bluuebunny/crossref_metadata_2025 huggingface dataset:
ATP and astrocytes play a prominent role in the control of the respiratory pattern generator in the lamprey
Authors: Cinelli Elenia , Iovino Ludovica , Mutolo Donatella
Published: July 2017

Key points

The paratrigeminal respiratory group (pTRG) is responsible for the respiratory pattern generation in the lamprey.

The role of ATP and astrocytes, known to control respiratory activity in mammals, was investigated in the lamprey respiratory network.

ATP microinjected into the pTRG induces a biphasic response consisting of marked increases in respiratory frequency mediated by P2X receptors followed by a decrease in the respiratory motor output due to the ATP metabolite adenosine.

We provide evidence that astrocytes are involved in the genesis of the normal respiratory pattern, ATP‐induced responses and acidification‐induced increases of the respiratory activity.

The function of astrocytes in rhythmic networks appears to be phylogenetically conserved.

The role of ATP and astrocytes in respiratory rhythm modulation has been recently investigated in neonatal rodents. However, no information on the role of ATP and astrocytes within the respiratory network of the lamprey is available, particularly within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator. To address these issues, the present study was carried out on isolated brainstems of the adult lamprey. Bath application of ATP caused marked increases in respiratory frequency followed by decreases in the respiratory motor output, mediated by the ATP metabolite adenosine at the level of the pTRG. Bath applications and microinjections of agonists and antagonists of purinergic receptors showed that ATP increased respiratory activity through an action on pTRG P2X receptors. To disclose the respiratory role of astrocytes, we used bath application of the gliotoxin aminoadipic acid, which dramatically depressed the respiratory motor output that, however, promptly recovered following glutamine application. Furthermore, the excitatory responses to ATP‐γ‐S (a non‐hydrolysable ATP analogue), but not to substance P, microinjected into the pTRG, were abolished. Finally, we also demonstrated that acidification‐induced increases in respiratory activity were ATP‐independent, but mediated by the astrocytes’ glutamate–glutamine cycle. The results show for the first time that ATP and especially astrocytes strongly contribute to the modulation of the lamprey respiratory pattern. Their role in the modulation or maintenance of rhythmic neuronal activities appears to be phylogenetically conserved.
Droplet Formation and Fission in Shear-Thinning/Newtonian Multiphase System Using Bilayer Bifurcating Microchannel
Authors: Ren Yong , Seng Koh Kai , Kai Chin Jit , Wang Jing , Wen Conghua , Yan Yuying
Published: July 2017

With a novel platform of bilayer polydimethylsiloxane microchannel formed by bifurcating junction, we aim to investigate droplet formation and fission in a multiphase system with complex three-dimensional (3D) structure and understand the variations in mechanism associated with droplet formation and fission in the microstructure between shear-thinning/Newtonian system versus Newtonian/Newtonian system. The investigation concentrates on shear-thinning fluid because it is one of the most ubiquitous rheological properties of non-Newtonian fluids. Sodium carboxymethyl cellulose (CMC) solution and silicone oil have been used as model fluids and numerical model has been established to characterize the shear-thinning effect in formation of CMC-in-oil emulsions, as well as breakup dynamics when droplets flow through 3D bifurcating junction. The droplet volume and generation rate have been compared between two systems at the same Weber number and capillary number. Variation in droplet fission has been found between two systems, demonstrating that the shear-thinning property and confining geometric boundaries significantly affect the deformation and breakup of each mother droplet into two daughter droplets at bifurcating junction. The understanding of the droplet fission in the novel microstructure will enable more versatile control over the emulsion formation and fission when non-Newtonian fluids are involved. The model systems in the study can be further developed to investigate the mechanical property of emulsion templated particles such as drug encapsulated microcapsules when they flow through complex media structures, such as blood capillaries or the porous tissue structure, which feature with bifurcating junction.
Visualization of Two-Phase Flow in Serpentine Heat Exchanger Passages With Microscale Pin Fins
Authors: Hoysall Dhruv C. , Keniar Khoudor , Garimella Srinivas
Published: July 2017

Microchannel heat exchangers offer the potential for high heat transfer coefficients; however, implementation challenges must be addressed to realize this potential. Maldistribution of phases among the microchannels and the changing phase velocities associated with phase change present design challenges. Flow maldistribution and oscillatory instabilities can affect transfer rates and pressure drops. In condensers, evaporators, absorbers, and desorbers, changing phase velocities can change prevailing flow regimes from favorable to unfavorable. Geometries with serpentine passages containing pin fins can be configured to maintain favorable flow regimes throughout the component for phase-change heat and mass transfer applications. Due to the possibility of continuous redistribution of the flow across the pin fins along the flow direction, maldistribution can also be reduced. These features enable high heat transfer coefficients, thereby achieving considerable compactness. The characteristics of two-phase flow through a serpentine passage with micro-pin fin arrays with diameter 350 μm and height 406 μm are investigated. An air–water mixture is used to represent two-phase flow through the serpentine test section, and flow features are investigated using high-speed photography. Improved flow distribution is observed in the serpentine geometry. Distinct flow regimes, different from those observed in microchannels, are also established. Void fraction and interfacial area along the length of the serpentine passages are compared with the corresponding values for microchannels. A model developed for the two-phase frictional pressure drops across this serpentine micro-pin fin geometry predicts experimental values with a mean absolute error (MAE) of 7.16%.
Computational Fluid Dynamics Modeling of Flow Boiling in Microchannels With Nonuniform Heat Flux
Authors: Lorenzini Daniel , Joshi Yogendra K.
Published: July 2017

