Informed Choices in Biobanking: An Examination of Participants' Understanding and Congruence between Knowledge, Values, and Decisions

The ethical foundation of clinical research is informed consent. Biobanking has added to the complexity of the informed consent process. Biomedical research with human biospecimens often occurs without any consent or with inadequately understood consent information. Yet, the use of biospecimens in research is not without controversy. One abundant source of biospecimens for research is residual dried blood spots (rDBS) from newborn screenings. Approximately 4 million infants are born annually in the United States (U.S.) and most have mandatory newborn screening. In 2010, the state of Michigan implemented a process of written parental consent for donating newborns’ residual dried blood spots to the Michigan BioTrust for research. Thus, biobanking of newborn rDBS in Michigan presented a prime opportunity to study mothers’ level of knowledge, attitudes, values, and decision-making after a broad consent process for donating their newborn’s rDBS for research. Therefore, the purposes of this dissertation research are to a) describe the current state of the science regarding participants’ understanding of informed consent for biobanking; b) describe the influence of mothers’ knowledge (understanding of biobanking), values (personal and religious), and perceptions of the informed consent process (content and context) on their decisions to donate their newborn’s rDBS for research purposes; c) compare and contrast mothers’ knowledge of and attitudes towards biobanking, socio-demographics, and personal and religious values with their decisions (yes or no) to donate their newborn’s rDBs for research purposes and determine the proportion of informed choices. A qualitative descriptive design, a non-experimental survey, and methodological triangulation are used in this three-paper style dissertation. The first of the three papers (Chapter 2) is a systematic review to evaluate participants’ level of understanding of the information presented during the consent process for donation of biological specimens for research purposes (i.e., for biobanking or genetic epidemiological studies). Results indicated many elements of informed consent unique to biobanking were inadequately understood by potential participants. Next, semi-structured interviews (Chapter 3) were used to describe mothers’ understanding of biobanking, attitudes about rDBS research, and the influence of personal values on the decision-making process. Findings indicated that while most mothers agreed (14/20; 70%) to donate the rDBS and expressed favorable attitudes about research, most decisions (16/20; 80%) were determined to be uniformed choices due to inadequate knowledge of the Michigan BioTrust and biobanking. A non-experimental, descriptive and correlational survey was randomly distributed to 500 mothers in the state of Michigan with a newborn age 0-3 months (Chapter 4) to examine knowledge, attitudes and values, and the proportion of informed choices in a larger sample using standardized instruments. Just over half of the mothers (55%) in this study were deemed to have made an informed choice; however, knowledge scores were still low. On average, respondents were only able to correctly answer approximately 8/16 biobanking questions. With 4 million American newborns having blood spots each year there are significant policy implications to this research (Chapter 5). Three recommendations are put forth: include the ethical implications of biobanking in educational materials, enhance consenters’ knowledge about rDBS research and their communication skills for conducting informed consent processes, and move the educational content about rDBS research to the prenatal setting (Chapter 5).PHDNursingUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/146015/1/eeisen_1.pd

Population survival impact of new targeted and immune based therapies for metastatic or unresectable melanoma

