bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of vertical integration and quality of care, efficiency, and patient-centered outcomes
Authors: Machta Rachel M. , Maurer Kristin A. , Jones David J. , Furukawa Michael F. , Rich Eugene C.
Published: April 2018

Background:

Small independent practices are increasingly giving way to more complex affiliations between provider organizations and hospital systems. There are several ways in which vertically integrated health systems could improve quality and lower the costs of care. But there are also concerns that integrated systems may increase the price and costs of care without commensurate improvements in quality and outcomes.

Purpose:

Despite a growing body of research on vertically integrated health systems, no systematic review that we know of compares vertically integrated health systems (defined as shared ownership or joint management of hospitals and physician practices) to nonintegrated hospitals or physician practices.

Methods:

We conducted a systematic search of the literature published from January 1996 to November 2016. We considered articles for review if they compared the performance of a vertically integrated health system and examined an outcome related to quality of care, efficiency, or patient-centered outcomes.

Results:

Database searches generated 7,559 articles, with 29 articles included in this review. Vertical integration was associated with better quality, often measured as optimal care for specific conditions, but showed either no differences or lower efficiency as measured by utilization, spending, and prices. Few studies evaluated a patient-centered outcome; among those, most examined mortality and did not identify any effects. Across domains, most studies were observational and did not address the issue of selection bias.

Practice Implications:

Recent evidence suggests the trend toward vertical integration will likely continue as providers respond to changing payment models and market factors. A growing body of research on comparative health system performance suggests that integration of physician practices with hospitals might not be enough to achieve higher-value care. More information is needed to identify the health system attributes that contribute to improved outcomes, as well as which policy levers can minimize anticompetitive effects and maximize the benefits of these affiliations.
Phacomorphic Angle-closure Following Silicone Oil Tamponade in a Pediatric Patient
Authors: Leung Victoria C. , Fung Simon S.M. , Muni Rajeev , Ali Asim
Published: April 2018

Purpose:

The purpose of this study was to report a case of phacomorphic glaucoma following retinal detachment repair with silicone oil (SO) in a pediatric patient.

Study Design:

Case report.

Methods:

A chart review was conducted at St. Michael’s Hospital and The Hospital for Sick Children (Toronto, Canada), where the patient received ophthalmic care from July 28, 2015 onwards.

Results:

A 14-year-old boy with a history of traumatic retinal detachment and proliferative vitreoretinopathy in the left eye, requiring 2 pars plana vitrectomies, membrane peel, and SO tamponade, presented with 1-day history of decreased vision in the left eye, severe headache, nausea, and vomiting. Visual acuity was hand motions; intraocular pressure (IOP) was 54 mm Hg; the pupil was middilated and minimally reactive with a reverse relative afferent pupillary defect. Slit-lamp examination revealed an injected eye with diffuse microcystic corneal edema, a shallow anterior chamber (AC), and an intumescent cataract. Gonioscopy demonstrated closed angles in 3 quadrants. Compared with his last examination 6 weeks prior, where only a mild posterior subcapsular cataract was noted, the patient’s presentation was suggestive of rapid lens intumescence causing acute angle-closure glaucoma. He was given topical and systemic treatment, including intravenous mannitol, and his IOP reduced to 22 mm Hg after 7 hours. Urgent lensectomy was performed the following day. Preoperative ultrasound biomicroscopy revealed a greatly increased lens thickness of 5.12 mm and an AC depth of 1.12 mm. The integrity of both anterior and posterior lens capsules was confirmed intraoperatively, and SO remained confined to the posterior segment. Postoperatively, the iris returned to a normal configuration with open angles, and IOP was 16 mm Hg with no antiglaucoma medications at the last follow-up.

Conclusions:

Acute angle-closure in children is a rare event. To our knowledge, this is the first reported case of phacomorphic glaucoma secondary to vitreoretinal surgery in the pediatric population. Although uncommon, ophthalmologists should be aware of this potential complication with the intraocular use of SO and administer urgent treatment accordingly.
Modality-specific effects of aversive expectancy in the anterior insula and medial prefrontal cortex
Authors: Sharvit Gil , Corradi-Dell'Acqua Corrado , Vuilleumier Patrik
Published: April 2018

Expectations modulate the subjective experience of pain by increasing sensitivity to nociceptive inputs, an effect mediated by brain regions such as the insula. However, it is still unknown whether the neural structures underlying pain expectancy hold sensory-specific information or, alternatively, code for modality-independent features (eg, unpleasantness), potentially common with other negative experiences. We used functional magnetic resonance imaging to investigate neural activity underlying the expectation of different, but comparably unpleasant, pain and disgust. We presented participants with visual cues predicting either a painful heat or disgusting odor, and assessed how they affected the subsequent subjective experience of stimuli from the same (within-modality) or opposite (cross-modal) modality. We found a reliable influence of expectancy on the subjective experience of stimuli whose modality matched that of the previous cue. At the brain level, this effect was mediated by the intermediate dysgranular section of the insula, whereas it was suppressed by more anterior agranular portions of the same region. Instead, no expectancy modulation was observed when the modality of the cue differed from that of the subsequent stimulus. Our data suggest that the insular cortex encodes prospective aversive events in terms of their modality-specific features, and whether they match with subsequent stimulations.
The Effect of Inflow Cannula Angle on the Intraventricular Flow Field of the Left Ventricular Assist Device–Assisted Heart: An In Vitro Flow Visualization Study
Authors: May-Newman Karen , Marquez-Maya Nikolas , Montes Ricardo , Salim Saniya
Published: April 2018

