bluuebunny/crossref_metadata_2025 huggingface dataset:
Computationally Efficient Variational Approximations for Bayesian Inverse Problems
Authors: Tsilifis Panagiotis , Bilionis Ilias , Katsounaros Ioannis , Zabaras Nicholas
Published: July 2016

The major drawback of the Bayesian approach to model calibration is the computational burden involved in describing the posterior distribution of the unknown model parameters arising from the fact that typical Markov chain Monte Carlo (MCMC) samplers require thousands of forward model evaluations. In this work, we develop a variational Bayesian approach to model calibration which uses an information theoretic criterion to recast the posterior problem as an optimization problem. Specifically, we parameterize the posterior using the family of Gaussian mixtures and seek to minimize the information loss incurred by replacing the true posterior with an approximate one. Our approach is of particular importance in underdetermined problems with expensive forward models in which both the classical approach of minimizing a potentially regularized misfit function and MCMC are not viable options. We test our methodology on two surrogate-free examples and show that it dramatically outperforms MCMC methods.
Design Principles: Literature Review, Analysis, and Future Directions
Authors: Fu Katherine K. , Yang Maria C. , Wood Kristin L.
Published: July 2016

Design principles are created to codify and formalize design knowledge so that innovative, archival practices may be communicated and used to advance design science and solve future design problems, especially the pinnacle, wicked, and grand-challenge problems that face the world and cross-cutting markets. Principles are part of a family of knowledge explication, which also include guidelines, heuristics, rules of thumb, and strategic constructs. Definitions of a range of explications are explored from a number of seminal papers. Based on this analysis, the authors pose formalized definitions for the three most prevalent terms in the literature—principles, guidelines, and heuristics—and draw more definitive distinctions between the terms. Current research methods and practices with design principles are categorized and characterized. We further explore research methodologies, validation approaches, semantic principle composition through computational analysis, and a proposed formal approach to articulating principles. In analyzing the methodology for discovering, deriving, formulating, and validating design principles, the goal is to understand and advance the theoretical basis of design, the foundations of new tools and techniques, and the complex systems of the future. Suggestions for the future of design principles research methodology for added rigor and repeatability are proposed.
Redundancy Allocation for Multistate Systems With Component Dependencies and Load Sharing
Authors: Wang Jing , Li Mian
Published: July 2016

Binary-state and component independent assumptions will lead to doubtful and misleading redundancy allocation schemes which may not satisfy the reliability requirements for real engineering applications. Most published works proposed methods to remove the first assumption by studying the degradation cases where multiple states of a component are from the best state to the degradation states then to the completely failed state. Fewer works focused on removing the second assumption and they only discussed dependent failures which are only a special case of component dependency. This work uses the Semi-Markov process to describe a two-component system for redundancy allocation. In this work, multiple states of a component are represented by multiple output levels, which are beyond the scope of degradation, and the component dependency is not limited to failure dependency only. The load sharing is also taken care of in the proposed work. The optimal redundancy allocation scheme is obtained by solving the corresponding redundancy allocation optimization problem with the reliability measure, the system availability, obtained through the Semi-Markov process model being constraint. Two case studies are presented, demonstrating the applicability of the propose method.
Robustness against distortion of fundamental frequency cues in simulated electro-acoustic hearing
Authors: Vermeulen Arthur , Verschuur Carl
Published: July 2016

Speech recognition by cochlear implant users can be improved by adding an audible low frequency acoustic signal to electrical hearing; the resulting improvement is deemed “electro-acoustic stimulation (EAS) benefit.” However, a crucial low frequency cue, fundamental frequency (F0), can be distorted via the impaired auditory system. In order to understand how F0 distortions may affect EAS benefit, normal-hearing listeners were presented monaurally with vocoded speech (frequencies >250 Hz) and an acoustical signal (frequencies <250 Hz) with differing manipulations of the F0 signal, specifically: a pure tone with the correct mean F0 but with smaller variations around this mean, or a narrowband of white noise centered around F0, at varying bandwidths; a pure tone down-shifted in frequency by 50 Hz but keeping overall frequency modulations. Speech-recognition thresholds improved when tones with reduced frequency modulation were presented, and improved significantly for noise bands maintaining F0 information. A down-shifted tone, or only a tone to indicate voicing, showed no EAS benefit. These results confirm that the presence of the target's F0 is beneficial for EAS hearing in a noisy environment, and they indicate that the benefit is robust to F0 distortion, as long as the mean F0 and frequency modulations of F0 are preserved.
A Comparison of Different Modes of Morning Priming Exercise on Afternoon Performance
Authors: Russell Mark , King Aden , Bracken Richard. M. , Cook Christian. J. , Giroud Thibault , Kilduff Liam. P.
Published: July 2016

Purpose:

To assess the effects of different modes of morning (AM) exercise on afternoon (PM) performance and salivary hormone responses in professional rugby union players.

