bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Antimicrobial Drug Usage in Animals: Methods and Applications
Authors: Werner Nicole , McEwen Scott , Kreienbrock Lothar
Published: July 2018

Monitoring antimicrobial drug usage in animals at the national and international levels is important for identification and tracking if and how often quantities are used. This information can be used for many purposes, including raising awareness, comparing use patterns across countries, identifying trends over time, integrating with antimicrobial resistance data, conducting risk assessment, and evaluating the effectiveness of measures to manage antimicrobial usage. The goal of this article is to describe how monitoring systems for antimicrobial drug usage in animals are set up and conducted, using examples from specific countries as well as international efforts. Several key figures and variables are used to describe and evaluate antimicrobial consumption in animals, including the amount in kilograms of active ingredient, standardized units (e.g., number of defined daily dose animals, DDDAs) and number of treatments (e.g., number of used daily doses, UDDA). Data can be collected from a variety of sources including pharmaceutical sales, pharmacy dispensing, veterinary prescriptions, and farm records. In many countries, data analysis and reporting at the national level provide statistics on overall quantities used in animals, in some cases by animal species. Antimicrobial consumption data should be contrasted to the respective animal population, for example, the weight of different categories of livestock and slaughtered animals. Several countries have established antimicrobial usage monitoring systems. Most report overall sales data, but some provide usage data to the levels of animal species and production type. At the international level, several organizations (e.g., European Union, World Organization for Animal Health, World Health Organization) have initiatives to support the development of antimicrobial consumption data collection and reporting. However, these initiatives are ongoing and so far lack harmonization, which will be the biggest challenge for the future.
Antimicrobial Resistance inEscherichia coli
Authors: Poirel Laurent , Madec Jean-Yves , Lupo Agnese , Schink Anne-Kathrin , Kieffer Nicolas , Nordmann Patrice , Schwarz Stefan
Published: July 2018

Multidrug resistance inEscherichia colihas become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide.E. coliis intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms inE. colicorrespond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), andmcrgenes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance inE. coliseems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition,E. coliof animal origin often also show resistances to other—mostly older—antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.
Present and Future Surveillance of Antimicrobial Resistance in Animals: Principles and Practices
Authors: Simjee S. , McDermott P. , Trott D.J. , Chuanchuen R.
Published: July 2018

There is broad consensus internationally that surveillance of the levels of antimicrobial resistance (AMR) occurring in various systems underpins strategies to address the issue. The key reasons for surveillance of resistance are to determine (i) the size of the problem, (ii) whether resistance is increasing, (iii) whether previously unknown types of resistance are emerging, (iv) whether a particular type of resistance is spreading, and (v) whether a particular type of resistance is associated with a particular outbreak. The implications of acquiring and utilizing this information need to be considered in the design of a surveillance system. AMR surveillance provides a foundation for assessing the burden of AMR and for providing the necessary evidence for developing efficient and effective control and prevention strategies. The codevelopment of AMR surveillance programs in humans and animals is essential, but there remain several key elements that make data comparisons between AMR monitoring programs, and between regions, difficult. Currently, AMR surveillance relies on uncomplicated
in vitro
antimicrobial susceptibility methods. However, the lack of harmonization across programs and the limitation of genetic information of AMR remain the major drawbacks of these phenotypic methods. The future of AMR surveillance is moving toward genotypic detection, and molecular analysis methods are expected to yield a wealth of information. However, the expectation that these molecular techniques will surpass phenotypic susceptibility testing in routine diagnosis and monitoring of AMR remains a distant reality, and phenotypic testing remains necessary in the detection of emerging resistant bacteria, new resistance mechanisms, and trends of AMR.
Antimicrobial Resistance in
Mycoplasma
spp
Authors: Gautier-Bouchardon Anne V.
Published: July 2018

Mycoplasmas are intrinsically resistant to antimicrobials targeting the cell wall (fosfomycin, glycopeptides, or β-lactam antibiotics) and to sulfonamides, first-generation quinolones, trimethoprim, polymixins, and rifampicin. The antibiotics most frequently used to control mycoplasmal infections in animals are macrolides and tetracyclines. Lincosamides, fluoroquinolones, pleuromutilins, phenicols, and aminoglycosides can also be active. Standardization of methods used for determination of susceptibility levels is difficult since no quality control strains are available and because of species-specific growth requirements. Reduced susceptibility levels or resistances to several families of antimicrobials have been reported in field isolates of pathogenic
Mycoplasma
species of major veterinary interest:
M. gallisepticum
and
M. synoviae
in poultry;
M. hyopneumoniae
,
M. hyorhinis
, and
M. hyosynoviae
in swine;
M. bovis
in cattle; and
M. agalactiae
in small ruminants. The highest resistances are observed for macrolides, followed by tetracyclines. Most strains remain susceptible to fluoroquinolones. Pleuromutilins are the most effective antibiotics
in vitro
. Resistance frequencies vary according to the
Mycoplasma
species but also according to the countries or groups of animals from which the samples were taken. Point mutations in the target genes of different antimicrobials have been identified in resistant field isolates,
in vitro
-selected mutants, or strains reisolated after an experimental infection followed by one or several treatments: DNA-gyrase and topoisomerase IV for fluoroquinolones; 23S rRNA for macrolides, lincosamides, pleuromutilins, and amphenicols; 16S rRNAs for tetracyclines and aminoglycosides. Further work should be carried out to determine and harmonize specific breakpoints for animal mycoplasmas so that
in vitro
information can be used to provide advice on selection of
in vivo
treatments.
Mechanisms of acute adductor longus injuries in male football players: a systematic visual video analysis
Authors: Serner Andreas , Mosler Andrea Britt , Tol Johannes L , Bahr Roald , Weir Adam
Published: July 2018

