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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.
Bipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples.
We assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive–Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity.
Among primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale–Brown Obsessive Compulsive Scale (Y-BOCS).
These findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.
The relative velocity and extra pressure drop of a single vesicle flowing through a square microchannel are quantified via boundary element simulations, lubrication theory and microfluidic experiments. The vesicle is modelled as a fluid sac enclosed by an inextensible, fluidic membrane with a negligible bending stiffness. All results are parametrized in terms of the vesicle sphericity (i.e. the reduced volume) and flow confinement (i.e. the ratio of the vesicle radius to the channel hydraulic radius). Direct comparison is made to previous studies of vesicle flow through circular tubes, revealing several distinct features of the square-channel geometry. Firstly, fluid in the suspending medium bypasses the vesicle through the corners of the channel, which in turn reduces the dissipation created by the vesicle. Secondly, the absence of rotational symmetry about the channel axis permits surface circulation in the membrane (tank treading), which in turn reduces the vesicle’s speed. At very high confinement, both theory and experiment indicate that the vesicle’s speed can be reduced below the mean speed of the suspending fluid through this mechanism. Finally, the contact area for lubrication is greatly reduced in the square-duct geometry, which in turn weakens the stress singularity predicted by lubrication theory. This fact directly leads to a breakdown of the lubrication approximation at low flow confinement, as verified by comparison to boundary element simulations. Since the only distinct property assumed of the membrane is its ability to preserve surface area locally, it is expected that the results of this study are applicable to other types of soft particles with immobilized surfaces (e.g. Pickering droplets, gel beads and biological cells).
The Turkana Basin of northwestern Kenya is well known for its rich Neogene–Quaternary vertebrate fossil record; however, it also represents one of the few locations in sub-Saharan Africa where Cretaceous vertebrate fossils, including dinosaurs and other archosaurs, are preserved. These Cretaceous deposits are colloquially referred to as the ‘Turkana Grits’, and assumed to be Cretaceous in age based on their limited biostratigraphy. The ‘Turkana Grits’ are overlain by Palaeogene volcanic rocks (<35 Ma), which are widely considered to record the earliest evidence of plume-related volcanism in the East African Rift System. In this study, we present the results of an integrated sedimentary provenance investigation of two units within the ‘Turkana Grits’ called the Lapur and Muruanachok sandstones. Analysis of U–Pb ages and Lu–Hf initial ɛHf(t) values from 1106 detrital zircons demonstrate that sediments are primarily derived from Neoarchaean and Neoproterozoic basement sources, except for six Palaeogene grains from the upper Lapur Sandstone, which are of unknown provenance. Considered together, these data point to the Mozambique Belt, which makes up the nearby rift flanks, as the primary provenance source. This is consistent with palaeocurrent data, and suggests localized sediment input by alluvial fans, which fed into NNW-directed fluvial systems. Perhaps the most surprising finding is the identification of the late Paleocene detrital zircons, which not only demonstrate that the depositional age for the top of the formation is Paleocene rather than Cretaceous, but also provides possible evidence for the oldest Palaeogene volcanic activity within the East African Rift System.
The inertialess motion of lipid-bilayer vesicles flowing through a circular tube is investigated via direct numerical simulation and lubrication theory. A fully three-dimensional boundary integral equation method, previously used to study unbounded and wall-bounded Stokes flows around freely suspended vesicles, is extended to study the hindered mobility of vesicles through conduits of arbitrary cross-section. This study focuses on the motion of a periodic train of vesicles positioned concentrically inside a circular tube, with particular attention given to the effects of tube confinement, vesicle deformation and membrane bending elasticity. When the tube diameter is comparable to the transverse dimension of the vesicle, axisymmetric lubrication theory provides an approximate solution to the full Stokes-flow problem. By combining the present numerical results with a previously reported asymptotic theory (Barakat & Shaqfeh, J. Fluid Mech., vol. 835, 2018, pp. 721–761), useful correlations are developed for the vesicle velocity
and extra pressure drop
. When bending elasticity is relatively weak, these correlations are solely functions of the geometry of the system (independent of the imposed flow rate). The prediction of Barakat & Shaqfeh (2018) supplies the correct limiting behaviour of
near maximal confinement, whereas the present study extends this result to all regimes of confinement. Vesicle–vesicle interactions, shape transitions induced by symmetry breaking, and unsteadiness introduce quantitative changes to
. By contrast, membrane bending elasticity can qualitatively affect the hydrodynamics at sufficiently low flow rates. The dependence of
on the membrane bending stiffness (relative to a characteristic viscous stress scale) is found to be rather complex. In particular, the competition between viscous forces and bending forces can hinder or enhance the vesicle’s mobility, depending on the geometry and flow conditions.