Methods:

On 4 occasions (randomized, crossover design), 15 professional rugby players provided AM (~8 AM) and PM (~2 PM) saliva samples before PM assessments of countermovement-jump height, reaction time, and repeated-sprint ability. Control (passive rest), weights (bench press: 5 × 10 repetitions, 75% 1-repetition maximum, 90-s intraset recovery), cycling (6 × 6-s maximal sprint cycling, 7.5% body mass load, 54-s intraset recovery), and running (6 × 40-m maximal sprints, 20-s intraset recovery) interventions preceded (~5 h) PM testing.

Results:

PM sprint performance improved (P < .05) after weights (>0.15 ± 0.19 s, >2.04% ± 2.46%) and running (>0.15 ± 0.17 s, >2.12% ± 2.22%) but not cycling (P > .05). PM jump height increased after cycling (0.012 ± 0.009 m, 2.31% ± 1.76%, P < .001) and running (0.020 ± 0.009 m, 3.90% ± 1.79%, P < .001) but not weights (P = .936). Reaction time remained unchanged between trials (P = .379). Relative to control (131 ± 21 pg/mL), PM testosterone was greater in weights (21 ± 23 pg/mL, 17% ± 18%, P = .002) and running (28 ± 26 pg/mL, 22% ± 20%, P = .001) but not cycling (P = .072). Salivary cortisol was unaffected by AM exercise (P = .540).

Conclusions:

All modes of AM exercise improved at least 1 marker of PM performance, but running appeared the most beneficial to professional rugby union players. A rationale therefore exists for preceding PM competition with AM exercise.
Without The Academic Part, It Wouldn’t Be Squash”: Youth Development in an Urban Squash Program
Authors: Hemphill Michael A. , Richards K. Andrew R.
Published: July 2016

Purpose:

The purpose of this study was to examine youth development outcomes in an Urban Squash program.

Methods:

A mixed method approach to was employed to address three research questions: 1) to what extent did the Urban Squash program exhibit features of a quality OST program?; 2) what aspects of the Urban Squash program were most valued by participants and stakeholders?; and 3) how were outcomes gained within urban squash transferred into the school day. The OST Observation Instrument was employed to provide a measure of fidelity related to the implementation of quality program structures. Youth participants (N = 21) and adults (N = 13) with knowledge of the program were interviewed in a semistructured format. Qualitative inductive analysis and constant comparison methods were used to generate themes.

Results:

Systematic observations demonstrated that the program reflected a strong program design with activities that were sequenced, active, personally focused, and explicit. Within that context, four qualitative themes related to quality programming include 1) academic enrichment, 2) academic transfer, 3) relationships, and 4) personal and social responsibility.

Conclusions:

Urban Squash provided a quality program structure. Transfer from the program to the school was evident with academic enrichment and personal and social responsibility.
Salmonella
Effectors SseF and SseG Interact with Mammalian Protein ACBD3 (GCP60) To Anchor
Salmonella
-Containing Vacuoles at the Golgi Network
Authors: Yu Xiu-Jun , Liu Mei , Holden David W.
Published: July 2016

Following infection of mammalian cells,
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) replicates within membrane-bound compartments known as
Salmonella
-containing vacuoles (SCVs). The
Salmonella
pathogenicity island 2 type III secretion system (SPI-2 T3SS) translocates approximately 30 different effectors across the vacuolar membrane. SseF and SseG are two such effectors that are required for SCVs to localize close to the Golgi network in infected epithelial cells. In a yeast two-hybrid assay, SseG and an N-terminal variant of SseF interacted directly with mammalian ACBD3, a multifunctional cytosolic Golgi network-associated protein. Knockdown of ACBD3 by small interfering RNA (siRNA) reduced epithelial cell Golgi network association of wild-type bacteria, phenocopying the effect of null mutations of
sseG
or
sseF
. Binding of SseF to ACBD3 in infected cells required the presence of SseG. A single-amino-acid mutant of SseG and a double-amino-acid mutant of SseF were obtained that did not interact with ACBD3 in
Saccharomyces cerevisiae
. When either of these was produced together with the corresponding wild-type effector by
Salmonella
in infected cells, they enabled SCV-Golgi network association and interacted with ACBD3. However, these properties were lost and bacteria displayed an intracellular replication defect when cells were infected with
Salmonella
carrying both mutant genes. Knockdown of ACBD3 resulted in a replication defect of wild-type bacteria but did not further attenuate the growth defect of a Δ
sseFG
mutant strain. We propose a model in which interaction between SseF and SseG enables both proteins to bind ACBD3, thereby anchoring SCVs at the Golgi network and facilitating bacterial replication.