Abstract: Previous studies have identified left ventricular assist device (LVAD) inflow cannula (IC) malposition as a significant risk for pump thrombosis. Thrombus development is a consequence of altered flow dynamics, which can produce areas of flow stasis or high shear that promote coagulation. The goal of this study was to measure the effect of IC orientation on the left ventricle (LV) flow field using a mock circulatory loop, and identify flow-based indices that are sensitive measures of cannula malposition. Experimental studies were performed with a customized silicone model of the dilated LV and the EVAHEART Centrifugal LVAS (Evaheart, Inc.; Houston TX). The velocity field of the LV midplane was measured for a transparent IC oriented parallel to and rotated 15° toward the septum under matched hemodynamic conditions. Vortex structures were analyzed and localized stasis calculated within the IC and combined with a map of normalized pulsatile velocity. The velocity fields revealed increased apical stasis and lower pulsatility with a small angulation of the IC. A significant change in vortex dynamics with the angled IC was observed, doubling the size of the counterclockwise (CCW) vortex while reducing the kinetic energy provided by LVAD support. A significant decrease in average and systolic velocities within the IC was found with cannula angulation, suggesting an increased resistance that affects primarily systolic flow and is worsened with increased LVAD support. These common echocardiographic indices offer the opportunity for immediate clinical application during ramp study assessment. Optimized IC positioning may be determined preoperatively using imaging techniques to develop patient-specific surgical recommendations.
Early Serum Gut Hormone Concentrations Associated With Time to Full Enteral Feedings in Preterm Infants
Authors: Shanahan Kristen H. , Yu Xinting , Miller Laura G. , Freedman Steven D. , Martin Camilia R.
Published: April 2018

Objectives:

The primary objective of this study was to evaluate early postnatal serum gut hormone concentrations in preterm infants as predictors of time to full enteral feedings. The secondary objective was to identify infant characteristics and nutritional factors that modulate serum gut hormone concentrations and time to full enteral feedings.

Methods:

Sixty‐four preterm infants less than 30 weeks of gestation were included in this retrospective cohort study. Serum gut hormone concentrations at postnatal days 0 and 7 were measured using enzyme‐linked immunosorbent assays. Linear regression and mediation analyses were performed.

Results:

Median (interquartile range) serum concentrations of glucose‐dependent insulinotropic peptide (GIP) and peptide YY (PYY) on postnatal day 7 were 31.3 pg/mL (18.2, 52.3) and 1181.7 pg/mL (859.0, 1650.2), respectively. GIP and PYY concentrations on day 7 were associated with days to full enteral feedings after adjustment for confounders (β = −1.1, P = 0.03; and β = −0.002, P = 0.02, respectively). Nutritional intake was correlated with serum concentrations of GIP and PYY on postnatal day 7 and time to full enteral feedings. Mediation analysis revealed that the effect of serum gut hormone concentrations on time to full enteral feedings was not fully explained by nutritional intake. Intrauterine growth restriction, mechanical ventilation on postnatal day 7, and patent ductus arteriosus treated with indomethacin were associated with longer time to full enteral feedings.

Conclusions:

Serum concentrations of GIP and PYY on postnatal 7 are independently associated with time to full enteral feedings. The link between serum gut hormone concentrations and time to full enteral feedings is not fully mediated by nutritional factors, suggesting an independent mechanism underlying the influence of gut hormones on feeding tolerance and time to full enteral feedings.
Long-Term Course of Shoulders After Ultrasound Therapy for Calcific Tendinitis
Authors: Pieber Karin , Grim-Stieger Martina , Kainberger Franz , Funovics Martin , Resch Karl-Ludwig , Bochdansky Thomas , Pablik Eleonore , Ebenbichler Gerold
Published: April 2018

Objective

The aim of the study was to follow both the structure- and function-related long-term course of shoulders that had been treated with therapeutic ultrasound for symptomatic calcific tendinitis.

Design

This is a long-term follow-up of 45 shoulders (37 patients) that had been treated for symptomatic calcific tendinitis with either a series of ultrasound or sham ultrasound 10 yrs ago. The main outcome variables were presence of calcium deposits and subacromial impingement on standardized x-ray imaging, shoulder symptoms (Binder score), and function (Constant score).

