Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair

Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multi-functionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-beta 1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. Copyright (C) 2011 S. Karger AG, Base

Magnetocardiography with a modular spin-exchange relaxation free atomic magnetometer array

We present a portable four-channel atomic magnetometer array operating in the spin exchange relaxation-free regime. The magnetometer array has several design features intended to maximize its suitability for biomagnetic measurement, specifically foetal magnetocardiography, such as a compact modular design, and fibre coupled lasers. The modular design allows the independent positioning and orientation of each magnetometer, in principle allowing for non-planar array geometries. Using this array in a magnetically shielded room, we acquire adult magnetocadiograms. These measurements were taken with a 6-11 fT Hz^(-1/2) single-channel baseline sensitivity that is consistent with the independently measured noise level of the magnetically shielded room.Comment: 15 pages, 5 figure

Model order reduction for seismic waveform modelling: inspiration from normal modes

The computational cost of full waveform simulation in seismological contexts is known to be expensive and generally requires large clusters of computers working in parallel. Although there have been many methods proposed over recent years to reduce this burden, in this work, we focus on a particular method called model order reduction (MOR) whereby a full waveform system of equations is projected onto a lower dimensional space to reduce computational and memory requirements at the cost of introducing approximation errors. In this paper, inspired by normal mode (NM) theory, we use the eigenmodes of the seismic wave equation to span this lower dimensional space. From this we argue that NM theory can be seen as an early form of MOR. Using this as inspiration, we demonstrate how free body oscillations and a form of Petrov–Galerkin projection can be applied in regional scale problems utilizing recent advanced eigensolvers to create a MOR scheme. We also demonstrate how this can be applied to inverse problems. We further conjecture that MOR will have an important role to play in future full waveform applications, particularly those of a time-critical nature such as seismic hazard monitoring

Early adolescent disclosure and parental knowledge regarding online activities: Social anxiety and parental rule-setting as moderators

Early adolescents spend a lot of time online, yet little is currently known about the links between parental rule-setting, adolescent disclosure about online activities, and whether social anxiety may interfere with these processes. Using a longitudinal sample of 526 adolescents (269 girls; Mage = 14.00) and their parents (79% mothers, Mage = 43.66), the results from the current study showed low correspondence between parental knowledge, adolescent disclosure, as well as parents’ and adolescents’ ratings of parental legitimacy to set boundaries about online activities. High social anxiety interacted with high adolescent-rated parental rule-setting in predicting the least disclosure about chatting with strangers and posting online content over time. Also, high social anxiety interacted with low parent-rated control to predict more adolescent disclosure about chatting with strangers and money spent online over time. Thus, social anxiety and parental rule-setting moderated the links between disclosure and knowledge for some early adolescent online activities. Our results conflict with the value typically placed on parental rule-setting in online contexts, at least for socially anxious adolescents

PHarmacist Avoidance or Reductions in Medical Costs in CRITically Ill Adults: PHARM-CRIT Study

OBJECTIVES: To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community hospitals and academic medical centers in the United States. PARTICIPANTS: ICU clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions;$5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions;$9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions;$1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was$418 per intervention, $845 per patient day, and$7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between$3.3:1 and $9.6:1. CONCLUSIONS: Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between$3.3:1 and $9.6:1

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

\ua9 The Author(s) 2024. Background: Neurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality of intellectual and social abilities and common daily functioning. The rapid development of exome sequencing (ES) techniques, together with trio-based analysis, nowadays leads to up to 50% diagnostic yield. Therefore, it is considered as the state-of-the-art approach in these diagnoses. Results: In our study, we present the results of ES in a cohort of 85 families with 90 children with severe NDDs and MCAs. The interconnection of the in-house bioinformatic pipeline and a unique algorithm for variant prioritization resulted in a diagnostic yield of up to 48.9% (44/90), including rare and novel causative variants (41/90) and intragenic copy-number variations (CNVs) (3/90). Of the total number of 47 causative variants, 53.2% (25/47) were novel, highlighting the clinical benefit of ES for unexplained NDDs. Moreover, trio-based ES was verified as a reliable tool for the detection of rare CNVs, ranging from intragenic exon deletions (GRIN2A, ZC4H2 genes) to a 6-Mb duplication. The functional analysis using PANTHER Gene Ontology confirmed the involvement of genes with causative variants in a wide spectrum of developmental processes and molecular pathways, which form essential structural and functional components of the central nervous system. Conclusion: Taken together, we present one of the first ES studies of this scale from the central European region. Based on the high diagnostic yield for paediatric NDDs in this study, 48.9%, we confirm trio-based ES as an effective and reliable first-tier diagnostic test in the genetic evaluation of children with NDDs

Static condensation optimal port/interface reduction and error estimation for structural health monitoring

Having the application in structural health monitoring in mind, we propose reduced port spaces that exhibit an exponential convergence for static condensation procedures on structures with changing geometries for instance induced by newly detected defects. Those reduced port spaces generalize the port spaces introduced in [K. Smetana and A.T. Patera, SIAM J. Sci. Comput., 2016] to geometry changes and are optimal in the sense that they minimize the approximation error among all port spaces of the same dimension. Moreover, we show numerically that we can reuse port spaces that are constructed on a certain geometry also for the static condensation approximation on a significantly different geometry, making the optimal port spaces well suited for use in structural health monitoring

Beliefs about the permissibility of abortion and their relationship to decisions regarding abortion

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43494/1/11111_2004_Article_BF00972499.pd