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The story of medicine
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Book
Prevalence of Multiple Chronic Conditions Among US Adults, 2018
This analysis provides prevalence estimates of diagnosed single and multiple (≥2) chronic conditions among the noninstitutionalized, civilian US adult population. Data from the 2018 National Health Interview Survey (NHIS) were used to estimate percentages for US adults by selected demographic characteristics. More than half (51.8%) of adults had at least 1 of 10 selected diagnosed chronic conditions (arthritis, cancer, chronic obstructive pulmonary disease, coronary heart disease, current asthma, diabetes, hepatitis, hypertension, stroke, and weak or failing kidneys), and 27.2% of US adults had multiple chronic conditions.
Journal Article
A & R pioneers : architects of American roots music on record
\"A&R Pioneers offers the first comprehensive account of the diverse group of men and women who pioneered artists-and-repertoire (A&R) work in the early US recording industry. In the process, they helped create much of what we now think of as American roots music. Resourceful, innovative, and, at times, shockingly unscrupulous, they scouted and signed many of the singers and musicians who came to define American roots music between the two world wars. They also shaped the repertoires and musical styles of their discoveries, supervised recording sessions, and then devised marketing campaigns to sell the resulting records. By World War II, they had helped redefine the canons of American popular music and established the basic structure and practices of the modern recording industry. Moreover, though their musical interests, talents, and sensibilities varied enormously, these A&R pioneers created the template for the job that would subsequently become known as \"record producer.\" Without Ralph Peer, Art Satherley, Frank Walker, Polk C. Brockman, Eli Oberstein, Don Law, Lester Melrose, J. Mayo Williams, John Hammond, Helen Oakley Dance, and a whole army of lesser known but often hugely influential A&R representatives, the music of Bessie Smith and Bob Wills, of the Carter Family and Count Basie, of Robert Johnson and Jimmie Rodgers may never have found its way onto commercial records and into the heart of America's musical heritage. This is their story\" -- Book jacket.
Book
Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate—Two randomized Phase II clinical trials in 18 to 49 and ≥50 years old adults
New influenza vaccines eliciting more effective protection are needed, particularly for the elderly who paid a large and disproportional toll of hospitalization and dead during seasonal influenza epidemics. Low (≤15 μg/strain) doses of a new plant-derived virus-like-particle (VLP) vaccine candidate have been shown to induce humoral and cellular responses against both homologous and heterologous strains in healthy adults 18-64 years of age. The two clinical trials reported here addressed the safety and immunogenicity of higher doses (≥15 μg/strain) of quadrivalent VLP candidate vaccine on 18-49 years old and ≥50 years old subjects. We also investigated the impact of alum on the immunogenicity induced by lower doses of the vaccine candidate.
In the first Phase II trial reported here (NCT02233816), 18-49 year old subjects received 15, 30 or 60 μg/strain of a hemagglutinin-bearing quadrivalent virus-like particle (QVLP) vaccine or placebo. In the second trial (NCT02236052), ≥50 years old subjects received QVLP as above or placebo with additional groups receiving 7.5 or 15 μg/strain with alum. Along with safety recording, the humoral and cell-mediated immune responses were analyzed.
Local and systemic side-effects were similar to those reported previously. The QVLP vaccine induced significant homologous and heterologous antibody responses at the two higher doses, the addition of alum having little-to-no effect. Serologic outcomes tended to be lower in ≥50 years old subjects previously vaccinated. The candidate vaccine also consistently elicited both homologous and heterologous antigen-specific CD4+ T cells characterized by their production of interferon-gamma (IFN-γ), interleukine-2 (IL-2) and/or tumor-necrosis factor alpha (TNF-α) upon ex vivo antigenic restimulation.
Overall, the 30 μg dose produced the most consistent humoral and cellular responses in both 18-49 and ≥50 years old subjects, strongly supporting the clinical development of this candidate vaccine. That particular dose was chosen to test in the ongoing Phase III clinical trial.
Journal Article
Genome-wide association studies for yield-related traits in soft red winter wheat grown in Virginia
Grain yield is a trait of paramount importance in the breeding of all cereals. In wheat (Triticum aestivum L.), yield has steadily increased since the Green Revolution, though the current rate of increase is not forecasted to keep pace with demand due to growing world population and increasing affluence. While several genome-wide association studies (GWAS) on yield and related component traits have been performed in wheat, the previous lack of a reference genome has made comparisons between studies difficult. In this study, a GWAS for yield and yield-related traits was carried out on a population of 322 soft red winter wheat lines across a total of four rain-fed environments in the state of Virginia using single-nucleotide polymorphism (SNP) marker data generated by a genotyping-by-sequencing (GBS) protocol. Two separate mixed linear models were used to identify significant marker-trait associations (MTAs). The first was a single-locus model utilizing a leave-one-chromosome-out approach to estimating kinship. The second was a sub-setting kinship estimation multi-locus method (FarmCPU). The single-locus model identified nine significant MTAs for various yield-related traits, while the FarmCPU model identified 74 significant MTAs. The availability of the wheat reference genome allowed for the description of MTAs in terms of both genetic and physical positions, and enabled more extensive post-GWAS characterization of significant MTAs. The results indicate a number of promising candidate genes contributing to grain yield, including an ortholog of the rice aberrant panicle organization (APO1) protein and a gibberellin oxidase protein (GA2ox-A1) affecting the trait grains per square meter, an ortholog of the Arabidopsis thaliana mother of flowering time and terminal flowering 1 (MFT) gene affecting the trait seeds per square meter, and a B2 heat stress response protein affecting the trait seeds per head.
