bluuebunny/crossref_metadata_2025 huggingface dataset:
Key animal welfare issues in commercially raised dairy calves: social environment, nutrition, and painful procedures
Authors: Costa Joao H.C. , Cantor Melissa C. , Adderley Nicola A. , Neave Heather W.
Published: September 2019

Dairy calf welfare concerns are growing and new evidence suggests that the early life environment influences appropriate physical, behavioral, and cognitive development lasting into adulthood. This review highlights key evidence for the impacts of housing, diets, and painful procedures on calf welfare. We argue that these topics are currently critical welfare concerns, but are not the only points of concern. In addition to environmental requirements to maintain optimal health, dairy calves experience other challenges including social and nutritional restrictions. Individual housing is associated with impaired behavioral development and cognitive ability. Pair and group housing can mitigate some of these negative effects and should be encouraged. Restrictive milk allowances (<15% of body weight) lead to poor growth and hunger; these welfare concerns can be addressed with proper enhanced milk allowances and gradual weaning programs. Finally, dehorning is a critical animal welfare issue when pain control is withheld; calves show negative behavioral, physiological, and emotional responses during and after dehorning. The combined use of local anaesthetics and analgesics can mitigate these effects. An industry shift toward providing social companionship, enhanced milk allowances, and pain control during painful procedures would help to improve the welfare of dairy calves in intensive commercial rearing facilities.
Extended review of contractor selection in construction projects
Authors: Khoso Ali Raza , Md Yusof Aminah
Published: September 2019

In construction project management, the contractor plays a primary role. Selection of the contractor is a matter of concern for clients as this is a key player who ensures better performance of a project. This paper structurally investigates the literature from credible databases and renowned journals from 2000 to 2018 in matters related to contractor selection. This investigation sets to accomplish three objectives. Firstly, it includes the identification of criteria and sub-criteria and their organization into a proper classification. Secondly, it highlights the types of decision-making techniques applied in articles published on contractor selection. The third objective covers a detailed investigation of current saturation and gaps of this area of study around the globe. The findings of the research are critically discussed in the light of the literature. As very limited work has been carried out in the area of contractor selection, this paper fills this gap in knowledge in the context of a structured review.
Retinoic acid attenuates cardiac injury induced by hyperglycemia in pre- and post-delivery mice
Authors: Liu Yun , Zhao Jinsong , Lu Meili , Wang Hongxin , Tang Futian
Published: September 2019

The aim of the present study is to explore the effect of retinoic acid (RA) on cardiac injury induced by gestational diabetes mellitus (GDM). GDM mice were given 3 mg/kg RA once daily until the 19th day of pregnancy or the 7th day of post-partum. Compared to normal control and normal pregnant control mice, GDM mice before and after delivery showed significantly cardiac injury. RA treatment attenuated cardiac injury as evidenced by decreased heart mass and left ventricular mass, mRNA expressions of ANP and BNP, and cardiac fibrosis compared with that in GDM mice. The protective effect of RA on GDM cardiomyopathy was related to the decreased MDA content and ROS generation, the increased GSH-Px and SOD content as well as the reduced TNF-α and IL-1β content and inhibition of NF-κB signaling. In addition, RA treatment delayed the continuous rise of blood glucose before delivery and decreased the higher level of glucose after delivery. In conclusion, RA treatment could increase the activity of the antioxidant enzyme and suppress the oxidative stress, inflammation response, and activation of NF-κB signaling, thereby improving blood glucose level and cardiac injury of GDM mice before and after delivery.
Risk factors for anxiety and depression in Chinese patients undergoing surgery for endometrial cancer
Authors: Wang Bin , Li Baohua , Tan Shuai , Zhai Jinguo , Chen Min
Published: September 2019

This study analyzed risk factors for anxiety and depression in 714 patients who received surgery for endometrial cancer. Our data indicate that the incidence of postoperative anxiety and depression in 714 patients with endometrial cancer was 15.55% and 32.77%, respectively. Univariate and logistic regression analysis showed postoperative pain (odds ratio (OR) = 3.166, P = 0.000) and combined liver disease (OR = 2.318, P = 0.001) were independent risk factors for postoperative anxiety. Additionally, CD4+/CD8+ (OR = 0.513, P = 0.042) and natural killer (NK) cell ratios (OR = 0.692, P = 0.021) were independent protective factors for postoperative anxiety. As for depression, low literacy (OR = 1.943, P = 0.042), postoperative pain (OR = 2.671, P = 0.001), high clinical stage (OR = 3.469, P = 0.009), and combined liver disease (OR = 4.865, P = 0.000) were independent risk factors for postoperative depression. CD4+/CD8+ (OR = 0.628, P = 0.002) and NK cell ratio (OR = 0.710, P = 0.013) were independent protective factors for postoperative depression. In conclusion, patients with endometrial cancer have a higher incidence of postoperative anxiety and depression where postoperative pain, liver disease, and decreased immune function are risk factors for both anxiety and depression in these patients.
Fractional hyperviscosity induced growth of bottlenecks in energy spectrum of Burgers equation solutions
Authors: Banerjee Debarghya
Published: September 2019

