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We study the three-dimensional hydrodynamic interaction of a pair of identical, initially spherical capsules freely suspended in a simple shear flow under Stokes flow conditions. The capsules are filled with a Newtonian liquid (same density and viscosity as the suspending fluid). Their membranes satisfy the neo-Hookean constitutive law. We consider the rarely studied case where the capsule centres are initially located in (or near) the plane defined by the flow direction and the vorticity vector, i.e. in two different shear planes. The motion and deformation of the capsules are modelled by means of a boundary integral technique to compute the flows, coupled to a finite element method to calculate the force exerted by the membranes on the fluids. We follow the motion and deformation of the capsules as they are convected towards each other after a sudden start of the flow. Our main finding is that, depending on their initial position and deformability, the two capsules may oscillate slowly about the flow gradient axis, get nearer to each other at each oscillation to finally interact strongly and separate. This minuet motion had not been identified previously. We identify the regions of space where either simple crossing or minuet occurs. This phenomenon has a marked influence on the irreversible trajectory drift of two capsules after crossing: the minuet process leads to a significant trajectory displacement along the flow gradient when none was expected, based on the previous studies where the two capsules had a significant relative velocity.
A systematic review and network meta-analysis (NMA) were conducted to address the question, ‘What is the efficacy of litter management strategies to reduce morbidity, mortality, condemnation at slaughter, or total antibiotic use in broilers?’ Eligible studies were clinical trials published in English evaluating the efficacy of litter management in broilers on morbidity, condemnations at slaughter, mortality, or total antibiotic use. Multiple databases and two conference proceedings were searched for relevant literature. After relevance screening and data extraction, there were 50 trials evaluating litter type, 22 trials evaluating litter additives, 10 trials comparing fresh to re-used litter, and six trials evaluating floor type. NMAs were conducted for mortality (61 trials) and for the presence or absence of footpad lesions (15 trials). There were no differences in mortality among the litter types, floor types, or additives. For footpad lesions, peat moss appeared beneficial compared to straw, based on a small number of comparisons. In a pairwise meta-analysis, there was no association between fresh versus used litter on the risk of mortality, although there was considerable heterogeneity among studies (I2 = 66%). There was poor reporting of key design features in many studies, and analyses rarely accounted for non-independence of observations within flocks.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.
We conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.
In this manuscript we use realistic data to conduct a network meta-analysis using a Bayesian approach to analysis. The purpose of this manuscript is to explain, in lay terms, how to interpret the output of such an analysis. Many readers are familiar with the forest plot as an approach to presenting the results of a pairwise meta-analysis. However when presented with the results of network meta-analysis, which often does not include the forest plot, the output and results can be difficult to understand. Further, one of the advantages of Bayesian network meta-analyses is in the novel outputs such as treatment rankings and the probability distributions are more commonly presented for network meta-analysis. Our goal here is to provide a tutorial for how to read the outcome of network meta-analysis rather than how to conduct or assess the risk of bias in a network meta-analysis.
Vaccination against putative causal organisms is a frequently used and preferred approach to controlling bovine respiratory disease complex (BRD) because it reduces the need for antibiotic use. Because approximately 90% of feedlots use and 90% of beef cattle receive vaccines in the USA, information about their comparative efficacy would be useful for selecting a vaccine. We conducted a systematic review and network meta-analysis of studies assessing the comparative efficacy of vaccines to control BRD when administered to beef cattle at or near their arrival at the feedlot. We searched MEDLINE, MEDLINE In-Process, MEDLINE Daily Epub Ahead of Print, AGRICOLA, Cambridge Agricultural and Biological Index, Science Citation Index, and Conference Proceedings Citation Index – Science and hand-searched the conference proceedings of the American Association of Bovine Practitioners and World Buiatrics Congress. We found 53 studies that reported BRD morbidity within 45 days of feedlot arrival. The largest connected network of studies, which involved 17 vaccine protocols from 14 studies, was included in the meta-analysis. Consistent with previous reviews, we found little compelling evidence that vaccines used at or near arrival at the feedlot reduce the incidence of BRD diagnosis.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy for clinical mastitis in lactating dairy cattle. Controlled trials in lactating dairy cattle with natural disease exposure were eligible if they compared an antimicrobial treatment to a non-treated control, placebo, or a different antimicrobial, for the treatment of clinical mastitis, and assessed clinical or bacteriologic cure. Potential for bias was assessed using a modified Cochrane Risk of Bias 2.0 tool. From 14775 initially identified records, 54 trials were assessed as eligible. Networks were established for bacteriologic cure by bacterial species group, and clinical cure. Disparate networks among bacteriologic cures precluded meta-analysis. Network meta-analysis was conducted for trials assessing clinical cure, but lack of precision of point estimates resulted in wide credibility intervals for all treatments, with no definitive conclusions regarding relative efficacy. Consideration of network geometry can inform future research to increase the utility of current and previous work. Replication of intervention arms and consideration of connection to existing networks would improve the future ability to determine relative efficacy. Challenges in the evaluation of bias in primary research stemmed from a lack of reporting. Consideration of reporting guidelines would also improve the utility of future research.
Prevention and control of respiratory disease is a major contributor to antibiotic use in swine. A systematic review was conducted to address the question, ‘What is the comparative efficacy of antimicrobials for the prevention of swine respiratory disease?’ Eligible studies were controlled trials published in English evaluating prophylactic antibiotics in swine, where clinical morbidity, mortality, or total antibiotic use was assessed. Four databases and the gray literature were searched for relevant articles. Two reviewers working independently screened titles and abstracts for eligibility followed by full-text articles, and then extracted data and evaluated risk of bias for eligible trials. There were 44 eligible trials from 36 publications. Clinical morbidity was evaluated in eight trials where antibiotics were used in nursery pigs and 10 trials where antibiotics were used in grower pigs. Mortality was measured in 22 trials in nursery pigs and 12 trials in grower pigs. There was heterogeneity in the antibiotic interventions and comparisons published in the literature; thus, there was insufficient evidence to allow quantification of the efficacy, or relative efficacy, of antibiotic interventions. Concerns related to statistical non-independence and quality of reporting were noted in the included trials.