Journal Article
Irish housing design 1950-1980 : out of the ordinary
\"This book examines the architectural design of housing projects in Ireland from the mid-twentieth century. This period represented a high point in the construction of the Welfare State project where the idea that architecture could and should shape and define community and social life was not yet considered problematic. Exploring a period when Ireland embraced the free market and the end of economic protectionism, the book is a series of case studies supported by critical narratives. Little known but of high quality, the schemes presented in this volume are by architects whose designs helped determine future architectural thinking in Ireland and elsewhere. Aimed at academics, students and researchers, the book is accompanied by new drawings and over 100 full colour images, with the example studies demonstrating rich architectural responses to a shifting landscape\"-- Provided by publisher.
Book
Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza
The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in Nicotiana benthamiana, we have recently demonstrated that a candidate Virus-Like Particle (VLP) vaccine can be generated within 3 weeks of release of sequence information. Herein we report that alum-adjuvanted plant-made VLPs containing the hemagglutinin (HA) protein of H5N1 influenza (A/Indonesia/5/05) can induce cross-reactive antibodies in ferrets. Even low doses of this vaccine prevented pathology and reduced viral loads following heterotypic lethal challenge. We further report on safety and immunogenicity from a Phase I clinical study of the plant-made H5 VLP vaccine in healthy adults 18-60 years of age who received 2 doses 21 days apart of 5, 10 or 20 µg of alum-adjuvanted H5 VLP vaccine or placebo (alum). The vaccine was well tolerated at all doses. Adverse events (AE) were mild-to-moderate and self-limited. Pain at the injection site was the most frequent AE, reported in 70% of vaccinated subjects versus 50% of the placebo recipients. No allergic reactions were reported and the plant-made vaccine did not significantly increase the level of naturally occurring serum antibodies to plant-specific sugar moieties. The immunogenicity of the H5 VLP vaccine was evaluated by Hemagglutination-Inhibition (HI), Single Radial Hemolysis (SRH) and MicroNeutralisation (MN). Results from these three assays were highly correlated and showed similar trends across doses. There was a clear dose-response in all measures of immunogenicity and almost 96% of those in the higher dose groups (2 × 10 or 20 µg) mounted detectable MN responses. Evidence of striking cross-protection in ferrets combined with a good safety profile and promising immunogenicity in humans suggest that plant-based VLP vaccines should be further evaluated for use in pre-pandemic or pandemic situations.
ClinicalTrials.gov NCT00984945.
Journal Article
Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP:
NCT04450004
). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18–55 years,
n
= 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.
Safety and immunogenicity results in humans of a two-dose SARS-CoV-2 vaccine made from plants support further assessment of potential efficacy.
Journal Article
Gains through selection for grain yield in a winter wheat breeding program
Increased genetic gain for complex traits in plant breeding programs can be achieved through different selection strategies. The objective of this study was to compare potential gains for grain yield in a winter wheat breeding program through estimating response to selection R values across several selection approaches including phenotypic (PS), marker-based (MS), genomic (GS), and a combination of PS and GS (PS+GS). Ten populations of Washington State University (WSU) winter wheat breeding lines including a diversity panel and F5 and double haploid lines evaluated from 2015 to 2019 growing seasons for grain yield in Lind and Pullman, WA, USA were used in the study. Selection was conducted by selecting the top 20% of lines based on observed yield (PS strategy), genomic estimated breeding values (GS), presence of yield \"enhancing\" alleles of the most significant single nucleotide polymorphism (SNP) markers identified from genome-wide association mapping (MS), and high observed yield and estimated breeding values (PS+GS). Overall, PS compared to other individual selection strategies (MS and GS) showed the highest mean response (R = 0.61) within the same environment. When combined with GS, a 23% improvement in R for yield was observed, indicating that gains could be improved by complementing traditional PS with GS within the same environment. Validating selection strategies in different environments resulted in low to negative R values indicating the effects of genotype-by-environment interactions for grain yield. MS was not successful in terms of R relative to the other selection approaches; using this strategy resulted in a significant (P < 0.05) decrease in response to selection compared with the other approaches. An integrated PS+GS approach could result in optimal genetic gain within the same environment, whereas a PS strategy might be a viable option for grain yield validated in different environments. Altogether, we demonstrated that gains through increased response to selection for yield could be achieved in the WSU winter wheat breeding program by implementing different selection strategies either exclusively or in combination.
Journal Article