Energy spectrum of turbulent fluids exhibit a bump at an intermediate wavenumber, between the inertial and the dissipation range. This bump is called bottleneck. Such bottlenecks are also seen in the energy spectrum of the solutions of hyperviscous Burgers equation. Previous work have shown that this bump corresponds to oscillations in real space velocity field. In this paper, we present numerical and analytical results of how the bottleneck and its real space signature, the oscillations, grow as we tune the order of hyperviscosity. We look at a parameter regime α ∈ [1, 2] where α = 1 corresponds to normal viscosity and α = 2 corresponds to hyperviscosity of order 2. We show that even for the slightest fractional increment in the order of hyperviscosity (α) bottlenecks show up in the energy spectrum.

Graphical abstract
Discrete mass-spring structure identification in nonlocal continuum space-fractional model
Authors: Szajek Krzysztof , Sumelka Wojciech
Published: September 2019

This paper considers discrete mass-spring structure identification in a nonlocal continuum space-fractional model, defined as an optimization task. Dynamic (eigenvalues and eigenvectors) and static (displacement field) solutions to discrete and continuum theories are major constituents of the objective function. It is assumed that the masses in both descriptions are equal (and constant), whereas the spring stiffness distribution in a discrete system becomes a crucial unknown. The considerations include a variety of configurations of the nonlocal parameter and the order of the fractional model, which makes the study comprehensive, and for the first time provides insight into the possible properties (geometric and mechanical) of a discrete structure homogenized by a space-fractional formulation.
On symmetries and conservation laws of some spacetimes in f(R, T) gravity
Authors: Bokhari Ashfaque H. , Kara A. H. , Gadjagboui B.
Published: September 2019

We undertake a detailed analysis of the symmetry structures of the plane symmetric and the locally rotationally symmetric (LRS) Bianchi type I spacetimes in the [Formula: see text] gravity. In particular, we construct all the variational symmetries associated with its Lagrangian and, in some cases, construct the associated conservation laws using Noether’s theorem. Giving a comparison between isometries and variational symmetries, we give symmetry structures of some well-known spacetimes.
Machine Learning Education for Artists, Musicians, and Other Creative Practitioners
Authors: Fiebrink Rebecca
Published: September 2019

This article aims to lay a foundation for the research and practice of machine learning education for creative practitioners. It begins by arguing that it is important to teach machine learning to creative practitioners and to conduct research about this teaching, drawing on related work in creative machine learning, creative computing education, and machine learning education. It then draws on research about design processes in engineering and creative practice to motivate a set of learning objectives for students who wish to design new creative artifacts with machine learning. The article then draws on education research and knowledge of creative computing practices to propose a set of teaching strategies that can be used to support creative computing students in achieving these objectives. Explanations of these strategies are accompanied by concrete descriptions of how they have been employed to develop new lectures and activities, and to design new experiential learning and scaffolding technologies, for teaching some of the first courses in the world focused on teaching machine learning to creative practitioners. The article subsequently draws on data collected from these courses—an online course as well as undergraduate and masters-level courses taught at a university—to begin to understand how this curriculum supported student learning, to understand learners’ challenges and mistakes, and to inform future teaching and research.
DNA Sequencing Technologies
Authors: Wong Ka-Chun , Zhang Jiao , Yan Shankai , Li Xiangtao , Lin Qiuzhen , Kwong Sam , Liang Cheng
Published: September 2019

The recent advances in DNA sequencing technology, from first-generation sequencing (FGS) to third-generation sequencing (TGS), have constantly transformed the genome research landscape. Its data throughput is unprecedented and severalfold as compared with past technologies. DNA sequencing technologies generate sequencing data that are big, sparse, and heterogeneous. This results in the rapid development of various data protocols and bioinformatics tools for handling sequencing data.

In this review, a historical snapshot of DNA sequencing is taken with an emphasis on data manipulation and tools. The technological history of DNA sequencing is described and reviewed in thorough detail. To manipulate the sequencing data generated, different data protocols are introduced and reviewed. In particular, data compression methods are highlighted and discussed to provide readers a practical perspective in the real-world setting. A large variety of bioinformatics tools are also reviewed to help readers extract the most from their sequencing data in different aspects, such as sequencing quality control, genomic visualization, single-nucleotide variant calling, INDEL calling, structural variation calling, and integrative analysis. Toward the end of the article, we critically discuss the existing DNA sequencing technologies for their pitfalls and potential solutions.
PlayeRank
Authors: Pappalardo Luca , Cintia Paolo , Ferragina Paolo , Massucco Emanuele , Pedreschi Dino , Giannotti Fosca
Published: September 2019

