ePortfolios: Mediating the minefield of inherent risks and tensions

The ePortfolio Project at the Queensland University of Technology (QUT) exemplifies an innovative and flexible harnessing of current portfolio thinking and design that has achieved substantial buy-in across the institution with over 23000 active portfolios. Robust infrastructure support, curriculum integration and training have facilitated widespread take-up, while QUT’s early adoption of ePortfolio technology has enabled the concomitant development of a strong policy and systems approach to deal explicitly with legal and design responsibilities. In the light of that experience, this paper will highlight the risks and tensions inherent in ePortfolio policy, design and implementation. In many ways, both the strengths and weaknesses of ePortfolios lie in their ability to be accessed by a wider, less secure audience – either internally (e.g. other students and staff) or externally (e.g. potential employees and referees). How do we balance the obvious requirement to safeguard students from the potential for institutionally-facilitated cyber-harm and privacy breaches, with this generation’s instinctive personal and professional desires for reflections, private details, information and intellectual property to be available freely and with minimal restriction? How can we promote collaboration and freeform expression in the blog and wiki world but also manage the institutional risk that unauthorised use of student information and work so palpably carries with it? For ePortfolios to flourish and to develop and for students to remain engaged in current reflective processes, holistic guidelines and sensible boundaries are required to help safeguard personal details and journaling without overly restricting students’ emotional, collaborative and creative engagement with the ePortfolio experience. This paper will discuss such issues and suggest possible ways forward

Perceptions of Licensure: A Survey of Michigan Genetic Counselors

This study by the Michigan Genetic Counselor Licensure Committee is the first known published documentation of genetic counselors’ beliefs and attitudes about licensure. The response rate from genetic counselors in Michigan was 66% (41/62). Ninety‐five percent of respondents were supportive of licensure. Respondents believed licensure would legitimize genetic counseling as a distinct allied healthcare profession (97.5%), increase the public’s protection (75%), and allow genetic counselors to practice independently (67%). While 45% felt licensure would increase counselor involvement in lawsuits, this did not impact licensure support (p = 0.744). Opinions were split regarding physician supervision and ordering tests. Even though 28% favored physician supervision, there was overwhelming support for genetic counselors performing some components of genetic testing (95%) and ordering some types of genetic tests (82%) independent of a physician. Use of this survey may be helpful in other states to assess genetic counselors’ interest in licensure and for drafting legislation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147114/1/jgc40357.pd

Issues of collaboration, representation, meaning and emotions: Utilising participant-led visual diaries to capture the everyday lives of people in mid to later life

In recent years there has been an increasing use of visual methods in ageing research. There are, however, limited reflections and critical explorations of the implications of using visual methods in research with people in mid to later life. This paper examines key methodological complexities when researching the daily lives of people as they grow older and the possibilities and limitations of using participant-generated visual diaries. The paper will draw on our experiences of an empirical study, which included a sample of 62 women and men aged 50 years and over with different daily routines. Participant-led photography was drawn upon as a means to create visual diaries, followed by in-depth, photo-elicitation interviews. The paper will critically reflect on the use of visual methods for researching the daily lives of people in mid to later life, as well as suggesting some wider tensions within visual methods that warrant attention. First, we explore the extent to which photography facilitates a ‘collaborative’ research process; second, complexities around capturing the ‘everydayness’ of daily routines are explored; third, the representation and presentation of ‘self’ by participants within their images and interview narratives is examined; and, finally, we highlight particular emotional considerations in visualising daily life

TAK1 Is Required for Survival of Mouse Fibroblasts Treated with TRAIL, and Does So by NF-κB Dependent Induction of cFLIPL

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a “death ligand”—a member of the TNF superfamily that binds to receptors bearing death domains. As well as causing apoptosis of certain types of tumor cells, TRAIL can activate both NF-κB and JNK signalling pathways. To determine the role of TGF-β-Activated Kinase-1 (TAK1) in TRAIL signalling, we analyzed the effects of adding TRAIL to mouse embryonic fibroblasts (MEFs) derived from TAK1 conditional knockout mice. TAK1−/− MEFs were significantly more sensitive to killing by TRAIL than wild-type MEFs, and failed to activate NF-κB or JNK. Overexpression of IKK2-EE, a constitutive activator of NF-κB, protected TAK1−/− MEFs against TRAIL killing, suggesting that TAK1 activation of NF-κB is critical for the viability of cells treated with TRAIL. Consistent with this model, TRAIL failed to induce the survival genes cIAP2 and cFlipL in the absence of TAK1, whereas activation of NF-κB by IKK2-EE restored the levels of both proteins. Moreover, ectopic expression of cFlipL, but not cIAP2, in TAK1−/− MEFs strongly inhibited TRAIL-induced cell death. These results indicate that cells that survive TRAIL treatment may do so by activation of a TAK1–NF-κB pathway that drives expression of cFlipL, and suggest that TAK1 may be a good target for overcoming TRAIL resistance

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, \u3c160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks\u27 gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.)

