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We analyse the turbulence characteristics and consider the closure modelling of the air entraining flow in the wake of three-dimensional, rectangular dry transom sterns obtained using high-resolution implicit large eddy simulations (iLES) (Hendrickson et al., J. Fluid Mech., vol. 875, 2019, pp. 854–883). Our focus is the incompressible highly variable density turbulence (IHVDT) in the near surface mixed-phase region
behind the stern. We characterize the turbulence statistics in
and determine it to be highly anisotropic due to quasi-steady wave breaking. Using unconditioned Reynolds decomposition for our analysis, we show that the turbulent mass flux (TMF) is important in IHVDT for the production of turbulent kinetic energy and is as relevant to the mean momentum equations as the Reynolds stresses. We develop a simple, regional explicit algebraic closure model for the TMF based on a functional relationship between the fluxes and tensor flow quantities. A priori tests of the model show mean density gradients and buoyancy effects are the main driving parameters for predicting the turbulent mass flux and the model is capable of capturing the highly localized nature of the TMF in
We present high-resolution implicit large eddy simulation (iLES) of the turbulent air-entraining flow in the wake of three-dimensional rectangular dry transom sterns with varying speeds and half-beam-to-draft ratios
. We employ two-phase (air/water), time-dependent simulations utilizing conservative volume-of-fluid (cVOF) and boundary data immersion (BDIM) methods to obtain the flow structure and large-scale air entrainment in the wake. We confirm that the convergent-corner-wave region that forms immediately aft of the stern wake is ballistic, thus predictable only by the speed and (rectangular) geometry of the ship. We show that the flow structure in the air–water mixed region contains a shear layer with a streamwise jet and secondary vortex structures due to the presence of the quasi-steady, three-dimensional breaking waves. We apply a Lagrangian cavity identification technique to quantify the air entrainment in the wake and show that the strongest entrainment is where wave breaking occurs. We identify an inverse dependence of the maximum average void fraction and total volume entrained with
. We determine that the average surface entrainment rate initially peaks at a location that scales with draft Froude number and that the normalized average air cavity density spectrum has a consistent value providing there is active air entrainment. A small parametric study of the rectangular geometry and stern speed establishes and confirms the scaling of the interface characteristics with draft Froude number and geometry. In Part 2 (Hendrikson & Yue, J. Fluid Mech., vol. 875, 2019, pp. 884–913) we examine the incompressible highly variable density turbulence characteristics and turbulence closure modelling.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Lipid-based nutrient supplements (LNS) may be beneficial for malnourished HIV-infected patients starting antiretroviral therapy (ART). We assessed the effect of adding vitamins and minerals to LNS on body composition and handgrip strength during ART initiation. ART-eligible HIV-infected patients with BMI <18·5 kg/m2 were randomised to LNS or LNS with added high-dose vitamins and minerals (LNS-VM) from referral for ART to 6 weeks post-ART and followed up until 12 weeks. Body composition by bioelectrical impedance analysis (BIA), deuterium (2H) diluted water (D2O) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VM v. LNS at 6 and 12 weeks investigated. BIA data were available for 1461, D2O data for 479, ADP data for 498 and handgrip strength data for 1752 patients. Fat mass tended to be lower, and fat-free mass correspondingly higher, by BIA than by ADP or D2O. At 6 weeks post-ART, LNS-VM led to a higher regain of BIA-assessed fat mass (0·4 (95 % CI 0·05, 0·8) kg), but not fat-free mass, and a borderline significant increase in handgrip strength (0·72 (95 % CI −0·03, 1·5) kg). These effects were not sustained at 12 weeks. Similar effects as for BIA were seen using ADP or D2O but no differences reached statistical significance. In conclusion, LNS-VM led to a higher regain of fat mass at 6 weeks and to a borderline significant beneficial effect on handgrip strength. Further research is needed to determine appropriate timing and supplement composition to optimise nutritional interventions in malnourished HIV patients.
Available twin-family data on sex differences in antisocial behavior (ASB) simultaneously suggest that ASB is far more prevalent in males than in females, and that its etiology (i.e. the effects of genes, environments, hormones, culture) does not differ across sex. This duality presents a conundrum: How do we make sense of mean sex differences in ASB if not via differences in genes, environments, hormones, and/or cultures? The current selective review and critique explores possible contributions to these seemingly incompatible sets of findings. We asked whether the presence of sex differences in behavior could be smaller than is typically assumed, or confined to a specific set of behaviors. We also asked whether there might be undetected differences in etiology across sex in twin-family studies. We found little evidence that bias or measurement invariance across sex account for phenotypic sex differences in ASB, but we did identify some key limitations to current twin-family approaches. These included the questionable ability of qualitative sex difference analyses to detect gender norms and prenatal exposure to testosterone, and concerns regarding specific analytic components of quantitative sex difference analyses. We conclude that the male preponderance in ASB is likely to reflect a true sex difference in observed behavior. It was less clear, however, that the genetic and environmental contributions to ASB are indeed identical across sex, as argued by prior twin-family studies. It is our hope that this review will inspire the development of new, genetically-informed methods for studying sex differences in etiology.
Callous-unemotional (CU) traits are critical to developmental, diagnostic, and clinical models of antisocial behaviors (AB). However, assessments of CU traits within large-scale longitudinal and neurobiologically focused investigations remain remarkably sparse. We sought to develop a brief measure of CU traits using items from widely administered instruments that could be linked to neuroimaging, genetic, and environmental data within already existing datasets and future studies.
Data came from a large and diverse sample (n = 4525) of youth (ages~9–11) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study. Moderated nonlinear factor analysis was used to assess measurement invariance across sex, race, and age. We explored whether CU traits were distinct from other indicators of AB, investigated unique links with theoretically-relevant outcomes, and replicated findings in an independent sample.
The brief CU traits measure demonstrated strong psychometric properties and evidence of measurement invariance across sex, race, and age. On average, boys endorsed higher levels of CU traits than girls and CU traits were related to, yet distinguishable from other indicators of AB. The CU traits construct also exhibited expected associations with theoretically important outcomes. Study findings were also replicated across an independent sample of youth.
In a large, multi-site study, a brief measure of CU traits can be measured distinctly from other dimensions of AB. This measure provides the scientific community with a method to assess CU traits in the ABCD sample, as well as in other studies that may benefit from a brief assessment of CU.
Healthcare institutions may often prohibit “cold-calling” or direct contact with a potential research participant when the person initiating contact is unknown to the patient. This policy aims to maintain patient privacy, but may have unintended consequences as a result of physician gatekeeping. In this review, we discuss recruitment policies at the top academic institutions. We propose an ethical framework for evaluating cold-call policies based on three principles of research ethics. In order to maximize engagement of potential research participants, while maintaining patient privacy and autonomy, we then propose several alternative solutions to restrictive cold-call policies, including opt-in or opt-out platforms, a team-based approach, electronic solutions, and best practices for recruitment. As healthcare has evolved with more collaborative, patient-centered, data-driven care, the engagement of potential research participants should similarly evolve.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
The family physician is key to facilitating access to psychiatric treatment for young people with first-episode psychosis, and this involvement can reduce aversive events in pathways to care. Those who seek help from primary care tend to have longer intervals to psychiatric care, and some people receive ongoing psychiatric treatment from the family physician.
Our objective is to understand the role of the family physician in help-seeking, recognition and ongoing management of first-episode psychosis.
We will use a mixed-methods approach, incorporating health administrative data, electronic medical records (EMRs) and qualitative methodologies to study the role of the family physician at three points on the pathway to care. First, help-seeking: we will use health administrative data to examine access to a family physician and patterns of primary care use preceding the first diagnosis of psychosis; second, recognition: we will identify first-onset cases of psychosis in health administrative data, and look back at linked EMRs from primary care to define a risk profile for undetected cases; and third, management: we will examine service provision to identified patients through EMR data, including patterns of contacts, prescriptions and referrals to specialised care. We will then conduct qualitative interviews and focus groups with key stakeholders to better understand the trends observed in the quantitative data.
These findings will provide an in-depth description of first-episode psychosis in primary care, informing strategies to build linkages between family physicians and psychiatric services to improve transitions of care during the crucial early stages of psychosis.
Discrepancies between population-based estimates of the incidence of psychotic disorder and the treated incidence reported by early psychosis intervention (EPI) programs suggest additional cases may be receiving services elsewhere in the health system. Our objective was to estimate the incidence of non-affective psychotic disorder in the catchment area of an EPI program, and compare this to EPI-treated incidence estimates.
