bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Suvorexant in Blood Using LC–MS-MS: Important Considerations for Matrix Effects and Quantitative Interferences in Targeted Assays
Authors: Skillman Britni , Kerrigan Sarah
Published: September 2019

Suvorexant (Belsomra®) is a novel dual orexin receptor antagonist used for the treatment of insomnia. The prevalence of suvorexant in forensic samples is relatively unknown, which demonstrates the need for robust analytical assays for the detection of this sedative hypnotic in forensic toxicology laboratories. In this study, suvorexant was isolated from whole blood using a simple acidic/neutral liquid–liquid extraction followed by analysis by liquid chromatography tandem mass spectrometry (LC–MS/MS). Matrix effects were evaluated qualitatively and quantitatively using various extraction solvents, proprietary lipid clean-up devices and source conditions. The method was validated in terms of limit of detection, limit of quantitation, precision, bias, calibration model, carryover, matrix effects and drug interferences. Electrospray is a competitive ionization process whereby compounds in the droplet compete for a limited number of charged sites at the surface. As such, it is capacity-limited, and LC–MS-based techniques must be carefully evaluated to ensure that matrix effects or coeluting drugs do not impact quantitative assay performance. In this report, we describe efforts to ameliorate such effects in the absence of an isotopically labeled internal standard. Matrix effects are highly variable and heavily dependent on the physico-chemical properties of the substance. Although there is no universal solution to their resolution, conditions at the electrospray interface can mitigate these issues. Using this approach, the LC–MS/MS assay was fully validated and limits of detection and quantitation of 0.1 and 0.5 ng/mL suvorexant were achieved in blood.
Economic Mobility Under Pressure
Authors: Markussen Simen , Røed Knut
Published: September 2019

Based on complete population data, with the exact same definitions of family class background and economic outcomes for a large number of birth cohorts, we examine post-war trends in intergenera-tional economic mobility in Norway. Standard summary statistics indicate stable or mildly declining rank–rank mobility for sons and sharply declining mobility for daughters. The most conspicuous trend in the mobility patterns is that men and women born into the lowest parts of the parental earnings distribution have fallen behind in terms of own earnings rank, as well as a number of other quality-of-life indicators. A considerable part of this development can be explained by changes in the class distribution of educational attainment and in its rising influence on earnings rank. We argue that although the educational revolution has diminished the role of inherited ability, it has enlarged the influence of the family as provider of a social learning environment.
Beliefs and Consumer Search in a Vertical Industry
Authors: Janssen Maarten , Shelegia Sandro
Published: September 2019

This paper studies vertical relations in a search market. As the wholesale arrangement between a manufacturer and its retailers is typically unobserved by consumers, their beliefs about who is to be blamed for a price deviation play a crucial role in determining wholesale and retail prices. The common assumption in the consumer search literature is that consumers exclusively blame an individual retailer for a price deviation. We show that in the vertical relations context, predictions based on this assumption are not robust in the sense that if consumers hold the upstream manufacturer at least partially responsible for the deviation, equilibrium predictions are qualitatively different. For robust beliefs, the vertical model can explain a variety of observations, such as retail price rigidity (or, alternatively, low cost pass-through), nonmonotonicity of retail prices in search costs, and (seemingly) collusive retail behavior. The model can be used to study a monopoly online platform that sells access to final consumers.
Constraints on high-J CO emission lines in z ∼ 6 quasars
Authors: Carniani S , Gallerani S , Vallini L , Pallottini A , Tazzari M , Ferrara A , Maiolino R , Cicone C , Feruglio C , Neri R , D’Odorico V , Wang R , Li J
Published: September 2019

We present Atacama Large Millimiter/submillimiter Array (ALMA) observations of eight highly excited CO (${\rm J_{\rm up}}$ >8) lines and continuum emission in two z ∼ 6 quasars: SDSS J231038.88+185519.7 (hereafter J2310), for which CO(8-7), CO(9-8), and CO(17-16) lines have been observed, and ULAS J131911.29+095951.4 (J1319), observed in the CO(14-13), CO(17-16) and CO(19-18) lines. The continuum emission of both quasars arises from a compact region (<0.9 kpc). By assuming a modified black-body law, we estimate dust masses of Log(Mdust/M⊙) = 8.75 ± 0.07 and Log(Mdust/M⊙) = 8.8 ± 0.2 and dust temperatures of Tdust = 76 ± 3 K and $T_{\rm dust}=66^{+15}_{-10}~{\rm K}$, respectively for J2310 and J1319. Only CO(8-7) and CO(9-8) in J2310 are detected, while 3σ upper limits on luminosities are reported for the other lines of both quasars. The CO line luminosities and upper limits measured in J2310 and J1319 are consistent with those observed in local AGN and starburst galaxies, and other z ∼ 6 quasars, except for SDSS J1148+5251 (J1148), the only quasar at z = 6.4 with a previous CO(17-16) line detection. By computing the CO SLEDs normalised to the CO(6-5) line and FIR luminosities for J2310, J1319, and J1149, we conclude that different gas heating mechanisms (X-ray radiation and/or shocks) may explain the different CO luminosities observed in these z ∼ 6 quasar. Future ${\rm J_{\rm up}}$ >8 CO observations will be crucial to understand the processes responsible for molecular gas excitation in luminous high-z quasars.
Long rotation period main-sequence stars from Kepler SAP light curves
Authors: Cui Kaiming , Liu Jifeng , Yang Shuhong , Gao Qing , Yang Huiqin , Soria Roberto , He Lin , Wang Song , Bai Yu , Yang Fan
Published: September 2019

