Exploring visitor meanings of place in the National Capital Parks - Central

This study uses a new approach to interpretative research based on (1) understanding the meanings visitors attach to park resources, and (2) examining the connections that visitors made after attending an on-site interpretive program. The study was conducted at the National Capital Parks in Washington, DC. This study revealed that many visitors to the Lincoln Memorial, the Vietnam Veterans Memorial, and the Korean War Veterans Memorial (i.e. the Triangle) seek something of value for themselves, including everything from connecting with the past and rededicating themselves to the ideals of the nation. The study incorporated mixed method design, including purposeful sampling for visitor interview participants, quasi-experimental pre-test/post-test design, focus group interview, and both quantitative and qualitative data analysis. During the summer of 1998, researchers conducted 89 focus group interviews and interviewed a total of 527 visitors. Study results suggest that visitors attach meanings and many of them desire quality interpretative experiences

Broiler Genetics Influences Proteome Profiles of Normal and Woody Breast Muscle

Wooden or woody breast (WB) is a myopathy of the pectoralis major in fast-growing broilers that influences the quality of breast meat and causes an economic loss in the poultry industry. The objective of this study was to evaluate growth and proteome differences between 5 genetic strains of broilers that yield WB and normal breast (NB) meat. Eight-week-old broilers were evaluated for the WB myopathy and divided into NB and WB groups. Differential expression of proteins was analyzed using 2-dimensional gel electrophoresis and LC-MS/MS to elucidate the mechanism behind the breast myopathy because of the genetic backgrounds of the birds. The percentages of birds with WB were 61.3, 68.8, 46.9, 45.2, and 87.5% for strains 1-5, respectively, indicating variability in WB myopathy among broiler strains. Birds from strains 1, 3, and 5 in the WB group were heavier than those in the NB group (P \u3c 0.05). Woody breast meat from all strains were heavier than NB meat (P \u3c 0.05). Within WB, strain 5 had a greater breast yield than strains 1, 3, and 4 (P \u3c 0.0001). Woody breast from strains 2, 3, 4, and 5 had a greater breast yield than NB (P \u3c 0.05). Six proteins were more abundant in NB of strain 5 than those of strains 2, 3, and 4, and these proteins were related to muscle growth, regeneration, contraction, apoptosis, and oxidative stress. Within WB, 14 proteins were differentially expressed between strain 5 and other strains, suggesting high protein synthesis, weak structural integrity, intense contraction, and oxidative stress in strain 5 birds. The differences between WB from strain 3 and strains 1, 2, and 4 were mainly glycolytic. In conclusion, protein profiles of broiler breast differed because of both broiler genetics and the presence of WB myopathy

Proteomic Characterization of Normal and Woody Breast Meat from Broilers of Five Genetic Strains

Woody breast (WB) is an emergent broiler myopathy that is macroscopically characterized by hardened areas of the Pectoralis major muscle. Five genetic strains (strains 1–5) of mixed-sex broilers were fed either a control or an amino acid (AA)-reduced diet (20% reduction of digestible lysine, total sulfur AAs, and threonine) for 8 wk. Differences between whole-muscle proteome profiles of normal breast (NB; n = 6 gels) and WB tissue (n = 6 gels) were characterized for (1) broiler strains 1–5 that were fed with a control diet and collected at 0 min; (2) strain 5 (control diet) that were collected at 15 min, 4 h, and 24 h; (3) strain 5 (0 min) that were fed with a control and an AA-reduced diet. Birds that yielded WB were heavier and had a greater pH at death (pH0min) than normal birds. Results indicated that 21 proteins were more abundant (P < 0.05) and 3 proteins were less abundant (P < 0.05) in WB compared with NB. The differentially abundant proteins in each comparison were consistently upregulated or downregulated in WB tissue although the different protein profiles were noticed for each comparison. Strains 2 and 5 had more protein profile differences between WB and NB meat than strains 1, 3, and 4, which potentially indicates a stronger genetic component for strains 2 and 5 with respect to WB formation. The proteins that were more abundant in WB compared to NB are involved in carbohydrate metabolism, oxidative stress, cytoskeleton structure, and transport and signaling. Ingenuity Pathway Analysis indicated that regulated pathways in WB were mainly related to carbohydrate metabolism, cellular repair, cellular organization and maintenance, and cell death and survival. The results support the potential causes of WB myopathy, including the presence of hypoxia, oxidative stress, increased apoptosis, misfolded proteins, and inflammation

Senior ID Access Card Research Report

Final Project for INST710: User Experience Research Methods (Fall 2020). University of Maryland, College Park.The Department of Parks and Recreation is seeking to increase both the number of sign-ups and participation of seniors in the M-NCPPC Senior ID program. This project supports the Department’s mission of assisting the physical, mental and social needs of Prince George’s County’s diverse and aging population through the Senior ID card. The shift to an online environment has created some barriers for seniors to enroll and stay engaged with the activities and events offered through the M-NCPPC Senior ID program. For instance, seniors in Prince George’s County have different levels of access to and expertise with the technology required to participate in remote activities and events. The Department of Parks and Recreation is also aiming to mitigate social isolation during these difficult times. Although Department staff periodically perform wellness check-ins with seniors, the number of activities and events has significantly reduced. In-person activities like walking groups, also have limited space due to social distancing measures or have been cancelled altogether. Nonetheless, some of the seniors interviewed expressed an interest in staying active by walking or participating in the Club 300 Walk Across America program offered by the Department. Therefore, the Department of Parks and Recreation is looking for ways to keep seniors engaged by facilitating online sign-up for the Senior ID program and to hear from users about their needs and desires for the program. The goal of this research is to understand how the Department can increase the number of Senior ID users by providing activities and services that meet the diverse needs of the Prince George’s County senior population. This research will identify barriers that prevent residents from signing up for a Senior ID and what opportunities exist to increase sign-ups. It will also highlight effective communication strategies to recruit new members and retain and increase participation in the Senior ID program. Finally, this research will explore how the Department can promote member socialization and connectivity in an online environment.Prince George’s Count

DeepSearch: A Simple and Effective Blackbox Attack for Deep Neural Networks

Although deep neural networks have been very successful in image-classification tasks, they are prone to adversarial attacks. To generate adversarial inputs, there has emerged a wide variety of techniques, such as black- and whitebox attacks for neural networks. In this paper, we present DeepSearch, a novel fuzzing-based, query-efficient, blackbox attack for image classifiers. Despite its simplicity, DeepSearch is shown to be more effective in finding adversarial inputs than state-of-the-art blackbox approaches. DeepSearch is additionally able to generate the most subtle adversarial inputs in comparison to these approaches

Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.

Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR 1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill &amp; Melinda Gates Foundation