bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous coronary artery dissection in a patient with hereditary polycystic kidney disease and a recent liver transplant: a case report
Authors: Verlaeckt Ezther , Van de Bruaene Laurens , Coeman Mathieu , Gevaert Sofie
Published: December 2019

Background

Spontaneous coronary artery dissection (SCAD) is an underestimated cause of acute coronary syndromes. A predisposing arteriopathy is often present and a stressor can sometimes be identified. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder; its associated arteriopathy has been described as a predisposing condition for SCAD.

Case summary

A 44-year-old woman with ADPKD presented in the emergency room with recent onset thoracic pain radiating to the left arm at rest. She had undergone a recent liver transplant, for which she had received high-dose corticosteroids during 1 month. She was still taking tacrolimus and mycophenolate mofetil. She had no traditional risk factors but had experienced stress postoperatively. She was known with moderate chronic kidney disease. The initial electrocardiogram (ECG) was normal but high-sensitive troponin T was significantly elevated. Coronary angiography demonstrated diffuse narrowing of the distal left anterior descending artery with preserved flow, compatible with a SCAD Type 2 that was treated conservatively. However, under dual antiplatelet therapy (DAPT) with clopidogrel, the coronary dissection was progressive with new ischaemic ECG changes, further rise of troponins and development of apicoseptal hypokinesia. Because of the small vessel diameter and the preserved distal flow, conservative treatment was maintained. Clopidogrel was interrupted and the patient remained stable.

Discussion

As SCAD remains an underestimated cause of myocardial infarction, clinicians should be aware of the possibility of SCAD in ADPKD patients with chest pain. This case report illustrates that the decision DAPT vs. aspirin should be individualized in these patients.
Management of atrial fibrillation in patients with chronic kidney disease in clinical practice: a joint European Heart Rhythm Association (EHRA) and European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) physician-based survey
Authors: Potpara Tatjana S , Ferro Charles , Lip Gregory Y H , Dan George A , Lenarczyk Radoslaw , Mallamaci Francesca , Ortiz Alberto , Sarafidis Pantelis , Ekart Robert , Dagres Nikolaos
Published: December 2019

The European Heart Rhythm Association (EHRA) and European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) jointly conducted a physician-based survey to gain insight into the management of atrial fibrillation (AF) in patients with chronic kidney disease (CKD) and adherence to current European Society of Cardiology AF Guidelines in contemporary clinical practice. Physician-based survey conducted during an 8-week period using an internet-based questionnaire sent to all EHRA and ERA/EDTA members, with voluntary and anonymous responses. Among 306 physicians (160 EHRA and 146 ERA/EDTA members; 56 countries), a multidisciplinary team for management of AF-CKD patients was available to only 20/300 respondents (6.7%) and 132/295 (44.7%) routinely screened CKD patients for AF. Oral anticoagulation (OAC) use was based on individual stroke risk in mild/moderate CKD but on shared decision-making in advanced CKD. The CHA2DS2-VASc score-based decisions were more common among cardiologists, with substantial intra- and inter-specialty heterogeneity in the use and dosing of specific OAC drugs across CKD stages, heterogeneous strategies for OAC monitoring (especially among nephrologists) and a modest impact of CKD on rate and rhythm control treatment decisions. The HAS-BLED score was generally not a determinant of OAC prescribing. Our survey provided important insights into contemporary management of AF patients with CKD in clinical practice, revealing certain differences between nephrologists and cardiologists and highlighting shared and specific knowledge gaps and unmet needs. These findings emphasize the need for streamlining the care for AF patients across different specialties and may inform development of tailored education interventions.
Impact of catheter ablation therapy for atrial fibrillation on healthcare expenditures in a middle European cohort
Authors: Martinek Martin , Pürerfellner Helmut , Blessberger Hermann , Pruckner Gerald
Published: December 2019

Aims

Atrial fibrillation (AF) is the most prevalent arrhythmia in western countries. It is associated with increased mortality and morbidity and responsible for hospitalization rates of 10–40% per patient per year. Studies from the UK and the USA have shown that AF is responsible for ∼1% of the total healthcare expenditures in these countries. The only potentially curative treatment is pulmonary vein isolation (PVI). Published health economic data on the impact of PVI mainly consist of simulations of expenditures with assumed efficacy taken from ablation studies. Real expenditure data are missing as well as pre-ablation period data and long-term data.

Methods and results

We analyse true healthcare expenditures based on inpatient and outpatient data from the Upper Austrian Health Insurance Fund social security system of patients undergoing PVI during 2005 to 2015. We identified 1135 patients undergoing PVI with 268 having multiple procedures. Days of hospitalization and days of sick leave started to rise in the year before ablation. PVI was able to lower both parameters to the level of 1 year before ablation. Comparing four quarters before and after a single-index ablation, a highly significant reduction in inpatient healthcare expenditures was documented. There was a significant, but numerically small increase in outpatient expenditures, resulting in a significant reduction in overall healthcare expenditures.