Stellar rotation plays a key role in stellar activity. The rotation period could be detected through light curve variations caused by star-spots. Kepler provides two types of light curves: one is the Pre-search Data Conditioning (PDC) light curves, and the other is the Simple Aperture Photometer (SAP) light curves. Compared with the PDC light curves, the SAP light curves keep the long-term trend, relatively suitable for searches of long-period signals. However, SAP data are inflicted by some artefacts such as quarterly rolls and instrumental errors, making it difficult to find the physical periods in the SAP light curves. We explore a systematic approach based on the light curve pre-processing, period detection, and candidate selection. We also develop a simulated light curve test to estimate our detection limits for the SAP-like LCs. After applying our method to the raw SAP light curves, we found more than 1000 main-sequence stars with periods longer than 30 d; 165 are newly discovered. Considering the potential flaw of the SAP, we also inspect the newly found objects with photometry methods, and most of our periodical signals are confirmed.
The g-mode spectrum of reactive neutron star cores
Authors: Andersson N , Pnigouras P
Published: September 2019

We discuss the impact of nuclear reactions on the spectrum of gravity g-modes of a mature neutron star, demonstrating the anticipated disappearance of these modes when the timescale associated with the oscillations is longer than that of nuclear reactions. This is the expected result, but different aspects of the demonstration may be relevant for related problems in neutron star astrophysics. In particular, we develop the framework required for an explicit implementation of finite-time nuclear reactions in neutron star oscillation problems and demonstrate how this formulation connects with the usual bulk viscosity prescription. We also discuss implications of the absence of very high order g-modes for problems of astrophysical relevance.
A dwarf disrupting – Andromeda XXVII and the North West Stream
Authors: Preston Janet , Collins Michelle L M , Ibata Rodrigo A , Tollerud Erik J , Rich R Michael , Bonaca Ana , McConnachie Alan W , Mackey Dougal , Lewis Geraint F , Martin Nicolas F , Peñarrubia Jorge , Chapman Scott C , Delorme Maxime
Published: September 2019

We present a kinematic and spectroscopic analysis of 38 red giant branch stars, in seven fields, spanning the dwarf spheroidal galaxy Andromeda XXVII and the upper segment of the North West Stream. Both features are located in the outer halo of the Andromeda galaxy at a projected radius of 50–80 kpc, with the stream extending for ∼3° on the sky. Our data are obtained as part of the PAndAS survey and enables us to confirm that Andromeda XXVII’s heliocentric distance is 827 ± 47 kpc and spectroscopic metallicity is $-2.1^{+0.4}_{-0.5}$. We also re-derive Andromeda XXVII’s kinematic properties, measuring a systemic velocity  = $-526.1^{+10.0}_{-11.0}$ km s−1 and a velocity dispersion that we find to be non-Gaussian but for which we derive a formal value of 27.0$^{+2.2}_{-3.9}$ km s−1. In the upper segment of the North West Stream we measure mean values for the metallicity = −1.8 ± 0.4, systemic velocity  = −519.4 ± 4.0 km s−1, and velocity dispersion  = 10.0 ± 4.0 km s−1. We also detect a velocity gradient of 1.7 ± 0.3 km s−1 kpc−1 on an infall trajectory towards M31. With a similar gradient, acting in the same direction, in the lower segment we suggest that the North West Stream is not a single structure. As the properties of the upper segment of the North West Stream and Andromeda XXVII are consistent within 90 per cent confidence limits, it is likely that the two are related and plausible that Andromeda XXVII is the progenitor of this stream.
Gravitomagnetism and pulsar beam precession near a Kerr black hole
Authors: Kocherlakota Prashant , Joshi Pankaj S , Bhattacharyya Sudip , Chakraborty Chandrachur , Ray Alak , Biswas Sounak
Published: September 2019

A rotating black hole causes the spin axis of a nearby pulsar to precess due to geodetic and gravitomagnetic frame-dragging effects. The aim of our theoretical work here is to explore how this spin precession can modify the rate at which pulses are received on Earth. Towards this end, we obtain the complete evolution of the beam vectors of pulsars moving on equatorial circular orbits in the Kerr space–time, relative to asymptotic fixed observers. We proceed to establish that such spin precession effects can significantly modify observed pulse frequencies and, in specific, we find that the observed pulse frequency rises sharply as the orbit shrinks, potentially providing a new way to locate horizons of Kerr black holes, even if observed for a very short time period. We also discuss implications for detections of sub-millisecond pulsars, pulsar nulling, quasi-periodic oscillations, multiply peaked pulsar Fourier profiles, and how Kerr black holes can potentially be distinguished from naked singularities.
Using large-scale structure data and a halo model to constrain generalized dark matter
Authors: Thomas Daniel B , Kopp Michael , Markovič Katarina
Published: September 2019