The computational fluid dynamics (CFD) modeling of boiling phenomena has remained a challenge due to numerical limitations for accurately simulating the two-phase flow and phase-change processes. In the present investigation, a CFD approach for such analysis is described using a three-dimensional (3D) volume of fluid (VOF) model coupled with a phase-change model accounting for the interfacial mass and energy transfer. This type of modeling allows the transient analysis of flow boiling mechanisms, while providing the ability to visualize in detail temperature, phase, and pressure distributions for microscale applications with affordable computational resources. Results for a plain microchannel are validated against benchmark correlations for heat transfer (HT) coefficients and pressure drop as a function of the heat flux and mass flux. Furthermore, the model is used for the assessment of two-phase cooling in microelectronics under a realistic scenario with nonuniform heat fluxes at localized regions of a silicon microchannel, relevant to the cooling layer of 3D integrated circuit (IC) architectures. Results indicate the strong effect of two-phase flow regime evolution and vapor accumulation on HT. The effects of reduced saturation pressure, subcooling, and flow arrangement are explored in order to provide insight about the underlying physics and cooling performance.
Antiplane Slip and Bonded Contact Waves at a Planar Interface Between Two Elastic Layers
Authors: Ranjith K.
Published: July 2017

Interfacial wave solutions for a planar interface between two finite layers have been obtained within the framework of antiplane elasticity. Solutions are found to exist both for slipping contact and for bonded contact at the interface. Both the slip and bonded contact waves are found to be dispersive and multivalued. One family of slip and bonded contact waves is found with phase velocity in between the shear wave speeds of the two solids. It is also found that two families of slip and bonded contact waves exist with phase velocity greater than the shear wave speed of both solids.
Thermo-Fluid Optimization of a Solar Porous Absorber With a Variable Pore Structure
Authors: Wang P. , Li J. B. , Vafai K. , Zhao L. , Zhou L.
Published: July 2017

Optimization based on reconstruction of the velocity, temperature, and radiation fields in a porous absorber with continuous linear porosity or pore diameter distribution is carried out in this work. This study analyzes three typical linear pore structure distributions: increasing (“I”), decreasing (“D”), and constant (“C”) types, respectively. In general, the D type porosity (ϕ) layout combined with the I type pore diameter (dp) distribution would be an excellent pore structure layout for a porous absorber. The poor performance range, which should be avoided in the absorber design, is found to be within a wide range of porosity layouts (ϕi = ∼0.7 and ϕo > 0.6) and pore diameter layouts (di = 1.5–2.5 mm), respectively. With a large inlet porosity (ϕi > 0.8), the D type layout with larger porosity gradient (Gp) has a better thermal performance; however, the I type dp layout with a smaller inlet pore diameter (di < 1.5 mm) and a larger pore diameter gradient (Gdp) is recommended when considering the lower pressure drop. Different pore structure layouts (D type or I type) have a significant effect on the pressure drop, even with the same average ϕa and da, the maximum deviation can be up to 70.1%. The comprehensive performance evaluation criteria (PEC) value shows that the D type ϕ layout with a larger ϕa has an excellent thermopressure drop performance, and a part of PEC values for the I type dp layout are greater than unity.
Casing Burst Strength Degradation Due to Casing Wear
Authors: Li Changning , Samuel Robello
Published: July 2017

Casing integrity management is crucial, especially in wells experiencing severe casing wall degradation. Knowledge of stress distribution in worn casing helps predict where a casing failure occurs first. In industrial practice, a common method is to estimate the reduction of the casing burst strength in worn casing using API burst strength equation with a linear reduction in the remaining wall thickness or wear percentage equivalent to a “uniform-worn” casing model. This study focuses on building a rigorous engineering model for burst strength degradation prediction based on “crescent shape” casing wear. This model calculates the hoop strength directly, including the local bending in the thinner portion of the “crescent-worn” casing. This paper has developed a mathematical model to calculate the hoop strength of worn out casing with force and moment balance equations. This study finds the calculation of reduced strength using the linear wear model to be overly conservative because it only focuses on the stress at the thinnest portion of the worn casing. The stress predicted in this paper is similar to the results obtained from the finite element method (FEM), which validates equations and results obtained from this paper. The developed model is generic and can apply to casings, risers, and tubings.
Internal Fuzzy Hybrid Charger System for a Hybrid Electrical Vehicle
Authors: Aymen Flah
Published: July 2017