We constructed a retrospective cohort (1997–2015) of incident cases of non-affective psychosis aged 16–50 years in an EPI program catchment using population-based linked health administrative data. Cases were identified by either one hospitalization or two outpatient physician billings within a 12-month period with a diagnosis of non-affective psychosis. We estimated the cumulative incidence and EPI-treated incidence of non-affective psychosis using denominator data from the census. We also estimated the incidence of first-episode psychosis (people who would meet the case definition for an EPI program) using a novel approach.
Our case definition identified 3245 cases of incident non-affective psychosis over the 17-year period. We estimate that the incidence of first-episode non-affective psychosis in the program catchment area is 33.3 per 100 000 per year (95% CI 31.4–35.1), which is more than twice as high as the EPI-treated incidence of 18.8 per 100 000 per year (95% CI 17.4–20.3).
Case ascertainment strategies limited to specialized psychiatric services may substantially underestimate the incidence of non-affective psychotic disorders, relative to population-based estimates. Accurate information on the epidemiology of first-episode psychosis will enable us to more effectively resource EPI services and evaluate their coverage.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
Background: The natural history of small unruptured intracranial aneurysms (UIAs) <7mm is 0 to 1.3% per year. Our centre provides cerebrovascular care for the entire province allowing for long-term follow-up. We studied the safety of observation for aneurysms <7mm. Methods: We performed a retrospective chart review of patients with intracranial aneurysm referred to our centre between July 2008 and April 2015. Aneurysm characteristics and current status (followed, treated, not followed), were collected along with patient factors. Follow-up duration for each aneurysm was used to calculate total follow-up in aneurysm-years. Statistical evaluation consisted of multivariate analysis and logistic regression analysis. Results: 428 patients harbouring 497 aneurysms <7mm were identified. 67 presented with rupture. Of the remaining 430 aneurysms, there was a 9.3% treatment rate. 2 cases of rupture occurred in those patients who were followed, creating a 0.5% rupture rate. 325 aneurysms were followed for 631.3 total cumulative aneurysm-years, an average of 1.9 aneurysm-years. Smoking status and hypertension associated with presence of aneurysm (p≈0.009,0.026, respectively). Conclusions: In our selected patient group there is a low yearly rate of aneurysm rupture, and observation of aneurysms <7mm is safe. Hypertension and smoking were associated with the development of aneurysm. 9.3% of patients were treated, likely leading to a reduced natural history risk.
Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are co-opted by GBM to further angiogenesis and invasion. There are no effective immunotherapies against GBM in part because GBM-associated MMs are not well understood. We hypothesized that the extent and inflammatory phenotype of MM infiltration into GBM is variable between patients. This variability could have important implications on immunotherapy selection and treatment outcomes. Methods: Using automated quantitation of fluorescently labeled human GBMs, flow cytometry/live cell sorting, collection of conditioned GBM-associated MM media, and corroboration with TCGA and previously published scRNA-seq data, we have uncovered there is surprisingly marked variation in the amount of MM infiltration between tumors. Results: MM infiltration can range from almost non-existent, to comprising ~70% of GBM cells. By detecting cell surface markers and secreted cytokines, we determined that a mixture of pro- and anti-inflammatory MMs are found in each tumor. The overall inflammatory phenotype did not depend on the amount of infiltration. Interestingly, IDH-mutant GBM-associated MMs are more pro-inflammatory and less heterogeneous than IDH-wildtype GBMs. Conclusions: Taken together, the highly variable immunologic status of GBMs suggests the success of immunotherapies hinges on selecting appropriately vulnerable tumors.