IMPORTANCE
Upon invasion of epithelial cells, the majority of vacuoles containing
Salmonella enterica
migrate to the perinuclear region-located Golgi network and remain in this region of the cell during the first few rounds of bacterial replication, forming a clustered microcolony of vacuoles. This process requires the action of SseF and SseG, two effector proteins that are translocated by the
Salmonella
SPI-2 type III secretion system. However, little is known about how they function. Here, we show that both proteins interact with the mammalian Golgi network-associated protein ACBD3. To our knowledge, the SseF-SseG-ACBD3 interaction is the first example of a tethering complex between a pathogen-containing vacuole and a host cell organelle.
CtaM Is Required for Menaquinol Oxidase
aa
3
Function in Staphylococcus aureus
Authors: Hammer Neal D. , Schurig-Briccio Lici A. , Gerdes Svetlana Y. , Gennis Robert B. , Skaar Eric P.
Published: July 2016

Staphylococcus aureus
is the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability of
S. aureus
to cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (
o
type,
bd
type, and
aa
3
type), the genome contains genes encoding only two respiratory oxygen reductases,
cydAB
and
qoxABCD
. Previous investigation showed that
cydAB
and
qoxABCD
are required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of the
cydAB
and
qoxABCD
in virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is an
aa
3
-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as a
bo
3
-type menaquinol oxidase. However, the
bo
3
form of QoxABCD restricts the carbon sources that can support the growth of
S. aureus
. In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiring
Firmicutes
. In total, these studies establish the heme A biosynthesis pathway in
S. aureus
, determine that QoxABCD is a type
aa
3
menaquinol oxidase, and reveal CtaM as a new protein required for type
aa
3
menaquinol oxidase function in multiple bacterial genera.

IMPORTANCE
Staphylococcus aureus
relies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of the
S. aureus
electron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain of
S. aureus
is comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration.
Metabolic Regulation as a Consequence of Anaerobic 5-Methylthioadenosine Recycling in Rhodospirillum rubrum
Authors: North Justin A. , Sriram Jaya , Chourey Karuna , Ecker Christopher D. , Sharma Ritin , Wildenthal John A. , Hettich Robert L. , Tabita F. Robert
Published: July 2016

Rhodospirillum rubrum
possesses a novel oxygen-independent, aerobic methionine salvage pathway (MSP) for recycling methionine from 5-methylthioadenosine (MTA), the MTA-isoprenoid shunt. This organism can also metabolize MTA as a sulfur source under anaerobic conditions, suggesting that the MTA-isoprenoid shunt may also function anaerobically as well. In this study, deep proteomics profiling, directed metabolite analysis, and reverse transcriptase quantitative PCR (RT-qPCR) revealed metabolic changes in response to anaerobic growth on MTA versus sulfate as sole sulfur source. The abundance of protein levels associated with methionine transport, cell motility, and chemotaxis increased in the presence of MTA over that in the presence of sulfate. Purine salvage from MTA resulted primarily in hypoxanthine accumulation and a decrease in protein levels involved in GMP-to-AMP conversion to balance purine pools. Acyl coenzyme A (acyl-CoA) metabolic protein levels for lipid metabolism were lower in abundance, whereas poly-β-hydroxybutyrate synthesis and storage were increased nearly 10-fold. The known
R. rubrum
aerobic MSP was also shown to be upregulated, to function anaerobically, and to recycle MTA. This suggested that other organisms with gene homologues for the MTA-isoprenoid shunt may also possess a functioning anaerobic MSP. In support of our previous findings that ribulose-1,5-carboxylase/oxygenase (RubisCO) is required for an apparently purely anaerobic MSP, RubisCO transcript and protein levels both increased in abundance by over 10-fold in cells grown anaerobically on MTA over those in cells grown on sulfate, resulting in increased intracellular RubisCO activity. These results reveal for the first time global metabolic responses as a consequence of anaerobic MTA metabolism compared to using sulfate as the sulfur source.