Controlling the charging power system in an electrical vehicle, presents a serious challenge for the engineer in order to find the best solution that guarantee the system effectiveness and performance. Related to this objective, this paper is presented to offer an intelligent power management algorithm, which guarantees the best process of power extraction and injection, respectively, from an electrical generator (EG) linked to an internal combustion engine (ICE) to a system of batteries via a direct current to alternative current power converter. This intelligent process was based on the fuzzy technology and the system tuning is made after a various test. Obtaining the necessary power in the exact moment and in the specific condition, that presents the goal of the presented algorithm. For obtaining the best instruction from the present intelligent process, the state of charge (SOC) of the battery, the measured output voltage from the battery and the acceleration decision of the user, are used as a real's input parameters for having a real statue of the electrical vehicle. This new process will be an asset to the highway electrical vehicle for optimizing the power consumption. To evaluate the algorithm performance matlab/simulink is used and a simulation results are presented and discussed.
Finite Element Analysis of the Friction Stir Forming Process
Authors: Lazarevic Sladjan , Miller Scott , Kruger Grant , van Niekerk Theo , Carlson Blair
Published: July 2017

Friction stir forming utilizes a friction stirring action to soften and extrude a base material into a cavity in a substrate material thereby forming a joint. In this research, Abaqus software was used to model the process in order to understand the key joint features of interest and provide direction for experimental optimization. A three dimensional, thermo-mechanical finite element model was developed and applied to simulate the process and obtain detailed stress and temperature distribution plots. Adaptive mesh and contact features were utilized for large deformation of the aluminum work material. It was found that the model accurately predicted the shape of the joint and flash extrusion during the process. The maximum temperature was found at the outer radius of the tool, but was much lower than temperatures in friction stir welding.
Electrically Assisted Drilling of Usibor 1500 Boron Steel and its Implications for Electrically Assisted Machining
Authors: Karumatt Nived Govind , Ruszkiewicz Brandt J. , Mears Laine
Published: July 2017

With the increasing demands in the automotive industry for passenger safety and higher structural strength and stiffness, the automotive industry is using more advanced high strength steels. The ability to reduce tool wear and drilling forces in post forming drilling of high strength steel parts is of high importance to the automotive industry. Electrically assisted drilling is a process in which electric current is passed through the drill bit to the workpiece resulting in local softening, and allowing for a reduction in cutting forces and potential increase in tool life. In this paper, tungsten carbide (WC)-tipped drill bits are used to study the effect of varying electrical current on 1500 Usibor® steel work pieces. The effects of current on the drilling process of high strength steel are investigated in this research by studying the maximum temperature during drilling, the dependence of chip formation, tool wear and the axial force during the drilling operation. It was found that the magnitude of current passed through the workpiece directly influences the axial force that the tool experiences, and thus the tool wear. This effect is modeled through Joule heating, leading to elevated temperature and thermal softening.
A laboratory nanoseismological study on deep-focus earthquake micromechanics
Authors: Wang Yanbin , Zhu Lupei , Shi Feng , Schubnel Alexandre , Hilairet Nadege , Yu Tony , Rivers Mark , Gasc Julien , Addad Ahmed , Deldicque Damien , Li Ziyu , Brunet Fabrice
Published: July 2017

Nanoseismological analyses on labquakes under controlled conditions shed new lights on mechanisms of deep-focus earthquakes.
Three-dimensional positioning and structure of chromosomes in a human prophase nucleus
Authors: Chen Bo , Yusuf Mohammed , Hashimoto Teruo , Estandarte Ana Katrina , Thompson George , Robinson Ian
Published: July 2017

High-resolution three-dimensional structure of chromosomes in a human prophase nucleus from electron microscopy.
Isotropic transmission of magnon spin information without a magnetic field
Authors: Haldar Arabinda , Tian Chang , Adeyeye Adekunle Olusola
Published: July 2017

A novel route for data processing is designed based on magnons where waves carry information unlike charges in electronics.
Heteroatom-assisted olefin polymerization by rare-earth metal catalysts
Authors: Wang Chunxiang , Luo Gen , Nishiura Masayoshi , Song Guoyong , Yamamoto Atsushi , Luo Yi , Hou Zhaomin
Published: July 2017

Heteroatoms enhance polymerization and copolymerization of functional olefins.
Dendritic cell–targeted lentiviral vector immunization uses pseudotransduction and DNA-mediated STING and cGAS activation
Authors: Kim Jocelyn T. , Liu Yarong , Kulkarni Rajan P. , Lee Kevin K. , Dai Bingbing , Lovely Geoffrey , Ouyang Yong , Wang Pin , Yang Lili , Baltimore David
Published: July 2017

Lentiviral vector preparations stimulate immune responses via the host STING and cGAS pathway and pseudotransduction.
Helicobacter
species are potent drivers of colonic T cell responses in homeostasis and inflammation
Authors: Chai Jiani N. , Peng Yangqing , Rengarajan Sunaina , Solomon Benjamin D. , Ai Teresa L. , Shen Zeli , Perry Justin S. A. , Knoop Kathryn A. , Tanoue Takeshi , Narushima Seiko , Honda Kenya , Elson Charles O. , Newberry Rodney D. , Stappenbeck Thaddeus S. , Kau Andrew L. , Peterson Daniel A. , Fox James G. , Hsieh Chyi-Song
Published: July 2017

