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Objective: Novel and minimally invasive neurotechnologies offer the potential to reduce the burden of epilepsy while avoiding the risks of conventional resective surgery. Few neurotechnologies have been tested in randomized controlled trials with pediatric populations, leaving clinicians to face decisions about whether to recommend these treatments with insufficient evidence about the relevant risks and benefits. This study specifically explores the preferences of clinicians for treating pediatric drug‐resistant epilepsy (DRE) with novel neurotechnologies. Methods: A discrete‐choice experiment (DCE) was designed to elicit the preferences of clinicians with experience in treating children with DRE using novel neurotechnological interventions. The preferences for six key attributes used when making treatment decisions (chances of clinically significant improvement in seizures, major and minor risks from intervention, availability of evidence, financial burden for the family, and access to the intervention) were estimated using a conditional logit model. The estimates from this model were then used to predict the adoption of existing novel neurotechnological interventions. Results: Sixty‐eight clinicians completed the survey: 33 neurosurgeons, 28 neurologists, and 7 other clinicians. Most clinicians were working in the United States (74%), and the remainder (26%) in Canada. All attributes, apart from the nearest location with access to the intervention, influenced preferences significantly. The chance of clinically significant improvement in seizures was the most positive influence on clinician preferences, but low‐quality evidence and a higher risk of major complications could offset these preferences. Of the existing neurotechnological interventions, vagus nerve stimulation was predicted to have the highest likelihood of adoption; deep brain stimulation had the lowest likelihood of adoption. Significance: The preferences of clinicians are drive primarily by the likelihood of achieving seizure freedom for their patients, but preferences for an intervention are largely eradicated if only low quality of evidence supporting the intervention is available. Until better evidence supporting the use of potentially effective, novel neurotechnologies becomes available, clinicians are likely to prefer more established treatments. [ABSTRACT FROM AUTHOR]

In northern Illinois, chronic wasting disease (CWD) was first identified in free‐ranging white‐tailed deer (Odocoileus virginianus; hereafter referred to as "deer") in 2002. To reduce CWD transmission rates in Illinois, wildlife biologists have conducted locally focussed culling of deer since 2003 in areas where CWD has been detected. We used retrospective spatial, temporal and space‐time scan statistical models to identify areas and periods where culling removed higher than expected numbers of CWD‐positive deer. We included 490 Public Land Survey "sections" (∼2.59 km2) from 15 northern Illinois counties in which at least one deer tested positive for CWD between 2003 and 2020. A negative binomial regression model compared the proportion of CWD positive cases removed from sections with at least one CWD case detected in the previous years, "local area 1 (L1)," to the proportion of CWD cases in adjacent sections—L2, L3, and L4—designated by their increasing distance from L1. Of the 14,661 deer removed and tested via culling, 325 (2.22 %) were CWD‐positive. A single temporal CWD cluster occurred in 2020. Three spatial clusters were identified, with a primary cluster located at the border of Boone and Winnebago counties. Four space‐time clusters were identified with a primary cluster in the northern portion of the study area from 2003 to 2005 that overlapped with the spatial cluster. The proportion of CWD cases removed from L1 (3.92, 95% CI, 2.56–6.01) and L2 (2.32, 95% CI, 1.50–3.59) were significantly higher compared to L3. Focussing culling efforts on accessible properties closest to L1 areas results in more CWD‐infected deer being removed, which highlights the value of collaborations among landowners, hunters, and wildlife management agencies to control CWD. Continuous evaluation and updating of the culling and surveillance programs are essential to mitigate the health burden of CWD on deer populations in Illinois. [ABSTRACT FROM AUTHOR]

In case 1, we hypothesise that the cephalohaematoma developed into subgaleal abscess with bacterial seeding from the antecedent urinary tract infection. The blood culture was also negative, white cell count (WCC) was 5.7 × 10 SP 9 sp /L and C-reactive protein (CRP) was 77.4 mg/L. Cranial ultrasound showed a lentiform 8.9 × 6.9 cm collection consistent with a large uncomplicated cephalohaematoma. If the cephalohaematoma does show signs of localised infection with possible extension, appropriate imaging with high diagnostic yield for osteomyelitis (CT or magnetic resonance imaging) is warranted with consideration given to debridement. [Extracted from the article]