Conclusion

Analysing a cohort of the Upper Austrian Health Insurance Fund undergoing PVI, we found significant cost-saving effects on post-interventional healthcare expenditures and a reduction in days of sick leave.
Whole Genome Sequencing and Assembly of the Asian Honey Bee Apis dorsata
Authors: Oppenheim Sara , Cao Xiaolong , Rueppel Olav , Krongdang Sasiprapa , Phokasem Patcharin , DeSalle Rob , Goodwin Sara , Xing Jinchuan , Chantawannakul Panuwan , Rosenfeld Jeffrey A
Published: December 2019

The Asian honey bee (Apis dorsata) is distinct from its more widely distributed cousin Apis mellifera by a few key characteristics. Most prominently, A. dorsata, nest in the open by forming a colony clustered around the honeycomb, whereas A. mellifera nest in concealed cavities. Additionally, the worker and reproductive castes are all of the same size in A. dorsata. In order to investigate these differences, we performed whole genome sequencing of A. dorsata using a hybrid Oxford Nanopore and Illumina approach. The 223 Mb genome has an N50 of 35 kb with the largest scaffold of 302 kb. We have found that there are many genes in the dorsata genome that are distinct from other hymenoptera and also large amounts of transposable elements, and we suggest some candidate genes for A. dorsata’s exceptional level of defensive aggression.
Differential gene expression and limited epigenetic dysregulation at the materno-fetal interface in preeclampsia
Authors: Leseva Milena N , Binder Alexandra M , Ponsonby Anne-Louise , Vuillermin Peter , Saffery Richard , Michels Karin B ,   Barwon Infant Study Investigator Group
Published: December 2019

Despite the many advances made in the diagnosis and management of preeclampsia, this syndrome remains a leading cause of maternal mortality and life-long morbidity, as well as adverse fetal outcomes. Successful prediction and therapeutic intervention require an improved understanding of the molecular mechanisms, which underlie preeclampsia pathophysiology. We have used an integrated approach to discover placental genetic and epigenetic markers of preeclampsia and validated our findings in an independent cohort of women. We observed the microRNA, MIR138, to be upregulated in singleton preeclamptic placentas; however, this appears to be a female infant sex-specific effect. We did not identify any significant differentially methylated positions (DMPs) in singleton pregnancies, indicating that DNA methylation changes in mild forms of the disease are likely limited. However, we identified infant sex-specific preeclampsia-associated differentially methylated regions among singletons. Disease-associated DMPs were more obvious in a limited sampling of twin pregnancies. Interestingly, 2 out of the 10 most significant changes in methylation over larger regions overlap between singletons and twins and correspond to NAPRT1 and ZNF417.
The effects of steroidal and non-steroidal anti-inflammatory drugs on tracheal wound healing in an experimental rat model
Authors: Duman Elif , Ceylan Kenan Can , Akpınar Deniz , Yücel Nur , Ünsal Şaban , Duman Soner , Kaya Şeyda Örs
Published: December 2019

OBJECTIVES

The effect of non-steroidal anti-inflammatory drugs (NSAID), mostly used for postoperative analgesic purposes for wound healing, is still a matter of debate. Our goal was to evaluate the effects of the most widely used NSAID and corticosteroids after surgical operations on tracheal wound healing in an experimental rat model.

METHODS

Thirty-nine male Wistar albino rats were included in this study. Tracheotomy was performed in 32 rats; then they were divided into 3 groups. After the first day, the animals in group 1 were treated with an NSAID (diclofenac 10 mg/kg/day) (NSAID, n = 12) for 7 days; the animals in group 2 were treated with a corticosteroid (dexamethasone, 2 × 0.1 mg/kg/day) (steroid, n = 10) for 7 days; the animals in group 3 (control, n = 10) were not given any medications. For a fourth group (histological control, n = 7), in order to evaluate normal morphological and histological characteristics, neither surgery nor medication was used. Five rats were eliminated from the study (2 rats in the NSAID group died and 3 rats in the steroid group developed local wound infections). The drop-out rate was 12.8%. Histological characteristics, inflammation, fibrosis, necrosis, neochondrogenesis, neovascularization and epithelization were evaluated in 34 rats. Non-parametric tests were used for statistical analysis.

RESULTS

Inflammation, vascularization and number of fibroblasts and chondrocytes were significantly higher in the control group than in the histological control group. There was some reduction in all parameters except vascularization in the NSAID group (P > 0.05). When the steroid group was compared to the NSAID group, inflammation (P < 0.05), vascularization and number of chondrocytes (P > 0.05) were more suppressed in the steroid group. The number of fibroblasts increased in the steroid group (P > 0.05).

