions:

These results indicate that expert providers utilize unique language patterns in vestibular notes that are highly conserved. These patterns have strong predictive power toward specific vestibular diagnoses. Such language elements can provide a simple vocabulary to aid nonexpert providers in formulating a differential diagnosis. They can also be incorporated into clinical decision support systems to facilitate accurate vestibular diagnosis in ambulatory settings.
INSM1 Is More Sensitive and Interpretable than Conventional Immunohistochemical Stains Used to Diagnose Merkel Cell Carcinoma
Authors: Lilo Mohammed T. , Chen Youdinghuan , LeBlanc Robert E.
Published: August 2018

Merkel cell carcinoma (MCC) is an extremely aggressive skin cancer that must be distinguished from other basaloid cutaneous neoplasms that have different treatments and prognoses. This is sometimes challenging in small shave specimens, crushed samples, lymph nodes, and core needle biopsies. Insulinoma-associated protein 1 (INSM1) immunohistochemistry is a sensitive nuclear marker of neuroendocrine differentiation. INSM1 staining was performed on 56 MCC (47 primary tumors, 9 nodal metastases), 50 skin control cases that included basal cell carcinomas, basaloid squamous cell carcinomas, Bowen disease, sebaceous neoplasms, melanoma, and B-cell lymphomas, and 28 lymph node control cases that included metastatic neuroendocrine neoplasms, melanomas, squamous cell carcinomas, lymphomas, and adenocarcinomas. Percent of staining nuclei (0, <25%, 25% to 50%, 50% to 75%, >75%) and intensity (weak, moderate, strong) were recorded for each sample. All 56 MCC expressed INSM1. By comparison, synaptophysin, CK20, and chromogranin were expressed in 96%, 92%, and 32% of MCC, respectively. While the 3 conventional markers showed significant variability in staining intensity and distribution, INSM1 stained >75% tumor nuclei in 89% of MCC and 50% to 75% of tumor nuclei in 11%. Staining intensity was strong in 85% and moderate in 15%. None of the 50 cutaneous basaloid non-MCC neoplasms in the control group stained with INSM1, and among the lymph node controls 5 of 5 neuroendocrine neoplasms expressed INSM1, confirming that INSM1 staining cannot distinguish MCC from metastatic extracutaneous neuroendocrine carcinoma. INSM1 holds promise as a neuroendocrine marker that can distinguish MCC from its mimickers in the skin and improve detection of sentinel lymph node metastases.
Concordance of “Case Level” Global, Highest, and Largest Volume Cancer Grade Group on Needle Biopsy Versus Grade Group on Radical Prostatectomy
Authors: Trpkov Kiril , Sangkhamanon Sakkarn , Yilmaz Asli , Medlicott Shaun A.C. , Donnelly Bryan , Gotto Geoffrey , Shea-Budgell Melissa
Published: August 2018

The practice of assigning “case level” biopsy Grade Group (GG) or Gleason Score is variable. To our knowledge, a comparison of the concordance of different biopsy “case level” GG with the prostatectomy GG has not been done in a post-2005 prostate cancer cohort. We evaluated the GG in 2527 patients who had biopsy and radical prostatectomy performed at our institution between 2005 and 2014. We compared the agreements, the upgrades, and the downgrades of 3 different “case level” biopsy GG, with the final GG: (1) Global GG (sum of most prevalent and highest Gleason grade in any biopsy part/site-specific specimen); (2) Highest GG (found in any biopsy part/site-specific specimen); and (3) Largest Volume Cancer GG (found in any biopsy part/site-specific specimen). The concordance between the biopsy and the final GG were evaluated using weighted kappa (κ) coefficient. The biopsy Global GG, Highest GG, and Largest Volume Cancer GG were the same as the final GG in 60.4%, 57.1%, and 54.3% cases, respectively (weighted κ values: 0.49, 0.48, and 0.44, respectively). When final GG contained tertiary 5, the overall GG agreement decreased: Global GG 41.5%, Highest GG 40.3%, and Largest Volume Cancer GG 37.1% (weighted κ: 0.22, 0.21, and 0.18, respectively). A subset analysis for cases in which the biopsy Global GG and Highest GG were different (n=180) showed an agreement of 62.4% (weighted κ: 0.37) and 18.8% (weighted κ: 0.16), respectively. In patients without a tertiary Gleason pattern on radical prostatectomy, the Global GG and the Highest GG were identical in 92.4% of biopsies. Assigning a biopsy “case level” Global GG versus using the Highest GG and the Largest Volume Cancer GG resulted in comparable and slightly improved agreement with the final GG in this cohort.
Integrating Palliative Care Into the ICU: From Core Competency to Consultative Expertise
Authors: Morrison Wynne E. , Gauvin France , Johnson Emily , Hwang Jennifer
Published: August 2018

