Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations

In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination

A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia

Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5-ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis, we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signaling disruption and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis and is influenced by cell-intrinsic, extrinsic, and therapeutic selective pressures. Keywords: cell plasticity; colorectal cancer; colorectal neoplasia; intestinal polyps; intestinal stem cells; molecular phenotyping; stem cells

A Blueprint to Evaluate One Health

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the “Network for Evaluation of One Health,” an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes (i.e., sustainability, health and welfare, interspecies equity and stewardship, effectiveness, and efficiency), which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy

Birds of a Feather? Magellan/IMACS Spectroscopy of the Ultra-faint Satellites Grus II, Tucana IV, and Tucana V*

We present Magellan/IMACS spectroscopy of three recently discovered ultra-faint Milky Way satellites, Grus II, Tucana IV, and Tucana V. We measure systemic velocities of vhel=-110.0 ± 0.5 kms-1, vhel= 15.9-1.7 +1.8kms-1 and vhel=-36.2-2.2 +2.5 kms-1 for the three objects, respectively. Their large relative velocities demonstrate that the satellites are unrelated despite their close physical proximity. We determine a velocity dispersion for Tuc IV of σ = 4.3-1.0 +1.7km s-1 but we cannot resolve the velocity dispersions of the other two systems. For Gru II, we place an upper limit (90% confidence) on the dispersion of σ < 1.9 kms-1 and for Tuc V, we do not obtain any useful limits. All three satellites have metallicities below, but none has a detectable metallicity spread. We determine proper motions for each satellite based on Gaia astrometry and compute their orbits around the Milky Way. Gru II is on a tightly bound orbit with a pericenter of 25-7 +6 kpc and orbital eccentricity of 0.45-0.05 +0.08. Tuc V likely has an apocenter beyond 100 kpc and could be approaching the Milky Way for the first time. The current orbit of Tuc IV is similar to that of Gru II, with a pericenter of 25-8 +11 kpc and an eccentricity of 0.36-0.06 +0.13. However, a backward integration of the position of Tuc IV demonstrates that it collided with the Large Magellanic Cloud at an impact parameter of 4 kpc ∼120 Myr ago, deflecting its trajectory and possibly altering its internal kinematics. Based on their sizes, masses, and metallicities, we classify Gru II and Tuc IV as likely dwarf galaxies, but the nature of Tuc V remains uncertain. © 2020 The American Astronomical Society. All rights reserved

The Ozone Monitoring Instrument: Overview of 14 years in space

This overview paper highlights the successes of the Ozone Monitoring Instrument (OMI) on board the Aura satellite spanning a period of nearly 14 years. Data from OMI has been used in a wide range of applications and research resulting in many new findings. Due to its unprecedented spatial resolution, in combination with daily global coverage, OMI plays a unique role in measuring trace gases important for the ozone layer, air quality, and climate change. With the operational very fast delivery (VFD; direct readout) and near real-time (NRT) availability of the data, OMI also plays an important role in the development of operational services in the atmospheric chemistry domain

Room Temperature Hydrogenation of CO2 Utilizing a Cooperative Phosphorus Pyridone‐Based Iridium Complex

The synthesis, characterization and application of a new complex, [Ir(κ2-P,N-6-DCyPon*)(COD)] (1), where 6-DCyPon* is the anionic species, 6-dicyclohexylphosphino-2-oxo-pyridinide, is reported herein. Complex 1 was found to be an active catalyst in the hydrogenation of CO2 at room temperature. The ligand, 6-DCyPon*, is derived via deprotonation of a novel pro-ligand, 6-DCyPon (6-dicyclohexylphosphino-2-pyridone) during the synthesis of 1. The ligand is shown to participate within the reversible hydrogenation of 1, via a cooperative process, in which the species, [IrH3(κ2-P,N-6-DCyPon)(COD)] (2), was spectroscopically characterized, where 1 reacts with two equivalents of H2

History-sensitive versus future-sensitive approaches to security in distributed systems

We consider the use of aspect-oriented techniques as a flexible way to deal with security policies in distributed systems. Recent work suggests to use aspects for analysing the future behaviour of programs and to make access control decisions based on this; this gives the flavour of dealing with information flow rather than mere access control. We show in this paper that it is beneficial to augment this approach with history-based components as is the traditional approach in reference monitor-based approaches to mandatory access control. Our developments are performed in an aspect-oriented coordination language aiming to describe the Bell-LaPadula policy as elegantly as possible. Furthermore, the resulting language has the capability of combining both history- and future-sensitive policies, providing even more flexibility and power.Comment: In Proceedings ICE 2010, arXiv:1010.530