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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.
Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.
Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.
Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.
Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8–24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43–4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61–2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.
Psychotic symptoms are common in children and adolescents and may be early manifestations of liability to severe mental illness (SMI), including schizophrenia. SMI and psychotic symptoms are associated with impairment in executive functions. However, previous studies have not differentiated between ‘cold’ and ‘hot’ executive functions. We hypothesized that the propensity for psychotic symptoms is specifically associated with impairment in ‘hot’ executive functions, such as decision-making in the context of uncertain rewards and losses.
In a cohort of 156 youth (mean age 12.5, range 7–24 years) enriched for familial risk of SMI, we measured cold and hot executive functions with the spatial working memory (SWM) task (total errors) and the Cambridge Gambling Task (decision-making), respectively. We assessed psychotic symptoms using the semi-structured Kiddie Schedule for Affective Disorders and Schizophrenia interview, Structured Interview for Prodromal Syndromes, Funny Feelings, and Schizophrenia Proneness Instrument – Child and Youth version.
In total 69 (44.23%) youth reported psychotic symptoms on one or more assessments. Cold executive functioning, indexed with SWM errors, was not significantly related to psychotic symptoms [odds ratio (OR) 1.36, 95% confidence interval (CI) 0.85–2.17, p = 0.204). Poor hot executive functioning, indexed as decision-making score, was associated with psychotic symptoms after adjustment for age, sex and familial clustering (OR 2.37, 95% CI 1.25–4.50, p = 0.008). The association between worse hot executive functions and psychotic symptoms remained significant in sensitivity analyses controlling for general cognitive ability and cold executive functions.
Impaired hot executive functions may be an indicator of risk and a target for pre-emptive early interventions in youth.
We compared accelerator mass spectrometry (AMS) 14C ages of large (>150 μm) pelagic foraminifera with radiometric bulk carbonate 14C ages in two northeastern Atlantic cores. The foraminiferal ages are consistently older than those of the bulk sediment (by + 0.76 ka in Core 11881 and by + 1.1 ka in Core 11886), whereas corresponding fine (<5 μm) fraction ages are similar to those of the bulk sediment carbonate. We calculated near-identical sediment accumulation rates from both the foraminiferal and bulk sediment age/depth relations (3.0 cm ka−1 in Core 11881 and 5.9 cm ka−1 in Core 11886). Consideration of various factors that might produce such offsets leads us to believe that they are not artifacts, but were most probably caused by differential bioturbation of the different size-fractions in the sediment surface mixed layer. The importance of this finding is that many paleoceanographic records, such as the oxygen isotope record, also derive from analyses of large foraminifera, so that these records must be offset in time from the bulk of the sediments that they characterize.
The Sellafield nuclear fuel reprocessing plant on the northwest coast of England is the largest source of anthropogenic radiocarbon to the UK coastal environment. In a mid-1990s study of 14C distribution around the UK coast, the pattern of dilution with increasing distance from Sellafield appeared to be perturbed by anomalously high 14C activities in marine biota in the coastal environment of northeast England. This present study was undertaken during 1998 and 1999 to determine whether this 14C enhancement was due to Sellafield or the nuclear power plants on the east coast. Seawater, seaweed (Fucus sp.), and mussel (Mytilus edulis) samples that were collected from the vicinity of the Torness and Hartlepool advanced gas-cooled reactor (AGR) nuclear power stations were all enhanced above the contemporary regional background activity derived from natural production and atmospheric nuclear weapons testing. We used previously published dilution factors and transfer times for 99Tc between Sellafield and various points on the UK coast to determine likely Sellafield-derived 14C contributions to the activities at the nuclear power plant sites. The results suggest that the activities observed at Torness, which are only marginally enhanced above the natural background activity, are possibly due to discharges from Sellafield; however, the significant 14C enhancements at Hartlepool are not Sellafield-derived. Furthermore, since both reactors have the same fundamental design, the low activities at the Torness AGR imply that the activities at Hartlepool are not from the AGR, suggesting that there is an input of 14C to the marine environment in the vicinity of Hartlepool which is probably non-nuclear-power related. However, there is no other authorized site in the area that could account for the observed 14C enrichments; therefore, further research is required to ascertain the source of this 14C.