IMPORTANCE
In nearly all organisms, sulfur-containing byproducts result from many metabolic reactions. Unless these compounds are further metabolized, valuable organic sulfur is lost and can become limiting. To regenerate the sulfur-containing amino acid methionine, organisms typically employ one of several variations of a “universal” methionine salvage pathway (MSP). A common aspect of the universal MSP is a final oxygenation step. This work establishes that the metabolically versatile bacterium
Rhodospirillum rubrum
employs a novel MSP that does not require oxygen under either aerobic or anaerobic conditions. There is also a separate, dedicated anaerobic MTA metabolic route in
R. rubrum
. This work reveals global changes in cellular metabolism in response to anaerobic MTA metabolism compared to using sulfate as a sulfur source. We found that cell mobility and transport were enhanced, along with lipid, nucleotide, and carbohydrate metabolism, when cells were grown in the presence of MTA.
Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
Authors: Liu Shu , Hossinger André , Hofmann Julia P. , Denner Philip , Vorberg Ina M.
Published: July 2016

Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast (
Saccharomyces cerevisiae
) are epigenetic elements of inheritance that induce phenotypic changes of their host cells. The prototype yeast prion is the translation termination factor Sup35. Prions composed of Sup35 or its modular prion domain NM are heritable and are transmitted vertically to progeny or horizontally during mating. Interestingly, in mammalian cells, protein aggregates derived from yeast Sup35 NM behave as true infectious entities that employ dissemination strategies similar to those of mammalian prions. While transmission is most efficient when cells are in direct contact, we demonstrate here that cytosolic Sup35 NM prions are also released into the extracellular space in association with nanometer-sized membrane vesicles. Importantly, extracellular vesicles are biologically active and are taken up by recipient cells, where they induce self-sustained Sup35 NM protein aggregation. Thus, in mammalian cells, extracellular vesicles can serve as dissemination vehicles for protein-based epigenetic information transfer.

IMPORTANCE
Prions are proteinaceous infectious particles that propagate by templating their quaternary structure onto nascent proteins of the same kind. Prions in yeast act as heritable epigenetic elements that can alter the phenotype when transmitted to daughter cells or during mating. Prion activity is conferred by so-called prion domains often enriched in glutamine and asparagine residues. Interestingly, many mammalian proteins also contain domains with compositional similarity to yeast prion domains. We have recently provided a proof-of-principle demonstration that a yeast prion domain also retains its prion activity in mammalian cells. We demonstrate here that cytosolic prions composed of a yeast prion domain are also packaged into extracellular vesicles that transmit the prion phenotype to bystander cells. Thus, proteins with prion-like domains can behave as proteinaceous information molecules that exploit the cellular vesicle trafficking machinery for intercellular long-distance dissemination.
Proteome Remodeling in Response to Sulfur Limitation in “
Candidatus
Pelagibacter ubique”
Authors: Smith Daniel P. , Nicora Carrie D. , Carini Paul , Lipton Mary S. , Norbeck Angela D. , Smith Richard D. , Giovannoni Stephen J.
Published: July 2016

“
Ca
. Pelagibacter ubique” is a key driver of marine biogeochemistry cycles and a model for understanding how minimal genomes evolved in free-living anucleate organisms. This study explores the unusual sulfur acquisition strategy that has evolved in these cells, which lack assimilatory sulfate reduction and instead rely on reduced sulfur compounds found in oxic marine environments to meet their cellular quotas. Our findings demonstrate that the sulfur acquisition systems are constitutively expressed but the enzymatic steps leading to the essential sulfur-containing amino acid methionine are regulated by a unique array of riboswitches and genes, many of which are encoded in a rapidly evolving genome region. These findings support mounting evidence that streamlined cells have evolved regulatory mechanisms that minimize transcriptional switching and, unexpectedly, localize essential sulfur acquisition genes in a genome region normally associated with adaption to environmental variation.
Precipitation changes in the western tropical Pacific over the past millennium
Authors: Richey J.N. , Sachs J.P.
Published: July 2016