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to determine the degree to which the use of a contralesionally-controlled brain-computer interface for stroke rehabilitation drives change in interhemispheric motor cortical activity. METHODS/STUDY POPULATION: Ten chronic stroke patients were trained in the use of a brain-computer interface device for stroke recovery. Patients perform motor imagery to control the opening and closing of a motorized hand orthosis. This device was sent home with patients for 12 weeks, and patients were asked to use the device 1 hour per day, 5 days per week. The Action Research Arm Test (ARAT) was performed at 2-week intervals to assess motor function improvement. Before the active motor imagery task, patients were asked to quietly rest for 90 seconds before the task to calibrate recording equipment. EEG signals were acquired from 2 electrodes—one each centered over left and right primary motor cortex. Signals were preprocessed with a 60 Hz notch filter for environmental noise and referenced to the common average. Power envelopes for 1 Hz frequency bands (1–30 Hz) were calculated through Gabor wavelet convolution. Correlations between electrodes were then calculated for each frequency envelope on the first and last 5 runs, thus generating one correlation value per subject, per run. The chosen runs approximately correspond to the first and last week of device usage. These correlations were Fisher Z-transformed for comparison. The first and last 5 run correlations were averaged separately to estimate baseline and final correlation values. A difference was then calculated between these averages to determine correlation change for each frequency. The relationship between beta-band correlation changes (13–30 Hz) and the change in ARAT score was determined by calculating a Pearson correlation. RESULTS/ANTICIPATED RESULTS: Beta-band inter-electrode correlations tended to decrease more in patients achieving greater motor recovery (Pearson’s r=−0.68, p=0.031). A similar but less dramatic effect was observed with alpha-band (8–12 Hz) correlation changes (Pearson’s r=−0.42, p=0.22). DISCUSSION/SIGNIFICANCE OF IMPACT: The negative correlation between inter-electrode power envelope correlations in the beta frequency band and motor recovery indicates that activity in the motor cortex on each hemisphere may become more independent during recovery. The role of the unaffected hemisphere in stroke recovery is currently under debate; there is conflicting evidence regarding whether it supports or inhibits the lesioned hemisphere. These findings may support the notion of interhemispheric inhibition, as we observe less in common between activity in the 2 hemispheres in patients successfully achieving recovery. Future neuroimaging studies with greater spatial resolution than available with EEG will shed further light on changes in interhemispheric communication that occur during stroke rehabilitation.
The increased use of uninhabited aerial vehicle systems (UAVS), known as drones, in modern warfare, is filled with paradoxes. Drone technology shields soldiers from harm, for example. And yet as legal scholar Paul Kahn has written, this very ethical motivation brings about the troubling military consequence in which one side of a war assumes all or most of the risk of being injured or killed. Scholars often call this an “asymmetric” war, and it is troubling not just because accomplishing a military objective may begin to resemble a video game under these circumstances but also because mutual assumption of risk, for traditional Just War theorists, is a necessary condition for acquiring the right to kill. A soldier acquires the right to kill only in virtue of needing to defend his/herself against harm, according to traditional Just War theory. So without the need to defend themselves against the threat of harm, it can be hard to see what gives individual soldiers the right to kill. Objections abound to the premises of this paradox, but it's hard to shake this import at least: that an ethical obligation like shielding soldiers from harm can have unforeseen, problematic, and even contradictory consequences.
Another paradox of the increasing use of drones in armed conflict is a function of the secrecy of drone strikes. Drones can be launched from thousands of miles away, strike, and then disappear almost instantly, leaving only a heap of rubble where minutes earlier a building, or a person, stood. The element of surprise is an essential military strategy. And yet that very sense of surprise and physical distance from the battlefield – which when presented on a high-definition screen does not necessarily feel so far away for the drone operators – separates the two sides physically and psychologically and opens up space for propagandists to redescribe drone strikes in their own terms, potentially recruiting people to join the ranks of the very armed group that drones strikes attempt to dismantle. It's not just that the secrecy of drone strikes has trade-offs; it's also that the most ethical of intentions in drone warfare – to strike quickly, precisely, and accurately – can lead to unethical consequences.
