bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive entropy through pointwise dynamics
Authors: Arbieto A. , Rego E.
Published: June 2019

We define some pointwise properties of topological dynamical systems and give pointwise conditions to guarantee the positiveness of the topological entropy of such a system. We also give sufficient conditions to obtain positive topological entropy for maps which are approximated by maps with the shadowing property in a uniform way.
Enlargeable metrics on nonspin manifolds
Authors: Cecchini Simone , Schick Thomas
Published: June 2019

We show that an enlargeable Riemannian metric on a (possibly nonspin) manifold cannot have uniformly positive scalar curvature. This extends a well-known result of Gromov and Lawson to the nonspin setting. We also prove that every noncompact manifold admits a nonenlargeable metric. In proving the first result, we use the main result of the recent paper by Schoen and Yau on minimal hypersurfaces to obstruct positive scalar curvature in arbitrary dimensions. More concretely, we use this to study nonzero degree maps

f
:

X
n

→

S
k

×

T

n
−
k

f\colon X^n\rightarrow S^k\times T^{n-k}

, with

k
=
1
,
2
,
3

k=1,2,3

. When

X
X

is a closed oriented manifold endowed with a metric

g
g

of positive scalar curvature and the map

f
f

is (possibly area) contracting, we prove inequalities relating the lower bound of the scalar curvature of

g
g

and the contracting factor of the map

f
f

.
A new proof for the Hartman-Grobman theorem for random dynamical systems
Authors: Zhao Junyilang , Shen Jun
Published: June 2019

In this paper, we give a new and quick proof for the Hartman-Grobman theorem for random dynamical systems. This approach does not involve any previously proved existence of the stable and unstable manifolds.
Perturbation bounds for eigenspaces under a relative gap condition
Authors: Jirak Moritz , Wahl Martin
Published: June 2019

A basic problem in operator theory is to estimate how a small perturbation affects the eigenspaces of a self-adjoint compact operator. In this paper, we prove upper bounds for the subspace distance, tailored for relative perturbations. As a main example, we consider the empirical covariance operator and show that a sharp bound can be achieved under a relative gap condition. The proof is based on a novel contraction phenomenon, contrasting previous spectral perturbation approaches.
Genetic Testing in the Diagnosis and Biology of Acute Leukemia
Authors: Harris Marian H , Czuchlewski David R , Arber Daniel A , Czader Magdalena
Published: June 2019

Objectives

The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology examined the role of molecular genetics in the diagnosis and biology of acute leukemia.

Methods

Acute leukemias were reviewed in two sessions: “Genetic Testing in Diagnosis of Acute Leukemias” (53 cases) and “Genetics Revealing the Biology of Acute Leukemias” (41 cases).

Results

Cases included acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemia of ambiguous lineage. Many cases demonstrated genetic alterations of known diagnostic, prognostic, and/or therapeutic significance, while others exhibited alterations that illuminated disease biology. The workshop highlighted the complexity of acute leukemia diagnosis and follow-up, while illustrating advantages and pitfalls of molecular genetic testing.

Conclusions

Our understanding of the molecular genetics of acute leukemias continues to grow rapidly. Awareness of the potential complexity of genetic architecture and environment is critical and emphasizes the importance of integrating clinical information with morphologic, immunophenotypic, and molecular genetic evaluation.
Focal mechanism and stress field in the northeastern Tibetan Plateau: insight into layered crustal deformations
Authors: Han Cunrui , Huang Zhouchuan , Xu Mingjie , Wang Liangshu , Mi Ning , Yu Dayong , Li Hua
Published: June 2019

Focal mechanism solutions (FMSs) reflect the stress field underground directly. They provide essential clue for crustal deformations and therefore improve our understanding of tectonic uplift and expansion of the Tibetan Plateau. In this study, we applied generalized Cut and Paste and P-wave first-motion methods to determine 334 FMSs (2.0 ≤ Mw ≤ 6.4) with the data recorded by a new temporary network deployed in the NE Tibetan Plateau by ChinArray project. We then used 1015 FMSs (including 681 published FMSs) to calculate the regional stress field with a damped linear inversion. The results suggest dominant thrust and strike-slip faulting environments in the NE Tibetan Plateau. From the Qilian thrust belt to the Qinling orogen, the maximum horizontal stress orientations (${S_\mathrm{ H}}$) rotate clockwise from NNE to NE, and further to EW, showing a fan-shaped pattern. The derived minimum horizontal stress orientations (${S_\mathrm{ h}}$) are parallel to the aligned fabrics in the mantle lithosphere indicated by shear wave splitting measurements, suggesting vertically coherent deformation in the NE Tibetan Plateau. Beneath the SW Qinling adjacent to the plateau, however, the stress orientations in the shallow and deep crust are different, whereas the deep crustal stress field indicates possible ductile crustal flow or shear.
Recreation centre managers’ perceptions of pricing interventions to promote healthy eating
Authors: Huse Oliver , Zorbas Christina , Jerebine Alethea , Kurzeme Ari , Blake Miranda , Ferguson Megan , Palermo Claire , Peeters Anna , Orellana Liliana , Brimblecombe Julie , Moodie Marj , Backholer Kathryn
Published: June 2019

Retailers have the capacity to improve the food and beverage environment by making healthier options more affordable and attractive for their consumers. The perspectives of retailers on feasible and acceptable pricing strategies are not known. The aim of this study was to understand retailers’ perceptions of factors that are relevant to feasible and acceptable health-promoting food and beverage pricing interventions. A convenience sample of 11 aquatic and recreation centre managers in Victoria, Australia was recruited to participate in semi-structured interviews. We took a pragmatic approach with the aim of understanding retailers’ perceptions of factors that affect the feasibility and acceptability of pricing interventions within their facilities. Thematic analysis was used to synthesize and interpret retailers’ perceptions of pricing interventions. Key themes identified were: structural and organizational characteristics (the internal and external characteristics of aquatic and recreation centres), characteristics of feasible pricing changes (type, magnitude and products targeted by pricing strategies) and business outcomes (profits and customer feedback). Results suggest that pricing interventions to promote healthy food and beverage choices can be feasible and acceptable to retailers, though contextual considerations are likely to be important. Future studies should use these findings to design interventions most likely to be acceptable to retailers, work with retailers to implement health-promoting food and beverage pricing interventions, evaluate the impact on business outcomes including customer perspectives and profitability, and test transferability to other retail settings.
A mouse model of Proteus syndrome
Authors: Lindhurst Marjorie J , Brinster Lauren R , Kondolf Hannah C , Shwetar Jasmine J , Yourick Miranda R , Shiferaw Henoke , Keppler-Noreuil Kim M , Elliot Gene , Rivas Cecilia , Garrett Lisa , Gomez-Rodriguez Julio , Sebire Neil J , Hewitt Stephen M , Schwartzberg Pamela L , Biesecker Leslie G
Published: June 2019

Proteus syndrome is a mosaic, progressive overgrowth disorder caused by a somatic activating variant c.49G > A p.(E17K) in AKT1. The presentation in affected individuals is variable, with a diversity of tissues demonstrating abnormalities. Common manifestations include skin and bony overgrowth, vascular malformations (VMs), cysts and benign tumors. We used two methods to create mouse models that had endogenously-regulated mosaic expression of the Proteus syndrome variant. Variant allele fractions (VAFs) ranged from 0% to 50% across numerous tissues in 44 Proteus syndrome mice. Mice were phenotypically heterogeneous with lesions rarely observed before 12 months of age. VMs were the most frequent finding with a total of 69 found in 29 of 44 Proteus syndrome mice. Twenty-eight cysts and ectasia, frequently biliary, were seen in 22 of 44 Proteus syndrome mice. Varying levels of mammary hyperplasia were seen in 10 of 16 female Proteus syndrome mice with other localized regions of hyperplasia and stromal expansion noted in several additional animals. Interestingly, 27 of 31 Proteus syndrome animals had non-zero blood VAF that is in contrast to the human disorder where it is rarely seen in peripheral blood. Identification of variant-positive cells by green fluorescent protein (GFP) staining in chimeric Proteus syndrome mice showed that in some lesions, hyperplastic cells were predominantly GFP/Akt1E17K-positive and showed increased pAKT signal compared to GFP-negative cells. However, hyperplastic mammary epithelium was a mixture of GFP/Akt1E17K-positive and negative cells with some GFP/Akt1E17K-negative cells also having increased pAKT signal suggesting that the variant-positive cells can induce lesion formation in a non-cell autonomous manner.
Hippocampal Subfields in Acute and Remitted Depression—an Ultra-High Field Magnetic Resonance Imaging Study
Authors: Kraus Christoph , Seiger Rene , Pfabigan Daniela M , Sladky Ronald , Tik Martin , Paul Katharina , Woletz Michael , Gryglewski Gregor , Vanicek Thomas , Komorowski Arkadiusz , Kasper Siegfried , Lamm Claus , Windischberger Christian , Lanzenberger Rupert
Published: June 2019

Background

Studies investigating hippocampal volume changes after treatment with serotonergic antidepressants in patients with major depressive disorder yielded inconsistent results, and effects on hippocampal subfields are unclear.

Methods

To detail treatment effects on total hippocampal and subfield volumes, we conducted an open-label study with escitalopram followed by venlafaxine upon nonresponse in 20 unmedicated patients with major depressive disorder. Before and after 12 weeks treatment, we measured total hippocampal formation volumes and subfield volumes with ultra-high field (7 Tesla), T1-weighted, structural magnetic resonance imaging, and FreeSurfer. Twenty-eight remitted patients and 22 healthy subjects were included as controls. We hypothesized to detect increased volumes after treatment in major depressive disorder.

Results

We did not detect treatment-related changes of total hippocampal or subfield volumes in patients with major depressive disorder. Secondary results indicated that the control group of untreated, stable remitted patients, compared with healthy controls, had larger volumes of the right hippocampal-amygdaloid transition area and right fissure at both measurement time points. Depressed patients exhibited larger volumes of the right subiculum compared with healthy controls at MRI-2. Exploratory data analyses indicated lower baseline volumes in the subgroup of remitting (n = 10) vs nonremitting (n = 10) acute patients.