The problem of evaluating the performance of soccer players is attracting the interest of many companies and the scientific community, thanks to the availability of massive data capturing all the events generated during a match (e.g., tackles, passes, shots, etc.). Unfortunately, there is no consolidated and widely accepted metric for measuring performance quality in all of its facets. In this article, we design and implement PlayeRank, a data-driven framework that offers a principled multi-dimensional and role-aware evaluation of the performance of soccer players. We build our framework by deploying a massive dataset of soccer-logs and consisting of millions of match events pertaining to four seasons of 18 prominent soccer competitions. By comparing PlayeRank to known algorithms for performance evaluation in soccer, and by exploiting a dataset of players’ evaluations made by professional soccer scouts, we show that PlayeRank significantly outperforms the competitors. We also explore the ratings produced by PlayeRank and discover interesting patterns about the nature of excellent performances and what distinguishes the top players from the others. At the end, we explore some applications of PlayeRank—i.e. searching players and player versatility—showing its flexibility and efficiency, which makes it worth to be used in the design of a scalable platform for soccer analytics.
Extraction and Analysis of Fictional Character Networks
Authors: Labatut Vincent , Bost Xavier
Published: September 2019

A
character network
is a graph extracted from a narrative in which vertices represent characters and edges correspond to interactions between them. A number of narrative-related problems can be addressed automatically through the analysis of character networks, such as summarization, classification, or role detection. Character networks are particularly relevant when considering
works of fiction
(e.g., novels, plays, movies, TV series), as their exploitation allows developing information retrieval and recommendation systems. However, works of fiction possess specific properties that make these tasks harder.

This survey aims at presenting and organizing the scientific literature related to the extraction of character networks from works of fiction, as well as their analysis. We first describe the extraction process in a generic way and explain how its constituting steps are implemented in practice, depending on the medium of the narrative, the goal of the network analysis, and other factors. We then review the descriptive tools used to characterize character networks, with a focus on the way they are interpreted in this context. We illustrate the relevance of character networks by also providing a review of applications derived from their analysis. Finally, we identify the limitations of the existing approaches and the most promising perspectives.
How Complex Is Your Classification Problem?
Authors: Lorena Ana C. , Garcia Luís P. F. , Lehmann Jens , Souto Marcilio C. P. , Ho Tin Kam
Published: September 2019

Characteristics extracted from the training datasets of classification problems have proven to be effective predictors in a number of meta-analyses. Among them, measures of classification complexity can be used to estimate the difficulty in separating the data points into their expected classes. Descriptors of the spatial distribution of the data and estimates of the shape and size of the decision boundary are among the known measures for this characterization. This information can support the formulation of new data-driven pre-processing and pattern recognition techniques, which can in turn be focused on challenges highlighted by such characteristics of the problems. This article surveys and analyzes measures that can be extracted from the training datasets to characterize the complexity of the respective classification problems. Their use in recent literature is also reviewed and discussed, allowing to prospect opportunities for future work in the area. Finally, descriptions are given on an R package named Extended Complexity Library (ECoL) that implements a set of complexity measures and is made publicly available.
PPSZ for
k
≥ 5: More Is Better
Authors: Scheder Dominik
Published: September 2019

We show that for
k
≥ 5, the PPSZ algorithm for
k
-SAT runs exponentially faster if there is an exponential number of satisfying assignments. More precisely, we show that for every
k
≥ 5, there is a strictly increasing function
f
: [0,1] → R with
f
(0) = 0 that has the following property. If
F
is a
k
-CNF formula over
n
variables and |sat(F)| = 2

δ
n

solutions, then PPSZ finds a satisfying assignment with probability at least 2

−
c

k

n
−
o
(
n
) +
f
(δ)
n

. Here, 2

−
c

k

n
−
o
(
n
)

is the success probability proved by Paturi et al. [11] for
k
-CNF formulas with a unique satisfying assignment.

Our proof rests on a combinatorial lemma: given a set
S
⊆ { 0,1}

n

, we can partition { 0,1}

n

into subcubes such that each subcube
B
contains exactly one element of
S
. Such a partition
B
induces a distribution on itself, via Pr [
B
] = |B| / 2

n

for each
B
∈
B
. We are interested in partitions that induce a distribution of high entropy. We show that, in a certain sense, the worst case (min

S
: |S| =
s

max

B

H
(
B
)) is achieved if
S
is a Hamming ball. This lemma implies that every set
S
of exponential size allows a partition of linear entropy. This in turn leads to an exponential improvement of the success probability of PPSZ.
New Resolution-Based QBF Calculi and Their Proof Complexity
Authors: Beyersdorff Olaf , Chew Leroy , Janota Mikoláš
Published: September 2019

Modern QBF solvers typically use two different paradigms, conflict-driven clause learning (CDCL) solving or expansion solving. Proof systems for quantified Boolean formulas (QBFs) provide a theoretical underpinning for the performance of these solvers, with Q-Resolution and its extensions relating to CDCL solving and ∀Exp+Res relating to expansion solving. This article defines two novel calculi, which are resolution-based and enable unification of some of the principal existing resolution-based QBF calculi, namely Q-resolution, long-distance Q-resolution and the expansion-based calculus ∀Exp+Res.

