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In recent years, the discovery of massive quasars at
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.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
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.
The increasing availability of automated milk dispensers on dairy farms facilitates ad libitum milk supply but weaning calves from high milk allowances is challenging. This study evaluated effects of gradual weaning methods on starter intake, growth, selected blood parameters and weaning distress in ad libitum fed dairy calves during weaning and early post-weaning periods. Thirty-six male Holstein (n = 30) or crossbred (n = 6) calves were individually housed from days 2 to 14 of age and had ad libitum access to milk replacer (MR) from teat buckets. From days 15 to 84 of age, calves were grouped and had ad libitum access to MR, starter, straw and water from automated feeders. At day 35, calves were blocked (age and breed), and randomly assigned to a weaning method: (1) linear fixed (LIN), MR supply was stepped down to 6 l/day on day 36, and linearly reduced between days 36 to 63 from 6 to 2 l/day. (2) Step-down (STEP), MR supply was stepped down to 6 l/day from days 36 to 48, 4 l/day from days 49 to 56 and 2 l/day from days 57 to 63. (3) Dynamic (DYN), at day 36, MR supply was reduced for each individual calf to 75% of the average voluntary consumption between day 29 and 35, then maintained for 9 days, reduced to 50% for 10 days, and to 25% for 9 days. The DYN calves received more MR during weaning than LIN calves, whereas STEP calves had intermediate MR intake. Starter intake was not affected by weaning method. The DYN calves (1.33±0.08 kg/day) grew faster and were heavier than STEP calves (1.10±0.08 kg/day) during post-weaning period, whereas no difference was observed between LIN calves (1.23±0.08 kg/day) and others. At days 70 and 84, concentrations of β-hydroxybutyric acid were higher in LIN calves compared to STEP and DYN calves. Hair cortisol concentrations were not affected by weaning method. During the gradual weaning process CP intake seemed to recovered earlier than metabolizable energy (ME) intake in all treatments, suggesting that ME rather than CP could be the first limiting factor for growth during weaning. These results highlight the post-weaning benefits of DYN and LIN weaning methods when compared with more abrupt step-down strategies.
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.
This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions.
A cohort of 209 community-dwelling individuals without dementia aged 47–90 years old was recruited for this 3-year study. Participants underwent neuropsychological and clinical assessments annually. Participants were divided into SMCs and non-memory complainers (NMCs) using a single question at baseline and a memory complaints questionnaire following baseline, to evaluate differential patterns of complaints. In addition, comprehensive assessment of memory complaints was undertaken to evaluate whether severity and consistency of complaints differentially predicted cognitive function.
SMC and NMC individuals were significantly different on various features of SMCs. Greater overall severity (but not consistency) of complaints was significantly associated with current and future cognitive functioning.
SMC individuals present distinctive features of memory complaints as compared to NMCs. Further, the severity of complaints was a significant predictor of future cognition. However, SMC did not significantly predict change over time in this sample. These findings warrant further research into the specific features of SMCs that may portend subsequent neuropathological and cognitive changes when screening individuals at increased future risk of dementia.
Genetic variants associated with dietary intake may be important as factors underlying the development of obesity. We investigated the associations between the obesity candidate genes (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor) and total energy intake and percentage of energy from macronutrients and ultra-processed foods before and during pregnancy. A sample of 149 pregnant women was followed up in a prospective cohort in Rio de Janeiro, Brazil. A FFQ was administered at 5–13 and 30–36 weeks of gestation. Genotyping was performed using real-time PCR. Associations between polymorphisms and the outcomes were investigated through multiple linear regression and ANCOVA having pre-pregnancy dietary intake as a covariate. The A-allele of FTO-rs9939609 was associated with a −6·5 % (95 % CI −12·3, −0·4) decrease in the percentage of energy from protein and positively associated with the percentage of energy from carbohydrates before pregnancy (β=2·6; 95 % CI 0·5, 4·8) and with a 13·3 % (95 % CI 0·7, 27·5) increase in the total energy intake during pregnancy. The C-allele of MC4R-rs17782313 was associated with a −7·6 % (95 % CI −13·8, −1·0) decrease in the percentage of energy from protein, and positively associated with the percentage of energy from ultra-processed foods (β=5·4; 95 % CI 1·1, 9·8) during pregnancy. ANCOVA results revealed changes in dietary intake from pre-pregnancy to pregnancy for FTO-rs9939609 (percentage of energy from ultra-processed foods, P=0·03), MC4R-rs17782313 (total energy intake, P=0·02) and LEP-rs7799039 (total energy intake, P=0·04; percentage of energy from protein, P=0·04). These findings suggest significant associations between FTO-rs9939609, MC4R-rs17782313 and LEP-rs7799039 genes and the components of dietary intake in pregnant women.
