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Assessing children’s diets is currently challenging and burdensome. Abbreviated FFQ have the potential to assess dietary patterns in a rapid and standardised manner. Using nationally representative UK dietary intake and biomarker data, we developed an abbreviated FFQ to calculate dietary quality scores for pre-school and primary school-aged children. UK National Diet and Nutrition Survey (2008–2016) weekly consumption frequencies of 129 food groups from 4-d diaries were cross-sectionally analysed using principal component analysis. A 129-item score was derived, alongside a 12-item score based on foods with the six highest and six lowest coefficients. Participants included 1069 pre-schoolers and 2565 primary schoolchildren. The first principal component explained 3·4 and 3·0 % of the variation in the original diet variables for pre-school and primary school groups, respectively, and described a prudent diet pattern. Prudent diet scores were characterised by greater consumption of fruit, vegetables and tap water and lower consumption of crisps, manufactured coated chicken/turkey products, purchased chips and soft drinks for both age groups. Correlations between the 129-item and 12-item scores were 0·86 and 0·84 for pre-school and primary school-aged children, respectively. Bland–Altman mean differences between the scores were 0·00 sd; 95 % limits of agreement were −1·05 to 1·05 and −1·10 to 1·10 sd for pre-school and primary school-aged children, respectively. Correlations between dietary scores and nutritional biomarkers showed only minor attenuation for the 12-item compared with the 129-item scores, illustrating acceptable congruence between prudent diet scores. The two 12-item FFQ offer user-friendly tools to measure dietary quality among UK children.
Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.
Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.
Thin spray-on liners (TSLs) have been found to be effective for structurally supporting the walls of mining tunnels and thus reducing the occurrence of rock bursts, an effect primarily due to the penetration of cracks by the liner. Surface tension effects are thus important. However, TSLs are also used to simply stabilize rock surfaces, for example, to prevent rock fall, and in this context crack penetration is desirable but not necessary, and the tensile and shearing strength and adhesive properties of the liner determine its effectiveness. We examine the effectiveness of nonpenetrating TSLs in a global lined tunnel and in a local rock support context. In the tunnel context, we examine the effect of the liner on the stress distribution in a tunnel subjected to a geological or mining event. We show that the liner has little effect on stresses in the surrounding rock and that tensile stresses in the rock surface are transmitted across the liner, so that failure is likely to be due to liner rupture or detachment from the surface. In the local rock support context, loose rock movements are shown to be better achieved using a liner with small Young’s modulus, but high rupture strength.
Despite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies.
Objectives
To assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.
Methods
In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.
Results
Pre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.
Conclusions
Pre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.
The behavioural reactions and blood Cortisol levels of cattle stunned using a penetrating captive-bolt pistol whilst standing free in a stunning box were compared with those obtained from cattle similarly stunned but with their heads held in a hydraulically operated chin-lift type of head restrainer. Few (8 out of 55) animals voluntarily put their heads into the restrainer, most had to be ‘persuaded’ to use the head-restrainer; some (5 out of 24) could not be. The mean time between entry into the stunning pen and the stun for 23 free standing animals was 5.6s and for 19 animals which could be persuaded to use the head restrainer was 34.2s. The Cortisol levels in the blood taken at the stick, from 30 animals stunned while standing free was 67.6 nmoVlitre while that from 30 stunned while head-restrained was 143.1 nmolHitre. The behaviour and Cortisol results suggest that enforced usage of this type of head restrainer could be a cause of distress to the cattle involved.
We previously reported that African (Loxodonta africana) and Asian (Elephas maximus) female elephants in European zoos have shorter adult lifespans than protected conspecifics in range countries. This effect was the cause of greatest concern in Asian elephants, and risk factors within this species included being zoo-born, transferred between zoos, and possibly removed early from the mother. Here, we investigate these risk factors further; assess fecundity and sustainability in European zoos; and propose testable hypotheses as to the causes of these animals’ problems. Although imported wild-born Asian elephants live longer than zoo-born conspecifics, being imported when juvenile or adult appears no more protective than being imported in infancy, suggesting that the benefits of being wild- rather than zoo-born are conferred early in life. Zoo-born Asian neonates are significantly heavier than those born to working animals in range countries, with a possible tendency to be fatter. In zoos, African elephants have tended to be removed from their mothers at older ages than young Asians, and were also transferred between zoos significantly less often: factors that could possibly underlie this species’ lower calf losses and improving adult survivorship in Europe. Both species have low fecundity in European zoos compared to in situ populations, and are not self-sustaining, declining at approximately 10% per annum if reliant on captive-bred females under historically prevailing conditions. Data from other species suggest that stress and/or obesity are parsimonious explanations for the suite of problems seen. We recommend specific screens for testing these hypotheses, and for potentially identifying vulnerable individuals within the extant zoo populations.
