bluuebunny/crossref_metadata_2025 huggingface dataset:
Ploidy Variation and Viability of Aneuploid Ornamental Koi Carp Obtained by Crossing Triploid Females with Diploid Males
Authors: Gomelsky Boris , Delomas Thomas A , Warner Jeffrey L
Published: June 2016

Results of crossing triploid females of ornamental koi, a variant of Common Carp Cyprinus carpio, with diploid koi males in two consecutive spawning seasons (2014 and 2015) are presented. A total of seven progenies from six triploid females (one female was spawned twice) were produced and analyzed. The same as normal diploid females, triploid females were highly fertile and produced hundreds of thousands of eggs (up to 400,000 per female). Processes of embryo incubation and hatching of larvae in progenies obtained from triploid females proceeded normally; however, mass mortality of hatched larvae occurred at the swim-up stage. Nevertheless about 200,000 swim-up larvae were obtained and stocked for further rearing. A total of about 1,000 juveniles (or 0.5% of the number of stocked larvae) was collected from outdoor tanks. As expected, all analyzed larvae and juveniles in control progenies obtained by crosses of diploid females with diploid males were diploid. About 95% of analyzed fish (larvae and juveniles) obtained by crossing triploid females with diploid males were aneuploids with ploidy ranging from 2.14n to 3.0n; mean values of fish ploidy in progenies obtained from different triploid females varied from 2.47n to 2.63n. Since aneuploid fish have in their genomes one haploid set from parental males, the data obtained indicate that triploid koi females produced aneuploid eggs with ploidy range from haploid to diploid level and a modal ploidy level around 1.5n, similar to the production of aneuploid spermatozoa observed earlier for triploid males in fish. About 5% of juveniles obtained from triploid females had ploidy range from 3.21n to 4.0n. Apparently these fish resulted from spontaneous suppression of the second meiotic division in aneuploid eggs.
Effects of Initial Feed Timing on Early Survival and Growth of Triploid Hatchery Rainbow Trout
Authors: Gunter Beau J , Grant Bryan L
Published: June 2016

The timing of initial feeding for trout fry varies greatly among hatchery professionals and may affect early survival and growth. The purpose of this study was to determine if there is a number of days posthatch to begin feeding triploid hatchery Rainbow Trout Oncorhynchus mykiss where they will experience the least mortality and most favorable growth rates. Treatment groups of triploid Rainbow Trout fry were fed for 30 d with initial feeding times of 13, 15, 17, 19, 21, and 25 d posthatch on 12.2°C water. Variations in survival, condition factor, size, and feed conversions between initial feed times were evaluated. The number of days posthatch prior to initial feeding did not have a significant impact on survival. The growth parameters measured showed significant variation depending on days posthatch prior to initial feeding, with the most favorable growth parameters found at 21 and 25 d posthatch.
Structural Complexity Improves the Rearing Performance of Rainbow Trout in Circular Tanks
Authors: Kientz Jeremy L , Barnes Michael E
Published: June 2016

While structural complexity has been used extensively during hatchery rearing in an attempt to improve poststocking survival, the potential impact of this complexity on hatchery rearing performance has largely been ignored. This study examined the growth and condition of juvenile Rainbow Trout Oncorhynchus mykiss reared in nearly fully covered circular tanks containing nine vertically oriented round aluminum rods (structurally complex) compared with that of trout reared in almost fully covered tanks with no rods (control) at two water velocities (2.0 body length (BL)/s and 2.75 BL/s). After 51 days, total tank weight gain was significantly higher in the structurally complex tanks than in the control tanks, regardless of water velocity. The feed conversion ratio was also significantly better in the structurally complex tanks [mean (SD) 1.25 (0.10)] than in the control tanks [1.66 (0.41)]. There were no significant differences in hepatosomatic index, splenosomatic index, and viscerosomatic index between the fish from the structurally complex and the control tanks. Total tank weight gain was significantly higher and the feed conversion ratio significantly lower in the lower water velocity tanks than in the higher water velocity tanks. These results indicate that vertically oriented aluminum rods can be used to increase structural complexity and improve Rainbow Trout rearing performance in circular rearing tanks, with minimal effects on regular tank cleaning.
Evaluation of Dietary Lipid Sources for the Juvenile Lost River Sucker
Authors: Twibell Ronald G , Barron James M , Gannam Ann L
Published: June 2016