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.
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.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
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.
Introduction: Telephone quitlines are an easily accessible and effective means for delivering cessation services including nicotine replacement therapy (NRT). Varenicline (VAR) may show superior quit rates to NRT, but has not been routinely evaluated in the context of quitlines.
Aims: To assess the feasibility of distributing VAR through a quitline, and preliminarily compare cessation rates between participants receiving VAR and NRT.
Methods: Participants were recruited through the New York State Smokers’ Quitline. Those randomised to VAR (n = 200) were instructed to obtain a prescription from their primary care physician (PCP) to be filled by mail through the research pharmacy. Those randomised to NRT (n = 100) were mailed NRT using an existing protocol. Outcome measures were number of submitted prescriptions and dispensed medication kits, and self-reported 7-day point prevalence abstinence at follow-up.
Results: The research pharmacy filled 100% of prescriptions through the quitline. However, only 27% of the VAR Arm submitted a prescription. An intent-to-treat analysis revealed that those receiving NRT were more likely to be abstinent at follow-up than the VAR Arm (OR, 2.42; 95% CI, 1.27–4.60; p < 0.01). The per-protocol analysis, which only included those in the VAR Arm who submitted a prescription, showed no difference in quit rates.
Conclusions: The present protocol resulted in successful delivery of VAR through the quitline, but a sizable proportion of the VAR Arm did not submit a prescription. Self-reported barriers included being unable to obtain a prescription from a PCP. Future studies should explore alternative methods for delivering VAR through quitlines.
This study assessed milk productivity, demographic characteristics and workload distribution on a single high-yield dairy ewe farm in Spain (Avila, Spain; continental climate, latitude of 40.90 N, altitude of 900 m) over a 7-year period considering a transition from a herd management system involving five lambings per year (5LY) to a system involving 10 lambings per year (10LY). The 5LY system was practiced on the farm from 2010 to 2012 and the 10LY system from 2014 to 2015, with 2009 and 2013 being considered transition years. During this period, 27 415 lactations were recorded from an average of 3746 Lacaune sheep/year. Several productivity parameters were higher in 2014 to 2015 than in 2010 to 2012: milk yield/lactation (370±156 v. 349±185 l), lactation length (218±75 v. 192±75 days) and dry period length (53.5±38.3 v. 69.1±34.8 days) (all P<0.0001). During 2014 to 2015, investment in new lambing facilities was possible, workload was distributed more uniformly throughout the year, workload per worker was smaller, rate of ewe culling was lower (35.39±0.53% v. 42.51±7.51%), ewe longevity was greater and higher-order lactations were more numerous (P<0.0001). On the other hand, during 2010 to 2012, daily production was higher (1.73±1.66 v. 1.70±0.62 l/day; P=0.038), the interlambing period was shorter (283±50 v. 302±44 days; P<0.0001) and lambings/ewe per year were greater (1.42±0.01 v. 1.30±0.01; P<0.05). These results suggest that a 10LY herd management system can be compatible with profitability, productivity and good animal and worker’s welfare on a high-yield dairy farm, and may even be associated with better outcomes than a 5LY system.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.