CONCLUSIONS

Steroids and NSAID may have negative effects on tracheal wound healing, probably by suppressing inflammation and fibroblast proliferation. NSAID was mostly used postoperatively for analgesic purposes and should be avoided.
A mixed-primal finite element method for the coupling of Brinkman–Darcy flow and nonlinear transport
Authors: Alvarez Mario , Gatica Gabriel N , Ruiz-Baier Ricardo
Published: December 2019

This paper is devoted to the mathematical and numerical analysis of a model describing the interfacial flow-transport interaction in a porous-fluidic domain. The medium consists of a highly permeable material, where the flow of an incompressible viscous fluid is governed by Brinkman equations (written in terms of vorticity, velocity and pressure), and a porous medium where Darcy’s law describes fluid motion using filtration velocity and pressure. Gravity and the local fluctuations of a scalar field (representing for instance, the solids volume fraction or the concentration of a contaminant) are the main drivers of the fluid patterns on the whole domain, and the Brinkman-Darcy equations are coupled to a nonlinear transport equation accounting for mass balance of the scalar concentration. We introduce a mixed-primal variational formulation of the problem and establish existence and uniqueness of solution using fixed-point arguments and small-data assumptions. A family of Galerkin discretizations that produce divergence-free discrete velocities is also presented and analysed using similar tools to those employed in the continuous problem. Convergence of the resulting mixed-primal finite element method is proven, and some numerical examples confirming the theoretical error bounds and illustrating the performance of the proposed discrete scheme are reported.
The Cone Structure Theorem
Authors: Batista Erica Boizan , Costa João Carlos Ferreira , Nuño-Ballesteros Juan José
Published: December 2019

We consider the topological classification of finitely determined map germs $f:(\mathbb {R}^n,0)\to (\mathbb {R}^p,0)$ with $f^{-1}(0)\neq \{0\}$. Associated with $f$ we have a link diagram, which is well defined up to topological equivalence. We prove that $f$ is topologically  $\mathcal {A}$-equivalent to the generalized cone of its link diagram.
Discrete Invariant Curve Flows, Orthogonal Polynomials, and Moving Frame
Authors: Wang Bao , Chang Xiang-Ke , Hu Xing-Biao , Li Shi-Hao
Published: December 2019

In this paper, an orthogonal polynomials-based (OPs-based) approach to generate discrete moving frames and invariants is developed. It is shown that OPs can provide explicit expressions for the discrete moving frame as well as the associated difference invariants, and this approach enables one to obtain the corresponding discrete invariant curve flows simultaneously. Several examples in the cases of centro-affine plane, pseudo-Euclidean plane, and high-dimensional centro-affine space are presented.
Open Saito Theory for A and D Singularities
Authors: Basalaev Alexey , Buryak Alexandr
Published: December 2019

A well-known construction of B. Dubrovin and K. Saito endows the parameter space of a universal unfolding of a simple singularity with a Frobenius manifold structure. In our paper, we present a generalization of this construction for the singularities of types $A$ and $D$ that gives a solution of the open WDVV equations. For the $A$-singularity, the resulting solution describes the intersection numbers on the moduli space of $r$-spin disks, introduced recently in a work of the 2nd author, E. Clader and R. Tessler. In the 2nd part of the paper, we describe the space of homogeneous polynomial solutions of the open WDVV equations associated to the Frobenius manifolds of finite irreducible Coxeter groups.
Factors Associated With Antiretroviral Therapy Reinitiation in Medicaid Recipients With Human Immunodeficiency Virus
Authors: Zhang T , Wilson I B , Youn B , Lee Y , Shireman T I
Published: December 2019

Background

This study was conducted to examine patient characteristics associated with antiretroviral therapy (ART) reinitiation in Medicaid enrollees.

Methods

This is a retrospective cohort study that uses Cox proportional hazard regression to examine the association between person-level characteristics and time from ART discontinuation to the subsequent reinitiation within 18 months.

Results

There were 45 409 patients who discontinued ART, and 44% failed to reinitiate. More outpatient visits (3+ vs 0 outpatient visits: adjusted hazard ratio (adjHR), 1.56; 99% confidence interval [CI], 1.45–1.67) and hospitalization (adjHR, 1.18; 99% CI,1.16–1.20) during follow-up were associated with reinitiation.

Conclusions

Failure to reinitiate ART within 18 months was common in this sample. Care engagement was associated with greater ART reinitiation.
Men and Women Have an Equal Oropharyngeal and Anorectal Chlamydia trachomatis Bacterial Load: A Comparison of 3 Anatomic Sites
Authors: Wijers Juliën N A P , Dukers-Muijrers Nicole H T M , van Liere Geneviève A F S , Dirks Jeanne A M C , Wolffs Petra F G , Hoebe Christian J P A
Published: December 2019

Background

The Chlamydia trachomatis bacterial load could have impact on transmission and sequelae. This is the first study providing comparison of C. trachomatis load at 3 anatomic sites estimated by cycle quantification (Cq) values.

Methods

Data from 7900 C. trachomatis-positive samples were included (2012–2018). Cq value was used as an inversely proportional measure for C. trachomatis load. Multivariable linear regression analyses assessed differences in mean Cq values.

