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Background Little is known about surgical site infection (SSI) risk among pediatric patients with reported beta-lactam allergy (BLA). Methods We performed a retrospective cohort study at a quaternary children’s hospital and compared procedures in patients ages 1–19 years old with and without BLA that required antimicrobial prophylaxis (AMP) during 2010–2017. Procedures were matched 1:1 by patient age, complex chronic conditions, year of surgery, and National Surgical Quality Improvement Program current procedural terminology category. The primary outcome was SSI as defined by National Healthcare Safety Network. The secondary outcome was AMP protocol compliance as per American Society of Health-System Pharmacists. Results Of the 11 878 procedures identified, 1021 (9%) had a reported BLA. There were 35 (1.8%) SSIs in the matched cohort of 1944 procedures with no significant difference in SSI rates in BLA procedures (1.8%) compared to no-BLA (1.9%) procedures. Tier 3 AMP was chosen more frequently among BLA procedures (P < .01). Unmatched analysis of all procedures showed that 23.7% of BLA procedures received beta-lactam-AMP (vs. 93.7% of procedures without BLA). There were no major differences in SSI on sensitivity analysis of BLA procedures that did not receive beta-lactam AMP (1.4%) compared to no-BLA procedures with beta-lactam AMP (1.6%). Conclusions Our retrospective matched analysis of 1944 pediatric procedures found no increase in SSIs in procedures with reported BLA, which differs from studies in adults. We observed that the choice of beta-lactam-AMP was common, even in BLA procedures. More data are needed to delineate an association between non-beta-lactam AMP and SSI in children.

Purpose To describe the proportion of children with an index hospitalization in 2014 who had established long-term invasive ventilator dependence (LTVD), and determine regional variation in hospital length of stay, charges, and readmissions. Design and methods Multicenter, longitudinal, retrospective cohort study using a recently established algorithm to identify children with LTVD from the Pediatric Health Information System database with an index hospitalization at least once during 2014, excluding normal newborn care or chemotherapy, and the subset with established LTVD. Hospitals were grouped by geographic regions. Analysis included descriptive statistics and multi-variable mixed modeling for length of stay, charges, and readmissions. Results Of the 615,883 unique children discharged from 45 children's hospitals in 2014, 2235 (0.4%) had established LTVD. Of these, 342 (15%) were hospitalized in the Northeast, 677 (30%) Midwest, 733 (32%) South and 481 (22%) West. Most had at least two complex chronic conditions (97%) and used a medical device for at least two body systems (71%). No statistically significant regional variation was found for length of stay, charges, or readmissions after adjustment for child demographics, admission type, disposition, primary diagnosis, ICU stay, and number of chronic conditions. Conclusions This study characterized the population of children with LTVD hospitalized in 2014. No regional variation was found for length of stay, charges, or readmissions. Practice implications Children with established LTVD make up a small subset of all children admitted to children's hospitals however, they require substantial, costly, multifaceted care as most have additional complex chronic conditions and require multiple medical devices.

Objectives Currently, very little literature exists regarding the "fifth vital sign" in pediatric orthopedics, pain. Multiple studies have highlighted the utility of non-narcotic pain medications in treating acute pain. The objective of this study is to determine the type and amount of pain medication(s) administered and subsequently prescribed to pediatric patients ages six months to five years old with femur fractures treated with spica casting in the ER (emergency room) and OR (operative room). We also determined the incidence of spica cast change necessary for the two groups as a secondary outcome. Methods A retrospective review was completed at a single level 1 pediatric trauma center, evaluating 82 patients who met the inclusion criteria between six months to five years of age with isolated femoral shaft fractures requiring intervention at one institution. Descriptive statistics and Wilcoxon Rank-Sum or Fisher'sFisher's Exact test were used to assess differences between OR and ER groups for either continuous or categorical variables, respectively. The electronic medical record was then queried for demographic information, location of spica cast placement, hours in the hospital, and amount and type of analgesic medications administered and prescribed. Results Overall, we noted a preponderance of femur fractures in young males (72%), with the mean age of our cohort being 2.3 years old. Our patients spent a median of 20.9 hours in the hospital and had a median worst pain score of 7/10 during their hospital stay. No difference was found between standardized amounts of morphine equivalent administration between groups in the hospital. Upon discharge from the hospital, most patients received opioid and acetaminophen prescriptions (72% and 83%), but few received an ibuprofen prescription (24.4%). More spica casts placed in the ER needed to be revised in the OR compared to spica casts placed in the OR (57% vs. 8%, p0.01). Conclusions There are various medication regimens for patients with femoral shaft fractures treated with spica casting at one institution. Our study revealed that patients received more prescription opioids if treated in the OR. Additionally, spica casting in the ER did not significantly decrease hospital stay, and it significantly increased the risk of needing a reduction in the OR in our institution.

