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Processing APT spectral backgrounds for improved quantification
No full textWe describe a method to estimate background noise in atom probe tomography (APT) mass spectra and to use this information to enhance both background correction and quantification. Our approach is mathematically general in form for any detector exhibiting Poisson noise with a fixed data acquisition time window, at voltages varying through the experiment. We show that this accurately estimates the background observed in real experiments. The method requires, as a minimum, the z-coordinate and mass-to-charge-state data as input and can be applied retrospectively. Further improvements are obtained with additional information such as acquisition voltage. Using this method allows for improved estimation of variance in the background, and more robust quantification, with quantified count limits at parts-per-million concentrations. To demonstrate applications, we show a simple peak detection implementation, which quantitatively suppresses false positives arising from random noise sources. We additionally quantify the detectability of 121-Sb in a standardized-doped Si microtip as (1.5 × 10−5, 3.8 × 10−5) atomic fraction, α = 0.95. This technique is applicable to all modes of APT data acquisition and is highly general in nature, ultimately allowing for improvements in analyzing low ionic count species in datasets
Mathematical analysis of a two-strain disease model with amplification
No full textWe investigate a two-strain disease model with amplification to simulate the prevalence of drug-susceptible (s) and drug-resistant (m) disease strains. Drug resistance first emerges when drug-susceptible strains mutate and become drug-resistant, possibly as a consequence of inadequate treatment, i.e. amplification. In this case, the drug-susceptible and drug-resistant strains are coupled. We perform a dynamical analysis of the resulting system and find that the model contains three equilibrium points: a disease-free equilibrium; a mono-existent disease-endemic equilibrium at which only the drug-resistant strain persists; and a co-existent disease-endemic equilibrium where both the drug-susceptible and drug-resistant strains persist. We found two basic reproduction numbers: one associated with the drug-susceptible strain (R0s); the other with the drug-resistant strain (R0m), and showed that at least one of the strains can spread in a population if max[R0s,R0m]>1. Furthermore, we also showed that if R0m>max[R0s,1], the drug-susceptible strain dies out but the drug-resistant strain persists in the population (mono-existent equilibrium); however if R0s>max[R0m,1], then both the drug-susceptible and drug-resistant strains persist in the population (co-existent equilibrium). We conducted a local stability analysis of the system equilibrium points using the Routh-Hurwitz conditions and a global stability analysis using appropriate Lyapunov functions. Sensitivity analysis was used to identify the key model parameters that drive transmission through calculation of the partial rank correlation coefficients (PRCCs). We found that the contact rate of both strains had the largest influence on prevalence. We also investigated the impact of amplification and treatment/recovery rates of both strains on the equilibrium prevalence of infection; results suggest that poor quality treatment/recovery makes coexistence more likely and increases the relative abundance of resistant infections
Del Pezzo surfaces with a single 1/k(1,1) singularity
No full textInspired by the recent progress by Coates–Corti–Kasprzyk et al. on Mirror Symmetry for del Pezzo surfaces, we show that for any positive integer k the deformation families of del Pezzo surfaces with a single 1k (1, 1) singularity (and no other singular points) fit into a single cascade. Additionally we construct models and toric degenerations of these surfaces embedded in toric varieties in codimension ≤ 2. Several of these directly generalise constructions of Reid–Suzuki (in the case k = 3). We identify a root system in the Picard lattice, and in light of the work of Gross–Hacking–Keel, comment on Mirror Symmetry for each of these surfaces. Finally we classify all del Pezzo surfaces with certain combinations of 1k(1, 1) singularities for k = 3, 5, 6 which admit a toric degeneration
Wing morphology predicts individual niche specialization in pteronotus mesoamericanus (Mammalia: Chiroptera)
No full textMorphological variation between individuals can increase niche segregation and decrease intraspecific competition when heterogeneous individuals explore their environment in different ways. Among bat species, wing shape correlates with flight maneuverability and habitat use, with species that possess broader wings typically foraging in more cluttered habitats. However, few studies have investigated the role of morphological variation in bats for niche partitioning at the individual level. To determine the relationship between wing shape and diet, we studied a population of the insectivorous bat species Pteronotus mesoamericanus in the dry forest of Costa Rica. Individual diet was resolved using DNA metabarcoding, and bat wing shape was assessed using geometric morphometric analysis. Inter-individual variation in wing shape showed a significant relationship with both dietary dissimilarity based on Bray-Curtis estimates, and nestedness derived from an ecological network. Individual bats with broader and more rounded wings were found to feed on a greater diversity of arthropods (less nested) in comparison to individuals with triangular and pointed wings (more nested). We conclude that individual variation in bat wing morphology can impact foraging efficiency leading to the observed overall patterns of diet specialization and differentiation within the population
