bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery: A Double-Blind Randomized Clinical Pilot Study Comparing Dobutamine and Milrinone*
Authors: Cavigelli-Brunner Anna , Hug Maja I. , Dave Hitendu , Baenziger Oskar , Buerki Christoph , Bettex Dominique , Cannizzaro Vincenzo , Balmer Christian
Published: March 2018

Objectives:

Dobutamine and milrinone are commonly used after open-heart surgery to prevent or treat low cardiac output syndrome. We sought to compare efficacy and safety of these drugs in pediatric patients.

Design:

Prospective, single-center, double-blinded, randomized clinical pilot study.

Setting:

Tertiary-care university children’s hospital postoperative pediatric cardiac ICU.

Patients:

After written consent, 50 consecutive patients (age, 0.2–14.2 yr; median, 1.2 yr) undergoing open-heart surgery for congenital malformations were included.

Interventions:

After cardiopulmonary bypass, a continuous infusion of either dobutamine or milrinone was administered for the first 36 postoperative hours. Maximum dose: dobutamine 6 µg/kg/min, milrinone 0.75 µg/kg/min.

Measurements and Main Results:

There were no significant differences in demographic data, complexity of surgery, and intraoperative characteristics between the two study groups (dobutamine vs milrinone). Efficacy was defined as need for additional vasoactive support, which did not differ between groups (dobutamine 61% vs milrinone 67%; p = 0.71). Sodium nitroprusside was used more often in the dobutamine group (42% vs 13%; p = 0.019). Systolic blood pressure showed a trend toward higher values in the dobutamine group, whereas both drugs increased heart rate early postoperatively. Echocardiography demonstrated a consistently good cardiac function in both groups. Central venous oxygen saturation, serum lactate levels, urine output, time to chest tube removal, length of mechanical ventilation, ICU, and hospital stay were similar in both groups. Both drugs were well tolerated, no serious adverse events occurred.

Conclusions:

Dobutamine and milrinone are safe, well tolerated, and equally effective in prevention of low cardiac output syndrome after pediatric cardiac surgery. The hemodynamic response of the two drugs is comparable. In uncomplicated cases, a trend toward the more cost-saving dobutamine might be anticipated; however, milrinone demonstrated a trend toward higher efficacy in afterload reduction.
Effect of a Sepsis Educational Intervention on Hospital Stay*
Authors: Fernández-Sarmiento Jaime , Carcillo Joseph A. , Salinas Claudia M. , Galvis Edgar F. , López Paula A. , Jagua-Gualdrón Andrés
Published: March 2018

Objectives:

To evaluate adherence to the sepsis bundle before and after an educational strategy and its impact on hospital stay.

Design:

A prospective, analytic, before-and-after study of children with severe sepsis and septic shock who presented to the emergency department.

Setting:

Carried out from January to December 2014 in the emergency department of a quaternary care hospital.

Patients:

Of a total of 19,836 children who presented to the emergency department, 4,383 had an infectious pathology, with 203 of these showing severe sepsis and septic shock (124 pre intervention, and 79 post intervention).

Interventions:

The healthcare providers caring for the patients in pediatric emergency received an educational intervention and an update on the bundle concepts proposed in 2010 by the Pediatric Advanced Life Support program of the American Heart Association and adapted by this study’s investigators.

Measurements and Main Results:

The main cause of sepsis in both groups was respiratory (59 vs 33; p = 0.72), without differences in the Pediatric Index of Mortality 2 score (7.23 vs 8.1; p = 0.23). The postintervention group showed a reduced hospital stay (11.6 vs 7.9 d; p = 0.01), a shorter time before ordering fluid boluses (247 vs 5 min; p = 0.001), the application of the first dose of antibiotic (343 vs 271 min; p = 0.03), and a decreased need for mechanical ventilation (20.1% vs 7.5%; p = 0.01). Postintervention adherence to the complete bundle was 19.2%, compared with the preintervention group, which was 27.7% (p = 0.17).

Conclusions:

Adherence to a bundle strategy is low following an educational intervention. However, when patients are managed after instruction in guideline recommendations, hospital stay may be significantly reduced.
Late-Onset Vitamin K Deficiency Presenting as Scrotal Bruising and Mediastinal Mass
Authors: Bruns Lauren A. , Isbey Sarah , Tanverdi Melisa , Kane Ian
Published: March 2018

Although there are several reports of intracranial hemorrhage associated with vitamin K deficient bleeding, there are few reported cases of extracranial manifestations, specifically involving the thymus. Here, we discuss the unique case of a 4-week-old infant presenting with scrotal discoloration, respiratory distress, and widened mediastinum, found to have thymic hemorrhage related to confirmed coagulopathy secondary to late-onset vitamin K deficiency bleeding of the newborn.
Low-Grade Malignant Fibrous Histiocytoma Originating From the Medial Rectus Muscle
Authors: Yan Jianhua
Published: March 2018

Purpose:

Fibrous histiocytomas (FHs) involving the orbit are uncommon. To our knowledge, here the authors report the first patient with an orbital low-grade malignant FH originating from the medial rectus muscle.