Helicobacter
in the intestine induce regulatory T cells during homeostasis and effector T cells during colonic inflammation.
Specific Signatures of the Gut Microbiota and Increased Levels of Butyrate in Children Treated with Fermented Cow's Milk Containing Heat-Killed Lactobacillus paracasei CBA L74
Authors: Berni Canani Roberto , De Filippis Francesca , Nocerino Rita , Laiola Manolo , Paparo Lorella , Calignano Antonio , De Caro Carmen , Coretti Lorena , Chiariotti Lorenzo , Gilbert Jack A. , Ercolini Danilo
Published: July 2017

We recently demonstrated that cow's milk fermented with the probioticLactobacillus paracaseiCBA L74 (FM-CBAL74) reduces the incidence of respiratory and gastrointestinal tract infections in young children attending school. This effect apparently derives from a complex regulation of non-immune and immune protective mechanisms. We investigated whether FM-CBAL74 could regulate gut microbiota composition and butyrate production. We randomly selected 20 healthy children (12 to 48 months) from the previous randomized controlled trial, before (t0) and after 3 months (t3) of dietary treatment with FM-CBAL74 (FM) or placebo (PL). Fecal microbiota was profiled using 16S rRNA gene amplicon sequencing, and the fecal butyrate concentration was also measured. Microbial alpha and beta diversities were not significantly different between groups prior to treatment. FM-CBAL74 but not PL treatment increased the relative abundance ofLactobacillus. IndividualBlautia,Roseburia, andFaecalibacteriumoligotypes were associated with FM-CBAL74 treatment and demonstrated correlative associations with immune biomarkers. Accordingly, PICRUSt analysis predicted an increase in the proportion of genes involved in butyrate production pathways, consistent with an increase in fecal butyrate observed only in the FM group. Dietary supplementation with FM-CBAL74 induces specific signatures in gut microbiota composition and stimulates butyrate production. These effects are associated with changes in innate and acquired immunity.

IMPORTANCEThe use of a fermented milk product containing the heat-killed probiotic strainLactobacillus paracaseiCBAL74 induces changes in the gut microbiota, promoting the development of butyrate producers. These changes in the gut microbiota composition correlate with increased levels of innate and acquired immunity biomarkers.
Structural and Mechanistic Insights into the Improvement of the Halotolerance of a Marine Microbial Esterase by Increasing Intra- and Interdomain Hydrophobic Interactions
Authors: Li Ping-Yi , Zhang Yi , Xie Bin-Bin , Zhang Yan-Qi , Hao Jie , Wang Yue , Wang Peng , Li Chun-Yang , Qin Qi-Long , Zhang Xi-Ying , Su Hai-Nan , Shi Mei , Zhang Yu-Zhong , Chen Xiu-Lan
Published: July 2017

Halotolerant enzymes are beneficial for industrial processes requiring high salt concentrations and low water activity. Most halophilic proteins are evolved to have reduced hydrophobic interactions on the surface and in the hydrophobic cores for their haloadaptation. However, in this study, we improved the halotolerance of a thermolabile esterase, E40, by increasing intraprotein hydrophobic interactions. E40 was quite unstable in buffers containing more than 0.3 M NaCl, and its
k
cat
and substrate affinity were both significantly reduced in 0.5 M NaCl. By introducing hydrophobic residues in loop 1 of the CAP domain and/or α7 of the catalytic domain in E40, we obtained several mutants with improved halotolerance, and the M3 S202W I203F mutant was the most halotolerant. (“M3” represents a mutation in loop 1 of the CAP domain in which residues R22-K23-T24 of E40 are replaced by residues Y22-K23-H24-L25-S26 of Est2.) Then we solved the crystal structures of the S202W I203F and M3 S202W I203F mutants to reveal the structural basis for their improved halotolerance. Structural analysis revealed that the introduction of hydrophobic residues W202 and F203 in α7 significantly improved E40 halotolerance by strengthening intradomain hydrophobic interactions of F203 with W202 and other residues in the catalytic domain. By further introducing hydrophobic residues in loop 1, the M3 S202W I203F mutant became more rigid and halotolerant due to the formation of additional interdomain hydrophobic interactions between the introduced Y22 in loop 1 and W204 in α7. These results indicate that increasing intraprotein hydrophobic interactions is also a way to improve the halotolerance of enzymes with industrial potential under high-salt conditions.