Results

Vaginal swabs had the lowest Cq values (31.0) followed by urine (32.5), anorectal swabs (34.0), and oropharyngeal swabs (36.8) (P < .001). Men and women had similar oropharyngeal (36.4 vs 37.3; P = .13) and anorectal (34.2 vs 33.9; P = .19) Cq values. Men (32.2) and women (30.7) aged <25 years had lower urogenital Cq values than men (32.8) and women (31.9) aged ≥25 years (P < .001). HIV-positive patients had higher urogenital Cq values than HIV-negative patients (33.8 vs 32.6; P < .03).

Conclusions

Men and women have a similar C. trachomatis load at extragenital locations arguing for similar transmission potential and clinical relevance. Older patients and HIV-coinfected patients had lower C. trachomatis load, suggesting exposure to previous C. trachomatis infections potentially leading to partial immunity reducing load.
Common ownership: an EU perspective
Authors: Burnside Alec J , Kidane Adam
Published: December 2019

Recent antitrust scholarship has claimed that parallel investments by institutional investors in competing firms may harm competition. Proponents of this theory, dubbed ‘common ownership’, posit that harm may arise even with small shareholdings, particularly in oligopolistic markets.  Although the debate has been focused on the U.S., the European Commission recently invoked common ownership as an ‘element of context’ in two merger decisions. This article examines common ownership through a European lens. A threshold issue will be whether levels of common ownership in Europe are comparable to those in the U.S.; the available evidence suggests they are not.  We note a number of misconceptions about the asset management industry, putting in doubt core elements of the common ownership hypothesis. We review the academic debate in which the theory has been vigorously contested on both methodological and theoretical grounds. We review the battle between empirical studies claiming to demonstrate and to disprove common ownership effects. The article considers whether the theory is sufficiently robust to provide a basis for enforcement, and (if so) whether current European Union competition law tools could be used to that end. The European Commission’s invocation of common ownership is subjected to critical evaluation. We conclude that it is premature to draw any conclusions as to the reality of alleged common ownership concerns or to base enforcement efforts on them. Until a better understanding of the underlying facts and a broad academic consensus emerge, reform prescriptions that have been advanced are a solution in search of a problem—to say nothing of the conflicts that would arise with other rules governing asset management.
Assessment of Hair Density and Sub-epidermal Tissue Thickness in Burn Scars Using High-Definition Ultrasound Imaging
Authors: Blome-Eberwein Sigrid A , Roarabaugh Chad , Gogal Christina
Published: December 2019

Burn scars show significant differences in structure, pigment, and hair density/sparsity from unburned skin, yet no formal documentation of these changes can be found in the literature. Evaluation of these differences is essential to assessing future intervention outcomes. The study was a prospective controlled clinical trial. Included were 19 adult burn survivors (18–63 years old, average age 47; 15 male, 4 female, 14 Caucasian, 2 African American, 1 Hispanic; 11 flame burns, 5 scald burns, 2 grease burns and 1 electrical burn, 2%–60% TBSA) with conspicuous, mature scars. All study subjects had either skin-grafted or nongrafted scars, as well as healthy skin in the same body area, to control for intraindividual variability. All scars were at least 9 months old and at a minimum 2 × 2 cm2 in size. On each individual, at least one nongrafted scar or one grafted scar and healthy skin was imaged with a high-definition ultrasound device (Longport, Inc., Glen Mills, PA, 35MHz probe, 1500 m/s). Vancouver scar scale was assessed. Although scarred skin had significantly fewer follicles than healthy skin in both grafted (P < .0001) and un-grafted sites (P = .0090), there were even significantly fewer follicles in grafted scars than un-grafted scars (P = .0095). In thickness of the sub-epidermal layer, there was no difference between grafted and un-grafted scars (P = .1900). Both kinds of scars had a significantly thicker sub-epidermal layer than healthy skin (P = .0010). Vancouver scar scale was 7.4 for grafted and 4.6 for nongrafted scars with grafted flame burn scars ranging higher than all others (5–11). There was no discomfort during the imaging, and no adverse events occurred during the study period. Our study demonstrates two clear morphologic differences between scars and healthy skin: thickness of the sub-epidermal layer and hair follicle density. Grafted burn scars were shown to contain fewer hair follicles than un-grafted scars.
Economic Injury Levels for Flea Beetles (Phyllotreta spp.; Coleoptera: Chrysomelidae) in Spring Oilseed Rape (Brassica napus; Brassicales: Brassicaceae)
Authors: Lundin Ola
Published: December 2019