Results

At 10 yrs, a similar proportion of calcium deposits had resolved in 78% of the originally ultrasound treated compared with 83% of sham-treated shoulders, whereas at 9 mos, significantly more calcium deposits had been resolved in the ultrasound group (P = 0.045). Relative to baseline, shoulder symptoms and function had significantly improved at both the 10-yr and 9-mo follow-up examinations with no significant differences between groups. Regular sports performance at baseline predicted a favorable long-term outcome.

Conclusions

Symptomatic calcific tendinitis of the shoulder has a good likelihood to completely resolve in the long term. Treating the calcium deposit effectively, however, may not be causal to the recovery from symptoms and function in calcific tendinitis.
Hamstring Co-Contraction in the Early Stage of Rehabilitation After Anterior Cruciate Ligament Reconstruction
Authors: Song Hongyun , Dai Xuesong , Li Jianhua , Zhu Sunan
Published: April 2018

Objective

Hamstring co-contraction may affect recovery from anterior cruciate ligament reconstruction. The aim of the study was to evaluate the changes in hamstring co-contraction during the early postoperative stages.

Design

Twenty-five patients with anterior cruciate ligament reconstruction were followed up for 1–3 mos postoperatively, during which the Lysholm and International Knee Documentation Committee questionnaires were completed and surface electromyograms were assessed during terminal knee extension maximum voluntary contraction and step-up tests. The integrated electromyogram of the tested muscles and co-contraction ratio were analyzed.

Results

Co-contraction ratio during terminal knee extension maximum voluntary contraction at 3 mos postoperatively was significantly less than that at 1 mo postoperatively (P < 0.0083), and it did not significantly differ from that of the uninvolved knee. In contrast, the co-contraction ratio during step-up was significantly higher at 2 and 3 mos postoperatively than that before surgery (P < 0.0167) and for the uninvolved knee (P < 0.05). Moreover, the postoperative hamstring co-contraction ratio in patients with a chronic injury was significantly higher during the step-up test than in patients with an early injury (P = 0.017).

Conclusions

Hamstring co-contraction ratio during terminal knee extension maximum voluntary contraction recovers during the early postoperative stages. However, hamstring co-contraction ratio during step-up, which may be related to knee joint proprioception, remains high, particularly for patients with a chronic injury.

Clinical Trial

ChiCTR-COC-17011167.
Current methods and challenges for acute pain clinical trials
Authors: Gilron Ian , Carr Daniel B. , Desjardins Paul J. , Kehlet Henrik
Published: April 2018

Introduction:

The clinical setting of acute pain has provided some of the first approaches for the development of analgesic clinical trial methods.

Objectives:

This article reviews current methods and challenges and provides recommendations for future design and conduct of clinical trials of interventions to treat acute pain.

Conclusion:

Growing knowledge about important diverse patient factors as well as varying pain responses to different acute pain conditions and surgical procedures has highlighted several emerging needs for acute pain trials. These include development of early-phase trial designs that minimize variability and thereby enhance assay sensitivity, minimization of bias through blinding and randomization to treatment allocation, and measurement of clinically relevant outcomes such as movement-evoked pain. However, further improvements are needed, in particular for the development of trial methods that focus on treating complex patients at high risk of severe acute pain.
Focal Myocardial Damage in Cardiac Sarcoidosis Characterized by Strain Analysis on Magnetic Resonance Tagged Imaging in Comparison with Fluorodeoxyglucose Positron Emission Tomography Accumulation and Magnetic Resonance Late Gadolinium Enhancement
Authors: Watanabe Yoshiaki , Nishii Tatsuya , Shimoyama Shinsuke , Ito Tatsuro , Mori Shumpei , Kono Atsushi K. , Takahashi Satoru , Hirata Ken-ichi , Sugimura Kazuro
Published: April 2018

Objective

The aims of this study were to characterize focal myocardial damage of cardiac sarcoidosis by strain analysis and to compare it with late gadolinium enhancement (LGE) and fluorodeoxyglucose (FDG) positron emission tomography.

Methods

We reviewed 208 segments from 13 cardiac sarcoidosis patients and measured the circumferential strain (Ecc) and the strain change per second (Ecc rate). The mean Ecc and Ecc rate values were compared between the FDG(+) and FDG(−), and the LGE(+) and LGE(−) segments using Welch's t test.

Results

The peak and max Ecc rates were better in the LGE(−) segments than in the LGE(+) segments (−11.8 vs −8.9%, 40.5 vs 29.7%/s, both P < 0.001). The max Ecc rate was higher in the FDG(−) segments than in the FDG(+) segments (39.2 vs 31.7%/s, P < 0.001), but the peak Ecc did not differ between the FDG(+) and FDG(−) segments (−11.2 vs −10.1%, P = 0.17).

