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High-order well-balanced finite volume schemes for hydrodynamic equations with nonlocal free energy
No full textWe propose high-order well-balanced finite-volume schemes for a broad class of hydrodynamic systems with attractive-repulsive interaction forces and linear and nonlinear damping. Our schemes are suitable for free energies containing convolutions of an interaction potential with the density, which are essential for applications such as the Keller--Segel model, more general Euler--Poisson systems, or dynamic-density functional theory. Our schemes are also equipped with a nonnegative-density reconstruction which allows for vacuum regions during the simulation. We provide several prototypical examples from relevant applications highlighting the benefit of our algorithms and also elucidate some of our analytical results
Public preferences for delayed or immediate antibiotic prescriptions in UK primary care: a choice experiment
No full textBackground:
Delayed (or ‘back-up’) antibiotic prescription, where the patient is given a prescription but advised to delay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care. However, this strategy is not widely used in the UK. This study aimed to identify factors influencing preferences among the UK public for delayed prescription, and understand their relative importance, to help increase appropriate use of this prescribing option.
Methods and Findings
We conducted an online choice experiment in two UK general population samples: adults, and parents of children under 18 years. Respondents were presented with twelve scenarios in which they, or their child, might need antibiotics for a respiratory tract infection, and asked to choose either an immediate or a delayed prescription. Scenarios were described by seven attributes. Data were collected between November 2018 and February 2019. Respondent preferences were modelled using mixed-effects logistic regression.
The survey was completed by 802 adults and 801 parents (75% of those who opened the survey). The samples reflected the UK population in age, sex, ethnicity and country of residence. The most important determinant of respondent choice was symptom severity, especially for cough-related symptoms. In the adult sample the probability of choosing delayed prescription was 0.53 (95% CI 0.50-).56, p
Conclusion
This study found that delayed prescription appears to be an acceptable approach to reducing antibiotic consumption. Certain groups appear to be more amenable to delayed prescription, suggesting particular opportunities for increased use of this strategy. Prescribing choices for sore throat may need additional explanation to ensure patient acceptance, and parents in particular may benefit from reassurance about the usual duration of these illnesses
Understanding electrical conduction and nanopore formation during controlled breakdown
No full textControlled breakdown has recently emerged as a highly appealing technique to fabricate solid-state nanopores for a wide range of biosensing applications. This technique relies on applying an electric field of approximately 0.4–1 V nm−1 across the membrane to induce a current, and eventually, breakdown of the dielectric. Although previous studies have performed controlled breakdown under a range of different conditions, the mechanism of conduction and breakdown has not been fully explored. Here, electrical conduction and nanopore formation in SiNx membranes during controlled breakdown is studied. It is demonstrated that for Si-rich SiNx, oxidation reactions that occur at the membrane-electrolyte interface limit conduction across the dielectric. However, for stoichiometric Si3N4 the effect of oxidation reactions becomes relatively small and conduction is predominately limited by charge transport across the dielectric. Several important implications resulting from understanding this process are provided which will aid in further developing controlled breakdown in the coming years, particularly for extending this technique to integrate nanopores with on-chip nanostructures
Civility’s Unfinished Revolution: Comments on John Keane, “Hopes for Civil Society,” Global Perspectives (2020)
No full textKeane offers a conception of civil society more nuanced and more attractive than leading contenders. But Keane’s conception also leaves certain questions for reexamination. Keane says little about what role his vision of civil society allows for governments. Many may struggle to share Keane’s optimism about the role of digital technology in helping to realize this vision. And one might also question how well the attitude of political hope that Keane urges ultimately serves us
A systematically reduced mathematical model for organoid expansion
No full textOrganoids are three-dimensional multicellular tissue constructs. When cultured in vitro, they recapitulate the structure, heterogeneity, and function of their in vivo counterparts. As awareness of the multiple uses of organoids has grown, e.g. in drug discovery and personalised medicine, demand has increased for low-cost and efficient methods of producing them in a reproducible manner and at scale. Here we focus on a bioreactor technology for organoid production, which exploits fluid flow to enhance mass transport to and from the organoids. To ensure large numbers of organoids can be grown within the bioreactor in a reproducible manner, nutrient delivery to, and waste product removal from, the organoids must be carefully controlled. We develop a continuum mathematical model to investigate how mass transport within the bioreactor depends on the inlet flow rate and cell seeding density, focusing on the transport of two key metabolites: glucose and lactate. We exploit the thin geometry of the bioreactor to systematically simplify our model. This significantly reduces the computational cost of generating model solutions, and provides insight into the dominant mass transport mechanisms. We test the validity of the reduced models by comparison with simulations of the full model. We then exploit our reduced mathematical model to determine, for a given inlet flow rate and cell seeding density, the evolution of the spatial metabolite distributions throughout the bioreactor. To assess the bioreactor transport characteristics, we introduce metrics quantifying glucose conversion (the ratio between the total amounts of consumed and supplied glucose), the maximum lactate concentration, the proportion of the bioreactor with intolerable lactate concentrations, and the time when intolerable lactate concentrations are first experienced within the bioreactor. We determine the dependence of these metrics on organoid-line characteristics such as proliferation rate and rate of glucose consumption per cell. Finally, for a given organoid line, we determine how the distribution of metabolites and the associated metrics depend on the inlet flow rate. Insights from this study can be used to inform bioreactor operating conditions, ultimately improving the quality and number of bioreactor-expanded organoids
Imprinting on time-structured acoustic stimuli in ducklings
No full textFilial imprinting is a dedicated learning process that lacks explicit reinforcement. The phenomenon itself is narrowly heritably canalized, but its content, the representation of the parental object, reflects the circumstances of the newborn. Imprinting has recently been shown to be even more subtle and complex than previously envisaged, since ducklings and chicks are now known to select and represent for later generalization abstract conceptual properties of the objects they perceive as neonates, including movement pattern, heterogeneity and inter-component relationships of same or different. Here, we investigate day-old Mallard (Anas platyrhynchos) ducklings’ bias towards imprinting on acoustic stimuli made from mallards’ vocalizations as opposed to white noise, whether they imprint on the temporal structure of brief acoustic stimuli of either kind, and whether they generalize timing information across the two sounds. Our data are consistent with a strong innate preference for natural sounds, but do not reliably establish sensitivity to temporal relations. This fits with the view that imprinting includes the establishment of representations of both primary percepts and selective abstract properties of their early perceptual input, meshing together genetically transmitted prior pre-dispositions with active selection and processing of the perceptual input
Uneven state distribution of homicides in Brazil and their effect on life expectancy, 2000–2015: a cross-sectional mortality study
No full textObjective To determine cause-specific and age-specific contributions to life expectancy changes between 2000 and 2015, separately by state and sex in Brazil, with a focus on homicides.