IMPORTANCE
Esterases and lipases for industrial application are often subjected to harsh conditions such as high salt concentrations, low water activity, and the presence of organic solvents. However, reports on halotolerant esterases and lipases are limited, and the underlying mechanism for their halotolerance is still unclear due to the lack of structures. In this study, we focused on the improvement of the halotolerance of a salt-sensitive esterase, E40, and the underlying mechanism. The halotolerance of E40 was significantly improved by introducing hydrophobic residues. Comparative structural analysis of E40 and its halotolerant mutants revealed that increased intraprotein hydrophobic interactions make these mutants more rigid and more stable than the wild type against high concentrations of salts. This study shows a new way to improve enzyme halotolerance, which is helpful for protein engineering of salt-sensitive enzymes.
Construction and Optimization of a Heterologous Pathway for Protocatechuate Catabolism in Escherichia coli Enables Bioconversion of Model Aromatic Compounds
Authors: Clarkson Sonya M. , Giannone Richard J. , Kridelbaugh Donna M. , Elkins James G. , Guss Adam M. , Michener Joshua K.
Published: July 2017

The production of biofuels from lignocellulose yields a substantial lignin by-product stream that currently has few applications. Biological conversion of lignin-derived compounds into chemicals and fuels has the potential to improve the economics of lignocellulose-derived biofuels, but few microbes are able both to catabolize lignin-derived aromatic compounds and to generate valuable products. While
Escherichia coli
has been engineered to produce a variety of fuels and chemicals, it is incapable of catabolizing most aromatic compounds. Therefore, we engineered
E. coli
to catabolize protocatechuate, a common intermediate in lignin degradation, as the sole source of carbon and energy via heterologous expression of a nine-gene pathway from
Pseudomonas putida
KT2440. We next used experimental evolution to select for mutations that increased growth with protocatechuate more than 2-fold. Increasing the strength of a single ribosome binding site in the heterologous pathway was sufficient to recapitulate the increased growth. After optimization of the core pathway, we extended the pathway to enable catabolism of a second model compound, 4-hydroxybenzoate. These engineered strains will be useful platforms to discover, characterize, and optimize pathways for conversions of lignin-derived aromatics.

IMPORTANCE
Lignin is a challenging substrate for microbial catabolism due to its polymeric and heterogeneous chemical structure. Therefore, engineering microbes for improved catabolism of lignin-derived aromatic compounds will require the assembly of an entire network of catabolic reactions, including pathways from genetically intractable strains. Constructing defined pathways for aromatic compound degradation in a model host would allow rapid identification, characterization, and optimization of novel pathways. We constructed and optimized one such pathway in
E. coli
to enable catabolism of a model aromatic compound, protocatechuate, and then extended the pathway to a related compound, 4-hydroxybenzoate. This optimized strain can now be used as the basis for the characterization of novel pathways.
Feral Swine in the United States Have Been Exposed to both Avian and Swine Influenza A Viruses
Authors: Martin Brigitte E. , Sun Hailiang , Carrel Margaret , Cunningham Fred L. , Baroch John A. , Hanson-Dorr Katie C. , Young Sean G. , Schmit Brandon , Nolting Jacqueline M. , Yoon Kyoung-Jin , Lutman Mark W. , Pedersen Kerri , Lager Kelly , Bowman Andrew S. , Slemons Richard D. , Smith David R. , DeLiberto Thomas , Wan Xiu-Feng
Published: July 2017

Influenza A viruses (IAVs) in swine can cause sporadic infections and pandemic outbreaks among humans, but how avian IAV emerges in swine is still unclear. Unlike domestic swine, feral swine are free ranging and have many opportunities for IAV exposure through contacts with various habitats and animals, including migratory waterfowl, a natural reservoir for IAVs. During the period from 2010 to 2013, 8,239 serum samples were collected from feral swine across 35 U.S. states and tested against 45 contemporary antigenic variants of avian, swine, and human IAVs; of these, 406 (4.9%) samples were IAV antibody positive. Among 294 serum samples selected for antigenic characterization, 271 cross-reacted with ≥1 tested virus, whereas the other 23 did not cross-react with any tested virus. Of the 271 IAV-positive samples, 236 cross-reacted with swine IAVs, 1 with avian IAVs, and 16 with avian and swine IAVs, indicating that feral swine had been exposed to both swine and avian IAVs but predominantly to swine IAVs. Our findings suggest that feral swine could potentially be infected with both avian and swine IAVs, generating novel IAVs by hosting and reassorting IAVs from wild birds and domestic swine and facilitating adaptation of avian IAVs to other hosts, including humans, before their spillover. Continued surveillance to monitor the distribution and antigenic diversities of IAVs in feral swine is necessary to increase our understanding of the natural history of IAVs.

IMPORTANCE
There are more than 5 million feral swine distributed across at least 35 states in the United States. In contrast to domestic swine, feral swine are free ranging and have unique opportunities for contact with wildlife, livestock, and their habitats. Our serological results indicate that feral swine in the United States have been exposed to influenza A viruses (IAVs) consistent with those found in both domestic swine and wild birds, with the predominant infections consisting of swine-adapted IAVs. Our findings suggest that feral swine have been infected with IAVs at low levels and could serve as hosts for the generation of novel IAVs at the interface of feral swine, wild birds, domestic swine, and humans.
Is more research always needed? Estimating optimal sample sizes for trials of retention in care interventions for HIV-positive East Africans
Authors: Uyei Jennifer , Li Lingfeng , Braithwaite R Scott
Published: July 2017

Introduction

Given the serious health consequences of discontinuing antiretroviral therapy, randomised control trials of interventions to improve retention in care may be warranted. As funding for global HIV research is finite, it may be argued that choices about sample size should be tied to maximising health.