Conclusions

The results demonstrate that monoaminergic antidepressant treatment in major depressive disorder patients was not associated with volume changes in hippocampal subfields. Studies with larger sample sizes to detect smaller effects as well as other imaging modalities are needed to further assess the impact of antidepressant treatment on hippocampal subfields.
Spaces of Abelian Differentials and Hitchin’s Spectral Covers
Authors: Bertola M , Korotkin D
Published: June 2019

Using the embedding of the moduli space of generalized $GL(n)$ Hitchin’s spectral covers to the moduli space of meromorphic Abelian differentials we study the variational formulæ of the period matrix, the canonical bidifferential, the prime form and the Bergman tau function. This leads to residue formulæ which generalize the Donagi–Markman formula for variations of the period matrix. The computation of second derivatives of the period matrix reproduces the formula derived in [2] using the framework of topological recursion.
Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy–Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial
Authors: Ekenberg Christina , Tang Man-Hung , Zucco Adrian G , Murray Daniel D , MacPherson Cameron Ross , Hu Xiaojun , Sherman Brad T , Losso Marcelo H , Wood Robin , Paredes Roger , Molina Jean-Michel , Helleberg Marie , Jina Nureen , Kityo Cissy M , Florence Eric , Polizzotto Mark N , Neaton James D , Lane H Clifford , Lundgren Jens D
Published: June 2019

The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy–naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed HLA alleles, and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex class I region (MHC I), with effect sizes ranging between 0.14 and 0.39 log10 VL (copies/mL). Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the (MHC I) is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of genome-wide association studies as being merely a screening tool.
Assessing the lymphoid tissue bioavailability of antiretrovirals in human primary lymphoid endothelial cells and in mice
Authors: Dyavar Shetty Ravi , Gautam Nagsen , Podany Anthony T , Winchester Lee C , Weinhold Jonathan A , Mykris Timothy M , Campbell Kayla M , Alnouti Yazen , Fletcher Courtney V
Published: June 2019

Background

The secondary lymphoid tissues (LTs), lymph nodes (LNs) and gut-associated lymphoid tissue (GALT) are considered reservoirs for HIV. Antiretrovirals (ARVs) have lower penetration into LT. In vitro models predictive of ARV LT penetration have not been established.

Objectives

To develop an in vitro model of LT bioavailability using human lymphoid endothelial cells (HLECs) and investigate its predictability with in vivo pharmacokinetic (PK) studies in mice.

Methods

ARV bioavailability in HLECs was evaluated at the maximum plasma concentration (Cmax) observed in HIV-infected patients. ARVs were: abacavir, atazanavir, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, maraviroc, raltegravir, rilpivirine, ritonavir, tenofovir disoproxil fumarate and the PK booster cobicistat. The LT PK of representative drugs showing high (efavirenz), intermediate (dolutegravir) and low (emtricitabine) HLEC bioavailability was investigated in BALB/c mice given 50/10/30 mg/kg efavirenz/dolutegravir/emtricitabine orally, daily for 3 days. The concordance of in vitro and in vivo ARV bioavailability was examined.

Results

ARVs showed high (>67th percentile; rilpivirine, efavirenz, elvitegravir and cobicistat), intermediate (67th–33rd percentile; ritonavir, tenofovir disoproxil fumarate, dolutegravir and maraviroc) and low (<33rd percentile; atazanavir, darunavir, raltegravir, emtricitabine and abacavir) HLEC bioavailability. The hierarchy of efavirenz, dolutegravir and emtricitabine bioavailability in LN, gut and brain tissues of mice was: efavirenz>dolutegravir>emtricitabine.

Conclusions

ARVs displayed distinct HLEC penetration patterns. PK studies of representative ARVs in LT of mice were concordant with HLEC bioavailability. These findings support further development of this approach and its translational predictability in humans.
Jasmonate and auxin perception: how plants keep F-boxes in check
Authors: Williams Clara , Fernández-Calvo Patricia , Colinas Maite , Pauwels Laurens , Goossens Alain
Published: June 2019

Phytohormones regulate the plasticity of plant growth and development, and responses to biotic and abiotic stresses. Many hormone signal transduction cascades involve ubiquitination and subsequent degradation of proteins by the 26S proteasome. The conjugation of ubiquitin to a substrate is facilitated by the E1 activating, E2 conjugating, and the substrate-specifying E3 ligating enzymes. The most prevalent type of E3 ligase in plants is the Cullin–RING ligase (CRL)-type, with F-box proteins (FBPs) as the substrate recognition component. The activity of these SKP–Cullin–F-box (SCF) complexes needs to be tightly regulated in time and place. Here, we review the regulation of SCF function in plants on multiple levels, with a focus on the auxin and jasmonate SCF-type receptor complexes. We discuss in particular the relevance of protein–protein interactions and post-translational modifications as mechanisms to keep SCF functioning under control. Additionally, we highlight the unique property of SCFTIR1/AFB and SCFCOI1 to recognize substrates by forming co-receptor complexes. Finally, we explore how engineered selective agonists can be used to study and uncouple the outcomes of the complex auxin and jasmonate signaling networks that are governed by these FBPs.
Overexpression of the peanut CLAVATA1-like leucine-rich repeat receptor-like kinase AhRLK1 confers increased resistance to bacterial wilt in tobacco
Authors: Zhang Chong , Chen Hua , Zhuang Rui-Rong , Chen Yu-Ting , Deng Ye , Cai Tie-Cheng , Wang Shuai-Yin , Liu Qin-Zheng , Tang Rong-Hua , Shan Shi-Hua , Pan Rong-Long , Chen Li-Song , Zhuang Wei-Jian
Published: June 2019

