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Results of in situ U–Pb dating of calcite spherulites, cone-in-cone (CIC) calcite and calcite fibres from a calcareous concretion of the upper Ediacaran of Finnmark, Arctic Norway, are reported. Calcite spherulites from the innermost layers of the concretion yielded a lower intercept age of 563 ± 70 Ma, which, although imprecise, is within uncertainty of the age of sedimentation based on fossil assemblages. Non-deformed CIC calcite from the bottom part of the concretion yielded an age of 475 ± 25 Ma, which is interpreted as the age of CIC calcite formation during a period of fluid overpressure induced during burial of the sediments. Deformed CIC calcite from the top part of the concretion yielded an age of 418 ± 23 Ma, which overlaps with a known Caledonian tectono-metamorphic event, and indicates a potential post-depositional overprint at this time. Calcite fibres that grew in small fissures along spherulite rims, which are interpreted as a recrystallization feature during deformation and formation of a cleavage, gave an imprecise age of 486 ± 161 Ma. Our results show that U–Pb dating of calcite can provide age constraints for ancient carbonates and syn- to post-depositional processes that operated during burial and metamorphic overprinting.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
OBJECTIVES/GOALS: Active surveillance (AS) is a recognized strategy to manage low-risk prostate cancer (PCa) in the absence of cancer progression. Little prospective data exists on the decisional factors associated with selecting and adhering to AS in the absence of cancer progression. We developed a survey instrument to predict AS uptake and adherence. METHODS/STUDY POPULATION: We utilized a three-step process to develop and refine a survey instrument designed to predict AS uptake and adherence among men with low-risk PCa: 1) We identified relevant conceptual domains based on prior research and a literature review. 2) We conducted 21 semi-structured concept elicitation interviews to identify patient-perceived barriers and facilitators to AS uptake and adherence among men with a low-risk PCa who had been on AS for ≥1 year. The identified concepts became the basis of our draft survey instrument. 3) We conducted two rounds of cognitive interviews with men with low-risk PCa (n = 12; n = 6) to refine and initially validate the instrument. RESULTS/ANTICIPATED RESULTS: Relevant concepts identified from the initial interviews included the importance of patient: knowledge of their PCa risk, value in delaying treatment, trust in urologist and the AS surveillance protocol, and perceived social support. Initially, the survey was drafted as a single instrument to be administered after a patient had selected AS comprising sections on patient health, AS selection, and AS adherence. Based on the first round of cognitive interviews, we revised the single instrument into two surveys to track shifts in patient preference and experience. The first, administered at diagnosis, focuses on selection, and the second, a 6-month follow up, focuses on adherence. Following revisions, participants indicated the revised 2-part instrument was clear and not burdensome to complete. DISCUSSION/SIGNIFICANCE OF IMPACT: The instrument’s content validity was evaluated through cognitive interviews, which supported that the survey items’ intended and understood meanings were isomorphic. In the next phase, we plan to conduct a large-scale prospective cohort study to evaluate the predictive validity, after which it will be available for public research use.
OBJECTIVES/GOALS: Access to biostatistics expertise is essential for a successful clinical and translational research program. However, demand for statistical support at academic research centers can strain the capacity of biostatistics units. Our objective was to efficiently increase access to statistical expertise. METHODS/STUDY POPULATION: In cooperation with the Cancer Center Biostatistics Shared Resource, we replaced an informal 1-hour drop-in consultation program with structured office hours to provide statistical support to clinical and translational researchers at the University of California, Davis Medical Center. We doubled office hours to 2 hours per week and established six 20-minute appointments. Two Ph.D. level statisticians staff office hours. Researchers schedule appointments through Acuity Scheduling, a free on-line resource. Availability of the service is advertised monthly by sending an informational flyer to various university listservs. RESULTS/ANTICIPATED RESULTS: Prior to implementing the program in 2014, we averaged 91 office hour consults per year. Subsequently, consultations jumped to 171 in 2014 and have averaged 150 per year since then. Office hours attract students, residents, staff and faculty from a wide range of disciplines including the Schools of Medicine, Nursing, Veterinary Medicine and basic science departments. Project types span the clinical and translational spectrum covering lab, animal, clinical and population-level studies. Most consults related to data analysis and interpretation (57%) followed by sample size calculations/study design (29%) and response to reviewers (4%), with general statistical advice as the remainder. DISCUSSION/SIGNIFICANCE OF IMPACT: With 6 micro-consults per week, we can meet with many investigators and triage their statistical support needs. This program has proved very popular and was highly rated in a recent user survey, with several investigators noting that the consults facilitated successful publications and proposals.
