p63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response.

Hyperproliferative keratinocytes induced by trauma, hyperkeratosis and/or inflammation display molecular signatures similar to those of palmoplantar epidermis. Inherited gain-of-function mutations in RHBDF2 (encoding iRHOM2) are associated with a hyperproliferative palmoplantar keratoderma and squamous oesophageal cancer syndrome (termed TOC). In contrast, genetic ablation of rhbdf2 in mice leads to a thinning of the mammalian footpad, and reduces keratinocyte hyperproliferation and migration. Here, we report that iRHOM2 is a novel target gene of p63 and that both p63 and iRHOM2 differentially regulate cellular stress-associated signalling pathways in normal and hyperproliferative keratinocytes. We demonstrate that p63-iRHOM2 regulates cell survival and response to oxidative stress via modulation of SURVIVIN and Cytoglobin, respectively. Furthermore, the antioxidant compound Sulforaphane downregulates p63-iRHOM2 expression, leading to reduced proliferation, inflammation, survival and ROS production. These findings elucidate a novel p63-associated pathway that identifies iRHOM2 modulation as a potential therapeutic target to treat hyperproliferative skin disease and neoplasia

Narrative Medicine: A Reflective Writing Workshop Series for Interprofessional Healthcare Students at Thomas Jefferson University

Introduction: Narrative medicine (NM) teaches reflective writing and close reading to help healthcare professionals think critically about themselves and others in order to offer more effective, empathic care. Few reports of NM methods document its value to facilitating collaboration and communication across students of different professional backgrounds. This study examines the effects of NM workshops on Thomas Jefferson University interprofessional healthcare students, and their utility to achieving these aims: 1) supporting thoughtfulness, mindfulness, and curiosity; 2) supporting the development and use of narrative in understanding the lives/contexts for self and others; 3) improving interactions and communication with others in professional and clinical contexts; 4) supporting humanism and whole person care (including self-care). Methods: Six bi-weekly, one-hour long NM reflective writing workshops were offered as a voluntary elective for interprofessional healthcare students. Participants completed a post-series questionnaire. Closed-ended responses were summarized, open-ended questions were analyzed using qualitative content analysis. Results: Twelve participants completed the questionnaire (8 medical students of different years, 1 MD/PhD student, 2 nursing students, 1 occupational therapy student). All participants reported that main aims 1) and 2) were achieved. 92% of participants reported that main aims 3) and 4) were achieved. 83% found the narrative exercises valuable to facilitating relationships with others of different professional backgrounds in the workshops, and to facilitating or advancing relationships with peers/colleagues outside of the workshops. 83% found the exercises helpful to reducing divides between interprofessional students. Qualitative analysis facilitated the organization of codes into 4 thematic categories: change, understanding, reflection, difference. Discussion: A NM intervention providing consistent exposure to NM methods was successfully implemented. This was a feasible, effective method for promoting reflection, understanding of self/others, whole person care/self-care, and communication and collaboration amongst interprofessional healthcare students. Workshop objectives were achieved, and participants reported personal and professional value and utility in participation

Views from within a narrative : Evaluating long-term human-robot interaction in a naturalistic environment using open-ended scenarios

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Date of acceptance: 16/06/2014This article describes the prototyping of human–robot interactions in the University of Hertfordshire (UH) Robot House. Twelve participants took part in a long-term study in which they interacted with robots in the UH Robot House once a week for a period of 10 weeks. A prototyping method using the narrative framing technique allowed participants to engage with the robots in episodic interactions that were framed using narrative to convey the impression of a continuous long-term interaction. The goal was to examine how participants responded to the scenarios and the robots as well as specific robot behaviours, such as agent migration and expressive behaviours. Evaluation of the robots and the scenarios were elicited using several measures, including the standardised System Usability Scale, an ad hoc Scenario Acceptance Scale, as well as single-item Likert scales, open-ended questionnaire items and a debriefing interview. Results suggest that participants felt that the use of this prototyping technique allowed them insight into the use of the robot, and that they accepted the use of the robot within the scenarioPeer reviewe

Machine Learning Enables Prompt Prediction of Hydration Kinetics of Multicomponent Cementitious Systems

Carbonaceous (e.g., limestone) and aluminosilicate (e.g., calcined clay) mineral additives are routinely used to partially replace ordinary portland cement in concrete to alleviate its energy impact and carbon footprint. These mineral additives—depending on their physicochemical characteristics—alter the hydration behavior of cement; which, in turn, affects the evolution of microstructure of concrete, as well as the development of its properties (e.g., compressive strength). Numerical, reaction-kinetics models—e.g., phase boundary nucleation-and-growth models; which are based partly on theoretically-derived kinetic mechanisms, and partly on assumptions—are unable to produce a priori prediction of hydration kinetics of cement; especially in multicomponent systems, wherein chemical interactions among cement, water, and mineral additives occur concurrently. This paper introduces a machine learning-based methodology to enable prompt and high-fidelity prediction of time-dependent hydration kinetics of cement, both in plain and multicomponent (e.g., binary; and ternary) systems, using the system’s physicochemical characteristics as inputs. Based on a database comprising hydration kinetics profiles of 235 unique systems—encompassing 7 synthetic cements and three mineral additives with disparate physicochemical attributes—a random forests (RF) model was rigorously trained to establish the underlying composition-reactivity correlations. This training was subsequently leveraged by the RF model: to predict time-dependent hydration kinetics of cement in new, multicomponent systems; and to formulate optimal mixture designs that satisfy user-imposed kinetics criteria

Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms

Research on iRHOM2 in the Kelsell group is funded by an MRC project grant, a MRC Clinical Fellowship (to TM) and a Cancer Research UK program grant

The Silk Road Health Project: How Mobility and Migration Status Influence HIV Risks among Male Migrant Workers in Central Asia

Objectives We examined whether mobility, migrant status, and risk environments are associated with sexually transmitted infections (STIs) and HIV risk behaviors (e.g. sex trading, multiple partners, and unprotected sex). Methods We used Respondent Driven Sampling (RDS) to recruit external male migrant market vendors from Kyrgyzstan, Uzbekistan, and Tajikistan as well internal migrant and non-migrant market vendors from Kazakhstan. We conducted multivariate logistic regressions to examine the effects of mobility combined with the interaction between mobility and migration status on STIs and sexual risk behaviors, when controlling for risk environment characteristics. Results Mobility was associated with increased risk for biologically-confirmed STIs, sex trading, and unprotected sex among non-migrants, but not among internal or external migrants. Condom use rates were low among all three groups, particularly external migrants. Risk environment factors of low-income status, debt, homelessness, and limited access to medical care were associated with unprotected sex among external migrants. Conclusion Study findings underscore the role mobility and risk environments play in shaping HIV/STI risks. They highlight the need to consider mobility in the context of migration status and other risk environment factors in developing effective prevention strategies for this population

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated