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Large-eddy simulations (LES) are widely used for computing high Reynolds number turbulent flows. Spatial filtering theory for LES is not without its shortcomings, including how to define filtering for wall-bounded flows, commutation errors for non-uniform filters and extensibility to flows with additional complexity, such as multiphase flows. In this paper, the theory for LES is reimagined using a coarsening procedure that imitates nature. This physics-inspired coarsening approach is equivalent to Gaussian filtering for single-phase wall-free flows but opens up new insights for both physical understanding and modelling even in that simple case. For example, an alternative to the Germano identity is introduced and used to define a dynamic procedure without the need for a test filter. Non-uniform resolution can be represented in this framework without commutation errors, and the divergence-free condition is retained for incompressible flows. Potential extensions of the theory to more complex physics such as multiphase flows are briefly discussed.
Important advances in biomedical and behavioral research ethics have occurred over the past few decades, many of them centered on identifying and eliminating significant harms to human subjects of research. Comprehensive attention has not been paid to the totality of harms experienced by animal subjects, although scientific and moral progress require explicit appraisal of these harms. Science is a public good and the prioritizing within, conduct of, generation of, and application of research must soundly address questions about which research is morally defensible and valuable enough to support through funding, publication, tenure, and promotion. Likewise, educational pathways of re-imagined science are critical.
The late congressman John Lewis spent most of his political life engaging Black Power's commitment to economic and political freedom through a political vocabulary that aligned with his deeply held beliefs in nonviolence, human rights activism, and moral faith. The tension between the Black radical left and establishment Black politics dates back to Lewis's clash with elite Black leaders over the content of his prepared address for the 1963 March on Washington. The address provides a glimpse into Lewis's complicated political legacy. The youngest speaker at the March, Lewis faced the daunting task of both representing the political philosophy of the Student Nonviolent Coordinating Committee (SNCC) and meeting the expectations of established civil rights leaders. Negotiating the political interests of the organizers of the March alongside the demands of SNCC foreshadowed the congressman's political vocation: a lifetime of civil rights advocacy through a politics of respectability and Black Power's political philosophy of freedom and economic transformation. Lewis's political legacy is complicated; and yet, it was fueled by an unabashed commitment to Black freedom struggles, human rights activism, and racial reconciliation.
Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.
Table for P.120
Current antiseizure medication
Infantile spasms, LGS, hyperkinetic movements
3y - EEG abnormality only
Sodium valproate (discontinued)
No clinical seizure
c.971G>A (p.Cys324Tyr)/LoF, VUS in KCNQ3
Abbreviations: *Father with similar history, y Years, m Months, GDD Global developmental delay, LGS Lennox-Gastaut syndrome, VUS Variant of unknown significance, LoF Loss-of-function, GoF Gain-of-function, EEG Electroencephalogram, F - Female, M - Male, CBD - Cannabidiol
Commercialization of 2,4-D-resistant soybean varieties allows for postemergence (POST) applications of 2,4-D in soybean. With the increase in POST applications of 2,4-D in soybean, shifts in weed populations may occur. A long-term field trial was conducted over seven years in a corn-soybean rotation. Weed populations were subjected to four herbicide strategies with variable levels of 2,4-D reliance. The strategies used included: 1) diversified glyphosate strategy with six herbicide sites of action (SOA); 2) 2,4-D reliant strategy with three SOA; 3) diversified 2,4-D reliant strategy with seven SOA; and 4) fully diversified strategy with eight SOA. Soil residual herbicides were utilized for both corn and soybean years, except for the 2,4-D reliant strategy which only utilized a residual herbicide during the corn years. A 52% or greater reduction in weed densities for all herbicide strategies, except the 2,4-D reliant strategy, was observed by the end of the study. However, the density of weeds tolerant to 2,4-D, such as monocots, increased after three years of selection pressure, and more than doubled after five years of selection pressure in the 2,4-D reliant strategy. Additionally, in the 2,4-D reliant strategy with three SOA, species richness was 30% higher in the soil seedbank compared to herbicides strategies with six or more SOA. In order to delay weed shifts, diversified herbicide strategies with more than three SOA that include residual herbicides should be used in corn:soybean rotational systems that utilize 2,4-D-resistant soybean.
Cover crops can be utilized to suppress weeds via direct competition for sunlight, water, and soil nutrients. Research was conducted to determine if cover crops can be used in label-mandated buffer areas in 2,4-D-resistant soybean cropping systems. Delaying termination of cover crops containing cereal rye to at or after soybean planting resulted in a 25 to more than 200 percentage point increase in cover crop biomass compared to a control treatment. Cover crops generally improved horseweed control when 2,4-D was not used. Cover crops reduced grass densities up to 54% at four of six site-years when termination was delayed to after soybean planting. Cover crops did not reduce giant ragweed densities. Cover crops reduced waterhemp densities by up to 45%. Cover crops terminated at or after planting were beneficial within buffer areas for control of grasses and waterhemp, but not giant ragweed. Yield reductions of 14% to 41% occurred when cover crop termination was delayed to after soybean planting at three of six site-years. Terminating the cover crops at planting time provided suppression of grasses and waterhemp within buffer areas and had similar yield to the highest-yielding treatment in five out of six site-years.
Virtual platforms can provide a socially distanced mechanism by which to promote ongoing research progress in the coronavirus disease 2019 (COVID-19) era and may change our approach to online research in the future. Understanding how to best utilise online research represents an important task for our field.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury 14 d after LP application was less than 10% for all application timings. Late-season weed control was reduced up to 30 and 53% if chloroacetamide application occurred PRE or LP only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made LP relative to other application timings. Chloroacetamide application at any timing except PRE alone minimized late season weed biomass. Yield was maximized by any treatment involving multiple applications or EP alone whereas applications PRE or LP alone resulted in up to 56 and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until EP, foregoing a PRE application is not advisable given the multiple factors that may delay timely POST applications such as inclement weather.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
The tendency of turbulent flows to produce fine-scale motions from large-scale energy injection is often viewed as a scale-wise cascade of kinetic energy driven by vorticity stretching. This has been recently evaluated by an exact, spatially local relationship (Johnson, P.L. Phys. Rev. Lett., vol. 124, 2020, p. 104501), which also highlights the contribution of strain self-amplification. In this paper, the role of these two mechanisms is explored in more detail. Vorticity stretching and strain amplification interactions between velocity gradients filtered at the same scale account for approximately half of the energy cascade rate, directly connecting the restricted Euler dynamics to the energy cascade. Multiscale strain amplification and vorticity stretching are equally important, however, and more closely resemble eddy viscosity physics. Moreover, ensuing evidence of a power-law decay of energy transfer contributions from disparate scales supports the notion of an energy cascade, albeit a ‘leaky’ one. Besides vorticity stretching and strain self-amplification, a third mechanism of energy transfer is introduced and related to the vortex thinning mechanism important for the inverse cascade in two dimensions. Simulation results indicate this mechanism also provides a net source of backscatter in three-dimensional turbulence, in the range of scales associated with the bottleneck effect. Taken together, these results provide a rich set of implications for large-eddy simulation modelling.
The limitations of self-report measures of dietary intake are well-known. Novel, technology-based measures of dietary intake may provide a more accurate, less burdensome alternative to existing tools. The first objective of this study was to compare participant burden for two technology-based measures of dietary intake among school-age children: the Automated-Self-Administered 24-hour Dietary Assessment Tool-2018 (ASA24-2018) and the Remote Food Photography Method (RFPM). The second objective was to compare reported energy intake for each method to the Estimated Energy Requirement for each child, as a benchmark for actual intake. Forty parent–child dyads participated in two, 3-d dietary assessments: a parent proxy-reported version of the ASA24 and the RFPM. A parent survey was subsequently administered to compare satisfaction, ease of use and burden with each method. A linear mixed model examined differences in total daily energy intake between assessments, and between each assessment method and the Estimated Energy Requirement (EER). Reported energy intake was 379 kcal higher with the ASA24 than the RFPM (P = 0·0002). Reported energy intake with the ASA24 was 231 kcal higher than the EER (P = 0·008). Reported energy intake with the RFPM did not differ significantly from the EER (difference in predicted means = −148 kcal, P = 0·09). Median satisfaction and ease of use scores were five out of six for both methods. A higher proportion of parents reported that the ASA24 was more time-consuming than the RFPM (74·4 % v. 25·6 %, P = 0·002). Utilisation of both methods is warranted given their high satisfaction among parents.
Cannabis is one of the most widely used recreational drugs among people with clinical psychosis, after nicotine and alcohol. There has been a debate in psychiatry about whether or not we can infer a cause-and-effect relationship between the use of cannabis and psychotic disorders. In this editorial, we first present and critically discuss the evidence to date of the association between heavy cannabis use and psychosis. We argue that while the biological mechanisms underlying individual susceptibility to develop a psychotic disorder following heavy cannabis use are still unknown, heavy cannabis use remains the most modifiable risk factor for the onset of psychotic disorders and for its clinical and functional outcome. This demands a clear move towards both primary and secondary prevention intervention to reduce the impact of heavy cannabis use on the incidence and prevalence of psychotic disorders.
To estimate the proportion of products meeting Fiji government labelling regulations, assess compliance with national Na reformulation targets and examine the Na and total sugar levels in packaged foods sold in selected major supermarkets.
