bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations in the Use of Perioperative Multimodal Analgesic Therapy
Authors: Ladha Karim S. , Patorno Elisabetta , Huybrechts Krista F. , Liu Jun , Rathmell James P. , Bateman Brian T. 
Published: January 2016

AbstractAbstract
In a review of nearly 800,000 patients undergoing four common major surgical procedures between 2007 and 2014, the probability of receiving multimodal analgesia was high (90%). There was large variability among hospitals in the use of multimodal analgesia, which could not be accounted for by patient or hospital characteristics.
Supplemental Digital Content is available in the text.

Background
Practice guidelines for perioperative pain management recommend that multimodal analgesic therapy should be used for all postsurgical patients. However, the proportion of patients who actually receive this evidence-based approach is unknown. The objective of this study was to describe hospital-level patterns in the utilization of perioperative multimodal analgesia.

Methods
Data for the study were obtained from the Premier Research Database. Patients undergoing below-knee amputation, open lobectomy, total knee arthroplasty, and open colectomy between 2007 and 2014 were included in the analysis. Patients were considered to have multimodal therapy if they received one or more nonopioid analgesic therapies. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of multimodal therapy use while adjusting for the case mix of patients and hospital characteristics and accounting for random variation.

Results
The cohort consisted of 799,449 patients who underwent a procedure at 1 of 315 hospitals. The mean probability of receiving multimodal therapy was 90.4%, with 95% of the hospitals having a predicted probability between 42.6 and 99.2%. A secondary analysis examined whether patients received two or more nonopioid analgesics, which gave an average predicted probability of 54.2%, with 95% of the hospitals having a predicted probability between 9.3 and 93.2%.

Conclusions
In this large nationwide sample of surgical admissions in the United States, the authors observed tremendous variation in the utilization of multimodal therapy not accounted for by patient or hospital characteristics. Efforts should be made to identify why there are variations in the use of multimodal analgesic therapy and to promote its adoption in appropriate patients.
Surgical Site Infections in Patients With Type 3 Open Fractures: Comparing Antibiotic Prophylaxis With Cefazolin Plus Gentamicin Versus Piperacillin/Tazobactam
Authors: Redfern Jenessa , Wasilko Scott M. , Groth Meghan E. , McMillian Wesley D. , Bartlett Craig S. 
Published: January 2016

Objectives:
The purpose of this study was to compare rates of surgical site infection (SSI) in patients with type 3 open fractures who had received cefazolin plus gentamicin versus piperacillin/tazobactam for antibiotic prophylaxis.

Design:
Retrospective cohort study.

Setting:
Level 1 trauma center.

Patients:
Seven hundred sixty-six patients admitted between January 1, 2004, and December 31, 2012, with open fractures were identified using the National Trauma Data Bank by searching International Classification of Diseases, Ninth Revision (ICD-9) codes. Electronic medical record review revealed 134 patients with type 3 open fractures, of which 72 were included in the final analysis.

Intervention:
Administration of cefazolin plus gentamicin or piperacillin/tazobactam for type 3 open fracture antibiotic prophylaxis.

Main Outcome Measurements:
SSI, nonunion, death, and rehospitalization rates at 1 year.

Results:
Surgical site infection at 1 year occurred in 12 of 37 patients (32.4%) in the cefazolin plus gentamicin group and 11 of 35 patients (31.4%) in the piperacillin/tazobactam group (P = 1.000). Nonunion, death, and rehospitalization rates at 1 year were similar between the 2 groups. Although there was no statistically significant difference in SSI at 30 days between groups, the rate was higher in the cefazolin plus gentamicin group (21.6% vs. 11.4%; P = 0.246).

Conclusions:
At our institution, use of piperacillin/tazobactam as compared with cefazolin plus gentamicin for antibiotic prophylaxis in patients with type 3 open fractures showed similar rates of SSI, nonunion, mortality, and rehospitalization at 1 year after injury.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
COTTON-WOOL SPOTS AFTER USE OF MACITENTAN FOR PULMONARY ARTERIAL HYPERTENSION
Authors: Khan Mohammed Ali , Ho Allen C. , Spirn Marc J. 
Published: January 2016

Purpose:
To report a case of transient, bilateral cotton spots after initiation of macitentan, an endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension.

Methods:
Case report.