Conclusions

Strain analysis could reveal focal myocardial damage in the FDG(+) or the LGE(+) segments.
Dual-Energy Computed Tomography–Based Iodine Quantitation for Response Evaluation of Lung Cancers to Chemoradiotherapy/Radiotherapy: A Comparison With Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography–Based Positron Emission Tomography/Computed Tomography Response Evaluation Criterion in Solid Tumors
Authors: Ren Yanping , Jiao Yuxin , Ge Weiqiang , Zhang Libo , Hua Yanqing , Li Cheng , Zhai Weihao , Tang Xi , He Wei , Fang Min , Zheng Xiangpeng
Published: April 2018

Objective

The objective of this study was to investigate the correlation between dual-energy computed tomography (DECT)–based iodine quantitation and fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for response evaluation of lung cancers to treatment.

Methods

In this prospective study, a total of 32 pairs of DECT and 18F-FDG PET/CT imaging acquired consecutively from 13 patients with primary or metastatic lung cancers receiving either radiotherapy alone or chemoradiotherapy were analyzed. Imaging examinations were performed before, immediately, and no later than 6 months after treatment for response evaluation. Iodine-related parameters including the total iodine uptake (TIU) and vital volume (VIV) from DECT and metabolic metrics such as the standardized uptake value normalized to lean body mass (SULpeak), metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) from 18F-FDG-PET/CT were generated and measured by semiautomatic approaches. Dual-energy CT and PET/CT metrics were calculated and followed up with comparison with response evaluation criteria in solid tumors (RECIST).

Results

Analysis of pretreatment imaging data revealed a strong correlation between DECT metrics (RECIST, TIU, and VIV) and 18F-FDG PET/CT metrics (MTV, TLG) with coefficients of R ranging from 0.86 to 0.90 (P < 0.01). With the delivery of treatment, all measured DECT and PET/CT metrics significantly decreased whereas the descending amplitude in RECIST was significantly smaller than that of the remaining parameters (P < 0.05). During follow-up examinations, both metrics followed a similar changing pattern. Overall, strong consistency was found between RECIST, TIU, VIV and SULpeak, MTV, TLG (R covers 0.78–0.96, P < 0.05).

Conclusions

Semiautomatic iodine-related quantitation in DECT correlated well with metabolism-based measurements in 18F-FDG PET/CT, suggesting that DECT-based iodine quantitation might be a feasible substitute for assessment of lung cancer response to chemoradiotherapy/radiotherapy with comparison with 18F-FDG PET/CT.
Motion Artifact Reduction From High-Pitch Dual-Source Computed Tomography Pulmonary Angiography
Authors: Bunch Paul M. , Fulwadhva Urvi P. , Wortman Jeremy R. , Primak Andrew N. , Madan Rachna , Steigner Michael L. , Sodickson Aaron D.
Published: April 2018

Purpose

The purpose of this study was to compare quantitative and qualitative measures of aortic, cardiac, and respiratory motion artifact between high-pitch dual-source (DS) and single-source (SS) computed tomography pulmonary angiography (CTPA) protocols.

Methods

This institutional review board–approved, Health Insurance Portability and Accountability Act–compliant study retrospectively reviewed 80 non–electrocardiogram-gated CTPA examinations acquired with a second-generation DS system at 100 kVp following 50 mL iodinated contrast injection — 40 consecutive SS and 40 consecutive DS studies. Quantitative measures of aortic, left ventricular, and diaphragmatic motion were recorded as the maximal excursion of a structure's “double image,” and 3 independent readers performed qualitative motion assessments. Pulmonary arterial contrast enhancement, image noise, and radiation dose metrics were recorded. Statistical analyses were performed with 1-way analysis of variance and Fisher exact test.

Results

Dual source outperformed SS technique in both quantitative and qualitative measures of motion. Mean distances between motion-artifact double images were reduced with DS protocol at each location (all P ≤ 0.004), and DS examinations were more likely to receive an assessment of no motion in all locations (all P < 0.0001). The DS protocol demonstrated increases in contrast enhancement, although increased image noise resulted in lower enhancement to noise ratio. Mean radiation dose was 60% lower using the DS protocol.

Conclusion

High-pitch DS CTPA significantly reduces artifacts resulting from ascending aortic, cardiac, and diaphragmatic motion.
Influence of postoperative hepatic angiography on mortality after laparotomy in Grade IV/V hepatic injuries
Authors: Matsumoto Shokei , Cantrell Emily , Jung Kyoungwon , Smith Alan , Coimbra Raul
Published: April 2018

BACKGROUND

Mortality rate for severe liver injuries remains high. As an adjunct to surgery, postoperative hepatic angiography (PHA) may have a positive impact on outcomes. This study sought to compare outcomes following surgical management of severe liver injuries with and without PHA using propensity score matching analysis.

METHODS

Data from the National Trauma Data Bank from 2007 to 2014 were analyzed. The study population consisted of patients older than 18 years, sustaining severe liver injuries (i.e., American Association for the Surgery of Trauma Organ Injury Scale (AAST-OIS) Grade IV or V) who underwent surgery. Patients were divided into two groups. The PHA group consisted of those undergoing surgery followed by PHA. In the surgery-only group, no angiography was performed. To determine the impact of PHA on outcomes, propensity score matching analysis (1:3) was used.