Overexpression of a novel peanut CLAVATA1-like gene significantly enhanced the resistance to Ralstonia solanacearum in tobacco via defense response signaling associated with EDS1-mediated R-gene pathways.
Hyperfine excitation of SH+ in collisions with para- and ortho-H2
Authors: Dagdigian Paul J
Published: June 2019

Time-independent close-coupling quantum scattering calculations are employed to compute hyperfine-resolved rate coefficients for (de-)excitation of SH+ in collisions with para- and ortho-H2. These calculations utilized a potential energy surface for the interaction of SH+(X3Σ−) with H2 recently computed by the explicitly correlated RCCSD(T)-F12a coupled-cluster method. Rate coefficients for temperatures ranging from 10 to 500 K were calculated for all transitions among the first 37 hyperfine energy levels of SH+, with rotational angular momenta n ≤ 6, in collisions with para- and ortho-H2. As a first application of these data, the rate coefficients were employed in simple radiative transfer calculations to simulate the excitation of SH+ in typical molecular clouds.
A nuclear ionized gas outflow in the Seyfert 2 galaxy UGC 2024
Authors: Muñoz-Vergara Dania , Nagar Neil M , Ramakrishnan Venkatessh , Finlez Carolina , Storchi-Bergmann Thaisa , Slater Roy , Firpo Veronica , Humire Pedro K , Soto-Pinto Pamela , Kraemer Steven B , Lena Davide , Robinson Andrew , Riffel Rogemar A , Crenshaw D Michael , Elvis Martin S , Fischer T C , Schnorr-Müller Allan , Schmitt Henrique R
Published: June 2019

As part of a high-resolution observational study of feeding and feedback processes occurring in the vicinity of the active galactic nucleus in 40 galaxies, we observed the inner 3${^{\prime\prime}_{.}}$5 × 5 arcsec of the nearby spiral and Seyfert 2 galaxy UGC 2024 with the integral field unit of the Gemini-South Telescope. The observations enabled a study of the stellar and gas kinematics in this region at a spatial resolution of 0${^{\prime\prime}_{.}}$5 (218 pc), and a spectral resolution of 36  km s−1 over the wavelength range 4100–7300 Å. For the strongest emission-lines (H β, [$\rm{O\,{\small III}}$] λ5007 Å, H α, [$\rm{N\,{\small II}}$] λ6584 Å, and [$\rm{S\,{\small II}}$] λλ6717,6731 Å) we derived maps of the flux, radial velocity, and velocity dispersion. The flux distribution and kinematics of the [$\rm{O\,{\small III}}$] emission line are roughly symmetric around the nucleus: the radial velocity is close to systemic over the full field of view. The kinematics of the other strong emission lines trace both this systemic velocity component, and ordered rotation (with kinematic centre 0${^{\prime\prime}_{.}}$2 north-west of the nucleus). The stellar continuum morphology and kinematics are, however, asymmetrical around the nucleus. We interpret these unusual kinematics as the superposition of a component of gas rotating in the galaxy disc plus a ‘halo’ component of highly ionized gas. This halo either traces a quasi-spherical fountain with average radial velocity 200 km s−1, in which case the total nuclear outflow mass and momentum are 2 × 105 M⊙ and 4 × 107 M⊙ km s−1, respectively, or a dispersion supported halo created by a past nuclear starburst.
A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2
Authors: Dubois Emilie L , Guitton-Sert Laure , Béliveau Mariline , Parmar Kalindi , Chagraoui Jalila , Vignard Julien , Pauty Joris , Caron Marie-Christine , Coulombe Yan , Buisson Rémi , Jacquet Karine , Gamblin Clémence , Gao Yuandi , Laprise Patrick , Lebel Michel , Sauvageau Guy , D. d’Andrea Alan , Masson Jean-Yves
Published: June 2019

Fanconi Anemia (FA) clinical phenotypes are heterogenous and rely on a mutation in one of the 22 FANC genes (FANCA-W) involved in a common interstrand DNA crosslink-repair pathway. A critical step in the activation of FA pathway is the monoubiquitination of FANCD2 and its binding partner FANCI. To better address the clinical phenotype associated with FANCI and the epistatic relationship with FANCD2, we created the first conditional inactivation model for FANCI in mouse. Fanci −/− mice displayed typical FA features such as delayed development in utero, microphtalmia, cellular sensitivity to mitomycin C, occasional limb abnormalities and hematological deficiencies. Interestingly, the deletion of Fanci leads to a strong meiotic phenotype and severe hypogonadism. FANCI was localized in spermatocytes and spermatids and in the nucleus of oocytes. Both FANCI and FANCD2 proteins co-localized with RPA along meiotic chromosomes, albeit at different levels. Consistent with a role in meiotic recombination, FANCI interacted with RAD51 and stimulated D-loop formation, unlike FANCD2. The double knockout Fanci−/− Fancd2−/− also showed epistatic relationship for hematological defects while being not epistatic with respect to generating viable mice in crosses of double heterozygotes. Collectively, this study highlights common and distinct functions of FANCI and FANCD2 during mouse development, meiotic recombination and hematopoiesis.
New therapeutic options for Alport syndrome
Authors: Torra Roser , Furlano Mónica
Published: June 2019

