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Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.
Introduction: Simulation has assumed an integral role in the Canadian healthcare system with applications in quality improvement, systems development, and medical education. High quality simulation-based research (SBR) is required to ensure the effective and efficient use of this tool. This study sought to establish national SBR priorities and describe the barriers and facilitators of SBR in Emergency Medicine (EM) in Canada. Methods: Simulation leads (SLs) from all fourteen Canadian Departments or Divisions of EM associated with an adult FRCP-EM training program were invited to participate in three surveys and a final consensus meeting. The first survey documented active EM SBR projects. Rounds two and three established and ranked priorities for SBR and identified the perceived barriers and facilitators to SBR at each site. Surveys were completed by SLs at each participating institution, and priority research themes were reviewed by senior faculty for broad input and review. Results: Twenty SLs representing all 14 invited institutions participated in all three rounds of the study. 60 active SBR projects were identified, an average of 4.3 per institution (range 0-17). 49 priorities for SBR in Canada were defined and summarized into seven priority research themes. An additional theme was identified by the senior reviewing faculty. 41 barriers and 34 facilitators of SBR were identified and grouped by theme. Fourteen SLs representing 12 institutions attended the consensus meeting and vetted the final list of eight priority research themes for SBR in Canada: simulation in CBME, simulation for interdisciplinary and inter-professional learning, simulation for summative assessment, simulation for continuing professional development, national curricular development, best practices in simulation-based education, simulation-based education outcomes, and simulation as an investigative methodology. Conclusion: Conclusion: This study has summarized the current SBR activity in EM in Canada, as well as its perceived barriers and facilitators. We also provide a consensus on priority research themes in SBR in EM from the perspective of Canadian simulation leaders. This group of SLs has formed a national simulation-based research group which aims to address these identified priorities with multicenter collaborative studies.
The commercially available collar device MooMonitor+ was evaluated with regards to accuracy and application potential for measuring grazing behavior. These automated measurements are crucial as cows feed intake behavior at pasture is an important parameter of animal performance, health and welfare as well as being an indicator of feed availability. Compared to laborious and time-consuming visual observation, the continuous and automated measurement of grazing behavior may support and improve the grazing management of dairy cows on pasture. Therefore, there were two experiments as well as a literature analysis conducted to evaluate the MooMonitor+ under grazing conditions. The first experiment compared the automated measurement of the sensor against visual observation. In a second experiment, the MooMonitor+ was compared to a noseband sensor (RumiWatch), which also allows continuous measurement of grazing behavior. The first experiment on n = 12 cows revealed that the automated sensor MooMonitor+ and visual observation were highly correlated as indicated by the Spearman’s rank correlation coefficient (rs) = 0.94 and concordance correlation coefficient (CCC) = 0.97 for grazing time. An rs-value of 0.97 and CCC = 0.98 was observed for rumination time. In a second experiment with n = 12 cows over 24-h periods, a high correlation between the MooMonitor+ and the RumiWatch was observed for grazing time as indicated by an rs-value of 0.91 and a CCC-value of 0.97. Similarly, a high correlation was observed for rumination time with an rs-value of 0.96 and a CCC-value of 0.99. While a higher level of agreement between the MooMonitor+ and both visual observation and RumiWatch was observed for rumination time compared to grazing time, the overall results showed a high level of accuracy of the collar device in measuring grazing and rumination times. Therefore, the collar device can be applied to monitor cow behavior at pasture on farms. With regards to the application potential of the collar device, it may not only be used on commercial farms but can also be applied to research questions when a data resolution of 15 min is sufficient. Thus, at farm level, the farmer can get an accurate and continuous measurement of grazing behavior of each individual cow and may then use those data for decision-making to optimize the animal management.
Infant protein intake has been associated with child growth, however, research on maternal protein intake during pregnancy is limited. Insulin-like growth factors (IGF) play a role in early fetal development and maternal protein intake may influence child body composition via IGF-1. The aim of this study was to investigate the association of maternal protein intake throughout pregnancy on cord blood IGF-1 and child body composition from birth to 5 years of age. Analysis was carried out on 570 mother–child dyads from the Randomised cOntrol trial of LOw glycaemic index diet study. Protein intake was recorded using 3-d food diaries in each trimester of pregnancy and protein intake per kg of maternal weight (g/d per kg) was calculated. Cord blood IGF-1 was measured at birth. Infant anthropometry was measured at birth, 6 months, 2 and 5 years of age. Mixed modelling, linear regression, and mediation analysis were carried out. Birth weight centiles were positively associated with early-pregnancy protein intake (g/d per kg), while weight centiles from 6 months to 5 years were negatively associated (B=−21·6, P<0·05). These associations were not mediated by IGF-1. Our findings suggest that high protein intake in early-pregnancy may exert an in utero effect on offspring body composition with a higher weight initially at birth but slower growth rates into childhood. Further research is needed to elucidate the exact mechanisms by which dietary protein modulates fetal growth.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Amorphous TiO2 and SnO2 electron transport layers (ETLs) were deposited by low-temperature atomic layer deposition (ALD). Surface morphology and x-ray photoelectron spectroscopy (XPS) indicate uniform and pinhole free coverage of these ALD hole blocking layers. Both mesoporous and planar perovskite solar cells were fabricated based on these thin films with aperture areas of 1.04 cm2 for TiO2 and 0.09 cm2 and 0.70 cm2 for SnO2. The resulting cell performance of 18.3 % power conversion efficiency (PCE) using planar SnO2 on 0.09 cm2 and 15.3 % PCE using mesoporous TiO2 on 1.04 cm2 active areas are discussed in conjunction with the significance of growth parameters and ETL composition.