Background

Change of direction and kicking have been described as the main actions resulting in adductor longus injury. Video descriptions of inciting events are lacking.

Objective

Perform a standardised visual video analysis of a series of acute adductor longus injuries in football.

Study design

Cross-sectional.

Methods

Video footage was reviewed by players, and assessed independently by five sports medicine professionals. Inciting events were described and categorised using standardised scoring, including playing situation, player/opponent behaviour, movement and body positions.

Results

Videos of acute adductor longus injuries in 17 professional male football players were analysed. Most injuries occurred in non-contact situations (71%), following a quick reaction to a change in play (53%). Injury actions were: change of direction (35%), kicking (29%), reaching (24%) and jumping (12%). Change of direction and reaching injuries were categorised as closed chain movements (59%), characterised by hip extension and abduction with external rotation. Kicking and jumping injuries were categorised as open chain (41%), characterised by a change from hip extension to hip flexion, and hip abduction to adduction, with external rotation.

Conclusion

Acute adductor longus injuries in football occur in a variety of situations. Player actions can be categorised into closed (change of direction and reaching) and open (kicking and jumping) chain movements involving triplanar hip motion. A rapid muscle activation during a rapid muscle lengthening appears to be the fundamental injury mechanism for acute adductor longus injuries.
Cardiovascular mortality and oral antidiabetic drugs: protocol for a systematic review and network meta-analysis
Authors: Goyat Rashmi , Thornton James Douglas , Tan Xi , Kelley George A
Published: July 2018

Introduction

Cardiovascular diseases are the leading cause of morbidity and mortality among individuals with diabetes. Despite the beneficial effects of antidiabetic drugs (ADDs) in terms of lowering haemoglobin A1c, several ADDs have been shown to increase the risk of cardiovascular events. Given the high prevalence of cardiovascular disease among individuals with diabetes, it is important to weigh the benefits of ADDs against their cardiovascular safety. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of different oral pharmacological classes of ADDs on cardiovascular safety.

Methods and analysis

Randomised clinical trials (RCTs) and observational studies published in English up to 31 January 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will be cardiovascular mortality. Secondary outcomes will include all-cause mortality, new event of acute myocardial infarction, stroke (haemorrhagic and ischaemic), hospitalisation for acute coronary syndrome and urgent revascularisation procedures. Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of ADDs that increase cardiovascular mortality.

Dissemination

The results of this study will be presented at a professional conference and submitted to a peer-reviewed journal.

PROSPERO registration number

CRD42017051220.
Speaking up about care concerns in the ICU: patient and family experiences, attitudes and perceived barriers
Authors: Bell Sigall K , Roche Stephanie D , Mueller Ariel , Dente Erica , O’Reilly Kristin , Sarnoff Lee Barbara , Sands Kenneth , Talmor Daniel , Brown Samuel M
Published: July 2018

Background

Little is known about patient/family comfort voicing care concerns in real time, especially in the intensive care unit (ICU) where stakes are high and time is compressed. Experts advocate patient and family engagement in safety, which will require that patients/families be able to voice concerns. Data on patient/family attitudes and experiences regarding speaking up are sparse, and mostly include reporting events retrospectively, rather than pre-emptively, to try to prevent harm. We aimed to (1) assess patient/family comfort speaking up about common ICU concerns; (2) identify patient/family-perceived barriers to speaking up; and (3) explore factors associated with patient/family comfort speaking up.

Methods

In collaboration with patients/families, we developed a survey to evaluate speaking up attitudes and behaviours. We surveyed current ICU families in person at an urban US academic medical centre, supplemented with a larger national internet sample of individuals with prior ICU experience.

