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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.
The development and subsistence strategies adopted in ancient settlements are crucial to the understanding of long-term human–environmental interaction in the past. Here, we reassess the chronology of the ancient walled settlement of Sanjiao in the Hexi Corridor in northwestern China through accelerator mass spectrometry radiocarbon (AMS 14C) dating and explore the subsistence of the settlers inside through the identification of carbonized seeds and charcoal. In addition, high-resolution paleoclimate records in the Hexi Corridor and nearby regions are employed to explore the reason for the construction of Sanjiao. Our results show that Sanjiao was built around 828 cal BC and remained inhabited through 384–116 cal BC. This indicates Sanjiao is the earliest known walled settlement in the Hexi Corridor. Ancient people at Sanjiao consumed crops such as barley, broomcorn millet, and foxtail millet, and used wood from Tamarix chinensis, Tamarix, Salix, Picea, Hippophae, Betulaceae, and Poaceae as fuel. The construction date of Sanjiao correlates with climate deterioration and social upheavals in the Hexi Corridor, potentially suggesting a defensive purpose for the site.
Major depressive disorder (MDD) commonly co-occurs with clinically significant levels of anxiety. However, anxiety symptoms are varied and have been inconsistently associated with clinical, functional, and antidepressant treatment outcomes. We aimed to identify and characterise dimensions of anxiety in people with MDD and their use in predicting antidepressant treatment outcome.
1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic, MDD were assessed at baseline on clinical features and cognitive/physiological functioning. Participants were then randomised to one of three commonly prescribed antidepressants and reassessed at 8 weeks regarding symptom change, as well as remission and response, on the 17-item Hamilton Rating Scale Depression (HRSD17) and the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16). Exploratory factor analysis was used on items from scales assessing anxiety symptoms, and resulting factors were assessed against clinical features and cognitive/physiological functioning. Factors were also assessed on their ability to predict treatment outcome.
Three factors emerged relating to stress, cognitive anxiety, and somatic anxiety. All factors showed high internal consistency, minimal cross-loadings, and unique clinical and functional profiles. Furthermore, only higher somatic anxiety was associated with poorer QIDS-SR16 remission, even after adjusting for covariates and multiple comparisons.
Anxiety symptoms in people with MDD can be separated onto distinct factors that differentially respond to treatment outcome. Furthermore, these factors do not align with subscales of established measures of anxiety. Future research should consider cognitive and somatic symptoms of anxiety separately when assessing anxiety in MDD and their use in predicting treatment outcome.
A method is described for determining the magnitude and sense of systematic errors in x-ray diffractometer stress measurements produced by focusing aberrations during diffraction from imperfect specimen contours and wide horizontal beam divergences. Corrections for such systematic errors are presently not made. However, if the highest accuracy and/or absolute values of stress are desired, these must be either taken into account or minimized by control of beam geometry. Equations and computer data are presented to indicate the errors in 2θ and stress (σ) resulting from use of flat, various convex and concave curvatures for primary beam divergences of 1° to 3°, Stress errors are calculated for both the parafocus technique of beam focusing and the stationary or non-focusing method.
The results show that convex and flat specimens always produce negative 2θ deviations from the condition of perfect focus and thus a net positive or tensile stress error. The magnitude of this error increases as the radius of the convex shape decreases and/or the ψangle and beam divergence is increased. Concave specimens with curvatures less than the radius of the concave shape required for perfect focus (see body of report) produce positive 2θ deviations and, therefore, negative or com-pressive stress errors.
The stationary or non-focusing technique produced systematic errors which were 1/3 of those produced by focusing aberrations with the parafocus technique. Fortunately, in both cases the actual errors are not very large (less than ±7.5 ksi), even with divergent beams as large as 3° and convex radii as small as 125”.
Over the past 25 years, numerous studies utilizing both X-ray diffraction (XRE) and differential scanning calorimetry (DSC) have been reported In the literature. Generally, conventional high-temperature X-ray data identifies solid-state transitions, then attempts to correlate them with thermal events observed by the calorimeter. Since changes occur in the sample during studies such as these, separate portions of the sample must be used for XRD and DSC experiments. When comparing results of the two experiments, questions arise concerning sample homogeniety as well as temperature and environmental differences. In fact, no conventional high-temperature X-ray diffraction instrument can give the precise control over temperature and heating rate available with a DSC, The problems of sample inhomogeneltles and Instrumental differences could be avoided if X-ray diffraction and DSC could be performed simultaneously on one sample.
