Nuclear factor of activated T cells (NFAT) was first identified more than two decades ago as a major stimulation-responsive DNA-binding factor and transcriptional regulator in T cells. It is now ...clear that NFAT proteins have important functions in other cells of the immune system and regulate numerous developmental programmes in vertebrates. Dysregulation of these programmes can lead to malignant growth and cancer. This Review focuses on recent advances in our understanding of the transcriptional functions of NFAT proteins in the immune system and provides new insights into their potential roles in cancer development.
Systematic review techniques are about to become the “new normal” in reviews of management research. However, there is not yet much advice on how to organize the sample selection process as part of ...such reviews. This article addresses this void and analyzes this vital part of systematic reviews in more detail. In particular, it offers a critical review of systematic literature reviews published in the Academy of Management Annals and the International Journal of Management Reviews between 2004 and 2018. Based on this methodological literature review, the article presents issues to consider in the most critical choices during the sample selection process. Furthermore, this review identifies several descriptive features such as the mean number of research items included in systematic reviews, the mean number of databases used, and the mean coverage period of such reviews. These numbers may be used as benchmark figures in future reviews.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic therapies in patients with type 2 diabetes mellitus and are associated with improved glycaemic control as well as with ...reductions in body mass and blood pressure. In large cardiovascular outcome trials in patients with diabetes, SGLT2 inhibitors improve cardiovascular and renal outcomes, including hospitalization for heart failure, with this benefit extending to patients without diabetes who have heart failure with reduced ejection fraction. The possible mechanisms of benefit are being extensively investigated because they are unlikely to be related to improved glycaemic control. Early natriuresis with a reduction in plasma volume, a consequent rise in haematocrit, improved vascular function, a reduction in blood pressure and changes in tissue sodium handling are all likely to have a role. Additional mechanisms of SGLT2 inhibitors that might be beneficial include a reduction in adipose tissue-mediated inflammation and pro-inflammatory cytokine production, a shift towards ketone bodies as the metabolic substrate for the heart and kidneys, reduced oxidative stress, lowered serum uric acid level, reduced glomerular hyperfiltration and albuminuria, and suppression of advanced glycation end-product signalling. Further outcome trials and mechanistic studies, including in patients with heart failure with preserved ejection fraction or non-diabetic kidney disease, might identify other possible mechanisms of benefit of SGLT2-inhibitor therapy.
Abstract
Motivation
The Robinson–Foulds (RF) metric is widely used by biologists, linguists and chemists to quantify similarity between pairs of phylogenetic trees. The measure tallies the number of ...bipartition splits that occur in both trees—but this conservative approach ignores potential similarities between almost-identical splits, with undesirable consequences. ‘Generalized’ RF metrics address this shortcoming by pairing splits in one tree with similar splits in the other. Each pair is assigned a similarity score, the sum of which enumerates the similarity between two trees. The challenge lies in quantifying split similarity: existing definitions lack a principled statistical underpinning, resulting in misleading tree distances that are difficult to interpret. Here, I propose probabilistic measures of split similarity, which allow tree similarity to be measured in natural units (bits).
Results
My new information-theoretic metrics outperform alternative measures of tree similarity when evaluated against a broad suite of criteria, even though they do not account for the non-independence of splits within a single tree. Mutual clustering information exhibits none of the undesirable properties that characterize other tree comparison metrics, and should be preferred to the RF metric.
Availability and implementation
The methods discussed in this article are implemented in the R package ‘TreeDist’, archived at https://dx.doi.org/10.5281/zenodo.3528123.
Supplementary information
Supplementary data are available at Bioinformatics online.
Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia.
The authors searched ...for randomized placebo-controlled trials testing systemic α2 agonists administrated in surgical patients and reporting on postoperative cumulative opioid consumption and/or pain intensity. Meta-analyses were performed when data from 5 or more trials and/or 100 or more patients could be combined.
Thirty studies (1,792 patients, 933 received clonidine or dexmedetomidine) were included. There was evidence of postoperative morphine-sparing at 24 h; the weighted mean difference was -4.1 mg (95% confidence interval, -6.0 to -2.2) with clonidine and -14.5 mg (-22.1 to -6.8) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 24 h; the weighted mean difference was -0.7 cm (-1.2 to -0.1) on a 10-cm visual analog scale with clonidine and -0.6 cm (-0.9 to -0.2) with dexmedetomidine. The incidence of early nausea was decreased with both (number needed to treat, approximately nine). Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) and postoperative hypotension (number needed to harm, 20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). Recovery times were not prolonged. No trial reported on chronic pain or hyperalgesia.
Perioperative systemic α2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and arterial hypotension. The impact of α2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.
Stochastic resetting and applications Evans, Martin R; Majumdar, Satya N; Schehr, Grégory
Journal of physics. A, Mathematical and theoretical,
05/2020, Letnik:
53, Številka:
19
Journal Article
Recenzirano
Odprti dostop
In this topical review we consider stochastic processes under resetting, which have attracted a lot of attention in recent years. We begin with the simple example of a diffusive particle whose ...position is reset randomly in time with a constant rate r, which corresponds to Poissonian resetting, to some fixed point (e.g. its initial position). This simple system already exhibits the main features of interest induced by resetting: (i) the system reaches a nontrivial nonequilibrium stationary state (ii) the mean time for the particle to reach a target is finite and has a minimum, optimal, value as a function of the resetting rate r. We then generalise to an arbitrary stochastic process (e.g. Lévy flights or fractional Brownian motion) and non-Poissonian resetting (e.g. power-law waiting time distribution for intervals between resetting events). We go on to discuss multiparticle systems as well as extended systems, such as fluctuating interfaces, under resetting. We also consider resetting with memory which implies resetting the process to some randomly selected previous time. Finally we give an overview of recent developments and applications in the field.
Phylogenetic analysis aims to establish the true relationships between taxa. Different analytical methods, however, can reach different conclusions. In order to establish which approach best ...reconstructs true relationships, previous studies have simulated datasets from known tree topologies, and identified the method that reconstructs the generative tree most accurately. On this basis, researchers have argued that morphological datasets should be analysed by Bayesian approaches, which employ an explicit probabilistic model of evolution, rather than parsimony methods-with implied weights parsimony sometimes identified as particularly inaccurate. Accuracy alone, however, is an inadequate measure of a tree's utility: a fully unresolved tree is perfectly accurate, yet contains no phylogenetic information. The highly resolved trees recovered by implied weights parsimony in fact contain as much useful information as the more accurate, but less resolved, trees recovered by Bayesian methods. By collapsing poorly supported groups, this superior resolution can be traded for accuracy, resulting in trees as accurate as those obtained by a Bayesian approach. By contrast, equally weighted parsimony analysis produces trees that are less resolved and less accurate, leading to less reliable evolutionary conclusions.
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