Results

105/125 (84%) of current families and 1050 internet panel participants with ICU history completed the surveys. Among the current ICU families, 50%–70% expressed hesitancy to voice concerns about possible mistakes, mismatched care goals, confusing/conflicting information and inadequate hand hygiene. Results among prior ICU participants were similar. Half of all respondents reported at least one barrier to voicing concerns, most commonly not wanting to be a ‘troublemaker’, ‘team is too busy’ or ‘I don’t know how’. Older, female participants and those with personal or family employment in healthcare were more likely to report comfort speaking up.

Conclusion

Speaking up may be challenging for ICU patients/families. Patient/family education about how to speak up and assurance that raising concerns will not create ‘trouble’ may help promote open discussions about care concerns and possible errors in the ICU.
Regulation of indoleamine 2,3 dioxygenase and its role in a porcine model of acute kidney allograft rejection
Authors: Wang Youli , Merchen Todd D , Fang Xuexiu , Lassiter Randi , Ho Chak-Sum , Jajosky Ryan , Kleven Daniel , Thompson Thomas , Mohamed Eslam , Yu Miao , Waller Jennifer L , Nahman N Stanley
Published: July 2018

In kidney transplantation acute allograft rejection is the most common cause of late allograft loss. Changes in indoleamine 2,3 dioxygenase (IDO) activity, which catabolizes the degradation of tryptophan to kynurenine, may predict rejection. However, exogenous IDO is immunosuppressive in rodent kidney transplantation. Thus, the increase in IDO activity observed in acute allograft rejection is insufficient to prevent rejection. To address this question, we assessed the regulation of IDO and its role in acute rejection in a porcine model of kidney transplant. In tissue samples from rejecting kidney allografts, we showed a 13-fold increase in IDO gene transcription and 20-fold increase in IDO enzyme activity when compared with autotransplanted kidneys. Allografts also demonstrated an over fourfold increase in tissue interferon (IFN)-γ, with marked increases in tumor necrosis factor (TNF)-α, TNF-β and interleukin 1β. Gene transcription and protein levels of kynurenine 3-monooxygenase (KMO) were decreased. KMO generates the immunosuppressive kynurenine, 3-hydroxykynurenine. The results of these studies demonstrate a clear association between rejection and increased allograft IDO expression, likely driven in part by IFN-γ and facilitated by other cytokines of the allogeneic response. Moreover, the loss of downstream enzymatic activity in the IDO metabolic pathway may suggest novel mechanisms for the perpetuation of rejection.
Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis
Authors: Cauli Alberto , Dessole Grazia , Piga Matteo , Angioni Maria Maddalena , Pinna Silvia , Floris Alberto , Congia Mattia , Mascia Enrico , Paladini Fabiana , Tedeschi Valentina , Sorrentino Rosa , Fiorillo Maria Teresa , Mathieu Alessandro
Published: July 2018

Background

Ankylosing spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of human leucocyte antigen (HLA)-B27 alleles. HLA-E molecules are non-classical major histocompatibility complex (MHC) class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis.‘’

Objective

To analyse the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27-positive patients with AS and healthy controls (HC) bearing the AS-associated B*2705 and the non-AS-associated B*2709 alleles.

Methods

The level of surface expression of HLA-E molecules on CD14+ peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27-negative HC using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3−CD56+ NK cells.

Results

HLA-E expression in CD14+ cells was significantly higher in patients with AS (587.0, IQR 424–830) compared with B*2705 HC (389, IQR 251.3–440.5; p=0.0007), B*2709 HC (294.5, IQR 209.5–422; p=0.0004) and HLA-B27-negative HC (380, IQR 197.3–515.0; p=0.01). A higher number of NK cells expressing NKG2A compared with NKG2C were found in all cohorts analysed, as well as a higher cell surface density.

Conclusion

The higher surface level of HLA-E molecules in patients with AS compared with HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis, accounting for the previously reported association between HLA-E and AS.
Regular elements determined by generalized inverses
Authors: Alahmadi Adel , Jain S. K. , Leroy André
Published: July 2018

In a semiprime ring, von Neumann regular elements are determined by their inner inverses. In particular, for elements [Formula: see text] of a von Neumann regular ring [Formula: see text], [Formula: see text] if and only if [Formula: see text], where [Formula: see text] denotes the set of inner inverses of [Formula: see text]. We also prove that, in a semiprime ring, the same is true for reflexive inverses.
Asymptotic analysis for affine point processes with large initial intensity
Authors: Yao Nian , Xiao Mingqing
Published: July 2018

In this paper, we consider a generalized stochastic model associated with affine point processes based on several classical models. In particular, we study the asymptotic behavior of the process when the initial intensity is large, i.e. the intensity of arriving events observed initially is considerably larger, which appears in many real applications. For our generalized model, we establish (i) the large deviation principle; (ii) the corresponding functional law of large numbers; (iii) the corresponding central limit theorem, that reflect the fundamentals of the process asymptotic behavior. Our obtained results include existing results as special cases with a more general structure.
A Contact Mechanics Model for Rough Surfaces Based on a New Fractal Characterization Method
Authors: Sun Jianjun , Ji Zhengbo , Zhang Yuyan , Yu Qiuping , Ma Chenbo
Published: July 2018