The establishment of a propagation program is among the recommended actions of the U.S. Fish and Wildlife Service recovery plan for the endangered Lost River Sucker Deltistes luxatus. As an initial step in diet development, a feeding trial was conducted to identify appropriate dietary lipid sources to feed juvenile Lost River Suckers at a rate of 0.47 g/fish. Six dietary treatments were produced by adding the following to a basal diet: (1) marine fish oil (Fish) as a control, (2) flaxseed oil (Flax), (3) soybean oil (Soy), or a 1:1 mixture of (4) fish and flax oil (Fish/Flax), (5) fish and soy oil (Fish/Soy), or (6) flax and soy oil (Flax/Soy). At the conclusion of the feeding trial weight gain of fish fed the control diet (Fish) was not significantly different than that of fish fed the other dietary treatments. However, weight gain of fish fed Soy was significantly higher than that of fish fed Fish/Flax. Whole-body lipid was significantly higher in fish fed Soy than in fish fed Fish, Flax, Fish/Flax, or Fish/Soy, but not significantly different than that in fish fed Flax/Soy. Generally, whole body fatty acid profiles reflected the fatty acid profiles of their respective dietary treatments. These results suggest soybean oil is an appropriate dietary lipid source for the Lost River Sucker, but more research on quantitative dietary requirements is needed for successful propagation of this species.
How to assess the efficiency of synchronization experiments in tokamaks
Authors: Murari A. , Craciunescu T. , Peluso E. , Gelfusa M. , Lungaroni M. , Garzotti L. , Frigione D. , Gaudio P.
Published: June 2016

Control of instabilities such as ELMs and sawteeth is considered an important ingredient in the development of reactor-relevant scenarios. Various forms of ELM pacing have been tried in the past to influence their behavior using external perturbations. One of the main problems with these synchronization experiments resides in the fact that ELMs are periodic or quasi-periodic in nature. Therefore, after any pulsed perturbation, if one waits long enough, an ELM is always bound to occur. To evaluate the effectiveness of ELM pacing techniques, it is crucial to determine an appropriate interval over which they can have a real influence and an effective triggering capability. In this paper, three independent statistical methods are described to address this issue: Granger causality, transfer entropy and recurrence plots. The obtained results for JET with the ITER-like wall (ILW) indicate that the proposed techniques agree very well and provide much better estimates than the traditional heuristic criteria reported in the literature. Moreover, their combined use allows for the improvement of the time resolution of the assessment and determination of the efficiency of the pellet triggering in different phases of the same discharge. Therefore, the developed methods can be used to provide a quantitative and statistically robust estimate of the triggering efficiency of ELM pacing under realistic experimental conditions.
The visual angle metric and quasiregular maps
Authors: Wang Gendi , Vuorinen Matti
Published: June 2016

The distortion of distances between points under maps is studied. We first prove a Schwarz-type lemma for quasiregular maps of the unit disk involving the visual angle metric. Then we investigate conversely the quasiconformality of a bilipschitz map with respect to the visual angle metric on convex domains. For the unit ball or half space, we prove that a bilipschitz map with respect to the visual angle metric is also bilipschitz with respect to the hyperbolic metric. We also obtain various inequalities relating the visual angle metric to other metrics such as the distance ratio metric and the quasihyperbolic metric.
Weak Gibbs measures as Gibbs measures for asymptotically additive sequences
Authors: Iommi Godofredo , Yayama Yuki
Published: June 2016

In this note we prove that every weak Gibbs measure for an asymptotically additive sequence is a Gibbs measure for another asymptotically additive sequence. In particular, a weak Gibbs measure for a continuous potential is a Gibbs measure for an asymptotically additive sequence. This allows us, for example, to apply recent results on dimension theory of asymptotically additive sequences to study multifractal analysis for weak Gibbs measure for continuous potentials.
Classifying and segmenting microscopy images with deep multiple instance learning
Authors: Kraus Oren Z. , Ba Jimmy Lei , Frey Brendan J.
Published: June 2016

Motivation : High-content screening (HCS) technologies have enabled large scale imaging experiments for studying cell biology and for drug screening. These systems produce hundreds of thousands of microscopy images per day and their utility depends on automated image analysis. Recently, deep learning approaches that learn feature representations directly from pixel intensity values have dominated object recognition challenges. These tasks typically have a single centered object per image and existing models are not directly applicable to microscopy datasets. Here we develop an approach that combines deep convolutional neural networks (CNNs) with multiple instance learning (MIL) in order to classify and segment microscopy images using only whole image level annotations.

Results : We introduce a new neural network architecture that uses MIL to simultaneously classify and segment microscopy images with populations of cells. We base our approach on the similarity between the aggregation function used in MIL and pooling layers used in CNNs. To facilitate aggregating across large numbers of instances in CNN feature maps we present the Noisy-AND pooling function, a new MIL operator that is robust to outliers. Combining CNNs with MIL enables training CNNs using whole microscopy images with image level labels. We show that training end-to-end MIL CNNs outperforms several previous methods on both mammalian and yeast datasets without requiring any segmentation steps.

Availability and implementation : Torch7 implementation available upon request.

Contact : oren.kraus@mail.utoronto.ca
Reconstructing the temporal progression of HIV-1 immune response pathways
Authors: Jain Siddhartha , Arrais Joel , Venkatachari Narasimhan J. , Ayyavoo Velpandi , Bar-Joseph Ziv
Published: June 2016

Motivation: Most methods for reconstructing response networks from high throughput data generate static models which cannot distinguish between early and late response stages.