Flea beetles (Phyllotreta spp.) are major insect pests in spring oilseed rape (SOSR; Brassica napus L.). Prohibited use of three neonicotinoid insecticides in the European Union means that there are currently no insecticide seed treatment options available. Insecticide spraying remains as a control option, but there is a need to estimate the economic threshold for crop injury. As a first step to this end, economic injury levels were determined for flea beetles in SOSR. Data from 16 field experiments were used to quantify the relationship between flea beetle crop injury and SOSR yield, and additional data from paired sprayed and unsprayed plots in 12 commercial SOSR fields were used to determine the reduction in crop injury from a pyrethroid spray. There was a strong linear negative effect of flea beetle injury with 19 kg/ha yield loss per percent crop injury to seedlings and a pyrethroid spray reduced crop injury by 39%. These results gave an economic injury level of 11% defoliation of SOSR seedlings under average oilseed rape prices and insecticide use costs in 2017. This is considerably lower than previously used nominal thresholds of 25–30% injury to cotyledons. Increased yields and increasingly cheaper pyrethroids might be the reason for the lower levels of crop injury that warrant chemical control. The economic injury levels presented here can be used to construct economic thresholds that preferably should also take into account crop growth stage, crop growth rate, and anticipated flea beetle activity.
What factors predict path tortuosity of Great Basin pocket mice in shrub-steppe habitat invaded by cheatgrass?
Authors: Melaschenko Natalie C , Hodges Karen E
Published: December 2019

Foraging animals choose habitats based on characteristics that often cannot be satisfied simultaneously, such as easy mobility, abundant or high-quality foods, and safety from predators. Invasive plants may alter habitat structure and provide novel foods; thus, measuring how animals forage in invaded landscapes offers insights into these new ecological relationships. We examined the movements of Great Basin pocket mice (Perognathus parvus) in sage-steppe habitats invaded by cheatgreass (Bromus tectorum) in southcentral British Columbia, Canada. The pathway tortuosity (fractal D) of pocket mice increased with vegetative cover and population density and decreased with open habitat, but these variables explained little of the variation in tortuosity. The fractal dimension of movement pathways of pocket mice was consistent over spatial scales ranging from 0.5 m to two-thirds of the home range size, unlike in other species where fractal dimensions are not consistent over multiple spatial scales. Collectively, our results indicate that foraging movements of pocket mice were not affected by the low densities of cheatgrass in this system.
Stylistic analysis of the French presidential speeches: Is Macron really different?
Authors: Labbé Dominique , Savoy Jacques
Published: December 2019

Presidential speeches indicate the government’s intentions and justifications supported by a dedicated style and rhetoric oscillating between explanation and controversy. Over a period of 60 years, can we observe stylistic variations by the different French presidents of the Fifth Republic (1958–2018)? Based on official transcripts of all their allocutions, this article illustrates the stylistic evolution and presents the underlying main trends. This study shows that de Gaulle’s rhetoric is not mainly dedicated to his own person, or that the two terms of J. Chirac are not fully similar. According to several overall stylistic indicators, Macron’s style does not appear as complex compared to his predecessors (F. Hollande or N. Sarkozy) but a more careful analysis clearly demonstrates his noticeable new style. Compared to the recent US presidents, the French ones present some similarities (e.g. similar mean sentence length) and dissimilarities (more I-words, less we-words). In this comparative analysis, Macron’s style is also clearly distinctive from both the US and former French presidents. Opting for a more abstract discourse, less anchored in space, using less numbers, E. Macron tends to use long sentences. These various stylistic and rhetorical features could explain his being misunderstood by the French people and his recurrent low approval ratings.
Properties of a fungicidal product formed from a reaction between L-cystine and pyridoxal
Authors: Johnston Elizabeth A , Lloyd Spencer B , Granger Donald L
Published: December 2019

Previously we found that three components of a commonly used mammalian cell culture medium incorporated into agar killed cryptococci (Granger and Call 2019). The components were L-cystine, iron [Fe(III)], and pyridoxal (CIP). We now report on a buffered solution at neutral pH of the three components, which was highly fungicidal without agar. We showed that CIP fungicidal activity, identical to the findings with cell culture medium, was inactivated by visible light and was unstable with storage in the dark. Congeners replacing either pyridoxal or L-cystine in CIP revealed structural requirements for fungicidal activity. Replacing pyridoxal in CIP with 2-hydroxy-5-nitrobenzaldehyde produced a solution that was equally fungicidal and maintained fungicidal activity upon storage in the dark for up to 50 days. We employed methods for excluding iron from CIP and found that fungicidal activity was not affected. Upon mixing L-cystine and pyridoxal in buffer at pH 7.0, diode array spectroscopy revealed a red-shift of absorbance maximum from 391 nm to 398 nm. Our findings point to Schiff base reaction between the pyridoxal aldehyde group of C1 with the alpha amino group(s) of cystine to yield a fungicidal compound. Light at wave length approximately 400 nm inactivates this complex accompanied by bleaching of the pyridine ring of pyridoxal. Our findings may be useful for design of a class of fungicidal compounds formed through Schiff base reaction of disulfide compounds with aromatic ring-bearing aldehydes.
Cosmology with galaxy–galaxy lensing on non-perturbative scales: emulation method and application to BOSS LOWZ
Authors: Wibking Benjamin D , Weinberg David H , Salcedo Andrés N , Wu Hao-Yi , Singh Sukhdeep , Rodríguez-Torres Sergio , Garrison Lehman H , Eisenstein Daniel J
Published: December 2019

