PLATINUM SENSITIVE 2 LIKE impacts growth, root morphology, seed set, and stress responses

Eukaryotic protein phosphatase 4 (PP4) is a PP2A-type protein phosphatase that is part of a conserved complex with regulatory factors PSY2 and PP4R2. Various lines of Arabidopsis thaliana with mutated PP4 subunit genes were constructed to study the so far completely unknown functions of PP4 in plants. Mutants with knocked out putative functional homolog of the PSY2 LIKE (PSY2L) gene were dwarf and bushy, while plants with knocked out PP4R2 LIKE (PP4R2L) looked very similar to WT. The psy2l seedlings had short roots with disorganized morphology and impaired meristem. Seedling growth was sensitive to the genotoxin cisplatin. Global transcript analysis (RNA-seq) of seedlings and rosette leaves revealed several groups of genes, shared between both types of tissues, strongly influenced by knocked out PSY2L. Receptor kinases, CRINKLY3 and WAG1, important for growth and development, were down-regulated 3–7 times. EUKARYOTIC ELONGATION FACTOR5A1 was down-regulated 4–6 fold. Analysis of hormone sensitive genes indicated that abscisic acid levels were high, while auxin, cytokinin and gibberellic acid levels were low in psy2l. Expression of specific transcription factors involved in regulation of anthocyanin synthesis were strongly elevated, e.g. the master regulator PAP1, and intriguingly TT8, which is otherwise mainly expressed in seeds. The psy2l mutants accumulated anthocyanins under conditions where WT did not, pointing to PSY2L as a possible upstream negative regulator of PAP1 and TT8. Expression of the sugar-phosphate transporter GPT2, important for cellular sugar and phosphate homeostasis, was enhanced 7–8 times. Several DNA damage response genes, including the cell cycle inhibitor gene WEE1, were up-regulated in psy2l. The activation of DNA repair signaling genes, in combination with phenotypic traits showing aberrant root meristem and sensitivity to the genotoxic cisplatin, substantiate the involvement of Arabidopsis PSY2L in maintenance of genome integrity.publishedVersio

Economic Evaluation of CPD Activities for Healthcare Professionals: A Scoping Review

CONTEXT: Continuing Professional Development (CPD) activities for healthcare professionals are central to the optimization of patient safety and person-centred care. Although there is some evidence on the economics of healthcare professionals training, very little is known about the costs and benefits of CPD. METHODS: This study aimed to review the research evidence on economic evaluations of CPD activities for healthcare professionals. CINAHL, MEDLINE/PubMed, Scopus, Econlit, and Web of Science databases were used to identify articles published between 2010 and 2021. RESULTS: Of the 6791 titles identified, 119 articles met the inclusion criteria and were included in this scoping review. The majority of articles were partial economic evaluations of CPD programmes (n = 70), half were from the USA. Studies that included multiple professions were most prevalent (n = 54), followed by nurses (n = 34) and doctors (n = 23). Patient outcomes were the most commonly reported outcome (n = 51), followed by change in clinical practice (n = 38), and healthcare professionals’ knowledge gain (n = 19). CONCLUSIONS: There is an urgent call for more evidence regarding the economic evaluations of CPD. This is particularly important in view of the rising costs of healthcare globally. The majority of studies included in this review did not provide detailed information on the evaluations and many focused exclusively on the cost of CPD activities rather than outcomes

Development of a European Centre of Excellence (Coe) for Research in Continuing Professional Development (UPGRADE)

The European Centre of Excellence (CoE) for Research in Continuing Professional Development (UPGRADE) is a pan-European network of researchers, clinicians, regulators, educators, and professional bodies, established in 2020 through a consensus group of experts, who defined its mission, vision, values, aims and objectives. The Centre’s aim is to advance the science of Continuing Professional Development (CPD) for healthcare professionals through research and dissemination of best practices for CPD. Debate among UPGRADE partners and interchange of research data will yield best practices across countries to optimise quality CPD programmes. Collaboration, information exchange and communication among CPD experts will be facilitated through UPGRADE via an online Community of Inquiry (CoI). UPGRADE aims to evolve as a driving force network of academics and health professional leaders in research, education, professional regulation, and clinical practice whose collaborative work ensures quality and safe person-centred care. UPGRADE members are from 22 European countries, represented by strategic leaders in diverse sectors of health, policy, academia, and professional organisations. Three research-working groups constitute the pillars of UPGRADE, which addresses gaps in research, collect and create critical databases, and solidify the effectiveness of CPD

Île-de-France

À la fois centre d’activités économiques, pôle culturel et destination de la grande majorité des exilés et réfugiés, l’Île-de-France, devenue une “région monde”, est un observatoire privilégié et singulier du phénomène migratoire, qui a contribué à son expansion territoriale et participé à son dynamisme économique. L’histoire de l’immigration postcoloniale en région continue, elle, à s’écrire au quotidien, et d’autres, comme celle des mouvements de sans-papiers et de mal-logés, y sont en deveni