However, the proof complexity of the QBF resolution proof systems is currently not well understood. In this article, we completely determine the relative power of the main QBF resolution systems, settling in particular the relationship between the two different types of resolution-based QBF calculi: proof systems for CDCL-based solvers (Q-resolution, universal, and long-distance Q-resolution) and proof systems for expansion-based solvers (∀Exp+Res and its generalizations IR-calc and IRM-calc defined here).

The most challenging part of this comparison is to exhibit hard formulas that underlie the exponential separations of the aforementioned proof systems. To this end, we exhibit a new and elegant proof technique for showing lower bounds in QBF proof systems based on strategy extraction. This technique provides a direct transfer of circuit lower bounds to lengths-of-proofs lower bounds. We use our method to show the hardness of a natural class of parity formulas for Q-resolution and universal Q-resolution. Variants of the formulas are hard for even stronger systems such as long-distance Q-resolution and extensions.

With a completely different and novel counting argument, we show the hardness of the prominent formulas of Kleine Büning et al. [51] for the strong expansion-based calculus IR-calc.
Revisiting the Fates of Dead Leaves That Fall into Streams
Authors: Marks Jane C.
Published: September 2019

As terrestrial leaf litter decomposes in rivers, its constituent elements follow multiple pathways. Carbon leached as dissolved organic matter can be quickly taken up by microbes, then respired before it can be transferred to the macroscopic food web. Alternatively, this detrital carbon can be ingested and assimilated by aquatic invertebrates, so it is retained longer in the stream and transferred to higher trophic levels. Microbial growth on litter can affect invertebrates through three pathways, which are not mutually exclusive. First, microbes can facilitate invertebrate feeding, improving food quality by conditioning leaves and making them more palatable for invertebrates. Second, microbes can be prey for invertebrates. Third, microbes can compete with invertebrates for resources bound within litter and may produce compounds that retard carbon and nitrogen fluxes to invertebrates. As litter is broken down into smaller particles, there are many opportunities for its elements to reenter the stream food web. Here, I describe a conceptual framework for evaluating how traits of leaf litter will affect its fate in food webs and ecosystems that is useful for predicting how global change will alter carbon fluxes into and out of streams.
The Arms Race Between KRAB–Zinc Finger Proteins and Endogenous Retroelements and Its Impact on Mammals
Authors: Bruno Melania , Mahgoub Mohamed , Macfarlan Todd S.
Published: September 2019

Nearly half of the human genome consists of endogenous retroelements (EREs) and their genetic remnants, a small fraction of which carry the potential to propagate in the host genome, posing a threat to genome integrity and cell/organismal survival. The largest family of transcription factors in tetrapods, the Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs), binds to specific EREs and represses their transcription. Since their first appearance over 400 million years ago, KRAB-ZFPs have undergone dramatic expansion and diversification in mammals, correlating with the invasions of new EREs. In this article we review our current understanding of the structure, function, and evolution of KRAB-ZFPs and discuss growing evidence that the arms race between KRAB-ZFPs and the EREs they target is a major driving force for the evolution of new traits in mammals, often accompanied by domestication of EREs themselves.
Collective Choice, Collaboration, and Communication
Authors: Stasser Garold , Abele Susanne
Published: September 2019

This article reviews recent empirical research on collective choice and collaborative problem solving. Much of the collective choice research focuses on hidden profiles. A hidden profile exists when group members individually have information favoring suboptimal choices but the group collectively has information favoring an optimal choice. Groups are notoriously bad at discovering optimal choices when information is distributed to create a hidden profile. Reviewed work identifies informational structures, individual processing biases, and social motivations that inhibit and facilitate the discovery of hidden profiles. The review of collaborative problem-solving research is framed by Larson's concept of synergy. Synergy refers to performance gains that are attributable to collaboration. Recent research has addressed factors that result in groups performing as well as their best member (weak synergy) and better than their best member (strong synergy). Communication dynamics underlying both collective choice and collaborative problem solving are discussed.
Unfairness and Radicalization
Authors: van den Bos Kees
Published: September 2019

This article reviews the relationship between people's perceptions of unfairness and their tendencies to think, feel, and act in radicalizing ways. Various theories of radicalization processes are reviewed that examine key aspects of the psychology of perceived unfairness. The review shows that experienced group deprivation and perceived immorality are among the core judgments that can drive Muslim radicalization, right-wing radicalization, and left-wing radicalization. Symbols of injustice, the legitimization of revolutionary thought, and the experience of unfair treatment can also increase radicalization. The review also examines core moderators (e.g., uncertainty and insufficient self-correction) and mediators (e.g., externally oriented emotions) of the linkage between perceived unfairness and core components of radicalization (e.g., rigidity of thoughts, hot-cognitive defense of cultural worldviews, and violent rejection of democratic principles and the rule of law). The review discusses how the study of unfairness and radicalization contributes to a robust and meaningful science of psychology.
Venous return and the physical connection between distribution of segmental pressures and volumes
Authors: Brengelmann George L.
Published: September 2019