We describe our non-linear emulation (i.e. interpolation) framework that combines the halo occupation distribution (HOD) galaxy bias model with N-body simulations of non-linear structure formation, designed to accurately predict the projected clustering and galaxy–galaxy lensing signals from luminous red galaxies in the redshift range 0.16 < z < 0.36 on comoving scales 0.6 < rp < 30 $h^{-1} \, \text{Mpc}$. The interpolation accuracy is ≲ 1–2 per cent across the entire physically plausible range of parameters for all scales considered. We correctly recover the true value of the cosmological parameter S8 = (σ8/0.8228)(Ωm/0.3107)0.6 from mock measurements produced via subhalo abundance matching (SHAM)-based light-cones designed to approximately match the properties of the SDSS LOWZ galaxy sample. Applying our model to Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 14 (DR14) LOWZ galaxy clustering and galaxy-shear cross-correlation measurements made with Sloan Digital Sky Survey (SDSS) Data Release 8 (DR8) imaging, we perform a prototype cosmological analysis marginalizing over wCDM cosmological parameters and galaxy HOD parameters. We obtain a 4.4 per cent measurement of S8 = 0.847 ± 0.037, in 3.5σ tension with the Planck cosmological results of 1.00 ± 0.02. We discuss the possibility of underestimated systematic uncertainties or astrophysical effects that could explain this discrepancy.
The effect of fluctuating fuzzy axion haloes on stellar dynamics: a stochastic model
Authors: El-Zant Amr A , Freundlich Jonathan , Combes Françoise , Halle Anaelle
Published: December 2019

Fuzzy dark matter of ultralight axions has gained attention, largely in light of the galactic scale problems associated with cold dark matter. But the large de Broglie wavelength, believed to possibly alleviate these problems, also leads to fluctuations that place constraints on ultralight axions. We adapt and extend a method, previously devised to describe the effect of gaseous fluctuations on cold dark matter cusps, in order to determine the imprints of ultralight axion haloes on the motion of classical test particles. We first evaluate the effect of fluctuations in a statistically homogeneous medium of classical particles, then in a similar system of ultralight axions. In the first case, one recovers the classical two body relaxation time (and diffusion coefficients) from white noise density fluctuations. In the second situation, the fluctuations are not born of discreteness noise but from the finite de Broglie wavelength; correlation therefore exists over this scale, while white noise is retained on larger scales, elucidating the correspondence with classical relaxation. The resulting density power spectra and correlation functions are compared with those inferred from numerical simulations, and the relaxation time arising from the associated potential fluctuations is evaluated. We then apply our results to estimate the heating of discs embedded in axion dark haloes. We find that this implies an axion mass $m \gtrsim 2 \times 10^{-22} \, {\rm eV}$. We finally apply our model to the case of the central cluster of Eridanus II, confirming that far stronger constraints on m may in principle be obtained, and discussing the limitations associated with the assumptions leading to these.
Ozone chemistry on tidally locked M dwarf planets
Authors: Yates Jack S , Palmer Paul I , Manners James , Boutle Ian , Kohary Krisztian , Mayne Nathan , Abraham Luke
Published: December 2019

We use the Met Office Unified Model to explore the potential of a tidally locked M dwarf planet, nominally Proxima Centauri b irradiated by a quiescent version of its host star, to sustain an atmospheric ozone layer. We assume a slab ocean surface layer, and an Earth-like atmosphere of nitrogen and oxygen with trace amounts of ozone and water vapour. We describe ozone chemistry using the Chapman mechanism and the hydrogen oxide (HOx, describing the sum of OH and HO2) catalytic cycle. We find that Proxima Centauri radiates with sufficient UV energy to initialize the Chapman mechanism. The result is a thin but stable ozone layer that peaks at 0.75 parts per million at 25 km. The quasi-stationary distribution of atmospheric ozone is determined by photolysis driven by incoming stellar radiation and by atmospheric transport. Ozone mole fractions are smallest in the lowest 15 km of the atmosphere at the substellar point and largest in the nightside gyres. Above 15 km the ozone distribution is dominated by an equatorial jet stream that circumnavigates the planet. The nightside ozone distribution is dominated by two cyclonic Rossby gyres that result in localized ozone hotspots. On the dayside the atmospheric lifetime is determined by the HOx catalytic cycle and deposition to the surface, with nightside lifetimes due to chemistry much longer than time-scales associated with atmospheric transport. Surface UV values peak at the substellar point with values of 0.01 W m−2, shielded by the overlying atmospheric ozone layer but more importantly by water vapour clouds.
Genomic Evidence for Complex Domestication History of the Cultivated Tomato in Latin America
Authors: Razifard Hamid , Ramos Alexis , Della Valle Audrey L , Bodary Cooper , Goetz Erika , Manser Elizabeth J , Li Xiang , Zhang Lei , Visa Sofia , Tieman Denise , van der Knaap Esther , Caicedo Ana L
Published: December 2019

