In recent years, the discovery of massive quasars at $z\sim7$ has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Microstructural analysis and bulk dielectric property analysis (real and imaginary permittivity at 95 GHz) were performed at temperatures ranging from 25 to 550 °C for ceramic composites comprising a hot-pressed aluminum nitride matrix (containing yttria and trace carbon as sintering additives) with molybdenum powder as a millimeter-wave radiation-absorbing additive. Loading percentages in the range of 0.25 vol% to 4.0 vol% Mo were characterized. For the temperature regime evaluated, the temperature-related changes in real and imaginary components of permittivity were found to be relatively modest compared with those driven by Mo loading. Energy-dispersive X-ray spectroscopic analysis of Mo grains and surrounding regions showed the presence of a mixed-phase layer, containing Mo2C, at the AlN–Mo interface. The Mo2C-containing mixed-phase layer, typically a few micrometers thick, surrounded the Mo grains. Further characterization of this mixed-phase layer is required to determine its contribution to the dielectric properties of the composite.

There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.

In order to begin to evaluate and model the suitability of high temperature ceramic composites, such as AlN:Mo, as susceptor materials for power beaming applications, the electromagnetic, thermal, and mechanical properties of the material must be known at elevated temperatures. Work reported here focuses on the development of thermal property datasets for AlN:Mo composites ranging from 0.25% to 4.0% Mo by volume. To calculate thermal conductivity of the AlN:Mo composite series, specific heat capacity, thermal diffusivity, and density data were acquired. The calculated specific heat capacity, Cp, of the set of AlN:Mo composites was, on average, found to be approximately 803 J/kgK at 100 °C and to increase to approximately 1133 J/kgK at 1000 °C, with all values to be within +/- 32 J/kgK of the average at a given temperature. These calculated specific heat capacity values matched values derived from DSC measurements to within the expected error of the measurements. Measured thermal diffusivity, α, of the set of AlN:Mo composites was, on average, found to be approximately 3.93 x 10-1 cm2/s at 100 °C and to increase to approximately 9.80 x 10-2 cm2/s at 1000 °C, with all values within +/- 1.84 x 10-2 cm2/s of the average at a given temperature. Thermal conductivity, k, for the set of AlN:Mo composites was found to be approximately 108 W/mK at 100 °C and to decrease to approximately 38 W/mK at 1000 °C, with all values within +/- 5.3 W/mK of the average at a given temperature. Data trends show that increasing Mo content correlates to lower values of of Cp, α, and k at a given temperature.

OBJECTIVES/SPECIFIC AIMS: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences.The objective was to test the effectiveness of a prediabetes SDM intervention. METHODS/STUDY POPULATION: This was a cluster-randomized controlled trial in 20 primary care clinics within a large regional health system. Participants were overweight/obese adults with prediabetes (BMI>24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics.Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention; DPP, DPP +/− metformin, metformin only, or usual care. RESULTS/ANTICIPATED RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n=351) than controls receiving usual care (n = 1,028; 38% vs. 2%, p<.001). At 12-months follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (−5.3 vs. −0.2, p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4-months and weight loss at 12-months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk.