Constraints on the properties of the cosmological dark matter have previously been obtained in a model-independent fashion using the generalized dark matter (GDM) framework. Here we extend that work in several directions: We consider the inclusion of WiggleZ matter power spectrum data (MPS), and show that this improves the constraints on the two perturbative GDM parameters, $c^2_\mathrm{ s}$ and $c^2_\text{vis}$, by a factor of 3, for a conservative choice of wavenumber range. A less conservative choice can yield an improvement of up to an order of magnitude compared to previous constraints. In order to examine the robustness of this result we develop a GDM halo model (HM) to explore how non-linear structure formation could proceed in this framework, since currently GDM has only been defined perturbatively and only linear theory has been used when generating constraints. We then examine how the HM affects the constraints obtained from the MPS data. The less-conservative wavenumber range shows a significant difference between linear and non-linear modelling, with the latter favouring GDM parameters inconsistent with ΛCDM, underlining the importance of careful non-linear modelling when using this data. We also use this HM to establish the robustness of previously obtained constraints, particularly those that involve weak gravitational lensing of the cosmic microwave background. Additionally, we show how the inclusion of neutrino mass as a free parameter affects previous constraints on the GDM parameters.
The nuclear environment of the NLS1 Mrk 335: Obscuration of the X-ray line emission by a variable outflow
Authors: Parker M L , Longinotti A L , Schartel N , Grupe D , Komossa S , Kriss G , Fabian A C , Gallo L , Harrison F A , Jiang J , Kara E , Krongold Y , Matzeu G A , Pinto C , Santos-Lleó M
Published: September 2019

We present XMM–Newton, NuSTAR, Swift, and Hubble Space Telescope observations of the Narrow-line Seyfert 1 galaxy Mrk 335 in a protracted low state in 2018 and 2019. The X-ray flux is at the lowest level so far observed, and the extremely low continuum flux reveals a host of soft X-ray emission lines from photoionized gas. The simultaneous UV flux drop suggests that the variability is intrinsic to the source, and we confirm this with broad-band X-ray spectroscopy. The dominance of the soft X-ray lines at low energies and distant reflection at high energies, is therefore due to the respective emission regions being located far enough from the X-ray source that they have not yet seen the flux drop. Between the two XMM–Newton spectra, taken 6 months apart, the emission line ratio in the O vii triplet changes drastically. We attribute this change to a drop in the ionization of intervening warm absorption, which means that the absorber must cover a large fraction of the line emitting region, and extend much further from the black hole than previously assumed. The HST spectrum, taken in 2018, shows that new absorption features have appeared on the blue wings of C iii*, Ly α, N v, Si iv, and C iv, likely due to absorbing gas cooling in response to the low flux state.
Phosphorylation of Drosophila CENP-A on serine 20 regulates protein turn-over and centromere-specific loading
Authors: Huang Anming , Kremser Leopold , Schuler Fabian , Wilflingseder Doris , Lindner Herbert , Geley Stephan , Lusser Alexandra
Published: September 2019

Centromeres are specialized chromosomal regions epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A is required for kinetochore formation which is essential for chromosome segregation during mitosis. Spatial restriction of CENP-A to the centromere is tightly controlled. Its overexpression results in ectopic incorporation and the formation of potentially deleterious neocentromeres in yeast, flies and in various human cancers. While the contribution of posttranslational modifications of CENP-A to these processes has been studied in yeast and mammals to some extent, very little is known about Drosophila melanogaster. Here, we show that CENP-A is phosphorylated at serine 20 (S20) by casein kinase II and that in mitotic cells, the phosphorylated form is enriched on chromatin. Importantly, our results reveal that S20 phosphorylation regulates the turn-over of prenucleosomal CENP-A by the SCFPpa-proteasome pathway and that phosphorylation promotes removal of CENP-A from ectopic but not from centromeric sites in chromatin. We provide multiple lines of evidence for a crucial role of S20 phosphorylation in controlling restricted incorporation of CENP-A into centromeric chromatin in flies. Modulation of the phosphorylation state of S20 may provide the cells with a means to fine-tune CENP-A levels in order to prevent deleterious loading to extra-centromeric sites.
Low temperature isothermal amplification of microsatellites drastically reduces stutter artifact formation and improves microsatellite instability detection in cancer
Authors: Daunay Antoine , Duval Alex , Baudrin Laura G , Buhard Olivier , Renault Victor , Deleuze Jean-François , How-Kit Alexandre
Published: September 2019

Microsatellites are polymorphic short tandem repeats of 1–6 nucleotides ubiquitously present in the genome that are extensively used in living organisms as genetic markers and in oncology to detect microsatellite instability (MSI). While the standard analysis method of microsatellites is based on PCR followed by capillary electrophoresis, it generates undesirable frameshift products known as ‘stutter peaks’ caused by the polymerase slippage that can greatly complicate the analysis and interpretation of the data. Here we present an easy multiplexable approach replacing PCR that is based on low temperature isothermal amplification using recombinase polymerase amplification (LT-RPA) that drastically reduces and sometimes completely abolishes the formation of stutter artifacts, thus greatly simplifying the calling of the alleles. Using HT17, a mononucleotide DNA repeat that was previously proposed as an optimal marker to detect MSI in tumor DNA, we showed that LT-RPA improves the limit of detection of MSI compared to PCR up to four times, notably for small deletions, and simplifies the identification of the mutant alleles. It was successfully applied to clinical colorectal cancer samples and enabled detection of MSI. This easy-to-handle, rapid and cost-effective approach may deeply improve the analysis of microsatellites in several biological and clinical applications.
A prognostic model to personalize monitoring regimes for patients with incidental asymptomatic meningiomas
Authors: Islim Abdurrahman I , Kolamunnage-Dona Ruwanthi , Mohan Midhun , Moon Richard D C , Crofton Anna , Haylock Brian J , Rathi Nitika , Brodbelt Andrew R , Mills Samantha J , Jenkinson Michael D
Published: September 2019