Modern seasonal and inter-annual precipitation variability in Palau is linked to both meridional movement of the Intertropical Convergence Zone (ITCZ) and changes in the Pacific Walker Circulation (PWC) associated with the El Niño–Southern Oscillation. Thus, Palau’s hydroclimate should be sensitive to mean shifts in the ITCZ and PWC on decadal to centennial time scales. Using compound-specific hydrogen isotope ratios (δ2H) of dinosterol in lake sediments, we generated a decadal-resolution proxy record of hydroclimatic variability in Palau spanning the past 800 yr. Results indicate a drying trend during the Little Ice Age in Palau, consistent with a southward displacement of the ITCZ. In addition to the secular drying trend, there are persistent large (∼20‰) multi-decadal to centennial oscillations in the δ2H record, the most recent of which indicates an abrupt shift to drier conditions in the mid-1970s that coincides with a decadal-scale negative shift in the Southern Oscillation Index.
Voluminous plutonism during volcanic quiescence revealed by thermochemical modeling of zircon
Authors: Tierney Casey R. , Schmitt Axel K. , Lovera Oscar M. , de Silva Shanaka L.
Published: July 2016

Five late Pleistocene lava domes with a combined eruptive volume of ∼40 km3 distributed over an area of ∼2000 km2 represent the waning stages of the 10–1 Ma ignimbrite flare-up in the Altiplano Puna Volcanic Complex (APVC) of the Central Andes. Zircon crystal face (on unsectioned rims) and interior (on sectioned crystals) ages (U-Th and U-Pb, respectively) for a total of 252 crystals indicate remarkably consistent zircon crystallization histories: the youngest zircon surface ages (ca. 104–83 ka) are near 40Ar/39Ar eruption ages from sanidine and biotite (ca. 120–87 ka), but a significant population of surface ages predates eruption, ranging to secular equilibrium (with U-Pb interior ages to 3.5 Ma). The essentially continuous zircon crystallization history implies protracted magma presence, which agrees with temporally invariant Ti-in-zircon model temperatures, backed by the homogeneity of indirectly temperature-dependent compositional parameters. Zircon age spectra modeled using a finite-difference thermal and mass-balance model for open-system magma evolution indicate protracted zircon production in the magma reservoirs that require time-integrated recharge rates of ∼1 × 10−3 km3/yr, corresponding to high intrusive to extrusive ratios of 75: 1. This rate is below the ∼5 × 10−3 km3/yr threshold proposed in the literature for incubating the supereruptions defining the flare-up. When accounting for the shorter durations of high versus low recharge episodes over the ∼10 m.y. lifetime of the APVC flare-up, the contributions to composite batholith formation in the shallow crust of the APVC remained broadly constant during peaks and lulls in eruptive activity. This connotes that eruptive fluxes are a poor measure for intrusive fluxes. A corollary of this interpretation is that commonly applied intrusive to extrusive ratios will severely underestimate pluton formation rates during periods of low eruptive flux.
Aridity-induced Miocene canyon incision in the Central Andes
Authors: Cooper F.J. , Adams B.A. , Blundy J.D. , Farley K.A. , McKeon R.E. , Ruggiero A.
Published: July 2016

The relationship between the rise of the Andean mountain chain and the onset of aridity on its western margin is poorly understood. Canyon incision on both the eastern and western flanks of the chain is interpreted generally as a direct response to increased rock uplift, but may equally have been the result of climate change. Here we record some of the oldest canyon incision on the western Andean margin by tracking the downward migration of the local water table using (U-Th)/He hematite geochronology on vertical drill-core transects. Our data constrain the incision history of the Quebrada de Parca canyon in northern Chile from ca. 16 Ma to the present day. The erosional and topographic response of the Quebrada de Parca river suggests that incision was induced by a switch to a more arid climate in the middle Miocene, which reduced regional precipitation and river discharge. Geomorphic analysis of the modern river suggests that the Central Andes have gained only ∼700 m of elevation since incision began, and had therefore reached at least 50% of their current elevation by middle Miocene time. We thus conclude that the onset of aridity at ca. 16 Ma occurred subsequent to the main Andean uplift.
Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol
Authors: Coutsoudis Anna , Daniels Brodie , Moodley-Govender Eshia , Ngomane Noluthando , Zako Linda , Spooner Elizabeth , Kiepiela Photini , Reddy Shabashini , Kuhn Louise , Ramjee Gita
Published: July 2016

Introduction

No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study.

Methods

A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity.

Ethics and dissemination

The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13).

Trial registration numbers

PACTR201311000621110 and DOH-27-0614-4728; Pre-results.
Intra-articular bupivacaine after joint arthroplasty: a systematic review and meta-analysis of randomised placebo-controlled studies
Authors: Cui Yang , Yang Tuo , Zeng Chao , Wei Jie , Xie Xi , Li Liangjun , Ding Xiang , Zhang Yi , Lei Guanghua
Published: July 2016

Objectives

To evaluate the efficacy and safety of intra-articular (IA) bupivacaine administered for pain relief after joint arthroplasty.

