Singularities in optimal structural design

Singularity conditions that arise during structural optimization can seriously degrade the performance of the optimizer. The singularities are intrinsic to the formulation of the structural optimization problem and are not associated with the method of analysis. Certain conditions that give rise to singularities have been identified in earlier papers, encompassing the entire structure. Further examination revealed more complex sets of conditions in which singularities occur. Some of these singularities are local in nature, being associated with only a segment of the structure. Moreover, the likelihood that one of these local singularities may arise during an optimization procedure can be much greater than that of the global singularity identified earlier. Examples are provided of these additional forms of singularities. A framework is also given in which these singularities can be recognized. In particular, the singularities can be identified by examination of the stress displacement relations along with the compatibility conditions and/or the displacement stress relations derived in the integrated force method of structural analysis

Derivatization and Separation of Natural Estrogens (estrone, 17β-estradiol, and estriol) Using Gas Chromatography with Flame Ionization Detection (GC-FID)

A major cause of concern for estrogens found in the environment is that even at very low concentrations (10-100 ng/L) they can have a negative effect on aquatic ecosystems by disrupting endocrine systems. Due to the increasing importance of monitoring the levels of estrogens in the environment, a detection method was developed to identify and quantify three natural estrogens (estrone, 17β-estradiol and estriol) using gas chromatography with flame ionization detection (GC-FID). In addition, the efficacy of two derivatizing agents, N,O-bis(trimethylsilyl) acetamide (BSTA) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), was evaluated. The GC detector (FID) was most responsive with E3, followed by E1 and E2. The lowest concentration detected in this study was 0.1 ng/μL for E1 and 1.0 ng/μL for E2. E3 was detectable at the lowest concentration examined (0.01 ng/μL) and is likely detectable at a much lower concentration. The response of the GC-FID to all three estrogens was linear from 0.01-100 ng/μL. The data suggest also that both derivatizing agents are effective for the three natural estrogens. This analytical method will be used in future studies to detect and quantify natural estrogens from environmental samples, and will be particularly useful when exploring the relative concentration of various estrogen compounds spatially and/or temporally

Environmental Predictors of Human West Nile Virus Infections, Colorado

To determine whether environmental surveillance of West Nile virus–positive dead birds, mosquito pools, equines, and sentinel chickens helped predict human cases in metropolitan Denver, Colorado, during 2003, we analyzed human surveillance data and environmental data. Birds successfully predicted the highest proportion of human cases, followed by mosquito pools, and equines

Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial.

BackgroundInfluenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses.MethodsWe did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime-boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050.FindingsBetween Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2-5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis.InterpretationThe tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed.FundingBill & Melinda Gates Foundation

Early-Season Avian Deaths from West Nile Virus as Warnings of Human Infection

An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds

Year-round West Nile Virus Activity, Gulf Coast Region, Texas and Louisiana

West Nile virus (WNV) was detected in 11 dead birds and two mosquito pools collected in east Texas and southern Louisiana during surveillance studies in the winter of 2003 to 2004. These findings suggest that WNV is active throughout the year in this region of the United States

Validation of the triple timed up‐and‐go test in Lambert‐Eaton myasthenia

Introduction There are no validated, practical, and quantitative measures of disease severity in Lambert‐Eaton myasthenia (LEM). Methods Data from the Effectiveness of 3,4‐Diaminopyridine in Lambert‐Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up‐and‐go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. Results The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4‐diaminopyridine free base. Worsening patient‐reported Weakness Self‐Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. Discussion The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM

Multi-Locus Sequence Typing of Bartonella henselae Isolates from Three Continents Reveals Hypervirulent and Feline-Associated Clones

Bartonella henselae is a zoonotic pathogen and the causative agent of cat scratch disease and a variety of other disease manifestations in humans. Previous investigations have suggested that a limited subset of B. henselae isolates may be associated with human disease. In the present study, 182 human and feline B. henselae isolates from Europe, North America and Australia were analysed by multi-locus sequence typing (MLST) to detect any associations between sequence type (ST), host species and geographical distribution of the isolates. A total of 14 sequence types were detected, but over 66% (16/24) of the isolates recovered from human disease corresponded to a single genotype, ST1, and this type was detected in all three continents. In contrast, 27.2% (43/158) of the feline isolates corresponded to ST7, but this ST was not recovered from humans and was restricted to Europe. The difference in host association of STs 1 (human) and 7 (feline) was statistically significant (P≤0.001). eBURST analysis assigned the 14 STs to three clonal lineages, which contained two or more STs, and a singleton comprising ST7. These groups were broadly consistent with a neighbour-joining tree, although splits decomposition analysis was indicative of a history of recombination. These data indicate that B. henselae lineages differ in their virulence properties for humans and contribute to a better understanding of the population structure of B. henselae

Disruption, dissonance and embodiment: creativity, health and risk in music narratives

This article explores notions of creativity, health and risk, drawing on interviews with freelance musicians in the UK. The social context of insecure music work is explored along with hegemonic discourses of creativity in which hedonism, risk and sacrifice are connected. The study draws on narrative analysis in order to examine responses to disruptions that affect creative work. It also explores ongoing accounts of dissonance in music work. The research builds on the new musicology in exploring the cultural basis of creative ideals: these extend beyond the arts to influence many areas of social life. It highlights the way in which the exercise of aesthetic judgements, including judgements about the self, serve to include and exclude particular identities, valuing and diminishing their contributions. The study also builds on sociological debates concerning the regulatory functions of reflexivity and body management in the context of late modernity. Here, strategies of embodiment are also seen in relation to empowerment as challenges to hegemonic notions of creativity. Finally, the research builds on methodological debates surrounding narrative analysis, adopting a sociological approach that emphasizes the particular context of music work and identifies core narratives that reveal connections between everyday experiences and deeper cultural processes

Racial disparities in acute care utilization among individuals with myasthenia gravis

ObjectiveIn myasthenia gravis (MG), evidence on the impact of social determinants of health on disparities in disease burden and healthcare resource utilization is limited. This study aimed to investigate the independent association between race/ethnicity and acute care utilization during the 2 years post-diagnosis among patients with MG.MethodsA retrospective cohort study was conducted among adults (≥18 years) with newly diagnosed MG in the United States using Optum’s de-identified Market Clarity Data from January 1, 2010, to December 31, 2019. Multivariable regression models were used to assess the association between acute care utilization and race/ethnicity, insurance, exacerbation at index, and other covariates.ResultsA total of 7,058 patients met the study inclusion criteria, of whom 57% (n = 4,052) identified as Caucasian, 6% (n = 445) African American, 3% (n = 235) Hispanic, 1% (n = 94) Asian, and 32% (n = 2,232) with missing race/ethnicity information. Compared with patients identifying as Caucasian, those identifying as African American had 37% higher odds of having an emergency department visit in year 1, and those identifying as Hispanic had 70% increase in odds of having a hospitalization event in year 2 post-diagnosis. Among other covariates, Medicaid usage, exacerbation at index, and number of outpatient visits were significantly associated with acute care utilization.ConclusionRacial disparities significantly impacted acute care utilization in the first 2 years post-MG diagnosis. Future studies should aim to examine specific factors that may contribute to disparities such as barriers to healthcare access, greater severity of MG symptoms, and poorly controlled disease