Results:
A 76-year-old woman with WHO Class IIIb pulmonary arterial hypertension was referred for evaluation of bilateral cotton-wool spots 1 week after starting macitentan therapy. The patient was asymptomatic and visual acuity was 20/25 in each eye. Fluorescein angiography and optical coherence tomography were completed. Given lack of symptoms and alternative treatment options, the patient was observed closely. The cotton-wool spots resolved 8 weeks after presentation and visual acuity remained stable at 20/25. Throughout the observation period, average mean arterial pressure was within normal limits at 84.8.

Conclusion:
In patients using endothelin receptor antagonists, medication side effect should be considered in the differential diagnosis of cotton-wool spots.
RUPTURED RETINAL ARTERIAL MACROANEURYSM ON THE OPTIC DISK
Authors: Rahimy Ehsan , Doyle Brian C. , Brown Gary C. 
Published: January 2016

Purpose:
To describe multimodal imaging findings in a patient presenting with an occult optic disk macroaneurysm.

Methods:
A 54-year-old woman presented with decreased vision in the right eye secondary to preretinal, intraretinal, and optic disk hemorrhage.

Results:
Ancillary fluorescein angiography revealed evidence of an occult optic disk macroaneurysm that was not realized on fundoscopic examination. Subsequent optical coherence tomography obtained once the hemorrhage resolved demonstrated a thrombosed macroaneurysm with an adjacent ring of exudate.

Conclusion:
Detection of optic disk macroaneurysms at the time of initial presentation can be difficult because of concurrent overlying hemorrhage, but should nevertheless be kept in the differential when macular hemorrhage in multiple retinal layers is observed.
Thirty Years of Cystocele/Rectocele Repair in the United States
Authors: Stewart James R. , Hamner Jennifer J. , Heit Michael H. 
Published: January 2016

Objective
A growing body of evidence suggests an increased role for apical support in the treatment of pelvic organ prolapse regardless of phenotype. The objective of this study was to determine whether changes in cystocele/rectocele diagnosis and surgical management for the last 30 years reflect this changing paradigm.

Methods
Data from the National Hospital Discharge Survey were mined from 1979 to 2009 for diagnosis and procedure codes. Records were categorized according to predefined combinations of diagnosis and procedure codes and weighted according to the National Hospital Discharge Survey data set. Pearson χ2 test was used to evaluate the changes in population proportions during the study interval.

Results
The proportion of isolated cystocele/rectocele diagnoses decreased from 1979 to 2009 (56.5%, n = 88,548, to 34.8%, n = 31,577). The proportion of isolated apical defect diagnoses increased from 1979 to 2009 (38.4%, n = 60,223, to 60.8%, n = 55,153). There was a decrease in the frequency of isolated cystocele/rectocele repair procedures performed from 1979 to 2009 (96.3%, n = 150,980, to 67.7%, n = 61,444), whereas there was an increase in isolated apical defect repair procedures (2.5%, n = 3929, to 22.5%, n = 20,450). The proportion of cystocele/rectocele plus apical defect procedures also increased (1.2%, n = 1879, to 9.7%, n = 8806). Furthermore, 87.0% of all studied diagnostic groups were managed by cystocele/rectocele repair alone.

Conclusions
Surgeons have responded to the increased contribution of apical support defects to cystocele/rectocele by modifying their diagnostic coding practices. Unfortunately, their surgical choices remain largely rooted in an older paradigm.
Vaginal Expression of LOXL1 in Premenopausal and Postmenopausal Women With Pelvic Organ Prolapse
Authors: Kow Nathan , Ridgeway Beri , Kuang Mei , Butler Robert S. , Damaser Margot S. 
Published: January 2016

Objectives
This study aimed to compare cellular expression of lysyl oxidase-like 1 (LOXL1), a key enzyme in elastin metabolism, of premenopausal women with pelvic organ prolapse (POP) compared with premenopausal controls without POP and postmenopausal women with POP. In addition, we examined whether variation of LOXL1 expression was dependent on biopsy site.

Methods
A standardized protocol was utilized to obtain vaginal biopsies from 30 women (10 premenopausal POP, 10 postmenopausal POP, and 10 premenopausal non-POP). Expression levels of messenger RNA (mRNA) and protein of LOXL1 were determined using real-time quantitative polymerase chain reactions and enzyme-linked immunosorbant assays. Analysis was performed to determine if there were differences between group or biopsy site.