Genome engineering has become more accessible thanks to the RNA programmable endonucleases such as the CRISPR/Cas9 system. However, using this editing technology in synthetic organs called ‘organoids’ is still very inefficient. This is due to the delivery methods used for the CRISPR-Cas9 machinery, which include electroporation of CRISPR/Cas9 DNA, mRNA or ribonucleoproteins (RNPs) containing the CAS9-gRNA complex. However, these procedures are toxic to some extent for the organoids. Here we describe the use of the ‘Nanoblade’ technology, which outperformed by far knock-out (KO) levels achieved to date by gene editing in murine and human tissue derived organoids. We reached up to 80% of gene KO in organoids after treatment with nanoblades. Indeed, high-level nanoblade-mediated KO for the androgen receptor (AR) encoding gene and the cystic fibrosis transmembrane conductance regulator (CFTR) gene was achieved with single gRNA or dual gRNA containing nanoblades in murine prostate and colon organoids. Likewise, nanoblades achieved high levels of gene editing in human organoids ranging between 20% and 50%.Most importantly, in contrast to other gene editing methods, this was obtained without toxicity for the organoids. Only four weeks are required to obtain stable gene KO in organoids and nanoblades simplify and allow rapid genome editing in organoids with little to no side-effects such as possible unwanted INDELS in off-target sites.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with poor health outcomes in adults. Resilience may mitigate this effect. There is limited evidence regarding how parents’ ACEs and resilience may be associated with their children’s health outcomes. OBJECTIVE: To determine the association of parental ACEs and resilience with their child’s risk of unanticipated healthcare reutilization. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study (August 2015 to October 2016) at a tertiary, freestanding pediatric medical center in Cincinnati, Ohio. Eligible participants were English-speaking parents of children hospitalized on a Hospital Medicine or Complex Services team. A total of 1,320 parents of hospitalized children completed both the ACE questionnaire and the Brief Resilience Scale Survey. EXPOSURE: Number of ACEs and Brief Resilience Scale Score among parents. MAIN OUTCOMES: Unanticipated reutilization by children, defined as returning to the emergency room, urgent care, or being readmitted to the hospital within 30 days of hospital discharge. RESULTS: In adjusted analyses, children of parents with 4 or more ACEs had 1.69-times higher odds (95% Confidence Interval 1.11-2.60) of unanticipated reutilization after an index hospitalization, compared with children of parents with no ACEs. Resilience was not significantly associated with reutilization. CONCLUSION: Parental history of ACEs is strongly associated with higher odds of their child having unanticipated healthcare reutilization after a hospital discharge, highlighting an intergenerational effect. Screening may be an important tool for outcome prediction and intervention guidance following pediatric hospitalization.

Chronic hepatitis B virus (HBV) infection persists due to the lack of therapies that effectively target the HBV covalently closed circular DNA (cccDNA). We used HBV-specific guide RNAs (gRNAs) and CRISPR-Cas9 and determined the fate of cccDNA after gene editing. We set up a ribonucleoprotein (RNP) delivery system in HBV-infected HepG2-NTCP cells. HBV parameters after Cas9 editing were analyzed. Southern blot (SB) analysis and DNA/RNA sequencing (DNA/RNA-seq) were performed to determine the consequences of cccDNA editing and transcriptional activity of mutated cccDNA. Treatment of infected cells with HBV-specific gRNAs showed that CRISPR-Cas9 can efficiently affect HBV replication. The appearance of episomal HBV DNA variants after dual gRNA treatment was observed by PCR, SB analysis, and DNA/RNA-seq. These transcriptionally active variants are the products of simultaneous Cas9-induced double-strand breaks in two target sites, followed by repair and religation of both short and long fragments. Following suppression of HBV DNA replicative intermediates by nucleoside analogs, mutations and formation of smaller transcriptionally active HBV variants were still observed, suggesting that established cccDNA is accessible to CRISPR-Cas9 editing. Targeting HBV DNA with CRISPR-Cas9 leads to cleavage followed by appearance of episomal HBV DNA variants. Effects induced by Cas9 were sustainable after RNP degradation/loss of detection, suggesting permanent changes in the HBV genome instead of transient effects due to transcriptional interference.

International audience; Trees depend on beneficial interactions between roots and soil microbes for their nutrition and protection against stresses. The soil microbiome provides the main reservoir of microbes for root colonization and is subject to natural variations that can affect its composition. It is not clear whether the tree's root system is able to buffer the natural variations occurring in the soil microbiome to capture a stable and effective microbiome or whether these variations affect its microbiome to impact its physiology. To address this question, we planted cuttings of Gray Poplar (Populus tremula × alba clone 717-1B4) in natural soil taken from a poplar stand under the same tree over two consecutive years and grew them in a greenhouse. We analyzed the soil and root microbiomes by high throughput Illumina MiSeq sequencing of fungal rDNA internal transcribed spacer and bacterial 16S rRNA amplicons and we characterized the root metabolome by gas chromatography-mass spectrometry. Soil and root microbial communities significantly shifted over the 2 years. A modification of the balance between endophytes, saprophytes, and mycorrhizal fungi occurred in the roots as well as a replacement of some dominant operational taxonomic units by others. These modifications were correlated with a significant alteration of the levels of about 10% of primary and secondary metabolites, suggesting that natural fluctuations in soil microbial communities can have a profound impact on tree root metabolism and physiology. Tree roots functioning may thus be indirectly strongly affected by the effects of future extreme climatic variations on the soil microbiome.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has democratized genome-editing in eukaryotic cells and led to the development of numerous innovative applications. However, delivery of the Cas9 protein and single-guide RNA (sgRNA) into target cells can be technically challenge. Classical viral vectors, such as those derived from lentiviruses (LVs) or adeno-associated viruses (AAVs), allow for efficient delivery of transgenes coding for the Cas9 protein and its associated sgRNA in many primary cells and in vivo. Nevertheless, these vectors can suffer from drawbacks such as integration of the transgene in the target cell genome, a limited cargo capacity, and long-term expression of the Cas9 protein and guide RNA in target cells. To overcome some of these problems, a delivery vector based on the murine Leukemia virus (MLV) was developed to package the Cas9 protein and its associated guide RNA in the absence of any coding transgene. By fusing the Cas9 protein to the C-terminus of the structural protein Gag from MLV, virus-like particles (VLPs) loaded with the Cas9 protein and sgRNA (named "Nanoblades") were formed. Nanoblades can be collected from the culture medium of producer cells, purified, quantified, and used to transduce target cells and deliver the active Cas9/sgRNA complex. Nanoblades deliver their ribonucleoprotein (RNP) cargo transiently and rapidly in a wide range of primary and immortalized cells and can be programmed for other applications, such as transient transcriptional activation of targeted genes, using modified Cas9 proteins. Nanoblades are capable of in vivo genome-editing in the liver of injected adult mice and in oocytes to generate transgenic animals. Finally, they can be complexed with donor DNA for "transfection-free" homology-directed repair. Nanoblade preparation is simple, relatively low-cost, and can be easily carried out in any cell biology laboratory.