RESULTS

A total of 3,871 patients met inclusion criteria. Of those, 205 (5.3%) patients underwent PHA. Prior to matching, patients in the PHA group had higher severity, but overall in-hospital mortality was found to be similar between the two groups. After 1:3 propensity-score matching, 196 patients in the PHA group were matched with 588 in the surgery-only group with well-balanced baseline characteristics. The in-hospital mortality was significantly lower in the PHA group compared with the surgery-only group (24.5% vs. 35.9%; odds ratio, 0.58; 95% confidence interval, 0.40–0.84). However, hospital length of stay was longer (16.0 [7.0–29.8] vs. 11 [1.0–25.0] days, p = 0.001), and the incidence of deep and organ/space surgical site infection (3.6% vs. 1.2%, 8.2% vs. 3.5%, respectively) was higher in the PHA group.

CONCLUSION

The use of PHA was associated with decreased mortality rates. A multimodality approach using both surgical intervention followed by PHA appears to identify patients that may benefit from arterial embolization, leading to decreased mortality of severe liver injuries.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
Management of cervical tracheoesophageal injuries: A 2018 EAST Master Class Video Presentation
Authors: Bardes James M. , Grabo Daniel , Inaba Kenji , Schellenberg Morgan , Polk Travis , Demetriades Demetrios
Published: April 2018

This video techniques article focuses on the choice of incision, and repair techniques, for cervical injuries to the trachea and esophagus.
Evaluation and management of traumatic diaphragmatic injuries: A Practice Management Guideline from the Eastern Association for the Surgery of Trauma
Authors: McDonald Amy A. , Robinson Bryce R.H. , Alarcon Louis , Bosarge Patrick L. , Dorion Heath , Haut Elliott R. , Juern Jeremy , Madbak Firas , Reddy Srinivas , Weiss Patricia , Como John J.
Published: April 2018

BACKGROUND

Traumatic diaphragm injuries (TDI) pose both diagnostic and therapeutic challenges in both the acute and chronic phases. There are no published practice management guidelines to date for TDI. We aim to formulate a practice management guideline for TDI using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

METHODS

The working group formulated five Patient, Intervention, Comparator, Outcome questions regarding the following topics: (1) diagnostic approach (laparoscopy vs. computed tomography); (2) nonoperative management of penetrating right-sided injuries; (3) surgical approach (abdominal or thoracic) for acute TDI, including (4) the use of laparoscopy; and (5) surgical approach (abdominal or thoracic) for delayed TDI. A systematic review was undertaken and last updated December 2016. RevMan 5 (Cochran Collaboration) and GRADEpro (Grade Working Group) software were used. Recommendations were voted on by working group members. Consensus was obtained for each recommendation.

RESULTS

A total of 56 articles were used to formulate the recommendations. Most studies were retrospective case series with variable reporting of outcomes measures and outcomes frequently not stratified to intervention or comparator. The overall quality of the evidence was very low for all Patient, Intervention, Comparator, Outcomes. Therefore, only conditional recommendations could be made.

CONCLUSION

Recommendations were made in favor of laparoscopy over computed tomography for diagnosis, nonoperative versus operative approach for right-sided penetrating injuries, abdominal versus thoracic approach for acute TDI, and laparoscopy (with the appropriate skill set and resources) versus open approach for isolated TDI. No recommendation could be made for the preferred operative approach for delayed TDI. Very low-quality evidence precluded any strong recommendations. Further study of the diagnostic and therapeutic approaches to TDI is warranted.

LEVEL OF EVIDENCE

Guideline; Systematic review, level IV.
Structural basis for substrate binding and specificity of a sodium/alanine symporter AgcS
Authors: Ma Jinming , Lei Hsiang-Ting , Reyes Francis E. , Sanchez-Martinez Silvia , Sarhan Maen , Gonen Tamir
Published: April 2018

The amino acid, polyamine, and organocation (APC) superfamily is the second largest superfamily of membrane proteins forming secondary transporters that move a range of organic molecules across the cell membrane. Each transporter in APC superfamily is specific for a unique sub-set of substrates, even if they possess a similar structural fold. The mechanism of substrate selectivity remains, by and large, elusive. Here we report two crystal structures of an APC member fromMethanococcus maripaludis, the alanine or glycine:cation symporter (AgcS), with L- or D-alanine bound. Structural analysis combined with site-directed mutagenesis and functional studies inform on substrate binding, specificity, and modulation of the AgcS family and reveal key structural features that allow this transporter to accommodate glycine and alanine while excluding all other amino acids. Mutation of key residues in the substrate binding site expand the selectivity to include valine and leucine. Moreover, as a transporter that binds both enantiomers of alanine, the present structures provide an unprecedented opportunity to gain insights into the mechanism of stereo-selectivity in APC transporters.
Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
Authors: Nguemaha Valery , Zhou Huan-Xiang
Published: April 2018