Results
Significant differences in LOXL1 mRNA expression were found between patient groups (P = 0.0033). LOXL1 mRNA expression (relative to 18S) was upregulated in the postmenopausal POP group (54.5 ± 14.7) compared with the premenopausal POP group (5.2 ± 14.7, P = 0.0034) and the premenopausal non-POP group (23 ± 18, P = 0.0359). No significant differences in LOXL1 protein expression (nanogram/milliliter per microgram total protein) were seen between groups (premenopausal POP, 3.2 × 10−3 ± 6.3 × 10−4; postmenopausal POP, 4.3 × 10−3 ± 6.3 × 10−4; premenopausal non-POP, 5.0 × 10−3 ± 7.7 × 10−4; P = 0.15). No differences in mRNA expression were seen between sites (P = 0.74), but significant variation was noted in protein expression (P = 0.001).

Conclusions
Premenopausal and postmenopausal women with POP exhibit differential expression of LOXL1 suggesting different pathways in the pathogenesis of POP. The role of biopsy location on LOXL1 expression requires further investigation.
A Novel Cystometric Model of Pelvic Floor Dysfunction After Rabbit Pelvic Floor Noxious Electrical Stimulation
Authors: Dobberfuhl Amy D. , Spettel Sara , Schuler Catherine , Dubin Andrew H. , Levin Robert M. , De Elise J.B. 
Published: January 2016

Objectives
Although a relationship between pelvic floor dysfunction and lower urinary tract symptoms is described in the literature, the mechanism and pathways need further characterization. We developed an animal model of pelvic floor dysfunction after noxious stimulation of the pubococcygeus (PC) muscle.

Methods
Fifteen female adult rabbits were evaluated with cystometry (CMG) and electromyography (EMG) recordings from the PC muscle. Cystometry/EMG was performed before and after treatment animal (n = 11) received noxious pelvic floor electrical stimulation through the PC EMG electrode, and controls (n = 4) underwent sham needle placement. Two animals underwent S3 dorsal rhizotomy to demonstrate that the observed results required afferent innervation.

Results
Voiding changes were demonstrated in 9 of 11 rabbits after stimulation. Most of the rabbits (7/9) exhibited a prolonged-dysfunctional voiding pattern with larger capacity (mean, 17 mL [SEM, ±8 mL]), longer intercontractile interval (227% [SEM, ±76%]) and duration (163% [SEM, ±20%]), and increased postvoid residual (24 mL [SEM, ±6 mL]). The remaining dysfunctional rabbits (2/9) exhibited an overactive-dysfunctional voiding pattern with lower capacity (−26 mL [SEM, ±6 mL]), shortened intercontractile interval (16% [SEM, ±9%]) and duration (56% [SEM, ±30%]), and decreased postvoid residual (−27 mL [SEM, ±6 mL]). Nonresponder rabbits (2/11) were relatively unchanged in their micturition cycles after stimulation. Rhizotomy animals were acontractile and filled until overflow incontinence occurred.

Conclusions
Using noxious electrical stimulation of the pelvic musculature, we were able to produce an animal model of pelvic floor dysfunction in most rabbits as hallmarked by a larger bladder capacity, an increased intercontractile interval, and prolonged contraction duration.
Impact of Pelvic Floor Physical Therapy on Quality of Life and Function After Obstetric Anal Sphincter Injury: A Randomized Controlled Trial
Authors: Oakley Susan H. , Ghodsi Vivian C. , Crisp Catrina C. , Estanol Maria Victoria , Westermann Lauren B. , Novicki Kathleen M. , Kleeman Steven D. , Pauls Rachel N. 
Published: January 2016

Objectives
There is no standard of care for women sustaining an obstetric anal sphincter injury (OASIS). We sought to determine whether pelvic floor physical therapy (PFPT) would improve the quality of life and function in women 12 weeks after OASIS.

Methods
This institutional review board–approved randomized trial enrolled primiparous women 2 weeks after delivery complicated by OASIS. After informed consent, all subjects underwent vaginal electromyography and anorectal manometry and completed validated questionnaires; measures were repeated for all subjects at 12 weeks after delivery. The intervention arm completed 4 PFPT sessions. The primary outcome was a change in the Fecal Incontinence Quality of Life.