Optogenetics enables genome manipulations with high spatiotemporal resolution, opening exciting possibilities for fundamental and applied biological research. Here, we report the development of LiCre, a novel light-inducible Cre recombinase. LiCre is made of a single flavin-containing protein comprising the AsLOV2 photoreceptor domain of Avena sativa fused to a Cre variant carrying destabilizing mutations in its N-terminal and C-terminal domains. LiCre can be activated within minutes of illumination with blue light without the need of additional chemicals. When compared to existing photoactivatable Cre recombinases based on two split units, LiCre displayed faster and stronger activation by light as well as a lower residual activity in the dark. LiCre was efficient both in yeast, where it allowed us to control the production of β-carotene with light, and human cells. Given its simplicity and performances, LiCre is particularly suited for fundamental and biomedical research, as well as for controlling industrial bioprocesses., eLife digest In a biologist’s toolkit, the Cre protein holds a special place. Naturally found in certain viruses, this enzyme recognises and modifies specific genetic sequences, creating changes that switch on or off whatever gene is close by. Genetically engineering cells or organisms so that they carry Cre and its target sequences allows scientists to control the activation of a given gene, often in a single tissue or organ. However, this relies on the ability to activate the Cre protein ‘on demand’ once it is in the cells of interest. One way to do so is to split the enzyme into two pieces, which can then reassemble when exposed to blue light. Yet, this involves the challenging step of introducing both parts separately into a tissue. Instead, Duplus-Bottin et al. engineered LiCre, a new system where a large section of the Cre protein is fused to a light sensor used by oats to detect their environment. LiCre is off in the dark, but it starts to recognize and modify Cre target sequences when exposed to blue light. Duplus-Bottin et al. then assessed how LiCre compares to the two-part Cre system in baker's yeast and human kidney cells. This showed that the new protein is less ‘incorrectly’ active in the dark, and can switch on faster under blue light. The improved approach could give scientists a better tool to study the role of certain genes at precise locations and time points, but also help them to harness genetic sequences for industry or during gene therapy.

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into human blood cells can be challenging. Here, we have utilized "nanoblades," a new technology that delivers a genomic cleaving agent into cells. These are modified murine leukemia virus (MLV) or HIV-derived virus-like particle (VLP), in which the viral structural protein Gag has been fused to Cas9. These VLPs are thus loaded with Cas9 protein complexed with the guide RNAs. Highly efficient gene editing was obtained in cell lines, IPS and primary mouse and human cells. Here, we showed that nanoblades were remarkably efficient for entry into human T, B, and hematopoietic stem and progenitor cells (HSPCs) thanks to their surface co-pseudotyping with baboon retroviral and VSV-G envelope glycoproteins. A brief incubation of human T and B cells with nanoblades incorporating two gRNAs resulted in 40 and 15% edited deletion in the Wiskott-Aldrich syndrome (WAS) gene locus, respectively. CD34+ cells (HSPCs) treated with the same nanoblades allowed 30-40% exon 1 drop-out in the WAS gene locus. Importantly, no toxicity was detected upon nanoblade-mediated gene editing of these blood cells. Finally, we also treated HSPCs with nanoblades in combination with a donor-encoding rAAV6 vector resulting in up to 40% of stable expression cassette knock-in into the WAS gene locus. Summarizing, this new technology is simple to implement, shows high flexibility for different targets including primary immune cells of human and murine origin, is relatively inexpensive and therefore gives important prospects for basic and clinical translation in the area of gene therapy. ispartof: Frontiers in Genome Editing vol:3 ispartof: location:Switzerland status: published

