274 research outputs found

    Patterning in Placental 11-B Hydroxysteroid Dehydrogenase Methylation According to Prenatal Socioeconomic Adversity

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    Background: Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from the maternal environment. The association of prenatal socioeconomic adversity and placental HSD11B2 methylation has not been examined. Following a developmental origins of disease framework, prenatal socioeconomic adversity may alter fetal response to the postnatal environment through functional epigenetic alterations in the placenta. Therefore, we hypothesized that prenatal socioeconomic adversity would be associated with less HSD11B2 methylation. Methods and Findings: We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 444 healthy term newborn infants and several markers of prenatal socioeconomic adversity: maternal education, poverty, dwelling crowding, tobacco use and cumulative risk. We also examined whether such associations were sex-specific. We found that infants whose mothers experienced the greatest levels of socioeconomic adversity during pregnancy had the lowest extent of placental HSD11B2 methylation, particularly for males. Associations were maintained for maternal education when adjusting for confounders (p\u3c0.05). Conclusions: Patterns of HSD11B2 methylation suggest that environmental cues transmitted from the mother during gestation may program the developing fetus’s response to an adverse postnatal environment, potentially via less exposure to cortisol during development. Less methylation of placental HSD11B2 may therefore be adaptive and promote the effective management of stress associated with social adversity in a postnatal environment

    Sweet Talk: A qualitative study exploring attitudes towards sugar, sweeteners and sweet-tasting foods in the United Kingdom

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    Worldwide initiatives currently aim to reduce free sugar intakes, but success will depend on consumer attitudes towards sugar and the alternatives. This work aimed to explore attitudes towards sugar, sweeteners and sweet-tasting foods, towards consumption and related policies, in a sample of the general public of the UK. Focus groups and interviews were conducted with 34 adults (7 males, ages: 18–65 years). Thematic analysis identified six themes: ‘Value’ (e.g., pleasure, emotions), ‘Angle’ (e.g., disinterest), ‘Personal Relevance’ (to be concerned and/or change one’s own behavior), ‘Personal Responsibility’ (one has an active relationship with these food items), ‘Understanding’ (the acquisition, comprehension and application of information) and ‘It’s Not Up to Me’ (a passive approach, because intake is subjected to other factors). Both positive and negative attitudes towards sugar, sweeteners and sweet-tasting foods were expressed in all themes. Participants also reported varied engagement with and motivations towards all food items, with implications for intakes. Suggested challenges and potential strategies for reducing free sugar intakes highlighted the need for differing approaches. Future work should assess associations between attitudes and intakes. For greatest population benefit, evidence of the dominant attitudes in those in greatest need of reduced free sugar intakes would be of value

    Baseline characteristics of the 3096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischemic Stroke' trial.

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    Background The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design The triple antiplatelets for reducing dependency after ischemic stroke trial was an international multicenter prospective randomized open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute ischemic stroke or transient ischemic attack. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life), and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviation, SD). Results Recruitment ran from April 2009 to March 2016; 3096 patients were recruited from 106 sites in four countries (Denmark 1.6%, Georgia 2.7%, New Zealand 0.2%, UK 95.4%). Randomization characteristics included: age 69.0 (10.1) years; male 1945 (62.8%); time onset to randomization 29.4 (11.9) h; stroke severity (National Institutes for Health Stroke Scale) 2.8 (3.6); blood pressure 143.5 (18.2)/79.5 (11.4) mmHg; IS 2143 (69.2%), transient ischemic attack 953 (30.8%). Conclusion Triple antiplatelets for reducing dependency after ischemic stroke was a large trial of intensive/triple antiplatelet therapy in acute ischemic stroke and transient ischemic attack, and included participants from four predominantly Caucasian countries who were representative of patients in many western stroke services

    Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

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    Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

    Conventional and microwave-assisted pyrolysis of biomass under different heating rates

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    Biomass was subjected to conventional and microwave pyrolysis, to determine the influence of each process on the yield and composition of the derived gas, oil and char products. The influence of pyrolysis temperature and heating rate for the conventional pyrolysis and the microwave power was investigated. Two major stages of gas release were observed during biomass pyrolysis, the first being CO/CO and the second one CH/H. This two-stage gas release was much more obvious for the conventional pyrolysis. While similar yield of liquid was obtained for both cases of conventional and microwave pyrolysis (∼46 wt.%), higher gas yield was produced for the conventional pyrolysis; it is suggested that microwave pyrolysis is much faster. When the heating rate was increased, the peak release of CO and CO was moved to higher reaction temperature for both conventional (500 °C) and microwave pyrolysis (200 °C). The production of CH and H were very low at a conventional pyrolysis temperature of 310 °C and microwave pyrolysis temperature of 200 °C (600 and 900 W). However, at higher heating rate of microwave pyrolysis, clear release of CH was observed. This work tentatively demonstrates possible connections and difference for biomass pyrolysis using two different heating resources (conventional and microwave heating)

    Probing the Dust Properties of Galaxies at Submillimetre Wavelengths II. Dust-to-gas mass ratio trends with metallicity and the submm excess in dwarf galaxies

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    We are studying the effects of submm observations on the total dust mass and thus dust-to-gas mass ratio measurements. We gather a wide sample of galaxies that have been observed at submm wavelengths to model their Spectral Energy Distributions using submm observations and then without submm observational constraints in order to quantify the error on the dust mass when submm data are not available. Our model does not make strong assumptions on the dust temperature distribution to precisely avoid submm biaises in the study. Our sample includes 52 galaxies observed at submm wavelengths. Out of these, 9 galaxies show an excess in submm which is not accounted for in our fiducial model, most of these galaxies being low- metallicity dwarfs. We chose to add an independant very cold dust component (T=10K) to account for this excess. We find that metal-rich galaxies modelled with submm data often show lower dust masses than when modelled without submm data. Indeed, these galaxies usually have dust SEDs that peaks at longer wavelengths and require constraints above 160 um to correctly position the peak and sample the submillimeter slope of their SEDs and thus correctly cover the dust temperature distribution. On the other hand, some metal-poor dwarf galaxies modelled with submm data show higher dust masses than when modelled without submm data. Using submm constraints for the dust mass estimates, we find a tightened correlation of the dust-to-gas mass ratio with the metallicity of the galaxies. We also often find that when there is a submm excess present, it occurs preferentially in low-metallicity galaxies. We analyse the conditions for the presence of this excess and find a relation between the 160/850 um ratio and the submm excess.Comment: 19 pages, 10 figures, 1 table, accepted for publication in A&

    Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

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    Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p&lt;0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p&lt;0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p&lt;0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation
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