More than sixty years ago, Guyton and coworkers related their observations of venous return to a mathematical model. Showing steady-state flow (F) as proportional to the difference between mean systemic pressure (Pms) and right atrial pressure (Pra), the model fit their data. The parameter defined by the ratio (Pms − Pra)/F, first called an “impedance,” came to be called the “resistance to venous return.” The interpretation that Pra opposes Pms and that, to increase output, the heart must act to reduce back pressure at the right atrium was widely accepted. Today, the perceived importance of Pms is evident in the efforts to find reliable ways to estimate it in patients. This article reviews concepts about venous return, criticizing some as inconsistent with elementary physical principles. After review of basic background topics—the steady-state vascular compliance; stressed versus unstressed volume—simulations from a multicompartment model based on data and definitions from Rothe’s classical review of the venous system are presented. They illustrate the obligatory connection between flow-dependent compartment pressures and the distribution of volume among vascular compartments. An appendix shows that the pressure profile can be expressed either as decrements relative to arterial pressure or as increments relative to Pra (the option taken in the original model). Conclusion: The (Pms − Pra)/F formulation was never about Pms physically driving venous return; it was about how intravascular volume distributes among compliant compartments in accordance with their flow-dependent distending pressures, arbitrarily expressed relative to Pra rather than arterial pressure.
GATA3-Controlled Nucleosome Eviction Drives MYC Enhancer Activity in T-cell Development and Leukemia
Authors: Belver Laura , Yang Alexander Y. , Albero Robert , Herranz Daniel , Brundu Francesco G. , Quinn S. Aidan , Pérez-Durán Pablo , Álvarez Silvia , Gianni Francesca , Rashkovan Marissa , Gurung Devya , Rocha Pedro P. , Raviram Ramya , Reglero Clara , Cortés Jose R. , Cooke Anisha J. , Wendorff Agnieszka A. , Cordó Valentina , Meijerink Jules P. , Rabadan Raúl , Ferrando Adolfo A.
Published: September 2019

Long-range enhancers govern the temporal and spatial control of gene expression; however, the mechanisms that regulate enhancer activity during normal and malignant development remain poorly understood. Here, we demonstrate a role for aberrant chromatin accessibility in the regulation of MYC expression in T-cell lymphoblastic leukemia (T-ALL). Central to this process, the NOTCH1-MYC enhancer (N-Me), a long-range T cell–specific MYC enhancer, shows dynamic changes in chromatin accessibility during T-cell specification and maturation and an aberrant high degree of chromatin accessibility in mouse and human T-ALL cells. Mechanistically, we demonstrate that GATA3-driven nucleosome eviction dynamically modulates N-Me enhancer activity and is strictly required for NOTCH1-induced T-ALL initiation and maintenance. These results directly implicate aberrant regulation of chromatin accessibility at oncogenic enhancers as a mechanism of leukemic transformation.

Significance:

MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. Here, we show a major role for GATA3-mediated enhancer nucleosome eviction as a driver of MYC expression and leukemic transformation. These results support the role of aberrant chromatin accessibility and consequent oncogenic MYC enhancer activation in NOTCH1-induced T-ALL.

This article is highlighted in the In This Issue feature, p. 1631
Predictores de la terminación de la terapia de presión positiva en las vías aéreas en pacientes con apnea obstructiva del sueño
Authors: Romero-López Zaira
Published: September 2019

Background: There is a lack of robust data about factors predicting continuation (or termination) of positive airway pressure therapy (PAP) for sleep apnea. This analysis of big data from a German homecare provider describes patients treated with PAP, analyzes the therapy termination rate over the first year, and investigates predictive factors for therapy termination. Methods: Data from a German homecare service provider were analyzed retrospectively. Patients who had started their first PAP therapy between September 2009 and April 2014 were eligible. Patient demographics, therapy start date, and the date of and reason for therapy termination were obtained. At 1 year, patients were classified as having compliance-related therapy termination or remaining on therapy. These groups were compared, and significant predictors of therapy termination determined. Results: Of 98,329 patients included in the analysis, 11,702 (12%) terminated PAP therapy within the first year (after mean 171 ± 91 days). There was a U-shaped relationship between therapy termination and age; therapy termination was higher in the youngest (<30 years, 15.5%) and oldest (≥ 80 years, 19.8%) patients, and lower in those aged 50-59 years (9.9%). Therapy termination was significantly more likely in females versus males (hazard ratio 1.48, 95% confidence interval 1.42-1.54), in those with public versus private insurance (1.75, 1.64-1.86) and in patients whose first device was automatically adjusting or fixed-level continuous positive airway pressure versus bilevel or adaptive servo-ventilation (1.28, 1.2-1.38). Conclusions: This analysis of the largest dataset investigating PAP therapy termination identified a number of predictive factors. These can help health care providers chose the most appropriate PAP modality, identify specific patient phenotypes at higher risk of stopping PAP and target interventions to support ongoing therapy to these groups, as well as allow them to develop a risk stratification tool.
Neumonía adquirida en la comunidad: Seguridad cardíaca del tratamiento con antibióticos en pacientes hospitalizados
Authors: Torre-Bouscoulet Luis
Published: September 2019