OBJECTIVES:Effective communication is critical for safely discharging hospitalized children, including those with limited English proficiency (LEP), who are at high risk of reuse. Our objective was to describe and compare the safety and family centeredness of nurse communication at hospital discharge for English-proficient (EP) and LEP families.METHODS:In this single-center, cross-sectional study, we used direct observation of hospital discharges for EP and LEP children. Observers recorded quantitative and qualitative details of nurse-family communication, focusing on 3 domains: safe discharge, family centeredness, and family engagement. Patient characteristics and percentages of encounters in which all components were discussed within each domain were compared between EP and LEP encounters by using Fisher’s exact tests. We used field notes to supplement quantitative findings.RESULTS:We observed 140 discharge encounters; 49% were with LEP families. Nurses discussed all safe discharge components in 31% of all encounters, most frequently omitting emergency department return precautions. Nurses used all family-centered communication components in 11% and family-engagement components in 89% of all encounters. Nurses were more likely to discuss all components of safe discharge in EP encounters when compared with LEP encounters (53% vs 9%; P < .001; odds ratio: 11.5 [95% confidence interval 4.4–30.1]). There were no differences in family centeredness or family engagement between LEP and EP encounters.CONCLUSIONS:Discharge encounters of LEP patients were less likely to include all safe discharge communication components, compared with EP encounters. Opportunities to improve nurse-family discharge communication include providing written discharge instructions in families’ primary language, ensuring discussion of return precautions, and using teach-back to optimize family engagement and understanding.

International audience; In this article, we present a tool to annotate an unstructured or semi-structured resource, in order to automate the import of its data in a generic environment that facilitates and standardizes its use. This tool is based on the computation of a signature, characterizing the resource with accounting information about its elements, and on heuristics using signature statistics to identify the entries and microstructure of each entry in the case of a lexical resource to be imported into the Jibiki lexical database platform. The product result is managed in iPolex, a lexical data warehouse dedicated to processing lexical resource files to add metadata. The Jibiki platform accesses iPoLex to directly import lexical resources. The import process thus constituted is used to create and populate lexical bases in Jibiki. The imported resources are then available for consultation and editing online; Dans cet article, nous présentation un outil pour annoter une ressource non structurée ou semi-structurée, de façon à automatiser l'import de ses données dans un environnement générique facilitant et uniformisant son exploitation. Cet outil s'appuie sur le calcul d'une signature, caractérisant la ressource par des informations comptables sur ses éléments, et sur des heuristiques exploitant les statistiques de la signature pour repérer les entrées et la microstructure de chaque entrée dans le cas d'une ressource lexicale à importer dans la plateforme de bases lexicales Jibiki. Le résultat produit est géré dans iPolex, un entrepôt dédié aux traitements de fichiers de ressources lexicales permettant d'y ajouter des méta-données. La plateforme Jibiki accède à iPoLex pour importer directement des ressources lexicales bien formées et suffisamment renseignées. Le processus d'import ainsi constitué est utilisé pour créer et peupler des bases lexicales dans Jibiki. Les ressources ainsi importées sont ensuite consultables et éditables en ligne.

Concernant le couple de langues français-japonais, les ressources disponibles sur le Web sont peu nombreuses et de taille modeste. Il existe cependant de nombreux dictionnaire imprimés de qualité et à large couverture. C’est pourquoi nous avons lancé le projet jibiki.fr de construction d’un dictionnaire japonais-français de qualité et à large couverture à partir de récupération de données issues du dictionnaire de Jean-Baptiste Cesselin (1940) que nous avons numérisé et lu optiquement. Nous avons complété ces données par d’autres issues du dictionnaire JMdict de Jim Breen (2004) et de Wikipedia pour pallier le manque de vocabulaire récent. Nous avons ensuite installé ces données sur une plateforme de gestion de ressources lexicales en ligne. Les utilisateurs peuvent alors consulter le dictionnaire et corriger les erreurs qu’ils trouvent lors de la consultation. La plateforme possède également une interface de programmation (API) qui permet de programmer des scripts afin de corriger automatiquement certains phénomènes repérés lors de consultations. La ressource ainsi construite est disponible en téléchargement libre de droits. Cet article décrit certaines techniques de correction automatique et manuelle à l’issue des 3 ans et demi du projet.

Through their roots, trees interact with a highly complex community of microorganisms belonging to various trophic guilds and contributing to tree nutrition, development and protection against stresses. Tree roots select for specific microbial species from the bulk soil communities. The root microbiome formation is a dynamic process but little is known on how the different microorganisms colonize the roots and how the selection occurs. To decipher if the final composition of the root microbiome is the product of several waves of colonization by different guilds of microorganisms, we planted sterile rooted cuttings of Gray Poplar obtained from plantlets propagated in axenic conditions in natural soil taken from a poplar stand. We analyzed the root microbiome at different time points between 2 and 50 days of culture by combining high-throughput Illumina MiSeq sequencing of fungal rDNA ITS and bacterial 16S rRNA amplicons with Confocal Laser Scanning Microscope observations. The microbial colonisation of poplar roots took place in three stages but the dynamic was different between bacteria and fungi. Root bacterial communities were clearly different from the soil after two days of culture. By contrast, if fungi were also already colonizing roots after two days, the initial communities were very close to the one of the soil and were dominated by saprotrophs. Those were slowly replaced by endophytes and ectomycorhizal fungi. The replacement of the most abundant fungal and bacterial community members observed in poplar roots along time suggest potential competition effect between microorganisms and/or a selection by the host.ImportanceThe tree root microbiome is composed of a very diverse set of bacterial and fungal communities. These microorganisms have a profound impact on tree growth, development and protection against different types of stress. They mainly originate from the bulk soil and colonize the root system which provides a unique nutrient rich-environment for a diverse assemblage of microbial communities. In order to better understand how the tree root microbiome is shaped along time, we observed the composition of root-associated microbial communities of naïve plantlets of poplar transferred in natural soil. The composition of the final root microbiome rely on a series of colonization stages characterized by the dominance of different fungal guilds and bacterial community members along time. Our observations suggest an early stabilization of bacterial communities, whereas fungal communities are established following a more gradual pattern.

