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The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Introduction: Trauma and injury play a significant role in the population's burden of disease. Limited research exists evaluating the role of trauma bypass protocols. The objective of this study was to assess the impact and effectiveness of a newly introduced prehospital field trauma triage (FTT) standard, allowing paramedics to bypass a closer hospital and directly transport to a trauma centre (TC) provided transport times were within 30 minutes. Methods: We conducted a 12-month multi-centred health record review of paramedic call reports and emergency department health records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness, step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as an urgent transport to hospital, that met one of the 4 steps of the FTT standard and would allow for a bypass consideration. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions. The primary outcome was the rate of appropriate triage to a TC, defined as any of the following: injury severity score ≥12, admitted to an intensive care unit, underwent non-orthopedic operation, or death. We report descriptive and univariate analysis where appropriate. Results: 570 adult patients were included with the following characteristics: mean age 48.8, male 68.9%, attended by Advanced Care Paramedic 71.8%, mechanisms of injury: MVC 20.2%, falls 29.6%, stab wounds 10.5%, median initial GCS 14, mean initial BP 132, prehospital fluid administered 26.8%, prehospital intubation 3.5%, transported to a TC 74.6%. Of those transported to a TC, 308 (72.5%) had bypassed a closer hospital prior to TC arrival. Of those that bypassed a closer hospital, 136 (44.2%) were determined to be “appropriate triage to TC”. Bypassed patients more often met the step 1 or step 2 of the standard (186, 66.9%) compared to the step 3 or step 4 (122, 39.6%). An appropriate triage to TC occurred in 104 (55.9%) patients who had met step 1 or 2 and 32 (26.2%) patients meeting step 3 or 4 of the FTT standard. Conclusion: The FTT standard can identify patients who should be bypassed and transported to a TC. However, this is at a cost of potentially burdening the system with poor sensitivity. More work is needed to develop a FTT standard that will assist paramedics in appropriately identifying patients who require a trauma centre.
Introduction: Trauma is a common cause of mortality across all age groups and is projected to become the third greatest contributor to global disease burden. Recent studies have demonstrated that survival from traumatic cardiac arrest (TCA) is more favourable than once believed and further research on this population is being encouraged. Currently, it is unclear whether existing databases, such as the National Ambulatory Care Reporting system (NACRS), which includes all emergency department visits, could be used to identify TCAs for population-based studies. We aimed to determine the accuracy of NACRS administrative codes in identifying TCA patients. Methods: This retrospective validation study used data acquired from NACRS and our institutional Patient Care System. We identified a number of International Classification of Diseases, tenth revision (ICD-10) diagnostic, procedural and cause of injury codes that we hypothesized would be consistent with TCA. NACRS was subsequently searched for patients meeting the diagnostic code criteria (January 1 - December 31, 2015). The following inclusion criteria were: an eligible ICD-10 diagnostic code or a qualifying Canadian Classification of Health Interventions (CCI) procedure code and an eligible ICD-10 external cause of injury code. Electronic medical records for these patients were then reviewed to determine whether true TCAs had occurred. Results: Eighty-five patients met the inclusion criteria and one was excluded from analysis due to inaccessible health records, leaving 84 patients eligible for chart review. Overall, 55% (n = 46) of patients were found to have true TCA, 35% (n = 29) sustained a cardiac arrest of non-traumatic etiology and 11% (n = 9) were considered “unclear” (i.e. could not determine whether it was a true TCA based on the medical records). We found that true TCA patients were most accurately identified using a combination of ICD-10 CA cardiac arrest and external cause of injury codes (Positive predictive value: 70.6%, 95% CI 46.9-86.7). Conclusion: TCA patients were identified with moderate accuracy using the NACRS database. Further efforts to integrate specific data fields for TCA cases within existing population databases and trauma registries is necessary to facilitate future studies focused on this patient population.
The cognitive process of worry, which keeps negative thoughts in mind and elaborates the content, contributes to the occurrence of many mental health disorders. Our principal aim was to develop a straightforward measure of general problematic worry suitable for research and clinical treatment. Our secondary aim was to develop a measure of problematic worry specifically concerning paranoid fears.