Background: Guidelines recommend macrolides and fluoroquinolones in patients hospitalized with communityacquired pneumonia (CAP), but their use has been associated with cardiac events. We quantified associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards. Methods: This was a post-hoc analysis of a cluster-randomized trial as a cohort study; including patients with a working diagnosis of CAP admitted to non-ICU wards without a cardiac event on admission. We calculated causespecific hazard ratio's (HR's) for effects of time-dependent macrolide and fluoroquinolone exposure as compared to beta-lactam monotherapy on cardiac events, defined as new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization. Results: Cardiac events occurred in 146 (6.9%) of 2107 patients, including heart failure (n = 101, 4.8%), arrhythmia (n = 53, 2.5%), and myocardial ischemia (n = 14, 0.7%). These occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. HR's for erythromycin, compared to beta-lactam monotherapy, on any cardiac event and heart failure were 1.60 (95% CI 1.09;2.36) and 1.89 (95% CI 1.22;2.91), respectively. HR's for levofloxacin and moxifloxacin, compared to beta-lactam monotherapy, on any cardiac event were 0.40 (95% CI 0.18;0.87)and 0.56 (95% CI 0.36;0.87), respectively. Findings remained consistent after adjustment for confounders and/or in a sensitivity analysis of radiologically confirmed CAP (n = 1604, 76.1%). Conclusions: Among patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure. Although our study does not fully exclude confounding bias, findings remained largely unchanged in crude, adjusted, and sensitivity analyses. These findings may caution the use of erythromycin as empirical therapy in these patients.
Tuberculosis: Estrategias futuras para una enfermedad antigua
Authors: Pérez-Guzmán Carlos , Barrera-Rodríguez Raúl , Pérez-Malagon Carlos David
Published: September 2019

The emergence and spread of drug-resistant strains of Mycobacterium tuberculosis is worsening the global threat of tuberculosis (TB). There is a need and urgency for the development of new treatments for TB, for the management of drug resistant TB (MDR-TB) and for improved regimens against drug-susceptible TB, with the goal of reducing toxicity and length of therapy that will boost patience compliance. The paucity of new drugs is a major obstacle to design new regimens while host-directed therapies (HDTs) are emerging as a promising area of research and are opening new avenues to fight TB. In this review, we discuss examples of potentially promising strategies aimed at improving the host response to M. tuberculosis, and argue how a better understanding of TB pathogenesis, with the fine characterization of the immun ological mediators involved, may pave the way for the design of new therapies, the identification of new drugs or the repurposing of some already in use for other diseases. We emphasize that any HDTs shall be included as adjunct therapy to the drug-combination regimens already in use for TB, with the goal to reduce tissue damage and immunopathology and enhance bacterial clearance. We anticipate that the benefits of HDTs against TB will be highest against MDR-TB, where the activity of current regimens is poor and the cost high.
Mineralocorticoid Receptor Antagonists Stimulate Human Hair Growth ex vivo
Authors: Hundt Jennifer E. , Sass Stephanie , Funk Wolfgang , Bíró Tamás , Farman Nicolette , Langan Ewan A. , Paus Ralf
Published: September 2019

Whilst topical steroids represent one of the most frequently administered treatments for skin and hair diseases, predominantly based on their glucocorticoid receptor-mediated anti-inflammatory effects, the mineralocorticoid effects of topical steroids have received surprisingly little attention. However, the role of mineralocorticoid receptor (MR) signaling is now known to extend beyond the kidney, with human skin, including the hair follicle (HF), expressing the MR. Using microdissected female HFs treated ex vivo with MR agonists and antagonists, we sought to determine the effects of MR-mediated signaling in the cutaneous context. Indeed, not only did the skin and HF epithelium express the MR at both the gene and protein level, but its expression was hair cycle dependent. Moreover, the selective MR antagonist eplerenone promoted hair shaft elongation and hair matrix keratinocyte proliferation whilst delaying catagen (HF regression). These novel observations suggest that the female human HF is sensitive to the inhibition of MR signaling and provide the first evidence that sustained MR signaling may even be required to maintain the growth phase (anagen) of human scalp HFs. Indeed, these data encourage the systematic evaluation of MR agonists and antagonists in human hair growth control so as to identify much-needed, novel anti-hirsutism and/or hair growth-promoting agents, respectively.
Life-Threatening Extrarenal Manifestations in an Infant with Atypical Hemolytic Uremic Syndrome Caused by a Complement 3-Gene Mutation
Authors: Han Sa Ra , Cho Myung Hyun , Moon Jin Soo , Ha Il Soo , Cheong Hae Il , Kang Hee Gyung
Published: September 2019