The tree root microbiome is composed of a very diverse set of bacterial and fungal communities. These microorganisms have a profound impact on tree growth, development, and protection against different types of stress., Through their roots, trees interact with a highly complex community of microorganisms belonging to various trophic guilds and contributing to tree nutrition, development, and protection against stresses. Tree roots select for specific microbial species from the bulk soil communities. The root microbiome formation is a dynamic process, but little is known on how the different microorganisms colonize the roots and how the selection occurs. To decipher whether the final composition of the root microbiome is the product of several waves of colonization by different guilds of microorganisms, we planted sterile rooted cuttings of gray poplar obtained from plantlets propagated in axenic conditions in natural poplar stand soil. We analyzed the root microbiome at different time points between 2 and 50 days of culture by combining high-throughput Illumina MiSeq sequencing of the fungal ribosomal DNA internal transcribed spacer and bacterial 16S rRNA amplicons with confocal laser scanning microscopy observations. The microbial colonization of poplar roots took place in three stages, but bacteria and fungi had different dynamics. Root bacterial communities were clearly different from those in the soil after 2 days of culture. In contrast, if fungi were also already colonizing roots after 2 days, the initial communities were very close to that in the soil and were dominated by saprotrophs. They were slowly replaced by endophytes and ectomycorhizal fungi. The replacement of the most abundant fungal and bacterial community members observed in poplar roots over time suggest potential competition effect between microorganisms and/or a selection by the host. IMPORTANCE The tree root microbiome is composed of a very diverse set of bacterial and fungal communities. These microorganisms have a profound impact on tree growth, development, and protection against different types of stress. They mainly originate from the bulk soil and colonize the root system, which provides a unique nutrient-rich environment for a diverse assemblage of microbial communities. In order to better understand how the tree root microbiome is shaped over time, we observed the composition of root-associated microbial communities of naive plantlets of poplar transferred in natural soil. The composition of the final root microbiome relies on a series of colonization stages characterized by the dominance of different fungal guilds and bacterial community members over time. Our observations suggest an early stabilization of bacterial communities, whereas fungal communities are established following a more gradual pattern.

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into human blood cells can be challenging. Here, we have utilized “nanoblades,” a new technology that delivers a genomic cleaving agent into cells. These are modified murine leukemia virus (MLV) or HIV-derived virus-like particle (VLP), in which the viral structural protein Gag has been fused to Cas9. These VLPs are thus loaded with Cas9 protein complexed with the guide RNAs. Highly efficient gene editing was obtained in cell lines, IPS and primary mouse and human cells. Here, we showed that nanoblades were remarkably efficient for entry into human T, B, and hematopoietic stem and progenitor cells (HSPCs) thanks to their surface co-pseudotyping with baboon retroviral and VSV-G envelope glycoproteins. A brief incubation of human T and B cells with nanoblades incorporating two gRNAs resulted in 40 and 15% edited deletion in the Wiskott-Aldrich syndrome (WAS) gene locus, respectively. CD34+ cells (HSPCs) treated with the same nanoblades allowed 30–40% exon 1 drop-out in the WAS gene locus. Importantly, no toxicity was detected upon nanoblade-mediated gene editing of these blood cells. Finally, we also treated HSPCs with nanoblades in combination with a donor-encoding rAAV6 vector resulting in up to 40% of stable expression cassette knock-in into the WAS gene locus. Summarizing, this new technology is simple to implement, shows high flexibility for different targets including primary immune cells of human and murine origin, is relatively inexpensive and therefore gives important prospects for basic and clinical translation in the area of gene therapy.

Background Patients with established tracheostomy and ventilator dependence are hospitalized more frequently and use more healthcare resources than other patients with complex chronic conditions. However, data to compare variation in hospitalization and resource use among patients in this population across the United States is deficient, partly due to the lack of structured methods to query national databases. Aim Determine the best method for identifying the subset of children with established tracheostomy and ventilator dependence in Pediatric Health Information System (PHIS). Hypothesis A combination of identifiable characteristics coded in the PHIS database can be used to identify the population of patients with established tracheostomy and ventilator dependence who are admitted to the hospital. Methods This cross-sectional, retrospective cohort study used established methods to extract data from PHIS and assessed the sensitivity and specificity of an algorithm to identify patients with established tracheostomy and ventilator dependence as compared with a local registry of ventilator dependent patients. Results A newly created algorithm identified >90% of the 157 patients with established tracheostomy and ventilator dependence hospitalized at our organization during 2014. The sensitivity and specificity of the algorithm to identify these patients was 91% and 99%, respectively. Conclusions This new algorithm can be used to reliably identify and further study healthcare utilization by this population of patients with established tracheostomy and ventilator dependence. In addition, future work can determine the applicability of this algorithm to other administrative datasets.