Results: We present TimePath, a new method that integrates time series and static datasets to reconstruct dynamic models of host response to stimulus. TimePath uses an Integer Programming formulation to select a subset of pathways that, together, explain the observed dynamic responses. Applying TimePath to study human response to HIV-1 led to accurate reconstruction of several known regulatory and signaling pathways and to novel mechanistic insights. We experimentally validated several of TimePaths’ predictions highlighting the usefulness of temporal models.

Availability and Implementation: Data, Supplementary text and the TimePath software are available from http://sb.cs.cmu.edu/timepath

Contact:  zivbj@cs.cmu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
phRAIDER: Pattern-Hunter based Rapid Ab Initio Detection of Elementary Repeats
Authors: Schaeffer Carly E. , Figueroa Nathaniel D. , Liu Xiaolin , Karro John E.
Published: June 2016

Motivation : Transposable elements (TEs) and repetitive DNA make up a sizable fraction of Eukaryotic genomes, and their annotation is crucial to the study of the structure, organization, and evolution of any newly sequenced genome. Although RepeatMasker and nHMMER are useful for identifying these repeats, they require a pre-compiled repeat library—which is not always available. De novo identification tools such as Recon, RepeatScout or RepeatGluer serve to identify TEs purely from sequence content, but are either limited by runtimes that prohibit whole-genome use or degrade in quality in the presence of substitutions that disrupt the sequence patterns.

Results : phRAIDER is a de novo TE identification tool that address the issues of excessive runtime without sacrificing sensitivity as compared to competing tools. The underlying model is a new definition of elementary repeats that incorporates the PatternHunter spaced seed model, allowing for greater sensitivity in the presence of genomic substitutions. As compared with the premier tool in the literature, RepeatScout, phRAIDER shows an average 10× speedup on any single human chromosome and has the ability to process the whole human genome in just over three hours. Here we discuss the tool, the theoretical model underlying the tool, and the results demonstrating its effectiveness.

Availability and implementation : phRAIDER is an open source tool available from https://github.com/karroje/phRAIDER .

Contact : karroje@miamiOH.edu or

Supplementary information:  Supplementary data are available at Bioinformatics online.
Ensemble-based evaluation for protein structure models
Authors: Jamroz Michal , Kolinski Andrzej , Kihara Daisuke
Published: June 2016

Motivation: Comparing protein tertiary structures is a fundamental procedure in structural biology and protein bioinformatics. Structure comparison is important particularly for evaluating computational protein structure models. Most of the model structure evaluation methods perform rigid body superimposition of a structure model to its crystal structure and measure the difference of the corresponding residue or atom positions between them. However, these methods neglect intrinsic flexibility of proteins by treating the native structure as a rigid molecule. Because different parts of proteins have different levels of flexibility, for example, exposed loop regions are usually more flexible than the core region of a protein structure, disagreement of a model to the native needs to be evaluated differently depending on the flexibility of residues in a protein.

Results: We propose a score named FlexScore for comparing protein structures that consider flexibility of each residue in the native state of proteins. Flexibility information may be extracted from experiments such as NMR or molecular dynamics simulation. FlexScore considers an ensemble of conformations of a protein described as a multivariate Gaussian distribution of atomic displacements and compares a query computational model with the ensemble. We compare FlexScore with other commonly used structure similarity scores over various examples. FlexScore agrees with experts’ intuitive assessment of computational models and provides information of practical usefulness of models.

Availability and implementation:  https://bitbucket.org/mjamroz/flexscore

Contact:  dkihara@purdue.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
deBWT: parallel construction of Burrows–Wheeler Transform for large collection of genomes with de Bruijn-branch encoding
Authors: Liu Bo , Zhu Dixian , Wang Yadong
Published: June 2016

Motivation : With the development of high-throughput sequencing, the number of assembled genomes continues to rise. It is critical to well organize and index many assembled genomes to promote future genomics studies. Burrows–Wheeler Transform (BWT) is an important data structure of genome indexing, which has many fundamental applications; however, it is still non-trivial to construct BWT for large collection of genomes, especially for highly similar or repetitive genomes. Moreover, the state-of-the-art approaches cannot well support scalable parallel computing owing to their incremental nature, which is a bottleneck to use modern computers to accelerate BWT construction.

Results : We propose de Bruijn branch-based BWT constructor (deBWT), a novel parallel BWT construction approach. DeBWT innovatively represents and organizes the suffixes of input sequence with a novel data structure, de Bruijn branch encoding. This data structure takes the advantage of de Bruijn graph to facilitate the comparison between the suffixes with long common prefix, which breaks the bottleneck of the BWT construction of repetitive genomic sequences. Meanwhile, deBWT also uses the structure of de Bruijn graph for reducing unnecessary comparisons between suffixes. The benchmarking suggests that, deBWT is efficient and scalable to construct BWT for large dataset by parallel computing. It is well-suited to index many genomes, such as a collection of individual human genomes, with multiple-core servers or clusters.