The Canine Oral Microbiome

Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S rRNA-gene sequence comparison, shared between humans and dogs, two divergent mammalian species. Second, canine oral bacteria are of interest to veterinary and human medical communities for understanding their roles in health and infectious diseases. The bacteria involved are mostly unnamed and not linked by 16S rRNA-gene sequence identity to a taxonomic scheme. This manuscript describes the analysis of 5,958 16S rRNA-gene sequences from 65 clone libraries. Full length 16S rRNA reference sequences have been obtained for 353 canine bacterial taxa, which were placed in 14 bacterial phyla, 23 classes, 37 orders, 66 families, and 148 genera. Eighty percent of the taxa are currently unnamed. The bacterial taxa identified in dogs are markedly different from those of humans with only 16.4% of oral taxa are shared between dogs and humans based on a 98.5% 16S rRNA sequence similarity cutoff. This indicates that there is a large divergence in the bacteria comprising the oral microbiomes of divergent mammalian species. The historic practice of identifying animal associated bacteria based on phenotypic similarities to human bacteria is generally invalid. This report describes the diversity of the canine oral microbiome and provides a provisional 16S rRNA based taxonomic scheme for naming and identifying unnamed canine bacterial taxa

CSI 2264: Simultaneous optical and infrared light curves of young disk-bearing stars in NGC 2264 with CoRoT and Spitzer-- evidence for multiple origins of variability

Anne Marie Cody, et al, 'CSI 2264: SIMULTANEOUS OPTICAL AND INFRARED LIGHT CURVES OF YOUNG DISK-BEARING STARS IN NGC 2264 WITH CoRoT and SPITZER—EVIDENCE FOR MULTIPLE ORIGINS OF VARIABILITY', The Astronomical Journal, 147:82 (47pp), 2014 April doi:10.1088/0004-6256/147/4/82 © 2014. The American Astronomical Society.We present the Coordinated Synoptic Investigation of NGC 2264, a continuous 30-day multi-wavelength photometric monitoring campaign on more than 1000 young cluster members using 16 telescopes. The unprecedented combination of multi-wavelength, high-precision, high-cadence, and long-duration data opens a new window into the time domain behavior of young stellar objects. Here we provide an overview of the observations, focusing on results from Spitzer and CoRoT. The highlight of this work is detailed analysis of 162 classical T Tauri stars for which we can probe optical and mid-infrared flux variations to 1% amplitudes and sub-hour timescales. We present a morphological variability census and then use metrics of periodicity, stochasticity, and symmetry to statistically separate the light curves into seven distinct classes, which we suggest represent different physical processes and geometric effects. We provide distributions of the characteristic timescales and amplitudes, and assess the fractional representation within each class. The largest category (>20%) are optical "dippers" having discrete fading events lasting ~1-5 days. The degree of correlation between the optical and infrared light curves is positive but weak; notably, the independently assigned optical and infrared morphology classes tend to be different for the same object. Assessment of flux variation behavior with respect to (circum)stellar properties reveals correlations of variability parameters with H$\alpha$ emission and with effective temperature. Overall, our results point to multiple origins of young star variability, including circumstellar obscuration events, hot spots on the star and/or disk, accretion bursts, and rapid structural changes in the inner disk.Peer reviewe

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Effects of sign language experience on categorical perception of dynamic ASL pseudosigns

We investigated effects of sign language experience on deaf and hearing participants’ categorical perception of minimal manual contrast stimuli that met key criteria of speech perception research. A continuum of meaningless dynamic stimuli was created with a morphing approach, which manipulated videorecorded productions of phonotactically permissible pseudosigns differing between American Sign Language (ASL) handshapes that contrast on a single articulatory dimension (U—V: finger-spreading). AXB discrimination and AXB categorization and goodness ratings on the target items were completed by deaf early (native) signers (DE), deaf late (nonnative) signers (DL), hearing late (L2) signers (HL), and hearing nonsigners (HN). Categorization and goodness functions were less categorical and had different boundaries for DL participants than for DE and HL participants. Shape and level of discrimination functions also differed by ASL experience and hearing status, with DL signers showing better performance than DE, HL, and especially HN participants, particularly at the U end of the continuum. Although no group displayed a peak in discrimination at the category boundary, thus failing to support classic categorical perception, discrimination was consistent with categorization in other ways that differed among the groups. Thus, perception of phonetic variations underlying this minimal sign contrast is systematically affected by language experience

Modeling, building and evaluating an ontology for the automatic characterization of adverse drug effects during pharmacovigilance.

International audienceBACKGROUND: The characterization of spontaneous reported cases is fundamental for pharmacovigilance. This task is time consuming and its reproducibility is low. OBJECTIVE: To develop a system founded on an ontology that automatically instantiates spontaneous reported cases as "known" adverse drug effects (ADE) only if the reported ADEs are described in drug compendia. METHODS: A simple ontology of drugs and their related adverse effects represented in description logics was developed from a drug database. Manual evaluation was carried out on 378 spontaneous reported cases instantiated as "known ADE of a chemical class". The initial manual characterization was reviewed by a pharmacovigilance expert to validate the generated automatic characterization. RESULTS: The ontology is composed by 57,04 concepts and 5 relations. It was successfully validated thanks to Pellet reasoner and it contains neither inconsistencies nor cycles. In this validation, 86% of the instantiated spontaneous reported cases effectively concerned notorious ADEs, whereas only 75% were initially identified manually as related to notorious ADEs. CONCLUSION: This system can assist characterization by applying a reasoning process similar to that used by experts in the search for ADEs