In recent years, the most common technique for radiocarbon dating of deep-ocean sediments has been accelerator mass spectrometry (AMS) analysis of hand-picked planktonic foraminifera (forams). Some studies have exposed age offsets between different sediment size fractions from the same depth within a core and this has important implications when establishing a chronological framework for palaeoceanographic records associated with a particular sediment component. The mechanisms generating the age offsets are not fully understood, a problem compounded by the fact that the fraction defined as “large” varies between different studies. To explore this problem, we dated samples of hand-picked forams from two Biogeochemical Ocean Flux Study (BOFS) cores, for which the presence of an offset between the bulk carbonate and >150 μm foraminiferal calcite had already been demonstrated. The presence of a constant age offset between bulk carbonate and coarse fraction material at the two BOFS sites has been confirmed, but the magnitude of the offset is dependent on whether a simple size-separation technique or hand-picking of well-preserved forams is applied. This may be explained if the selection of well preserved forams biases the sample towards those specimens that have spent least time in the surface mixed layer (SML) or have undergone less size selective mixing. Modeling of the 14C profiles demonstrates that SML depth and sediment accumulation rates are the same for both the bulk and coarse sediment fractions, which is consistent with the hypothesis that size-selective mixing is responsible for the age offset.
Radiocarbon is an important constituent of the low level, liquid, radioactive effluent discharged from the Sellafield nuclear fuel reprocessing plant in northwest England, but despite the fact that it gives the highest collective dose commitment of all the nuclides in the waste, its behavior in the Irish Sea is poorly defined. There is therefore a clear requirement for an improved understanding of 14C behavior in the Irish Sea, to assist with dose evaluation modeling and definition of the mixing and accumulation characteristics of the sediment in this area. In this context, results are presented here for a temporal study of 14C activities in four geochemical fractions of seawater and in a sediment core from the vicinity of the Sellafield effluent outfall. Clear 14C enrichments in the dissolved inorganic carbon (DIC) and particulate organic carbon (POC) components of seawater were observed, with temporal trends in activity that were related to variations in the Sellafield discharge. Smaller, but nevertheless detectable, enrichments were also observed for particulate inorganic carbon (PIC) and dissolved organic carbon (DOC) in the seawater. The distribution of 137Cs and 241Am revealed that the sediment core could be classified into three zones in which the intensity of mixing decreased discontinuously with depth. Bulk carbonate 14C analyses of the core demonstrated the presence of glacial or pre-glacial carbonate in the system, but failed to show any evidence of contaminant 14C input or provide information on sediment accumulation processes. In contrast, analysis of bulk organic matter from the sediment provided clear evidence of the recent perturbation of a well mixed system by input of younger material, consistent with the recent input of contaminant 14C from Sellafield and possibly weapons testing fallout.
The intertidal biota from Parton beach, close to the Sellafield nuclear fuel reprocessing plant, were all found to be enriched in radiocarbon relative to ambient background. The degree of enrichment appears to reflect the positions of the biota in the food chain once the dilution in seaweed from atmospheric uptake is taken into account. Close to the low-water mark, the order was mussels > limpets > anemones winkles > seaweed. The same order was observed close to the high-water mark, except that anemones were absent from this area. The activities in the biogeochemical fractions of the water column reflect the fact that discharges are primarily in the form of dissolved inorganic carbon (DIC), which is subsequently transferred to the particulate organic carbon (POC) and, to a lesser extent, the dissolved organic carbon (DOC), and finally, the particulate inorganic carbon (PIC). Analysis of intertidal sediment suggests that there is likely to be a gradual increase in the specific activity of 14C in the inorganic component of this material as Sellafield contaminated organisms die and their shells are ground down by natural processes.