There are mainly two kinds of contact mechanics models for rough surfaces. One is based on the statistical characteristic parameters and depends on the measurement scale of rough surface topography. The other is based on the fractal parameters, which is independent of the measurement scale. However, most of the contact models for rough surfaces based on fractal theory use the size that is corresponding to the contact area of an asperity or the sample length as the base diameter of an asperity to describe the initial profile of asperities. As a result, the obtained deformation mechanism of asperities is not correct. To solve this problem, a new fractal characterization method for rough surfaces based on the fractal dimension [Formula: see text], fractal roughness [Formula: see text] and the highest asperity height is proposed, and then a fractal contact model independent of the measurement scale is established. The contact mechanism of asperities and variation trends of the real contact area and contact stiffness are discussed. When the contact pressure of the rough surface is less than its yield strength, its normal contact stiffness can be expressed as the first derivative of the contact pressure versus the normal compression, regardless of the deformation forms of asperities.
Solvent-mediated crystalline phases of NixSy anchored on rGO sheets as electrocatalysts for hydrogen evolution application
Authors: Yu Hou Lin , Shi Wenliang , Li Shuaishuai , Zhang Junma , Zhang Xiaobo , Wu Huaping , Zhao Tingyu , Liu Aiping
Published: July 2018

A facile, one-pot solvent-mediated hydrothermal process was adopted to prepare nickel sulfide nanoparticles decorated on reduced graphene oxide (NixSy/rGO) as electrocatalysts for hydrogen evolution reaction (HER). The designed solvent (ethylene glycol and deionized water) played a decisive role in controlling both crystalline phase and morphology of NixSy/rGO composites, leading to pure [Formula: see text]-NiS nanoparticles uniformly distributed on rGO sheets under suitable volume ratio of ethylene glycol and deionized water (2:1). The optimized [Formula: see text]-NiS/rGO showed prominent HER catalytic performance with a rather small Tafel slope of 93[Formula: see text]mV/decade and prominent current density of 10[Formula: see text]mA/cm2 at the overpotential of 177[Formula: see text]mV in alkaline environments when compared to pristine [Formula: see text]-NiS and NiS2/rGO catalysts. The excellent catalytic performance and long-term durability even after 8000 cycles confirmed the potential of [Formula: see text]-NiS/rGO composites as efficient electrocatalysts for HER in the alkaline media.
A portable and low-cost parallel-plate capacitor sensor for alkali and heavy metal ions detection
Authors: Kholimatussadiah Septia , Prijo Tri Anggono
Published: July 2018

A portable and low-cost design of parallel-plate capacitor sensor is proposed and investigated for detection of heavy and alkali metal ions concentration in liquid solution. The application of a thin and long-sided parallel PCB plate allows one to measure the dielectric response of each sample through capacitive sensing technique. The measurements were based on the peak output voltage corresponding to the capacitance of the output measured by an oscilloscope with metal ions concentration of the solution varying from 0 to 10[Formula: see text]ppm and input frequency ranging from 1[Formula: see text]kHz to 10[Formula: see text]MHz. The ICF of Li, Na and K in chloride solution was 2.4, 2.1 and 1.9[Formula: see text]MHz, respectively. The ICF of Na and K in hydroxide solution was 1.5[Formula: see text]MHz and 1.1[Formula: see text]MHz, respectively, while the ICF of Pb(NO[Formula: see text] was 490[Formula: see text]kHz. The detected ICF was applied to further construct the portable sensor system, which is simple in design, low-cost in fabrication and easy to operate. The finding of ICF of each chemical element is necessary to solve the selectivity challenge of the capacitance-based sensor, which will be appropriate for chemical, environmental and engineering applications.
Path-ZVA
Authors: Reijsbergen Daniël , Boer Pieter-Tjerk De , Scheinhardt Werner , Juneja Sandeep
Published: July 2018

We introduce Path-ZVA: an efficient simulation technique for estimating the probability of reaching a rare goal state before a regeneration state in a (discrete-time) Markov chain. Standard Monte Carlo simulation techniques do not work well for rare events, so we use importance sampling; i.e., we change the probability measure governing the Markov chain such that transitions “towards” the goal state become more likely. To do this, we need an idea of distance to the goal state, so some level of knowledge of the Markov chain is required. In this article, we use graph analysis to obtain this knowledge. In particular, we focus on knowledge of the shortest paths (in terms of “rare” transitions) to the goal state. We show that only a subset of the (possibly huge) state space needs to be considered. This is effective when the high dependability of the system is primarily due to high component reliability, but less so when it is due to high redundancies. For several models, we compare our results to well-known importance sampling methods from the literature and demonstrate the large potential gains of our method.
Efficient Simulation for Expectations over the Union of Half-Spaces
Authors: Ahn Dohyun , Kim Kyoung-Kuk
Published: July 2018