We selected five major supermarkets in 2018 and collected the product information and nutritional content from the labels of all packaged foods sold. We organised 4278 foods into fourteen major food categories and thirty-six sub-categories and recorded the proportion of products labelled in accordance with the Fiji labelling regulations. We looked at the levels of Na and total sugar in each food category and assessed how many products complied with the Fiji reformulation targets set for Na. We also listed the companies responsible for each product.
Fourteen percentage of packaged foods in fourteen major categories met Fiji national labelling regulations. Na was labelled on 95·4 % products, and total sugar labelled on 92·4 %. The convenience foods category had the highest Na levels (1699 mg/100 g), while confectionery had the highest content of total sugar (52·6 g/100 g). Forty percentage of eligible products did not meet the proposed voluntary Na reformulation targets.
Our findings indicate significant room for improvement in nutrient labelling, as well as a need for further enforcement of reformulation targets and monitoring of changes in food composition. Through enacting these measures and establishing additional regulations such as mandatory front-of-pack labelling, government and food industry can drive consumers towards healthier food choices and improve the nutritional quality of packaged foods in Fiji.
Sherita Johnson considers a region much more associated with African Americans in Reconstruction in her “Reconstruction of the South in African American Literature.” Johnson examines the transformations of a place, people, and Black literary tradition(s) responding to the political and cultural conflicts of the era and finds that Elizabeth Keckley, Frances Ellen Watkins Harper, William Wells Brown, James Madison Bell, Albery A. Whitman and Pauline Hopkins all present “Black witnesses” to Reconstruction in their works: slaves emancipating themselves, freedmen and women staking claims to Southern homes built by generational struggles, and black citizens enacting the promises of democracy. Ultimately, her chapter provides case studies of diverse texts – travel narratives, epic poems, autobiographical sketches, and moral theatre – to consider how such works by African American writers help to correct the historical record of Reconstruction and of Southern literary history.
Palpable thyroid nodules are present in approximately 5–7% of the adult population, and of these, 5–10% harbor malignancy. Additional thyroid nodules are found incidentally on imaging for other medical reasons, including screening for malignancies of other organs or evaluation of vasculature. Ultrasound (US) imaging of the neck with evaluation of the thyroid and lymph nodes is typically used and recommended to characterize thyroid nodules. The American Thyroid Association (ATA) classification, and the Thyroid Imaging, Reporting, and Data System (TIRADS) of the American College of Radiology (ACR-TIRADS) risk stratification systems are commonly used.
Breaking waves generate a distribution of bubble sizes that evolves over time. Knowledge of how this distribution evolves is of practical importance for maritime and climate studies. The analytical framework developed in Part 1 (Chan, Johnson & Moin, J. Fluid Mech., vol. 912, 2021, A42) examined how this evolution is governed by the bubble-mass flux from large- to small-bubble sizes which depends on the rate of break-up events and the distribution of child bubble sizes. These statistics are measured in Part 2 as ensemble-averaged functions of time by simulating ensembles of breaking waves, and identifying and tracking individual bubbles and their break-up events. The large-scale break-up dynamics is seen to be statistically unsteady, and two intervals with distinct characteristics were identified. In the first interval, the dissipation rate and bubble-mass flux are quasi-steady, and the theoretical analysis of Part 1 is supported by all observed statistics, including the expected $-10/3$ power-law exponent for the super-Hinze-scale size distribution. Strong locality is observed in the corresponding bubble-mass flux, supporting the presence of a super-Hinze-scale break-up cascade. In the second interval, the dissipation rate decays, and the bubble-mass flux increases as small- and intermediate-sized bubbles become more populous. This flux remains strongly local with cascade-like behaviour, but the dominant power-law exponent for the size distribution increases to $-8/3$ as small bubbles are also depleted more quickly. This suggests the emergence of different physical mechanisms during different phases of the breaking-wave evolution, although size-local break-up remains a dominant theme. Parts 1 and 2 present an analytical toolkit for population balance analysis in two-phase flows.
Breaking waves entrain gas beneath the surface. The wave-breaking process energizes turbulent fluctuations that break bubbles in quick succession to generate a wide range of bubble sizes. Understanding this generation mechanism paves the way towards the development of predictive models for large-scale maritime and climate simulations. Garrett et al. (J. Phys. Oceanogr., vol. 30, 2000, pp. 2163–2171) suggested that super-Hinze-scale turbulent break-up transfers entrained gas from large- to small-bubble sizes in the manner of a cascade. We provide a theoretical basis for this bubble-mass cascade by appealing to how energy is transferred from large to small scales in the energy cascade central to single-phase turbulence theories. A bubble break-up cascade requires that break-up events predominantly transfer bubble mass from a certain bubble size to a slightly smaller size on average. This property is called locality. In this paper, we analytically quantify locality by extending the population balance equation in conservative form to derive the bubble-mass-transfer rate from large to small sizes. Using our proposed measures of locality, we show that scalings relevant to turbulent bubbly flows, including those postulated by Garrett et al. (J. Phys. Oceanogr., vol. 30, 2000, pp. 2163–2171) and observed in breaking-wave experiments and simulations, are consistent with a strongly local transfer rate, where the influence of non-local contributions decays in a power-law fashion. These theoretical predictions are confirmed using numerical simulations in Part 2 (Chan et al., J. Fluid. Mech. vol. 912, 2021, A43), revealing key physical aspects of the bubble break-up cascade phenomenology. Locality supports the universality of turbulent small-bubble break-up, which simplifies the development of cascade-based subgrid-scale models to predict oceanic small-bubble statistics of practical importance.
