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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.
The wheat bZip transcription factor TaABF1 mediates both abscisic acid (ABA)-induced and ABA-suppressed gene expression. As levels of TaABF1 protein do not change in response to ABA, and TaABF1 is in a phosphorylated state in vivo, we investigated whether TaABF1 could be regulated at the post-translational level. In bombarded aleurone cells, a TaABF1 protein carrying phosphomimetic mutations (serine to aspartate) at four sites (S36D, S37D, S113D, S115D) was three to five times more potent than wild-type TaABF1 in activating HVA1, an ABA-responsive gene. The phosphomimetic mutations also increased the ability of TaABF1 to downregulate the ABA-suppressed gene Amy32b. These findings strongly suggest that phosphorylation at these sites increases the transcriptional regulatory activity of TaABF1. In contrast to the activation observed by the quadruple serine to aspartate mutation, a single S113D mutation completely eliminated the ability of TaABF1 to upregulate HVA1 or downregulate Amy32b. Thus phosphorylation of TaABF1 can either stimulate or inhibit the activity of TaABF1 in regulating downstream genes, depending on the site and pattern of phosphorylation. Mutation of S318 and S322 (in the bZIP domain) eliminated the ability of TaABF1 to activate HVA1, but had no effect on the ability of TaABF1 to downregulate Amy32b, suggesting that TaABF1 represses Amy32b expression through a mechanism other than direct DNA binding. An important step towards understanding how ABA and gibberellin (GA) signals are integrated through TaABF1 phosphorylation to regulate downstream gene expression is to clarify the effects of those hormones on the expression of specific genes. In contrast to some other ABA-induced genes, we found that HVA1 induction by ABA or TaABF1 is not inhibited by GA.
Field and greenhouse studies were conducted in 2016 and 2017 to determine sweetpotato tolerance to herbicides applied to plant propagation beds. Herbicide treatments included PRE application of flumioxazin (107 g ai ha−1), S-metolachlor (800 g ai ha−1), fomesafen (280 g ai ha−1), flumioxazin plus S-metolachlor (107 g ai ha−1 + 800 g ai ha−1), fomesafen plus S-metolachlor (280 g ai ha−1 + 800 g ai ha−1), fluridone (1,120 or 2,240 g ai ha−1), fluridone plus S-metolachlor (1,120 g ai ha−1 + 800 g ai ha−1), napropamide (1,120 g ai ha−1), clomazone (420 g ai ha−1), linuron (560 g ai ha−1), linuron plus S-metolachlor (560 g ai ha−1 + 800 g ai ha−1), bicyclopyrone (38 or 49.7 g ai ha−1), pyroxasulfone (149 g ai ha−1), pre-mix of flumioxazin plus pyroxasulfone (81.8 g ai ha−1 + 104.2 g ai ha−1), or metribuzin (294 g ai ha−1). Paraquat plus non-ionic surfactant (280 g ai ha−1 + 0.25% v/v) POST was also included. After plants in the propagation bed were cut and sweetpotato slip number, length, and weight had been determined, the slips were then transplanted to containers and placed either in the greenhouse or on an outdoor pad to determine any effects from the herbicide treatments on initial sweetpotato growth. Sweetpotato slip number, length, and/or weight were affected by flumioxazin with or without S-metolachlor, S-metolachlor with or without fomesafen, clomazone, and all fluridone treatments. In the greenhouse studies, initial root growth of plants after transplanting was inhibited by fluridone (1,120 g ai ha−1) and fluridone plus S-metolachlor. However, by 5 wk after transplanting few differences were observed between treatments. Fomesafen, linuron with or without S-metolachlor, bicyclopyrone (38 or 49.7 g ai ha−1), pyroxasulfone with or without flumioxazin, metribuzin, and paraquat did not cause injury to sweetpotato slips in any of the studies conducted.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Treatment for hoarding disorder is typically performed by mental health professionals, potentially limiting access to care in underserved areas.
We aimed to conduct a non-inferiority trial of group peer-facilitated therapy (G-PFT) and group psychologist-led cognitive–behavioural therapy (G-CBT).
We randomised 323 adults with hording disorder 15 weeks of G-PFT or 16 weeks of G-CBT and assessed at baseline, post-treatment and longitudinally (≥3 months post-treatment: mean 14.4 months, range 3–25). Predictors of treatment response were examined.
G-PFT (effect size 1.20) was as effective as G-CBT (effect size 1.21; between-group difference 1.82 points, t = −1.71, d.f. = 245, P = 0.04). More homework completion and ongoing help from family and friends resulted in lower severity scores at longitudinal follow-up (t = 2.79, d.f. = 175, P = 0.006; t = 2.89, d.f. = 175, P = 0.004).
Peer-led groups were as effective as psychologist-led groups, providing a novel treatment avenue for individuals without access to mental health professionals.