Alport syndrome (AS) is the most frequent inherited kidney disease after autosomal dominant polycystic kidney disease. It has three different patterns of inheritance—autosomal dominant, autosomal recessive and X-linked—which in part explains the wide spectrum of disease, ranging from isolated microhaematuria to end-stage renal disease early in life. The search for a treatment for AS is being pursued vigorously, not only because of the obvious unmet need but also because AS is a rare disease and any drug approved will have an orphan drug designation with its various benefits. Moreover, AS patients are quite young with very few comorbidities, which facilitates clinical trials. This review identifies the particularities of each pattern of inheritance but focuses mainly on new drugs or therapeutic targets for the disease. Most treatment-related investigations are directed not at the main abnormality in AS, namely collagen IV composition, but rather at the associated inflammation and fibrosis. Thus, AS may serve as a proof of concept for numerous drugs of potential value in many diseases that cause chronic kidney disease.
A direct method for Bloch wave excitation by scattering at the edge of a lattice. Part II: Finite size effects
Authors: Brougham R I , Thompson I
Published: June 2019

A method for determining the reflection and transmission properties of a periodic structure occupying a half-space, previously developed for lattices formed from point scatterers, is generalized to allow for finite size effects. This facilitates the consideration of much higher frequencies (or more precisely, much higher scatterer size to wavelength ratios), and also a wider range of boundary conditions. The method is presented in a general context of linear wave theory, and physical interpretations are given for acoustics, elasticity, electromagnetism and water waves.
Dynamic Asset Sales with a Feedback Effect
Authors: Frenkel Sivan
Published: June 2019

I analyze a dynamic model of over-the-counter asset sales in which the seller receives stock-sensitive compensation, and the transaction conveys information about the firm’s value. I examine how the market’s response to an asset sale feeds back to the seller’s decision on the timing and the sale price and analyze the unique pattern of stock prices before and after the sale. The implications of bargaining power, inventories, gains from synergy, and the introduction of a vesting period are discussed. The model sheds light on observed properties of corporate sell-offs and explains market dry-ups during downturn periods.

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.
Monosodium urate crystal interleukin-1β release is dependent on Toll-like receptor 4 and transient receptor potential V1 activation
Authors: Rossato Mateus F. , Hoffmeister Carin , Trevisan Gabriela , Bezerra Fabio , Cunha Thiago M. , Ferreira Juliano , Silva Cassia R.
Published: June 2019

Objective

The present study aimed to elucidate the mechanisms involved in MSU-induced IL-1β release in a rodent animal model of acute gout arthritis.

Methods

Painful (mechanical and thermal hypersensitivity, ongoing pain and arthritis score) and inflammatory (oedema, plasma extravasation, cell infiltration and IL-1β release) parameters were assessed several hours after intra-articular injection of MSU (100 µg/articulation) in wild-type or knockout mice for Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), transient receptor potential (TRP) V1 and the IL-1 receptor (IL-1R). Also, wild-type animals were treated with clodronate, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) (TLR4 antagonist), spleen tyrosine kinase (SYK) inhibitor (iSYK), aminoguanidine (AMG, an iNOS inhibitor) or SB366791 (TRPV1 antagonist). Nitrite/nitrate and IL-1β levels were measured on the synovial fluid of wild-type mice, 2 h after intra-articular MSU injections, or medium from macrophages stimulated for MSU (1000 μg) for 2 h.

Results

Intra-articular MSU injection caused robust nociception and severe inflammation from 2 up to 6 h after injection, which were prevented by the pre-treatment with clodronate, LPS-RS, iSYK, AMG and SB366791, or the genetic ablation of TLR4, iNOS, TRPV1 or IL-1R. MSU also increased nitrite/nitrate and IL-1β levels in the synovial fluid, which was prevented by clodronate, LPS-RS, iSYK and AMG, but not by SB366791. Similarly, MSU-stimulated peritoneal macrophages released nitric oxide, which was prevented by LPS-RS, iSYK and AMG, but not by SB366791, and released IL-1β, which was prevented by LPS-RS, iSYK, AMG and SB366791.