An item pool concerning worry in the past month was evaluated in 250 non-clinical individuals and 50 patients with psychosis in a worry treatment trial. Exploratory factor analysis and item response theory (IRT) informed the selection of scale items. IRT analyses were repeated with the scales administered to 273 non-clinical individuals, 79 patients with psychosis and 93 patients with social anxiety disorder. Other clinical measures were administered to assess concurrent validity. Test-retest reliability was assessed with 75 participants. Sensitivity to change was assessed with 43 patients with psychosis.
A 10-item general worry scale (Dunn Worry Questionnaire; DWQ) and a five-item paranoia worry scale (Paranoia Worries Questionnaire; PWQ) were developed. All items were highly discriminative (DWQ a = 1.98–5.03; PWQ a = 4.10–10.7), indicating small increases in latent worry lead to a high probability of item endorsement. The DWQ was highly informative across a wide range of the worry distribution, whilst the PWQ had greatest precision at clinical levels of paranoia worry. The scales demonstrated excellent internal reliability, test-retest reliability, concurrent validity and sensitivity to change.
The new measures of general problematic worry and worry about paranoid fears have excellent psychometric properties.
The Flat Rocks locality in the Wonthaggi Formation (Strzelecki Group) of the Gippsland Basin, southeastern Australia, hosts fossils of a late Barremian vertebrate fauna that inhabited the ancient rift between Australia and Antarctica. Known from its dentary, Qantassaurus intrepidus Rich and Vickers-Rich, 1999 has been the only dinosaur named from this locality. However, the plethora of vertebrate fossils collected from Flat Rocks suggests that further dinosaurs await discovery. From this locality, we name a new small-bodied ornithopod, Galleonosaurus dorisae n. gen. n. sp. from craniodental remains. Five ornithopodan genera are now named from Victoria. Galleonosaurus dorisae n. gen. n. sp. is known from five maxillae, from which the first description of jaw growth in an Australian dinosaur is provided. The holotype of Galleonosaurus dorisae n. gen. n. sp. is the most complete dinosaur maxilla known from Victoria. Micro-CT imagery of the holotype reveals the complex internal anatomy of the neurovascular tract and antorbital fossa. We confirm that Q. intrepidus is uniquely characterized by a deep foreshortened dentary. Two dentaries originally referred to Q. intrepidus are reassigned to Q. ?intrepidus and a further maxilla is referred to cf. Atlascopcosaurus loadsi Rich and Rich, 1989. A further ornithopod dentary morphotype is identified, more elongate than those of Q. intrepidus and Q. ?intrepidus and with three more tooth positions. This dentary might pertain to Galleonosaurus dorisae n. gen. n. sp. Phylogenetic analysis recovered Cretaceous Victorian and Argentinian nonstyracosternan ornithopods within the exclusively Gondwanan clade Elasmaria. However, the large-bodied taxon Muttaburrasaurus langdoni Bartholomai and Molnar, 1981 is hypothesised as a basal iguanodontian with closer affinities to dryomorphans than to rhabdodontids.
There has recently been growing interest in various atomic and nuclear techniques for the measurement of elements in the body. This has arisen through the realisation that (a) clinically-important amounts of toxic elements can be absorbed as a result of low-level environmental exposure, and (b) important information about the nutritional status of a patient can be obtained from measurements of major body elements. Where such information can be obtained by taking samples, a very wide range of analytical techniques is available, some capable of a sensitivity measured in parts-per-billion. Sampling is not possible, however, when the whole-body content (e.g. of nitrogen) is required, and is clinically undesirable when the element in question is concentrated in particular organs, for example as lead accumulates in the bones, and cadmium and many other toxic elements accumulate in the kidneys. It is in such cases that the various in vivo techniques are particularly important.