Introduction New classes of drugs for metastatic or unresectable melanoma (MM) have shown improved survival in randomized trials (e.g., anti-CTLA-4, anti-PD-1, BRAF/MEK inhibitors). We sought to describe uptake of these new drugs and their impact on population-based survival outcomes of MM. Objectives and Approach We sought to describe uptake of these new drugs and their impact on population-based survival outcomes of MM. This was a retrospective, population-based cohort study of all treated MM in Ontario 2007-2015. Administrative data sources from the Institute for Clinical Evaluative Sciences (ICES) were utilized. Within ICES, cutaneous and non-cutaneous primaries were identified in the Ontario Cancer Registry. Administrative sources from Cancer Care Ontario, Ministry of Health and Long-Term Care, and Canadian Institute for Health Information identified patients treated with palliative systemic therapy, radiotherapy and metastatectomy. Temporal trends in utilization and survival were investigated. Survival by drug class was described. Results We identified 2,793 MM patients. First treatment was systemic therapy (46%), radiotherapy (41%) or metastatectomy (14%). MM patient number increased from 270 in 2007 to 418 in 2015. Systemic treatment rose from 125 MM first treated in 2007 to 343 in 2015. New drug treatments increased from <6% of reported first-line regimens in 2007 to 82\% in 2015. 1-year and 2-year overall survival (OS) was 28% and 15% respectively for all MM in 2007-2009, rising to 46% and 35% for 2014-2015 (logrank p<0.001; adjusted hazard ratio (AHR) 0.56, 95% confidence interval (CI): (0.49,0.63)). Survival gains were largely in the subset treated primarily systemically, where new drugs were increasingly utilized (2-year OS 16% 2007-2009 vs. 44% 2014-2015 logrank p<0.001; AHR 0.46, 95% CI: (0.38,0.56)). Conclusion/Implications Utilization of systemic therapy for MM has increased considerably in routine practice during 2007-2015; at least some of this increase relates to use of novel agents since 2011. In line with randomized trial findings, new drug adoption was associated with substantial increases in population-based MM survival

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report

Background: New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers. Methods: Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies - particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development. Conclusions: Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology. (C) 2020 The Authors. Published by Elsevier Ltd

Complex spectral line profiles resulting from cryogenic deformation of the SINFONI/SPIFFI diffraction gratings

The integral field spectrograph, spectrometer for infrared faint field imaging (SPIFFI), has complex line profile shapes that vary with wavelength and pixel scale, the origins of which have been sought since the instrument construction. SPIFFI is currently operational as part of SINFONI at the Very Large Telescope (VLT) and will be upgraded and incorporated into the VLT instrument enhanced resolution imager and spectrograph (ERIS). We conducted an investigation of the line profiles based on the measurements we could take with the instrument calibration unit, as well as laboratory measurements of spare SPIFFI optical components. Cryogenic measurements of a spare SPIFFI diffraction grating showed significant periodic deformation. These measurements match the cryogenic deformation expected from bimetallic bending stress based on a finite element analysis of the lightweighted grating blank. The periodic deformation of the grating surface gives rise to satellite peaks in the diffraction pattern of the grating. An optical simulation including the cryogenic grating deformation reproduces the behavior of the SPIFFI line profiles with both wavelength and pixel scale as measured with the instrument calibration unit. The conclusion is that cryogenic deformation of the diffraction gratings is responsible for the nonideal line profiles, and that the diffraction gratings should be replaced during the upgrade for optimal instrument performance.ISSN:2329-4221ISSN:2329-412

State of Knowledge of Soil Biodiversity: Status, Challenges, and Potentialities

This report presents the threats to soil biodiversity and the solutions that soil biodiversity can provide to problems in different fields, including agriculture, environmental conservation, climate change adaptation and mitigation, nutrition, medicine and pharmaceuticals, remediation of polluted sites, and many others. There is increasing attention on the importance of biodiversity for food security and nutrition, especially above-ground biodiversity such as plants and animals. Less attention is being paid to the biodiversity beneath our feet: soil biodiversity. Yet the rich diversity of soil organisms drives many processes that produce food, regenerate soil or purify water. This report is the result of an inclusive process involving more than 300 scientists from around the world under the auspices of FAO's Global Soil Partnership and its Intergovernmental Technical Panel on Soils, the Convention on Biological Diversity, the Global Soil Biodiversity Initiative, and the European Commission