Availability and implementation : deBWT is implemented in C language, the source code is available at https://github.com/hitbc/deBWT or https://github.com/DixianZhu/deBWT

Contact: ydwang@hit.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
Linear effects models of signaling pathways from combinatorial perturbation data
Authors: Szczurek Ewa , Beerenwinkel Niko
Published: June 2016

Motivation: Perturbations constitute the central means to study signaling pathways. Interrupting components of the pathway and analyzing observed effects of those interruptions can give insight into unknown connections within the signaling pathway itself, as well as the link from the pathway to the effects. Different pathway components may have different individual contributions to the measured perturbation effects, such as gene expression changes. Those effects will be observed in combination when the pathway components are perturbed. Extant approaches focus either on the reconstruction of pathway structure or on resolving how the pathway components control the downstream effects.

Results: Here, we propose a linear effects model, which can be applied to solve both these problems from combinatorial perturbation data. We use simulated data to demonstrate the accuracy of learning the pathway structure as well as estimation of the individual contributions of pathway components to the perturbation effects. The practical utility of our approach is illustrated by an application to perturbations of the mitogen-activated protein kinase pathway in Saccharomyces cerevisiae .

Availability and Implementation: lem is available as a R package at http://www.mimuw.edu.pl/∼szczurek/lem .

Contact:  szczurek@mimuw.edu.pl ; niko.beerenwinkel@bsse.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
Using genomic annotations increases statistical power to detect eGenes
Authors: Duong Dat , Zou Jennifer , Hormozdiari Farhad , Sul Jae Hoon , Ernst Jason , Han Buhm , Eskin Eleazar
Published: June 2016

Motivation: Expression quantitative trait loci (eQTLs) are genetic variants that affect gene expression. In eQTL studies, one important task is to find eGenes or genes whose expressions are associated with at least one eQTL. The standard statistical method to determine whether a gene is an eGene requires association testing at all nearby variants and the permutation test to correct for multiple testing. The standard method however does not consider genomic annotation of the variants. In practice, variants near gene transcription start sites (TSSs) or certain histone modifications are likely to regulate gene expression. In this article, we introduce a novel eGene detection method that considers this empirical evidence and thereby increases the statistical power.

Results: We applied our method to the liver Genotype-Tissue Expression (GTEx) data using distance from TSSs, DNase hypersensitivity sites, and six histone modifications as the genomic annotations for the variants. Each of these annotations helped us detected more candidate eGenes. Distance from TSS appears to be the most important annotation; specifically, using this annotation, our method discovered 50% more candidate eGenes than the standard permutation method.

Contact:  buhm.han@amc.seoul.kr or eeskin@cs.ucla.edu
Data-driven mechanistic analysis method to reveal dynamically evolving regulatory networks
Authors: Intosalmi Jukka , Nousiainen Kari , Ahlfors Helena , Lähdesmäki Harri
Published: June 2016

Motivation: Mechanistic models based on ordinary differential equations provide powerful and accurate means to describe the dynamics of molecular machinery which orchestrates gene regulation. When combined with appropriate statistical techniques, mechanistic models can be calibrated using experimental data and, in many cases, also the model structure can be inferred from time–course measurements. However, existing mechanistic models are limited in the sense that they rely on the assumption of static network structure and cannot be applied when transient phenomena affect, or rewire, the network structure. In the context of gene regulatory network inference, network rewiring results from the net impact of possible unobserved transient phenomena such as changes in signaling pathway activities or epigenome, which are generally difficult, but important, to account for.

Results: We introduce a novel method that can be used to infer dynamically evolving regulatory networks from time–course data. Our method is based on the notion that all mechanistic ordinary differential equation models can be coupled with a latent process that approximates the network structure rewiring process. We illustrate the performance of the method using simulated data and, further, we apply the method to study the regulatory interactions during T helper 17 (Th17) cell differentiation using time–course RNA sequencing data. The computational experiments with the real data show that our method is capable of capturing the experimentally verified rewiring effects of the core Th17 regulatory network. We predict Th17 lineage specific subnetworks that are activated sequentially and control the differentiation process in an overlapping manner.

Availability and Implementation: An implementation of the method is available at http://research.ics.aalto.fi/csb/software/lem/ .

Contacts:  jukka.intosalmi@aalto.fi or harri.lahdesmaki@aalto.fi
Read-based phasing of related individuals
Authors: Garg Shilpa , Martin Marcel , Marschall Tobias
Published: June 2016

Motivation: Read-based phasing deduces the haplotypes of an individual from sequencing reads that cover multiple variants, while genetic phasing takes only genotypes as input and applies the rules of Mendelian inheritance to infer haplotypes within a pedigree of individuals. Combining both into an approach that uses these two independent sources of information—reads and pedigree—has the potential to deliver results better than each individually.

