A new approach to equipment testing

Considerable controversy has arisen during the recent discussions over a new version of the RTCA DO160C/ED 14C Section 22 document at the European Committee for Aviation Electronics. Section 22 is concerned with lightning waveform tests to equipment. Investigations of some of these controversies with circuit analysis and measurements indicate the impedance characteristics required of the transient generators and the possibility of testing to a voltage limit even for current waveforms

Health care insurance and advance directive completion: A population based study

Background: The relationship between advance directive (AD) completion and health insurance status is rarely studied. Method: AD completion information was collected through the 2008 Nevada Behavior Risk Factor Surveillance System (BRFSS), a statewide cross-sectional telephone survey. Nevada non-institutionalized population over 18 were randomly selected as a population sample. Respondents were divided to “health care plan group” (HCPG) and “no health care plan group” (NHCPG). Demographic and behavior risk factors were also collected. Weighted multiple logistic regressions were utilized to assess the relationships between ADs, healthcare coverage and other factors. Results: Of 4,461 respondents completing the survey, HCPG were six times more likely to have completed an AD than the NHCPG (unadjusted odds ratio: 6.08, 95% CI: 4.34-8.51). After controlling for demographic factors, the HCPG were still more than twice as likely to have completed an AD as NHCPG (AOR = 2.67, 95% CI:1.80-3.97). Only slight differences emerged for AD completion between HPCG and NHCPG when health status (AOR = 2.74, 95% CI, 1.81-4.14) and health behaviors (AOR = 2.63, 95% CI: 1.73-3.98) were added to the model. Conclusion: Health insurance, after age and college education, is the third strongest predictor of AD completion

Linked Fate: Justice and the Criminal Legal System During the COVID-19 Pandemic

The concept of “linked fate” has taken on new meaning in the face of the COVID-19 pandemic. People all over the world – from every walk of life, spanning class, race, gender, and nationality – face a potentially deadly threat requiring cooperation and sacrifice. The plight of the most vulnerable among us affects the capacity of the larger community to cope with, recover, and learn from COVID-19’s devastating impact. COVID-19 makes visible and urgent the need to embrace our linked fate, “develop a sense of commonality and shared circumstances,” and unstick dysfunctional and inequitable political and legal systems. Nowhere is the hazard of failing to recognize linked fate more urgent than in the criminal legal system. COVID-19 pandemic has hit people who live and work in correctional institutions particularly hard. The government bears legal and moral responsibility for people incarcerated in prisons, jails, and juvenile detention facilities, who cannot leave and must depend for their survival of the pandemic on the state. The movement in and out of correctional facilities by those employed to fulfill government’s responsibility also ensures the spread of infection. One study, for example, found that increases in a county\u27s jail incarceration rate were associated with significant rates of infectious disease deaths. The collective failure to attend to the circumstances that enmesh people in the criminal legal system – poverty, racial discrimination, poor health and mental care health care – also make prisons and jails a ground zero of the pandemic\u27s spread

PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid ω-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria β-oxidation with an increase in both peroxisomal β-oxidation, and microsomal ω-oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARα activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid β-oxidation and ω-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4α with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the ω-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARα. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid ω-hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA) CYP4A and long-chain fatty acid (LCFA) CYP4Fω-hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis

Understanding uncertainty in a swan wave model using a Bayesian Emulator

This is the author accepted manuscript. The final version is available from EWTEC via the link in this recordNumerical simulation is used widely in the marine renewable energy sector. Wave and flow models are used to understand and predict the conditions experienced at offshore energy sites. Like all numerical simulations, wave models have uncertainties in their output caused by uncertainty about the various input data (which may themselves be model outputs), and uncertainty about how well the model simulates the real world. Understanding these uncertainties is important in order to hold confidence in the models accuracy. Classical Monte Carlo uncertainty analysis requires a large number of model runs which is impossible in large complex models if the computational run time is more than a few seconds. By substituting a much more computationally efficient mathematical model, known as an emulator, for the complex simulation then processing time can be decreased to a level where uncertainty analysis can be undertaken. A simple’toy’ wave model has been produced using SWAN. By using a Bayesian methodology on output from a small number of correctly designed model runs, a mathematical emulator is constructed to provide a statistical approximation of output from the model. Importantly this emulator provides not just an approximation of the output but a full probability distribution describing how close the emulator output is to the model. As this emulator provides results in a fraction of a second (compared to several seconds for the toy simulator and considerably longer for actual wave models) it can be run many thousands of times as is required for a Monte Carlo analysis. This paper describes the methodology used to construct an emulator of a simulation and provides method and results using the emulator to undertake uncertainty quantification. The methods described here can be scaled up and employed on large wave models, flow models or any deterministic numerical simulator.European Regional Development Fund (ERDF