Recently many cellular functions have been associated with membraneless organelles, or protein droplets, formed by liquid-liquid phase separation (LLPS). Proteins in these droplets often contain RNA-binding domains, but the effects of RNA on LLPS have been controversial. To gain better understanding on the roles of RNA, here we used Gibbs-ensemble simulations to determine phase diagrams of two-component patchy particles, as models for mixtures of proteins with RNA or other regulatory components. Protein-like particles have four patches, with attraction strength εPP; regulatory particles experience mutual steric repulsion but have two attractive patches toward proteins, with the strength εPR tunable. At low εPR, the regulator, due to steric repulsion, preferentially partitions in the dispersed phase, thereby displacing the protein into the droplet phase and promoting LLPS. At moderate εPR, the regulator starts to partition and displace the protein in the droplet phase, but only to weaken bonding networks and thereby suppress LLPS. At εPR > εPP, the enhanced bonding ability of the regulator initially promotes LLPS, but at higher amounts, the resulting displacement of the protein suppresses LLPS. These results illustrate how RNA can have disparate effects on LLPS, thus able to perform diverse functions in different organelles.
A Stochastic Model for Cancer Metastasis: Branching Stochastic Process with Settlement
Authors: Frei Christoph , Hillen Thomas , Rhodes Adam
Published: April 2018

We introduce a new stochastic model for metastatic growth, which takes the form of a branching stochastic process with settlement. The moving particles are interpreted as clusters of cancer cells while stationary particles correspond to micro-tumors and metastases. The analysis of expected particle location, their locational variance, the furthest particle distribution, and the extinction probability leads to a common type of differential equation, namely, a non-local integro-differential equation with distributed delay. We prove global existence and uniqueness results for this type of equation. The solutions’ asymptotic behavior for long time is characterized by an explicit index, a metastatic reproduction number R0: metastases spread for R0 > 1 and become extinct for R0 < 1. Using metastatic data from mouse experiments, we show the suitability of our framework to model metastatic cancer.
Synonymous lysine codon usage modification in a mobile antibiotic resistance gene similarly alters protein production in bacterial species with divergent lysine codon usage biases because it removes a duplicate AAA lysine codon
Authors: Alorabi Mohammed , AlAmri Aisha M. , Takebayashi Yuiko , Heesom Kate J. , Avison Matthew B.
Published: April 2018

The mobile antibiotic resistance gene blaIMP-1 is clinically important and has a synonymous AAA:AAG lysine codon usage bias of 73:27. This bias is like that seen in experimentally determined highly expressed genes in Escherichia coli and Acinetobacter baumanii, but quite different from that seen in Pseudomonas aeruginosa (26:74 AAA:AAG). Here we show that, paradoxically, shifting the AAA:AAG lysine codon bias to 8:92 in blaIMP-1 expressed from a natural promoter results in significantly more IMP-1 production in all three species. Sequential site directed mutagenesis revealed that increased IMP-1 production occurs following removal of an AAA,AAA double lysine codon and that otherwise, lysine codon usage had no observable impact on IMP-1 production. We conclude that ribosomal slippage at this poly-adenosine region reduces efficient translation of IMP-1 and that punctuating the region with guanine reduces ribosomal slippage and increases IMP-1 production.
Differential carbohydrate utilization and organic acid production by honey bee symbionts
Authors: Lee Fredrick J. , Miller Kayla I. , McKinlay James B. , Newton Irene L. G.
Published: April 2018

The honey bee worker gut is host to a community of bacteria that primarily comprises 8-10 bacterial species. Collectively, these microbes break down and ferment saccharides present in the host’s diet. The model of metabolism for these gut symbionts is rooted in previous analyses of genomes, metagenomes, and metatranscriptomes of this environment. Importantly, there is a correlation between the composition of the gut microbiome and weight gain in the honey bee, suggesting that bacterial production of organic acids might contribute to the observed phenomenon. Here we identify potential metabolic contributions of symbionts within the honey bee gut. We show significant variation in the metabolic capabilities of these microbes, highlighting the fact that although the microbiota appears simple and consistent based on 16S rRNA gene profiling, strains are highly variable in their ability to use specific carbohydrates and produce organic acids. Finally, we confirm that the honey bee core microbes, especially a clade of γ-proteobacteria (i.e.Gilliamella), are highly activein vivo, expressing key enzymatic genes critical for utilizing plant-derived molecules and producing organic acids. These results suggest thatGilliamella, and other core taxa, may contribute significantly to weight gain in the honey bee, specifically through the production of organic acids.
Candidate Gene Networks for Acylsugar Metabolism and Plant Defense in Wild TomatoSolanum pennellii
Authors: Mandal Sabyasachi , Ji Wangming , McKnight Thomas D.
Published: April 2018