Results: We provide a theoretical framework combining read-based phasing with genetic haplotyping, and describe a fixed-parameter algorithm and its implementation for finding an optimal solution. We show that leveraging reads of related individuals jointly in this way yields more phased variants and at a higher accuracy than when phased separately, both in simulated and real data. Coverages as low as 2× for each member of a trio yield haplotypes that are as accurate as when analyzed separately at 15× coverage per individual.

Availability and Implementation:  https://bitbucket.org/whatshap/whatshap

Contact:  t.marschall@mpi-inf.mpg.de
Compacting de Bruijn graphs from sequencing data quickly and in low memory
Authors: Chikhi Rayan , Limasset Antoine , Medvedev Paul
Published: June 2016

Motivation : As the quantity of data per sequencing experiment increases, the challenges of fragment assembly are becoming increasingly computational. The de Bruijn graph is a widely used data structure in fragment assembly algorithms, used to represent the information from a set of reads. Compaction is an important data reduction step in most de Bruijn graph based algorithms where long simple paths are compacted into single vertices. Compaction has recently become the bottleneck in assembly pipelines, and improving its running time and memory usage is an important problem.

Results : We present an algorithm and a tool bcalm 2 for the compaction of de Bruijn graphs. bcalm 2 is a parallel algorithm that distributes the input based on a minimizer hashing technique, allowing for good balance of memory usage throughout its execution. For human sequencing data, bcalm 2 reduces the computational burden of compacting the de Bruijn graph to roughly an hour and 3 GB of memory. We also applied bcalm 2 to the 22 Gbp loblolly pine and 20 Gbp white spruce sequencing datasets. Compacted graphs were constructed from raw reads in less than 2 days and 40 GB of memory on a single machine. Hence, bcalm 2 is at least an order of magnitude more efficient than other available methods.

Availability and Implementation : Source code of bcalm 2 is freely available at: https://github.com/GATB/bcalm

Contact:  rayan.chikhi@univ-lille1.fr
Analysis of differential splicing suggests different modes of short-term splicing regulation
Authors: Topa Hande , Honkela Antti
Published: June 2016

Motivation: Alternative splicing is an important mechanism in which the regions of pre-mRNAs are differentially joined in order to form different transcript isoforms. Alternative splicing is involved in the regulation of normal physiological functions but also linked to the development of diseases such as cancer. We analyse differential expression and splicing using RNA-sequencing time series in three different settings: overall gene expression levels, absolute transcript expression levels and relative transcript expression levels.

Results: Using estrogen receptor α signaling response as a model system, our Gaussian process-based test identifies genes with differential splicing and/or differentially expressed transcripts. We discover genes with consistent changes in alternative splicing independent of changes in absolute expression and genes where some transcripts change whereas others stay constant in absolute level. The results suggest classes of genes with different modes of alternative splicing regulation during the experiment.

Availability and Implementation: R and Matlab codes implementing the method are available at https://github.com/PROBIC/diffsplicing . An interactive browser for viewing all model fits is available at http://users.ics.aalto.fi/hande/splicingGP/

Contact:  hande.topa@helsinki.fi or antti.honkela@helsinki.fi

Supplementary information:  Supplementary data are available at Bioinformatics online.
Creating a scalable clinical pharmacogenomics service with automated interpretation and medical record result integration – experience from a pediatric tertiary care facility
Authors: Manzi Shannon F , Fusaro Vincent A , Chadwick Laura , Brownstein Catherine , Clinton Catherine , Mandl Kenneth D , Wolf Wendy A , Hawkins Jared B
Published: June 2016

Objective: This paper outlines the implementation of a comprehensive clinical pharmacogenomics (PGx) service within a pediatric teaching hospital and the integration of clinical decision support in the electronic health record (EHR).

Materials and Methods: An approach to clinical decision support for medication ordering and dispensing driven by documented PGx variant status in an EHR is described. A web-based platform was created to automatically generate a clinical report from either raw assay results or specified diplotypes, able to parse and combine haplotypes into an interpretation for each individual and compared to the reference lab call for accuracy.

Results: Clinical decision support rules built within an EHR provided guidance to providers for 31 patients (100%) who had actionable PGx variants and were written for interacting medications. A breakdown of the PGx alerts by practitioner service, and alert response for the initial cohort of patients tested is described. In 90% (355/394) of the cases, thiopurine methyltranferase genotyping was ordered pre-emptively.

Discussion: This paper outlines one approach to implementing a clinical PGx service in a pediatric teaching hospital that cares for a heterogeneous patient population. There is a focus on incorporation of PGx clinical decision support rules and a program to standardize report text within the electronic health record with subsequent exploration of clinician behavior in response to the alerts.