Knowledge of pelvic floor problems: a study of third trimester, primiparous women

INTRODUCTION AND HYPOTHESIS: Pelvic floor problems in women (urinary incontinence, faecal incontinence, uterovaginal prolapse) are common, and have an adverse effect on quality of life. We hypothesized that there is low knowledge of these problems amongst primiparous women in their third trimester of pregnancy. METHODS: We conducted a cross-sectional study in antenatal clinics of three hospitals in London, UK, from 2011 to 2013. Primiparous women aged ≥18 years and in the third trimester of pregnancy answered questions on pelvic floor problems. Knowledge scores were calculated based on the proportion of questions answered correctly. RESULTS: A total of 249 women completed the question set. The average knowledge score across all domains was low at 45 %. Scores were lowest for the less common problems of faecal incontinence (35 %) and prolapse (36 %). The score for urinary incontinence was higher at 63 %, but low when questions explored more detailed levels of knowledge (41 %). Knowledge scores were positively associated with both education to tertiary level and the use of books as the information source on pregnancy and delivery. Only 35 % of women cited antenatal classes as a source. CONCLUSIONS: Knowledge of pelvic floor problems is low amongst third-trimester, primiparous women in this London-based population. Adequate knowledge of these problems is important for women to be able to make informed choices about their antenatal care and to seek help if problems arise. The data suggest scope for health-care professionals to raise these issues early during pregnancy, and to help women access accurate sources of information

Antiapoptotic herpesvirus Bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins

The antiapoptotic Bcl-2 and Bcl-x(L) proteins of mammals are converted into potent proapoptotic factors when they are cleaved by caspases, a family of apoptosis-inducing proteases (E. H.-Y. Cheng, D. G. Kirsch, R. J. Clem, R. Ravi, M. B. Kastan, A. Bedi, K. Ueno, and J. M. Hardwick, Science 278:1966-1968, 1997; R. J. Clem, E. H.-Y. Cheng, C. L. Karp, D. G. Kirsch, K. Ueno, A. Takahashi, M. B. Kastan, D. E. Griffin, W. C. Earnshaw, M. A. Veliuona, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 95:554-559, 1998). Gamma herpesviruses also encode homologs of the Bcl-2 family. All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (gammaHV68) and bovine herpesvirus 4 (BHV4), as described here. To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. Only the viral Bcl-2 protein encoded by gammaHV68 was susceptible to caspase digestion. However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x(L), and Bid, which are potent inducers of apoptosis, the cleavage product of gammaHV68 Bcl-2 lacked proapoptotic activity. KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. The Bcl-2 homologs encoded by herpesvirus saimiri, Epstein-Barr virus, and BHV4 were not cleaved by apoptotic cell extracts and did not possess latent proapoptotic activities. Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death

The Septins Function in G1 Pathways that Influence the Pattern of Cell Growth in Budding Yeast