Results
Three hundred four women were screened; 250 were excluded, and 54 were randomized. After four were lost to follow-up, analysis included 27 in the intervention arm and 23 in the control arm. Overall, mean age was 29.8 ± 4.7 years, and there were no demographic differences between groups.
Fecal Incontinence Quality of Life domain scores showed improvement for both groups from baseline to 12 weeks for coping (P = 0.006) and depression (P = 0.009); however, there was no difference in domain scores between groups. For the secondary outcome of anorectal manometry, squeezing pressure improved for all subjects (P = 0.035) from baseline to 12 weeks. Vaginal EMG strength (microvolts) increased for all subjects in measures of rest average (P < 0.000), rapid peak (P = 0.006), and work average (P < 0.000), with no difference based on therapeutic arm.

Conclusions
All women showed improvements in quality of life and function at 12 weeks after delivery, regardless of treatment allocation. Further study is needed to determine whether PFPT provides a significant benefit to women having OASIS.
MetaFlow: Metagenomic profiling based on whole-genome coverage analysis with min-cost flows
Authors: Sobih Ahmed , Tomescu Alexandru I. , Mäkinen Veli 
Published: January 2016

AbstractHigh-throughput sequencing (HTS) of metagenomes is proving essential in understanding the environment and diseases. State-of-the-art methods for discovering the species and their abundances in an HTS metagenomic sample are based on genome-specific markers, which can lead to skewed results, especially at species level. We present MetaFlow, the first method based on coverage analysis across entire genomes that also scales to HTS samples. We formulated this problem as an NP-hard matching problem in a bipartite graph, which we solved in practice by min-cost flows. On synthetic data sets of varying complexity and similarity, MetaFlow is more precise and sensitive than popular tools such as MetaPhlAn, mOTU, GSMer and BLAST, and its abundance estimations at species level are two to four times better in terms ofℓ1-norm. On a real human stool data set, MetaFlow identifiesB.uniformisas most predominant, in line with previous human gut studies, whereas marker-based methods report it as rare. MetaFlow is freely available athttp://cs.helsinki.fi/gsa/metaflow
False Discovery Rates: A New Deal
Authors: Stephens Matthew 
Published: January 2016

AbstractWe introduce a new Empirical Bayes approach for large-scale hypothesis testing, including estimating False Discovery Rates (FDRs), and effect sizes. This approach has two key differences from existing approaches to FDR analysis. First, it assumes that the distribution of the actual (unobserved) effects is unimodal, with a mode at 0. This “unimodal assumption” (UA), although natural in many contexts, is not usually incorporated into standard FDR analysis, and we demonstrate how incorporating it brings many benefits. Specifically, the UA facilitates efficient and robust computation – estimating the unimodal distribution involves solving a simple convex optimization problem – and enables more accurate inferences provided that it holds. Second, the method takes as its input two numbers for each test (an effect size estimate, and corresponding standard error), rather than the one number usually used (pvalue, orzscore). When available, using two numbers instead of one helps account for variation in measurement precision across tests. It also facilitates estimation of effects, and unlike standard FDR methods our approach provides interval estimates (credible regions) for each effect in addition to measures of significance. To provide a bridge between interval estimates and significance measures we introduce the term “local false sign rate” to refer to the probability of getting the sign of an effect wrong, and argue that it is a superior measure of significance than the local FDR because it is both more generally applicable, and can be more robustly estimated. Our methods are implemented in an R package ashr available fromhttp://github.com/stephens999/ashr.
Cell re-entry assays do not support models of pathogen-independent translocation of AvrM and AVR3a effectors into plant cells
Authors: Petre Benjamin , Kopischke Michaela , Evrard Alexandre , Robatzek Silke , Kamoun Sophien 
Published: January 2016