Declaration of interest
C.A.M. has received grant funding from the National Institutes of Health (NIH) and travel reimbursement and speakers’ honoraria from the Tourette Association of America (TAA), as well as honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. K.D. receives research support from the NIH and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. R.S.M. receives research support from the National Institute of Mental Health, National Institute of Aging, the Hillblom Foundation, Janssen Pharmaceuticals (research grant) and the Alzheimer's Association. R.S.M. has also received travel support from the National Institute of Mental Health for Workshop participation. J.Y.T. receives research support from the NIH, Patient-Centered Outcomes Research Institute and the California Tobacco Related Research Program, and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. All other authors report no conflicts of interest.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
This paper summarises developments in understanding sea level change during the Quaternary in Scotland since the publication of the Quaternary of Scotland Geological Conservation Review volume in 1993. We present a review of progress in methodology, particularly in the study of sediments in isolation basins and estuaries as well as in techniques in the field and laboratory, which have together disclosed greater detail in the record of relative sea level (RSL) change than was available in 1993. However, progress in determining the record of RSL change varies in different areas. Studies of sediments and stratigraphy offshore on the continental shelf have increased greatly, but the record of RSL change there remains patchy. Studies onshore have resulted in improvements in the knowledge of rock shorelines, including the processes by which they are formed, but much remains to be understood. Studies of Late Devensian and Holocene RSLs around present coasts have improved knowledge of both the extent and age range of the evidence. The record of RSL change on the W and NW coasts has disclosed a much longer dated RSL record than was available before 1993, possibly with evidence of Meltwater Pulse 1A, while studies in estuaries on the E and SW coasts have disclosed widespread and consistent fluctuations in Holocene RSLs. Evidence for the meltwater pulse associated with the Early Holocene discharge of Lakes Agassiz–Ojibway in N America has been found on both E and W coasts. The effects of the impact of storminess, in particular in cliff-top storm deposits, have been widely identified. Further information on the Holocene Storegga Slide tsunami has enabled a better understanding of the event, but evidence for other tsunami events on Scottish coasts remains uncertain. Methodological developments have led to new reconstructions of RSL change for the last 2000 years, utilising state-of-the-art GIA models and alongside coastal biostratigraphy to determine trends to compare with modern tide gauge and documentary evidence. Developments in GIA modelling have provided valuable information on patterns of land uplift during and following deglaciation. The studies undertaken raise a number of research questions which will require addressing in future work.
Older adults are a potentially medically vulnerable population with increased mortality rates during and after disasters. To evaluate the impact of a natural disaster on this population, we performed a temporal and geospatial analysis of emergency department (ED) use by adults aged 65 years and older in New York City (NYC) following Hurricane Sandy’s landfall.
We used an all-payer claims database to analyze demographics, insurance status, geographic distribution, and health conditions for post-disaster ED visits among older adults. We compared ED patterns of use in the weeks before and after Hurricane Sandy throughout NYC and the most afflicted evacuation zones.
We found significant increases in ED utilization by older adults (and disproportionately higher in those aged ≥85 years) in the 3 weeks after Hurricane Sandy, especially in NYC evacuation zone one. Primary diagnoses with notable increases included dialysis, electrolyte disorders, and prescription refills. Secondary diagnoses highlighted homelessness and care access issues.
Older adults display heightened risk for worse health outcomes with increased ED visits after a disaster. Our findings suggest the need for dedicated resources and planning for older adults following a natural disaster by ensuring access to medical facilities, prescriptions, dialysis, and safe housing and by optimizing health care delivery needs to reduce the burden of chronic disease. (Disaster Med Public Health Preparedness. 2018;12:184–193)
We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.
The Kulshan caldera formed at ∼1.15 Ma on the present-day site of Mt. Baker, Washington State, northwest USA and erupted a compositionally zoned (dacite-rhyolite) magma and a correlative eruptive, the Lake Tapps tephra. This tephra has previously been described, but only from the Puget Lowland of NW Washington. Here an occurrence of a Kulshan caldera correlative tephra is described from the Quaternary Palouse loess at the Washtucna site (WA-3). Site WA-3 is located in east-central Washington, ∼340 km southeast of the Kulshan caldera and ∼300 km east-southeast of the Lake Tapps occurrence in the Puget Lowland. Major- and trace element chemistry and location of the deposit at Washtucna within reversed polarity sediments indicates that it is not correlative with the Mesa Falls, Rockland, Bishop Ash, Lava Creek B or Huckleberry Ridge tephras. Instead the Washtucna deposit is related to the Lake Tapps tephra by fractional crystallisation, but is chemically distinct, a consequence of its eruption from a compositionally zoned magma chamber. The correlation of the Washtucna occurrence to the Kulshan caldera-forming eruption indicates that it had an eruptive volume exceeding 100 km3, and that its tephra could provide a valuable early-Pleistocene chronostratigraphic marker in the Pacific Northwest.
This paper reviews our recent investigations of compound semiconductors and heterovalent interfaces using the technique of aberration-corrected scanning transmission electron microscopy. Bright-field imaging of compound semiconductors with a collection angle that is comparable in size to the incident-beam convergence angle is demonstrated to provide better atomic-column visibility for lighter elements in comparison with the more traditional high-angle annular-dark-field approach. Several pairs of Group II–VI/Group III–V compound semiconductors with zincblende structure have been studied in detail. These combinations are all valence-mismatched (i.e., heterovalent), and include CdTe/InSb (Δa/a ≤ 0.05%), ZnTe/InP (Δa/a = 3.8%), and ZnTe/GaAs (Δa/a = 7.4%). CdTe/InSb (001) interfaces are observed to be defect-free with a slight lattice contraction at the interface plane. For interfaces with larger lattice-parameter mismatch, the primary interfacial defects are identified as Lomer edge dislocations and perfect 60° dislocations. However, the atomic structure of the dislocation cores has not yet been unambiguously determined.