We consider the problem of estimating expectations over the union of half-spaces. Such a problem arises in many applications such as option pricing and stochastic activity networks. More recent applications include systemic risk measurements of financial networks. Assuming that random variables follow a multivariate elliptical distribution, we develop a conditional Monte Carlo method and prove its asymptotic efficiencies. We then demonstrate the numerical performance of the proposed method in three different application areas.
An Active Sleep Monitoring Framework Using Wearables
Authors: Hossain H. M. Sajjad , Ramamurthy Sreenivasan R. , Khan Md Abdullah Al Hafiz , Roy Nirmalya
Published: July 2018

Sleep is the most important aspect of healthy and active living. The right amount of sleep at the right time helps an individual to protect his or her physical, mental, and cognitive health and maintain his or her quality of life. The most durative of the Activities of Daily Living (ADL), sleep has a major synergic influence on a person’s fuctional, behavioral, and cognitive health. A deep understanding of sleep behavior and its relationship with its physiological signals, and contexts (such as eye or body movements), is necessary to design and develop a robust intelligent sleep monitoring system. In this article, we propose an intelligent algorithm to detect the microscopic states of sleep that fundamentally constitute the components of good and bad sleeping behaviors and thus help shape the formative assessment of sleep quality. Our initial analysis includes the investigation of several classification techniques to identify and correlate the relationship of microscopic sleep states with overall sleep behavior. Subsequently, we also propose an online algorithm based on change point detection to process and classify the microscopic sleep states. We also develop a lightweight version of the proposed algorithm for real-time sleep monitoring, recognition, and assessment at scale. For a larger deployment of our proposed model across a community of individuals, we propose an active-learning-based methodology to reduce the effort of ground-truth data collection and labeling. Finally, we evaluate the performance of our proposed algorithms on real data traces and demonstrate the efficacy of our models for detecting and assessing the fine-grained sleep states beyond an individual.
Variance and Derivative Estimation of Virtual Performance
Authors: Lin Yujing , Nelson Barry L.
Published: July 2018

Virtual performance is a class of time-dependent performance measures conditional on a particular event occurring at time τ
0
for a (possibly) nonstationary stochastic process; virtual waiting time of a customer arriving to a queue at time τ
0
is one example. Virtual statistics are estimators of the virtual performance. In this article, we go beyond the mean to propose estimators for the variance, and for the derivative of the mean with respect to time, of virtual performance, examining both their small-sample and asymptotic properties. We also provide a modified
K
-fold cross validation method for tuning the parameter
k
for the difference-based variance estimator, and we evaluate the performance of both variance and derivative estimators via controlled studies and a realistic illustration. The variance and derivative provide useful information that is not apparent in the mean of virtual performance.
Atomic and Ionized Microstructures in the Diffuse Interstellar Medium
Authors: Stanimirović Snežana , Zweibel Ellen G.
Published: July 2018

It has been known for half a century that the interstellar medium (ISM) of our Galaxy is structured on scales as small as a few hundred kilometers, more than 10 orders of magnitude smaller than typical ISM structures and energy input scales. In this review we focus on neutral and ionized structures on spatial scales of a few to ∼104 AU, which appear to be highly overpressured, as these have the most important role in the dynamics and energy balance of interstellar gas: the tiny scale atomic structures (TSASs) and extreme scattering events (ESEs) as the most overpressured example of the tiny scale ionized structures (TSISs). We review observational results and highlight key physical processes at AU scales. We present evidence for and against microstructures as part of a universal turbulent cascade and as discrete structures, and we review their association with supernova remnants, the Local Bubble, and bright stars. We suggest a number of observational and theoretical programs that could clarify the nature of AU structures. TSAS and TSIS probe spatial scales in the range of what is expected for turbulent dissipation scales and are therefore of key importance for constraining exotic and not-well-understood physical processes that have implications for many areas of astrophysics. The emerging picture is one in which a magnetized, turbulent cascade, driven hard by a local energy source and acting jointly with phenomena such as thermal instability, is the source of these microstructures.
Weak Lensing for Precision Cosmology
Authors: Mandelbaum Rachel
Published: July 2018

Weak gravitational lensing, the deflection of light by mass, is one of the best tools to constrain the growth of cosmic structure with time and reveal the nature of dark energy. I discuss the sources of systematic uncertainty in weak lensing measurements and their theoretical interpretation, including our current understanding and other options for future improvement. These include long-standing concerns such as the estimation of coherent shears from galaxy images or redshift distributions of galaxies selected on the basis of photometric redshifts, along with systematic uncertainties that have received less attention to date because they are subdominant contributors to the error budget in current surveys. I also discuss methods for automated systematics detection using survey data of the 2020s. The goal of this review is to describe the current state of the field and what must be done so that if weak lensing measurements lead toward surprising conclusions about key questions such as the nature of dark energy, those conclusions will be credible.
The Evolution of Performance Management: Searching for Value
Authors: Pulakos Elaine D. , Mueller-Hanson Rose , Arad Sharon
Published: July 2018