Depuis 2010, l’Office national de l’eau et des milieux aquatiques (Onema), aujourd’hui integre a l’Agence francaise pour la biodiversite (AFB), les agences de l’eau et leurs partenaires constituent un reseau de sites de demonstration pour la restauration hydromorphologique des cours d’eau. Les sites de demonstration doivent faire l’objet d’un suivi scientifique homogene appele « suivi scientifique minimal » (SSM), ce qui permet d’acquerir des donnees de suivi standardisees sur le long terme et d’etudier les effets des operations de restauration sur le milieu. L’organisation du projet repose sur l’emboitement des echelles d’actions : coordination et cadrage scientifique au niveau national, choix des sites et organisation de la mise en œuvre au niveau des grands bassins hydrographiques, realisation des suivis au niveau local. Sur le territoire metropolitain, le reseau de sites de demonstration compte actuellement une quarantaine de sites potentiels pour un objectif minimum de 60 sites d’ici fin 2018. Dans le cadre d’une strategie globale de suivi de ses operations de restauration de l’hydromorphologie, l’agence de l’eau Rhin-Meuse participe a ce projet en promouvant la mise en œuvre du SSM aupres des porteurs de projets ou en prenant en charge la mise en œuvre des suivis. L’operation de remeandrage du Longeau, portee par le Syndicat intercommunal d’amenagement du Longeau et de la Seigneulle, beneficie ainsi d’un suivi de type SSM. La reussite du reseau de sites de demonstration passe par la bonne articulation entre les differentes echelles de travail et une bonne synergie entre les aspects scientifiques et operationnels du projet. En effet, l’experience de chacun est mise a profit pour alimenter la reflexion generale.

Alarm fatigue has been linked to patient morbidity and mortality in hospitals due to delayed or absent responses to monitor alarms. We sought to describe alarm rates at 5 freestanding children’s hospitals during a single day and the types of alarms and proportions of patients monitored by using a point-prevalence, cross-sectional study design. We collected audible alarms on all inpatient units and calculated overall alarm rates and rates by alarm type per monitored patient per day. We found a total of 147,213 alarms during the study period, with 3-fold variation in alarm rates across hospitals among similar unit types. Across hospitals, one-quarter of monitored beds were responsible for 71%, 61%, and 63% of alarms in medical-surgical, neonatal intensive care, and pediatric intensive care units, respectively. Future work focused on addressing nonactionable alarms in patients with the highest alarm counts may decrease alarm rates. Journal of Hospital Medicine 2018;13:396–398. Published online first April 25, 2018. © 2018 Society of Hospital Medicine

The present work, performed in the frameworks of the CleanSKY project AeroPZT, is devoted to the numerical analysis of innovative actuators made of piezoelectric materials. An advanced numerical tool, based on the Carrera Unified Formulation, have been used to perform numerical analyses of the device. A refined one-dimensional structural model has been used in the analyses to provide accurate results with a low computational cost. Thermal loads and the effects of the encapsulation, which is used to protect the piezoelectric element from the external environment, have been evaluated. Amplified Piezoelectric Actuators (APAs) and a Multi-Layered Actuators (MLAs) have been analysed. The obtained results have been used to derive guidelines for the development of the final design of the actuator able to satisfy the project requirements.

Multilayer piezoelectric actuators operating in quasi-static conditions under high electrical field find more and more applications in demanding environments, such as in the field of aerospace. Naturally, increasing amounts of data are being published on the behavior of PZT materials under large signal conditions. However, the information is often incomplete and not directly usable by mechanical design engineers. Using a pragmatic approach, the present work aims at drawing a complete set of parameters for designers to use when selecting a piezoelectric actuator, in particular for applications at elevated temperature (up to 200 °C). For the design process, it is important to characterize apparent capacitance, apparent losses, free stroke, blocking force and height according to temperature. In addition, non-linear effects such as creep must be considered. The present paper focuses mostly on apparent capacitance, losses and displacement. The evolution of capacitance with field is not linear and strongly temperature dependent. Measurements on NCE51 (soft-doped) and NCE46 (hard-doped) indicate a very different behavior. As signal amplitude increases, capacitance increases, reaches a maximum then decreases. This maximum shifts with temperature, so that at 200 °C, NCE51 reaches a maximum at 0,8 kV/mm while NCE46 peaks at 1,8 kV/mm. Results are presented also for the apparent loss factor (tangent δ) and free displacement. At 200 °C, NCE51 and NCE46 provide respectively 23 % and 15 % additional free displacement. Furthermore, the loss factor at maximum field decreases for NCE51, so the basis for material choice (soft-doped or hard-doped) is challenged. Using these measurements, the operating envelope of the actuators can be calculated for different temperatures. The comparison of the two materials highlights the advantage of NCE51 at low frequency. At high frequency, NCE46 maintains an advantage, particularly for energy-intensive applications.

IntroductionTo identify interstage best practices associated with lower mortality, we studied National Pediatric Cardiology Quality Improvement Collaborative centres registry using a positive deviance approach.MethodsPositive deviant and control centre team members were interviewed to identify potential interstage best practices. Subsequently, all collaborative centres were surveyed on the use of these practices to test their associations with centre mortality. Questionnaires were scored using Likert scales; the overall score was linearly transformed to a 0–100-point scale with higher scores indicating increased use of practices. Mortality was based on patients enrolled after a centre’s first year in the collaborative. Centre mortality rates were divided into tertiles. Survey scores for the low mortality tertile were compared with the other tertiles.ResultsFor this study, seven positive deviant and four control teams were interviewed. A total of 20 potential best practices were identified, including team composition, improvement practices, and parent involvement. Questionnaires were completed by 36/43 eligible centres, providing 1504 patients for analysis. Average survey score was 50.2 (SD 13.4). Average mortality was 6.1% (SD 4.1). There was no correlation between survey scores and mortality (r=0.14, p=0.41). The one practice associated with the low mortality tertile was frequency of discussion of interstage results: 58.3% of low mortality teams discussed results at least monthly versus 8.4% of the middle and high tertile centres (p=0.02).ConclusionsLow-mortality centres more frequently discuss interstage results than high-mortality centres. Heightened awareness of outcomes may influence practice; however, further study is needed to understand the variation in outcomes across centres.