Background

Asymptomatic meningioma is a common incidental finding with no consensus on the optimal management strategy. We aimed to develop a prognostic model to guide personalized monitoring of incidental meningioma patients.

Methods

A prognostic model of disease progression was developed in a retrospective cohort (2007–2015), defined as: symptom development, meningioma-specific mortality, meningioma growth or loss of window of curability. Secondary endpoints included non-meningioma-specific mortality and intervention.

Results

Included were 441 patients (459 meningiomas). Over a median of 55 months (interquartile range, 37–80), 44 patients had meningioma progression and 57 died (non-meningioma-specific). Forty-four had intervention (at presentation, n = 6; progression, n = 20; nonprogression, n = 18). Model parameters were based on statistical and clinical considerations and included: increasing meningioma volume (hazard ratio [HR] 2.17; 95% CI: 1.53–3.09), meningioma hyperintensity (HR 10.6; 95% CI: 5.39–21.0), peritumoral signal change (HR 1.58; 95% CI: 0.65–3.85), and proximity to critical neurovascular structures (HR 1.38; 95% CI: 0.74–2.56). Patients were stratified based on these imaging parameters into low-, medium- and high-risk groups and 5-year disease progression rates were 3%, 28%, and 75%, respectively. After 5 years of follow-up, the risk of disease progression plateaued in all groups. Patients with an age-adjusted Charlson comorbidity index ≥6 (eg, an 80-year-old with chronic kidney disease) were 15 times more likely to die of other causes than to receive intervention at 5 years following diagnosis, regardless of risk group.

Conclusions

The model shows that there is little benefit to rigorous monitoring in low-risk and older patients with comorbidities. Risk-stratified follow-up has the potential to reduce patient anxiety and associated health care costs.
Designing ionic channels in novel carbons for electrochemical energy storage
Authors: Ye Jianglin , Simon Patrice , Zhu Yanwu
Published: September 2019

Tremendous efforts have been dedicated to developing high-performance energy storage devices based on the micro- or nano-manipulation of novel carbon electrodes, as certain nanocarbons are perceived to have advantages such as high specific surface areas, superior electric conductivities, excellent mechanical properties and so on. In typical electrochemical electrodes, ions are intercalated/deintercalated into/from the bulk (for batteries) or adsorbed/desorbed on/from the surface (for electrochemical capacitors). Fast ionic transport, significantly determined by ionic channels in active electrodes or supporting materials, is a prerequisite for the efficient energy storage with carbons. In this report, we summarize recent design strategies for ionic channels in novel carbons and give comments on the promising features based on those carbons towards tailorable ionic channels.
Termite colonies from mid-Cretaceous Myanmar demonstrate their early eusocial lifestyle in damp wood
Authors: Zhao Zhipeng , Yin Xiangchu , Shih Chungkun , Gao Taiping , Ren Dong
Published: September 2019

Insect eusociality is characterized by cooperative brood care, reproductive division of labour and multiple generations of adults within a colony. The morphological specializations of the different termite castes from Burmese amber were recently reported, indicating the termites possessed advanced sociality in the mid-Cretaceous. Unfortunately, all the reported Cretaceous termites are individually preserved, which does not cover the behaviours of the cooperative brood care and multiple generations of adults in the nests of the Cretaceous termites. Herein, we report three eusocial aggregations from colonies of the oldest known Stolotermitidae, Cosmotermesgen. nov., in 100 Ma mid-Cretaceous Burmese amber. One large aggregation, comprising 8 soldiers, 56 workers/pseudergates and 25 immatures of different instars, additionally presents the behaviours of cooperative brood care and overlapping generations. Furthermore, taphonomic evidence indicates Cosmotermes most probably dwelled in damp/rotting wood, which provides a broader horizon of the early societies and ecology of the eusocial Cosmotermes.
Exceeding WHO Framework Convention on Tobacco Control (FCTC) Obligations: Nepal Overcoming Tobacco Industry Interference to Enact a Comprehensive Tobacco Control Policy
Authors: Bhatta Dharma N , Bialous Stella , Crosbie Eric , Glantz Stanton
Published: September 2019

Background

The tobacco industry works to block, delay, and weaken national tobacco control legislation to implement the WHO Framework Convention on Tobacco Control (FCTC). This article reviews how Nepal overcame industry opposition and to a comprehensive tobacco control law implementing the FCTC.

Methods

We triangulated newspaper articles and policy documents with key informant interviews.