The process of plant domestication is often protracted, involving underexplored intermediate stages with important implications for the evolutionary trajectories of domestication traits. Previously, tomato domestication history has been thought to involve two major transitions: one from wild Solanum pimpinellifolium L. to a semidomesticated intermediate, S. lycopersicum L. var. cerasiforme (SLC) in South America, and a second transition from SLC to fully domesticated S. lycopersicum L. var. lycopersicum in Mesoamerica. In this study, we employ population genomic methods to reconstruct tomato domestication history, focusing on the evolutionary changes occurring in the intermediate stages. Our results suggest that the origin of SLC may predate domestication, and that many traits considered typical of cultivated tomatoes arose in South American SLC, but were lost or diminished once these partially domesticated forms spread northward. These traits were then likely reselected in a convergent fashion in the common cultivated tomato, prior to its expansion around the world. Based on these findings, we reveal complexities in the intermediate stage of tomato domestication and provide insight on trajectories of genes and phenotypes involved in tomato domestication syndrome. Our results also allow us to identify underexplored germplasm that harbors useful alleles for crop improvement.
Enhancers Facilitate the Birth of De Novo Genes and Gene Integration into Regulatory Networks
Authors: Majic Paco , Payne Joshua L
Published: December 2019

Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of “who regulates whom.” Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing adaptive changes in gene expression. Here, we use whole-tissue and single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific intergenic open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Mouse-specific intergenic open reading frames that are proximal to enhancers are more highly and stably transcribed than those that are not proximal to enhancers or promoters, and they are transcribed in a limited diversity of cellular contexts. Furthermore, we report several instances of mouse-specific intergenic open reading frames proximal to promoters showing evidence of being repurposed enhancers. We also show that open reading frames gradually acquire interactions with enhancers over macroevolutionary timescales, helping integrate genes—those that have arisen de novo or by other means—into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.
HdaB: a novel and conserved DnaA-related protein that targets the RIDA process to stimulate replication initiation
Authors: Frandi Antonio , Collier Justine
Published: December 2019

Exquisite control of the DnaA initiator is critical to ensure that bacteria initiate chromosome replication in a cell cycle-coordinated manner. In many bacteria, the DnaA-related and replisome-associated Hda/HdaA protein interacts with DnaA to trigger the Regulatory Inactivation of DnaA (RIDA) and prevent over-initiation events. In the Caulobacter crescentus Alphaproteobacterium, the RIDA process also targets DnaA for its rapid proteolysis by Lon. The impact of the RIDA process on adaptation of bacteria to changing environments remains unexplored. Here, we identify a novel and conserved DnaA-related protein, named HdaB, and show that homologs from three different Alphaproteobacteria can inhibit the RIDA process, leading to over-initiation and cell death when expressed in actively growing C. crescentus cells. We further show that HdaB interacts with HdaA in vivo, most likely titrating HdaA away from DnaA. Strikingly, we find that HdaB accumulates mainly during stationary phase and that it shortens the lag phase upon exit from stationary phase. Altogether, these findings suggest that expression of hdaB during stationary phase prepares cells to restart the replication of their chromosome as soon as conditions improve, a situation often met by free-living or facultative intracellular Alphaproteobacteria.
Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion
Authors: Webster Lynn , Gudin Jeffrey , Raffa Robert B , Kuchera Jay , Rauck Richard , Fudin Jeffrey , Adler Jeremy , Mallick-Searle Theresa
Published: December 2019

Objective

An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management.

Methods

The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine.

Results

The panel recommended that buprenorphine’s classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended that buprenorphine be considered before some Schedule II, III, or IV opioids in patients with a favorable risk/benefit profile on the basis of metabolic factors, abuse potential, and tolerability and that buprenorphine be continued during the perioperative/trauma period. In addition, switching patients from a full µ-opioid receptor agonist to buprenorphine should be considered with no weaning period at starting doses that are based on the previous opioid dose.

Conclusions

These recommendations provide a framework for clinicians to address most clinical scenarios regarding buprenorphine use. The overall consensus of the panel was that buprenorphine is a unique Schedule III opioid with favorable pharmacologic properties and a safety profile that may be desirable for chronic pain management.
Miswiring of Frontostriatal Projections in Schizophrenia
Authors: Levitt James J , Nestor Paul G , Kubicki Marek , Lyall Amanda E , Zhang Fan , Riklin-Raviv Tammy , O′Donnell Lauren J , McCarley Robert W , Shenton Martha E , Rathi Yogesh
Published: December 2019

We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way.

We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions.

We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P  = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P  = .04) with a left (P  = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P  = .045) driven by differences in left hemisphere limbic (P  = .007) and associative (P  = .01), but not sensorimotor, striatum.