Objective: This paper empirically tests the three theories put forward to explain the male marriage premium. Background: Married men continue to earn more than single across the Western world, despite significant changes to family life. Three theories are put forward to explain this phenomenon: (a) Marriage makes men more productive; (b) more productive men select into marriage; (c) employers prefer married men and therefore offer them higher wages. Method: We use a multi‐pronged strategy to test all three theories. First, we analyze a Swiss national panel survey using fixed‐effects regressions with observations matched using entropy balancing, as well as fixed‐effects individual slopes (FEIS) models to isolate the selection effect. Second, we use a factorial survey experiment of over 500 recruiters in Switzerland to study the preferences of employers. Results: Pooled ordinary least squares regressions showed a marriage premium of 11%, which is reduced to approximately 3.5% when accounting for selection and 2.5–3% when introducing controls related to in‐work productivity. The results of the survey experiment showed that employers assign wages 2% higher to married men, with large differences between occupations. They are also more likely to invite married men to a job interview. Conclusion: While selection is found to be the largest contributor to the male marriage premium, it does not explain it fully. Both employer preferences and productivity changes also play a small role. [ABSTRACT FROM AUTHOR]

Colorectal cancer liver metastases (CRCLM) that present with a replacement histopathological growth pattern (HGP) are resistant to neoadjuvant anti‐angiogenic therapy. Surrogate biomarkers are not available to preoperatively identify patients with these tumors. Here we identify differentially expressed genes between CRCLM with a replacement HGP and those with a desmoplastic HGP using RNA sequencing. We demonstrate that LOXL4 is transcriptionally upregulated in replacement HGP CRCLM compared with desmoplastic HGP CRCLM and the adjacent normal liver. Interestingly, lysyl oxidase‐like 4 (LOXL4) protein was expressed by neutrophils present in the tumor microenvironment in replacement HGP CRCLM. We further demonstrate that LOXL4 expression is higher in circulating neutrophils of cancer patients compared with healthy control patients and its expression can be induced by stimulation with lipopolysaccharide and TNF‐α. Our study is the first to show the expression of LOXL4 in neutrophils and reveals the potential for LOXL4‐expressing neutrophils to support the replacement HGP phenotype and to serve as a surrogate biomarker for this subtype of CRCLM. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We give upper bounds on the principal Dirichlet eigenvalue associated to a smoothly bounded domain in a complete Riemannian manifold; the bounds involve [ABSTRACT FROM AUTHOR]

Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally. Accordingly, STK or Syk inhibition decreases the phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk. Our data therefore significantly extend our understanding of which neutrophil responses are governed by STKs and Syk and pinpoint some signaling intermediates that are likely involved. In view of the foremost role of neutrophils in several chronic inflammatory conditions, our findings identify potential molecular targets that could be exploited for future therapeutic intervention. [ABSTRACT FROM AUTHOR]

Neutrophils are generally the first leukocytes to arrive at sites of inflammation or injury, where they release a variety of inflammatory mediators, which contribute to shaping the ensuing immune response. Here, we show that in neutrophils exposed to physiological stimuli (i.e. LPS and TNF-α), inhibition of the PI3K signaling pathway impairs the synthesis and secretion of IL-8, Mip-1α, and Mip-1β. Further investigation showed that Mip-1α and Mip-1β gene transcription was similarly decreased, whereas IL-8 transcription and steady-state mRNA levels were unaffected. Accordingly, PI3K inhibition had no impact on NF-κB or C/EBP activation, which are essential for IL-8 transcription, but the basis for this selective inhibition of chemokine transcription remains elusive. We nevertheless identified translational targets of the PI3K pathway (S6, S6 kinase, 4E-BP1). Inhibitor studies and overexpression experiments further established that the various effects of PI3K on chemokine production can be ascribed to p85α and p110δ subunits. Finally, we show that in LPS- and TNF-activated neutrophils, PI3K acts downstream of the kinases p38 MAPK and TAK1. Given the importance of neutrophils and their products in numerous chronic inflammatory disorders, the PI3K pathway could represent an attractive therapeutic target. [ABSTRACT FROM AUTHOR]