Many plants in the Solanaceae family secrete acylsugars, which are branched-chain and straight-chain fatty acids esterified to glucose or sucrose. These compounds have important roles in plant defense and potential commercial applications. However, several acylsugar metabolic genes remain unidentified, and little is known about regulation of this pathway. We used comparative transcriptomic analysis between low- and high-acylsugar-producing accessions ofSolanum pennelliiand found that expression levels of most acylsugar metabolic genes, including known acylsucrose biosynthetic genes and novel candidate genes (putatively encoding a ketoacyl-ACP synthase IV/II-like enzyme, peroxisomal acyl-activating enzymes, ABC transporters, and central carbon metabolic enzymes), were positively correlated with acylsugar accumulation, except two acylglucose biosynthetic genes. Genes putatively encoding oxylipin metabolic proteins, subtilisin-like proteases, and other antimicrobial defense proteins were upregulated in low-acylsugar-producing accessions, possibly to compensate for diminished defense activities of acylsugars. Gene co-expression network analysis clustered most differentially expressed genes into two separate modules and identified genetic networks associated with acylsugar production and plant defense. Transcriptome analysis after inhibition of biosynthesis of branched-chain amino acids (precursors to branched-chain fatty acids) further supported the coordinated regulation of most acylsugar candidate genes and identified three putative AP2-family transcription factor genes that form a strong co-expression network with many acylsugar metabolic genes.
Effects of protein-crystal hydration and temperature on side-chain conformational heterogeneity in monoclinic lysozyme crystals
Authors: Atakisi Hakan , Moreau David W. , Thorne Robert E.
Published: April 2018

The modulation of main-chain and side-chain conformational heterogeneity and solvent structure in monoclinic lysozyme crystals by dehydration (related to water activity) and temperature is examined. Decreasing the relative humidity (from 99 to 11%) and decreasing the temperature both lead to contraction of the unit cell, to an increased area of crystal contacts and to remodeling of primarily contact and solvent-exposed residues. Both lead to the depopulation of some minor side-chain conformers and to the generation of new conformations. Side-chain modifications and main-chain r.m.s.d.s associated with cooling from 298 to 100 K depend on relative humidity and are minimized at 85% relative humidity (r.h.). Dehydration from 99 to 93% r.h. and cooling from 298 to 100 K result in a comparable number of remodeled residues, with dehydration-induced remodeling somewhat more likely to arise from contact interactions. When scaled to equivalent temperatures based on unit-cell contraction, the evolution of side-chain order parameters with dehydration shows generally similar features to those observed on cooling toT= 100 K. These results illuminate the qualitative and quantitative similarities between structural perturbations induced by modest dehydration, which routinely occurs in samples prepared for 298 and 100 K data collection, and cryocooling. Differences between these perturbations in terms of energy landscapes and occupancies, and implications for variable-temperature crystallography between 180 and 298 K, are discussed. It is also noted that remodeling of a key lysozyme active-site residue by dehydration, which is associated with a radical decrease in the enzymatic activity of lysozyme powder, arises due to a steric clash with the residue of a symmetry mate.
The crystal structure of the lipoaminopeptaibol helioferin, an antibiotic peptide fromMycogone rosea
Authors: Gessmann Renate , Brückner Hans , Berg Albrecht , Petratos Kyriacos
Published: April 2018

The crystal structure of the natural nonapeptide antibiotic helioferin has been determined and refined to 0.9 Å resolution. Helioferin consists of helioferin A and B, which contain 2-(2′-aminopropyl)aminoethanol (Apae) and 2-[(2′-aminopropyl)methylamino]ethanol (Amae) at their respective alkanolamine termini. In addition, helioferin contains the unusual amino-acid residues α-aminoisobutyric acid (Aib) and (2S,4S,6S)-2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (Ahmod). The amino-terminus is capped with 2-methyl-n-1-octanoic acid (M8a). The peptide crystallizes with a 1:1 molar ratio of helioferin A and B in the monoclinic space groupC2, with unit-cell parametersa= 34.711,b= 10.886,c= 17.150 Å, β = 93.05°. The peptide backbone folds in a regular right-handed α-helical conformation, with eight intramolecular hydrogen bonds, all but one forming 5→1 interactions. The two aliphatic chains of the fatty-acyl (M8a) and the second residue (Ahmod) extend out of the α-helical structure in opposite directions and lead to a corkscrew-like shape of the peptide molecule. Halogen anions (Cl−and F−) have been co-crystallized with the peptide molecules, implying a positive charge at the aminoalcohol end of the peptide. In the tightly packed crystal the helices are linked head to tailviathe anions by electrostatic, hydrogen-bond and van der Waals interactions, forming continuous helical rods. Two nonparallel rods (forming an angle of 118°) interact directlyviahydrogen bonds andviathe anions, forming a double layer. Successive double layers are held together onlyviavan der Waals contacts. The helical axes of successive double layers are also related by an angle of 118°. The structure of helioferin reported here and the previously determined structure of the homologous leucinostatin A have a total straight length of about 21 Å, indicating a different membrane-modifying bioactivity from that of long-chain, amphiphilic peptaibols.
Structures of theMycobacterium tuberculosisGlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition
Authors: Wolf Nina M. , Gutka Hiten J. , Movahedzadeh Farahnaz , Abad-Zapatero Celerino
Published: April 2018