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment caused by uncontrolled activation of the complement system. About 20% of patients show extrarenal manifestations, with central nervous system involvement being the most frequent. We described the clinical course and management of aHUS in an infant, that was caused by a complement 3 (C3) gene mutation with severe extrarenal manifestations. Case Presentation: A 4-month-old girl visited our hospital for jaundice and petechiae. Laboratory tests revealed microangiopathic hemolytic anemia, thrombocytopenia, and hyperazotemia. She was diagnosed with aHUS with a C3 p.E1160K mutation. Daily fresh-frozen plasma (FFP) therapy was administered; however, she experienced the severe extrarenal manifestations of pulmonary hemorrhage and gastrointestinal bleeding. With aggressive treatment, supportive care, and daily FFP transfusion, the patient recovered and was discharged after 72 days of hospital stay, on a regular FFP transfusion. Four months after diagnosis, she was switched to eculizumab treatment. Twenty months have passed since then and she has been relapse-free until now. Conclusion: aHUS is rare but has a devastating course if not properly treated. Severe extrarenal manifestations, such as pulmonary hemorrhage and gastrointestinal bleeding, can develop in aHUS caused by a C3 mutation. In our case, long-term management with eculizumab resulted in relapse-free survival.
Lifestyle Interventions for Weight Management in People with Serious Mental Illness: A Systematic Review with Meta-Analysis, Trial Sequential Analysis, and Meta-Regression Analysis Exploring the Mediators and Moderators of Treatment Effects
Authors: Speyer Helene , Jakobsen Ane Storch , Westergaard Casper , Nørgaard Hans Christian Brix , Pisinger Charlotta , Krogh Jesper , Hjorthøj Carsten , Nordentoft Merete , Gluud Christian , Correll Christoph U. , Jørgensen Kirstine Bro
Published: September 2019

Background: Serious mental illness (SMI) reduces life expectancy, primarily due to somatic comorbidity linked to obesity. Meta-analyses have found beneficial effects of lifestyle interventions in people with SMI and recommended their implementation to manage obesity. Objective: The objective of this systematic review was to assess the benefits and harms of individualized lifestyle interventions for weight in people diagnosed with SMI and to explore potential mediators and moderators of the effect. Methods: The protocol was registered at PROSPERO (CRD42016049093). Randomized clinical trials (RCTs) assessing the effect of individualized lifestyle interventions on weight management in people with SMI were included. Primary outcomes were differences in endpoint body mass index (BMI) and the proportion achieving clinically relevant weight loss (≥5%). Secondary outcomes included quality of life, cardiometabolic risk factors, and adverse effects. Results: We included 41 RCTs (n = 4,267). All trials were at high risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. The experimental interventions reduced the mean difference in BMI by –0.63 kg/m2 (95% confidence interval [CI] = –1.02 to –0.23; p = 0.002; I2 = 70.7%) compared to the control groups. At postintervention follow-up (17 RCTs), the effect size remained similar but was no longer significant (BMI = –0.63 kg/m2; 95% CI = –1.30 to 0.04; p = 0.07; I2 = 48.8%). The risk ratio for losing ≥5% of baseline weight was 1.51 (95% CI = 1.07–2.13; p = 0.02) compared to the control groups. GRADE showed very low or low quality of evidence. Conclusion: There is a statistically significant, but clinically insignificant, mean effect of individualized lifestyle interventions for weight reduction in people with SMI.
Evaluating the Outcome of Two Different Regimes in Adhesive Capsulitis: A Prospective Clinical Study
Authors: Anjum Rashid , Aggarwal Jatin , Gautam Rakesh , Pathak Subodh , Sharma Aryan
Published: September 2019

Objective: Adhesive capsulitis or frozen shoulder is a painful condition affecting up to 5% of the general population. We conducted this study with the aim of evaluating the results of physiotherapy plus intra-articular methylprednisolone injection versus physiotherapy alone in idiopathic frozen shoulder. Methods: This prospective clinical study was conducted in a tertiary care center between August 2016 and August 2018. Patients who were diagnosed with idiopathic frozen shoulder were included in the study, and each patient was randomly allocated to one of two groups: physiotherapy alone (group A) and physiotherapy plus intra-articular steroid injection (group B). Results: A total of 52 cases diagnosed with idiopathic frozen shoulder were included and treated with the two modalities. There was a significant improvement in group B compared to group A at 6 weeks and 3 months in the range of flexion, abduction, and external rotation. The Shoulder Pain and Disability Index showed improvement in both pain and disability score in group B ­compared to group A, and improvement was significant at 6 weeks and 3 months. Conclusion: The results demonstrate the advantages of physiotherapy plus intra-articular steroid injection in idiopathic frozen shoulder. The predictability of results with physiotherapy plus intra-articular steroid injection in selected patients is excellent, and it is a better modality of treatment compared to physiotherapy alone.
Detection of Device-Related Thrombosis Following Left Atrial Appendage Occlusion
Authors: Korsholm Kasper , Jensen Jesper Møller , Nørgaard Bjarne Linde , Nielsen-Kudsk Jens Erik
Published: September 2019

Background:

Device-related thrombosis (DRT) following left atrial appendage occlusion is a rare but feared complication. The diagnostic value of cardiac compute tomography (CT) for detection of DRT is unknown. This study sought to evaluate the clinical value of cardiac CT for detection of DRT using transesophageal echocardiography (TEE) as the reference standard and to provide insights into the causes, natural history, and risk of DRT.

