Outcomes of Immune Checkpoint Inhibitor-Mediated Colitis: Multicenter Cohort Study

Title from PDF of title page viewed June 6, 2022VitaIncludes bibliographical references (pages 39-43)Thesis (M.S.)--School of Medicine. University of Missouri--Kansas City, 2022Thesis advisor: Monica GaddisImmune checkpoint inhibitor (ICI)-mediated colitis (IMC) is a common and serious toxicity. Multiple reports have described the clinical presentation and course of IMC based on limited data. This was a collaborative effort from several cancer institutes to investigate features and outcomes of IMC. This was a retrospective, cohort study of patients who received ICI and developed endoscopically/histologically confirmed IMC between 1/1/2011 and 12/31/2019. Multivariate logistic regression analyses were conducted to assess predictors of IMC recurrence and long duration of corticosteroids (> 60 days). A total of 674 patients were included. 383 patients were males (56.8%). Median age was 63 years. Melanoma was the most common cancer type (48.4%). Most patients (53.1%) received CTLA-4 inhibitor, as monotherapy or in combination with PD-(L)-1. Median time from ICI therapy to IMC was 61.5 days (31.8-126). IMC was grade 2 in 475 patients (71.3%), grade 3 in 177 (26.6%), and grade 4 in 14 (2.1%). On endoscopy, 153 patients (22.7%) had mucosal ulceration, 130 of patients had severe features (deep, large, or multiple ulcers); 336 patients (49.9%) had non-ulcerative inflammation. Most patients were admitted to the hospital for management of IMC (64.9%). Fifteen patients (2.5%) needed ICU-level of care. Corticosteroids were given to 576 patients (85.5%). Median length of corticosteroid therapy was 52 days. TNF inhibitors were given to 244 patients (36.2%). Ninety patients (13.4%) received vedolizumab. After resolution of symptoms, 201 patients (29.8%) had recurrent IMC. Predictors of IMC recurrence were days of hospitalization (P=0.003) , grade 4 IMC (P=0.001), and use of TNF inhibitor or vedolizumab (P=0.003). Factors associated with long (> 60 days) corticosteroid therapy were grade 3 IMC (P=0.049) and reception of infliximab or vedolizumab (P=0.044). Sixteen patients (2.4%) had colonic perforation, 7 of them underwent surgical resection of a part of the colon. No IMC-related death was recorded. In conclusion, IMC can lead to colonic perforation requiring surgical intervention and ICU admission. Higher grades of IMC or diarrhea and the use of TNF inhibitors or vedolizumab were associated with worse IMC outcomes, and therefore, patients with these features should be monitored closely and treated aggressively early in the course.Introduction -- Review of literature -- Methodology -- Results -- Discussion -- Appendi

Deuterium nuclear magnetic resonance (NMR) and rheology of microgel colloids at ambient and high pressure

Microgel colloids exhibit a polymer collapse transition resulting in a large reduction in colloid particle volume at high temperatures or pressures. They are of interest because of their potential for applications in areas, like drug delivery and chemical separation, that involve the uptake, encapsulation and release of small or biological molecules. The goal of this work is to obtain a microscopic understanding of the internal structure and microscopic dynamics of microgels by examining the temperature and pressure dependence of the collapse transition. Deuterium NMR (²H NMR) has been used to probe the microscopic dynamics of crosslinked poly N-isopropylacrylamide (polynipam) chains, in microgel colloids, as a function of temperature and pressure for a series of four crosslink densities (Cd). Each crosslinked microgel colloids was synthesized with deuteron labels on the nipam backbone (d3 nipam). Macroscopic properties of unlabeled colloids having the same crosslink densities were characterized by dynamic light scattering (DLS) and rheology. Rheological characterization as a function of temperature (T) and particle concentration (C), and for 4 crosslink densities, showed that the microgel viscosity decreases as temperature is increased. The Krieger- Dougherty model of the relative viscosity as a function of volume fraction was employed for viscosity analysis. The measured viscosity in the colloidal regime (at high T, low C) collapsed onto one line when plotted against volume fraction. This yields a measure of the water content in the particles as function of T. The water volume fraction in the microgel particle at 45ᴼC was always found to be 0.6 for any Cd. ²H NMR spectra of the d3 nipam suspensions for all Cd indicated freely moving chains at low temperature and a nearly immobilized fraction above 35ᴼC. This is consistent with DLS observations of a transition from swollen to collapsed colloids. Nipam segments in the collapsed phase of the d3 nipam suspension were more mobile than those in the dry powder. This suggests significant amounts of water in the collapsed phase, a finding consistent with the rheology observations. Variable pressure NMR (up to 90 MPa) showed a slight increase in transition temperature with pressure for all Cd values studied

Trajectories to reconcile sharing and commercialization in the maker movement

Maker technologies, including collaborative digital fabrication tools like 3-D printers, enable entrepreneurial opportunities and new business models. To date, relatively few highly successful maker startups have emerged, possibly due to the dominant mindset of the makers being one of cooperation and sharing. However, makers also strive for financial stability and many have profit motives. We use a multiple case study approach to explore makers' experiences regarding the tension between sharing and commercialization and their ways of dealing with it. We conducted interviews with maker initiatives across Europe including Fab Labs, a maker REtD center, and other networks of makers. We unpack and contextualize the concepts of sharing and commercialization. Our cross-case analysis leads to a new framework for understanding these entrepreneurs' position with respect to common good versus commercial offerings. Using the framework, we describe archetypal trajectories that maker initiatives go through in the dynamic transition from makers to social enterprises and social entrepreneurs. (C) 2017 Kelley School of Business, Indiana University. Published by Elsevier Inc. All rights reserved