Conclusion: The incorporation of PGx data at the time of prescribing and dispensing, if done correctly, has the potential to impact the incidence of adverse drug events, a significant cause of morbidity and mortality.
Electronic tools to support medication reconciliation: a systematic review
Authors: Marien Sophie , Krug Bruno , Spinewine Anne
Published: June 2016

Objectives: Medication reconciliation (MedRec) is essential for reducing patient harm caused by medication discrepancies across care transitions. Electronic support has been described as a promising approach to moving MedRec forward. We systematically reviewed the evidence about electronic tools that support MedRec, by (a) identifying tools; (b) summarizing their characteristics with regard to context, tool, implementation, and evaluation; and (c) summarizing key messages for successful development and implementation.

Materials and Methods: We searched PubMed, the Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, and the Cochrane Library, and identified additional reports from reference lists, reviews, and patent databases. Reports were included if the electronic tool supported medication history taking and the identification and resolution of medication discrepancies. Two researchers independently selected studies, evaluated the quality of reporting, and extracted data.

Results: Eighteen reports relative to 11 tools were included. There were eight quality improvement projects, five observational effectiveness studies, three randomized controlled trials (RCTs) or RCT protocols (ie, descriptions of RCTs in progress), and two patents. All tools were developed in academic environments in North America. Most used electronic data from multiple sources and partially implemented functionalities considered to be important. Relevant information on functionalities and implementation features was frequently missing. Evaluations mainly focused on usability, adherence, and user satisfaction. One RCT evaluated the effect on potential adverse drug events.

Conclusion: Successful implementation of electronic tools to support MedRec requires favorable context, properly designed tools, and attention to implementation features. Future research is needed to evaluate the effect of these tools on the quality and safety of healthcare.
A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2
Authors: Diaz-Gil Daniel , Haerter Friederike , Falcinelli Shane , Ganapati Shweta , Hettiarachchi Gaya K. , Simons Jeroen C. P. , Zhang Ben , Grabitz Stephanie D. , Moreno Duarte Ingrid , Cotten Joseph F. , Eikermann-Haerter Katharina , Deng Hao , Chamberlin Nancy L. , Isaacs Lyle , Briken Volker , Eikermann Matthias
Published: June 2016

Background

Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery.

Methods

To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity.

Results

Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium–based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-à-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16:1 (95% CI, 10 to 26:1) for the reversal of ketamine and 3:1 (95% CI, 2 to 5:1) for the reversal of etomidate.

Conclusions

Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.
Contrast MRI Findings for Spinal Schwannoma as Predictors of Tumor Proliferation and Motor Status
Authors: Kobayashi Kazuyoshi , Imagama Shiro , Ando Kei , Hida Tetsuro , Ito Kenyu , Tsushima Mikito , Ishikawa Yoshimoto , Matsumoto Akiyuki , Morozumi Masayoshi , Tanaka Satoshi , Ishiguro Naoki
Published: June 2016

Study Design.

Retrospective analysis.

Objective.

The goal of this study was to examine the relationship of the proliferation potency based on the MIB-1 index and motor status with features of T2-weighted images (T2WI) and contrast T1-weighted images (T1WI) of spinal schwannoma.

Summary of Background Data.

Spinal schwannomas account for 55% of spinal tumors, but the relationship of cellular proliferation with MRI findings for spinal schwannoma is unknown.

Methods.

The subjects were 48 patients (22 males and 26 females) with spinal schwannoma who were classified into three subgroups: iso/homo, high/rim, and hetero/hetero, based on T2WI/contrast T1WI. A retrospective analysis of tumor size and MIB-1 index was performed in the context of these MRI findings. Intraoperative findings and pre- and postoperative motor performance were also examined.

Results.

The average tumor size was 32.4 mm (range 10–130 mm) and the average MIB-1 index was 3.8% (range 1–12). In the three subgroups, there were no significant differences in sex, age, duration of disease, tumor lesion, and dumbbell type. In the hetero/hetero group, the tumor size was significantly greater and the MIB-1 index was significantly higher (both P < 0.05), than the other two groups. The tumor adherence rate was significantly higher for hetero tumors (P < 0.05) and preoperative paralysis was more common in cases with tumor adhesion. The rate of paralysis improvement at 1 month was significantly lower for hetero tumors, but all cases had improved at 6 months.

Conclusion.

Contrast T1WI MRI was useful for prediction of the proliferative activity and growth of spinal schwannomas, which are associated with increased tumor size and adhesion. A heterogeneous pattern on contrast T1WI indicated an increase in size and adhesion of the tumor. This pattern reflected the preoperative motor status and postoperative motor recovery.

Level of Evidence: 4
Intrathecal Versus Intravenous Morphine in Minimally Invasive Posterior Lumbar Fusion
Authors: Araimo Morselli Fabio Silvio Mario , Zuccarini Francesco , Caporlingua Federico , Scarpa Ilaria , Imperiale Carmela , Caporlingua Alessandro , De Biase Lorenzo , Tordiglione Paolo
Published: June 2016

Study Design.