Conclusion

Our data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.
What matters the adherence with BP 24-hr self-monitoring wearable device among hypertensive patients? A population-based survey
Authors: Zhang Yuting , Yang Ningxi , Si Guanglin , Zhang Yupeng , Dong Zhuangzhuang , Huang Yuwei , Tan Xiaodong
Published: June 2019

Wearable mobile health (mHealth) technologies are a convenient and cost-effective community-based intervention to improve management of hypertension in resource-limited populations. This study was designed to evaluate user characteristics of blood pressure (BP) wearable technology among a community-based population in a rural area of China. During the period of April through July 2018, a self-monitoring intervention program for hypertension control was implemented in a remote area of central China. Participants completed a cross-sectional survey which included demographic characteristics, Technology Fluency, the Compliance of Hypertensive Patients’ Scale, and the Health-related Quality of Life Survey. Participants were given a wearable BP-monitoring device which wirelessly uploaded data and monitored for 1 month. Participants (n = 317) were 64.57 years (SD = 11.68), 53.94% were male. During the 30-day monitoring, 52.68% of the sample uploaded BP wristband data daily were identified as “BP device users.” No differences existed between device users and nonusers related to cardiovascular health measurements, technology fluency, and health-related quality of life. Device users were more likely to report a higher level of hypertension compliance. Individuals reporting a higher level of compliance in hypertension management are more likely to interact with a wearable BP-monitoring device than persons with lower levels of compliance. Further evaluation of mobile health systems involving a wearable device as part of a hypertension management program is needed in a resource-limited community-based setting.
Mediation and arbitration: the process of enforcement
Authors: Zeller Bruno , Trakman Leon
Published: June 2019

Mediation is an important means of resolving international commercial disputes. The mediators whom the parties appoint can help to avoid contentious, dilatory and costly conflicts, including by resort to arbitration and/or litigation. The problem is the recognition and enforcement of mediated agreements often diverges from one state to the next. This makes it difficult to predict whether a mediated agreement will be enforced in a particular jurisdiction. The draft 2018 Singapore Mediation Convention [SMC] seeks to address this problem by providing uniform rules to govern the recognition and enforcement of mediated agreements. The obstacle faced by the SMC is that leading commercial states, notably in the EU, have resisted signing onto the SMC. They argue that mediation is, and ought to be, regulated domestically; and that the SMC is likely to marginalize domestic conceptions of mediation.

This article evaluates the significance of mediation in resolving international commercial disputes. It stresses the growing importance of mediation in international commercial dealings, how the SMC can assist to fill a void in regulating such mediation, and how it can prevent commercial disputes from regressing into protracted arbitration with ensuing enforcement complications. Focusing on the SMC's rules governing the enforcement of mediation agreements, it examines how those rules are likely to operate in law, and their perceived strengths and limitations in practice.
Genetic Differences in Barley Govern the Responsiveness to N-Acyl Homoserine Lactone
Authors: Shrestha Abhishek , Elhady Ahmed , Adss Shimaa , Wehner Gwendolin , Böttcher Christoph , Heuer Holger , Ordon Frank , Schikora Adam
Published: June 2019

Enhanced resistance in barley (Hordeum vulgare) against pathogens, such as the powdery mildew-causing fungus Blumeria graminis f. sp. hordei, is of high importance. The beneficial effects of bacterial quorum sensing molecules on resistance and plant growth have been shown in different plant species. Here, we present the effects of the N-3-oxotetradecanoyl-l-homoserine lactone (oxo-C14-HSL) on the resistance of different barley genotypes. Genetically diverse accessions of barley were identified and exposed to the beneficial, oxo-C14-HSL-producing bacterium Ensifer meliloti or the pure N-acyl homoserine lactone (AHL) molecule. Metabolic profiling along with expression analysis of selected genes and physiological assays revealed that the capacity to react varies among different barley genotypes. We demonstrate that upon pretreatment with AHL molecule, AHL-primable barley genotype expresses enhanced resistance against B. graminis f. sp. hordei. We further show that pretreatment with AHL correlates with stronger activation of barley MAP kinases and regulation of defense-related PR1 and PR17b genes after a subsequent treatment with chitin. Noticeable was the stronger accumulation of lignin. Our results suggest that appropriate genetic background is required for AHL-induced priming. At the same time, they bear potential to use these genetic features for new breeding and plant protection approaches.
Analyzing the Influence of Landscape Aggregation on Disease Spread to Improve Management Strategies
Authors: Picard Coralie , Soubeyrand Samuel , Jacquot Emmanuel , Thébaud Gaël
Published: June 2019

Epidemiological models are increasingly used to predict epidemics and improve management strategies. However, they rarely consider landscape characteristics although such characteristics can influence the epidemic dynamics and, thus, the effectiveness of disease management strategies. Here, we present a generic in silico approach which assesses the influence of landscape aggregation on the costs associated with an epidemic and on improved management strategies. We apply this approach to sharka, one of the most damaging diseases of Prunus trees, for which a management strategy is already applied in France. Epidemic simulations were carried out with a spatiotemporal stochastic model under various management strategies in landscapes differing in patch aggregation. Using sensitivity analyses, we highlight the impact of management parameters on the economic output of the model. We also show that the sensitivity analysis can be exploited to identify several strategies that are, according to the model, more profitable than the current French strategy. Some of these strategies are specific to a given aggregation level, which shows that management strategies should generally be tailored to each specific landscape. However, we also identified a strategy that is efficient for all levels of landscape aggregation. This one-size-fits-all strategy has important practical implications because of its simple applicability at a large scale.
An innovative warming strategy to increase patient satisfaction
Authors: Palmer Jonathan , Soucier Michael , Deeds Jacob
Published: June 2019