Deuterium NMR and rheology of microgel colloids at ambient and high pressure

Microgel colloids exhibit a polymer collapse transition resulting in a large reduction in colloid size at high temperatures or pressures. Our goal is to obtain a microscopic understanding of the internal structure and microscopic dynamics of microgels by examining the temperature and pressure dependence of the collapse transition. We have conducted a systematic study of how the nature of this collapse transition is affected by crosslink density (Cd). We used deuterium NMR (2H-NMR) to probe the microscopic dynamics of cross-linked poly-N-isopropylacrylamide (p-nipam) chains, in microgel colloids, as a function of temperature and pressure. Four differently crosslinked microgels colloids were synthesized with deuteron labels on the nipam backbone (d3- nipam). Corresponding macroscopic properties of unlabeled colloids having the same crosslink densities were characterized by dynamic light scattering (DLS) and rheology. Rheological characterization as a function of temperature (T) and particle concentration (c), and for 4 crosslink densities, showed that the microgel viscosity decreases as temperature is increased, and that in the high T/low c regime, there is a collapse of the viscosity as a function of T and c when plotted against volume fraction: this yields a measure of the water content in the particles as function of T. 2H-NMR spectra of the d3-nipam suspensions for all Cd indicated freely moving chains at low temperature and a nearly immobilized fraction above 35°C. This is consistent with DLS observations of a transition from swollen to collapsed colloids. 2H-NMR spectra for the dry powder indicated totally immobilized segments in the particle. Nipam segments in the collapse phase of the d3-nipam suspension were more mobile than those in the dry powder. This suggests significant amounts of water in the collapsed phase, a finding consistent with the rheology observations. For the highest two values of Cd, microgel spectra showed the presence of an immobilized fraction of segments even in the swollen phase. Variable pressure NMR (up to 90 MPa) showed a slight increase in transition temperature with pressure for all Cd values studied

Environmental Life Cycle Assessment

Environmental Life Cycle Assessment is a pivotal guide to identifying environmental problems and reducing related impacts for companies and organizations in need of life cycle assessment (LCA). LCA, a unique sustainability tool, provides a framework that addresses a growing demand for practical technological solutions. Detailing each phase of the LCA methodology, this textbook covers the historical development of LCA, presents the general principles and characteristics of LCA, and outlines the corresponding standards for good practice determined by the International Organization for Standardization. It also explains how to identify the critical aspects of an LCA, provides detailed examples of LCA analysis and applications, and includes illustrated problems and solutions with concrete examples from water management, electronics, packaging, automotive, and other industries. In addition, readers will learn how to: Use consistent criteria to realize and evaluate an LCA independently of individual interests Understand the LCA methodology and become familiar with existing databases and methods based on the latest results of international research Analyze and critique a completed LCA Apply LCA methodology to simple case studies Geared toward graduate and undergraduate students studying environmental science and industrial ecology, as well as practicing environmental engineers, and sustainability professionals who want to teach themselves LCA good practices, Environmental Life Cycle Assessment demonstrates how to conduct environmental assessments for products throughout their life cycles. It presents existing methods and recent developments in the growing field of LCA and systematically covers goal and system definition, life cycle inventory, life cycle impact assessment, and interpretation

Groundwater balance politics: Aquifer overexploitation in the Orontes River Basin

Aquifer overexploitation is widely used to describe negative effects on groundwater resources but has no agreed scientific definition. Usually viewed as a situation where average aquifer abstraction exceeds average recharge, a diagnosis of groundwater overdraft calls upon specific hydrogeological instruments, based on the groundwater balance approach. An analytical method for assessing changes in water flows and stocks through time and space, groundwater balance is also a tool for the investigation of knowledge construction and its embeddedness within power relations. We propose to discuss the politics of groundwater overexploitation diagnoses in Syria and more specifically the Orontes River Basin prior to the 2011 uprising and subsequent conflict. Groundwater overdraft at the national level became a matter of concern in official discourse in the late 1990s as diagnoses of groundwater overexploitation became commonplace in international reports. The steady increase in groundwater abstraction in relation to Syria’s centralised agricultural planning from the 1960s onward had undeniable consequences on the hydro-social system. However, the way diagnoses of groundwater overexploitation – in particular groundwater balances – were constructed and used to support water policies implemented from the mid-1990s onwards question the rationalities and interests lying behind technical arguments and actions

Overview On The Epidemiological Situation And The Brucellosis’ Control, Between 1974 -2014, In West Bank, Palestine

Brucellosis in Palestine is a problem of huge concern due to the human health impact, as consequence of the high prevalence level of the infection in livestock. The purpose of the research was to give an insight of the current epidemiological peculiarities of the brucellosis in livestock versus human population. This paper processed all data of the brucellosis’ control program and the epidemio-surveillance results. The seroprevalence of brucellosis in 1999, was 18% in sheep and goat and 80% in flocks, and more than 800 human cases. As result of mass vaccination, with 80% coverage vaccination rate, the decrease of brucellosis was registered: 4.8% in animals and 40% in flock; human infection less than 200 cases. The main conclusion of our study is that the vaccination must be in force up to the level of prevalence, below 2% in animals, allowing the next step, the “test-and-slaughter” strategy, toward the eradication goal