Results

With the support of international health groups, local tobacco control advocates worked with policymakers in Nepal to pass a comprehensive tobacco control law that exceeded FCTC obligations. The tobacco industry exploited a time of political transition to block consideration by Parliament, arranged and sponsored foreign tours for legislators, made death threats to tobacco control advocates and their families, and argued for the economic importance of tobacco farms. Despite strong interference from Health, and Law and Justice ministers, a 2009 Supreme Court ruling helped tobacco control advocates secure a comprehensive tobacco control law in 2011 that included rotating pictorial health warning labels covering 75% of both sides of cigarette packages, 100% smoke free public places and workplaces, private homes and vehicles, and a tobacco advertising, promotion, and sponsorship ban.

Conclusions

Advocates in developing countries should utilize Nepal's experience to reject tobacco industry offers of compromise and continue educating politicians and legislators to generate political support to pass a comprehensive tobacco control law. Technical and financial support from international agencies, and effective collaboration and coordination of civil societies, and utilization of domestic litigation are helpful in LMICs where governance is weak (the abstract in Nepali is available as a Supplementary Material).

Implications

The tobacco industry exploited a time of political transition in Nepal in its effort to block comprehensive tobacco control policy in Parliament by sponsoring foreign tours of legislatures, making death threats to tobacco control advocates and their families, and arguing for the economic importance of tobacco farms. Tobacco control advocates used litigation to raise awareness and educate legislators and promote strong legislation with the involvement of international health groups. Technical and financial support from international agencies, and effective collaboration and coordination of civil societies, and utilization of domestic litigation are helpful in LMICs where governance is weak.
A yeast display immunoprecipitation screen for targeted discovery of antibodies against membrane protein complexes
Authors: Lajoie Jason M , Cho Yong Ku , Frost Dustin , Bremner Samantha , Li Lingjun , Shusta Eric V
Published: September 2019

Yeast display immunoprecipitation is a combinatorial library screening platform for the discovery and engineering of antibodies against membrane proteins using detergent-solubilized membrane fractions or cell lysates as antigen sources. Here, we present the extension of this method for the screening of antibodies that bind to membrane protein complexes, enabling discovery of antibodies that target antigens involved in a functional protein-protein interaction of interest. For this proof-of-concept study, we focused on the receptor-mediated endocytosis machinery at the blood-brain barrier, and adaptin 2 (AP-2) was chosen as the functional interaction hub. The goal of this study was to identify antibodies that bound to blood-brain barrier (BBB) membrane protein complexes containing AP-2. Screening of a nonimmune yeast display antibody library was carried out using detergent-solubilized BBB plasma membranes as an antigen pool, and antibodies that could interact with protein complexes containing AP-2 were identified. Downstream characterization of isolated antibodies confirmed targeting of proteins known to play important roles in membrane trafficking. This functional yeast display immunoprecipitation screen may be applied to other systems where antibodies against other functional classes of protein complexes are sought.
Spontaneous generation of spin current from the vacuum by strong electric fields
Authors: Huang Xu-Guang , Matsuo Mamoru , Taya Hidetoshi
Published: September 2019

We discuss spontaneous spin current generation from the vacuum by strong electric fields as a result of interplay between the Schwinger mechanism and a spin–orbit coupling. By considering a homogeneous slow strong electric field superimposed by a fast weak transverse electric field, we explicitly evaluate the vacuum expectation value of a spin current (the Bargmann–Wigner spin current) by numerically solving the Dirac equation. We show that a non-vanishing spin current polarized in the direction perpendicular to the electric fields flows mostly in the longitudinal direction. We also find that a relativistic effect due to helicity conservation affects the direction/polarization of a spin current.
Thermal fluctuations to the thermodynamics of a non-rotating BTZ black hole
Authors: Nadeem-ul-islam  , Ganai Prince A , Upadhyay Sudhaker
Published: September 2019

We discuss the effect of small statistical thermal fluctuations around the equilibrium of the thermodynamics of a small non-rotating BTZ black hole. This is done by evaluating the leading-order corrections to the thermodynamical equations of state, namely entropy, free energy, internal energy, pressure, enthalpy, Gibbs free energy, and specific heat, quantitatively. In order to analyze the effects of perturbations on the thermodynamics, we plot various graphs and compare corrected and non-corrected thermodynamic quantities with respect to the event horizon radius of a non-rotating BTZ black hole. We also derive the first-order corrections to isothermal compressibility.
Identifying evidence of effectiveness in the co-creation of research: a systematic review and meta-analysis of the international healthcare literature
Authors: Halvorsrud Kristoffer , Kucharska Justyna , Adlington Katherine , Rüdell Katja , Brown Hajdukova Eva , Nazroo James , Haarmans Maria , Rhodes James , Bhui Kamaldeep
Published: September 2019

Background

To investigate and address the evidence gap on the effectiveness of co-creation/production in international health research.

Methods

An initial systematic search of previous reviews published by 22 July 2017 in Medline, Embase, PsycINFO, Scopus and Web of Science. We extracted reported aims, elements and outcomes of co-creation/production from 50 reviews; however, reviews rarely tested effectiveness against intended outcomes. We therefore checked the reference lists in 13 included systematic reviews that cited quantitative studies involving the public/patients in the design and/or implementation of research projects to conduct meta-analyses on their effectiveness using standardized mean difference (SMD).