The updated vancomycin guideline for treatment of serious methicillin-resistant Staphylococcus aureus infections prompted institutions to convert from trough to area-under-the-curve monitoring. The physician perception of the transition, coupled with that of pharmacists, was measured by pre- and postimplementation surveys. Both groups believed safety would be increased without efficacy changes.
The COVID-19 pandemic presented a challenge to established seed grant funding mechanisms aimed at fostering collaboration in child health research between investigators at the University of Minnesota (UMN) and Children’s Hospitals and Clinics of Minnesota (Children’s MN). We created a “rapid response,” small grant program to catalyze collaborations in child health COVID-19 research. In this paper, we describe the projects funded by this mechanism and metrics of their success.
Methods:
Using seed funds from the UMN Clinical and Translational Science Institute, the UMN Medical School Department of Pediatrics, and the Children’s Minnesota Research Institute, a rapid response request for applications (RFAs) was issued based on the stipulations that the proposal had to: 1) consist of a clear, synergistic partnership between co-PIs from the academic and community settings; and 2) that the proposal addressed an area of knowledge deficit relevant to child health engendered by the COVID-19 pandemic.
Results:
Grant applications submitted in response to this RFA segregated into three categories: family fragility and disruption exacerbated by COVID-19; knowledge gaps about COVID-19 disease in children; and optimizing pediatric care in the setting of COVID-19 pandemic restrictions. A series of virtual workshops presented research results to the pediatric community. Several manuscripts and extramural funding awards underscored the success of the program.
Conclusions:
A “rapid response” seed funding mechanism enabled nascent academic-community research partnerships during the COVID-19 pandemic. In the context of the rapidly evolving landscape of COVID-19, flexible seed grant programs can be useful in addressing unmet needs in pediatric health.
Diamondback moth, Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae), a globally important pest of Brassicaceae crops, migrates into all provinces of Canada annually. Life tables were used to determine the mortality levels contributed by the parasitoid complexes associated with diamondback moth in British Columbia, Ontario, Prince Edward Island, and insular Newfoundland. Overall, diamondback moth populations showed high generational mortality (> 90%) in all provinces, although parasitism levels were generally low. The net reproductive rate of increase in diamondback moth was less than 1.0 (populations declined) in both years in British Columbia and in each of two years in Newfoundland and Ontario, but it was greater than 1.0 in all three years in Prince Edward Island. Lower parasitism levels were found in Prince Edward Island (3.0–6.3%) compared with other provinces (8.4–17.6%, except one year in British Columbia). Diadegma insulare was the main larval parasitoid found; it was present in all provinces. Microplitis plutellae was present in all provinces except British Columbia. Oomyzus sokolowskii was found in British Columbia and Ontario. The parasitoid community documented from sentinel sampling was less diverse than that found through destructive sampling. Hypotheses are provided to explain the presence of major parasitoids. Increasing larval parasitism would have the largest effect on diamondback moth population growth in Canada.
Diamondback moth, Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae), was first recorded in North America from Europe about 150 years ago and can be a significant pest of canola in Western Canada. Because parasitism of P. xylostella in Canada is generally low, the introduction of one or more additional exotic parasitoids from Europe is being considered to increase the suppression of P. xylostella populations. Life table studies to determine the impact of parasitoids on diamondback moth populations in Europe were conducted in northwestern Switzerland in 2014–2016. Net reproductive rates were found to be less than one in seven out of eight life tables, suggesting that P. xylostella populations in Switzerland are mostly driven by immigration and recolonisation. In total, seven primary parasitoid species and one hyperparasitoid were associated with diamondback moth. Pupal parasitism by D. collaris reached up to 30%, but because generational mortality was mainly driven by abiotic mortality factors and predation of larvae, the overall contribution of pupal parasitism was low (< 6%). In regions of Canada, where P. xylostella may have increasing populations and low larval mortality, the addition of D. collaris may be a promising approach. Life table studies across Canada are necessary to determine the need for such intervention.
