An eHealth capabilities framework for graduates and health professionals: Mixed-methods study

© Melissa Brunner, Deborah McGregor, Melanie Keep, Anna Janssen, Heiko Spallek, Deleana Quinn, Aaron Jones, Emma Tseris, Wilson Yeung, Leanne Togher, Annette Solman, Tim Shaw. Background: The demand for an eHealth-ready and adaptable workforce is placing increasing pressure on universities to deliver eHealth education. At present, eHealth education is largely focused on components of eHealth rather than considering a curriculum-wide approach. Objective: This study aimed to develop a framework that could be used to guide health curriculum design based on current evidence, and stakeholder perceptions of eHealth capabilities expected of tertiary health graduates. Methods: A 3-phase, mixed-methods approach incorporated the results of a literature review, focus groups, and a Delphi process to develop a framework of eHealth capability statements. Results: Participants (N=39) with expertise or experience in eHealth education, practice, or policy provided feedback on the proposed framework, and following the fourth iteration of this process, consensus was achieved. The final framework consisted of 4 higher-level capability statements that describe the learning outcomes expected of university graduates across the domains of (1) digital health technologies, systems, and policies; (2) clinical practice; (3) data analysis and knowledge creation; and (4) technology implementation and codesign. Across the capability statements are 40 performance cues that provide examples of how these capabilities might be demonstrated. Conclusions: The results of this study inform a cross-faculty eHealth curriculum that aligns with workforce expectations. There is a need for educational curriculum to reinforce existing eHealth capabilities, adapt existing capabilities to make them transferable to novel eHealth contexts, and introduce new learning opportunities for interactions with technologies within education and practice encounters. As such, the capability framework developed may assist in the application of eHealth by emerging and existing health care professionals. Future research needs to explore the potential for integration of findings into workforce development programs

Seasonal cycle of precipitation variability in South America on intraseasonal timescales

The seasonal cycle of the intraseasonal (IS) variability of precipitation in South America is described through the analysis of bandpass filtered outgoing longwave radiation (OLR) anomalies. The analysis is discriminated between short (10--30 days) and long (30--90 days) intraseasonal timescales. The seasonal cycle of the 30--90-day IS variability can be well described by the activity of first leading pattern (EOF1) computed separately for the wet season (October--April) and the dry season (May--September). In agreement with previous works, the EOF1 spatial distribution during the wet season is that of a dipole with centers of actions in the South Atlantic Convergence Zone (SACZ) and southeastern South America (SESA), while during the dry season, only the last center is discernible. In both seasons, the pattern is highly influenced by the activity of the Madden--Julian Oscillation (MJO). Moreover, EOF1 is related with a tropical zonal-wavenumber-1 structure superposed with coherent wave trains extended along the South Pacific during the wet season, while during the dry season the wavenumber-1 structure is not observed. The 10--30-day IS variability of OLR in South America can be well represented by the activity of the EOF1 computed through considering all seasons together, a dipole but with the stronger center located over SESA. While the convection activity at the tropical band does not seem to influence its activity, there are evidences that the atmospheric variability at subtropical-extratropical regions might have a role. Subpolar wavetrains are observed in the Pacific throughout the year and less intense during DJF, while a path of wave energy dispersion along a subtropical wavetrain also characterizes the other seasons. Further work is needed to identify the sources of the 10--30-day-IS variability in South America

The CORDEX Flagship Pilot Study in southeastern South America: a comparative study of statistical and dynamical downscaling models in simulating daily extreme precipitation events