As a result of interest stemming from shock wave studies carried out at Lawrence Livermore Laboratory, we have developed a capability to conduct x-ray diffraction studies in submicrosecond time intervals. This involves the use of a low impedance flash x-ray device. While there are many applications to which these techniques can be put, our first experiments deal with samples undergoing shock wave compression. These particular experiments are conducted by synchronizing a 40 to 50 nsec flash x-ray device to a shock front which is produced by the detonation of a high explosive placed in contact with a sample. Diffracted radiation is usually recorded on very sensitive film protected by a blast cassette. Thus far we have subjected lithium fluoride, aluminum, and carbon to pressures in the range of 100 to 300 kbar. Either powder or single crystal samples can be used. The principal difficulties of this experiment are the lack of sufficient intensity and the synchronization of the x-ray pulse to the shock front.
The e-commerce chapters in South Korea's Free Trade Agreements (FTAs) cover a wide range of issues, ranging from non-discrimination to electronic signatures. Across the agreements, the country's provisions on consumer protection, paperless trading, and data protection are uniquely consistent, while those on other issues are not. With the aid of a framework (Framer v. Follower) that captures the dynamics of bilateral negotiations, this paper argues that in Korea's case, the more consistent a particular set of provisions is portfolio-wide, the more likely it was for Korea to have prioritized the relevant issue and actively pushed its preferred terms in the FTAs.
GravityCam is a new concept of ground-based imaging instrument capable of delivering significantly sharper images from the ground than is normally possible without adaptive optics. Advances in optical and near-infrared imaging technologies allow images to be acquired at high speed without significant noise penalty. Aligning these images before they are combined can yield a 2.5–3-fold improvement in image resolution. By using arrays of such detectors, survey fields may be as wide as the telescope optics allows. Consequently, GravityCam enables both wide-field high-resolution imaging and high-speed photometry. We describe the instrument and detail its application to provide demographics of planets and satellites down to Lunar mass (or even below) across the Milky Way. GravityCam is also suited to improve the quality of weak shear studies of dark matter distribution in distant clusters of galaxies and multiwavelength follow-ups of background sources that are strongly lensed by galaxy clusters. The photometric data arising from an extensive microlensing survey will also be useful for asteroseismology studies, while GravityCam can be used to monitor fast multiwavelength flaring in accreting compact objects and promises to generate a unique data set on the population of the Kuiper belt and possibly the Oort cloud.
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.
Gut symbionts can augment resistance to pathogens by stimulating host-immune responses, competing for space and nutrients, or producing antimicrobial metabolites. Gut microbiota of social bees, which pollinate many crops and wildflowers, protect hosts against diverse infections and might counteract pathogen-related bee declines. Bumble bee gut microbiota, and specifically abundance of Lactobacillus ‘Firm-5’ bacteria, can enhance resistance to the trypanosomatid parasite Crithidia bombi. However, the mechanism underlying this effect remains unknown. We hypothesized that the Firm-5 bacterium Lactobacillus bombicola, which produces lactic acid, inhibits C. bombi via pH-mediated effects. Consistent with our hypothesis, L. bombicola spent medium inhibited C. bombi growth via reduction in pH that was both necessary and sufficient for inhibition. Inhibition of all parasite strains occurred within the pH range documented in honey bees, though sensitivity to acidity varied among strains. Spent medium was slightly more potent than HCl, d- and l-lactic acids for a given pH, suggesting that other metabolites also contribute to inhibition. Results implicate symbiont-mediated reduction in gut pH as a key determinant of trypanosomatid infection in bees. Future investigation into in vivo effects of gut microbiota on pH and infection intensity would test the relevance of these findings for bees threatened by trypanosomatids.
Migration was a key social process contributing to the creation of the ‘Chaco World’ between AD 800 and 1200. Dynamic social network analysis allows for evaluation of several migration scenarios, and demonstrates that Chaco’s earliest ninth-century networks show interaction with areas to the west and south, rather than migration to the Canyon from the Northern San Juan. By the late eleventh century, Chaco Canyon was tied strongly to the Middle and Northern San Juan, while a twelfth-century retraction of networks separated the Northern and Southern San Juan areas prior to regional depopulation. Understanding Chaco migration is important for comprehending both its uniqueness in U.S. Southwest archaeology and for comparison with other case studies worldwide.