The positive effect of plant diversity on soil carbon depends on climate

Little is currently known about how climate modulates the relationship between plant diversity and soil organic carbon and the mechanisms involved. Yet, this knowledge is of crucial importance in times of climate change and biodiversity loss. Here, we show that plant diversity is positively correlated with soil carbon content and soil carbon-to-nitrogen ratio across 84 grasslands on six continents that span wide climate gradients. The relationships between plant diversity and soil carbon as well as plant diversity and soil organic matter quality (carbon-to-nitrogen ratio) are particularly strong in warm and arid climates. While plant biomass is positively correlated with soil carbon, plant biomass is not significantly correlated with plant diversity. Our results indicate that plant diversity influences soil carbon storage not via the quantity of organic matter (plant biomass) inputs to soil, but through the quality of organic matter. The study implies that ecosystem management that restores plant diversity likely enhances soil carbon sequestration, particularly in warm and arid climates.EEA Santa CruzFil: Spohn, Marie. Swedish University of Agricultural Sciences (SLU). Department of Soil and Environment; SueciaFil: Bagchi, Sumanta. Indian Institute of Science; India.Fil: Biederman, Lori A. Iowa State University. Department of Ecology, Evolution, and Organismal Biology; Estados UnidosFil: Borer, Elizabeth T. University of Minnesota. Department of Ecology, Evolution, and Behavior; Estados UnidosFil: Bråthen, Kari Anne. Arctic University of Norway. Department of Arctic and Marine Biology; NoruegaFil: Bugalho, Miguel N. University of Lisbon. Centre for Applied Ecology “Prof. Baeta Neves” (CEABN-InBIO). School of Agriculture; Portugal.Fil: Caldeira, Maria C. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Catford, Jane A. King’s College London. Department of Geography; Reino UnidoFil: Catford, Jane A. University of Melbourne. School of Agriculture, Food and Ecosystem Sciences; Australia.Fil: Collins, Scott L. University of New Mexico. Department of Biology; Estados UnidosFil: Eisenhauer, Nico. German Centre for Integrative Biodiversity Research (iDiv). Halle-Jena-Leipzig; AlemaniaFil: Eisenhauer, Nico. Leipzig University. Institute of Biology; AlemaniaFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Yahdjian, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA); Argentina.Fil: Yahdjian, Laura. Universidad de Buenos Aires. Facultad de Agronomía; Argentina

Nutrient Availability Controls the Impact of Mammalian Herbivores on Soil Carbon and Nitrogen Pools in Grasslands

Grasslands are subject to considerable alteration due to human activities globally, including widespread changes in populations and composition of large mammalian herbivores and elevated supply of nutrients. Grassland soils remain important reservoirs of carbon (C) and nitrogen (N). Herbivores may affect both C and N pools and these changes likely interact with increases in soil nutrient availability. Given the scale of grassland soil fluxes, such changes can have striking consequences for atmospheric C concentrations and the climate. Here, we use the Nutrient Network experiment to examine the responses of soil C and N pools to mammalian herbivore exclusion across 22 grasslands, under ambient and elevated nutrient availabilities (fertilized with NPK + micronutrients). We show that the impact of herbivore exclusion on soil C and N pools depends on fertilization. Under ambient nutrient conditions, we observed no effect of herbivore exclusion, but under elevated nutrient supply, pools are smaller upon herbivore exclusion. The highest mean soil C and N pools were found in grazed and fertilized plots. The decrease in soil C and N upon herbivore exclusion in combination with fertilization correlated with a decrease in aboveground plant biomass and microbial activity, indicating a reduced storage of organic matter and microbial residues as soil C and N. The response of soil C and N pools to herbivore exclusion was contingent on temperature – herbivores likely cause losses of C and N in colder sites and increases in warmer sites. Additionally, grasslands that contain mammalian herbivores have the potential to sequester more N under increased temperature variability and nutrient enrichment than ungrazed grasslands. Our study highlights the importance of conserving mammalian herbivore populations in grasslands worldwide. We need to incorporate local‐scale herbivory, and its interaction with nutrient enrichment and climate, within global‐scale models to better predict land–atmosphere interactions under future climate change