Methods:

A clinical report relating clinical features as well as imaging and histopathologic findings is presented.

Results:

A 26-year-old female presented with a left eye proptosis that had been present for 4 months. A small left exotropia was observed and ocular motility evaluation revealed a −3 adduction and −1 abduction of the left eye. B-mode ultrasonic scans demonstrated a 2.5 × 2.0 cm mass with medium internal echo and a clear boundary located in the nasal region of the left orbit. Magnetic resonance imaging (MRI) showed a 2.8 × 2.0 cm oval extraconal orbital mass, with isointensity on T1-weighted MRI and hyperintensity on T2-weighted MRI. An anterior orbitotomy was performed and the tumor was completely removed. The mass originated from the medial rectus muscle. Histopathologic evaluation confirmed a low-grade malignant FH. After surgery, the left exotropia was no longer present. Ocular motility revealed a −1 adduction and −1 abduction of the left eye. No recurrence was evident at 1 year after surgery.

Conclusions:

This rare patient demonstrates that FH may originate from the medial rectus muscle. With careful surgical dissection, a near normal function of the involved muscle can be restored.
Relations Between Hyoid-Related Cephalometric Measurements and Severity of Obstructive Sleep Apnea
Authors: Bilici Suat , Yigit Ozgur , Celebi Ozlem Onerci , Yasak Ahmet Gorkem , Yardimci Aytul Hande
Published: March 2018

Objective:

To evaluate the relationship between the hyoid-related cephalometric measurements and the apnea-hypopnea index (AHI) in patients diagnosed with obstructive sleep apnea (OSA).

Methods:

A total of 56 subjects were evaluated by lateral cephalometric radiography and polysomnography (PSG). The OSA diagnosis was made according to the patients’ AHI. Included were 13 primary snoring, 16 mild OSA, 10 moderate OSA, and 17 severe OSA. C3-hyoid distance and mentum-hyoid distance were measured on lateral cephalogram. Cephalometric measurements and PSG parameters were compared among the different OSA groups.

Results:

The distance between the mentum and hyoid was significantly longer in the severe OSA group than in the primary snoring, mild OSA, and moderate OSA groups (P = 0.029). There was a significant positive correlation between the AHI value and the distance of the mentum hyoid (r = 0.368,P = 0.005). The C3-hyoid distance among the groups was not statistically significant different (P = 0.889).

Conclusion:

The mentum-hyoid distance of patients with severe OSA was longer compared to the other OSA groups. These patients might have more benefit from the surgeries that have an impact on the position of the hyoid bone compared to other patients with OSA.
Determining suicide risk in trauma patients using a universal screening program
Authors: Imran Jonathan B. , Richmond Robyn E. , Madni Tarik D. , Roaten Kimberly , Clark Audra T. , Huang Emily Y. , Mokdad Ali A. , Taveras Luis R. , Abdelfattah Kareem R. , Cripps Michael W. , Eastman Alexander L.
Published: March 2018

BACKGROUND

Trauma patients may be at elevated risk for subsequent suicide; however, it is unclear whether patients at risk can be identified during their initial presentation following injury. The objectives of this study were to evaluate the use of a standardized clinical decision support system for suicide risk screening developed by our hospital system and to determine the incidence of positive suicide screenings in our trauma population.

METHODS

Adult trauma patient screenings were performed by nursing staff during the triage process using the Columbia Suicide Severity Rating Scale, Clinical Practice Screener, Recent (C-SSRS). Adult trauma patients who had a suicide risk screening completed from February 2015 to November 2015 were evaluated retrospectively. Patients were divided into cohorts consisting of those with positive and negative screening assessments. Significance was set at α = 0.05. Statistical analysis was performed using Student t test and a χ2 test where appropriate.

RESULTS

Overall, 3,623 of 3,712 patients (98%) completed a suicide risk screening during the study period. Those who went unscreened were not evaluated due to altered mental status/intubation/emergent surgery (97%), death (1%), or an unwillingness to cooperate (2%). The suicide risk screening result was positive in 161 of 3,623 patients (4%) in the study cohort. On univariate analysis, patients with a positive suicide risk screen result were more likely to be white (43% vs 32%; p = 0.01), identify English as their primary language (91% vs 73%; p < 0.01), have insurance coverage (48% vs 28%; p < 0.01), and were more likely to initiate a low-level trauma activation (27% vs 16%; p <0.01) than those who had a negative screening result. A positive suicide risk assessment result was moderately associated with patients of white race (odds ratio, 1.83; 95% confidence interval, 1.27–2.65) on multivariable logistic regression.

CONCLUSION

Our universal suicide screening process identifies an at-risk subpopulation of trauma patients.

LEVEL OF EVIDENCE

Prognostic study, level III; therapeutic, level IV.
A Randomized Trial of Oral and Transdermal Rivastigmine for Postural Instability in Parkinson Disease Dementia
Authors: McDonald Jaime , Pourcher Emmanuelle , Nadeau Alexandra , Corbeil Philippe
Published: March 2018

Objectives

The objective of this study was to compare the efficacy and safety of oral and transdermal rivastigmine for postural instability in patients with Parkinson disease dementia (PDD) who were candidates for a cholinesterase inhibitor. The primary outcome was the change in mean velocity of the center of pressure (CoP) after 6 months. Secondary outcomes included structural parameters of dynamic posturography, clinical rating scales, and adverse events requiring dose reduction.