Methods

For an East African setting, we calculated expected value of sample information and expected net benefit of sampling to identify the optimal sample size (greatest return on investment) and to quantify net health gains associated with research. Two hypothetical interventions were analysed: (1) one aimed at reducing disengagement from HIV care and (2) another aimed at finding/relinking disengaged patients.

Results

When the willingness to pay (WTP) threshold was within a plausible range (1–3 × GDP; US$1377–4130/QALY), the optimal sample size was zero for both interventions, meaning that no further research was recommended because the pre-research probability of an intervention's effectiveness and value was sufficient to support a decision on whether to adopt the intervention and any new information gained from additional research would likely not change that decision. In threshold analyses, at a higher WTP of $5200 the optimal sample size for testing a risk reduction intervention was 2750 per arm. For the outreach intervention, the optimal sample size remained zero across a wide range of WTP thresholds and was insensitive to variation. Limitations, including not varying all inputs in the model, may have led to an underestimation of the value of investing in new research.

Conclusion

In summary, more research is not always needed, particularly when there is moderately robust prestudy belief about intervention effectiveness and little uncertainty about the value (cost-effectiveness) of the intervention. Users can test their own assumptions athttp://torchresearch.org.
Does expanding primary healthcare improve hospital efficiency? Evidence from a panel analysis of avoidable hospitalisations in 5506 municipalities in Brazil, 2000–2014
Authors: Silva Everton Nunes da , Powell-Jackson Timothy
Published: July 2017

Background

Hospitals account for the major share of health expenditure. Primary healthcare may improve efficiency at the hospital level by reducing avoidable admissions. We examined whether rapid expansion of primary healthcare in the context of Brazil’s Family Health Strategy (FHS) was associated with a reduction in avoidable hospitalisations.

Methods

We constructed panel data for 5506 municipalities over 2000–2014. Our primary outcome was the rate of avoidable hospitalisations, defined with reference to the official list of ambulatory care sensitive conditions (ACSC). The exposure variable was FHS coverage. We used first-difference models at the municipality level, controlling for municipality characteristics and confounding trends. We ran similar models for each of the 19 diseases in the list of ACSCs.

Findings

FHS coverage expanded from 14% to 64% of the population between 2000 and 2014. Over the same period, the rate of avoidable hospitalisations fell from 17 to 10 per 1000 population. Results from the econometric analysis show that the FHS at full coverage was associated with an increase of 0.6 (95% CI 0.3 to 0.9; p<0.001) in the rate of avoidable hospital admissions. Expansion of the FHS was associated with an increase of 866 (95% CI 762 to 970; p<0.001) in the rate of primary care consultations. The FHS was not significantly associated with a reduction in hospitalisations for any of the 19 conditions.

Conclusions

While high-quality primary healthcare can deliver considerable health benefits to the population, it may not always be effective in addressing inefficiencies at the hospital level due to avoidable admissions.
Implementation of effective practices in health facilities: a systematic review of cluster randomised trials
Authors: Allanson Emma R , Tunçalp Özge , Vogel Joshua P , Khan Dina N , Oladapo Olufemi T , Long Qian , Gülmezoglu Ahmet Metin
Published: July 2017

Background

The capacity for health systems to support the translation of research in to clinical practice may be limited. The cluster randomised controlled trial (cluster RCT) design is often employed in evaluating the effectiveness of implementation of evidence-based practices. We aimed to systematically review available evidence to identify and evaluate the components in the implementation process at the facility level using cluster RCT designs.

Methods

All cluster RCTs where the healthcare facility was the unit of randomisation, published or written from 1990 to 2014, were assessed. Included studies were analysed for the components of implementation interventions employed in each. Through iterative mapping and analysis, we synthesised a master list of components used and summarised the effects of different combinations of interventions on practices.

Results

Forty-six studies met the inclusion criteria and covered the specialty groups of obstetrics and gynaecology (n=9), paediatrics and neonatology (n=4), intensive care (n=4), internal medicine (n=20), and anaesthetics and surgery (n=3). Six studies included interventions that were delivered across specialties. Nine components of multifaceted implementation interventions were identified: leadership, barrier identification, tailoring to the context, patient involvement, communication, education, supportive supervision, provision of resources, and audit and feedback. The four main components that were most commonly used were education (n=42, 91%), audit and feedback (n=26, 57%), provision of resources (n=23, 50%) and leadership (n=21, 46%).

