Determination of the tension softening curve of nuclear graphites using the incremental displacement collocation method

postprin

A La Autoantigen Homologue Is Required for the Internal Ribosome Entry Site Mediated Translation of Giardiavirus

Translation of Giardiavirus (GLV) mRNA is initiated at an internal ribosome entry site (IRES) in the viral transcript. The IRES localizes to a downstream portion of 5′ untranslated region (UTR) and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of trans-activating protein factors. A La autoantigen homologue in the viral host Giardia lamblia, GlLa, was proposed as one of the potential trans-activating factors based on its specific binding to GLV-IRES in vitro. In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in Giardia by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in Giardia moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA), known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities in vitro and in vivo, was also found to bind to GlLa protein in vitro and inhibited GLV-IRES function in vivo. The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200–348aa) of GlLa in Giardia showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of Giardia, thus supporting a primary role of GlLa in translation initiation in Giardiavirus

A systematic review of the effects of residency training on patient outcomes

<p>Abstract</p> <p>Background</p> <p>Residents are vital to the clinical workforce of today and tomorrow. Although in training to become specialists, they also provide much of the daily patient care. Residency training aims to prepare residents to provide a high quality of care. It is essential to assess the patient outcome aspects of residency training, to evaluate the effect or impact of global investments made in training programs. Therefore, we conducted a systematic review to evaluate the effects of relevant aspects of residency training on patient outcomes.</p> <p>Methods</p> <p>The literature was searched from December 2004 to February 2011 using MEDLINE, Cochrane, Embase and the Education Resources Information Center databases with terms related to residency training and (post) graduate medical education and patient outcomes, including mortality, morbidity, complications, length of stay and patient satisfaction. Included studies evaluated the impact of residency training on patient outcomes.</p> <p>Results</p> <p>Ninety-seven articles were included from 182 full-text articles of the initial 2,001 hits. All studies were of average or good quality and the majority had an observational study design.Ninety-six studies provided insight into the effect of 'the level of experience of residents' on patient outcomes during residency training. Within these studies, the start of the academic year was not without risk (five out of 19 studies), but individual progression of residents (seven studies) as well as progression through residency training (nine out of 10 studies) had a positive effect on patient outcomes. Compared with faculty, residents' care resulted mostly in similar patient outcomes when dedicated supervision and additional operation time were arranged for (34 out of 43 studies). After new, modified or improved training programs, patient outcomes remained unchanged or improved (16 out of 17 studies). Only one study focused on physicians' prior training site when assessing the quality of patient care. In this study, training programs were ranked by complication rates of their graduates, thus linking patient outcomes back to where physicians were trained.</p> <p>Conclusions</p> <p>The majority of studies included in this systematic review drew attention to the fact that patient care appears safe and of equal quality when delivered by residents. A minority of results pointed to some negative patient outcomes from the involvement of residents. Adequate supervision, room for extra operation time, and evaluation of and attention to the individual competence of residents throughout residency training could positively serve patient outcomes. Limited evidence is available on the effect of residency training on later practice. Both qualitative and quantitative research designs are needed to clarify which aspects of residency training best prepare doctors to deliver high quality care.</p

Macrosomia and large for gestational age in Asia:One size does not fit all

Macrosomia, usually defined as infant birth weight of >= 4000 g, does not consider gestational age, sex, or country/region-specific differences in mean birth weight and maternal body weight. This issue is particularly relevant for Asia, where 60% of the world's population lives, due to variations in maternal size and birth weights across populations. Large for gestational age (LGA), defined as birth weight > 90th centile, is a more sensitive measure as it considers gestational age and sex, though it is dependent on the choice of growth charts. We aimed to review reporting of macrosomia and LGA in Asia. We reviewed the literature on prevalence and risk of macrosomia and LGA in Asia over the last 29 years. Prevalence of macrosomia ranged from 0.5% (India) to 13.9% (China) while prevalence of LGA ranged from 4.3% (Korea) to 22.1% (China), indicating substantial variation in prevalence within and between Asian countries. High pre-pregnancy body mass index, excessive gestational weight gain, and impaired glucose tolerance conferred risk of macrosomia/LGA. Incidence of macrosomia and LGA varies substantially within and between Asian countries, as do the growth charts and definitions. The latter makes it impossible to make comparisons but suggests differences in intrauterine growth between populations. Reporting LGA, using standardized country/regional growth charts, would better capture the incidence of high birth weight and allow for comparison and identification of contributing factors. Better understanding of local drivers of excessive intrauterine growth could enable development of improved strategies for prevention and management of LGA