Methods

Patients with PDD were randomized in a 1:1 ratio to oral or transdermal rivastigmine with target doses of 6 mg twice daily and 9.5 mg/10 cm2 daily, respectively. Outcomes were assessed at baseline and 6 months. Results were compared within and between groups.

Results

Nineteen patients completed the study (n = 8 oral, n = 11 transdermal). Mean daily doses of 9.4 (±1.5 mg) and 16.4 (±3.6 mg) were achieved in the oral and transdermal groups, respectively. The transdermal group demonstrated a significant 15.8% decrease in mean velocity of CoP (patch: P < 0.05; oral: 10.0% decrease, P = 0.16) in the most difficult scenario (eyes closed with sway-referenced support). There was no difference between groups (P = 0.27). For structural parameters, significant improvements were seen in the mean duration of peaks (patch) and interpeak distance (oral) in the most difficult condition. No changes were observed in clinical rating scales. Six patients experienced nonserious adverse events requiring dose reduction (n = 5 oral; n = 1 transdermal).

Conclusions

Rivastigmine may improve certain elements of postural control, notably the mean velocity of CoP. Benefits appear to be more obvious under more taxing sensory conditions.
Ability to modulate birdsong across social contexts develops without imitative social learning
Authors: James Logan S. , Dai Jennifer B. , Sakata Jon T.
Published: March 2018

Many important behaviours are socially learned. For example, the acoustic structure of courtship songs in songbirds is learned by listening to and interacting with conspecifics during a sensitive period in development. Signallers modify the spectral and temporal structures of their vocalizations depending on the social context, but the degree to which this modulation requires imitative social learning remains unknown. We found that male zebra finches (Taeniopygia guttata) that were not exposed to context-dependent song modulations throughout development significantly modulated their song in ways that were typical of socially reared birds. Furthermore, the extent of these modulations was not significantly different between finches that could or could not observe these modulations during tutoring. These data suggest that this form of vocal flexibility develops without imitative social learning in male zebra finches.
Model reduction enables Turing instability analysis of large reaction–diffusion models
Authors: Smith Stephen , Dalchau Neil
Published: March 2018

Synthesizing a genetic network which generates stable Turing patterns is one of the great challenges of synthetic biology, but a significant obstacle is the disconnect between the mathematical theory and the biological reality. Current mathematical understanding of patterning is typically restricted to systems of two or three chemical species, for which equations are tractable. However, when models seek to combine descriptions of intercellular signal diffusion and intracellular biochemistry, plausible genetic networks can consist of dozens of interacting species. In this paper, we suggest a method for reducing large biochemical systems that relies on removing the non-diffusible species, leaving only the diffusibles in the model. Such model reduction enables analysis to be conducted on a smaller number of differential equations. We provide conditions to guarantee that the full system forms patterns if the reduced system does, and vice versa. We confirm our technique with three examples: the Brusselator, an example proposed by Turing, and a biochemically plausible patterning system consisting of 17 species. These examples show that our method significantly simplifies the study of pattern formation in large systems where several species can be considered immobile.
Plant-inspired pipettes
Authors: Nakamura Keigo , Hisanaga Tetsuya , Fujimoto Koichi , Nakajima Keiji , Wada Hirofumi
Published: March 2018

The female sex organ of the liverwort (
Marchantia polymorpha
) has a characteristic parasol-like form highly suitable for collecting water droplets containing sperm for fertilization. Motivated by this observation and using three-dimensional printing techniques, we develop a parasol-like rigid object that can grab, transport and release water droplets of a maximum size of about 1 cm. By combining experiments and scaling theory, we quantify the object's fundamental wetting and fluid dynamical properties. We construct a stability phase diagram and suggest that it is largely insensitive to properties of liquids such as surface tension and viscosity. A simple scaling argument is developed to explain the phase boundary. Our study provides basic design rules of a simple pipette-like device with bubble-free capture and drop of liquids, which can be used in laboratory settings and has applications within soft robotics. Through systematic experimental investigations, we suggest the optimal design criteria of the liverwort-inspired object to achieve maximal pipetting performance. We also provide, based on our scalable model experiments, a biological implication for the mechanistic advantage of this structure in liverwort reproduction.
Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition
Authors: Koch Franziska , Müller Michael , König Finja , Meyer Nina , Gattlen Jasmin , Pieles Uwe , Peters Kirsten , Kreikemeyer Bernd , Mathes Stephanie , Saxer Sina
Published: March 2018