Design

Meta-analysis.

Methods

A systematic review was conducted to identify the randomised controlled trials using IA bupivacaine for postoperative pain relief from MEDLINE, Cochrane Library and EMBASE databases (up to October 2015). The standardised mean difference (SMD), the relative risk (RR) and their corresponding 95% CIs were calculated using the RevMan statistical software.

Results

A total of 11 randomised controlled trials were included. Statistically significant differences between IA bupivacaine and placebo were observed for the mean visual analogue scale (VAS) values (SMD −0.55; 95% CI −0.89 to −0.22; p<0.001) and narcotic consumption (SMD −0.32; 95% CI −0.55 to −0.08; p=0.008) during the period of 24 hours postoperatively and narcotic consumption during the period between 24 and 48 hours postoperatively (SMD −0.32; 95% CI −0.55 to −0.08; p=0.009). However, there was no significant difference in the mean VAS pain score during the period between 24  and 48 hours postoperatively (SMD −0.09, 95% CI −0.30 to 0.11; p=0.37) and in the incidence of adverse effects 24–72 hours postoperatively (RR 0.97; 95% CI 0.60 to 1.57; p=0.91).

Conclusions

The administration of IA bupivacaine after joint arthroplasty is effective for pain relief without increasing adverse effects.
Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol
Authors: Mineiro Maria Alexandra , Marques da Silva Pedro , Alves Marta , Virella Daniel , Marques Gomes Maria João , Cardoso João
Published: July 2016

Introduction

Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness.

Methods and analysis

This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central—CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea–hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time.

Ethics and dissemination

This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals.

Trial registration number

NCT02273089; Pre-results.
Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study
Authors: Dondo T B , Hall M , Timmis A D , Yan A T , Batin P D , Oliver G , Alabas O A , Norman P , Deanfield J E , Bloor K , Hemingway H , Gale C P
Published: July 2016

Objectives

To investigate geographic variation in guideline-indicated treatments for non-ST-elevation myocardial infarction (NSTEMI) in the English National Health Service (NHS).

Design

Cohort study using registry data from the Myocardial Ischaemia National Audit Project.

Setting

All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS.

Participants

357 228 patients with NSTEMI between 1 January 2003 and 30 June 2013.

Main outcome measure

Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication.

Results

The proportion of NSTEMI who received optimal care was low (48 257/357 228; 13.5%) and varied between CCGs (median 12.8%, IQR 0.7–18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0–40.0%) and least for use of an ECG (96.7%, 92.5–98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6–97.1%), and aspirin (90.1%, 85.1–93.3%) and statins (86.4%, 82.3–91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7–16.6%), dietary advice (32.4%, 23.9–41.7%) and the prescription of P2Y12inhibitors (39.7%, 32.4–46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between-hospital differences (median 64.7%, IQR 57.4–70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 0.976 to 0.999).

Conclusions

Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths.

Trial registration number

NCT02436187.
External validation of the emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP)
Authors: Flaws Dylan , Than Martin , Scheuermeyer Frank Xavier , Christenson James , Boychuk Barbara , Greenslade Jaimi H , Aldous Sally , Hammett Christopher J , Parsonage William A , Deely Joanne M , Pickering John W , Cullen Louise
Published: July 2016

Objective

The emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP) facilitates low-risk ED chest pain patients early to outpatient investigation. We aimed to validate this rule in a North American population.

Methods

We performed a retrospective validation of the EDACS-ADP using 763 chest pain patients who presented to St Paul's Hospital, Vancouver, Canada, between June 2000 and January 2003. Patients were classified as low risk if they had an EDACS <16, no new ischaemia on ECG and non-elevated serial 0-hour and 2-hour cardiac troponin concentrations. The primary outcome was the number of patients who had a predetermined major adverse cardiac event (MACE) at 30 days after presentation.

Results

Of the 763 patients, 317 (41.6%) were classified as low risk by the EDACS-ADP. The sensitivity, specificity, negative predictive value and positive predictive value of the EDACS-ADP for 30-day MACE were 100% (95% CI 94.2% to 100%), 46.4% (95% CI 42.6% to 50.2%), 100% (95% CI 98.5% to 100.0%) and 17.5% (95% CI 14.1% to 21.3%), respectively.