Dissecting Bioethics, edited by Tuija Takala and Matti Hayry, welcomes contributions on the conceptual and theoretical dimensions of bioethics. The department is dedicated to the idea that words defined by bioethicists and others should not be allowed to imprison people’s actual concerns, emotions, and thoughts. Papers that expose the many meanings of a concept, describe the different readings of a moral doctrine, or provide an alternative angle to seemingly self-evident issues are particularly appreciated. To submit a paper or to discuss a suitable topic, contact Tuija Takala at email@example.com.
A singular perturbation theory is developed for the steady, inertialess motion of a lipid-bilayer vesicle flowing through a narrow tube. The vesicle is treated as a sac of fluid enclosed by an inextensible membrane that admits a bending stiffness. Matched asymptotic expansions are developed in terms of a clearance parameter
in order to calculate the flow field and vesicle shape. Mild restrictions are applied to the ratio of viscosities
and the ratio of bending stresses to viscous stresses
; in particular, the theory holds for
. The ratio of the vesicle length to the tube radius
is included as a parameter and asymptotic solutions in the limit of negligible bending stiffness are developed for long, cylindrical vesicles and short, spherical vesicles. The main result of the theory is a prediction for the vesicle speed and extra pressure drop due to the presence of the vesicle in the tube. The effects of confinement, vesicle length, and membrane bending elasticity are examined. The theoretical predictions show good agreement with experimental measurements reported for vesicles and red blood cells in highly confined channel flow. Previously reported models for red blood cells (Secomb et al., J. Fluid Mech., vol. 163, 1986, pp. 405–423; Halpern & Secomb, J. Fluid Mech., vol. 203, 1989, pp. 381–400) are clarified and extended in light of the new theory.
Shallow ice cores were obtained from widely distributed sites across the West Antarctic ice sheet, as part of the United States portion of the International Trans-Antarctic Scientific Expedition (US ITASE) program. The US ITASE cores have been dated by annual-layer counting, primarily through the identification of summer peaks in non-sea-salt sulfate (nssSO42–) concentration. Absolute dating accuracy of better than 2 years and relative dating accuracy better than 1 year is demonstrated by the identification of multiple volcanic marker horizons in each of the cores, Tambora, Indonesia (1815), being the most prominent. Independent validation is provided by the tracing of isochronal layers from site to site using high-frequency ice-penetrating radar observations, and by the timing of mid-winter warming events in stable-isotope ratios, which demonstrate significantly better than 1 year accuracy in the last 20 years. Dating precision to ±1 month is demonstrated by the occurrence of summer nitrate peaks and stable-isotope ratios in phase with nssSO42–, and winter-time sea-salt peaks out of phase, with phase variation of <1 month. Dating precision and accuracy are uniform with depth, for at least the last 100 years.
Annually dated ice cores from West and East Antarctica provide proxies for past changes in atmospheric circulation over Antarctica and portions of the Southern Ocean, temperature in coastal West and East Antarctica, and the frequency of South Polar penetration of El Niño events. During the period AD 1700–1850, atmospheric circulation over the Antarctic and at least portions of the Southern Hemisphere underwent a mode switch departing from the out-of-phase alternation of multi-decadal long phases of EOF1 and EOF2 modes of the 850 hPa field over the Southern Hemisphere (as defined in the recent record by Thompson and Wallace, 2000; Thompson and Solomon, 2002) that characterizes the remainder of the 700 year long record. From AD 1700 to 1850, lower-tropospheric circulation was replaced by in-phase behavior of the Amundsen Sea Low component of EOF2 and the East Antarctic High component of EOF1. During the first phase of the mode switch, both West and East Antarctic temperatures declined, potentially in response to the increased extent of sea ice surrounding both regions. At the end of the mode switch, West Antarctic coastal temperatures rose and East Antarctic coastal temperatures fell, respectively, to their second highest and lowest of the record. Polar penetration of El Niño events increased during the mode switch. The onset of the AD 1700–1850 mode switch coincides with the extreme state of the Maunder Minimum in solar variability. Late 20th-century West Antarctic coastal temperatures are the highest in the record period, and East Antarctic coastal temperatures close to the lowest. Since AD 1700, extratropical regions of the Southern Hemisphere have experienced significant climate variability coincident with changes in both solar variability and greenhouse gases.