Thermal comfort helps patients maintain normothermia, decreases preoperative anxiety, and increases their sense of well-being. This article details an initiative to improve surgical patient satisfaction with thermal comfort using reflective blankets at a 115-bed major medical center and Level III trauma center in the Southwest US.
Simulation for Continuing Pharmacy Education: Development and Implementation of a Simulation-Based Workshop on Medicines Reconciliation for Pharmacists
Authors: Katoue Maram G. , Ker Jean
Published: June 2019

Introduction:

Simulation has been increasingly used to train health care professionals on clinical skills. Little is published on simulation-based education in the context of continuing pharmacy education (CPE) of pharmacists. This article describes the development implementation and evaluation of simulation-based workshop to train hospital pharmacists on medicines reconciliation in Kuwait. The study aimed to explore pharmacists' perceptions about simulation use in CPE. It also assessed the impact of the workshops on pharmacists' attitudes toward, knowledge, and comfort level to apply medicines reconciliation.

Methods:

One hundred ten pharmacists attended 11 simulation-based workshops. Data were collected using focus groups and self-administered surveys in a mixed-method research design. Focus groups were audio-recorded, transcribed verbatim, and analyzed for content. Descriptive statistics were used to report surveys' findings.

Results:

The workshops were well-received by pharmacists. Few pharmacists recalled previous exposure to simulation in CPE activities. Pharmacists' perceived challenges to simulation integration into their professional training were the need for good preparation/setting, qualified faculty, well-trained simulated patients, and time constrains. Participants felt that simulation enhanced their attitudes toward, knowledge, and comfort level to apply medicines reconciliation. They rated their knowledge level as having increased by 62.3% and comfort level as having increased by 37.0%. They overwhelmingly welcomed more integration of simulation in CPE activities.

Discussion:

A simulation-based continuing education workshop was well-received by pharmacists and enhanced their self-reported knowledge, comfort level, and preparedness to apply medicines reconciliation. Efforts are needed to expand simulation use in the development, refinement, and maintenance of clinical skills of pharmacists throughout their educational continuum including CPE.
Microsatellite Instability and Adjuvant Chemotherapy in Stage II Colon Cancer
Authors: Koenig Julie L. , Toesca Diego A.S. , Harris Jeremy P. , Tsai Chiaojung Jillian , Haraldsdottir Sigurdis , Lin Albert Y. , Pollom Erqi L. , Chang Daniel T.
Published: June 2019

Background:

Randomized control trials and population-based studies do not demonstrate a definitive benefit for adjuvant chemotherapy (ACT) in stage II colon cancer (CC). Tumor sidedness and microsatellite instability (MSI) status may predict response to ACT, but previous studies have limited microsatellite data. We assessed the efficacy of ACT and possible interaction with MSI status and tumor sidedness in patients with resected stage II CC diagnosed between 2010 and 2013 using the National Cancer Database.

Materials and Methods:

Overall survival was evaluated with the Kaplan-Meier method and multivariate and propensity score matched Cox proportional hazards models. The interaction between receipt of ACT, MSI status, and tumor sidedness was evaluated. The efficacy of ACT was assessed in patient subgroups by MSI status and tumor sidedness.

Results:

Among 6964 stage II CC patients with known MSI status, 1497 (21.5%) received ACT, 843 had MSI tumors, and 6121 had microsatellite stable (MSS) tumors. In multivariate and propensity score matched analyses, ACT was associated with improved survival after adjusting for factors including high-risk features, MSI status, and tumor sidedness (multivariate hazard ratio, 0.52; P<0.001). There was no interaction between receipt of ACT and MSI status (P=0.25). Patients with MSS tumors benefitted from ACT (multivariate hazard ratio, 0.47; P<0.001), even without other high-risk features. Patients with MSI tumors did not (P=0.671). ACT was associated with improved survival regardless of tumor sidedness.

Conclusions:

MSS alone may warrant ACT in stage II CC while patients with MSI tumors may not derive significant benefit from ACT.
Survival Trends of Patients With Surgically Resected Gastric Cardia Cancer From 1988 to 2015
Authors: Ze-Long Yang , Guo-Hui Mei , Lin Zhu , Wei-Hong Yang , Ke-Cheng Zhang , Yan-Wen Jin
Published: June 2019

Background:

The incidence of gastric cardia cancer (GCC) patients has been increasing, while the survival trends of GCC patients over time remains unclear. Thus, the aim of our study was to determine the survival trends of GCC patients over time using a population-based data in the United States.

Methods:

A total of 9044 surgically resected GCC patients during 1988 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were identified. The survival probabilities were calculated by Kaplan-Meier method and the different survival probabilities between groups were examined by log-rank test.

Results:

The median overall survival time was 27 (interquartile range, 12 to 99) months, and the median disease-specific survival time was 32 (interquartile range, 13 to 320) months for GCC patients. There was a statistically significant increase in median overall survival time (17 to 46 mo; P<0.001) and disease-specific survival time (19 to 67 mo; P<0.001) from 1988 to 1997 to 2008 to 2015. More GCC patients were diagnosed at an early stage in recent years. Meanwhile, adequate lymph nodes examined (eLNs) were obtained in more GCC patients during surgery. Also, the proportion of GCC patients who received chemoradiotherapy increased significantly. Moreover, early diagnosis, adequate eLNs, and chemoradiotherapy were associated with mortality.