This article reviews the history of performance management (PM), beginning with performance evaluation. We discuss various strategies that have been used to enable accurate ratings as well as cognitive processes and contextual factors that have been shown to significantly impact ratings. We raise questions about the concept of true performance and whether raters can be enabled and motivated to make accurate ratings. We progress to discussing more structured and comprehensive PM processes that typically involve cascading goals, goal setting, competency modeling, evaluation of behavior and results, and implementation. These systems have proven to be tedious and low-value, resulting in unprecedented, wide-spread experimentation with innovative practices to move companies away from heavy PM processes to simpler, cost-effective strategies that actually drive performance. These have ranged from abandoning ratings to implementing innovations in goal-setting, real-time feedback, coaching, and PM behavior change. Directions for future research and practice are discussed.
Estudios Sobre Religión en America Latina
Authors: de la Torre Renée , Martín Eloisa
Published: July 2018

Este artículo presenta una revisión crítica de las contribuciones recientes de la investigación sobre religión en América Latina. Por mucho tiempo, los cientistas sociales han considerado que la religión católica es un rasgo característico de la cultura y las sociedades de esta región, motivo por el cual, los primeros estudios privilegiaron la influencia política de la Iglesia católica con respecto al Estado y a la sociedad en su conjunto. La “otredad” de las religiones vernáculas o populares recibieron menos atención, con investigadores que desvalorizaron la presencia de las religiosidades indígenas y africanas. Sumado a ello, el campo religioso de América Latina está actualmente experimentando un proceso de diversificación y reconfiguración debido en parte al crecimiento de diferentes denominaciones cristianas, particularmente evangélicas y pentecostales. El cambio religioso está también ocurriendo en los márgenes de las Iglesias institucionales a través de las espiritualidades Nueva Era, neopaganas, neoindias, neoesotéricas, y las religiosidades “a mi manera”, así como a través de las hibridaciones de la religiosidad popular, indicando nuevas vías de experimentación de lo sagrado. Esta dinámica propone retos teóricos y conceptuales a los académicos que se dedican a analizar la diversidad religiosa y el rol renovado que las religiones juegan en las sociedades contemporáneas con respecto a la secularización, el sincretismo y la hibridación, así como en su relaci´on con la emergencia de identidades alternativas (de género, sexuales, ideológicas y políticas).
Noninvasive wave intensity analysis predicts functional worsening in children with pulmonary arterial hypertension
Authors: Schäfer Michal , Wilson Neil , Ivy D. Dunbar , Ing Richard , Abman Steven , Browne Lorna P. , Morgan Gareth , Ross Michael , McLennan Daniel , Barker Alex J. , Fonseca Brian , Di Maria Michael , Hunter Kendall S. , Truong Uyen
Published: July 2018

The purpose of the present study was to characterize pulmonary vascular stiffness using wave intensity analysis (WIA) in children with pulmonary arterial hypertension (PAH), compare the WIA indexes with catheterization- and MRI-derived hemodynamics, and assess the prognostic ability of WIA-derived biomarkers to predict the functional worsening. WIA was performed in children with PAH ( n = 40) and healthy control subjects ( n = 15) from phase-contrast MRI-derived flow and area waveforms in the main pulmonary artery (MPA). From comprehensive WIA spectra, we collected and compared with healthy control subjects forward compression waves (FCW), backward compression waves (BCW), forward decompression waves (FDW), and wave propagation speed ( c-MPA). There was no difference in the magnitude of FCW between PAH and control groups (88 vs. 108 mm5·s−1·ml−1, P = 0.239). The magnitude of BCW was increased in patients with PAH (32 vs. 5 mm5·s−1·ml−1, P < 0.001). There was no difference in magnitude of indexed FDW (32 vs. 28 mm5·s−1·ml−1, P = 0.856). c-MPA was increased in patients with PAH (3.2 vs. 1.6 m/s, P < 0.001). BCW and FCW correlated with mean pulmonary arterial pressure, right ventricular volumes, and ejection fraction. Elevated indexed BCW [heart rate (HR) = 2.91, confidence interval (CI): 1.18–7.55, P = 0.019], reduced indexed FDW (HR = 0.34, CI: 0.11–0.90, P = 0.030), and increased c-MPA (HR = 3.67, CI: 1.47–10.20, P = 0.004) were strongly associated with functional worsening of disease severity. Our results suggest that noninvasively derived biomarkers of pulmonary vascular resistance and stiffness may be helpful for determining prognosis and monitoring disease progression in children with PAH.