Methylation of the LEP gene promoter in blood at 12 months and BMI at 4 years of age—a population-based cohort study
No full textIncreasing evidence links epigenetic variation to anthropometric and metabolic measures. Leptin signalling regulates appetite and energy expenditure, and in pregnancy is important for nutrient supply to the foetus. Maternal metabolic health and foetal growth are linked to infant blood leptin gene (LEP) methylation, which has been cross-sectionally associated with adolescent obesity. Despite this, few studies have explored the relationship between infant LEP methylation and childhood anthropometry, or the impact of genetic variation on these relationships. Using a prospective birth cohort, we investigated whether blood LEP promoter methylation at birth and 12 months predicts weight and adiposity at 4-years. Locus-specific methylation data was analysed by partial correlation tests and multivariable linear regression. There was weak evidence of an association of birth LEP methylation with anthropometry measures at 4 years. Methylation at a specific site (cg19594666) at 12 months was inversely associated with 4-year weight (r = −0.11, p = 0.02) and body-mass index (BMI) (r = −0.13, p = 0.007), which persisted following adjustment for weight at birth and at 12 months. Neither association was influenced by genotype. We report the first evidence of an association between LEP methylation in infancy and childhood weight. Replication in additional cohorts is required to determine if this relationship persists
Hospital outcomes associated with new-onset atrial fibrillation during ICU admission: A multicentre competing risks analysis
No full textPurpose
New onset atrial fibrillation (NOAF) in critically ill patients has been associated with increased short-term mortality. Analyses that do not take into account the time-varying nature of NOAF can underestimate its association with hospital outcomes.
We investigated the prognostic association of NOAF with hospital outcomes using competing risks methods.
Materials and methods
We undertook a retrospective cohort study in three general adult intensive care units (ICUs) in the UK from June 2008 to December 2015. We excluded patients with known prior atrial fibrillation or an arrhythmia within four hours of ICU admission.
To account for the effect of NOAF on the rate of death per unit time and the rate of discharge alive per unit time we calculated subdistribution hazard ratios (SDHRs).
Results
Of 7541 patients that fulfilled our inclusion criteria, 831 (11.0%) developed NOAF during their ICU admission. NOAF was associated with an increased duration of hospital stay (CSHR 0.68 (95% CI 0.63–0.73)) and an increased rate of in-hospital death per unit time (CSHR 1.57 (95% CI 1.37–1.1.81)). This resulted in a strong prognostic association with dying in hospital (adjusted SDHR 2.04 (1.79–2.32)). NOAF lasting over 30 min was associated with increased hospital mortality.
Conclusions
Using robust methods we demonstrate a stronger prognostic association between NOAF and hospital outcomes than previously reported
Stormy water on Mars: the distribution and saturation of atmospheric water during the dusty season
No full textThe loss of water from Mars to space is thought to result from the transport of water to the upper atmosphere, where it is dissociated to hydrogen and escapes the planet. Recent observations have suggested large, rapid seasonal intrusions of water into the upper atmosphere, boosting the hydrogen abundance. We use the Atmospheric Chemistry Suite on the ExoMars Trace Gas Orbiter to characterize the water distribution by altitude. Water profiles during the 2018–2019 southern spring and summer stormy seasons show that high-altitude water is preferentially supplied close to perihelion, and supersaturation occurs even when clouds are present. This implies that the potential for water to escape from Mars is higher than previously thought
Adaptive Manipulator Control using Active Inference with Precision Learning
No full textActive inference provides a framework for decisionmaking where the optimization is achieved by minimizing freeenergy. Previous work has used this framework for control and state-estimation of a robotic manipulator. This required manual definition of precision matrices which serve as controller gains. This paper provides an implementation for control and state-estimation where the precision matrices are tuned during execution-time (precision learning). Learning the precision matrices means automatically adjusting the controller’s gains which decreases oscillations and overshoot
Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
No full textBackground: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited.
Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10−5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16–0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07–0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses.
Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk.
Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer
Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials
No full textObjective: To explore the effect on perinatal outcome of different fetal monitoring strategies for early‐onset fetal growth restriction (FGR).
Methods: This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age.
Results: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P
Conclusions: This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early‐onset FGR is a combination of cCTG and DV Doppler assessment