A 141m ice core was recovered from Combatant Col (51.385° N, 125.258° W; 3000ma.s.l.), Mount Waddington, Coast Mountains, British Columbia, Canada. Records of black carbon, dust, lead and water stable isotopes demonstrate that unambiguous seasonality is preserved throughout the core, despite summer surface snowmelt and temperate ice. High accumulation rates at the site (>4 m ice eq. a-1) limit modification of annual stratigraphy by percolation of surface meltwater. The ice-core record spans the period 1973–2010. An annually averaged time series of lead concentrations from the core correlates well with historical records of lead emission from North America, and with ice-core records of lead from the Greenland ice sheet. The depth-age scale for the ice core provides sufficient constraint on the vertical strain to allow estimation of the age of the ice at bedrock. Total ice thickness at Combatant Col is ~250 m; an ice core to bedrock would likely contain ice in excess of 200 years in age. Accumulation at Combatant Col is significantly correlated with both regional precipitation and large-scale geopotential height anomalies.
On 1 December 2011 the West Antarctic Ice Sheet (WAIS) Divide ice-core project reached its final depth of 3405 m. The WAIS Divide ice core is not only the longest US ice core to date, but is also the highest-quality deep ice core, including ice from the brittle ice zone, that the US has ever recovered. The methods used at WAIS Divide to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the US National Ice Core Laboratory (NICL) and the methods used to process and sample the ice at the NICL are described and discussed.
The WAIS (West Antarctic Ice Sheet) Divide deep ice core was recently completed to a total depth of 3405 m, ending 50 m above the bed. Investigation of the visual stratigraphy and grain characteristics indicates that the ice column at the drilling location is undisturbed by any large-scale overturning or discontinuity. The climate record developed from this core is therefore likely to be continuous and robust. Measured grain-growth rates, recrystallization characteristics, and grain-size response at climate transitions fit within current understanding. Significant impurity control on grain size is indicated from correlation analysis between impurity loading and grain size. Bubble-number densities and bubble sizes and shapes are presented through the full extent of the bubbly ice. Where bubble elongation is observed, the direction of elongation is preferentially parallel to the trace of the basal (0001) plane. Preferred crystallographic orientation of grains is present in the shallowest samples measured, and increases with depth, progressing to a vertical-girdle pattern that tightens to a vertical single-maximum fabric. This single-maximum fabric switches into multiple maxima as the grain size increases rapidly in the deepest, warmest ice. A strong dependence of the fabric on the impurity-mediated grain size is apparent in the deepest samples.
Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster.
We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties.
The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature.
The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127–137)
Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients.
A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson’s chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable.
14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables.
Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.
This article reports on the effects of domestic election observers on electoral fraud and violence. Using an experimental research design and polling station data on fraud and violence during Ghana’s 2012 elections, it shows that observers reduced fraud and violence at the polling stations which they monitored. It is argued that local electoral competition shapes party activists’ response to observers. As expected, in single-party dominant areas, parties used their local political networks to relocate fraud to polling stations without an election observer, and, in contrast, party activists relocated violence to stations without observers in competitive areas – a response that requires less local organizational capacity. This highlights how local party organization and electoral incentives can shape the manipulative electoral strategies employed by parties in democratic elections.
Anxiety disorders are prevalent yet under-recognized in late life. We examined the prevalence of anxiety disorders in a representative sample of community dwelling older adults in Hong Kong.
Data on 1,158 non-demented respondents aged 60–75 years were extracted from the Hong Kong Mental Morbidity survey (HKMMS). Anxiety was assessed with the revised Clinical Interview Schedule (CIS-R).
One hundred and thirty-seven respondents (11.9%, 95% CI = 10–13.7%) had common mental disorders with a CIS-R score of 12 or above. 8% (95% CI = 6.5–9.6%) had anxiety, 2.2% (95% CI = 1.3–3%) had an anxiety disorder comorbid with depressive disorder, and 1.7% (95% CI = 1–2.5%) had depression. Anxious individuals were more likely to be females (χ2 = 25.3, p < 0.001), had higher chronic physical burden (t = −9.3, p < 0.001), lower SF-12 physical functioning score (t = 9.2, p < 0.001), and poorer delayed recall (t = 2.3, p = 0.022). The risk of anxiety was higher for females (OR 2.8, 95% C.I. 1.7–4.6, p < 0.001) and those with physical illnesses (OR 1.4, 95% C.I. 1.3–1.6, p < 0.001). The risk of anxiety disorders increased in those with disorders of cardiovascular (OR 1.9, 95% C.I. 1.2–2.9, p = 0.003), musculoskeletal (OR 2.0, 95% C.I. 1.5–2.7, p < 0.001), and genitourinary system (OR 2.0, 95% C.I. 1.3–3.2, p = 0.002).
The prevalence of anxiety disorders in Hong Kong older population was 8%. Female gender and those with poor physical health were at a greater risk of developing anxiety disorders. Our findings also suggested potential risk for early sign of memory impairment in cognitively healthy individuals with anxiety disorders.