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Neurodevelopment is sensitive to genetic and pre/postnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri/postnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes; (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological sampling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program — Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.
OBJECTIVES/SPECIFIC AIMS: Clinical guidelines recommend using predicted atherosclerotic cardiovascular disease (ASCVD) risk to inform treatment decisions. The objective was to compare the contribution of changes in modifiable risk factors Versus aging to the development of high 10-year predicted ASCVD risk. METHODS/STUDY POPULATION: Prospective follow-up of the Jackson Heart Study, an exclusively African-American cohort, at visit 1 (2000–2004) and visit 3 (2009–2012). Analyses included 1115 African-American participants without a high 10-year predicted ASCVD risk (<7.5%), hypertension, diabetes, or ASCVD at visit 1. We used the Pooled Cohort equations to calculate the incidence of high (≥7.5%) 10-year predicted ASCVD risk at visit 3. We recalculated the percentage with a high 10-year predicted ASCVD risk at visit 3 assuming each risk factor [age, systolic blood pressure (SBP), antihypertensive medication use, diabetes, smoking, total and high-density lipoprotein cholesterol], one at a time, did not change from visit 1. RESULTS/ANTICIPATED RESULTS: The mean age at visit 1 was 45.2±9.5 years. Overall, 30.9% (95% CI 28.3%–33.4%) of participants developed high 10-year predicted ASCVD risk. Aging accounted for 59.7% (95% CI 54.2%–65.1%) of the development of high 10-year predicted ASCVD risk compared with 32.8% (95% CI 27.0%–38.2%) for increases in SBP or antihypertensive medication initiation and 12.8% (95% CI 9.6%–16.5%) for incident diabetes. Among participants <50 years, the contribution of increases in SBP or antihypertensive medication initiation was similar to aging. DISCUSSION/SIGNIFICANCE OF IMPACT: Increases in SBP and antihypertensive medication initiation are major contributors to the development of high 10-year predicted ASCVD risk in African Americans, particularly among younger adults.
Immigrants and their children who return to their country of origin to visit friends and relatives (VFR) are at increased risk of acquiring infectious diseases compared to other travellers. VFR travel is an important disease control issue, as one quarter of Australia's population are foreign-born and one quarter of departing Australian international travellers are visiting friends and relatives. We conducted a 1-year prospective enhanced surveillance study in New South Wales and Victoria, Australia to determine the contribution of VFR travel to notifiable diseases associated with travel, including typhoid, paratyphoid, measles, hepatitis A, hepatitis E, malaria and chikungunya. Additional data on characteristics of international travel were collected. Recent international travel was reported by 180/222 (81%) enhanced surveillance cases, including all malaria, chikungunya and paratyphoid cases. The majority of cases who acquired infections during travel were immigrant Australians (96, 53%) or their Australian-born children (43, 24%). VFR travel was reported by 117 (65%) travel-associated cases, highest for typhoid (31/32, 97%). Cases of children (aged <18 years) (86%) were more frequently VFR travellers compared to adult travellers (57%, P < 0·001). VFR travel is an important contributor to imported disease in Australia. Communicable disease control strategies targeting these travellers, such as targeted health promotion, are likely to impact importation of these travel-related infections.
The SIESTA magnetohydrodynamic (MHD) equilibrium code has been used to compute a sequence of ideally stable equilibria resulting from numerical variation of the helical resonant magnetic perturbation (RMP) applied to an axisymmetric DIII-D plasma equilibrium. Increasing the perturbation strength at the dominant
resonant surface leads to lower MHD energies and increases in the equilibrium island widths at the
(and sidebands) surfaces, in agreement with theoretical expectations. Island overlap at large perturbation strengths leads to stochastic magnetic fields which correlate well with the experimentally inferred field structure. The magnitude and spatial phase (around the dominant rational surfaces) of the resonant (shielding) component of the parallel current are shown to change qualitatively with the magnetic island topology.
Major and minor coronary artery anomalies in tetralogy of Fallot is a well-described finding. The importance of determining the coronary distribution impacts upon the decision making for surgery and subsequent management. Traditionally, the coronary distribution is relied classically on echocardiography and cardiac catheterisation; however, they have well-known limitations. The use of CT as a first-line investigation modality for coronary artery distribution is discussed.