These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.
Wide spectrum and high frequency of genomic structural variation, including transposable elements, in large double-stranded DNA viruses
Authors: Loiseau Vincent , Herniou Elisabeth A , Moreau Yannis , Lévêque Nicolas , Meignin Carine , Daeffler Laurent , Federici Brian , Cordaux Richard , Gilbert Clément
Published: December 2019

Our knowledge of the diversity and frequency of genomic structural variation segregating in populations of large double-stranded (ds) DNA viruses is limited. Here, we sequenced the genome of a baculovirus (Autographa californica multiple nucleopolyhedrovirus [AcMNPV]) purified from beet armyworm (Spodoptera exigua) larvae at depths >195,000× using both short- (Illumina) and long-read (PacBio) technologies. Using a pipeline relying on hierarchical clustering of structural variants (SVs) detected in individual short- and long-reads by six variant callers, we identified a total of 1,141 SVs in AcMNPV, including 464 deletions, 443 inversions, 160 duplications, and 74 insertions. These variants are considered robust and unlikely to result from technical artifacts because they were independently detected in at least three long reads as well as at least three short reads. SVs are distributed along the entire AcMNPV genome and may involve large genomic regions (30,496 bp on average). We show that no less than 39.9 per cent of genomes carry at least one SV in AcMNPV populations, that the vast majority of SVs (75%) segregate at very low frequency (<0.01%) and that very few SVs persist after ten replication cycles, consistent with a negative impact of most SVs on AcMNPV fitness. Using short-read sequencing datasets, we then show that populations of two iridoviruses and one herpesvirus are also full of SVs, as they contain between 426 and 1,102 SVs carried by 52.4–80.1 per cent of genomes. Finally, AcMNPV long reads allowed us to identify 1,757 transposable elements (TEs) insertions, 895 of which are truncated and occur at one extremity of the reads. This further supports the role of baculoviruses as possible vectors of horizontal transfer of TEs. Altogether, we found that SVs, which evolve mostly under rapid dynamics of gain and loss in viral populations, represent an important feature in the biology of large dsDNA viruses.
Quality Assurance in Higher Education: Evaluation of Adjunct Clinical Faculty
Authors: Barker Nancy
Published: December 2019

The clinical experience is often thought of as an opportunity to tie theory to practice. However, with the current shortage of full-time nursing faculty and the increased dependence on adjunct faculty, how do administrators ensure quality? The purpose of this exploratory descriptive study was to determine the evaluation practices of administrators from accredited universities. Administrators’ (n = 26) methods of evaluation were collected via survey with follow-up interviews. Several themes emerged that may assist with the identification of issues in the evaluation of adjunct clinical faculty.
Targeted therapies in melanoma beyond BRAF: targeting NRAS-mutated and KIT-mutated melanoma
Authors: Delyon Julie , Lebbe Céleste , Dumaz Nicolas
Published: December 2019

Purpose of review

Melanoma treatment have been revolutionized since 2010 by the development of immune checkpoint inhibitors, and, for BRAF-mutated melanoma, targeted therapies based on BRAF and MEK inhibitors, which is a model of effective targeted therapy in cancer. However, patients with BRAF wild type cannot benefit for such treatments. In this review, we will focus on the current clinical development of targeted therapies beyond BRAF, in NRAS-mutated and KIT-altered melanoma.

Recent findings

In NRAS-mutated melanoma, targeted therapies based on MEK inhibition are being developed as monotherapy or in combination with MAPK, PI3K or CDK4/6 inhibitor. Targeted therapies of KIT-altered melanoma patients is based in KIT inhibitor (mostly imatinib, nilotinib), although for both melanoma subtypes, results are for now disappointing as compared with BRAF and MEK inhibitors in BRAF-mutated melanoma.

Combined therapeutic targeted strategies are awaited in NRAS-mutated and KIT-altered melanoma and could provide additional benefit.
Prototype Development, Usability, and Preference of a Culturally-relevant Pictorial Aid to Facilitate Comprehension of Likert-type Levels of Agreement in Caregivers of Children Living With HIV in Ghana
Authors: Ramos S. Raquel , Paintsil Elijah , Ofori-Atta Angela , Kusah Jonas Tettey , Amissah Kofi Aikins , Alhassan Amina , Ofori Irene Pokuaa , Reynolds Nancy R.
Published: December 2019

Pictorial illustrations of Likert-type scales are culturally useful and may reduce error associated with usage of Westernized self-report measures in low- and middle-income countries. Pictorial illustrations can be encounter-specific decision aids in populations with low literacy or English proficiency. In an unanticipated finding from the SANKOFA study, caregivers of children living with human immunodeficiency virus experienced challenges comprehending Likert-type scales. A cross-sectional, qualitative study was conducted with a SANKOFA participant subset (n = 30) in Ghana. Using an informatics-based formative design approach, we developed a culturally-relevant pictorial aid to assess usability and preference when compared to a Likert-type self-report measure. Ninety percent (n = 27) of substudy participants preferred the pictorial of a traditional Bolga basket over a shallow basket. Forty-three percent (n = 13) preferred the pictorial aid over the Likert-type measure. Fifty percent reported the pictorial aid was easy to use. Fifty-seven percent preferred the Likert-type measure, potentially because English proficiency is regarded in Ghana as a means of upward social and financial mobility. Such cultural norms may have contributed to the lack of consensus and must be considered for pictorial aids to be meaningful. Pictorial aids have been designed for use in clinical and research settings. They reduce barriers associated with lower textual literacy while facilitating comprehension and decision-making.