The search for novel analgesics: re-examining spinal cord circuits with new tools

In this perspective, we propose the absence of detailed information regarding spinal cord circuits that process sensory information remains a major barrier to advancing analgesia. We highlight recent advances showing that functionally discrete populations of neurons in the spinal cord dorsal horn play distinct roles in processing sensory information. We then discuss new molecular, electrophysiological, and optogenetic techniques that can be employed to understand how dorsal horn circuits process tactile and nociceptive information. We believe this information can drive the development of entirely new classes of pharmacotherapies that target key elements in spinal circuits to selectively modify sensory function and blunt pain

Predictive Lateral Logic for Numerical Entry Guidance Algorithms

Recent entry guidance algorithm development123 has tended to focus on numerical integration of trajectories onboard in order to evaluate candidate bank profiles. Such methods enjoy benefits such as flexibility to varying mission profiles and improved robustness to large dispersions. A common element across many of these modern entry guidance algorithms is a reliance upon the concept of Apollo heritage lateral error (or azimuth error) deadbands in which the number of bank reversals to be performed is non-deterministic. This paper presents a closed-loop bank reversal method that operates with a fixed number of bank reversals defined prior to flight. However, this number of bank reversals can be modified at any point, including in flight, based on contingencies such as fuel leaks where propellant usage must be minimized

Poster 481 Metastatic Crohn Disease Manifesting as Skin Ulcerations in a Stroke Patient With Quadriplegia: A Case Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146877/1/pmr2s343.pd

Happiness as stable extraversion : internal consistency reliability and construct validity of the Oxford Happiness Questionnaire among undergraduate students

The Oxford Happiness Questionnaire (OHQ) was developed by Hills and Argyle (2002) to provide a more accessible equivalent measure of the Oxford Happiness Inventory (OHI). The aim of the present study was to examine the internal consistency reliability, and construct validity of this new instrument alongside the Eysenckian dimensional model of personality. The Oxford Happiness Questionnaire was completed by a sample of 131 undergraduate students together with the abbreviated form of the Revised Eysenck Personality Questionnaire. The data demonstrated good internal consistency reliability (alpha = .92) and good construct validity in terms of positive association with extraversion (r = .38 p < .001) and negative association with neuroticism (r = −.57 p < .001). The kind of happiness measured by the OHQ is clearly associated with stable extraversion

Addressing health literacy in patient decision aids

MethodsWe reviewed literature for evidence relevant to these two aims. When high-quality systematic reviews existed, we summarized their evidence. When reviews were unavailable, we conducted our own systematic reviews.ResultsAim 1: In an existing systematic review of PtDA trials, lower health literacy was associated with lower patient health knowledge (14 of 16 eligible studies). Fourteen studies reported practical design strategies to improve knowledge for lower health literacy patients. In our own systematic review, no studies reported on values clarity per se, but in 2 lower health literacy was related to higher decisional uncertainty and regret. Lower health literacy was associated with less desire for involvement in 3 studies, less question-asking in 2, and less patient-centered communication in 4 studies; its effects on other measures of patient involvement were mixed. Only one study assessed the effects of a health literacy intervention on outcomes; it showed that using video to improve the salience of health states reduced decisional uncertainty. Aim 2: In our review of 97 trials, only 3 PtDAs overtly addressed the needs of lower health literacy users. In 90% of trials, user health literacy and readability of the PtDA were not reported. However, increases in knowledge and informed choice were reported in those studies in which health literacy needs were addressed.ConclusionLower health literacy affects key decision-making outcomes, but few existing PtDAs have addressed the needs of lower health literacy users. The specific effects of PtDAs designed to mitigate the influence of low health literacy are unknown. More attention to the needs of patients with lower health literacy is indicated, to ensure that PtDAs are appropriate for lower as well as higher health literacy patients

Peer Review Report: Ontologies Relevant to Behaviour Change Interventions, version 1

In “Ontologies Relevant to behaviour change interventions: A Method for their Development” Wright, et al. outline a step by step process for building ontologies of behaviour modification – what the authors call the Refined Ontology Developmental Method (RODM) – and demonstrate its use in the development of the Behaviour Change Intervention Ontology (BCIO). RODM is based on the principles of good ontology building used by the Open Biomedical Ontology (OBO) Foundry in addition to those outlined in (Arp, Smith, and Spear 2015). BCIO uses as its top-level ontology Basic Formal Ontology (BFO). The methods outlined in Wright, et al. are a valuable contribution to the field, especially the use of formal mechanisms for literature annotation and expert stakeholder review, and the BCIO will certainly play an important role in the extension of OBO Foundry ontologies into the behavioural domain

Down-regulation of sfrp1 in a mammary epithelial cell line promotes the development of a cd44high/cd24low population which is invasive and resistant to anoikis

<p>Abstract</p> <p>Background</p> <p>The Wnt family of secreted proteins is implicated in the regulation of cell fate during development, as well as in cell proliferation, morphology, and migration. Aberrant activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway by competing with the Frizzled receptor for Wnt ligands resulting in an attenuation of the signal transduction cascade. Loss of SFRP1 expression is observed in breast cancer, along with several other cancers, and is associated with poor patient prognosis. However, it is not clear whether the loss of SFRP1 expression predisposes the mammary gland to tumorigenesis.</p> <p>Results</p> <p>When SFRP1 is knocked down in a non-malignant immortalized mammary epithelial cell line (76 N TERT), nuclear levels of β-catenin rise and the Wnt pathway is stimulated. The SFRP1 knockdown cells exhibit increased expression of the pro-proliferative Cyclin D1 gene and increased cellular proliferation, undergo a partial epithelial-mesenchymal transition (EMT), are resistant to anchorage-independent cell death, exhibit increased migration, are significantly more invasive, and exhibit a CD24^low/CD44^highcell surface marker expression pattern.</p> <p>Conclusion</p> <p>Our study suggests that loss of SFRP1 allows non-malignant cells to acquire characteristics associated with breast cancer cells.</p

More than a cognitive experience: unfamiliarity, invalidation, and emotion in organizational learning

Literature on organizational learning (OL) lacks an integrative framework that captures the emotions involved as OL proceeds. Drawing on personal construct theory, we suggest that organizations learn where their members reconstrue meaning around questions of strategic significance for the organization. In this 5-year study of an electronics company, we explore the way in which emotions change as members perceive progress or a lack of progress around strategic themes. Our framework also takes into account whether OL involves experiences that are familiar or unfamiliar and the implications for emotions. We detected similar patterns of emotion arising over time for three different themes in our data, thereby adding to OL perspectives that are predominantly cognitive in orientation