Results

Twenty-six primary studies were included, showing moderate positive effects for community functions (SMD = 0.56, 95%CI = 0.29–0.84, n = 11) and small positive effects for physical health (SMD = 0.25, 95%CI = 0.07–0.42, n = 9), health-promoting behaviour (SMD = 0.14, 95%CI = 0.03–0.26, n = 11), self-efficacy (SMD = 0.34, 95%CI = 0.01–0.67, n = 3) and health service access/receipt (SMD = 0.36, 95%CI = 0.21–0.52, n = 12). Non-academic stakeholders that co-created more than one research stage showed significantly favourable mental health outcomes. However, co-creation was rarely extended to later stages (evaluation/dissemination), with few studies specifically with ethnic minority groups.

Conclusions

The co-creation of research may improve several health-related outcomes and public health more broadly, but research is lacking on its longer term effects.
COUNTING INTEGERS WITH A SMOOTH TOTIENT
Authors: Banks W D , Friedlander J B , Pomerance C , Shparlinski I E
Published: September 2019

In an earlier paper we considered the distribution of integers $n$ for which Euler’s totient function at $n$ has all small prime factors. Here we obtain an improvement that is likely to be best possible.
Quantitative Easing and Equity Prices: Evidence from the ETF Program of the Bank of Japan
Authors: Barbon Andrea , Gianinazzi Virginia
Published: September 2019

Since the introduction of its quantitative and qualitative easing program in 2013, the Bank of Japan has been increasing its holdings of Japanese equity through large-scale purchases of index-linked ETFs, to lower risk premiums. We exploit the cross-sectional heterogeneity of the supply shock to identify a positive and persistent impact on stock prices, consistent with a portfolio balance channel. The evidence suggests that long-run demand curves for stocks are downward sloping with unitary price elasticity. We show that the purchases of ETFs tracking the price-weighted Nikkei 225 generate pricing distortions relative to a value-weighted benchmark.

Received April 13, 2018; editorial decision July 18, 2019 by Editor Thierry Foucault. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Cretaceous beetles (Insecta: Coleoptera) in amber: the palaeoecology of this most diverse group of insects
Authors: Peris David , Rust Jes
Published: September 2019

Beetles, the most successful group of invertebrates on Earth, have a worldwide distribution and an outstanding fossil record. In addition, they are well known as inclusions in fossil resin. In historical studies of fossil material, specimens were often named and described without placing the taxa in an ecological context. However, the research philosophy for fossil beetles has changed over the past few years. In this article, we summarize the palaeoecological interpretations of fossil beetles from Cretaceous ambers, which includes species from 69 families, most of which were described during the last 3 years. By analysing current habits of those families, we argue that saproxylicity was the most common feeding strategy for these fossil beetles. More specifically, fungivorous species appear to dominate. In contrast, we find only anecdotal evidence for the presence of wood-boring groups, and it is thus necessary to identify alternative abiotic or biotic processes that are responsible for the copious resin production at this time. Finally, the recent description of some beetles as gymnosperm pollinators during the Cretaceous lends more weight to the importance of amber studies in addressing the role of beetles in the evolution of pollination strategies.
Changes in brain kynurenine levels via gut microbiota and gut‐barrier disruption induced by chronic ethanol exposure in mice
Authors: Giménez‐Gómez Pablo , Pérez‐Hernández Mercedes , O'Shea Esther , Caso Javier R. , Martín‐Hernandez David , Cervera Luis Alou , Centelles María Luisa Gómez‐Lus , Gutiérrez‐Lopez María Dolores , Colado Maria Isabel
Published: September 2019

Inflammatory processes have been shown to modify tryptophan (Trp) metabolism. Gut microbiota appears to play a significant role in the induction of peripheral and central inflammation. Ethanol (EtOH) exposure alters gut permeability, but its effects on Trp metabolism and the involvement of gut microbiota have not been studied. We analyzed several parameters of gut‐barrier and of peripheral and central Trp metabolism following 2 different EtOH consumption patterns in mice, the binge model, drinking in the dark (DID), and the chronic intermittent (CI) consumption paradigm. Antibiotic treatment was used to evaluate gut microbiota involvement in the CI model. Mice exposed to CI EtOH intake, but not DID, show bacterial translocation and increased plasma LPS immediately after EtOH removal. Gut‐barrier permeability to FITC‐dextran is increased by CI, and, furthermore, intestinal epithelial tight‐junction (TJ) disruption is observed (decreased expression of zonula occludens 1 and occludin) associated with increased matrix metalloproteinase (MMP)‐9 activity and iNOS expression. CI EtOH, but not DID, increases kynurenine (Kyn) levels in plasma and limbic forebrain. Intestinal bacterial decontamination prevents the LPS increase but not the permeability to FITC‐dextran, TJ disruption, or the increase in MMP‐9 activity and iNOS expression. Although plasma Kyn levels are not affected by antibiotic treatment, the elevation of Kyn in brain is prevented, pointing to an involvement of microbiota in CI EtOH‐induced changes in brain Trp metabolism. Additionally, CI EtOH produces depressive‐like symptoms of anhedonia, which are prevented by the antibiotic treatment thus pointing to an association between anhedonia and the increase in brain Kyn and to the involvement of gut microbiota.—Giménez‐Gómez, P., Pérez‐Hernández, M., O'Shea, E., Caso, J. R., Martín‐Hernández, D., Cervera, L. A., Centelles. M. L. G.‐L., Gutiérrez‐Lopez, M. D., Colado, M. I. Changes in brain kynurenine levels via gut microbiota and gut‐barrier disruption induced by chronic ethanol exposure in mice. FASEB J. 33, 12900–12914 (2019). www.fasebj.org
Updated concepts in the diagnosis and management of community-acquired pneumonia
Authors: Hunton Ryan
Published: September 2019