A systematic review and network meta-analysis (MA) was conducted to address the question, ‘What is the efficacy of bacterial vaccines to prevent respiratory disease in swine?’ Four electronic databases and the grey literature were searched to identify clinical trials in healthy swine where at least one intervention arm was a commercially available vaccine for one or more bacterial pathogens associated with respiratory disease in swine, including Mycoplasma hyopneumoniae, Actinobacillus pleuropneumonia, Actinobacillus suis, Bordetella bronchiseptica, Pasteurella multocida, Stretococcus suis, Haemophils parasuis, and Mycoplasma hyorhinis. To be eligible, trials had to measure at least one of the following outcomes: incidence of clinical morbidity, mortality, lung lesions, or total antibiotic use. There were 179 eligible trials identified in 146 publications. Network MA was undertaken for morbidity, mortality, and the presence or absence of non-specific lung lesions. However, there was not a sufficient body of research evaluating the same interventions and outcomes to allow a meaningful synthesis of the comparative efficacy of the vaccines. To build this body of research, additional rigor in trial design and analysis, and detailed reporting of trial methods and results are warranted.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
Supersonic turbulent flows at Mach 2.7 over concave surfaces for two different radii of curvature were investigated and compared with a flat plate turbulent boundary layer using direct numerical simulations. The streamwise velocity reduces in the outer part of the boundary layer due to compression, while it increases near the wall due to curvature, with a higher shape factor for the concave cases. The near-wall spanwise streak spacing reduces compared to the flat plate, with large-scale streaks and turbulence amplification also observed. Streamwise velocity iso-surfaces and streamlines show the generation of Görtler-like vortices, consistent with significant centrifugal effects. Abundant small vortices are shown to be associated with large baroclinic production of vorticity that is caused by the density and pressure gradients that are associated with concave compression. Profiles of turbulent kinetic energy and turbulent Mach number exhibit a characteristic two-layer structure in the concave boundary layer cases. In the outer layer, turbulence is greatly amplified, whereas a local balance exists in the inner layer. Turbulent energy budget analysis shows that both production and dissipation increase near the concave wall, whereas in the outer part of the boundary layer, the production is increased and ultimately balanced by convection and turbulent transport.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.
The solar active region (AR) 12192 was one of the most flare productive region of solar cycle 24, which produced many X-class flares; the most energetic being an X3.1 flare on October 24, 2014 at 21:10 UT. Customarily, such events are believed to be triggered by magnetic reconnection in coronal magnetic fields. Here we use the vector magnetograms from solar photosphere, obtained from Heliospheric Magnetic Imager (HMI) to investigate the magnetic field topology prior to the X3.1 event, and ascertain the conditions that might have caused the flare. To infer the coronal magnetic field, a novel non-force-free field (NFFF) extrapolation technique of the photospheric field is used, which suitably mimics the Lorentz forces present in the photospheric plasma. We also highlight the presence of magnetic null points and quasi-separatrix layers (QSLs) in the magnetic field topology, which are preferred sites for magnetic reconnections and discuss the probable reconnection scenarios.
Magnetic reconnections (MRs) for various magnetic field line (MFL) topologies are believed to be the initiators of solar eruptive events like flares and coronal mass ejections (CMEs). Consequently, important is a thorough understanding and quantification of the MFL topology and their evolution which leads to MRs. Contemporary standard is to extrapolate the coronal MFLs using equilibrium models where the Lorentz force on the coronal plasma is zero everywhere. In tandem, a non-force-free-field (NFFF) extrapolation scheme has evolved and allows for a Lorentz force which is non-zero only at the photosphere but asymptotically vanishes with height. The paper reports magnetohydrodynamic (MHD)- simulations initiated by NFFF extrapolation of the coronal MFLs for a flare producing active region NOAA 11158. Interestingly, quasi-separatrix layers (QSLs) which facilitate MRs are detected in the extrapolated MFLs and, here the paper makes an attempt to asses the role of QSLs in the flare onsets.
An underwater shock loading experimental device is used to simulate underwater explosion shock waves. The aim of this study is to investigate the influence of flyer momentum on the response of an aluminium plate to this underwater shock loading experimental device. The simulation accuracy can be verified by comparing theoretical data with the simulation and experimental results. Through simulations, an aluminium plate’s deformation and pressure specific impulse can be determined when flyers impact the piston at different velocities but at the same momentum. The aluminium plate's deformation and pressure specific impulse are constant when the flyers had constant momentum because both are directly proportional to the flyer momentum. The results have an important practical value for understanding and using this type of experimental device.
Monolithic large-aperture diffraction grating tiling is desired to increase the output capability of multi-kilojoule petawatt laser facilities. However, the wavefront errors of input pulse and gratings will degrade the focal spot quality and the compressibility of the output pulse. In this work, the effects of wavefront error of input pulse, deformation and wave aberration of the grating for the large-aperture tiled-grating compressor are investigated theoretically. A series of numerical simulations are presented to discuss the changing trends of focal spot energy caused by wavefront error of input pulse and obtain the error tolerance for specific goals. The influences of coating stress and the wave aberration of holographic exposure gratings on the diffraction wavefront are also discussed. Some advice is proposed for improving the performance of large-aperture tiled-grating. This work paves the way for the design of practical large-aperture tiled-grating compressor for ultrahigh intensity laser facilities in the future.