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Background: Plasma pTau217 is a robust biomarker for the diagnosis of Alzheimer’s disease (AD). However, most pTau217 assays are not widely available for clinical testing. We assessed the performance of two commercially available plasma pTau217 immunoassays in a clinical diagnostic laboratory for AD diagnosis. Methods: 219 plasma samples from healthy controls with negative amyloid PET, 115 plasma samples from pathology-confirmed and 263 samples with confirmed amyloid PET were selected. Plasma pTau217 levels were measured using the ALZpath pTau217 assay on the Quanterix HD-X Simoa platform and the Lumipulse pTau217 assay on the Lumipulse G1200 platform at and BC Neuroimmunology Lab and Neurocode USA. Results: For the ALZpath assay, the coefficients were 10.4%, 10.4%, and 9.9%, and for the Fujirebio assay, were 12.1%, 12.2%, and 5.3%, respectively. Sample stability and interference were similar between the two assays, although moderate heterophilic antibody interference and reduced frozen sample stability at -20˚C were observed for the Fujirebio assay. Both assays demonstrated similar clinical performance and differentiated individuals with AD (ALZpath AUC = 0.94; Fujirebio AUC = 0.90). Conclusions: The performance of the two pTau 217 assays was comparable. The clinical separation between the healthy controls and those with Amyloid pathology was nearly complete for both assays.
Mentored undergraduate research experiences (UREs) can play a critical role in developing science identity and skills, especially for students from historically underrepresented backgrounds. This study investigates science identity and responsibility for scientific roles among scholars in a program aiming to diversify the biomedical workforce. Scholars were placed in UREs at either their home institution (a minority-serving institution [MSI]) or at a research-intensive medical institution with a Clinical and Translational Science Award (CTSA).
Methods:
We analyze data from surveys administered annually to the scholars. We first compare changes in science identity for scholars placed at the MSI and the CTSA site from the term after the scholar started their URE to one year later. We then analyze differences in responsibility in scientific roles performed by scholars at the two institutions.
Results:
We found evidence of gains in science identity after a year for scholars placed at both institutions but of a somewhat larger magnitude at the CTSA site. However, no significant differences were observed across institutions on science identity at the endpoint. An exploration of scientific roles suggests that scholars at the CTSA site assumed more responsibility in roles related to data curation and analysis, while scholars at the MSI had higher responsibility for resource acquisition-related roles.
Conclusion:
These results suggest that CTSA site URE placements may offer distinct opportunities for both identity formation and skill development beyond placements at home institutions. Overall, these results suggest opportunities for partnerships between MSIs and CTSA sites in the training of biomedical researchers.
This book brings together political philosophers, democratic theorists, empirical political scientists and policy experts to examine how democratic systems might be designed so that the long-term consequences of our decisions are considered in policymaking processes. It examines these topics from many different perspectives - it is interdisciplinary and globally oriented - but it also explores Finland as an example of how future-regarding governance might be done. Finland has one of the most advanced governmental foresight systems in the world, including a unique parliamentary institution called the 'Committee for the Future', and it has enjoyed a stable, multiparty government for decades. The contributors identify tensions between the present and the future, as well as between reversibility and commitment, independence and politicisation, and trust and critique, which have to be navigated in order to achieve long-term, collective goals. The book concludes that elite-driven institutions should be complemented by robust institutions for public participation and deliberation in order to retain responsiveness while at the same time forging public commitments for future-regarding action.
The thermal reaction sequence of a synthetic hectorite (Laponite CP) was studied by X-ray diffraction, i.r. spectroscopy and thermal analysis. Although most of the interlayer water is removed at 200°C, a smally steady weight loss occurs until dehydroxylation is complete at about 700°C, indicating that an anhydrous intermediate phase is not formed prior to dehydroxylation. Immediately after dehydroxylation, enstatite and cristobalite can be identified, but lithium silicates are formed only from lithium-saturated hectorite. Around 1200°C a glass is formed by reaction of the alkalis with cristobalite, and removal of silica from the enstatite produces some forsterite. An inhomogeneous mechanism of dehydroxylation is postulated by analogy with that proposed for talc.
Background: Frontotemporal dementia (FTD) often presents with varying neuropsychiatric symptoms (NPS), which may differ based on genetic mutations. We hypothesized distinct NPS trajectories in FTD progression among carriers of chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) mutations. Methods: We analyzed 1662 participants from ALLFTD, including 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers. We categorized participants into four stages based on CDR plus NACC FTLD global scores: 1) Presymptomatic (consistent CDR=0), 2) Early conversion (CDR increasing from 0 to 0.5), 3) Advanced conversion (CDR increasing from 0.5 to ≥1.0), and 4) Symptomatic (CDR>1.0). The Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed NPS changes, analyzed using a mixed-effects model, accounting for age and baseline scores. Results: Our results indicated similar NPS trajectories in the presymptomatic stage for all groups. Notably, during early conversion, C9orf72 and GRN carriers exhibited significantly higher NPI-Q score increases than MAPT carriers, primarily in psychosis and hyperactivity domains. In later stages, increases in NPS were similar across groups. Conclusions: This study suggests familial FTD progression, particularly in TDP-43 pathology, may involve more severe NPS like psychosis or hyperactivity, differing from tau pathology or sporadic FTD. Further research is needed to explore these distinct trajectories.
Burial diagenetic reactions of di- and trioctahedral clay minerals were compared in Brazilian offshore, basinal sediment sequences of Cretaceous age. Originally dioctahedral smectite-rich shales of three basins—Potiguar,Ceara, and Ilha de Santana—exhibited the classical smectite-to-illite burial pattern. Trioctahedral clay-rich shales and trioctahedral clay-mineral cements in sandstones, however, showed a burial sequence of saponite to mixed-layer chlorite/saponite with progressive increase in the percentage of chlorite layers with increasing burial depth.
The change from disordered to ordered interstratifications of chlorite/saponite occurred in the temperature range 60°-70°C at a vitrinite reflectance value of about 0.65. These values are lower than those found for the ordering of illite/smectite clays. Increasing substitution of Al for Si in tetrahedral sites, followed by fixation of interlayer hydroxide sheets was found to be the major chemical change promoting transformation of saponite to chlorite via corrensite.
Solid-state nuclear magnetic resonance (NMR) spectroscopy, thermal analysis, and X-ray powder diffraction data on the tubular, hydrous aluminosilicate imogolite were found to be fully consistent with a previously proposed crystal structure consisting of a rolled-up, 6-coordinate Al-O(OH) sheet, bonded to isolated orthosilicate groups. The calculated 29Si chemical shift of this structure agreed with the observed shift within 3 ppm. Thermal dehydroxylation of the Al-O(OH) sheet produced predominantly NMR-transparent 5-coordinate Al, but a few 4- and 6-coordinate sites and some residual hydroxyl groups may also have formed, as shown by NMR spectroscopy. Changes in the 29Si NMR spectrum on dehydroxylation suggest a condensation of the orthosilicate groups, but steric considerations rule out bonding between adjacent silicons. To account for these observations, an alternative mechanism to orthosilicate condensation has been proposed, involving the fracture and unrolling of the tubes, followed by the condensation of fragments to form a layer structure. The layer structure has a calculated 29Si chemical shift of -95.6 ppm, in good agreement with the observed value of -93 ppm.
Examination of two volcanic and two precipitated allophanes by solid-state NMR, thermal analysis and X-ray powder diffraction shows three of the samples to contain structural features similar to both tubular imogolite and defect layer-lattice aluminosilicates such as kaolinite. The fourth allophane, a precipitated sample from New Zealand, had no imogolite-like features and contained tetrahedral as well as octahedral aluminum. The imogolite-like units in allophane are less stable thermally than tubular imogolite. The NMR spectra and their changes on heating can be accounted for by a structural model in which a two-sheet, kaolinite-like structure containing defects (holes in the tetrahedral sheet) is curved into a sphere in which imogolite-like orthosilicate units are anchored into the octahedral sheet and fit into the tetrahedral defects. Computer simulation shows that the model is crystallographically sound, and accounts for all the known facts, including the spherical morphology, the solid-state NMR spectra and the thermal dehydroxylation behavior of all except the New Zealand allophane, which is of a different structural type.
Common data elements (CDEs) for concussion, as established by international bodies, are not being widely used in Ontario, resulting in significant variability in the data being assessed and collected across clinics. CDEs support standardization of care as well as large-scale data sharing for high impact research. A collaborative network – Concussion Ontario Network: Neuroinformatics to Enhance Clinical care and Translation (CONNECT) – comprised of health care professionals, researchers, members from advocacy groups, and patients was formed to establish and implement CDEs for concussion care and research. While the seeds have been planted and initial effectiveness demonstrated, future challenges exist.
Brazilian peppertree (Schinus terebinthifolia Raddi) is an aggressive shrub that infests more than 280,000 ha in Florida. Individual plant treatments (IPT), including basal bark and cut stump application with triclopyr butoxyethylester and triethylamine formulations, respectively, have been used for decades. While they are both effective, resprouting can occur, which requires retreatment for control. Recent research on other woody invasive plants has indicated additional non-crop herbicides used in natural areas can be effective with these IPT techniques and therefore warrant testing on S. terebinthifolia. In 2018 and 2019, basal bark and cut stump studies were conducted at Cape Canaveral Air Force Station in natural areas infested with S. terebinthifolia. In the basal bark application studies, we found aminocyclopyrachlor applied at 12 and 24 g L−1 and triclopyr acid applied at 34 and 69 g L−1 each provided 100% defoliation of multistemmed S. terebinthifolia individuals with a mean root collar diameter up to 20.2 cm at 360 d after treatment (DAT). These were not different from triclopyr ester applied at 96 g L−1. Imazamox applied at 30 g L−1 resulted in 86% defoliation at 360 DAT. However, we observed formulation incompatibility when imazamox was mixed with basal bark oil which may limit its utility. In cut stump studies, we found aminocyclopyrachlor and aminopyralid each individually applied at 6, 12, and 24 g L−1, resulted in stump mortality that was not different from the commercial standard triclopyr amine applied at 180 g L−1. Similar results were found for a triclopyr acid formulation applied at 86 and 172 g L−1 and imazamox applied at 60 g L−1. For both treatment techniques, we found that alternative treatments provided control at lower herbicide concentrations than triclopyr ester and amine commercial standards. These results advance our understanding of IPT and expand access to additional effective herbicide options for S. terebinthifolia management.
Brazilian peppertree (Schinus terebinthifolia Raddi) is a multistemmed shrub or small tree from South America that is invasive in Florida, Texas, Hawaii, and Australia. It forms multistemmed trunks with spreading branches that create dense thickets. State agencies in Florida manage it at annual costs of over $3 million, and individual plant treatment (IPT) techniques are widely used for control. Recent research testing novel hack and squirt approaches with aminopyralid and aminocyclopyrachlor and basal bark treatment with a new triclopyr formulation has shown these treatments are highly effective. However, they have not been evaluated at larger scales, which would be useful to land managers. Therefore, our objective was to compare the reduced hack and squirt technique using aminopyralid and aminocyclopyrachlor herbicides to basal bark treatment with triclopyr on a field scale. We used two contractor crews to apply treatments to twenty-four 0.2-ha plots. Treatments included aminocyclopyrachlor (120 g L−1) or aminopyralid (120 g L−1) applied with the reduced hack and squirt technique and triclopyr ester (108 g L−1) and triclopyr acid (34 g L−1) formulations applied with two basal bark treatment techniques. We confirmed that reduced hack and squirt significantly reduced the amount of herbicide and carrier applied compared with the basal bark treatments. By 540 d after treatment, aminocyclopyrachlor more effectively controlled S. terebinthifolia than aminopyralid with reduced hack and squirt and resulted in control comparable to that seen with either triclopyr basal bark treatment. These results verify reduced hack and squirt treatment with aminocyclopyrachlor and basal bark treatment with triclopyr acid as alternatives to basal bark treatment with triclopyr ester. Both resulted in significantly less herbicide use with comparable efficacy. This operational research approach has accelerated our understanding of novel IPT strategies and their implementation in the field.
Background: Patient registries are an effective tool in tracking the natural history of rare diseases as well as post-marketing surveillance of novel therapies. The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects Spinal Muscular Atrophy (SMA)-specific data in 28 clinics across Canada. The objective of this study is to describe real-world data from the CNDR-SMA patient population. Methods: We report cross-sectional data from Canadian SMA patients. Patients were included in analysis if they were active (alive and with follow-up within 24 months). Results: Of 171 SMA patients included in analyses, 37% currently use non-invasive ventilation, 2% invasive ventilation, and 61% no ventilation support. Feeding tubes are used by 27% of patients. and 28% of patients have a history of scoliosis surgery. Of the 171 patients, 137 have had disease-modifying therapy: 96 on nusinersen, 22 on risdiplam, and 19 on onasemnogene abeparvovec (OA). Median (min,max) years of age at therapy initiation was 7 (0,54), 20.5 (5,53), and 1 (0,6), respectively. At therapy initiation, functional status was 32% non-sitters, 38% sitters, and 30% walkers. Conclusions: The CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada.
Can democratic institutions help us to act in future-regarding ways? Many people – even committed democrats – have their doubts. Representative democracies, especially those with well-functioning bureaucracies, tend to provide their people with relatively high levels of economic prosperity and social welfare (Norris 2012). Overall, democratic systems fare better in this respect than autocratic ones, even those with high levels of state capacity. But it is not clear that democratic systems are equally good at ensuring the welfare of their people over the long term or acting with the potential interests of future others in mind.
Governments have failed to address climate change, plastics pollution, the loss of biodiversity, generational reproductions of racism and inequality, and many other long-term problems. Most countries also have huge – and growing – public debts that cannot be sustained over the long term. Furthermore, it is now apparent that no country was adequately prepared to deal with the Covid-19 pandemic, despite advance warnings from many public health experts. Even wealthy, stable democracies, such as Switzerland, often have trouble making investments in the future. Recent attempts to reform the Swiss public pension system by raising the retirement age have been rejected several times in referenda, even though it is clear that the system, as it exists, is unsustainable over the long term (Bello and Galasso 2021).
These examples seem to suggest that democracies – like other regimes – are myopic and seek to maximise short-term welfare at the expense of the future. As Alan Jacobs (2008) points out, politics is not just about the distribution of costs and benefits between people, it is also about the distribution of costs and benefits over time. But political regimes, of all types, have reasons to neglect the future in favour of the present. As the authors of the Brundtland Report state in their opening chapter: ‘We act as we do because we can get away with it: future generations do not vote; they have no political or financial power; they cannot challenge our decisions’ (World Commission on Environment and Development 1987: 8).