Self-assembling peptide hydrogels can be modified regarding their biodegradability, their chemical and mechanical properties and their nanofibrillar structure. Thus, self-assembling peptide hydrogels might be suitable scaffolds for regenerative therapies and tissue engineering. Owing to the use of various peptide concentrations and buffer compositions, the self-assembling peptide hydrogels might be influenced regarding their mechanical characteristics. Therefore, the mechanical properties and stability of a set of self-assembling peptide hydrogels, consisting of 11 amino acids, made from four beta sheet self-assembling peptides in various peptide concentrations and buffer compositions were studied. The formed self-assembling peptide hydrogels exhibited stiffnesses ranging from 0.6 to 205 kPa. The hydrogel stiffness was mostly affected by peptide sequence followed by peptide concentration and buffer composition. All self-assembling peptide hydrogels examined provided a nanofibrillar network formation. A maximum self-assembling peptide hydrogel dissolution of 20% was observed for different buffer solutions after 7 days. The stability regarding enzymatic and bacterial digestion showed less degradation in comparison to the self-assembling peptide hydrogel dissolution rate in buffer. The tested set of self-assembling peptide hydrogels were able to form stable scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are suitable for a regenerative therapy.
Explicit solutions to correlation matrix completion problems, with an application to risk management and insurance
Authors: Georgescu Dan I. , Higham Nicholas J. , Peters Gareth W.
Published: March 2018

We derive explicit solutions to the problem of completing a partially specified correlation matrix. Our results apply to several block structures for the unspecified entries that arise in insurance and risk management, where an insurance company with many lines of business is required to satisfy certain capital requirements but may have incomplete knowledge of the underlying correlation matrix. Among the many possible completions, we focus on the one with maximal determinant. This has attractive properties and we argue that it is suitable for use in the insurance application. Our explicit formulae enable easy solution of practical problems and are useful for testing more general algorithms for the maximal determinant correlation matrix completion problem.
Vertical exploration and dimensional modularity in mice
Authors: Wexler Yair , Benjamini Yoav , Golani Ilan
Published: March 2018

Exploration is a central component of animal behaviour studied extensively in rodents. Previous tests of free exploration limited vertical movement to rearing and jumping. Here, we attach a wire mesh to the arena wall, allowing vertical exploration. This provides an opportunity to study the morphogenesis of behaviour along the vertical dimension, and examine the context in which it is performed. In the current set-up, the mice first use the doorway as a point reference for establishing a borderline linear path along the circumference of the arena floor, and then use this path as a linear reference for performing horizontal forays towards the centre (incursions) and vertical forays on the wire mesh (ascents). Vertical movement starts with rearing on the wall, and commences with straight vertical ascents that increase in extent and complexity. The mice first reach the top of the wall, then mill about within circumscribed horizontal sections, and then progress horizontally for increasingly longer distances on the upper edge of the wire mesh. Examination of the sequence of borderline segments, incursions and ascents reveals dimensional modularity: an initial series (bout) of borderline segments precedes alternating bouts of incursions and bouts of ascents, thus exhibiting sustained attention to each dimension separately. The exhibited separate growth in extent and in complexity of movement and the sustained attention to each of the three dimensions disclose the mice's modular perception of this environment and validate all three as natural kinds.
Vibration of carbon nanotubes with defects: order reduction methods
Authors: Hudson Robert B. , Sinha Alok
Published: March 2018

Order reduction methods are widely used to reduce computational effort when calculating the impact of defects on the vibrational properties of nearly periodic structures in engineering applications, such as a gas-turbine bladed disc. However, despite obvious similarities these techniques have not yet been adapted for use in analysing atomic structures with inevitable defects. Two order reduction techniques, modal domain analysis and modified modal domain analysis, are successfully used in this paper to examine the changes in vibrational frequencies, mode shapes and mode localization caused by defects in carbon nanotubes. The defects considered are isotope defects and Stone–Wales defects, though the methods described can be extended to other defects.
On the theory of drainage area for regular and non-regular points
Authors: Bonetti S. , Bragg A. D. , Porporato A.
Published: March 2018

The drainage area is an important, non-local property of a landscape, which controls surface and subsurface hydrological fluxes. Its role in numerous ecohydrological and geomorphological applications has given rise to several numerical methods for its computation. However, its theoretical analysis has lagged behind. Only recently, an analytical definition for the specific catchment area was proposed (Gallant & Hutchinson. 2011
Water Resour. Res.
47
, W05535. (
doi:10.1029/2009WR008540
)), with the derivation of a differential equation whose validity is limited to regular points of the watershed. Here, we show that such a differential equation can be derived from a continuity equation (Chen
et al.
2014
Geomorphology
219
, 68–86. (
doi:10.1016/j.geomorph.2014.04.037
)) and extend the theory to critical and singular points both by applying Gauss’s theorem and by means of a dynamical systems approach to define basins of attraction of local surface minima. Simple analytical examples as well as applications to more complex topographic surfaces are examined. The theoretical description of topographic features and properties, such as the drainage area, channel lines and watershed divides, can be broadly adopted to develop and test the numerical algorithms currently used in digital terrain analysis for the computation of the drainage area, as well as for the theoretical analysis of landscape evolution and stability.
Giant kelp,
Macrocystis pyrifera
, increases faunal diversity through physical engineering
Authors: Miller Robert J. , Lafferty Kevin D. , Lamy Thomas , Kui Li , Rassweiler Andrew , Reed Daniel C.
Published: March 2018