NEW & NOTEWORTHY Wave intensity analysis (WIA) studies are lacking in children with pulmonary arterial hypertension (PAH) partially because WIA, which is necessary to assess vascular stiffness, requires an invasive pressure-derived waveform along with simultaneous flow measurements. We analyzed vascular stiffness using WIA in children with PAH who underwent phase-contrast MRI and observed significant differences in WIA indexes between patients with PAH and control subjects. Furthermore, WIA indexes were predictive of functional worsening and were associated with standard catheterization measures.
Characterization of a mouse model of obesity-related fibrotic cardiomyopathy that recapitulates features of human heart failure with preserved ejection fraction
Authors: Alex Linda , Russo Ilaria , Holoborodko Volodymir , Frangogiannis Nikolaos G
Published: July 2018

Heart failure with preserved ejection fraction (HFpEF) is caused, or exacerbated by, a wide range of extracardiac conditions. Diabetes, obesity, and metabolic dysfunction are associated with a unique HFpEF phenotype, characterized by inflammation, cardiac fibrosis, and microvascular dysfunction. Development of new therapies for HFpEF is hampered by the absence of reliable animal models. The leptin-resistant db/ db mouse has been extensively studied as a model of diabetes-associated cardiomyopathy; however, data on the functional and morphological alterations in db/ db hearts are conflicting. In the present study, we report a systematic characterization of the cardiac phenotype in db/ db mice, focusing on the time course of functional and histopathological alterations and on the identification of sex-specific cellular events. Although both male and female db/ db mice developed severe obesity, increased adiposity, and hyperglycemia, female mice had more impressive weight gain and exhibited a modest but significant increase in blood pressure. db/ db mice had hypertrophic ventricular remodeling and diastolic dysfunction with preserved ejection fraction; the increase in left ventricular mass was accentuated in female mice. Histological analysis showed that both male and female db/ db mice had cardiomyocyte hypertrophy and interstitial fibrosis, associated with marked thickening of the perimysial collagen, and expansion of the periarteriolar collagen network, in the absence of replacement fibrosis. In vivo and in vitro experiments showed that fibrotic changes in db/ db hearts were associated with increased collagen synthesis by cardiac fibroblasts, in the absence of periostin, α-smooth muscle actin, or fibroblast activation protein overexpression. Male db/ db mice exhibited microvascular rarefaction. In conclusion, the db/ db mouse model recapitulates functional and histological features of human HFpEF associated with metabolic dysfunction. Development of fibrosis in db/ db hearts, in the absence of myofibroblast conversion, suggests that metabolic dysfunction may activate an alternative profibrotic pathway associated with accentuated extracellular matrix protein synthesis.

NEW & NOTEWORTHY We provide a systematic analysis of the sex-specific functional and structural myocardial alterations in db/ db mice. Obese diabetic C57BL6J db/ db mice exhibit diastolic dysfunction with preserved ejection fraction, associated with cardiomyocyte hypertrophy, interstitial/perivascular fibrosis, and microvascular rarefaction, thus recapitulating aspects of human obesity-related heart failure with preserved ejection fraction. Myocardial fibrosis in db/ db mice is associated with a matrix-producing fibroblast phenotype, in the absence of myofibroblast conversion, suggesting an alternative mechanism of activation.
Regional and temporal changes in left ventricular strain and stiffness in a porcine model of myocardial infarction
Authors: Torres William M. , Jacobs Julia , Doviak Heather , Barlow Shayne C. , Zile Michael R. , Shazly Tarek , Spinale Francis G.
Published: July 2018

The aim of the present study was to serially track how myocardial infarction (MI) impacts regional myocardial strain and mechanical properties of the left ventricle (LV) in a large animal model. Post-MI remodeling has distinct regional effects throughout the LV myocardium. Regional quantification of LV biomechanical behavior could help explain changes in global function and thus advance clinical assessment of post-MI remodeling. The present study is based on a porcine MI model to characterize LV biomechanics over 28 days post-MI via speckle-tracking echocardiography (STE). Regional myocardial strain and strain rate were recorded in the circumferential, radial, and longitudinal directions at baseline and at 3, 14, and 28 days post-MI. Regional myocardial wall stress was calculated using standard echocardiographic metrics of geometry and Doppler-derived hemodynamic measurements. Regional diastolic myocardial stiffness was calculated from the resultant stress-strain relations. Peak strain and phasic strain rates were nonuniformly reduced throughout the myocardium post-MI, whereas time to peak strain was increased to a similar degree in the MI region and border zone by 28 days post-MI. Elevations in diastolic myocardial stiffness in the MI region plateaued at 14 days post-MI, after which a significant reduction in MI regional stiffness in the longitudinal direction occurred between 14 and 28 days post-MI. Post-MI biomechanical changes in the LV myocardium were initially limited to the MI region but nonuniformly extended into the neighboring border zone and remote myocardium over 28 days post-MI. STE enabled quantification of regional and temporal differences in myocardial strain and diastolic stiffness, underscoring the potential of this technique for clinical assessment of post-MI remodeling.