Pneumonia accounts for about 1 million hospitalizations each year in the United States. It is the number one cause of death from infectious disease and eighth leading cause of death in the United States. This article reviews recent updates in best practices for diagnosing and managing pneumonia in the ED or primary care practice. Despite developments in the diagnosis of pneumonia, vital signs and chest examination findings can and should guide clinical management. Chest radiography is routinely used to diagnose pneumonia. However, a negative chest radiograph should not replace clinical impression. In immunocompetent patients with community-acquired pneumonia, the CURB-65 decision rule has a role in identifying high-risk patients, including those who will require ICU admission and a critical care intervention.
Predicted shortages of physicians might even disappear if we fully account for PAs and NPs
Authors: Morgan Perri
Published: September 2019

Healthcare workforce projections have important policy implications. Provider shortages can shortchange patients, and overproduction of providers imposes costs on society. The most publicized physician supply and demand projections, commissioned annually by the Association of American Medical Colleges, regularly predict dire physician shortages. These projections are based on unrealistically low estimates of the amount of physician work that can be replaced by physician assistants (PAs) and NPs. For example, the projections factor in the contribution of one primary care PA or NP as one-fourth that of a physician. If workforce projections used evidence-based productivity estimates, the predicted physician shortfalls would be much smaller and perhaps even disappear.
The Co-occurrence of Pediatric Chronic Pain and Anxiety
Authors: Jastrowski Mano Kristen E. , O’Bryan Emily M. , Gibler Robert C. , Beckmann Emily
Published: September 2019

The development and maintenance of pediatric chronic pain and anxiety are complex, underscoring the need to better understand the interactive forces contributing to their co-occurrence. The shared vulnerability model (SVM) was developed to explain the co-occurrence of chronic pain and posttraumatic stress disorder in adults. Although many core tenets have been well supported by pediatric research, the SVM has yet to be extended to pediatric pain populations. We propose a developmentally informed pediatric SVM for advancing our understanding of the co-occurrence of pediatric chronic pain and anxiety disorders. The proposed SVM postulates that youth at increased risk for the development of chronic pain and/or anxiety share predisposing vulnerabilities, including anxiety sensitivity, and that these shared vulnerabilities give rise to negative emotional responses (child and parent) in the context of stressful events. Consequences of fear and anxiety, including avoidance behavior, further contribute to the development of chronic pain, anxiety, and their co-occurrence. The parental, school, and peer contexts in which these problems develop and are maintained in youth are pertinent to integrate into a SVM, as pediatric chronic pain and anxiety disorders share several social-contextual risk and maintenance factors. We also highlight new areas of inquiry.
Statin therapy: does sex matter?
Authors: Faubion Stephanie S. , Kapoor Ekta , Moyer Ann M. , Hodis Howard N. , Miller Virginia M.
Published: September 2019

Objective:

Statins are a class of drugs that competitively bind to the active site of HMG-CoA reductase enzyme, thereby inhibiting the initial steps in cholesterol synthesis. Originally approved for use in lowering serum cholesterol, a risk factor for developing atherosclerosis and coronary heart disease, statins have subsequently been noted to have myriad extrahepatic effects, including potential effects on cognition, diabetes, breast cancer, bone, and muscle. This narrative review assesses the current state of the science regarding the risks and benefits of statin therapy in women to identify areas where additional research is needed.

Methods:

Basic and clinical studies were identified by searching PubMed with particular attention to inclusion of female animals, women, randomized controlled trials, and sex-specific analyses.

Results:

Statin therapy is generally recommended to reduce the risk of cardiovascular disease. None of the current clinical guidelines, however, offer sex-specific recommendations for women due to lack of understanding of sex differences and underlying mechanisms of disease processes. In addition, conclusions regarding efficacy of treatments do not consider lipid solubility for the drug, dosing, duration of treatment, interactions with estrogen, or comorbidities. Pleiotropic effects of statins are often derived from secondary analysis of studies with cardiovascular events as primary outcomes.

Conclusions:

Many of the trials that have established the efficacy and safety of statins were conducted predominantly or entirely in men, with results extrapolated to women. Additional research is needed to guide clinical recommendations specific to women.

Video Summary:
http://links.lww.com/MENO/A462.
Efficacy of the Fluorescein Tear Breakup Time Test in Dry Eye
Authors: Paugh Jerry R. , Tse June , Nguyen Tiffany , Sasai Alan , Chen Elaine , De Jesus Melinda Thomas , Kwan Justin , Nguyen Andrew Loc , Farid Marjan , Garg Sumit , Jester James V.
Published: September 2019

Purpose:

To examine the effects of volume and method on fluorescein tear breakup time (TBUT) values and to evaluate test efficacy in an independent sample free of selection bias.