Scientific, sustainability and regulatory challenges of cultured meat

Producing meat without the drawbacks of conventional animal agriculture would greatly contribute to future food and nutrition security. This Review Article covers biological, technological, regulatory and consumer acceptance challenges in this developing field of biotechnology. Cellular agriculture is an emerging branch of biotechnology that aims to address issues associated with the environmental impact, animal welfare and sustainability challenges of conventional animal farming for meat production. Cultured meat can be produced by applying current cell culture practices and biomanufacturing methods and utilizing mammalian cell lines and cell and gene therapy products to generate tissue or nutritional proteins for human consumption. However, significant improvements and modifications are needed for the process to be cost efficient and robust enough to be brought to production at scale for food supply. Here, we review the scientific and social challenges in transforming cultured meat into a viable commercial option, covering aspects from cell selection and medium optimization to biomaterials, tissue engineering, regulation and consumer acceptance

Trace metal distribution in the bed, bank and suspended sediment of the Ravensbourne River and its implication for sediment monitoring in an urban river

Purpose This study aims to identify a suitable sediment compartment for sediment quality monitoring by: (a) studying the concentration of trace metals (Cd, Cu, Ni, Pb and Zn) in the bed, bank and suspended sediment compartments of the Ravensbourne River to establish any differences in trace metal concentrations with compartment; (b) determining the influence of sediment particle size fractions ( 0.05) in the concentrations of metals between the suspended sediment and the < 63 μm bed sediment fraction, but there was a significant difference (p < 0.05) between the suspended sediment and the < 63 μm bank sediment fraction. There were also significant differences between the concentrations of metals in the < 63 μm and the 63 μm–2 mm fractions. Generally, the Ravensbourne River did not comply with the draft UK sediment quality guidelines for the metals analysed. Conclusions This study shows the importance of identifying a suitable sediment compartment to sample for compliance with sediment quality standards. The bed and suspended sediments are the most widely used sediment compartments for sediment monitoring, but collecting sufficient mass of the < 63 μm sediment fraction for monitoring presents a challenge for urban gravel bed rivers like the Ravensbourne River. It seems appropriate to establish individual monitoring regimes for different rivers

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Determination of coefficients of the crack tip asymptotic field by fractal hybrid finite elements

This paper applies the fractal finite element method (FFEM) together with 9-node Lagrangian hybrid elements to the calculation of linear elastic crack tip fields. An explicit stabilization scheme is employed to suppress the spurious kinematic modes of the sub-integrated Lagrangian element. An extensive convergence study has been conducted to examine the effects of the similarity ratio, reduced integration and the type of elements on the accuracy and stability of the numerical solutions. It is concluded that (i) a similarity ratio close to unity should be used to construct the fractal mesh, (ii) sub-integrated Lagrangian elements with occasionally unstable behaviour should not be used, and (iii) the good accuracy (with differences less than 0.5% with existing available solutions) and stability over a wide range of numerical tests support the use of fractal hybrid finite elements for determining crack tip asymptotic fields. © 2006 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

The fractal finite element method for unbounded problems

The fractal finite element method, previously developed for stress intensity factor calculation for crack problems in fracture mechanics, is extended to analyse some unbounded problems in half space. The concepts of geometrical similarity and two-level finite element mesh are applied to generate an infinite number of self-similar layers in the far field with a similarity ratio bigger than one; that is, one layer is bigger than the next in size but of the same shape. Only conventional finite elements are used and no new elements are generated. The global interpolating functions in the form of a truncated infinite series are employed to transform the infinite number of nodal variables to a small number of unknown coefficients associated with the global interpolating functions. Taking the advantage of geometrical similarity, transformation for one layer is enough because the relevant entries of the transformed matrix after assembling all layers are infinite geometric series of the similarity ratio and can be summed analytically. Accurate nodal displacements are obtained as shown in the numerical examples. © 2004 John Wiley and Sons, Ltd.link_to_subscribed_fulltex