Distinct Patterns of DNA Damage Response and Apoptosis Correlate with Jak/Stat and PI3Kinase Response Profiles in Human Acute Myelogenous Leukemia

BACKGROUND:Single cell network profiling (SCNP) utilizing flow cytometry measures alterations in intracellular signaling responses. Here SCNP was used to characterize Acute Myeloid Leukemia (AML) disease subtypes based on survival, DNA damage response and apoptosis pathways. METHODOLOGY AND PRINCIPAL FINDINGS:Thirty four diagnostic non-M3 AML samples from patients with known clinical outcome were treated with a panel of myeloid growth factors and cytokines, as well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K pathway responses in blasts from individual patient samples identified subgroups with distinct signaling profiles that were not seen in the absence of a modulator. In vitro exposure of patient samples to etoposide, a DNA damaging agent, revealed three distinct "DNA damage response (DDR)/apoptosis" profiles: 1) AML blasts with a defective DDR and failure to undergo apoptosis; 2) AML blasts with proficient DDR and failure to undergo apoptosis; 3) AML blasts with proficiency in both DDR and apoptosis pathways. Notably, AML samples from clinical responders fell within the "DDR/apoptosis" proficient profile and, as well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from clinical non responders had variable signaling profiles often with in vitro apoptotic failure and elevated PI3K pathway activity. Individual patient samples often harbored multiple, distinct, leukemia-associated cell populations identifiable by their surface marker expression, functional performance of signaling pathway in the face of cytokine or growth factor stimulation, as well as their response to apoptosis-inducing agents. CONCLUSIONS AND SIGNIFICANCE:Characterizing and tracking changes in intracellular pathway profiles in cell subpopulations both at baseline and under therapeutic pressure will likely have important clinical applications, potentially informing the selection of beneficial targeted agents, used either alone or in combination with chemotherapy

Application of the rainbow trout derived intestinal cell line (RTgutGC) for ecotoxicological studies: molecular and cellular responses following exposure to copper.

There is an acknowledged need for in vitro fish intestinal model to help understand dietary exposure to chemicals in the aquatic environment. The presence and use of such models is however largely restrictive due to technical difficulties in the culturing of enterocytes in general and the availability of appropriate established cell lines in particular. In this study, the rainbow trout (Oncorhynchus mykiss) intestinal derived cell line (RTgutGC) was used as a surrogate for the "gut sac" method. To facilitate comparison, RTgutGC cells were grown as monolayers (double-seeded) on permeable Transwell supports leading to a two-compartment intestinal model consisting of polarised epithelium. This two-compartment model divides the system into an upper apical (lumen) and a lower basolateral (portal blood) compartment. In our studies, these cells stained weakly for mucosubstances, expressed the tight junction protein ZO-1 in addition to E-cadherin and revealed the presence of polarised epithelium in addition to microvilli protrusions. The cells also revealed a comparable transepithelial electrical resistance (TEER) to the in vivo situation. Importantly, the cell line tolerated apical saline (1:1 ratio) thus mimicking the intact organ to allow assessment of uptake of compounds across the intestine. Following an exposure over 72 h, our study demonstrated that the RTgutGC cell line under sub-lethal concentrations of copper sulphate (Cu) and modified saline solutions demonstrated uptake of the metal with saturation levels comparable to short term ex situ gut sac preparations. Gene expression analysis revealed no significant influence of pH or time on mRNA expression levels of key stress related genes (i.e. CYP3A, GST, mtA, Pgp and SOD) in the Transwell model. However, significant positive correlations were found between all genes investigated suggesting a co-operative relationship amongst the genes studied. When the outlined characteristics of the cell line are combined with the division of compartments, the RTgutGC double seeded model represents a potential animal replacement model for ecotoxicological studies. Overall, this model could be used to study the effects and predict aquatic gastrointestinal permeability of metals and other environmentally relevant contaminants in a cost effective and high throughput manner

Data on vegetation across forest edges from the FERN(Forest Edge Research Network)

Published versionMany studies have focused on vegetation across forest edges to study impacts of edges created by human activities on forest structure and composition, or patterns of vegetation at inherent natural edges. Our objective was to create a database of plant-related variables across different types of edges from various studies (mainly from across Canada, but also in Brazil and Belize) to facilitate edge research. We compiled data on vegetation along more than 300 transects perpendicular to forest edges adjacent to clear-cuts, burned areas, bogs, lakes, barrens, insect disturbances, and riparian areas from 24 studies conducted over the past three decades. Data were compiled for more than 400 plant species and forest structure variables (e.g., trees, logs, canopy cover). All data were collected with a similar sampling design of quadrats along transects perpendicular to forest edges, but with varying numbers of transects and quadrats, and distances from the edge. The purpose for most of the studies was either to determine the distance of edge influence (edge width) or to explore the pattern of vegetation along the edge to interior gradient. We provide data tables for the cover of plant species and functional groups, the species and size of live and dead trees, the density of saplings, maximum height of functional groups and shrub species, and the cover of functional groups at different heights (vertical distribution of vegetation). The Forest Edge Research Network (FERN) database provides extensive data on many variables that can be used for further study including meta-analyses and can assist in answering questions important to conservation efforts (e.g., how is distance of edge influence from created edges affected by different factors?). We plan to expand this database with subsequent studies from the authors and we invite others to contribute to make this a more global database. The data are released under a CC0 license. When using these data, we ask that you cite this data paper and any relevant publications listed in our metadata file. We also encourage you to contact the first author if you are planning to use or contribute to this database

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant