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- Janssen, O., et al.
(author)
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Characteristics of subjective cognitive decline associated with amyloid positivity
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1832-1845
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Journal article (peer-reviewed)abstract
- Introduction The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) epsilon 4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE epsilon 4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion Next to age, setting, and APOE epsilon 4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
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- Franke, A., et al.
(author)
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Status and trends of circumpolar peregrine falcon and gyrfalcon populations
- 2020
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:3, s. 762-783
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Journal article (peer-reviewed)abstract
- The peregrine falcon (Falco peregrinus) and the gyrfalcon (Falco rusticolus) are top avian predators of Arctic ecosystems. Although existing monitoring efforts are well established for both species, collaboration of activities among Arctic scientists actively involved in research of large falcons in the Nearctic and Palearctic has been poorly coordinated. Here we provide the first overview of Arctic falcon monitoring sites, present trends for long-term occupancy and productivity, and summarize information describing abundance, distribution, phenology, and health of the two species. We summarize data for 24 falcon monitoring sites across the Arctic, and identify gaps in coverage for eastern Russia, the Arctic Archipelago of Canada, and East Greenland. Our results indicate that peregrine falcon and gyrfalcon populations are generally stable, and assuming that these patterns hold beyond the temporal and spatial extents of the monitoring sites, it is reasonable to suggest that breeding populations at broader scales are similarly stable. We have highlighted several challenges that preclude direct comparisons of Focal Ecosystem Components (FEC) attributes among monitoring sites, and we acknowledge that methodological problems cannot be corrected retrospectively, but could be accounted for in future monitoring. Despite these drawbacks, ample opportunity exists to establish a coordinated monitoring program for Arctic-nesting raptor species that supports CBMP goals.
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- Sexton, C. E., et al.
(author)
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Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 178-190
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Journal article (peer-reviewed)abstract
- The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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- Hoencamp, Claire, et al.
(author)
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3D genomics across the tree of life reveals condensin II as a determinant of architecture type
- 2021
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6545, s. 984-989
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Journal article (peer-reviewed)abstract
- We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.
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8. |
- Musahl, V., et al.
(author)
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Contributions of the anterolateral complex and the anterolateral ligament to rotatory knee stability in the setting of ACL Injury: a roundtable discussion
- 2017
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In: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 25:4, s. 997-1008
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Journal article (peer-reviewed)abstract
- Persistent rotatory knee laxity is increasingly recognized as a common finding after anterior cruciate ligament (ACL) reconstruction. While the reasons behind rotator knee laxity are multifactorial, the impact of the anterolateral knee structures is significant. As such, substantial focus has been directed toward better understanding these structures, including their anatomy, biomechanics, in vivo function, injury patterns, and the ideal procedures with which to address any rotatory knee laxity that results from damage to these structures. However, the complexity of lateral knee anatomy, varying dissection techniques, differing specimen preparation methods, inconsistent sectioning techniques in biomechanical studies, and confusing terminology have led to discrepancies in published studies on the topic. Furthermore, anatomical and functional descriptions have varied widely. As such, we have assembled a panel of expert surgeons and scientists to discuss the roles of the anterolateral structures in rotatory knee laxity, the healing potential of these structures, the most appropriate procedures to address rotatory knee laxity, and the indications for these procedures. In this round table discussion, KSSTA Editor-in-Chief Professor Jn Karlsson poses a variety of relevant and timely questions, and experts from around the world provide answers based on their personal experiences, scientific study, and interpretations of the literature.
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9. |
- Files, DC, et al.
(author)
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I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
- 2022
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In: BMJ open. - : BMJ. - 2044-6055. ; 12:6, s. e060664-
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Journal article (peer-reviewed)abstract
- The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021.Methods and analysisThe ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes—time to recovery and mortality. The statistical design uses a Bayesian model with ‘stopping’ and ‘graduation’ criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing.Ethics and disseminationISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals.Trial registration numberNCT04488081.
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10. |
- Musahl, V., et al.
(author)
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High-grade rotatory knee laxity may be predictable in ACL injuries
- 2018
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In: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:12, s. 3762-3769
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Journal article (peer-reviewed)abstract
- Purpose Lateral compartment acceleration and translation have been used to quantify rotatory knee laxity in the setting of anterior cruciate ligament (ACL) injury; however, their relationship remains elusive. The purpose of this study was to examine the correlation between lateral compartment acceleration and translation during pivot shift testing. It was hypothesized that a correlation would exist in ACL-injured and uninjured knees, irrespective of sex, but would be greatest in knees with combined ACL and lateral meniscus tear. Methods Seventy-seven patients (34 females, 25.2 +/- 9.0 years) undergoing primary single-bundle ACL reconstruction were prospectively enrolled in a 2-year study across four international centers. Patients underwent preoperative examination under anesthesia of the injured and uninjured knee using Image Analysis software and surface mounted accelerometer. Results A moderate correlation between lateral compartment acceleration and translation was observed in ACL-injured knees [rho = 0.36, p < 0.05), but not in uninjured knees (rho = 0.17, not significant (n.s.)]. A moderate correlation between acceleration and translation was demonstrated in ACL-injured knees with lateral meniscus tears (rho = 0.53, p < 0.05), but not in knees with isolated ACL-injury (rho = 0.32, n.s.), ACL and medial meniscus tears (rho = 0.14, n.s.), or ACL and combined medial and lateral meniscus tears (rho = 0.40, n.s.). A moderate correlation between acceleration and translation was seen in males (rho = 0.51, p < 0.05), but not in females (rho = 0.21, n.s.). Largest correlations were observed in males with ACL and lateral meniscus tears (rho = 0.75, p < 0.05). Conclusion Lateral compartment acceleration and translation were moderately correlated in ACL-injured knees, but largely correlated in males with combined ACL and lateral meniscus tears. ACL and lateral meniscus injury in males might, therefore, be suspected when both lateral compartment acceleration and translation are elevated. Surgeons should have a greater degree of suspicion for high-grade rotatory knee laxity in ACL-injured males with concomitant lateral meniscus tears. Future studies should investigate how these two distinct components of rotatory knee laxity-lateral compartment acceleration and translation-are correlated with patient outcomes and affected by ACL surgery.
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11. |
- Pavlik, Valory N., et al.
(author)
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Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD) : A Report of an International Research Collaboration Network
- 2022
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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:1, s. 31-45
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Research review (peer-reviewed)abstract
- Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer's disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed.
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- Zetterberg, Henrik, 1973, et al.
(author)
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Blood-based molecular biomarkers for Alzheimer's disease
- 2019
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In: Molecular Brain. - : Springer Science and Business Media LLC. - 1756-6606. ; 12
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Journal article (peer-reviewed)abstract
- A major barrier to the effective conduct of clinical trials of new drug candidates against Alzheimer's disease (AD) and to identifying patients for receiving future disease-modifying treatments is the limited capacity of the current health system to find and diagnose patients with early AD pathology. This may be related in part to the limited capacity of the current health systems to select those people likely to have AD pathology in order to confirm the diagnosis with available cerebrospinal fluid and imaging biomarkers at memory clinics. In the current narrative review, we summarize the literature on candidate blood tests for AD that could be implemented in primary care settings and used for the effective identification of individuals at increased risk of AD pathology, who could be referred for potential inclusion in clinical trials or future approved treatments following additional testing. We give an updated account of blood-based candidate biomarkers and biomarker panels for AD-related brain changes. Our analysis centres on biomarker candidates that have been replicated in more than one study and discusses the need of further studies to achieve the goal of a primary care-based screening algorithm for AD.
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