Objectives:

To propose a model describing levels of integration of palliative care into the care of ICU patients.

Data Sources:

Literature review and author opinion.

Conclusions:

All critical care team members should demonstrate and foster their core competencies in caring for patients with complex illness and uncertain prognosis, including at the end of life. We describe these core competencies of the ICU team member as “primary” palliative care skills. Some ICU team members will have special expertise in end-of-life care or symptom management and decision-making support and will serve as local experts within the ICU team as a resource to other team members. We call this skillset “secondary” palliative care. Some patients will benefit from the full range of expertise provided by a separate consulting team, with additional training, focused on caring for patients with palliative care needs across the full spectrum of patient locations within a health system. We term the skillset provided by such outside consultants “tertiary” palliative care. Solutions for meeting patients’ palliative care needs will be unique within each system and individual institution, depending on available resources, history, and structures in place. Providers from multiple professions will usually contribute to meeting patient needs.
Death and Dying 1987–2017: The Destination Is the Same, the Journey Is Different
Authors: Cox Peter N.
Published: August 2018

Objective:

A personal reflection on the changing landscape with regard to case mix, care, and staffing and how mortality and expectations have evolved over the past 30 years in a multidisciplinary Pediatric Critical Care Unit in a Quaternary level academic institution in Canada.

Conclusions:

Many of the preventable deaths have been prevented with Public Health initiatives. Death now is increasingly in complex patients with complicated treatment regimes in a society that has increasingly unrealistic expectations of what modern medicine can do. Many of these complex children do not die but are dependent on our technology and skill set—something we are often ill prepared for.
Organ Donation Following Neurologic and Circulatory Determination of Death
Authors: Nakagawa Thomas A. , Shemie Sam D. , Dryden-Palmer Karen , Parshuram Christopher S. , Brierley Joe
Published: August 2018

Objectives:

To describe important considerations during the process of caring for critically ill children who may be potential organ donors and supporting the family during the death of their child.

Design:

Literature review and expert commentary.

Measurement and Main Results:

Medical literature focusing on pediatric donation, best pediatric donation practices, donor management, and factors influencing donation were reviewed. Additional pediatric data were obtained and reviewed from the U.S. Organ Procurement and Transplantation Network. Achieving successful organ donation requires the coordinated efforts of the critical care team, organ donation organization, and transplant team to effectively manage a potential donor and recover suitable organs for transplantation. Collaboration between these teams is essential to ensure that all potential organs are recovered in optimal condition, to reduce death and morbidity in children on transplantation waiting lists as well as fulfilling the family’s wishes for their dying child to become a donor.

Conclusions:

Organ donation is an important component of end-of-life care and can help the healing process for families and medical staff following the death of a child. The process of pediatric organ donation requires healthcare providers to actively work to preserve the option of donation before the death of the child and ensure donation occurs after consent/authorization has been obtained from the family. Medical management of the pediatric organ donor requires the expertise of a multidisciplinary medical team skilled in the unique needs of caring for children after neurologic determination of death and those who become donors following circulatory death after withdrawal of life-sustaining medical therapies.