Since the early 1950s, the Sellafield nuclear fuel reprocessing plant in Northwest England has released radiocarbon into the Irish Sea in a mainly inorganic form as part of its authorized liquid effluent discharge. In contrast to the trend in which the activities of most radionuclides in the Sellafield liquid effluent have decreased substantially, 14C discharges have increased since 1994–95. This has largely been due to a policy change favoring marine discharges over atmospheric discharges. 14C is radiologically important due to its long half life, mobility in the environment, and propensity for entering the food chain. Current models for radionuclide dispersal in the Irish Sea are based on a reversible equilibrium distribution coefficient (kd), an approach which has been shown to be inadequate for 14C. Development of predictive models for the fate of Sellafield-derived 14C requires a thorough understanding of the biogeochemical fluxes between different carbon reservoirs and the processes controlling the net flux of 14C out of the Irish Sea, through the North Channel. In this study, both an empirical and a halving time approach indicate that close to 100% of the 14C that is discharged from Sellafield is dispersed beyond the Irish Sea on a time-scale of months in the form of DIC, with little transfer to the PIC, POC, and DOC fractions, indicating that the “dilute and disperse” mechanism is operating satisfactorily. This is consistent with previous research that indicated little transfer of 14C to Irish Sea sediments. While significant 14C enhancements have been observed in the biota of the Irish Sea, this observation is not necessarily in conflict with either of the above as the total biomass has to be taken into account in any calculations of 14C retention within the Irish Sea.
During the period from 1995 to 2011, radiocarbon measurements from the coast around Hartlepool in NE England have revealed anomalous enrichments in seawater, sediment, and marine biota. These cannot be explained on the basis of atomic weapons testing or authorized nuclear industry discharges, including those from the nearby advanced gas-cooled reactor. Enhanced 14C-specific activities have also been observed since 2005 in biota during routine monitoring at Hartlepool by the Food Standards Agency, but are reported as “likely” originating from a “nearby non-nuclear source.” Studies undertaken in Hartlepool and Teesmouth during 2005 and 2011 suggest that the 14C discharges are in the vicinity of Greatham Creek, with activity levels in biota analogous to those measured at Sellafield, which discharges TBq activities of 14C per annum. However, if the discharges are into Greatham Creek or even the River Tees, it is proposed that they would be much smaller than those at Sellafield and the high specific activities would be due to much smaller dilution factors. The discharge form of the 14C remains unclear. The activity patterns in biota are similar to those at Sellafield, suggesting that initial inputs are dissolved inorganic carbon (DI14C). However, the mussel/seaweed ratios are more akin to those found around Amersham International, Cardiff, which is known to discharge 14C in an organic form. 14C analysis of a sediment core from Seal Sands demonstrated excess 14C to the base of the core (43–44 cm). 210Pb dating of the core (0–32 cm) produced an accumulation rate of 0.7 g cm−2 yr−1, implying that 14C discharges have occurred from the 1960s until the present day.
From 1994 onwards, radiocarbon discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of northeast Irish Sea sediments would increase in 14C activity as mollusk shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and subtidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago.
This article reports on the fourth stage of an evolving study to develop a systems model for embedding education for sustainability (EfS) into preservice teacher education. The fourth stage trialled the extension of the model to a comprehensive state-wide systems approach involving representatives from all eight Queensland teacher education institutions and other key policy agencies and professional associations. Support for trialling the model included regular meetings among the participating representatives and an implementation guide. This article describes the first three stages of developing and trialling the model before presenting the case study and action research methods employed, four key lessons learned from the project, and the implications of the major outcomes for teacher education policies and practices. The Queensland-wide, multi-site case study revealed processes and strategies that can enable institutional change agents to engage productively in building capacity for embedding EfS at the individual, institutional, and state levels in preservice teacher education. Collectively, the project components provide a system-wide framework that offers strategies, examples, insights, and resources that can serve as a model for other states and/or territories wishing to implement EfS in a systematic and coherent fashion.