There is an increasing interest in pasture-based dairy systems in Europe, mainly because of increasing production costs for intensive dairying. Milk is a matrix of compounds that influence nutritional and manufacturing properties, many dependent on husbandry linked to pasture-based systems (increase in pasture intake, forage : concentrate ratio, clover inclusion in swards/silages and use of alternative dairy breeds). The present study investigated the impact of three grazing-based dairy systems with contrasting feeding intensity or reliance on pasture intakes (conventional high-intensity, low pasture intake [CH], organic medium-intensity, medium pasture intake [OM], conventional low-intensity, high pasture intake [CL]) on milk fatty acid (FA) profiles, protein composition and α-tocopherol and antioxidants concentrations. The proportion of animals of alternative breeds (e.g. Jersey) and crossbred cows in the herd increased with decreasing production intensity (CH < OM < CL). Milk constituents known to be beneficial for human health, such as vaccenic acid, rumenic acid, monounsaturated FA, polyunsaturated FA, antioxidants and caseins, were elevated with decreasing production intensity (CH < OM < CL), while less desirable saturated FA were lower, although not all differences between OM and CL were significant. Omega-3 FA were maximized under OM practices, primarily as a result of higher clover intake. Increases in pasture intake may explain the higher concentrations of desirable FA while increased use of crossbreed cows is likely to be responsible for higher total protein and casein content of milk; a combination of these two factors may explain increased antioxidant levels. The higher concentrations of vaccenic acid, rumenic acid, omega-3 FA, lutein, zeaxanthin, protein and casein in OM and CL milk were found over most sampling months and in both years, reinforcing the higher nutritional quality and manufacturing properties associated with milk from these systems. A switch to pasture-based dairy products would increase the intake of milk's beneficial compounds and reduce consumption of less desirable saturated FA.
Antibiotics are one of the most important medical discoveries of the 20th century and will remain an essential tool for treating animal and human diseases in the 21st century. However, antibiotic resistance among bacterial pathogens and concerns over their extensive use in food animals has garnered global interest in limiting antibiotic use in animal agriculture. Yet, limiting the availability of medical interventions to prevent and control animal diseases on the farm will directly impact global food security and safety as well as animal and human health. Insufficient attention has been given to the scientific breakthroughs and novel technologies that provide alternatives to antibiotics. The objectives of the symposium ‘Alternatives to Antibiotics’ were to highlight promising research results and novel technologies that could potentially lead to alternatives to conventional antibiotics, and assess challenges associated with their commercialization, and provide actionable strategies to support development of alternative antimicrobials. The symposium focused on the latest scientific breakthroughs and technologies that could provide new options and alternative strategies for preventing and treating diseases of animals. Some of these new technologies have direct applications as medical interventions for human health, but the focus of the symposium was animal production, animal health and food safety during food-animal production. Five subject areas were explored in detail through scientific presentations and expert panel discussions, including: (1) alternatives to antibiotics, lessons from nature; (2) immune modulation approaches to enhance disease resistance and to treat animal diseases; (3) gut microbiome and immune development, health and diseases; (4) alternatives to antibiotics for animal production; and (5) regulatory pathways to enable the licensure of alternatives to antibiotics.
Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms.
In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task.
The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC.
In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.
The Spitzer Legacy Program “Surveying the Agents of Galaxy Evolution in the Tidally-Stripped, Low-Metallicity Small Magellanic Cloud” (SAGE-SMC; Gordon et al. 2011) allows a global study of star formation in the SMC at high enough resolution to resolve individual cores and protostars at a range of mid-IR wavelengths. Using the SAGE-SMC IRAC (3.6 - 8.0 μm) and MIPS (24 and 70 μm) catalogs and images combined with the near-IR and optical data, we identified a population of ∼1100 intermediate- to high-mass Young Stellar Objects (YSOs) in the SMC (3 × more than previously known). We investigate the properties of the YSOs and how they relate to the galaxy's structure and gas and dust distribution.