Foundation species define the ecosystems they live in, but ecologists have often characterized dominant plants as foundational without supporting evidence. Giant kelp has long been considered a marine foundation species due to its complex structure and high productivity; however, there is little quantitative evidence to evaluate this. Here, we apply structural equation modelling to a 15-year time series of reef community data to evaluate how giant kelp affects the reef community. Although species richness was positively associated with giant kelp biomass, most direct paths did not involve giant kelp. Instead, the foundational qualities of giant kelp were driven mostly by indirect effects attributed to its dominant physical structure and associated engineering influence on the ecosystem, rather than by its use as food by invertebrates and fishes. Giant kelp structure has indirect effects because it shades out understorey algae that compete with sessile invertebrates. When released from competition, sessile species in turn increase the diversity of mobile predators. Sea urchin grazing effects could have been misinterpreted as kelp effects, because sea urchins can overgraze giant kelp, understorey algae and sessile invertebrates alike. Our results confirm the high diversity and biomass associated with kelp forests, but highlight how species interactions and habitat attributes can be misconstrued as direct consequences of a foundation species like giant kelp.
Eco-evolutionary feedbacks promote fluctuating selection and long-term stability of antagonistic networks
Authors: de Andreazzi Cecilia Siliansky , Guimarães Paulo R. , Melián Carlos J.
Published: March 2018

Studies have shown the potential for rapid adaptation in coevolving populations and that the structure of species interaction networks can modulate the vulnerability of ecological systems to perturbations. Although the feedback loop between population dynamics and coevolution of traits is crucial for understanding long-term stability in ecological assemblages, modelling eco-evolutionary dynamics in species-rich assemblages is still a challenge. We explore how eco-evolutionary feedbacks influence trait evolution and species abundances in 23 empirical antagonistic networks. We show that, if selection due to antagonistic interactions is stronger than other selective pressures, eco-evolutionary feedbacks lead to higher mean species abundances and lower temporal variation in abundances. By contrast, strong selection of antagonistic interactions leads to higher temporal variation of traits and on interaction strengths. Our results present a theoretical link between the study of the species persistence and coevolution in networks of interacting species, pointing out the ways by which coevolution may decrease the vulnerability of species within antagonistic networks to demographic fluctuation.
Plasticity for desiccation tolerance acrossDrosophilaspecies is affected by phylogeny and climate in complex ways
Authors: Kellermann Vanessa , Hoffmann Ary A. , Overgaard Johannes , Loeschcke Volker , Sgrò Carla M.
Published: March 2018

Comparative analyses of ectotherm susceptibility to climate change often focus on thermal extremes, yet responses to aridity may be equally important. Here we focus on plasticity in desiccation resistance, a key trait shaping distributions ofDrosophilaspecies and other small ectotherms. We examined the extent to which 32Drosophilaspecies, varying in their distribution, could increase their desiccation resistance via phenotypic plasticity involving hardening, linking these responses to environment, phylogeny and basal resistance. We found no evidence to support the seasonality hypothesis; species with higher hardening plasticity did not occupy environments with higher and more seasonal precipitation. As basal resistance increased, the capacity of species to respond via phenotypic plasticity decreased, suggesting plastic responses involving hardening may be constrained by basal resistance. Trade-offs between basal desiccation resistance and plasticity were not universal across the phylogeny and tended to occur within specific clades. Phylogeny, environment and trade-offs all helped to explain variation in plasticity for desiccation resistance but in complex ways. These findings suggest some species have the ability to counter dry periods through plastic responses, whereas others do not; and this ability will depend to some extent on a species' placement within a phylogeny, along with its basal level of resistance.
Experimental demonstration that offspring fathered by old males have shorter telomeres and reduced lifespans
Authors: Noguera José C. , Metcalfe Neil B. , Monaghan Pat
Published: March 2018

Offspring of older parents frequently show reduced longevity, but the mechanisms driving this so-called ‘Lansing effect' are unknown. While inheritance of short telomeres from older parents could underlie this effect, studies to date in different species have found mixed results, reporting positive, negative or no association between parental age and offspring telomere length (TL). However, most of the existing evidence is from non-experimental studies in which it is difficult to exclude alternative explanations such as differential survival of parents with different telomere lengths. Here we provide evidence in the zebra finch that offspring from older parents have reduced lifespans. As a first step in disentangling possible causes, we used an experimental approach to examine whether or not we could detect pre-natal paternal effects on offspring TL. We found that zebra finch embryos fathered by old males have shorter telomeres than those produced by the same mothers but with younger fathers. Since variation in embryonic TL persists into post-natal life, and early life TL is predictive of longevity in this species, this experimental study demonstrates that a paternally driven pre-natal TL reduction could at least in part underlie the reduced lifespan of offspring from older parents.
Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes
Authors: Johnston Luke W. , Liu Zhen , Retnakaran Ravi , Zinman Bernard , Giacca Adria , Harris Stewart B. , Bazinet Richard P. , Hanley Anthony J.
Published: March 2018

Aims

Our aim was to examine longitudinal associations of triacylglyceride fatty acid (TGFA) composition with insulin sensitivity (IS) and beta-cell function.