An 8-year-old girl with supraventricular tachycardia and an implanted vagus nerve stimulator underwent radiofrequency ablation of her supraventricular tachycardia substrate. No known literature exists addressing the potential interaction of these two technologies, although there are reported cases of interaction between radiofrequency and other implanted stimulating devices such as pacemakers. The procedure was performed successfully without observed interaction, and the patient’s family reported no significant change in frequency of seizure control.
The unique environment of the Mediterranean Sea makes fish stock assessment a major challenge. Stock identification of Mediterranean fisheries has been based mostly from data on biology, morphometrics, artificial tags, otolith shape and fish genetics, with less effort on the use of parasites as biomarkers. Here we use some case studies comparing Mediterranean vs Atlantic fish stocks in a multidisciplinary framework. The generalized Procrustes Rotation (PR) was used to assess the association between host genetics and larval Anisakis spp. datasets on demersal (hake) and pelagic (horse mackerel, swordfish) species. When discordant results emerged, they were due to the different features of the data. While fish population genetics can detect changes over an evolutionary timescale, providing indications on the cohesive action of gene flow, parasites are more suitable biomarkers when considering fish stocks over smaller temporal and spatial scales, hence giving information of fish movements over their lifespan. Future studies on the phylogeographic analysis of parasites suitable as biomarkers, and that of their fish host, performed on the same genes, will represent a further tool to be included in multidisciplinary studies on fish stock structure.
Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.
Bentonite is one of the more safety-critical components of the engineered barrier system in the disposal concepts developed for many types of radioactive waste. It is used due to its favourable properties (including plasticity, swelling capacity, colloid filtration, low hydraulic conductivity, high retardation of key radionuclides) and its stability in relevant geological environments. However, bentonite is unstable under alkaline conditions and this has driven interest in low-alkali cements (leachate pH of 10–11). To build a robust safety case, it is important to have supporting natural analogue data to confirm understanding of the likely long-term performance of bentonite. In Cyprus, the presence of natural bentonite in close proximity to natural alkaline groundwaters permits the zones of potential bentonite/alkaline water reaction to be studied as an analogy of the potential reaction zones in the repository. Here, the results indicate minimal volumetric reaction of bentonite, with production of a palygorskite secondary phase.
In this work we report a specialized reactive force field (ReaxFF) developed for the study of alumina/epoxy interfaces. Force field parameters were obtained by fitting the reactions of small clusters and separate components of epoxies on alumina surfaces in the alpha phase. We also introduce a procedure to obtain crosslinked epoxies based on a proximity criterion to drive reactions and induce crosslinking. Properties of the resulting polymer, like the coefficient of thermal expansion, are found to be of the same order of magnitude as in experiments. Molecular dynamics was used to calculate the adhesion between these polymers and different alumina surfaces: Al2O3-deficient, Al-terminated, O-terminated, 12% and 75% hydroxylated. Typical values for strong adhesion are about 0.70 J/m2 which compare well with previously reported works. The role of defects is also studied.
To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.
We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.
Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).
While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.
Samples from the various horizons of five soil profiles representative of diverse types widely occurring in north-east Scotland were intensively examined, after separation into particle-size fractions, by appropriate instrumental and chemical techniques including optical examination, X-ray diffraction, electron microscopy and diffraction, infra-red absorption spectroscopy, thermal analysis procedures, chemical analysis and selective chemical dissolution. The results obtained are presented and assessed with respect to quantitative estimation of the mixed SiO2-Al2O3-Fe2O3 gel system occurring in these soils. At best results can be only semiquantitative, but interesting trends are observable in each profile and marked differences are noted between profiles on different parent materials, although this effect is somewhat obscured under impeded drainage conditions. The maturity of the soil is also a significant factor. Results in general can be explained in terms of current concepts on pedogenesis.