A blinded, randomized, comparative prospective study.

Objective.

The aim of this study was to compare the use of intrathecal morphine to endovenous morphine on postoperative pain after posterior lumbar surgery.

Summary of Background Data.

Intrathecal morphine can provide significant safe analgesia for at least 12 hours and up to 24 hours in patients undergoing major surgery. Its dosages have been decreasing in the last 30 years, but currently, the optimal dose remains unknown. As of today, there are no studies comparing the efficacy and the side effects of this technique with intravenous morphine administration after minimally invasive lumbar fusion surgery.

Methods.

We randomized and compared two groups of 25 patients, who were given either 100 μg intrathecal (ITM group) or 5 ± 2 mg intravenous morphine delivered intravenously for 24 hours at 2 mL/h (IVM group) after minimally invasive posterior lumbar fusion. VAS score at 0, 6, 12, 24 hours, mobilization out of bed at 6 hours, hospitalization duration and complications as lower limbs paresthesia, urinary retention at 6 and 12 hours, nausea, vomit, itch, and constipation were evaluated.

Results.

Data showed a lower VAS score, a reduction of constipation, lower limbs paresthesia, or urinary retention at 12 hours in ITM rather than in the IVM group. None suffered of vomit, itch, or nausea in both groups. Urinary retention was observed more frequently in ITM group at 6 hours. Patients of ITM group were mobilized out bed earlier than those from IVM group.

Conclusion.

A low dosage of intrathecal morphine is safe and effective after minimally invasive lumbar fusion surgery. The reduction of pain in the study group permitted a shorter hospitalization and earlier mobilization out of bed, augmenting patients’ comfort.

Level of Evidence: 2
Epidemiology of Deep Surgical Site Infections After Pediatric Spinal Fusion Surgery
Authors: Warner Stephen J. , Uppstrom Tyler J. , Miller Andy O. , O’Brien Sean T. , Salvatore Christine M. , Widmann Roger F. , Perlman Stephanie L.
Published: June 2016

Study Design.

Single-institution, retrospective case series.

Objective.

To determine whether the microbiology of deep surgical site infections (SSIs) after spinal fusion surgery for deformity has changed over the last decade at our institution.

Summary of Background Data.

SSI after pediatric spinal deformity surgery results in significantly increased patient morbidity and health care costs. Although risk factors are multifactorial, prophylactic and treatment antibiotic coverage is based in part on historical epidemiologic data, which may evolve over time.

Methods.

This study represents a retrospective review of clinical and microbiology records of patients less than 21 years old who underwent spinal deformity surgery at a single institution between 2000 and 2012. Patients were included who underwent index surgery at our institution and developed a deep SSI. Patients with growth-preserving spine constructs were excluded.

Results.

The overall incidence of deep SSI was 3.6% (39/1094). The incidence of deep SSI following primary surgery was 3.3% (34/1034) and 8.3% (5/60) following revision surgery. The incidence of deep SSI varied by primary diagnosis: idiopathic (1.0%), neuromuscular (14.3%), syndromic (5.3%), congenital (5.7%), and kyphosis (0.0%). The most common inciting pathogens wereStaphylococcus epidermidis(26%), methicillin-sensitiveStaphylococcus aureus(MSSA, 18%),Propionibacterium acnes(P. acnes; 18%), andEscherichia coli(18%). Sixteen of the 18 (89%) gram-negative infections occurred in neuromuscular patients (P = 0.006). Between 2000 and 2006 and between 2007 and 2012, MSSA occurred in 2/18 (11%) and 5/21 (24%) of cases (P = 0.41), methicillin-resistantS. aureusoccurred in 1/18 (6%) and 3/21 (14%) (P = 0.61), andP. acnesoccurred in 3/18 (17%) and 4/21 (19%) (P = 1.0).

Conclusion.

The epidemiology of deep SSI following spinal fusion for deformity in pediatric patients at our institution has not changed significantly during 13 years. Prophylactic antibiotic coverage for both gram-positive and gram-negative organisms may be indicated for patients with primary neuromuscular diagnoses.