Introduction: It is unclear whether anticoagulant or antiplatelet medications increase the risk for intracranial bleeding in older adults after a fall. Our aim was to report the incidence of intracranial bleeding among older adults presenting to the emergency department (ED) with a fall, among patients taking anticoagulants, antiplatelet medications, both medications and neither medication. Methods: This was a systematic review and meta-analysis, PROSPERO reference CRD42019122626. Medline, EMBASE (via OVID 1946 - July 2019), Cochrane, Database of Abstracts of Reviews of Effects databases and the grey literature were searched for studies reporting on older adults who were evaluated after a fall. We included prospective studies conducted in the ED where more than 80% of the cohort were 65 years or older and had fallen. We contacted study authors for aggregate data on intracranial bleeding in patients prescribed anticoagulant medication, antiplatelet medication and neither medication. Incidences of intracranial bleeding were pooled using random effect models, and I2 index was used to assess heterogeneity. Results: From 7,240 publication titles, 10 studies met inclusion criteria. The authors of 8 of these 10 studies provided data (on 9,489 patients). All studies scored low or moderate risk of bias. The pooled incidence of intracranial bleeding among patients taking an anticoagulant medication was 5.1% (n = 5,016, 95% Confidence Interval (CI): 4.1 to 6.3%) I2 = 42%, a single antiplatelet 6.4% (n = 2,148, 95% CI: 5.4 to 7.6%) I2 = 75%, both anticoagulant and antiplatelet medications 5.9% (n = 212, 95% CI: 1.3 to 13.5%) I2 = 72%, and neither of these medications 4.8% (n = 1,927, 95% CI: 3.5 to 6.2%) I2 = 50%. A sensitivity analysis restricted to patients who had a head CT in the ED reported incidences of 6.1% (n = 3,561, 95% CI: 3 to 8.3%), 8.4% (n = 1,781, 95% CI: 5.5 to 11.8%), 6.7% (n = 206, 95% CI 1.5 to 15.2%) and 6.6% (n = 1,310, 95% CI: 5.0 to 8.4%) respectively. Conclusion: The incidence of fall-related intracranial bleeding in older ED patients was similar among patients who take anticoagulant medication, antiplatelet medication, both and neither medication, although there was heterogeneity between study findings.
A zirconolite glass-ceramic material is a candidate wasteform for immobilisation of chlorine contaminated plutonium residues, in which plutonium and chlorine are partitioned to the zirconolite and aluminosilicate glass phase, respectively. A preliminary investigation of chlorine speciation was undertaken by analysis of Cl K-edge X-ray Absorption Near Edge Spectroscopy (XANES), to understand the incorporation mechanism. Cl was found to be speciated as the Cl- anion within the glass phase, according to the characteristic chemical shift of the X-ray absorption edge. By comparison with Cl K-edge XANES data acquired from reference compounds, the local environment of the Cl- anion is most closely approximated by the mineral marialite, in which Cl is co-ordinate to 4 x Na and/or Ca atoms.
Solar coronal dimmings have been observed extensively in the past two decades and are believed to have close association with coronal mass ejections (CMEs). Recent study found that coronal dimming is the only signature that could differentiate powerful flares that have CMEs from those that do not. Therefore, dimming might be one of the best candidates to observe the stellar CMEs on distant Sun-like stars. In this study, we investigate the possibility of using coronal dimming as a proxy to diagnose stellar CMEs. By simulating a realistic solar CME event and corresponding coronal dimming using a global magnetohydrodynamics model (AWSoM: Alfvén-wave Solar Model), we first demonstrate the capability of the model to reproduce solar observations. We then extend the model for simulating stellar CMEs by modifying the input magnetic flux density as well as the initial magnetic energy of the CME flux rope. Our result suggests that with improved instrument sensitivity, it is possible to detect the coronal dimming signals induced by the stellar CMEs.
In support of the disposal system safety case for a geological disposal facility (GDF) there is a requirement to consider 'what-if' hypothetical scenarios for post-closure nuclear criticality. Although all such scenarios are considered very unlikely, one 'what-if' scenario is the mobilization of fissile material from a number of waste packages and its slow accumulation within the GDF or the immediate surroundings. Should sufficient fissile material accumulate a quasi-steady-state (QSS) transient criticality event could result. A computer model has been developed to understand the evolution and consequences of such an event.