The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) fromMycobacterium tuberculosisat 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase fromSynechocystis(strain 6803) as well as the equivalent enzyme fromThermosynechococcus elongatus. This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII fromEscherichia coliand is probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII fromM. tuberculosis(MtFBPaseII) is conserved and is analogous to that described previously for theE. colienzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures ofMtFBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for theSynechocystisenzyme. The structural and functional insights derived from the structure ofMtFBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.
Genre analysis of the “About Us” sections of Asian Association of Open Universities websites
Authors: Villanueva Louise S. , Dolom Mary Aizel C. , Belen Jennifer S.
Published: April 2018

Purpose

This paper is a corpus-driven study of written electronic texts, particularly the “About Us” sections in the university websites of 41 members of the Asian Association of Open Universities (AAOU). This inquiry is important because it will provide an insight as to how AAOU members describe and portray themselves in the World Wide Web, a platform which is highly utilized in the field of distance education. This will also lead to the understanding of conventional knowledge among AAOU members during the period of study. The paper aims to discuss these issues.

Design/methodology/approach

Guided by Swales’ (1990) seminal work on genre analysis, the researchers conducted a three-part genre analysis which involved identification and analysis of moves, keywords, and concordance lines.

Findings

Results of the keyword analysis were conducted using the AntConc application. Anthony (2017) found that the top 100 keywords with positive keyness exemplified inherent characteristics of open and distance learning institutions as well as characteristics common to higher education institutions and their thrusts. The analysis also found that the use of adjectives and verbs with positive denotations is common in the “About Us” sections. Concordance for several keywords related to the overarching theme of the AAOU 2017 Conference then revealed that the AAOU members are active in the discourse about accessibility, assessment, and quality, while there is not much discourse on openness, inclusivity, and justice. Meanwhile, subscribing to equality and equity could still be a point of discussion among the AAOU members as the concordance analysis revealed more discourse on equality than equity as a goal and principle. Overall, results of the genre analysis resonated with previous studies of the academic genre as the “About Us” sections are promotional in both authoritarian and inclusive ways.

Originality/value

The inquiry will provide the members of the AAOU with an overview of their common communicative purposes, overused or underused keywords, and their usage of these words which they may opt to work on in the future.
From statistics, through new requirements to mathematical modelling of SAT aircraft safety
Authors: Dziugiel Bartosz , Goraj Zdobyslaw Jan
Published: April 2018

Purpose

The purpose of this study is to investigate the influence of the technical and operational specifications of the Small Aircraft Transport System (SAT/SATS) to the achieved safety level.

Design/methodology/approach

Safety estimation was made with the use of mathematical model of safety of light aircraft in commercial operations developed on the basis of Federal Aviation Administration (FAA) data. The analysis was conducted for two different SATS business models based on Direct AiR Transport (DART) concept. It allowed for the investigation of the impact of technical specifications of the aircraft included into the SATS fleet as well as the selected elements of the applied business model on SATS safety level.

Findings

It was found that the proposed changes to DART system resulted in a significant improvement of safety. Mean Time Between Incidents and Accident (MTBIA) increased by 200 per cent. Additionally, the introduced alterations impacted the weights of particular domains and pilot’s error became less critical than the technical reliability.

Practical implications

It was shown that the application of new requirements influences both the safety level and the cost of operation, which was demonstrated within the ESPOSA and DART projects. Additionally, it was indicated that further effort to improve the light aircraft safety is absolutely necessary.

Originality/value

Originality consists in combining in one mathematical model both the aircraft configuration and the rules for business operation. Optimization of selected parameters of the system leads to a significant reduction in the accident number and to keeping the cost increment at a reasonable level. It was also found that the resulted improvement sometimes cannot be sufficient to consider a small aircraft operation fully safe, mainly owing to the numerous restrictions because of its small weight and loading capacity.
Structural dynamics of a gyrocopter: numerical approach in some emergency cases
Authors: Dacko Adam , Borkowski Pawel , Lindstedt Lukasz Pawel , Rzymkowski Cezary , Rodzewicz Miroslaw
Published: April 2018

Purpose

This paper aims to present the assumptions, analysis and sample results of numerical modeling and analysis of dynamic events encountered in emergency cases during deployment of parachute rescue system (PRS) and hard landing of a small gyrocopter. The optimal design requires knowledge of structural loads and structural response – the information obtained often from experiment. Numerical simulation is presented as an alternative tool for estimating these data.

Design/methodology/approach

Structural analyses were performed using MSC.Nastran. Multibody simulations were done using MADYMO system.

Findings

Initial design parameters were evaluated and verified in numerical simulations. Some of the resulting conclusions were proven during the test flights.

Practical implications

Some chosen results of simulation of dynamic problems are presented. They can be useful as reference values for similar cases for light aircraft analysis.

Originality/value

The paper presents an alternative way of assessing structural response parameters in the case of emergency dynamic events of usage of PRS. The results can be used in other projects.