Background: The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) formed to improve outcomes in infants with hypoplastic left heart syndrome. The collaborative sought to (1) decrease mortality, (2) reduce growth failure, and (3) reduce hospital readmissions due to major medical problems during the interstage period between discharge following stage 1 palliation (S1P) and admission for stage 2 palliation (S2P). Methods: The NPC-QIC is a learning network, coproduced by parents and clinicians, of 65 pediatric cardiology centers that contribute clinical data on care processes and outcomes to a shared registry. The adapted Breakthrough Series Model structure brings teams together regularly to review data, share lessons, and plan improvements. Outcomes are monitored using statistical process control methods. Results: Between 2008 and 2016, interstage mortality decreased by >40%, from 9.5% to 5.3%. Identification and use of a nutrition bundle led to improved infant growth, with a 28% reduction in interstage growth failure. The rate of serious hospital readmissions was low and did not significantly change. Importantly, a formed partnership with the parent group Sisters by Heart fostered the coproduction of tools and strategies and an emphasis on data transparency and outcomes. Conclusions: The NPC-QIC’s initial efforts led to improvements in interstage growth and mortality. The NPC-QIC has modeled the use of data for improvement and research, the value of coproduction with parents, and the concept “all teach, all learn,” demonstrating the power of the learning network model.

Supplemental_material for Power of a Learning Network in Congenital Heart Disease by Jeffrey B. Anderson, David W. Brown, Stacy Lihn, Colleen Mangeot, Katherine E. Bates, Andrew H. Van Bergen, Nancy A. Rudd, Samuel Hanke, Jim Tweddell, Carole Lannon, and in World Journal for Pediatric and Congenital Heart Surgery

Background Hospitalized children generate up to 152 alarms per patient per day outside of the intensive care unit. In that setting, as few as 1% of alarms are clinically important. How nurses make decisions about responding to alarms, given an alarm's low specificity for detecting clinical deterioration, remains unclear. Objective Our objective was to describe how bedside nurses think about and act upon monitor alarms for hospitalized children. Design, setting, participants This was a qualitative study that involved the direct observation of nurses working on a general pediatric unit at a large children's hospital. Measurements We used a structured tool that included predetermined categories to assess nurse responses to monitor alarms. Data on alarm frequency and type were pulled from bedside monitors. Results We conducted 61.3 patient-hours of observation with nine nurses, in which we documented 207 nurse responses to patient alarms. For 67% of alarms heard outside of the room, the nurse decided not to respond without further assessment. Nurses most commonly cited reassuring clinical context (eg, medical team in room), as the rationale for alarm nonresponse. The nurse deemed clinical intervention necessary in only 14 (7%) of the observed responses. Conclusion Nurses rely on clinical and contextual details to determine how to respond to alarms. Few of the alarm responses in our study resulted in a clinical intervention. These findings suggest that multiple system-level and educational interventions may be necessary to improve the efficacy and safety of continuous monitoring.

BACKGROUND: The Pediatric Infectious Diseases Society and Infectious Diseases Society of America national childhood community-acquired pneumonia (CAP) guideline encouraged the standard evaluation and treatment of children who were managed as outpatients. Our objectives were to (1) increase adherence to guideline-recommended diagnostics and antibiotic treatment of CAP at 5 pediatric primary care practices (PPCPs) by using quality-improvement methods and (2) evaluate the association between guideline adherence and unscheduled follow-up visits. METHODS: Immunocompetent children >3 months of age with no complex chronic conditions and who were diagnosed with CAP were eligible for inclusion in this stepped-wedge study. Interventions were focused on education, knowledge of colleagues’ prescribing practices, and feedback sessions. Statistical process control charts were used to assess changes in recommendations and antibiotic treatment. Unscheduled follow-up visits were compared across time by using generalized estimating equations that were clustered by PPCP. RESULTS: CAP was diagnosed in 1906 children. Guideline recommended therapy and pulse oximetry use increased from a mean baseline of 24.9% to a mean of 68.0% and from 4.3% to 85.0%, respectively, over the study period. Among children >5 years of age, but not among those who were younger, the receipt of guideline recommended antibiotics, as compared with nonguideline therapy, was associated with the increased likelihood of unscheduled follow-up (adjusted odds ratio, 2.12; 95% confidence interval: 1.31–3.43). Chest radiographs and complete blood cell counts were rarely performed at baseline. CONCLUSIONS: Recommendations for limited use of chest radiographs and complete blood cell counts and standardized antibiotic therapy in children is supported at PPCPs. However, the guideline may need to include macrolide monotherapy as appropriate antibiotic therapy for older children.

This paper, “Diode laser a cavite externe auto-alignee et contlnument accordable en longueur d'onde," was presented as part of International Conference on Space Optics—ICSO 1997, held in Toulouse, France.