We compared sepsis “time zero” and Centers for Medicare and Medicaid Services (CMS) SEP-1 pass rates among 3 abstractors in 3 hospitals. Abstractors agreed on time zero in 29 of 80 (36%) cases. Perceived pass rates ranged from 9 of 80 cases (11%) to 19 of 80 cases (23%). Variability in time zero and perceived pass rates limits the utility of SEP-1 for measuring quality.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.
We present a multi-frequency study of the intermediate spiral SAB(r)bc type galaxy NGC 6744, using available data from the Chandra X-Ray telescope, radio continuum data from the Australia Telescope Compact Array and Murchison Widefield Array, and Wide-field Infrared Survey Explorer infrared observations. We identify 117 X-ray sources and 280 radio sources. Of these, we find nine sources in common between the X-ray and radio catalogues, one of which is a faint central black hole with a bolometric radio luminosity similar to the Milky Way’s central black hole. We classify 5 objects as supernova remnant (SNR) candidates, 2 objects as likely SNRs, 17 as H ii regions, 1 source as an AGN; the remaining 255 radio sources are categorised as background objects and one X-ray source is classified as a foreground star. We find the star-formation rate (SFR) of NGC 6744 to be in the range 2.8–4.7 M⊙~yr − 1 signifying the galaxy is still actively forming stars. The specific SFR of NGC 6744 is greater than that of late-type spirals such as the Milky Way, but considerably less that that of a typical starburst galaxy.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
In the context of water use for agricultural production, water footprints (WFs) have become an important sustainability indicator. To understand better the water demand for beef and sheep meat produced on pasture-based systems, a WF of individual farms is required. The main objective of this study was to determine the primary contributors to freshwater consumption up to the farm gate expressed as a volumetric WF and associated impacts for the production of 1 kg of beef and 1 kg of sheep meat from a selection of pasture-based farms for 2 consecutive years, 2014 and 2015. The WF included green water, from the consumption of soil moisture due to evapotranspiration, and blue water, from the consumption of ground and surface waters. The impact of freshwater consumption on global water stress from the production of beef and sheep meat in Ireland was also computed. The average WF of the beef farms was 8391 l/kg carcass weight (CW) of which 8222 l/kg CW was green water and 169 l/kg CW was blue water; water for the production of pasture (including silage and grass) contributed 88% to the WF, concentrate production – 10% and on-farm water use – 1%. The average stress-weighted WF of beef was 91 l H2O eq/kg CW, implying that each kg of beef produced in Ireland contributed to freshwater scarcity equivalent to the consumption of 91 l of freshwater by an average world citizen. The average WF of the sheep farms was 7672 l/kg CW of which 7635 l/kg CW was green water and 37 l/kg CW was blue water; water for the production of pasture contributed 87% to the WF, concentrate production – 12% and on-farm water use – 1%. The average stress-weighted WF was 2 l H2O eq/kg CW for sheep. This study also evaluated the sustainability of recent intensification initiatives in Ireland and found that increases in productivity were supported through an increase in green water use and higher grass yields per hectare on both beef and sheep farms.
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.
Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5–4.4). The median age at first clinic visit was 10.3 years (IQR 7.1–13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3–0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.
Late-life depression (LLD) is associated with a decline in physical activity. Typically this is assessed by self-report questionnaires and, more recently, with actigraphy. We sought to explore the utility of a bespoke activity monitor to characterize activity profiles in LLD more precisely.
The activity monitor was worn for 7 days by 29 adults with LLD and 30 healthy controls. Subjects underwent neuropsychological assessment and quality of life (QoL) (36-item Short-Form Health Survey) and activities of daily living (ADL) scales (Instrumental Activities of Daily Living Scale) were administered.
Physical activity was significantly reduced in LLD compared with controls (t = 3.63, p < 0.001), primarily in the morning. LLD subjects showed slower fine motor movements (t = 3.49, p < 0.001). In LLD patients, activity reductions were related to reduced ADL (r = 0.61, p < 0.001), lower QoL (r = 0.65, p < 0.001), associative learning (r = 0.40, p = 0.036), and higher Montgomery–Åsberg Depression Rating Scale score (r = −0.37, p < 0.05).
Patients with LLD had a significant reduction in general physical activity compared with healthy controls. Assessment of specific activity parameters further revealed the correlates of impairments associated with LLD. Our study suggests that novel wearable technology has the potential to provide an objective way of monitoring real-world function.
XSHAPE has been developed to aid the better understanding of the 3D morphologies and kinematics of PNe and novae, by producing models which closely predict the observed 2D images and long-slit spectra of these objects. Early successes include plausible simulations for the elliptical PN Sa 2-21 and the nova HR Del.