Methods

Adults at-risk for T2D (n=477) had glucose and insulin measured from a glucose challenge at 3 time points over 6 years. The outcome variables Matsuda index (ISI), HOMA2-%S, Insulinogenic Index over HOMA-IR (IGI/IR), and Insulin Secretion-Sensitivity Index-2 (ISSI-2) were computed from the glucose challenge. Gas chromatography quantified TGFA composition from the baseline. We used adjusted generalized estimating equations (GEE) models and partial least squares (PLS) regression for the analysis.

Results

In adjusted GEE models, four TGFA (14:0, 16:0, 14:1n-7, 16:1n-7 as mol%) had strong negative associations with IS while others (e.g. 18:1n-7, 18:1n-9, 20:2n-6, 20:5n-3) had strong positive associations. Few associations were seen for beta-cell function, except for 16:0, 18:1n-7, and 20:2n-6. PLS analysis indicated four TGFA (14:0, 16:0, 14:1n-7, 16:1n-7) that clustered together and strongly related with lower IS. These four TGFA also correlated highly (r>0.4) with clinically measured TG.

Conclusions

We found that higher proportions of a cluster of four TGFA strongly related with lower IS as well as hypertriglyceridemia, suggesting only a few fatty acids within the TGFA composition may primarily explain lipids’ role in glucose dysregulation.
A mechanosensitive RhoA pathway that protects epithelia against acute tensile stress
Authors: Acharya Bipul R , Nestor-Bergmann Alexander , Liang Xuan , Budnar Srikanth , Jensen Oliver E. , Bryant Zev , Yap Alpha S.
Published: March 2018

Adherens junctions are tensile structures that couple epithelial cells together. Junctional tension can arise from cell-intrinsic application of contractility or from the cell-extrinsic forces of tissue movement. In all these circumstances, it is essential that epithelial integrity be preserved despite the application of tensile stress. In this study, we identify junctional RhoA as a mechanosensitive signaling pathway that responds to epithelial stress. The junctional specificity of this response is mediated by the heterotrimeric protein Gα12, which is recruited by E-cadherin and, in turn, recruits p114 RhoGEF to activate RhoA. Further, we identify Myosin VI as a key mechanosensor, based on its intrinsic capacity to anchor E-cadherin to F-actin when exposed to tensile load. Tension-activated RhoA signaling was necessary to preserve epithelial integrity, which otherwise undergoes fracture when monolayer stress is acutely increased by calyculin. Paradoxically, this homeostatic RhoA signaling pathway increases junctional actomyosin, a contractile response that might be expected to itself promote fracture. Simulations of a vertex-based model revealed that the protective effect of RhoA signaling can be explained through increased yield limit at multicellular vertices, where experiments showed p114 RhoGEF was necessary to increase E-cadherin and promote actin assembly and organization.
Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study
Authors: Zhai Jing , Knox Kenneth , Twigg Homer L. , Zhou Hua , Zhou Jin J.
Published: March 2018

In the metagenomics studies, testing the association of microbiome composition and clinical conditions translates to testing the nullity of variance components. Computationally efficient score tests have been the major tools. But they can only apply to the null hypothesis with a single variance component and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to solve the problems of (1) testing the association of the overall microbiome composition in a longitudinal design and (2) detecting the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of human immunodeficiency virus (HIV) infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed lights on the impact of lung microbiome to HIV complexities. The method is implemented in the open source, high-performance computing language Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.
Complex Structural Variants Resolved by Short-Read and Long-Read Whole Genome Sequencing in Mendelian Disorders
Authors: Sanchis-Juan Alba , Stephens Jonathan , French Courtney E , Gleadall Nicholas , Mégy Karyn , Penkett Christopher , Stirrups Kathleen , Delon Isabelle , Dewhurst Eleanor , Dolling Helen , Erwood Marie , Grozeva Detelina , Arno Gavin , Webster Andrew R , Cole Trevor , Austin Topun , Branco Ricardo Garcia ,   NIHR BioResource, Ouwehand Willem H , Raymond F Lucy , Carss Keren J
Published: March 2018