Level of Evidence:4
Jiangsu Four Cancers Study: a large case–control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China
Authors: Zhao Jin-Kou , Wu Ming , Kim Claire H. , Jin Zi-Yi , Zhou Jin-Yi , Han Ren-Qiang , Yang Jie , Zhang Xiao-Feng , Wang Xu-Shan , Liu Ai-Ming , Gu Xiaoping , Su Ming , Hu Xu , Sun Zheng , Li Gang , Li Liming , Mu Lina , Zhang Zuo-Feng
Published: June 2016

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case–control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case–control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.
Competing risks survival of older patients with metastatic cutaneous melanoma: a SEER population-based study
Authors: Hoag Jessica R. , Hegde Upendra , Zweifler Rebecca , Berwick Marianne , Swede Helen
Published: June 2016

Mortality from metastatic cutaneous melanoma is substantially heterogeneous as reflected in three distant metastatic (M1) subtypes with metastasis to skin, subcutaneous tissue, or distant lymph nodes (M1a), conferring nearly half the risk of death compared with distant visceral metastasis (M1c). It remains unknown whether older patients experience the survival benefit from the M1a subtype given a higher overall mortality risk. Surveillance, Epidemiology, and End Result data were retrieved from 1878 metastatic melanoma patients, from 2005 to 2009, with follow-up through 2011. Hazard ratios (HRs) for 2-year overall survival were estimated for M1 subtypes among older (≥65) and younger (<65) patients. Proportional subdistribution hazard ratios (SHRs) were calculated for melanoma-specific and competing risk mortality. For both older and younger patients, worse overall survival was observed for the M1c compared to the M1a subtype [HR: 2.65, 95% confidence interval (CI): 2.02–3.49; and, SHR: 3.36, 95% CI: 2.56–4.41; respectively]. For competing mortality, older compared to younger patients had increased risk in the M1a and M1b subtypes (SHR: 6.07, 95% CI: 1.94–19.0, and SHR: 2.34, 95% CI: 1.08–5.05, respectively). Conversely, when examining melanoma-specific mortality, older patients had decreased risk in M1a and M1b subtypes (SHR: 0.28, 95% CI: 0.14–0.53, and SHR: 0.60, 95% CI: 0.38–0.94, respectively) compared to those under 65 years. The persistent prognostic advantage of M1a among older patients should be considered when calculating the risk–benefit ratio for treatment. Prior reports of a protective effect of older age on melanoma-specific mortality, when based on traditional competing risks analyses, might be explained as an artifact of increased competing mortality risk.
Robotic-Assisted Upper Face Rejuvenation
Authors: Rybakin Arthur V. , Borovikov Alexei M. , Manturova Natalia E. , Gladyshev Dmitriy V. , Kamalov David M. , Shcherbakov Kirill G. , Staisupov Valeriy J. , Kuzin Danila A.
Published: June 2016

Robotic-assisted technology has not been used in aesthetic surgery so far. The authors examined the feasibility and potential advantages of robotic-assisted technology in upper face rejuvenation surgery, as well as utility of the tools available in the market. Forehead lift was performed along with blepharoplasty in 4 patients. Robotic da Vinci Surgical System (Intuitive Surgical, Inc.) was used at the stage of dissection. The stereo endoscope 30 degrees, 12 mm and later 8.5 mm in diameter, and the set of tools, 8 mm and later 5 mm in diameter, were used. Overall results appeared to be essentially the same as after usual endoscope-assisted brow lift. The advantages of the robotic-assisted surgery were as follows: the best possible display, scalability of the picture; lack of tremor, scalability of the movements’ amplitude; high degree of freedom of movements exceeding human capabilities; quick and easy switch between the endoscope and any of the 3 manipulating arms; and enhanced comfort for a surgeon. The drawbacks noted were as follows: cost, steep learning curve, lack of tactile feedback, and absence of instruments specially adjusted for aesthetic surgery. The authors conclude that robots will enter the field of aesthetic plastic surgery in the same way as endoscopy, the proviso being to adjust tools to the specific needs.
Aligning for accountable care
Authors: Hilligoss Brian , Song Paula H. , McAlearney Ann Scheck
Published: June 2016

Background:

Alignment within accountable care organizations (ACOs) is crucial if these new entities are to achieve their lofty goals. However, the concept of alignment remains underexamined, and we know little about the work entailed in creating alignment.

Purpose:

The aim of this study was to develop the concept of aligning by identifying and describing the strategic practices administrators use to align the structures, processes, and behaviors of their organizations and individual providers in pursuit of accountable care.

Approach:

We conducted 2-year qualitative case studies of four ACOs that have assumed full risk for the costs and quality of care for defined populations.

Findings:

Five strategic aligning practices were used by all four ACOs. Informing both aligns providers’ understandings with the goals and value proposition of the ACO and aligns the providers’ attention with the drivers of performance. Involving both aligns ACO leaders’ understandings with the realities facing providers and aligns the policies of the ACO with the needs of providers. Enhancing both aligns the operations of individual provider practices with the operations of the ACO and aligns the trust of providers with the ACO. Motivating aligns what providers value with the goals of the ACO. Finally, evolving is a metapractice of learning and adapting that guides the execution of the other four practices.

Practice Implications:

Our findings suggest that there are second-order cognitive (e.g., understandings and attention) and cultural (e.g., trust and values) levels of alignment, as well as a first-order operational level (organizational structures, processes, and incentives). A well-aligned organization may require ongoing repositioning at each of these levels, as well as attention to both cooperative and coordinative dimensions of alignment. Implications for research and practice are discussed.