Methods:

Subjects were assessed using a battery of dry eye tests (DETs). Efficacy study: Subjects were randomized to the DET, standard strip, and liquid NaFl on separate days. A masked examiner measured TBUTs from video recordings. Verification study: Subjects were investigated for efficacy using volumes of 5.0 and 2.0 μL mL of NaFl for TBUT.

Results:

Efficacy study: 46 subjects completed the study. Log-transformed TBUTs were significantly different, normal subjects versus dry subjects, for all 3 methods (all P values < 0.001). Area under the curves (AUCs), cut-points, sensitivity, and specificity were 1) DET: 0.873, 4.4 seconds, 0.97, and 0.67, respectively; 2) 2.0 mL: 0.901, 3.22 seconds, 0.90, and 0.87, respectively; and 3) standard strip: 0.912, 3.42 seconds, 0.97, and 0.80, respectively. Verification study: Data splitting analysis for the 2.0 μL data (n = 174 dry subjects and 97 normal subjects) generated an AUC of 0.917 and a cut-point of 6.05 seconds for a sensitivity of 0.87 and a specificity of 0.81. The 5.0 μL sample yielded an AUC of 0.940, with a sensitivity and specificity of 0.92 and 0.83, respectively, at a cut-point of 5.5 seconds.

Conclusions:

Little difference in TBUT was found using the 3 clinical methods with video recordings. Analysis using liquid NaFl suggests that the TBUT test has excellent diagnostic accuracy and that a cut-point of 5.3 to 6.0 seconds is the optimum to differentiate normals from persons with dry eye.
Appalachian Status Is a Negative Predictor of Breast Reconstruction Following Breast Cancer Resection
Authors: DeCoster Ryan C. , Stout Megan A. , Burns Jack C. , Shrout Max A. , Wetzel Margaret , Dugan Adam J. , Rinker Brian D. , Butterfield Timothy A. , Webster J. Matthew , Vasconez Henry C.
Published: September 2019

Background

Health care disparities in Appalachia are well documented. However, no previous studies have examined possible differences in the utilization of breast reconstruction (BR) in Appalachia. This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky.

Methods

A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR.

Results

Bivariate testing showed differences (P < 0.0001) in BR utilization between Appalachian and non-Appalachian women in Kentucky (15.0% and 26.3%, respectively). Multivariate analysis showed that women from Appalachia (odds ratio, 0.54; confidence interval (95), 0.48–0.61; P < 0.0001) were less likely to undergo BR than non-Appalachian women. Interestingly, the rate of BR increased over time in both Appalachian (r = 0.115; P < 0.0001) and non-Appalachian women (r = 0.148; P < 0.0001).

Conclusions

Despite the benefits of BR, women from Appalachia undergo BR at lower rates and are less likely to receive BR than non-Appalachian Kentuckians. Although the rates of BR increased over time in both populations, access to comprehensive breast cancer care remains a challenge for women from Kentucky's Appalachian region.
Course Review
Authors: Rivers C. M.
Published: September 2019

The Newcastle Surgical Training Centre Cadaveric Speech and Palate Surgery Course is an interactive and practical 1-day course for plastic surgery, ear, nose and throat surgery, and maxillofacial surgery trainees wishing to develop skills in cleft palate and speech surgery. The course is delivered by an expert faculty with delegates attending from the United Kingdom and abroad and costs £495 (US $650) to attend. This review provides information and an evaluation of the course.
Can Nicotine Replacement Therapy Decrease Complications in Plastic Surgery?
Authors: Xu Zhenzhen , Norwich-Cavanaugh Amanda , Hsia Henry C.
Published: September 2019

Cigarette smoking has been well demonstrated to be associated with adverse outcomes and increased complications in surgical patients in the operative and postoperative periods. There is general agreement that smoking cessation decreases such risks; however, much debate still exists regarding the most effective modalities for risk mitigation, especially concerning modalities involving nicotine replacement in some form. This article reviews the discussion regarding smoking cessation therapies, in particular those involving nicotine replacement, in the context of mitigating risk in plastic surgery procedures. The recent rise in popularity of electronic cigarettes poses further challenges for clinicians in minimizing risk and optimizing outcomes for patients. Prospective studies including high-level evidence such as randomized controlled clinical trials will be required to help plastic surgeons develop guidelines that will enable optimization of patient safety and clinical outcomes.
A Deceptive Diagnosis
Authors: Mella Juan Rodolfo , Maselli Amy M. , Guo Lifei
Published: September 2019

Postsurgical pyoderma gangrenosum is a rare neutrophilic dermatosis that presents with characteristic ulcerative lesions and systemic signs and symptoms of inflammation. It has been well documented after both cosmetic and reconstructive breast surgeries. Given its similarity to postoperative infectious processes, a high index of suspicion is necessary to initiate treatment with immunosuppression and avoid unnecessary and potentially disfiguring debridements. We present our experience with 4 cases of pyoderma gangrenosum after breast reconstruction and review the existing literature regarding pyoderma gangrenosum after breast surgery.