Since a postulated QSS criticality could persist for many millennia, building confidence in the modelling approach is difficult. However, the Oklo natural reactors in Africa operated for similar durations around two billion years ago, providing a natural analogue for comparison. This paper describes the modelling approach, its application to hypothetical criticality events for a GDF, and how the model can be compared to Oklo. The model results are found to be in agreement with the observational evidence from Oklo, building confidence in the use of the QSS model to simulate postulated post-closure criticality events in GDFs.
A combination of ion-microprobe (for Li) and electron-microprobe (for other major elements including F) methods has been used to analyse Li-rich micas from the S.W. England batholith (mainly the St Austell granite) and the Massif Central, France. Rocks showing various degrees of hydrothermal alteration were studied in order to separate the original compositional trends from alteration trends. The original compositional trend is essentially one of increasing Li with increasing degree of evolution. The main atomic substitution in the original micas is 3Li substituting for A1 and 2 vacancies in octahedral sites; substitution of Li for R2+ (Fe, Mn, Mg) in octahedral co-ordination is generally subordinate. Alteration trends involve a loss of Li, Fe, F, Rb and Cs, and a gain in A1. The effects of volatile elements on phase relations of granites are reviewed and it is concluded that the original Li-micas were primary, i.e. crystallized from the melt. It is suggested that the late-magmatic stage passed transitionally into the hydrothermal stage leading inevitably to subsolidus recrystallization (autometasomatism) of the primary minerals, so introducing further textural and mineralogical complexities to the rocks.
The distribution of the minor impurities, aluminium and silicon, between co-existing phases in altered ilmenite grains from three Western Australian localities has been investigated using SEM and electronmicroprobe analyses. A striking dependence of the impurity levels on the Ti/(Ti + Fe) fraction is observed. For compositions with Ti/(Ti + Fe) between 0.45 and 0.60, i.e. between ferrian-ilmenite and pseudorutile, the impurity content is virtually independent of Ti/(Ti + Fe), and is very low (0.2 wt. % Al2O3. 0.05 wt. % SiO2). For compositions between those of rutile and pseudorutile, there is a direct correlation between the impurity contents and the Ti content of the alteration phase. The impurity levels increase with increasing Ti/(Ti+Fe) to about 3 wt. % Al2O3 and 1 wt. % SiO2 for compositions close to TiO2. Thus during the latter stages of ilmenite alteration, alumina and silica are extracted from the ambient environment and are coprecipitated with, or adsorbed on to, the alteration products. The observed dependence of the alumina and silica contents on extent of alteration is consistent with a two-stage alteration mechanism earlier proposed (Grey and Reid, 1975).
The Environment Agency Guidance on Requirements for Authorisation (GRA) of a geological disposal facility (GDF) requires a demonstration that "the possibility of a local accumulation of fissile material such as to produce a neutron chain reaction is not a significant concern." A neutron chain reaction that is just self-sustaining is also known as critical.
Waste packages can be designed to ensure that criticality is impossible during the transport and operational phases of a GDF, and for a significant period post-closure. Over longer times, however, packages may degrade, and groundwater flows could lead to a localized accumulation of fissile material. Hence, even though the initial distribution of materials would need to change substantially, criticality cannot be ruled out completely.
This paper describes how an accumulation of fissile material could, hypothetically, lead to a critical configuration; how such a system could evolve; what the local consequences could be; and how the engineered and geological barriers could be affected. The conclusion from studies to date is that, even for large (and very unlikely) fissile accumulations, the consequences of a post-closure criticality event are not a significant concern.
This computational aerodynamics textbook is written at the undergraduate level, based on years of teaching focused on developing the engineering skills required to become an intelligent user of aerodynamic codes. This is done by taking advantage of CA codes that are now available and doing projects to learn the basic numerical and aerodynamic concepts required. This book includes a number of unique features to make studying computational aerodynamics more enjoyable. These include:The computer programs used in the book's projects are all open source and accessible to students and practicing engineers alike on the book's website, www.cambridge.org/aerodynamics. The site includes access to images, movies, programs, and moreThe computational aerodynamics concepts are given relevance by CA Concept Boxes integrated into the chapters to provide realistic asides to the conceptsReaders can see fluids in motion with the Flow Visualization Boxes carefully integrated into the text.