Bovine herpes virus 1 (BHV-1) manifests as a latent viral infection putatively affecting bovines. Understanding its effect on cattle herds is critical to maintaining sustainable beef and dairy production systems, as well as aiding in the development of herd health policies. The primary objective of the current study was, therefore, to use a whole-farm bio-economic model to evaluate the effect of herd seroprevalence to BHV-1 on the productive and economic performance of a spring calving beef cow herd. As part of a wider epidemiological study of herd pathogen status, a total of 4240 cows from 134 spring calving beef cow herds across the Republic of Ireland were blood sampled to measure the seroprevalence to BHV-1. Using data from a national breeding database, productive and reproductive performance indicators were used to parameterize a single year, static and deterministic whole-farm bio-economic model. A spring-calving, pasture-based suckler beef cow production system with an emphasis on calf-to-weanling production was simulated. The impact of BHV-1 seropositivity on whole-farm technical and economic performance was relatively small, with a marginal drop in the net margin of 4% relative to a baseline seronegative herd. Subsequent risk factors for increased pathogenicity were considered such as total herd size, percentage of intra-herd movements and vaccination status for BHV-1. In contrast to all others, scenarios representing herds that were either small in size or those which indicated an active vaccination policy for BHV-1 had no reduction in net margin against the baseline as a result of seropositivity to BHV-1.
Modifying finishing strategies within established production systems has the potential to increase beef output and farm profit while reducing greenhouse gas (GHG) emissions. Thus, the objectives of this study were to investigate the effects of finishing duration on animal performance of Holstein-Friesian (HF) bulls and steers and evaluate the profitability and GHG emissions of these finishing strategies. A total of 90 HF calves were assigned to a complete randomised block design; three bull and three steer finishing strategies. Calves were rotationally grazed in a paddock system for the first season at pasture, housed and offered grass silage ad libitum plus 1.5 kg DM of concentrate per head daily for the first winter and returned to pasture for a second season. Bulls were slaughtered at 19 months of age and either finished indoors on concentrates ad libitum for 100 days (19AL), finished at pasture supplemented with 5 kg DM of concentrate per head daily for 100 (19SP) or 150 days (19LP). Steers were slaughtered at 21 months of age and finished at pasture, supplemented with 5 kg DM of concentrate per head daily for 60 (21SP) and 110 days (21LP) or slaughtered at 24 months of age and finished indoors over the second winter on grass silage ad libitum plus 5 kg DM of concentrate per head daily (24MO). The Grange Dairy Beef Systems Model and the Beef Systems Greenhouse Gas Emissions Model were used to evaluate profitability and GHG emissions, respectively. Average daily gain during the finishing period (P<0.001), live weight at slaughter (P<0.01), carcass weight (P<0.05) and fat score (P<0.001) were greater for 19AL than 19SP and 19LP, respectively. Similarly, concentrate dry matter intake was greater for 19AL than 19SP; 19LP was intermediate (P<0.001). Live weight at slaughter (P<0.001), carcass weight (P<0.001), conformation score (P<0.05) and fat score (P<0.001) were greater for 24MO than 21SP and 21LP, respectively. During the finishing period concentrate dry matter intake was greater for 21LP than 21SP with 24MO intermediate; 542, 283 and 436 kg DM, respectively. Although pasture-based finishing strategies had lower gross output values, concentrate feed costs were also reduced thus net margin was greater than indoor finishing strategies. Reducing concentrate input increased GHG emissions for bulls and steers slaughtered at the same age, respectively. Although prolonging the finishing duration reduced GHG emissions for bull and steer production systems, finishing bulls and steers over a longer period at pasture did not enhance animal performance and profit.
In response to the 2014 Ebola virus disease (EVD) outbreak in West Africa, the Georgia Department of Public Health developed the Infectious Disease Network (IDN) based on an EVD preparedness needs assessment of hospitals and Emergency Medical Services (EMS) providers. The network consists of 12 hospitals and 16 EMS providers with staff specially trained to provide a coordinated response and utilize appropriate personal protective equipment (PPE) for the transport or treatment of a suspected or confirmed serious communicable disease patient. To become a part of the network, each hospital and EMS provider had to demonstrate EVD capabilities in areas such as infection control, PPE, waste management, staffing and ongoing training, and patient transport and placement. To establish the network, the Georgia Department of Public Health provided training and equipment for EMS personnel, evaluated hospitals for EVD capabilities, structured communication flow, and defined responsibilities among partners. Since March 2015, the IDN has been used to transport, treat, and/or evaluate suspected or confirmed serious communicable disease cases while ensuring health care worker safety. Integrated infectious disease response systems among hospitals and EMS providers are critical to ensuring health care worker safety, and preventing or mitigating a serious communicable disease outbreak. (Disaster Med Public Health Preparedness. 2018;12:765-771)