Conclusions

This study validated the EDACS-ADP in a novel context and supports its safe use in a North American population. It confirms that EDACS-ADP can facilitate progression to early outpatient investigation in up to 40% of ED chest pain patients within 2 hours.
Cardiovascular disease risk factors in relation to smoking behaviour and history: a population-based cohort study
Authors: Keto Jaana , Ventola Hanna , Jokelainen Jari , Linden Kari , Keinänen-Kiukaanniemi Sirkka , Timonen Markku , Ylisaukko-oja Tero , Auvinen Juha
Published: July 2016

Objective

To investigate how individual risk factors for cardiovascular disease (CVD) (blood pressure, lipid levels, body mass index, waist and hip circumference, use of antihypertensive or hypolipidemic medication, and diagnosed diabetes) differ in people aged 46 years with different smoking behaviour and history.

Methods

This population-based cohort study is based on longitudinal data from the Northern Finland Birth Cohort 1966 project. Data were collected at the 31-year and 46-year follow-ups, when a total of 5038 and 5974 individuals participated in clinical examinations and questionnaires. Data from both follow-ups were available for 3548 participants. In addition to individual CVD risk factors, Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms were used to assess the absolute risk of a CVD event within the next decade.

Results

The differences in individual risk factors for CVD reached statistical significance for some groups, but the differences were not consistent or clinically significant. There were no clinically significant differences in CVD risk as measured by Framingham or SCORE algorithms between never smokers, recent quitters and former smokers (7.5%, 7.4%, 8.1% for men; 3.3%, 3.0%, 3.2% for women; p<0.001).

Conclusions

The effect of past or present smoking on individual CVD risk parameters such as blood pressure and cholesterol seems to be of clinically minor significance in people aged 46 years. In other words, smoking seems to be above all an independent risk factor for CVD in the working-age population. Quitting smoking in working age may thus reduce calculated CVD risk nearly to the same level with people who have never smoked.
Prospective observational study of point-of-care creatinine in trauma
Authors: Carden Anthony J , Salcedo Edgardo S , Tran Nam K , Gross Eric , Mattice Jennifer , Shepard Jan , Galante Joseph M
Published: July 2016

Background

Patients with trauma are at risk for renal dysfunction from hypovolemia or urological injury. In austere environments, creatinine values are not available to guide resuscitation. A new portable device, the Stat Sensor Point-of-care (POC) Whole Blood Creatinine Analyzer, provides accurate results in <30 s and requires minimal training. This device has not been evaluated in trauma despite the theoretical benefit it provides. The purpose of this study is to determine the clinical impact of the POC device in trauma.

Methods

40 patients with trauma were enrolled in a prospective observational study. One drop of blood was used for creatinine determination on the Statsensor POC device. POC creatinine results were compared to the laboratory. Turnaround time (TAT) for POC and laboratory methods was calculated as well as time elapsed to CT scan if applicable.

Results

Patients (n=40) were enrolled between December 2014 and March 2015. POC creatinine values were similar to laboratory methods with a mean bias of 0.075±0.27 (p=0.08). Mean analytical TATs for the POC measurements were significantly faster than the laboratory method (11.6±10.0 min vs 78.1±27.9 min, n=40, p<0.0001). Mean elapsed time before arrival at the CT scanner was 52.9±34.2 min.

Conclusions

The POC device reported similar creatinine values to the laboratory and provided significantly faster results. POC creatinine testing is a promising development for trauma practice in austere environments and workup of a subset of stable patients with trauma. Further study is warranted to determine clinical impact, both in hospital-based trauma and austere environments.
Temperature characterization of dielectric permittivity and AC conductivity of nano copper oxide-doped polyaniline composite
Authors: Shubha L. N. , Madhusudana Rao P.
Published: July 2016

The polyaniline/copper oxide (PANI/CuO) nanocomposite was prepared by mixing solutions of polyaniline and copper oxide nanoparticles in dimethyl sulfoxide (DMSO). The synthesized polymer nanocomposites were characterized by X-ray powder diffraction (XRD), scanning electron microscope (SEM) and UV–visible spectroscopy. The characteristic peaks in XRD and UV–visible spectra confirmed the presence of CuO in the polymer structure. SEM images indicated morphological changes in the composite matrix as compared to the pristine PANI. The DC conductivity measurements were performed using two-probe method for various temperatures. AC conductivity and dielectric response of the composites were investigated in the frequency range of [Formula: see text]–[Formula: see text][Formula: see text]Hz using LCR meter. Dielectric permittivity [Formula: see text] and dielectric loss factor [Formula: see text] were investigated. It was observed that [Formula: see text] and [Formula: see text] decrease with increase in frequency at all temperatures. At a particular frequency it is observed that both [Formula: see text] and [Formula: see text] increase with increase in temperature. It was also observed that AC conductivity increased with increase in frequency and temperature.
Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents
Authors: Perry Rachel J. , Cardone Rebecca L. , Petersen Max C. , Zhang Dongyan , Fouqueray Pascale , Hallakou-Bozec Sophie , Bolze Sébastien , Shulman Gerald I. , Petersen Kitt Falk , Kibbey Richard G.
Published: July 2016

Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c(1–3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin.
Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis
Authors: Wharfe Michaela D. , Wyrwoll Caitlin S. , Waddell Brendan J. , Mark Peter J.
Published: July 2016

Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes. Maternal liver and plasma ( n = 6–8/group) were collected across 24-h periods (0800, 1200, 1600, 2000, 0000, 0400) from C57Bl/6J mice under isoflurane-nitrous oxide anesthesia prior to and on days 6, 10, 14 and 18 of pregnancy (term = day 19). Hepatic expression of clock genes and glucoregulatory genes was determined by RT-qPCR. Hepatic clock gene expression was substantially altered across pregnancy, most notably in late gestation when the circadian rhythmicity of several clock genes was attenuated (≤64% reduced amplitude on day 18). These changes were associated with a similar decline in rhythmicity of the key glucoregulatory genes Pck1, G6Pase, and Gk, and by day 18, Pck1 was no longer rhythmic. Overall, our data show marked adaptations in the liver clock during mouse pregnancy, changes that may contribute to the altered circadian variation in glucoregulatory genes near term. We propose that the observed reduction of daily oscillations in glucose metabolism ensure a sustained supply of glucose to meet the high demands of fetal growth.
Posttranslational modifications and dysfunction of mitochondrial enzymes in human heart failure
Authors: Sheeran Freya L. , Pepe Salvatore
Published: July 2016

Deficiency of energy supply is a major complication contributing to the syndrome of heart failure (HF). Because the concurrent activity profile of mitochondrial bioenergetic enzymes has not been studied collectively in human HF, our aim was to examine the mitochondrial enzyme defects in left ventricular myocardium obtained from explanted end-stage failing hearts. Compared with nonfailing donor hearts, activity rates of complexes I and IV and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase, and aconitase were lower in HF, as determined spectrophotometrically. However, activity rates of complexes II and III and citrate synthase did not differ significantly between the two groups. Protein expression, determined by Western blotting, did not differ between the groups, implying posttranslational perturbation. In the face of diminished total glutathione and coenzyme Q10levels, oxidative modification was explored as an underlying cause of enzyme dysfunction. Of the three oxidative modifications measured, protein carbonylation was increased significantly by 31% in HF ( P < 0.01; n = 18), whereas levels of 4-hydroxynonenal and protein nitration, although elevated, did not differ. Isolation of complexes I and IV and F1FoATP synthase by immunocapture revealed that proteins containing iron-sulphur or heme redox centers were targets of oxidative modification. Energy deficiency in end-stage failing human left ventricle involves impaired activity of key electron transport chain and Krebs cycle enzymes without altered expression of protein levels. Augmented oxidative modification of crucial enzyme subunit structures implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, thus contributing further to reduced bioenergetics in human HF.
Flight-Test Evaluation of Kinematic Precise Point Positioning of Small UAVs
Authors: Gross Jason N. , Watson Ryan M. , D’Urso Stéphane , Gu Yu
Published: July 2016

An experimental analysis of Global Positioning System (GPS) flight data collected onboard a Small Unmanned Aerial Vehicle (SUAV) is conducted in order to demonstrate that postprocessed kinematic Precise Point Positioning (PPP) solutions with precisions approximately 6 cm 3D Residual Sum of Squares (RSOS) can be obtained on SUAVs that have short duration flights with limited observational periods (i.e., only ~≤5 minutes of data). This is a significant result for the UAV flight testing community because an important and relevant benefit of the PPP technique over traditional Differential GPS (DGPS) techniques, such as Real-Time Kinematic (RTK), is that there is no requirement for maintaining a short baseline separation to a differential GNSS reference station. Because SUAVs are an attractive platform for applications such as aerial surveying, precision agriculture, and remote sensing, this paper offers an experimental evaluation of kinematic PPP estimation strategies using SUAV platform data. In particular, an analysis is presented in which the position solutions that are obtained from postprocessing recorded UAV flight data with various PPP software and strategies are compared to solutions that were obtained using traditional double-differenced ambiguity fixed carrier-phase Differential GPS (CP-DGPS). This offers valuable insight to assist designers of SUAV navigation systems whose applications require precise positioning.