Complex structural variants (cxSVs) are genomic rearrangements comprising multiple structural variants, typically involving three or more breakpoint junctions. They contribute to human genomic variation and can cause Mendelian disease, however they are not typically considered during genetic testing. Here, we investigate the role of cxSVs in Mendelian disease using short-read whole genome sequencing (WGS) data from 1,324 individuals with neurodevelopmental or retinal disorders from the NIHR BioResource project. We present four cases of individuals with a cxSV affecting Mendelian disease-associated genes. Three of the cxSVs are pathogenic: a de novo duplication-inversion-inversion-deletion affecting ARID1B in an individual with Coffin-Siris syndrome, a deletion-inversion-duplication affecting HNRNPU in an individual with intellectual disability and seizures, and a homozygous deletion-inversion-deletion affecting CEP78 in an individual with cone-rod dystrophy. Additionally, we identified a de novo duplication-inversion-duplication overlapping CDKL5 in an individual with neonatal hypoxic-ischaemic encephalopathy. Long-read sequencing technology used to resolve the breakpoints demonstrated the presence of both a disrupted and an intact copy of CDKL5 on the same allele; therefore, it was classified as a variant of uncertain significance. Analysis of sequence flanking all breakpoint junctions in all the cxSVs revealed both microhomology and longer repetitive sequences, suggesting both replication and homology based processes. Accurate resolution of cxSVs is essential for clinical interpretation, and here we demonstrate that long-read WGS is a powerful technology by which to achieve this. Our results show cxSVs are an important although rare cause of Mendelian disease, and we therefore recommend their consideration during research and clinical investigations.
Unraveling rice tolerance mechanisms againstSchizotetranychus oryzaemite infestation
Authors: Bufon Giseli , dos Reis Blasi Édina Aparecida , Rativa Angie Geraldine Sierra , Lamb Thainá Inês , Gastmann Rodrigo , Adamski Janete Mariza , Schwambach Joséli , Ricachenevsky Felipe Klein , Heringer Angelo Schuabb , Silveira Vanildo , Lopes Mara Cristina Barbosa , Sperotto Raul Antonio
Published: March 2018

Infestation ofSchizotetranychus oryzae(Acari: Tetranychidae) causes great losses in rice productivity. Infestation in Puitá INTA-CL cultivar reduced the number of seeds/plant, percentage of full seeds, 1,000 seeds weight, and seed length, whereas infestation in IRGA423 increased 1,000 seeds weight and seed length. Reduction in seed weight/plant caused by infestation was higher in Puitá INTA-CL than IRGA423. Thus, Puitá INTA-CL was established as susceptible, and IRGA423 as tolerant toS. oryzaeinfestation. Photosynthetic parameters were less affected by infestation in IRGA423 than in Puitá INTA-CL. Infestation also caused accumulation of H2O2, decreased cell membrane integrity and accelerated senescence in leaves of Puitá INTA-CL, while leaves of IRGA423 presented higher levels of phenolics compounds. Using proteomic analysis, we identified proteins related to plant defense, such as jasmonate synthesis, and related to other mechanisms of tolerance such as oxidative stress, photosynthesis, and DNA structure maintenance, more abundant in IRGA423 after seven days of infestation. We detected higher levels of silicon (as amorphous silica cells) in leaves of infested IRGA423 plants compared to Puitá INTA-CL, an element previously linked to plant defense. Our data shows that IRGA423 presents tolerance toS. oryzaeinfestation, and that multiple mechanisms might be employed by this cultivar.

Highlight

This is the first report evaluating the defense responses (tolerance and susceptiblity) of two contrasting rice cultivars toSchizotetranychus oryzaemite infestation.
Estimation of population divergence times from SNP data and a test for treeness
Authors: Theunert Christoph , Slatkin Montgomery
Published: March 2018

We present a method for estimating population divergence times from genome sequences when one individual is sampled from each population. Our method is a simplified version of one presented by Rassmussen et al. (2014) for testing for direct ancestry of an archaic genome. Our method does not require distinguishing ancestral from derived alleles or assumptions about demographic history before population divergence. We discuss the relationship of our method to two similar methods, one introduced by Green et al. (2010) and denoted by F(A | B) and the other introduced by Schlebusch et al. (2017) and called the TT method. When our method is applied to individuals from three or more populations, it provides a test of whether the population history is treelike. We illustrate the use of our method by applying it to three high-coverage archaic genomes, two Neanderthals (Vindija and Altai) and a Denisovan.
Prevalent polymorphism in benzophenones
Authors: Soqaka Antonia A. , Esterhuysen Catharine , Lemmerer Andreas
Published: March 2018

We report here the crystal structures of dimorphs of 4-hydroxybenzophenone, C13H10O2, and 4-(dimethylamino)benzophenone, C15H15NO, as well as trimorphs of 4,4′-dimethylbenzophenone, C15H14O. The polymorphs were isolated from slow-evaporation conditions or from cocrystallization attempts. The main differences between the polymorphs involve differences in packing rather than differences in conformation, owing to the limited conformational freedom of the three molecules. 4-Hydroxybenzophenone is the exception, exhibiting almost identical packing arrangements in the two polymorphs, with the only major changes being in the interplanar orientations. The lattice energies of the respective polymorphs of the three compounds reported here are all within 1 kcal mol−1 of each other. The existence of nine further polymorphic benzophenone derivatives in the literature suggests that there is a good deal of polymorphic space in this class of compounds.
The vanadate garnet Ca2NaCd2V3O12: a single-crystal X-ray diffraction study
Authors: Tokuda Makoto , Yoshiasa Akira , Mashimo Tsutomu , Iishi Kazuake , Nakatsuka Akihiko
Published: March 2018