New information on acritarchs from the Duolbagáisá Formation, Digermulen Peninsula, Arctic Norway, enable recognition of the three Cambrian Series 2 acritarch-based zones: the Skiagia ornata–Fimbriaglomerella membranacea, Heliosphaeridium dissimilare–Skiagia ciliosa and Volkovia dentifera–Liepaina plana Assemblage zones. Acritarchs of the Skiagia ornata–Fimbriaglomerella membranacea Zone (Cambrian Stage 3) appear near the base of the unit, close to an undetermined trilobite. In the Upper Member of the Duolbagáisá Formation, in levels with Kjerulfia n. sp. and Elliptocephala n. sp., appears an assemblage with abundant Skiagia ciliosa, indicative of the Heliosphaeridium dissimilare–Skiagia ciliosa Zone. A few metres higher appear Liepaina plana, Heliosphaeridium notatum and Retisphaeridium dichamerum, which indicate the Volkovia dentifera–Liepaina plana Zone (Cambrian Stage 4). The transition between the Duolbagáisá Formation and the overlying Kistedalen Formation is marked by the appearance of Comasphaeridium longispinosum, Multiplicisphaeridium llynense and Eliasum llaniscum, diagnostic of the Miaolingian Series. This coincides with the disappearance of Skiagia; occurrences of Skiagia in Miaolingian strata consist of reworked material related to the Hawke Bay regression at the Cambrian Stage 4–Wuliuan transition. The absence of Skiagia in higher levels of the Duolbagáisá Formation and Kistedalen Formation suggests that no unconformity formed during the Hawke Bay regression in this area. The chronostratigraphical significance of the Skiagia ornata–Fimbriaglomerella membranacea, Heliosphaeridium dissimilare–Skiagia ciliosa and Volkovia dentifera–Liepaina plana zones is critically analysed. Correlation of the Duolbagáisá Formation with peri-Gondwanan terrains of Avalonia and Iberia is established. The Digermulen Peninsula has great potential as a reference section for establishing a Cambrian chronostratigraphy based on acritarchs.
Commercially available business (CAB) datasets for food environments have been investigated for error in large urban contexts and some rural areas, but there is a relative dearth of literature that reports error across regions of variable rurality. The objective of the current study was to assess the validity of a CAB dataset using a government dataset at the provincial scale.
A ground-truthed dataset provided by the government of Newfoundland and Labrador (NL) was used to assess a popular commercial dataset. Concordance, sensitivity, positive-predictive value (PPV) and geocoding errors were calculated. Measures were stratified by store types and rurality to investigate any association between these variables and database accuracy.
The current analysis used store-level (ecological) data.
Of 1125 stores, there were 380 stores that existed in both datasets and were considered true-positive stores. The mean positional error between a ground-truthed and test point was 17·72 km. When compared with the provincial dataset of businesses, grocery stores had the greatest agreement, sensitivity = 0·64, PPV = 0·60 and concordance = 0·45. Gas stations had the least agreement, sensitivity = 0·26, PPV = 0·32 and concordance = 0·17. Only 4 % of commercial data points in rural areas matched every criterion examined.
The commercial dataset exhibits a low level of agreement with the ground-truthed provincial data. Particularly retailers in rural areas or belonging to the gas station category suffered from misclassification and/or geocoding errors. Taken together, the commercial dataset is differentially representative of the ground-truthed reality based on store-type and rurality/urbanity.
