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IntroductionAs new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings.Methods and analysisThe TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events.Ethics and disseminationTARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals.Trial registration numberNCT03661866, pre-results.

Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first-line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S. Food and Drug Administration approved obeticholic acid to be used in certain patients with PBC. Off-label therapies are also used, and several other therapies are currently under evaluation. Real-world effectiveness of newly approved and off-label therapies remains unknown. TARGET-PBC is a 5-year, longitudinal, observational study of patients with PBC that will evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. Enrollment will take place at both academic and community sites. In addition to consenting to medical records review, participants will be asked to provide an annual blood sample and complete patient reported outcome surveys at predetermined intervals. Any available liver biopsies will be digitally preserved. Conclusion: Key study outcomes will be the evaluation of the safety and effectiveness of PBC interventions and the assessment of disease progression under real-world conditions. (Hepatology Communications 2018;2:484-491).

We document a set of artistic reconstructions of Elliot Eisner's "The Educational Imagination" which took place during a graduate seminar in contemporary curriculum discourses. In this project, students and their instructor collaboratively explored "The Educational Imagination" as a site for an arts-based examination of knowing, identity, and textual authority. Participants created sculptural representations of the text. The sculptures functioned alternately as artworks and experimental places of learning, thus suggesting alternative practices by which the educational experience might be reimagined. In producing these textual/artistic reconstructions, participants created an intersubjective/interpersonal dialogue as they analyzed the educational, aesthetic, and ideological factors which shaped their thinking about curriculum as remade from Eisner's text.

Chaperone‐mediated autophagy (CMA) is a lysosome‐dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age‐associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age‐associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS‐32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age‐related bone loss, we hypothesized that declining CMA contributes to the age‐associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA‐deficient mice and controls up to 24 months of age and examined age‐associated changes in bone mass and architecture. We showed that lack of CMA did not alter age‐associated decline in bone mineral density as measured by dual x‐ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA‐deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age‐related bone loss. [ABSTRACT FROM AUTHOR]

"transeant Things": Materialism and Mortality in the Lyrics of Lucy Hutchinson and Margaret C... Graph. [Extracted from the article]

Sex Before Sex: Figuring the Act in Early Modern England James Bromley and Will Stockton, eds. Minneapolis: University of Minnesota Press, 2013 Since the publication of Alan Bray's Homosexuality in [...]

This essay argues that we should understand Margaret Cavendish and Lucy Hutchinson as secretaries in the practically activist humanist tradition. Both women served as keepers of (family and political) secrets, and as readers, writers, and record keepers of papers. Hutchinson calls herself 'the faithful depository' of her husband's 'secrets', and alludes to her facility with his signature, or 'character', throughout the Memoirs. In many ways, the Memoirs themselves are a vindication of his belief in her capacities. Margaret Cavendish similarly presents herself as her husband's secretary, including in her 'Life of William Cavendish' not only a robust and notably politic account of her husband's expenditures on behalf of the monarchy – 'a Computation of My Lord's Losses' – but also a record of 'some Essayes and Discourses of My Lords, together with some Notes and Remarques of mine own'. In doing so, Cavendish remarshalls the consiliary wisdom of William Cavendish's own advice to princes as ballast for his continued political relevance and for her own secretarial and advisory competency. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) patients undergoing treatment may only experience partial improvements in their itch and skin lesions. However, partial improvement may not translate into optimal patient outcomes. There is limited evidence describing the impact of achieving higher efficacy measures in AD. Objectives To assess the independent and combined effects of itch and skin of improvement on patient-reported symptoms and quality-of-life outcomes. Methods The study included adult participants (age ≥18 years) with AD enrolled in TARGET-DERM AD, an observational, longitudinal study of >4,000 participants across 52 academic/community centers in the United States and Canada. Itch severity was assessed by the Patient-Reported Outcome Measurement Information System (PROMIS) Itch-Severity[3] item evaluating "itch at its worst" on a 0–10 numeric rating scale (NRS). A score of 0 or 1 indicated no/minimal itch (NRS-Itch 0/1). Skin severity was assessed by the validated Investigator Global Assessment of AD (vIGA-AD), with 0 or 1 representing clear/almost clear skin (vIGA-AD 0/1). The association of itch and skin severity with scores representing an ideal state in AD symptoms and quality of life outcomes were assessed as follows: patient-reported clear/almost clear disease (Patient-Oriented Eczema Measure [POEM] 0–2), little or no impact of AD on quality of life (Dermatology Life Quality Index [DLQI] 0/1), little or no sleep impact (NRS-Sleep 0/1), and little or no pain (NRS-Pain 0/1). Associations were assessed using descriptive statistics and logistic regression models including main and interaction effects for itch and skin severity. Results Among adult participants (n=1920; mean age 45 years, 59% female; 55% Non-Hispanic White), data was available from participants at enrollment for the outcomes as follows: vIGA-AD (99%, 1,913), NRS-Itch (54%, 1,042), DLQI (50%, 967), POEM (51%, 974), NRS-Sleep (50%, 958), and NRS-Pain (50%, 965). The proportion reporting ideal state scores was highest among those with NRS-Itch 0/1 (52% DLQI 0/1; 54% POEM 0–2; 57% NRS-Sleep 0/1; 83% NRS-Pain 0/1) and clear/almost clear skin (45% DLQI 0/1; 44% POEM 0–2; 45% NRS-Sleep 0/1; 74% NRS-Pain 0/1), with decreasing proportions generally observed at greater itch and skin severity levels. Among patients who had vIGA-AD 0/1, the proportion of participants with an ideal state score for all PROs increases substantially when patients also attain NRS itch 0/1: 69% DLQI 0/1, 78% POEM 0–2, 68% NRS-Sleep 0/1, and 92% NRS-Pain 0/1. The adjusted odds ratio of reporting DLQI 0/1, POEM 0–2, NRS-Sleep 0/1, and NRS-Pain 0/1 was highest among those with both no/minimal itch and clear/almost clear skin (20.0, 41.6, 6.0, and 16.1, respectively), followed by no/minimal itch only (6.1, 6.7, 3.1, and 4.3, respectively), and clear/almost clear skin only (4.4, 5.0, 1.6, and 3.0, respectively). Conclusions Achieving complete or almost complete resolution of itch and skin lesions is associated with greater odds of achieving an ideal state in terms of patient reported symptoms and quality of life (DLQI, POEM, NRS-Sleep, and NRS-Pain) with itch relief exhibiting a slightly higher impact than skin clearance. These results underscore the importance of assessing and documenting both itch severity and skin clearance to support shared decision-making. Moreover, simultaneous resolution of both itch and skin lesions should be considered when setting treatment goals in AD patients. [ABSTRACT FROM AUTHOR]