Neutrophils are key players of innate immunity and influence inflammatory and immune reactions through the production of numerous cytokines. Interleukin-18 (IL-18) is known to stimulate several neutrophil responses, and recent evidence suggests that neutrophils might represent a source of IL-18. Here, we show that neutrophils constitutively produce both IL-18 and its antagonist, IL-18BP. Cell activation does not affect IL-18BP release but leads to an increased gene expression and secretion of IL-18, a process that depends on NF-κB activation. Moreover, endogenous IL-18 feeds back on the neutrophils to augment cytokine generation in lipopolysaccharide-treated cells. Accordingly, exogenous IL-18 can induce the gene expression and release of several inflammatory cytokines in neutrophils, including its own expression. We finally report that IL-18 activates the p38 MAPK, MEK/ERK, and PI3K/Akt pathways in neutrophils. The IKK cascade is also activated by IL-18, resulting in IKB-α degradation, NF-κB activation, and RelA phosphorylation. Accordingly, these pathways contribute to the generation of inflammatory cytokines in IL-18-stimulated neutrophils. By contrast, the phosphorylation and DNA-binding activity of various STAT proteins were not induced by IL-18. Collectively, our results unveil new interactions between IL-18 and neutrophils and further support a role for these cells in influencing both innate and adaptive immunity. [ABSTRACT FROM AUTHOR]

The development of a methodologically naturalistic approach to physiological and experimental psychology in the nineteenth century was not primarily driven by a naturalistic agenda. The work of R. Hermann Lotze and G. T. Fechner help to illustrate this claim. I examine a selected set of central commitments in each thinkers philosophical outlook, particularly regarding the human soul and the nature of God, that departed strongly from a reductionist materialism. Yet, each contributed significantly to the formation of experimental and physiological psychology. Their work was influenced substantively by their respective philosophical commitments. Nevertheless, the evaluation of the merits of their specific proposals, Fechner's psychophysics and Lotze's local sign hypothesis respectively, did not depend upon sharing their metaphysical views regarding the human soul or the nature of God. A moderate, but significant, distinction between the contexts of discovery and of justification aids in understanding this balancing act. [ABSTRACT FROM AUTHOR]

This article examines how commerce promotes peace between states. It diverges from the commercial peace literature and its predominant focus on international trade by looking inside the domestic economy to see how its structure influences conflict. Drawing on selectorate theory, I argue that substantial quantities of public property generate fiscal autonomy for governments, strengthen their hold on the domestic reigns of power, and create opportunities to pursue more aggressive foreign policies. A series of statistical tests shows that greater quantities of publicly held assets increase the likelihood that a state will participate in military conflict. Given that the predominance of privately held property is one of the defining institutions of capitalism, these results support the claim that capitalism promotes peace. [ABSTRACT FROM AUTHOR]

The distribution of cytosolic phospholipase A&sub2; (cPLA&sub2;), arachidonate 5-lipoxygenase, and 5-lipoxygenase-activating protein (5-LAP) was investigated in subcellular fractions of human neutrophils disrupted by three techniques. As determined by immunoblot analysis, the bulk of cPLA&sub2; and 5-lipoxygenase was detected in cytosolic fractions of unstimulated neutrophils disrupted by sonication or cavitation. After cell stimulation with the calcium ionophore A23187, both proteins accumulated primarily in nuclei-containing fractions; this accumulation was accompanied by a loss of these enzymes from cytosolic fractions. Further resolution of nuclear fractions revealed that 5-lipoxygenase and cPLA&sub2; were localized in a fraction that contained nuclear membranes. In comparison, 5-LAP was localized to the nuclear-membrane fraction of resting and activated neutrophils, as determined by immunoblotting and photoaffinity labeling. In agreement with the immunoblot data, A23187 stimulation markedly enhanced 5-lipoxygenase enzymatic activity in the nuclear-membrane fraction, which was accompanied by decreased cytosolic 5-lipoxygenase activity. Similarly, neutrophil activation caused increased phosphorylation of cPLA&sub2;, a process that is known to result in enhanced catalytic activity. Our data demonstrate that in activated human neutrophils, the key proteins involved in leukotriene synthesis colocalize at the nuclear membrane, in a catalytically active state. [ABSTRACT FROM AUTHOR]

Discusses the author's experience of asking consent for surgical operation from the First Nations family members of a child patient with brain tumor. Reaction of the patient's mother to the diagnosis; Description of the strength of the family of the patient.