ABSTRACTThe cell re-entry assay is widely used to evaluate pathogen effector protein uptake into plant cells. The assay is based on the premise that effector proteins secreted out of a leaf cell would translocate back into the cytosol of the same cell via a yet unknown host-derived uptake mechanism. Here, we critically assess this assay by expressing domains of the effector proteins AvrM-A ofMelampsora liniand AVR3a ofPhytophthora infestansfused to a signal peptide and fluorescent proteins inNicotiana benthamiana. We found that the secreted fusion proteins do not re-enter plant cells from the apoplast and that the assay is prone to false-positives. We therefore emit a cautionary note on the use of the cell re-entry assay for protein trafficking studies.
The genetic architecture of local adaptation II: The QTL landscape of water-use efficiency for foxtail pine (Pinus balfourianaGrev. & Balf.)
Authors: Eckert Andrew J. , Harwood Douglas E. , Lind Brandon M. , Hobson Erin M. , Delfino Mix Annette , Maloney Patricia E. , Friedline Christopher J. 
Published: January 2016

AbstractWater availability is an important driver of the geographic distribution of many plant species, although its importance relative to other climatic variables varies across climate regimes and species. A common indirect measure of water-use efficiency (WUE) is the ratio of carbon isotopes (δ13C) fixed during photosynthesis, especially when analyzed in conjunction with a measure of leaf-level resource utilization (δ15N). Here, we test two hypotheses about the genetic architecture of WUE for foxtail pine (Pinus balfourianaGrev. & Balf.) using a novel mixture of double digest restriction site associated DNA sequencing, species distribution modeling, and quantitative genetics. First, we test the hypothesis that water availability is an important determinant of the geographical range of foxtail pine. Second, we test the hypothesis that variation in δ13C and δ15N is genetically based, differentiated between regional populations, and has genetic architectures that include loci of large effect. We show that precipitation-related variables structured the geographical range of foxtail pine, climate-based niches differed between regional populations, and δ13C and δ15N were heritable with moderate signals of differentiation between regional populations. A set of large-effect QTLs (n= 11 for δ13C;n= 10 for δ15N) underlying δ13C and δ15N variation, with little to no evidence of pleiotropy, was discovered using multiple-marker, half-sibling regression models. Our results represent a first approximation to the genetic architecture of these phenotypic traits, including documentation of several patterns consistent with δ13C being a fitness-related trait affected by natural selection.
Non-linear tumor-immune interactions arising from spatial metabolic heterogeneity
Authors: Robertson-Tessi Mark , Gillies Robert J. , Gatenby Robert A. , Anderson Alexander R. A. 
Published: January 2016

AbstractA hybrid multiscale mathematical model of tumor growth is used to investigate how tumoral and microenvironmental heterogeneity affect the response of the immune system. The model includes vascular dynamics and evolution of metabolic tumor phenotypes. Cytotoxic T cells are simulated, and their effect on tumor growth is shown to be dependent on the structure of the microenvironment and the distribution of tumor phenotypes. Importantly, no single immune strategy is best at all stages of tumor growth.
Last-Century Increases in Intrinsic Water-Use Efficiency of Grassland Communities Have Occurred over a Wide Range of Vegetation Composition, Nutrient Inputs, and Soil pH
Authors: Köhler Iris H. , Macdonald Andy J. , Schnyder Hans 
Published: January 2016

Abstract
Last-century climate change has led to variable increases of the intrinsic water-use efficiency (W i; the ratio of net CO2 assimilation to stomatal conductance for water vapor) of trees and C3 grassland ecosystems, but the causes of the variability are not well understood. Here, we address putative drivers underlying variable W i responses in a wide range of grassland communities. W i was estimated from carbon isotope discrimination in archived herbage samples from 16 contrasting fertilizer treatments in the Park Grass Experiment, Rothamsted, England, for the 1915 to 1929 and 1995 to 2009 periods. Changes in W i were analyzed in relation to nitrogen input, soil pH, species richness, and functional group composition. Treatments included liming as well as phosphorus and potassium additions with or without ammonium or nitrate fertilizer applications at three levels. W i increased between 11% and 25% (P &lt; 0.001) in the different treatments between the two periods. None of the fertilizers had a direct effect on the change of W i (ƊW i). However, soil pH (P &lt; 0.05), species richness (P &lt; 0.01), and percentage grass content (P &lt; 0.01) were significantly related to ƊW i. Grass-dominated, species-poor plots on acidic soils showed the largest ƊW i (+14.7 μmol mol−1). The ƊW i response of these acidic plots was probably related to drought effects resulting from aluminum toxicity on root growth. Our results from the Park Grass Experiment show that W i in grassland communities consistently increased over a wide range of nutrient inputs, soil pH, and plant community compositions during the last century.