The collisions in a dilute polydisperse suspension of sub-Kolmogorov spheres with negligible inertia settling in a turbulent flow and interacting through hydrodynamics including continuum breakdown on close approach are studied. A statistically significant decrease in ideal collision rate without gravity is resolved via a Lagrangian stochastic velocity-gradient model at Taylor microscale Reynolds number larger than those accessible by current direct numerical simulation capabilities. This arises from the difference between the mean inward velocity and the root-mean-square particle relative velocity. Differential sedimentation, comparable to the turbulent shear relative velocity, but minimally influencing the sampling of the velocity gradient, diminishes the Reynolds number dependence and enhances the ideal collision rate i.e. the rate without interactions. The collision rate is retarded by hydrodynamic interactions between sphere pairs and is governed by non-continuum lubrication as well as full continuum hydrodynamic interactions at larger separations. The collision efficiency (ratio of actual to ideal collision rate) depends on the relative strength of differential sedimentation and turbulent shear, the size ratio of the interacting spheres and the Knudsen number (defined as the ratio of the mean-free path of the gas to the mean radius of the interacting spheres). We develop an analytical approximation to concisely report computed results across the parameter space. This accurate closed form expression could be a critical component in computing the evolution of the size distribution in applications such as water droplets in clouds or commercially valuable products in industrial aggregators.
Collisions in a dilute polydisperse suspension of spheres of negligible inertia interacting through non-continuum hydrodynamics and settling in a slow uniaxial compressional flow are studied. The ideal collision rate is evaluated as a function of the relative strength of gravity and uniaxial compressional flow and it deviates significantly from a linear superposition of these driving terms. This non-trivial behaviour is exacerbated by interparticle interactions based on uniformly valid non-continuum hydrodynamics, that capture non-continuum lubrication at small separations and full continuum hydrodynamic interactions at larger separations, retarding collisions driven purely by sedimentation significantly more than those driven purely by the linear flow. While the ideal collision rate is weakly dependent on the orientation of gravity with the axis of compression, the rate including hydrodynamic interactions varies by more than $100\,\%$ with orientation. This dramatic shift can be attributed to complex trajectories driven by interparticle interactions that prevent particle pairs from colliding or enable a circuitous path to collision. These and other important features of the collision process are studied in detail using trajectory analysis at near unity and significantly smaller than unity size ratios of the interacting spheres. For each case analysis is carried for a large range of relative strengths and orientations of gravity to the uniaxial compressional flow, and Knudsen numbers (ratio of mean free path of the media to mean radius).
In March 2020, academic medical center (AMC) pharmacies were compelled to implement practice changes in response to the COVID-19 pandemic. These changes were described by survey data collected by the Clinical and Translational Science Awards (CTSA) program which were interpreted by a multi-institutional team of AMC pharmacists and physician investigators.
The CTSA program surveyed 60 AMC pharmacy departments. The survey included event timing, impact on pharmacy services, and corrective actions taken.
Almost all departments (98.4%) reported at least one disruption. Shortages of personal protective equipment (PPE) were common (91.5%) as were drug shortages (66.0%). To manage drug shortages, drug prioritization protocols were utilized, new drug supply vendors were identified (79.3%), and onsite compounding was initiated. PPE shortages were managed by incorporating the risk mitigation strategies recommended by FDA and others. Research pharmacists supported new clinical research initiatives at most institutions (84.0%), introduced use of virtual site visits, and shipped investigational drugs directly to patients. Some pharmacies formulated novel investigational products for clinical trial use. Those AMC pharmacies within networked health systems assisted partner rural and inner-city hospitals by sourcing commercial and investigational drugs to alleviate local disease outbreaks and shortages in underserved populations. Pharmacy-based vaccination practice was expanded to include a wider range of pediatric and adult vaccines.
The COVID-19 pandemic radically altered hospital pharmacy practice. By adopting innovative methods and adapting to regulatory imperatives, pharmacies at CTSA sites played an extremely important role supporting continuity of care and collaborating on critical clinical research initiatives.