The septins are a conserved family of proteins that have been proposed to carry out diverse functions. In budding yeast, the septins become localized to the site of bud emergence in G1 but have not been thought to carry out important functions at this stage of the cell cycle. We show here that the septins function in redundant mechanisms that are required for formation of the bud neck and for the normal pattern of cell growth early in the cell cycle. The Shs1 septin shows strong genetic interactions with G1 cyclins and is directly phosphorylated by G1 cyclin-dependent kinases, consistent with a role in early cell cycle events. However, Shs1 phosphorylation site mutants do not show genetic interactions with the G1 cyclins or obvious defects early in the cell cycle. Rather, they cause an increased cell size and aberrant cell morphology that are dependent upon inhibitory phosphorylation of Cdk1 at the G2/M transition. Shs1 phosphorylation mutants also show defects in interaction with the Gin4 kinase, which associates with the septins during G2/M and plays a role in regulating inhibitory phosphorylation of Cdk1. Phosphorylation of Shs1 by G1 cyclin-dependent kinases plays a role in events that influence Cdk1 inhibitory phosphorylation

Mass spectrometric characterisation of the circulating peptidome following oral glucose ingestion in control and gastrectomised patients.

RATIONALE: Meal ingestion triggers secretion of a variety of gut and endocrine peptides important in diabetes research which are routinely measured by immunoassays. However, similarities between some peptides (glucagon, oxyntomodulin and glicentin) can cause specificity issues with immunoassays. We used a liquid chromatography/tandem mass spectrometry (LC/MS/MS) methodology to unambiguously monitor multiple gut peptides in human plasma. METHODS: A simple acetonitrile-based protein precipitation step, followed by evaporation and solid-phase extraction, removed high-abundance proteins from samples prior to nano-LC/MS/MS analysis on an Orbitrap Q-Exactive Plus mass spectrometer using a data-dependent methodology. Database searching using PEAKS identified multiple gut-derived peptides, including peptides in the mid-pg/mL range. The relative levels of these and previously characterised peptides were assessed in plasma samples from gastrectomised and control subjects during an oral glucose tolerance test. RESULTS: Analysis of plasma extracts revealed significantly elevated levels of a number of peptides following glucose ingestion in subjects who had undergone gastrectomy compared with controls. These included GLP-1(7-36), GLP-1(9-36), glicentin, oxyntomodulin, GIP(1-42), GIP(3-42), PYY(1-36), PYY(3-36), neurotensin, insulin and C-peptide. Motilin levels decreased following glucose ingestion. Results showed good correlation with immunoassay-derived concentrations of some peptides in the same samples. The gastrectomy group also had higher, but non-glucose-dependent, circulating levels of peptides from PIGR and DMBT1. CONCLUSIONS: Overall, the approach showed that a fast, generic and reproducible LC/MS/MS methodology requiring only a small volume of plasma was capable of the multiplexed detection of a variety of diabetes-related peptides.Wellcome Trust and MR

Adalimumab in Juvenile Idiopathic Arthritis–Associated Uveitis:5-Year Follow-up of the Bristol Participants of the SYCAMORE Trial

PURPOSE:To determine longer-term outcomes of participants enrolled from a single center in the SYCAMORE trial, a randomized placebo-controlled trial of adalimumab versus placebo in children with juvenile idiopathic arthritis-associated uveitis (JIA-U) uncontrolled on methotrexate. DESIGN:Retrospective interventional case series. METHODS:Medical records of all 28 SYCAMORE participants recruited at the Bristol Eye Hospital were reviewed at approximately 3-monthly intervals up to 5 years from the trial randomization date. Uveitis activity, treatment course, visual outcomes, ocular complications and adverse events were recorded. Data are presented using summary statistics. RESULTS:Following withdrawal of the investigational medicinal product (IMP), 25 of the 28 participants were started on adalimumab for active juvenile idiopathic arthritis-associated uveitis (JIA-U). Of the 12 participants in the active treatment arm of the SYCAMORE study, 11 (92%) were restarted on adalimumab after withdrawal of the IMP for active JIA-U (median time to flare 188 days (range 42-413)). Two participants stopped adalimumab for uncontrolled JIA-U. One participant had a reduction in vision to 0.3 due to cataract. Mean visual acuity for the remaining 27 participants was -0.04 (right eye) and -0.05 (left eye). CONCLUSIONS:Drug-induced remission of JIA-U did not persist when adalimumab was withdrawn after 1-2 years treatment. Adalimumab was well tolerated and visual acuity outcomes were excellent