Quasi-static multilayer piezoelectric actuators are finding more and more applications, for example, in the field of aerospace; however, their properties are still not fully characterised, in particular at a high temperature. The present study targets the full characterisation of both soft-doped and hard-doped lead zirconate titanate (PZT) up to 200°C. A simple set of tests and test results are presented, focusing particularly on dielectric losses and creep effect. Dielectric losses were found to decrease with the increasing field for soft-doped PZT, while they tend to increase for hard-doped PZT. The interpretation is that soft-doped PZT has less hysteresis at high field. The creep behaviour is also significantly different. While soft-doped PZT follows a logarithmic model with low and stable creep rates, hard-doped PZT exhibits non-logarithmic creep with increasing or decreasing rates depending on the temperature. This behaviour is attributed to the generation of additional poling in the material.

The preservation of intact RNA is a limiting step when gene expression profiling is performed using field-collected plant material. The use of liquid nitrogen ensures the optimal preservation of RNA, however it is not always practical, especially if the plant material has to be sampled in remote locations. Ethanol is known to preserve DNA in plant tissues even after a long storage period and here its suitability to preserve the RNA of textile hemp cortical tissues was tested. Hemp (Cannabis sativa L.) is an economically important fibre crop because it supplies cellulosic bast fibres used in different industrial sectors. In this study we demonstrate the suitability of ethanol for RNA preservation by analyzing tissues stored at 4 °C for 1, 2, 4 and 8 days. We show that in all the cases the extracted RNA is intact. We finally analyze hemp stem tissues stored in ethanol for 1 month and demonstrate the preservation of the tissue structure, particularly of bast fibres.

Infants with univentricular congenital heart disease (CHD), including those with hypoplastic left heart syndrome (HLHS), regularly pose dilemmas in decision-making because their anatomy and physiology are often unique and variable. The typical staged surgical course for infants with complex univentricular anatomy with systemic outflow obstruction begins with the Norwood (stage 1) operation or variant shortly after birth, followed several months later by superior cavopulmonary anastomosis (stage 2 palliation) with an ultimate goal of a Fontan-type operation several years later.1–3 Improvement in surgical and postoperative management has led to considerable improvement in early post-Norwood survival in the recent era.4–7 However, after the Norwood procedure and before stage 2 palliation, a high-risk time period termed interstage, mortality has been previously been reported at 10% to 15%.8–10 The rare nature of this disorder has limited robust learning about successful strategies to improve survival undertaken by single-surgical centers, and a gap exists in our ability to further improve mortality in this population. The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC), the first multicenter learning network within pediatric cardiology,11 was established with the goal of improving care and outcomes for children with univentricular heart after the Norwood operation and specifically to (1) improve interstage mortality, (2) decrease interstage growth failure, and (3) reduce interstage hospital readmissions for major medical events. There were several perceived challenges to success in changing clinical outcomes before starting the NPC-QIC collaborative. A primary challenge in collaboration among multiple sites can be agreement on best practices that should be implemented. This is especially true for rare diseases, such as univentricular heart disease, where evidence-based clinical guidelines are not available to clinicians. As noted above, major variation persists in management practices among individuals and institutions caring for children with HLHS and other …

Les departements d’outre-mer (DOM) sont porteurs d’enjeux particulierement sensibles en matiere d’assainissement. Soumis au meme cadre reglementaire que la metropole (directive cadre sur l’eau, directive sur les eaux residuaires urbaines), ils se distinguent des departements metropolitains par de nombreux aspects pouvant affecter le bon developpement de l’assainissement de ces territoires, dont la dependance a l’importation de materiels techniques, la sensibilite a la corrosion, les fortes variations de charges hydrauliques, etc. L’utilisation de filtres plantes permet de repondre a la problematique des petites et moyennes collectivites par le developpement de filieres favorisant des reseaux courts, robustes, face aux variations de charges et utilisant principalement une main-d’oeuvre et des materiaux locaux. Face a la problematique de gestion des boues dans l es DOM, les offices de l’eau favorisent la filiere francaise sans pretraitement. Cependant, l’adaptation de cette filiere au climat tropical necessite d’integrer differentes contraintes locales, raison pour laquelle l’Onema a lance un programme de recherche et de validation en partenariat avec des acteurs locaux (offices de l’eau, syndicats, entreprises) et Irstea. Cet article resume les premiers enseignements obtenus sur les systemes a ecoulement vertical alimentes en eaux usees brutes. Il permet de presenter l’effet positif du climat sur les performances de ces systemes et dresse de premieres recommandations de dimensionnement compact de ces filieres.

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into target cells can be technically challenging when working with primary cells or in vivo. Using engineered murine leukemia virus-like particles loaded with Cas9/sgRNA ribonucleoproteins (“Nanoblades”), we were able to induce efficient genome-editing in cell lines and primary cells including human induced pluripotent stem cells, human hematopoietic stem cells and mouse bone-marrow cells. Transgene-free Nanoblades were also capable of in vivo genome-editing in mouse embryos and in the liver of injected mice. Nanoblades can be complexed with donor DNA for “all-in-one” homology-directed repair or programmed with modified Cas9 variants to mediate transcriptional up-regulation of target genes. Nanoblades preparation process is simple, relatively inexpensive and can be easily implemented in any laboratory equipped for cellular biology.