Neonates with CHD are at increased risk of developing necrotising enterocolitis due to mesenteric hypoperfusion. Necrotising enterocolitis results in repeated feed interruptions contributing to poor growth during the early post-operative phase. Poor weight gain and longer hospital stay are risk factors for death in neonates with CHD. Abdominal radiography is used as a diagnostic tool for necrotising enterocolitis; however, its utility is limited in the early stages of necrotising enterocolitis when pneumatosis intestinalis is absent. Calprotectin is a neutrophil activation biomarker, and elevated levels are evident in inflammatory diseases such as necrotising enterocolitis. The aim of this study was to determine whether there is a correlation between faecal calprotectin concentration and gut inflammation in neonates with CHD. This prospective single-centre study recruited newly diagnosed term patients with duct-dependent CHD between March 2018 and March 2019. Faecal calprotectin concentrations were measured in post-surgical patients using enzyme-linked immunosorbent assay methods. A total of 30 patients were included in the analysis. Calprotectin concentration for patients who developed necrotising enterocolitis was 3528 µg/g compared with 390 µg/g without, compared with 1339 µg/g in patients with suspected necrotising enterocolitis (p = 0.0001). Patients with suspected necrotising enterocolitis had a significantly longer length of hospital stay, on average 18 days longer compared to patients without necrotising enterocolitis (p = 0.03). Faecal calprotectin concentrations may reflect severity of gut inflammation in neonates with CHD. Suspected necrotising enterocolitis contributes to longer days nil by mouth and an increase in length of hospital stay.
Following an outbreak of highly pathogenic avian influenza virus (HPAIV) in a poultry house, control measures are put in place to prevent further spread. An essential part of the control measures based on the European Commission Avian Influenza Directive 2005/94/EC is the cleansing and disinfection (C&D) of infected premises. Cleansing and disinfection includes both preliminary and secondary C&D, and the dismantling of complex equipment during secondary C&D is also required, which is costly to the owner and also delays the secondary cleansing process, hence increasing the risk for onward spread. In this study, a quantitative risk assessment is presented to assess the risk of re-infection (recrudescence) occurring in an enriched colony-caged layer poultry house on restocking with chickens after different C&D scenarios. The risk is expressed as the number of restocked poultry houses expected before recrudescence occurs. Three C&D scenarios were considered, namely (i) preliminary C&D alone, (ii) preliminary C&D plus secondary C&D without dismantling and (iii) preliminary C&D plus secondary C&D with dismantling. The source-pathway-receptor framework was used to construct the model, and parameterisation was based on the three C&D scenarios. Two key operational variables in the model are (i) the time between depopulation of infected birds and restocking with new birds (TbDR) and (ii) the proportion of infected material that bypasses C&D, enabling virus to survive the process. Probability distributions were used to describe these two parameters for which there was recognised variability between premises in TbDR or uncertainty due to lack of information in the fraction of bypass. The risk assessment estimates that the median (95% credible intervals) number of repopulated poultry houses before recrudescence are 1.2 × 104 (50 to 2.8 × 106), 1.9 × 105 (780 to 5.7 × 107) and 1.1 × 106 (4.2 × 103 to 2.9 × 108) under C&D scenarios (i), (ii) and (iii), respectively. Thus for HPAIV in caged layers, undertaking secondary C&D without dismantling reduces the risk by 16-fold compared to preliminary C&D alone. Dismantling has an additional, although smaller, impact, reducing the risk by a further 6-fold and thus around 90-fold compared to preliminary C&D alone. On the basis of the 95% credible intervals, the model demonstrates the importance of secondary C&D (with or without dismantling) over preliminary C&D alone. However, the extra protection afforded by dismantling may not be cost beneficial in the context of reduced risk of onward spread.
True Colours is an automated symptom monitoring programme used by National Health Service psychiatric services. This study explored whether patients with unipolar treatment-resistant depression (TRD) found this a useful addition to their treatment regimes. Semi-structured qualitative interviews were conducted with 21 patients with TRD, who had engaged in True Colours monitoring as part of the Lithium versus Quetiapine in Depression study. A thematic analysis was used to assess participant experiences of the system.
Six main themes emerged from the data, the most notable indicating that mood monitoring increased patients' insight into their disorder, but that subsequent behaviour change was absent.