Conclusions:

The survival rates of surgically resected GCC patients had a significant improvement from 1988 to 1997 to 2008 to 2015 in the United States, which might relate to the early discovery of GCC, greater utilization of adequate eLNs, and chemoradiotherapy.
Patterns of Care and Outcomes of Definitive External Beam Radiotherapy and Radioembolization for Localized Hepatocellular Carcinoma
Authors: Bitterman Danielle S. , Sanford Nina N. , Niemierko Andrzej , Mahal Brandon A. , Qadan Motaz , Ganguli Suvranu , Blaszkowsky Lawrence S. , Zhu Andrew X. , Hong Theodore S. , Devlin Phillip M. , Goyal Lipika , Wo Jennifer Y.
Published: June 2019

Objectives:

Most localized hepatocellular carcinoma (HCC) patients are not surgically operable or transplantation candidates, increasing the role for nonsurgical therapies. Ablative external beam radiotherapy (XRT) and transarterial radioembolization (TARE) are emerging radiotherapeutic treatments for localized HCC. We sought to evaluate their utilization and efficacy in a large nationwide cohort.

Materials and Methods:

We conducted an observational study of 2685 patients from the National Cancer Database (NCDB) diagnosed with American Joint Committee on Cancer 7th edition clinical stage I to III HCC between 2004 and 2015, treated with definitive-intent XRT delivered in 1 to 15 fractions or TARE. The association between treatment modality (XRT vs. TARE) and overall survival (OS) was defined using propensity score–weighted Kaplan-Meier estimators and propensity score–weighted multivariable Cox regressions.

Results:

Among 2685 patients, 2007 (74.7%) received TARE and 678 (25.3%) received XRT, with increasing usage for both from 2004 to 2015 (P
trend<0.001), but with overall greater uptake and absolute usage of TARE. Patients who received TARE were more likely to have elevated alpha fetoprotein and more advanced stage (P<0.05 for all). Median OS was 14.5 months for the entire cohort. XRT was associated with an OS advantage compared with TARE on propensity score–unadjusted analysis (adjusted hazard ratio [AHR], 0.89; 95% confidence interval, 0.79-1.00; P=0.049), but not on propensity score–adjusted analysis (AHR, 0.99; 95% confidence interval, 0.86-1.13; P=0.829).

Conclusions:

Our study demonstrates that while both XRT and TARE usage have increased with time, there was greater uptake and absolute use of TARE. We found no difference in survival between XRT and TARE after propensity score adjustment.
Focus group reactions to an arts-based educational exhibit on menopausal hot flashes
Authors: Carpenter Janet S. , Schmidt Karen K. , Jarvis Lynsey M. , Lapum Jennifer L. , Kesling Mark D.
Published: June 2019

Objective:

To assess public reactions to an arts-based educational exhibit designed to immerse and engage people in scientific facts to increase their conceptual understanding of hot flashes. Our ultimate goals were to stimulate learning and conversations about menopausal hot flashes to change interactions between menopausal women and providers, and menopausal women and other people (family, friends, etc). Focus groups reacted to the concept art (graphics, miniaturized model); and a questionnaire for quickly assessing reactions.

Methods:

Using a qualitative descriptive methodology, six focus groups of diverse people (n = 50) aged 13 to 64 years described their reactions to the art and questionnaire. Recruitment methods were word of mouth, advertisements on university websites, and a university-based participant registry. Data were analyzed using qualitative content analysis and inductively derived codes.

Results:

Reactions to the concept art were generally favorable. Participants remarked on appealing and less appealing aspects and age appropriateness. Appealing aspects were resonance with women's experiences, clear information, use of symbolism, and overall design. Less appealing aspects lacked resonance, contained confusing information, or unappealing design elements. Participants felt the exhibit should be open to all ages. The final questionnaire reflected participants’ descriptions of the art's ability to stimulate learning, dispel myths, spur dialog, and increase empathy.

Conclusions:

The concept art is an appropriate tool for improving knowledge and communication about hot flashes. Displaying the concept art and/or future full-scale exhibit in healthcare settings or public venues may facilitate learning and communication among three groups—menopausal women, healthcare providers, and others.
Public survey reactions to an arts-based educational menopausal hot flash exhibit
Authors: Carpenter Janet S. , Rand Kevin L. , Schmidt Karen K. , Lapum Jennifer L. , Kesling Mark D.
Published: June 2019

Objective:

The aim of this study was to obtain public survey reactions to concept art for an exhibit about menopausal hot flashes designed to stimulate learning, dispel myths, spur dialogue, and increase empathy.

Methods:

Immediately before viewing the art, participants provided demographic information and answered one open-ended question. Immediately after viewing the art, participants answered the same open-ended question, one additional open-ended question, and completed quantitative survey questions.

Results:

Overall, public reactions to the concept art were positive. Qualitative and quantitative data indicated that the public thought the exhibit was appealing, stimulated learning, dispelled myths, spurred desire to have conversations about hot flashes, and increased empathy for women with menopausal hot flashes.

Conclusions:

The exhibit concept art was appealing and was reported to have a positive impact on the public. Study findings provide support for building the exhibit full-scale as a traveling educational resource that might change public discourse around menopausal hot flashes.