The aim of this work is to present preliminary results of the statistical and dynamical simulations carried out within the framework of the Flagship Pilot Study in southeastern South America (FPS-SESA) endorsed by the Coordinated Regional Climate Downscaling Experiments (CORDEX) program. The FPS-SESA initiative seeks to promote inter-institutional collaboration and further networking with focus on extreme rainfall events. The main scientific aim is to study multi-scale processes and interactions most conducive to extreme precipitation events through both statistical and dynamical downscaling techniques, including convection-permitting simulations. To this end, a targeted experiment was designed considering the season October 2009 to March 2010, a period with a record number of extreme precipitation events within SESA. Also, three individual extreme events within that season were chosen as case studies for analyzing specific regional processes and sensitivity to resolutions. Four dynamical and four statistical downscaling models (RCM and ESD respectively) from different institutions contributed to the experiment. In this work, an analysis of the capability of the set of the FPS-SESA downscaling methods in simulating daily precipitation during the selected warm season is presented together with an integrated assessment of multiple sources of observations and available CORDEX Regional Climate Model simulations. Comparisons among all simulations reveal that there is no single model that performs best in all aspects evaluated. The ability in reproducing the different features of daily precipitation depends on the model. However, the evaluation of the sequence of precipitation events, their intensity and timing suggests that FPS-SESA simulations based on both RCM and ESD yield promising results. Most models capture the extreme events selected, although with a considerable spread in accumulated values and the location of heavy precipitation.Thanks to CORDEX for endorsing the FPS-SESA. This work was supported by the University of Buenos Aires 2018- 20020170100117BA grant; JMG, MLB, SAS, RPR funding from the Spanish Research Council (CSIC) I-COOP+ Program “reference COOPB20374”. JMG, JF and AL-G acknowledge support from the Spanish R&D Program through projects MULTI-SDM (CGL2015-66583-R) and INSIGNIA (CGL2016-79210-R), co-funded by the European Regional Development Fund (ERDF/FEDER). AL-G acknowledges support from the Spanish R&D Program through the predoctoral contract BES-2016-078158. Universidad de Cantabria simulations have been carried out on the Altamira Supercomputer at the Instituto de Física de Cantabria (IFCA-CSIC), member of the Spanish Supercomputing Network. MB acknowledges support from the Simons Associateship of the Abdus Salam International Centre for Theoretical Physics. RH acknowledges support from the project LTT17007 funded by the Ministry of Education, Youth, and Sports of the Czech Republic

Scrutinizing environmental governance in a digital age: New ways of seeing, participating, and intervening

Digital technologies play an increasingly important role in addressing environmental challenges, such as climate change and resource depletion. Yet, the characteristics and implications of digitalized environmental governance are still under-conceptualized. In this perspective, we distinguish three dimensions of governance: (1) seeing and knowing, (2) participation and engagement, and (3) interventions and actions. For each dimension, we provide a critical perspective on the shifts that digital technologies generate in governance. We argue against the assumption that the use of digital technologies automatically results in improved outcomes or in more democratic decision-making. Instead, attention needs to be paid to the wider political and normative context in which digital technologies are proposed, designed, and used as environmental governance tools. We conclude with key questions for academics and policymakers to broaden the debate on responsible design and use of digital technologies in environmental governance

Targeting oncogenic Src homology 2 domain-containing phosphatase 2 (SHP2) by inhibiting its protein-protein interactions

We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2

Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib

Inflammatory response in hematopoietic stem and progenitor cells triggered by activating SHP2 mutations evokes blood defects

Gain-of-function mutations in the protein-tyrosine phosphatase SHP2 are the most frequently occurring mutations in sporadic juvenile myelomonocytic leukemia (JMML) and JMML-like myeloproliferative neoplasm (MPN) associated with Noonan syndrome (NS). Hematopoietic stem and progenitor cells (HSPCs) are the disease propagating cells of JMML. Here, we explored transcriptomes of HSPCs with SHP2 mutations derived from JMML patients and a novel NS zebrafish model. In addition to major NS traits, CRISPR/Cas9 knock-in Shp2 D61G mutant zebrafish recapitulated a JMML-like MPN phenotype, including myeloid lineage hyperproliferation, ex vivo growth of myeloid colonies, and in vivo transplantability of HSPCs. Single-cell mRNA sequencing of HSPCs from Shp2 D61G zebrafish embryos and bulk sequencing of HSPCs from JMML patients revealed an overlapping inflammatory gene expression pattern. Strikingly, an anti-inflammatory agent rescued JMML-like MPN in Shp2 D61G zebrafish embryos. Our results indicate that a common inflammatory response was triggered in the HSPCs from sporadic JMML patients and syndromic NS zebrafish, which potentiated MPN and may represent a future target for JMML therapies

The sixth international RASopathies symposium: Precision medicine—From promise to practice

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion