| 1. |
- Cable, Jennifer, et al.
(författare)
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Lessons from the pandemic : Responding to emerging zoonotic viral diseases-a Keystone Symposia report
- 2022
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1518:1, s. 209-225
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
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| 2. |
- Mullin, Stephen, et al.
(författare)
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Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial.
- 2020
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 77:4, s. 427-34
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Tidskriftsartikel (refereegranskat)abstract
- Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD.To assess safety, tolerability, cerebrospinal fluid (CSF) penetration, and target engagement of ambroxol therapy with GCase in patients with PD with and without GBA1 mutations.An escalating dose of oral ambroxol to 1.26 g per day.This single-center open-label noncontrolled clinical trial was conducted between January 11, 2017, and April 25, 2018, at the Leonard Wolfson Experimental Neuroscience Centre, a dedicated clinical research facility and part of the University College London Queen Square Institute of Neurology in London, United Kingdom. Participants were recruited from established databases at the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London. Twenty-four patients with moderate PD were evaluated for eligibility, and 23 entered the study. Of those, 18 patients completed the study; 1 patient was excluded (failed lumbar puncture), and 4 patients withdrew (predominantly lumbar puncture-related complications). All data analyses were performed from November 1 to December 14, 2018.Primary outcomes at 186 days were the detection of ambroxol in the CSF and a change in CSF GCase activity.Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P<.001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, -0.115 to -0.002; P=.04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P=.01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P=.002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, -10.4 to -3.1; P=.001). These changes were observed in patients with and without GBA1 mutations.The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD.ClinicalTrials.gov identifier: NCT02941822; EudraCT identifier: 2015-002571-24.
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| 3. |
- Read, Joy, et al.
(författare)
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The Lived Experience of Caregiving and Perception of Service Provision among Family-Caregivers of People with Late-Stage Parkinson's : A Qualitative Study
- 2023
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Ingår i: Parkinson's Disease. - : Hindawi Limited. - 2042-0080 .- 2090-8083. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Background: The complex nature of late-stage Parkinson's requires multiagency support and leads to an increased burden on family members who assume a multiplicity of responsibilities. The aim of this study is to further understand the lived experiences of family-caregivers and their perception of, and satisfaction with, service provision. Methods. This qualitative substudy was a part of the European multicentre Care of Late-Stage Parkinsonism (CLaSP) project. Purposive sampling resulted in a sample of eleven family-caregivers of people with late-stage Parkinson's, who were interviewed using semistructured open-ended questions. Thematic analysis followed. Findings. Three overarching themes were developed from the data: ensuring continuous support is vital to providing care at home, perceiving unmet service provision needs, and advocating and co-ordinating all aspects of care take their toll. These themes include not only experience of services that caregivers find supportive in order to deliver care but also of disjointed care between multiple agencies, a perceived lack of Parkinson's expertise, and there was a lack of anticipatory future planning. The constancy and scope of the family-caregiver role is described, including the need to project manage multiple aspects of care with multiple agencies, to be an advocate, and to assume new roles such as managing finances. Multiple losses were reported, which in part was mitigated by gaining expertise through information and support from professionals and organised and informal support. Conclusion. The intricacies and consequences of the family-caregivers' role and their experience of service provision indicate the need to acknowledge and consider their role and needs, fully involve them in consultations and provide information and joined-up support to improve their well-being, and ensure their continuous significant contribution to the ongoing care of the person with Parkinson's.
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| 4. |
- Zuntini, Alexandre R., et al.
(författare)
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Phylogenomics and the rise of the angiosperms
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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