Conclusions

Future implementation research should focus on better reporting of multifaceted approaches, incorporating sets of components that facilitate the translation of research into practice, and should employ rigorous monitoring and evaluation.
Rλ3-inspired black holes
Authors: Kováčik Samuel
Published: July 2017

We study a black hole with a blurred mass density instead of a singular one, which is caused by the noncommutativity of three-space. Depending on its mass, such object has either none, one or two event horizons. It possesses properties, which become important on a microscopic scale, in particular, the Hawking temperature does not increase indefinitely as the mass goes to zero, but vanishes instead. Such frozen and extremely dense pieces of matter are good dark matter candidates.
Circum-Arctic Lithosphere Evolution (CALE) Transect C: displacement of the Arctic Alaska–Chukotka microplate towards the Pacific during opening of the Amerasia Basin of the Arctic
Authors: Miller Elizabeth L. , Meisling Kristian E. , Akinin Vyacheslav V. , Brumley Kelley , Coakley Bernard J. , Gottlieb Eric S. , Hoiland Carl W. , O'Brien Timothy M. , Soboleva Anna , Toro Jaime
Published: July 2017

This paper synthesizes the framework and geological evolution of the Arctic Alaska–Chukotka microplate (AACM), from its origin as part of the continental platform fringing Baltica and Laurentia to its southward motion during the formation of the Amerasia Basin (Arctic Ocean) and its progressive modification as part of the dynamic northern palaeo-Pacific margin. A synthesis of the available data refines the crustal identity, limits and history of the AACM and, together with regional geological constraints, provides a tectonic framework to aid in its pre-Cretaceous restoration. Recently published seismic reflection data and interpretations, integrated with regional geological constraints, provide the basis for a new crustal transect (the Circum-Arctic Lithosphere Evolution (‘CALE’) Transect C) linking the Amerasia Basin and the Pacific margin along two paths that span 5100 km from the Lomonosov Ridge (near the North Pole), across the Amerasia Basin, Chukchi Sea and Bering Sea, and ending at the subducting Pacific plate margin in the Aleutian Islands. We propose a new plate tectonic model in which the AACM originated as part of a re-entrant in the palaeo-Pacific margin and moved to its present position during slab-related magmatism and the southward retreat of palaeo-Pacific subduction, largely coeval with the rifting and formation of the Amerasia Basin in its wake.
How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+pumps are crucial
Authors: Blaustein Mordecai P.
Published: July 2017

Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na+pumps, however, have demonstrated that cardiac ouabain-sensitive α2-Na+pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α2-Na+pumps and in mice with cardiac-selective knockout or transgenic overexpression of α2-Na+pumps. The latter, seemingly paradoxical, findings can be explained by comparing the numbers of available (ouabain-free) high-affinity (α2) ouabain-binding sites in wild-type, knockout, and transgenic hearts. Conversely, hypertrophy was accelerated in α2-ouabain-resistant (R) mice in which the normally ouabain-resistant α1-Na+pumps were mutated to an ouabain-sensitive (S) form (α1S/Sα2R/Ror “SWAP” vs. wild-type or α1R/Rα2S/Smice). Furthermore, transaortic constriction-induced hypertrophy in SWAP mice was prevented/reversed by immunoneutralizing circulating endogenous ouabain (EO). These findings show that EO and its receptor, ouabain-sensitive α2, are critical factors in pressure overload-induced cardiac hypertrophy. This complements reports linking elevated plasma EO to hypertension, cardiac hypertrophy, and failure in humans and elucidates the underappreciated role of the EO-Na+pump pathway in cardiovascular disease.
Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression
Authors: Toussaint Jimmy , Raval Chirag Bharavi , Nguyen Tieuvi , Fadaifard Hadi , Joshi Shripad , Wolberg George , Quarfordt Steven , Jan Kung-ming , Rumschitzki David S.
Published: July 2017

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.

NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop.
The Dorsoulnar Artery Perforator Adipofascial Flap in the Treatment of Distal Radioulnar Synostosis
Authors: Pagnotta Alessia , Antonietti Giorgio , Molayem Iakov
Published: July 2017

Posttraumatic radioulnar synostosis (RUS) is a rare event following forearm fractures. Consequences are disabling for patients who suffer from functional limitation in forearm pronosupination. Distal RUS are even more rare and more difficult to treat because of high recurrence rates. The patient we describe in this paper came to our attention with a double distal RUS recurrence and a Darrach procedure already performed. We performed a radical excision of RUS and interposition with a vascularized dorsoulnar artery (DUA) adipofascial perforator flap. Four years after surgery, the patient shows the same complete range of motion in pronosupination, and MRI confirms that the flap is still in place with signs of vascularization. Simple synostosis excision has been proven ineffective in many cases. Interposition is recommended after excision, and biological material interposition seems to be more effective than foreign material. Surgeons are increasingly performing vascularized interposition, and the results are very encouraging.
Valve Calcification in Aortic Stenosis: Etiology and Diagnostic Imaging Techniques
Authors: Izquierdo-Gómez María Manuela , Hernández-Betancor Iván , García-Niebla Javier , Marí-López Belén , Laynez-Cerdeña Ignacio , Lacalzada-Almeida Juan
Published: July 2017