When supplementing lamb diets with vitamin E, an equivalence factor of 1.36 is used to discriminate between RRR-α-tocopheryl acetate and all-rac-α-tocopheryl acetate. However, more recent studies suggest a need for new equivalence factors for livestock animals. The current study aimed to determine the effect of RRR- and all-rac-α-tocopheryl acetate supplementation on α-tocopherol deposition in lamb tissues. A total of 108 Rasa Aragonesa breed lambs were fed increasing amounts of all-rac-α-tocopheryl acetate (0.25, 0.5, 1.0 and 2.0 g/kg compound feed) or RRR-α-tocopheryl acetate (0.125, 0.25, 0.5 and 1.0 g/kg compound feed) by adding them to a basal diet that contained 0.025 g/kg feed of all-rac-α-tocopheryl acetate as part of the standard vitamin and mineral mixture. The diets were fed for the last 14 days before slaughtering at 25.8±1.67 kg BW. Within 20 min after slaughter samples of muscle, heart, liver, brain and spleen were frozen at −20°C until α-tocopherol analysis. Increased supplementation of either vitamin E sources led to a significant increase (P < 0.001) in α-tocopherol concentration in all tissues studied. The tissue with the highest α-tocopherol concentration was the liver followed by spleen, heart and muscle. At similar supplementation levels (0.25, 0.50 and 1.0 g/kg compound feed), α-tocopherol content in the selected tissues was not affected by α-tocopherol source. However, the ratios between RRR- and all-rac-α-tocopheryl acetate increased with the increasing α-tocopherol supplementation (at 0.25 and 1.0 g/kg compound feed), from 1.06 to 1.16 in muscle, 1.07 to 1.15 in heart, 0.91 to 0.94 in liver and 0.98 to 1.10 in spleen. The highest relative proportion of Ʃ2S (sum of SSS-, SSR-, SRS- and SRR-α-tocopherol)-configured stereoisomers was found in the liver of lambs supplemented with all-rac-α-tocopheryl acetate accounting for up to 35 to 39% of the total α-tocopherol retained, whereas the proportion of Ʃ2S-configured stereoisomers in the other tissues accounted for <14%. Increasing all-rac-α-tocopheryl acetate supplementation was also found to affect the 2R-configured stereoisomer profile in muscle, heart and spleen with increasing proportions of RRS-, RSR- and RSS- at the cost of RRR-α-tocopherol. In all tissues, the relative proportion of all non-RRR-stereoisomers in lambs receiving RRR-α-tocopheryl acetate was lower than RRR-α-tocopherol. These results confirm that the relative bioavailability of RRR- and all-rac-α-tocopheryl acetate is dose- and tissue-dependent and that a single ratio to discriminate the two sources cannot be used.

The increase of sheep meat competitiveness in international markets can be attributed to the rise of the quantity and the improvement of the quality of the edible portion of sheep carcasses. Usually, carcass yield is established after the slaughter of the animals. Yet, when carcass yield is determined in vivo, it can be both a costly and subjective method. This study proposes models for predicting the physical characteristics of lamb carcass using bioimpedance analysis (BIA) in live animals. Thirty-one Texel × Ile de France crossbreed ram lambs were slaughtered at 20, 26, 32 or 38 kg of BW. Before the slaughter, values of resistance (Rs) and reactance (Xc) were collected using a single-frequency BIA equipment (Model RJL Quantum II Bioelectrical Body Composition Analyzer). Then, BIA main variables such as body bioelectrical volume (V), phase angle (PA), resistive density (RsD) and reactive density (XcD) were calculated. After slaughter, cold carcass weight (CCW), cold carcass yield (CCY), subcutaneous fat thickness (SFT), soft tissue weight (STW) and soft tissue yield (STY) were also measured. Multiple regression analyses were carried out using the physical characteristics as dependent variables and the bioimpedance values as independent variables. Predictive performance of the models was assessed using leave-one-out cross-validation. The prediction model of CCW was obtained using the V, PA and RsD (R2 = 0.97), STW through the V, RsD and XcD (R2 = 0.97), CCY by Rs, Z and XcD (R2 = 0.69), STY by V and XcD (R2 = 0.67), and SFT only for XcD (R2 = 0.84). The results indicated that BIA has the potential to predict carcass characteristics of lambs at different body masses.

Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.

OBJECTIVES/SPECIFIC AIMS: Rodent models can be used to study neonatal abstinence syndrome (NAS), but the applicability of findings from the models to NAS in humans is not well understood. The objective of this study was to develop a rat model of norbuprenorphine-induced NAS and validate its translational value by comparing blood concentrations in the norbuprenorphine-treated pregnant rat to those previously reported in pregnant women undergoing buprenorphine treatment. METHODS/STUDY POPULATION: Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or norbuprenorphine (0.3–3 mg/kg/d) on gestation day 9. Within 12 hours of delivery, pups were tested for spontaneous or precipitated opioid withdrawal by injecting them with saline (10 mL/kg, i.p.) or naltrexone (1 or 10 mg/kg, i.p), respectively, and observing them for well-validated neonatal withdrawal signs. Blood was sampled via indwelling jugular catheters from a subset of norbuprenorphine-treated dams on gestation day 8, 10, 13, 17, and 20. Norbuprenorphine concentrations in whole blood samples were quantified using LC/MS/MS. RESULTS/ANTICIPATED RESULTS: Blood concentrations of norbuprenorphine in rats exposed to 1–3 mg/kg/d of norbuprenorphine were similar to levels previously reported in pregnant women undergoing buprenorphine treatment. Pups born to dams treated with these doses exhibited robust withdrawal signs. Blood concentrations of norbuprenorphine decreased across gestation, which is similar to previous reports in humans. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that dosing dams with 1–3 mg/kg/day norbuprenorphine produces maternal blood concentrations and withdrawal severity similar to those previously reported in humans. This provides evidence that, at these doses, this model is useful for testing hypotheses about norbuprenorphine that are applicable to NAS in humans.

The use of natural clays for the removal of dyes from wastewater, an important part of environmental remediation, is desirable due, not least, to their low cost. Palygorskite (PAL), a rigid-structure clay, is a good candidate for use in the elimination of industrial effluents, based on its exceptional adsorptive properties. Recently, a new palygorskite deposit has been discovered in Cuba and its use in the adsorption of dyes has not yet been explored in detail. In the present study, the use of unmodified natural Cuban palygorskite as a host for dyes was evaluated. Congo red (CR) and methylene blue (MB) were the anionic and cationic dyes tested, respectively, because of their wide use and toxicity to the environment. Several physical-chemical parameters were studied in order to establish the best experimental conditions under which to achieve the greatest dye load per gram of clay. Natural mixtures with different percentages of montmorillonite were also tested to evaluate their effect on the adsorption of the dyes. The results indicated that at pH values of ~7–9 and an initial dye concentration of 0.1 mg mL–1, the process was efficient. X-ray diffraction (XRD) analysis proved the surface adsorption of both dyes on the clays. The main interactions involved in the clay-dye system were electrostatic forces and H-bonds. Adsorption of CR seemed to be controlled fundamentally by the palygorskite phase. Such results support the use of this natural clay as an efficient host for the removal of MB and CR from wastewater.

Intensive farming may involve the use of diets, environments or management practices that impose physiological and psychological stressors on the animals. In particular, early weaning is nowadays a common practice to increase the productive yield of pig farms. Still, it is considered one of the most critical periods in swine production, where piglet performance can be seriously affected and where they are predisposed to the overgrowth of opportunistic pathogens. Pig producers nowadays face the challenge to overcome this situation in a context of increasing restrictions on the use of antibiotics in animal production. Great efforts are being made to find strategies to help piglets overcome the challenges of early weaning. Among them, a nutritional strategy that has received increasing attention in the last few years is the use of probiotics. It has been extensively documented that probiotics can reduce digestive disorders and improve productive parameters. Still, research in probiotics so far has also been characterized as being inconsistent and with low reproducibility from farm to farm. Scientific literature related to probiotic effects against gastrointestinal pathogens will be critically examined in this review. Moreover, the actual practical approach when using probiotics in these animals, and potential strategies to increase consistency in probiotic effects, will be discussed. Thus, considering the boost in probiotic research observed in recent years, this paper aims to provide a much-needed, in-depth review of the scientific data published to-date. Furthermore, it aims to be useful to swine nutritionists, researchers and the additive industry to critically consider their approach when developing or using probiotic strategies in weaning piglets.

Introduction: With the increasing volume of medical literature published each year, it is difficult for clinicians to translate the latest research into practice. Awareness is the first step of knowledge translation and journals have begun using social media to increase the dissemination and awareness of their publications. Infographics can describe research findings visually, are shared broadly on social media, and may be a more effective way to convey information. We hypothesized that infographic abstracts would increase the social media dissemination and online readership of research articles relative to traditional abstracts. Methods: In this randomized controlled trial, 24 original research articles were chosen from the six issues of the Canadian Journal of Emergency Medicine (CJEM) published between July 2016 and May 2017 (4 articles per issue). Half were randomized to the infographic and control groups within each issue. Infographic articles were promoted using a visual infographic outlining the findings of the article. Control articles were promoted using a screen capture image of each articles abstract. Both were disseminated through the journals social media accounts (Twitter and Facebook) along with the link to the selected article. Infographics were also published on CanadiEM.org. Abstract views, full text views, and the change in Altmetric score were tracked for 30 days and compared between groups. Unpaired two-tailed t-tests were used to detect significant differences. Results: Abstract views (mean, SD) were significantly higher for infographic articles (378.9, 162.0) than control articles (175.5, 69.2, p<0.001). Mean Altmetric scores were significantly higher for infographic articles (26.4, 13.8) than control articles (3.4, 1.7, p<0.0001). There was no statistically significant difference in full-text views between infographic (49.7, 90.4) and control articles (25.3, 12.3). Conclusion: CJEM articles promoted on social media using infographics had higher abstract viewership and Altmetric scores than those promoted with traditional abstracts. Although there was no difference in full-text readership, our results suggest that infographic abstracts may have a role in increasing the dissemination of medical literature.