This replication study examined protective effects of positive childhood memories with caregivers (“angels in the nursery”) against lifespan and intergenerational transmission of trauma. More positive, elaborated angel memories were hypothesized to buffer associations between mothers’ childhood maltreatment and their adulthood posttraumatic stress disorder (PTSD) and depression symptoms, comorbid psychopathology, and children's trauma exposure. Participants were 185 mothers (M age = 30.67 years, SD = 6.44, range = 17–46 years, 54.6% Latina, 17.8% White, 10.3% African American, 17.3% other; 24% Spanish speaking) and children (M age = 42.51 months; SD = 15.95, range = 3–72 months; 51.4% male). Mothers completed the Angels in the Nursery Interview (Van Horn, Lieberman, & Harris, 2008), and assessments of childhood maltreatment, adulthood psychopathology, children's trauma exposure, and demographics. Angel memories significantly moderated associations between maltreatment and PTSD (but not depression) symptoms, comorbid psychopathology, and children's trauma exposure. For mothers with less positive, elaborated angel memories, higher levels of maltreatment predicted higher levels of psychopathology and children's trauma exposure. For mothers with more positive, elaborated memories, however, predictive associations were not significant, reflecting protective effects. Furthermore, protective effects against children's trauma exposure were significant only for female children, suggesting that angel memories may specifically buffer against intergenerational trauma from mothers to daughters.
We extend some observations of Popken (2) on the algebraic foundations of the theory of asymptotic series. The main result is the theorem in §5 which characterizes, for a particular function space, a class of linear functionals defined in §4. In §3 we discuss another class of linear functionals related to asymptotic series. In the first two paragraphs we give definitions which render this note self-contained.
The Canadian Stroke Best Practice Recommendations suggests that patients suspected of transient ischemic attack (TIA)/minor stroke receive urgent brain imaging, preferably computed tomography angiography (CTA). Yet, high requisition rates for non-cerebrovascular patients overburden limited radiological resources, putting patients at risk. We hypothesize that our clinical decision support tool (CDST) developed for risk stratification of TIA in the emergency department (ED), and which incorporates Canadian guidelines, could improve CTA utilization.
Retrospective study design with clinical information gathered from ED patient referrals to an outpatient TIA unit in Victoria, BC, from 2015-2016. Actual CTA orders by ED and TIA unit staff were compared to hypothetical CTA ordering if our CDST had been used in the ED upon patient arrival.
For 1,679 referrals, clinicians ordered 954 CTAs. Our CDST would have ordered a total of 977 CTAs for these patients. Overall, this would have increased the number of imaged-TIA patients by 89 (10.1%) while imaging 98 (16.1%) fewer non-cerebrovascular patients over the 2-year period. Our CDST would have ordered CTA for 18 (78.3%) of the recurrent stroke patients in the sample.
Our CDST could enhance CTA utilization in the ED for suspected TIA patients, and facilitate guideline-based stroke care. Use of our CDST would increase the number of TIA patients receiving CTA before ED discharge (rather than later at TIA units) and reduce the burden of imaging stroke mimics in radiological departments.
Despite the advances of molecular tools, new nematode species are still described mainly based on morphological characters. Parapharyngodon and Thelandros are two genera of oxyurids with unclear related taxonomic histories. Here we use morphological characters (linear measurements and categorical variables) and genetic information (18S rRNA, 28S rRNA and COI partial gene sequences) to confirm the relationships between representatives of these two genera and to determine whether they can be discriminated morphologically. Genetic results confirm the existence of two main clades, mostly congruent with Parapharyngodon and Thelandros genera but with several discordances. Thelandros is polyphyletic, with two of the species analysed (T. filiformis and T. tinerfensis) being part of the Thelandros clade, but with a third one (T. galloti) falling within the Parapharyngodon clade. Regarding the Parapharyngodon clade, P. cubensis, P. scleratus and Parapharyngodon sp. from Mexico form congruent lineages, while most P. echinatus samples cluster in another group, with one exception. Interestingly, P. micipsae samples are scattered across the Parapharyngodon clade, suggesting that they were misidentified or rather represent alternative morphotypes of other species. Morphological analysis identified the length of the tail, number of caudal papillae, position of the nerve ring, presence of caudal alae and length of the lateral alae as reliable characters to distinguish between Parapharyngodon and Thelandros genetic clades. Our study highlights the current taxonomic inconsistency in these groups, mainly derived from the exclusive use of morphological data. As such, we advocate for the routine implementation of molecular data in nematode taxonomic studies.
Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science—sponsored Clinical and Translational Science Award (CTSA) program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA program and other National Institutes of Health (NIH) Institutes and Centers that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN’s mission is to execute high-quality trials in a quick, cost-efficient manner. The TIN awardees are composed of 3 Trial Innovation Centers, the Recruitment Innovation Center, and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) Institutional Review Board system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH Institutes and Centers across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN-related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.