Methods:

We reviewed 301 consecutive patients undergoing left atrial appendage occlusion at Aarhus University Hospital, Denmark, between 2010 and 2017. Of these, 248 patients had cardiac CT and TEE imaging available at 8-week follow-up; 139 had complete 12-month imaging. A blinded investigator analyzed all images. On TEE, an echo-dense mass attached to the device was defined as DRT. Cardiac CT was analyzed for presence of hypoattenuated thickening (HAT) on the device, which was subclassified as low grade or high grade. High-grade HAT was considered as definite DRT.

Results:

At 8 weeks, TEE detected 5 (2%) cases with DRT; and cardiac CT 6 (2.4%) cases with high-grade HAT. At 12 months, both TEE and cardiac CT detected 2 (1.4%) cases with DRT or high-grade HAT, respectively. Cardiac CT demonstrated low-grade HAT in 9 (3.6%) cases at 8 weeks; and 13 cases (9.4%) at 12-months. High-grade HAT/DRT was associated with thromboembolism in 2 cases, whereas low-grade HAT was not related to embolic events. Low-grade HAT resolved spontaneously over time.

Conclusions:

Cardiac CT seems equally good as TEE for detection of DRT. In addition, cardiac CT demonstrates cases with low-grade HAT, not visualized by TEE. The clinical significance hereof requires further investigation.
Ballot Measures and Subversion of Direct Democracy: Initiatives to Outlaw Aerial Wolf Killing in Alaska
Authors: Simon Alexander , Clark Steven C.
Published: September 2019

Activists often utilize ballot measures to protect wildlife. However, state executive branches may employ a variety of means to subvert direct democracy. We examine some of these tactics via a case study of two nearly identical ballot initiatives that were intended to outlaw the aerial killing of wolves in Alaska. In the first case, the language that appeared on the ballot was created by an executive branch sympathetic to the measure. In the second case, the ballot language was created by an executive branch opposed to the measure. In the first case, the ballot language accurately communicated the intent of the initiative and it passed. In the second case, it did not communicate the intent of the initiative or pass. Moreover, in the second case, the Palin administration utilized public funds to persuade voters not to support the initiative.
Towards a Fresh Engagement in Rule-of-Law Cooperation: Supporting the Compliance Movement in Russia
Authors: Kruessmann Thomas
Published: September 2019

Rule-of-law dialogue between the West and Russia has effectively run into a dead end. This paper attempts to open up a new perspective by addressing the corporation as a sub-unit of society. Observing that Russia, before adopting a comprehensive legal framework for risk management in Summer 2018, has had almost 20 years of experience in various approaches to risk management and corporate compliance, the question is whether corporate law has finally reached the point of shedding some of the characteristic features of Russian law in general to turn the corporate sphere into a space in which citizens are able to pursue their business interests in a safe and legally protected manner. Thus, we may be on the eve of witnessing the emergence of a rule-of-law culture outside the traditional domain of citizen-state relations. This would open up avenues for a renewed dialogue on rule of law between the West and Russia.
Work in the Teachings of R. Ẓvi Yehudah Kook
Authors: Mashiach Amir
Published: September 2019

R. Ẓvi Yehudah ha-Kohen Kook (RẒiYah, 1891–1982), the head of the yeshivah at “Merkaz ha-Rav” in Jerusalem, was one of the most prominent religious Zionist leaders of the twentieth century. He was also the son of R. Abraham Isaac ha-Kohen Kook, a relationship that had a decisive impact on his thought and work throughout his life. The purpose of the present study is to shed light on RẒiYah’s attitude toward work. Did he see work as a basic human obligation spelled out by the physical need for survival? Did he associate an ideological value with work, as part of a worldview integrating religious values with extra-religious ones, similar to socialism? Or did he see work as a religious value, one that stemmed from his theology?
The cicada genus Muda Distant (Hemiptera: Cicadidae) from Sundaland: species and relationships
Authors: Duffels J.P.
Published: September 2019

A diagnosis is provided of the cicada genus Muda
Distant, 1897, with descriptions, illustrations and distribution maps for the five species found in Sundaland. Three of these, Muda obtusa (Walker, 1858), M. virguncula (Walker, 1856) and M. tua Duffels, 2004, are redescribed. Muda beccarii (Distant, 1888) and M. concolor
Distant, 1897 are junior synonyms of M. virguncula. Abroma tahanensis (Moulton, 1923) is transferred to Muda and redescribed. Muda kinabaluana is described as new to science, and is very peculiar, missing the timbals. An identification key is provided. Characters and taxonomic position of Muda kuroiwae (Matsumura, 1913) from the Ryukyu Islands of southern Japan are discussed. Muda is characterized by two supposed synapomorphies, viz., the mediodorsal carina of the male pygofer and the movable upper pygofer lobes; these characters are also found in species of Katoa. Further comparative study of Muda and Katoa is needed to reveal their relationships.