Patients with TRD can benefit from mood monitoring via True Colours, making it a worthwhile addition to treatment. Further development of such systems and additional support may be required for patients with TRD to experience further benefits as reported by other patient groups.
The dysfunctional cognitive and reasoning biases which underpin psychotic symptoms are likely to present prior to the onset of a diagnosable disorder and should therefore be detectable along the psychosis continuum in individuals with schizotypal traits. Two reasoning biases, Bias Against Disconfirmatory Evidence (BADE) and Jumping to Conclusions (JTC), describe how information is selected and weighed under conditions of uncertainty during decision making. It is likely that states such as elevated stress exacerbates JTC and BADE in individuals with high schizotypal traits vulnerable to displaying these information gathering styles. Therefore, we evaluated whether stress and schizotypy interacted to predict these reasoning biases using separate samples from the US (JTC) and England (BADE). Generally speaking, schizotypal traits and stress were not independently associated with dysfunctional reasoning biases. However, across both studies, the interaction between schizotypy traits and stress significantly predicted reasoning biases such that increased stress was associated with increased reasoning biases, but only for individuals low in schizotypal traits. These patterns were observed for positive schizotypal traits (in both samples), for negative traits (in the England sample only), but not for disorganization traits. For both samples, our findings suggest that the presence of states such as stress is associated with, though not necessarily dysfunctional, reasoning biases in individuals with low schizotypy. These reasoning biases seemed, in some ways, relatively immutable to stress in individuals endorsing high levels of positive schizotypal traits.
Gut microbiota data obtained by DNA sequencing are not only complex because of the number of taxa that may be detected within human cohorts, but also compositional because characteristics of the microbiota are described in relative terms (e.g., “relative abundance” of particular bacterial taxa expressed as a proportion of the total abundance of taxa). Nutrition researchers often use standard principal component analysis (PCA) to derive dietary patterns from complex food data, enabling each participant's diet to be described in terms of the extent to which it fits their cohort's dietary patterns. However, compositional PCA methods are not commonly used to describe patterns of microbiota in the way that dietary patterns are used to describe diets. This approach would be useful for identifying microbiota patterns that are associated with diet and body composition. The aim of this study is to use compositional PCA to describe gut microbiota profiles in 5 year old children and explore associations between microbiota profiles, diet, body mass index (BMI) z-score, and fat mass index (FMI) z-score. This study uses a cross-sectional data for 319 children who provided a faecal sample at 5 year of age. Their primary caregiver completed a 123-item quantitative food frequency questionnaire validated for foods of relevance to the gut microbiota. Body composition was determined using dual-energy x-ray absorptiometry, and BMI and FMI z-scores calculated. Compositional PCA identified and described gut microbiota profiles at the genus level, and profiles were examined in relation to diet and body size. Three gut microbiota profiles were found. Profile 1 (positive loadings on Blautia and Bifidobacterium; negative loadings on Bacteroides) was not related to diet or body size. Profile 2 (positive loadings on Bacteroides; negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was associated with a lower BMI z-score (r = -0.16, P = 0.003). Profile 3 (positive loadings on Faecalibacterium, Eubacterium and Roseburia) was associated with higher intakes of fibre (r = 0.15, P = 0.007); total (r = 0.15, P = 0.009), and insoluble (r = 0.13, P = 0.021) non-starch polysaccharides; protein (r = 0.12, P = 0.036); meat (r = 0.15, P = 0.010); and nuts, seeds and legumes (r = 0.11, P = 0.047). Further regression analyses found that profile 2 and profile 3 were independently associated with BMI z-score and diet respectively. We encourage fellow researchers to use compositional PCA as a method for identifying further links between the gut, diet and obesity, and for developing the next generation of research in which the impact on body composition of dietary interventions that modify the gut microbiota is determined.