Design Retrospective cross-sectional demographic analysis of mortality.
Setting and population Brazilian population by age, sex and state from 2000 to 2015.
Main outcome measure Using mortality data from the Brazilian Mortality Information System and population estimates from the National Statistics Office, we used death distribution methods and the linear integral decomposition model to estimate levels and changes in life expectancy. We also examine how multiple causes of death, including those attributable to homicides and amenable/avoidable mortality, contributed to these changes from 2000 to 2015.
Results Between 2000 and 2015, life expectancy in Brazil increased from 71.5 to 75.1 years. Despite state-level variation in gains, life expectancy increased in almost all states over this period. However across Brazil, homicide mortality contributed, to varying degrees, to either attenuated or decreased male life expectancy gains. In Alagoas in 2000–2007 and Sergipe in 2007–2015, homicides contributed to a reduction in life expectancy of 1.5 years, offsetting gains achieved through improvements due to medically amenable causes. In the period 2007–2015, male life expectancy could have been improved by more than half a year in 12 of Brazil’s states if homicide mortality had remained at the levels of 2007.
Conclusions Homicide mortality appears to offset life expectancy gains made through recent improvements to mortality amenable to medical services and public health interventions, with considerable subnational heterogeneity in the extent of this phenomenon. Efforts combating the causes of homicides can increase life expectancy beyond what has been achieved in recent decades
The nonhuman primate neuroimaging and neuroanatomy project
No full textMulti-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, 'ground truth' validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how "functional connectivity" from fMRI and "tractographic connectivity" from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior
Recursion and sequentiality in categories of sheaves
No full textWe present a fully abstract model of a call-by-value language with higher-order functions, recursion and natural numbers, as an exponential ideal in a topos. Our model is inspired by the fully abstract models of O'Hearn, Riecke and Sandholm, and Marz and Streicher. In contrast with semantics based on cpo’s, we treat recursion as just one feature in a model built by combining a choice of modular components
Longitudinal trends in malaria testing rates in the face of elimination in eastern Myanmar: a 7-year observational study
No full textBackground
Providing at-risk communities with uninterrupted access to early diagnosis and treatment is a key component in reducing malaria transmission and achieving elimination. As programmes approach malaria elimination targets it is critical that each case is tested and treated early, which may present a challenge when the burden of malaria is reduced. In this paper we investigate whether malaria testing rates decline over time and assess the impacts of integrating malaria and non-malaria services on testing rates in the malaria elimination task force (METF) programme in the Kayin state of Myanmar.
Methods
A retrospective analysis was conducted using weekly collected data on testing rates from a network of more than 1200 malaria posts during the period from 2014 to 2020. To determine whether monthly testing rates changed over the years of programme operations, and whether integrating malaria and non-malaria services impacted these testing rates, we fitted negative binomial mixed-effects regression models to aggregate monthly data, accounting for malaria seasonal variation.
Results
In the first year of malaria post operation, testing rates declined, correlating with a decline in attendance by people from outside the malaria post catchment area, but then remained fairly constant (the Rate Ratio (RR) for 2nd versus 1st year open ranged from 0.68 to 0.84 across the four townships included in the analysis, the RR for 3rd to 6th year versus 1st year open were similar, ranging from 0.59–0.78). The implementation of a training programme, which was intended to expand the role of the malaria post workers, had minimal impact on testing rates up to 24 months after training was delivered (RR for integrated versus malaria-only services ranged from 1.00 to 1.07 across METF townships).
Conclusion
Despite the decline in malaria incidence from 2014 to 2020, there has been no decline in the malaria testing rate in the METF programme after the establishment of the complete malaria post network in 2016. While the integration of malaria posts with other health services provides benefits to the population, our evaluation questions the necessity of integrated services in maintaining malaria testing rates in areas approaching elimination of malaria