Single crystals of the vanadate garnet Ca2NaCd2V3O12 (dicalcium sodium dicadmium trivanadate) were synthesized using the floating-zone method and the crystal structure was investigated using single-crystal X-ray diffraction. We considered the effectiveness of substitution of the Y-site cation with reference to previous structural studies of vanadate garnets. The structures of vanadate garnets are subject to geometric constraints similar to those of silicate garnets. These constraints force the tetrahedral–dodecahedral shared edge length in vanadate garnets to become shorter than the unshared dodecahedral edge length, as in ugrandite (uvarovite, grossular and andradite) garnets. However, the vanadate garnet Ca2NaCd2V3O12 exhibits the normal structural feature, similar to pyralspite (pyrope, almandine and spessartine) garnets, namely that the dodecahedral–dodecahedral shared edge length is shorter than the unshared dodecahedral edge length. With increasing ionic radius of the Y-site cation, the atomic coordinates x, y and z of oxygen adopt values which satisfy Pauling's third rule.
A phenomenological approach to diagnosing psychosis in autism spectrum disorder and intellectual disability: a case series
Authors: Rai Rahul , Tromans Samuel , Kapugama Chaya , Chester Verity , Gunaratna Ignatius , Langdon Peter , Alexander Regi T.
Published: March 2018

Purpose

The diagnosis of psychosis in individuals with autism spectrum disorder (ASD) poses a unique clinical challenge. The presence of intellectual disability (ID) further complicates the diagnostic picture. Reliable and timely diagnosis of psychosis in such individuals minimises the duration of untreated psychotic symptoms and the subsequent impact on the quality of life of the patients concerned. The paper aims to discuss this issue.

Design/methodology/approach

The authors present four patients with psychosis, ASD and ID, who have received care within forensic mental health and ID settings. These examples demonstrate the interaction between these conditions, as well as issues pertaining to diagnosis and management.

Findings

In all four patients, sustained use of antipsychotic medication was objectively associated with an improvement in psychotic symptoms and quality of life. In instances where autistic phenomena were accentuated upon development of psychosis, such features returned to the baseline levels evident prior to the onset of psychosis.

Practical implications

The discussion and related case examples could improve the understanding of the possibility of psychosis in individuals with ASD and ID, and increase awareness of this diagnostic possibility among healthcare professionals.

Originality/value

This is the first published case series illustrating the challenges of diagnosing psychosis in individuals with ASD and ID.
Estimating the size of the national logistics market
Authors: Solakivi Tomi , Ojala Lauri , Lorentz Harri , Töyli Juuso , Laari Sini
Published: March 2018

Purpose

The size of the logistics market is typically estimated from the national accounting and market data. However, this data does not take certain in-house logistics services into account and most likely underestimates the true size of the market. The purpose of this paper is to develop a method for estimating the potential size of the logistics market in terms of overall logistics expenditure and to also account for in-house services.

Design/methodology/approach

The research approach involves combining longitudinal industry- and firm-level turnover data, incorporating survey data from Finland on logistics outsourcing and costs, and calculating yearly logistics expenditure and the market demand for logistics services. Descriptive statistics, weighted arithmetic means and analyses of variance are employed in the estimations.

Findings

The research suggests and demonstrates a rigorous method for estimating the size of the logistics market, including both market-based demand and in-house services.

Research limitations/implications

The empirical data used to illustrate the result are limited to a single country. The methodology should be further validated with data from other countries. The quality of the survey data could be improved by targeting multiple informants from a single firm.

Social implications

One outcome of the research is that policymakers will be better able to estimate the size of the logistics market on a national level. For service providers, the results provide additional information on the market potential of logistics services.

Originality/value

The novelty of the research lies in combining multiple data sources and expanding the estimation of the logistics market to include services provided in-house.
Consumer-driven e-commerce
Authors: Lim Stanley Frederick W.T. , Jin Xin , Srai Jagjit Singh
Published: March 2018

Purpose

The purpose of this paper is to re-examine the extant research on last-mile logistics (LML) models and consider LML’s diverse roots in city logistics, home delivery and business-to-consumer distribution, and more recent developments within the e-commerce digital supply chain context. The review offers a structured approach to what is currently a disparate and fractured field in logistics.

Design/methodology/approach

The systematic literature review examines the interface between e-commerce and LML. Following a protocol-driven methodology, combined with a “snowballing” technique, a total of 47 articles form the basis of the review.

Findings

The literature analysis conceptualises the relationship between a broad set of contingency variables and operational characteristics of LML configuration (push-centric, pull-centric, and hybrid system) via a set of structural variables, which are captured in the form of a design framework. The authors propose four future research areas reflecting likely digital supply chain evolutions.

Research limitations/implications

To circumvent subjective selection of articles for inclusion, all papers were assessed independently by two researchers and counterchecked with two independent logistics experts. Resulting classifications inform the development of future LML models.

Practical implications

The design framework of this study provides practitioners insights on key contingency and structural variables and their interrelationships, as well as viable configuration options within given boundary conditions. The reformulated knowledge allows these prescriptive models to inform practitioners in their design of last-mile distribution.

Social implications

Improved LML performance would have positive societal impacts in terms of service and resource efficiency.

Originality/value

This paper provides the first comprehensive review on LML models in the modern e-commerce context. It synthesises knowledge of LML models and provides insights on current trends and future research directions.