Aortic stenosis is the most common valvulopathy in the Western world. Its prevalence has increased significantly in recent years due to population aging; hence, up to 8% of westerners above the age of 84 now have severe aortic stenosis (Lindroos et al., 1993). This causes increased morbidity and mortality and therein lies the importance of adequate diagnosis and stratification of the degree of severity which allows planning the best therapeutic option in each case. Long understood as a passive age-related degenerative process, it is now considered a rather more complex entity involving mechanisms and factors similar to those of atherosclerosis (Stewart et al., 1997). In this review, we summarize the pathophysiological mechanisms underlying the onset and progression of the disease and analyze the current role of cardiac imaging techniques for diagnosis.
Selective Phenome Growth Adapted NK Model: A Novel Landscape to Represent Aptamer Ligand Binding
Authors: Kinghorn Andrew Brian , Tanner Julian Alexander
Published: July 2017

Aptamers are single-stranded oligonucleotides selected by evolutionary approaches from massive libraries with significant potential for specific molecular recognition in diagnostics and therapeutics. A complete empirical characterisation of an aptamer selection experiment is not feasible due to the vast complexity of aptamer selection. Simulation of aptamer selection has been used to characterise and optimise the selection process; however, the absence of a good model for aptamer-target binding limits this field of study. Here, we generate theoretical fitness landscapes which appear to more accurately represent aptamer-target binding. The method used to generate these landscapes, selective phenome growth, is a new approach in which phenotypic contributors are added to a genotype/phenotype interaction map sequentially in such a way so as to increase the fitness of a selected fit sequence. In this way, a landscape is built around the selected fittest sequences. Comparison to empirical aptamer microarray data shows that our theoretical fitness landscapes more accurately represent aptamer ligand binding than other theoretical models. These improved fitness landscapes have potential for the computational analysis and optimisation of other complex systems.
Whole-Body SPECT/CT versus Planar Bone Scan with Targeted SPECT/CT for Metastatic Workup
Authors: Rager Olivier , Nkoulou René , Exquis Nadia , Garibotto Valentina , Tabouret-Viaud Claire , Zaidi Habib , Amzalag Gaël , Lee-Felker Stephanie Anne , Zilli Thomas , Ratib Osman
Published: July 2017

Purpose. The use of SPECT/CT in bone scans has been widespread in recent years, but there are no specific guidelines concerning the optimal acquisition protocol. Two strategies have been proposed: targeted SPECT/CT for equivocal lesions detected on planar images or systematic whole-body SPECT/CT. Our aim was to compare the diagnostic accuracy of the two approaches. Methods. 212 consecutive patients with a history of cancer were referred for bone scans to detect bone metastases. Two experienced readers randomly evaluated for each patient either planar images with one-field SPECT/CT targeted on equivocal focal uptakes (targeted SPECT/CT) or a whole-body (two-field) SPECT/CT acquisition from the base of the skull to the proximal femurs (whole-body SPECT/CT). The exams were categorized as “nonmetastatic,” “equivocal,” or “metastatic” on both protocols. The presence or absence of any extra-axial skeletal lesions was also assessed. The sensitivity and specificity of both strategies were measured using the results of subsequent imaging follow-up as the reference standard. Results. Whole-body SPECT/CT had a significantly higher sensitivity than targeted SPECT/CT to detect bone metastases (p=0.0297) and to detect extra-axial metastases (p=0.0266). There was no significant difference in specificity among the two approaches. Conclusion. Whole-body SPECT/CT is the optimal modality of choice for metastatic workup, including detection of extra-axial lesions, with improved sensitivity and similar specificity compared to targeted SPECT/CT.
The Relationship between VEGFA and TGFB1 Polymorphisms and Target Lesion Revascularization after Elective Percutaneous Coronary Intervention
Authors: Osadnik Tadeusz , Lekston Andrzej , Bujak Kamil , Strzelczyk Joanna Katarzyna , Poloński Lech , Gąsior Mariusz
Published: July 2017

Background and Aim. The specific association between genetic variation and in-stent restenosis is still only partly understood. The aim of this study is to analyze the relationship between functional polymorphisms in the genes encoding vascular endothelial growth factor A (VEGF-A; rs699947) and transforming growth factor beta 1 (TGF-β1; rs1800470) and target lesion revascularization (TLR) risk. Methods. A total of 676 patients (805 lesions) with stable coronary artery disease (SCAD) who received elective percutaneous coronary intervention (PCI) with at least one bare-metal stent implantation were included. The primary study endpoint was TLR at a 4-year follow-up. Results. The TLR rate was higher in patients with the VEGFA A/A genotype (15.4%) than in patients with the VEGFA A/C (7.9%) and C/C (8.9%) genotypes (p=0.009). The VEGFA A/A genotype, after adjustment for clinical and procedural covariates, remained significantly and independently associated with the TLR (hazard ratio—2.09 [95% confidence interval 1.32–3.33, p=0.0017]). However, we found no association between TLR and the TGFB1 genotype. Conclusion. The VEGFA A/A genotype is significantly and independently associated with TLR risk in Polish SCAD patients who received elective PCI with bare-metal stent implantation.