Introduction: Despite revolutionary changes in the medical education landscape, journal club (JC) continues to be a ubiquitous pedagogical tool and is a primary way that residency programs review new evidence and teach evidence-based medicine. JC is a community of practice among physicians, which may help translate research findings into practice. Program representatives state that JC should have a goal of translating novel research into changes in clinical care, but there has been minimal evaluation of the success of JC in achieving this goal. Specifically, emergency medicine resident perspectives on the utility of JC remain unknown. Methods: We designed a multi-centre qualitative study for three distinct academic environments at the University of British Columbia (Vancouver, Victoria and Kelowna). Pilot testing was performed to generate preliminary themes and to finalize the interview script. An exploratory, semi-structured focus group was performed, followed by multiple one-on-one interviews using snowball sampling. Iterative thematic analysis directed data collection until thematic sufficiency was achieved. Analysis was conducted using a constructivist Grounded Theory method with communities of practice as a theoretical lens. Themes were compared to the existing literature to corroborate or challenge existing educational theory. Results: Pilot testing has revealed the following primary themes: (1) Only select residents are able to increase their participation in JC over the course of residency and navigate the transition from peripheral participant to core member; (2) These residents use their increased clinical experience to perceive relevance in JC topics, and; (3) Residents who remain peripheral participants identify a lack time to prepare for journal club and a lack of staff physician attendance as barriers to resident engagement. We will further develop these themes during the focus group and interview phases of our study. Conclusion: JC is a potentially valuable educational resource for residents. JC works as a community of practice only for a select group of residents, and many remain peripheral participants for the duration of their residency. Incorporation of Free Open-Access Medical Education resources may also decrease preparation time for residents and staff physicians and increase buy-in. To augment clinical impact, the JC community of practice may need to expand beyond emergency medicine and include other specialties.
For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between ‘soil health’, ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed.
Water cultures were significantly more sensitive than concurrently collected swab cultures (n=2,147 each) in detecting Legionella pneumophila within a Veterans Affairs healthcare system. Sensitivity for water versus swab cultures was 90% versus 30% overall, 83% versus 48% during a nosocomial Legionnaires’ disease outbreak, and 93% versus 22% post outbreak.
We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different 13C-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production.
Ribosomes are remarkable ribonucleoprotein complexes that are responsible for protein synthesis in all forms of life. They polymerize polypeptide chains programmed by nucleotide sequences in messenger RNA in a mechanism mediated by transfer RNA. One of the most challenging problems in the ribosome field is to understand the mechanism of coupled translocation of mRNA and tRNA during the elongation phase of protein synthesis. In recent years, the results of structural, biophysical and biochemical studies have provided extensive evidence that translocation is based on the structural dynamics of the ribosome itself. Detailed structural analysis has shown that ribosome dynamics, like aminoacyl-tRNA selection and catalysis of peptide bond formation, is made possible by the properties of ribosomal RNA.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Risk adjustment is needed to fairly compare central-line–associated bloodstream infection (CLABSI) rates between hospitals. Until 2017, the Centers for Disease Control and Prevention (CDC) methodology adjusted CLABSI rates only by type of intensive care unit (ICU). The 2017 CDC models also adjust for hospital size and medical school affiliation. We hypothesized that risk adjustment would be improved by including patient demographics and comorbidities from electronically available hospital discharge codes.
Using a cohort design across 22 hospitals, we analyzed data from ICU patients admitted between January 2012 and December 2013. Demographics and International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) discharge codes were obtained for each patient, and CLABSIs were identified by trained infection preventionists. Models adjusting only for ICU type and for ICU type plus patient case mix were built and compared using discrimination and standardized infection ratio (SIR). Hospitals were ranked by SIR for each model to examine and compare the changes in rank.
Overall, 85,849 ICU patients were analyzed and 162 (0.2%) developed CLABSI. The significant variables added to the ICU model were coagulopathy, paralysis, renal failure, malnutrition, and age. The C statistics were 0.55 (95% CI, 0.51–0.59) for the ICU-type model and 0.64 (95% CI, 0.60–0.69) for the ICU-type plus patient case-mix model. When the hospitals were ranked by adjusted SIRs, 10 hospitals (45%) changed rank when comorbidity was added to the ICU-type model.
Our risk-adjustment model for CLABSI using electronically available comorbidities demonstrated better discrimination than did the CDC model. The CDC should strongly consider comorbidity-based risk adjustment to more accurately compare CLABSI rates across hospitals.
Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.
In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.
Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.
Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5 % of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose–effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.