Multivitamins are the most commonly consumed dietary supplement in the United States and worldwide. Micronutrient insufficiency and clinical deficiency are more common in middle-aged to older adults, and multivitamin use has been shown to improve status in this population. This analysis aimed to assess contributions of sporadic and consistent multivitamin use to total usual micronutrient intakes and associated nutritional biomarkers among middle-aged to older U.S. adults age 351 years, stratified by obesity status. Self-reported dietary intake and laboratory measures from the National Health and Nutrition Examination Survey were used in these analyses. The National Cancer Institute method was used to assess usual intakes of 18 micronutrients. Compared with food alone, multivitamin use was associated with a lower prevalence of inadequacies and improved nutritional biomarker status for folate, iodine, selenium, and vitamins B6, B12, and D. Consistent use decreased the prevalence of inadequacy for most micronutrients assessed, except for those micronutrients typically not found (or in miniscule amounts) in standard multivitamin products. In addition to a lower prevalence of inadequacy for many micronutrients associated with consistent use of multivitamins, sporadic use decreased the prevalence of inadequacy for a greater number of micronutrients in obese versus nonobese individuals. Multivitamin use (sporadic and consistent) also increased the proportion of individuals who exceeded the tolerable upper intake level for folic acid to 8–10%. Nutritional biomarker data indicate that obese individuals may be at greater risk of clinical deficiency in vitamins B6and D. Use of gender- and age-specific multivitamins may serve as a practical means to increase micronutrient status and decrease prevalences of clinical deficiency in the middle-aged to older population, particularly in those who are obese.
The objective of this study is to compare aneuploidy rates between three distinct areas of the human trophectoderm: mural, polar and a region in between these two locations termed the ‘mid’ trophectoderm. This is a cohort study on in vitro fertilization (IVF) patients undergoing comprehensive chromosome screening at the blastocyst stage at a private IVF clinic. All embryos underwent assisted hatching on day 3 with blastocyst biopsy and comprehensive chromosome screening. Biopsied blastocysts were divided into three groups depending on which area (polar, mid, or mural) of the trophectoderm was protruding from the zona pellucida and biopsied. Aneuploidy rates were significantly higher with cells from the polar region of the trophectoderm (56.2%) compared with cells removed from the mural region of the trophectoderm (30.0%; P = 0.0243). A comparison of all three areas combined also showed a decreasing trend, but this did not reach clinical significance, polar (56.2%), mid (47.4%) and mural trophectoderm (30.0%; P = 0.1859). The non-concordance demonstrated between polar and mural trophectoderm can be attributed to biological occurrences including chromosomal mosaicism or procedural differences between embryologists.
The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942–1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9–12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the ‘common’ environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960–1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68–72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study.
This article explores the justification for providing separate experiences for twins. The focus is on Dorothy Burlingham’s (1952; Twins: A study of three sets of identical twins with 30 charts. London, UK: Imago) classic, in-depth study of three identical twin-pairs. Implications for how twins are raised currently will be examined. Reviews are presented of twin research concerning monozygotic twins with maturity-onset diabetes, gene editing of fetal Chinese twins, educational disadvantage of early-born twins, and developmental trajectories of twins’ prenatal movements. Some unusual experiences and situations involving twins that warrant media attention are also summarized. They include twins with nearly identical license plates, a rare case of fetus-in-fetu, twin brothers killed at Pearl Harbor, the death of a 96-year-old twin Holocaust survivor, the accidental death of male–female twin toddlers in a heated car and confusion over identical twin politicians.
The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989–2004. We summarize early recruitment, assessment, retention and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and nontwin siblings. Our adolescent and young adult neuroimaging sample (N = 600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives.
Since our last report on the voluntary Hungarian Twin Registry (HTR) in 2012, the number of pairs or multiplets included increased from 310 to 1044. Efforts to turn the registry into a population-based one are on the way. Nearly 128,000 twins living in Hungary (98,500 adults) will be mailed information on how to register on the new HTR website. Twins will be asked to invite their spouses and immediate family members. Meanwhile, strong cooperation through exchange programs has been developed with other foreign twin registries. Current research focuses on radiogenomics, musculoskeletal, cardiovascular and respiratory diseases, gut microbiome as well as basic molecular research and yielded new awards and further publications.
Neurodevelopment is sensitive to genetic and pre/postnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri/postnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes; (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological sampling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program — Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.