NEW & NOTEWORTHY For the first time, speckle-tracking echocardiography was used to serially track regional biomechanical behavior and mechanical properties postmyocardial infarction (post-MI). We found that changes initially confined to the MI region extended throughout the myocardium in a nonuniform fashion over 28 days post-MI. Speckle-tracking echocardiography-based evaluation of regional changes in left ventricular biomechanics could advance both clinical assessment of left ventricular remodeling and therapeutic strategies that target aberrant biomechanical behavior post-MI.
Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal aortic aneurysm
Authors: Yokoyama Utako , Arakawa Noriaki , Ishiwata Ryo , Yasuda Shota , Minami Tomoyuki , Goda Motohiko , Uchida Keiji , Suzuki Shinichi , Matsumoto Masataka , Koizumi Nobusato , Taguri Masataka , Hirano Hisashi , Yoshimura Koichi , Ogino Hitoshi , Masuda Munetaka , Ishikawa Yoshihiro
Published: July 2018

Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified a smooth muscle cell (SMC)-specific biomarker for AAA. We cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium were subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was identified as a SMC-specific protein in the tunica media-derived secretions of all patients. We then examined myosin-11 protein concentrations by ELISA in plasma samples from patients with AAA ( n = 35) and age-matched healthy control subjects ( n = 34). Circulating myosin-11 levels were significantly higher in patients with AAA than control subjects. The area under the receiver-operating characteristic curve (AUC) of myosin-11 was 0.77, with a specificity of 65% at a sensitivity of 91%. Multivariate logistic regression analysis showed a significant association between the myosin-11 level and presence of AAA. When the myosin-11 level was combined with hypertension, it improved the prediction of AAA (AUC 0.88) more than hypertension per se. We then investigated the correlation between aortic diameter and circulating myosin-11 levels using AAA serum samples from patients undergoing endovascular aneurysm repair ( n = 20). Circulating myosin-11 levels were significantly correlated with maximum aortic diameter. Furthermore, changes in myosin-11 concentrations from the baseline 12 mo after endovascular aneurysm repair were associated with those in aortic diameter. These data suggest that circulating levels of myosin-11, which is a SMC-specific myosin isoform, may be useful as a biomarker for AAA.

NEW & NOTEWORTHY Extensive studies have revealed that inflammation- or proteolysis-related proteins are proposed as biomarkers for abdominal aortic aneurysm (AAA). Changes in these protein concentrations are not specific for smooth muscle, which is a major part of AAA pathologies. Hence, no disease-specific circulating markers for AAA are currently available. We found, using secretome-based proteomic analysis on human AAA tunica media, that myosin heavy chain 11 was associated with AAA. Circulating myosin heavy chain 11 may be a new tissue-specific AAA marker.
Transcript profile distinguishes variability in human myogenic progenitor cell expansion capacity
Authors: Riddle Emily S. , Bender Erica L. , Thalacker-Mercer Anna E.
Published: July 2018

Primary human muscle progenitor cells (hMPCs) are commonly used to understand skeletal muscle biology, including the regenerative process. Variability from unknown origin in hMPC expansion capacity occurs independently of disease, age, or sex of the donor. We sought to determine the transcript profile that distinguishes hMPC cultures with greater expansion capacity and to identify biological underpinnings of these transcriptome profile differences. Sorted (CD56+/CD29+) hMPC cultures were clustered by unbiased, K-means cluster analysis into FAST and SLOW based on growth parameters (saturation density and population doubling time). FAST had greater expansion capacity indicated by significantly reduced population doubling time (−60%) and greater saturation density (+200%), nuclei area under the curve (AUC, +250%), and confluence AUC (+120%). Additionally, FAST had fewer % dead cells AUC (−44%, P < 0.05). RNA sequencing was conducted on RNA extracted during the expansion phase. Principal component analysis distinguished FAST and SLOW based on the transcript profiles. There were 2,205 differentially expressed genes (DEgenes) between FAST and SLOW (q value ≤ 0.05); 362 DEgenes met a more stringent cut-off (q value ≤ 0.001 and 2.0 fold-change). DEgene enrichment suggested FAST (vs. SLOW) had promotion of the cell cycle, reduced apoptosis and cellular senescence, and enhanced DNA replication. Novel (RABL6, IRGM1, and AREG) and known (FOXM1, CDKN1A, Rb) genes emerged as regulators of identified functional pathways. Collectively the data suggest that variation in hMPC expansion capacity occurs independently of age and sex and is driven, in part, by intrinsic mechanisms that support the cell cycle.