398 research outputs found
Liver Transplantation for Advanced Liver Disease with Alpha-1antitrypsin Deficiency
ALPHA-1-antitrypsin deficiency associated with chronic obstructive airway disease was recognized in 1963 by Laurell and Ericksson.1 In 1969, Sharp2 described the first cases of alpha-1-antitrypsin-deficiency disease in children with cirrhosis. Since then, this inborn error has been recognized as one of the more common factors in cirrhosis of infancy and childhood,3 including “neonatal hepatitis.”4 Alpha-1-antitrypsin is a glycoprotein that accounts for a major portion of the alpha-1 globulin fraction of the serum.5 It is responsible for approximately 90 per cent of the antitrypsin activity6 of the serum, and it also inhibits several other plasma enzymes, including plasmin,7 elastase,8 collagenase,9 and. © 1980, Massachusetts Medical Society. All rights reserved
The incidence of childhood and adolescent seizures in the UK from 1999 to 2011:a retrospective cohort study using the Clinical Practice Research Datalink
Libri novi
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43281/1/11046_2005_Article_BF02052587.pd
Correction: Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.
The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials
Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.
The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials
Understanding visual hallucinations: a new synthesis.
Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active inference, and Thalamocortical Dysrhythmia Default Mode Network Decoupling. Each was derived from different understandings of brain organisation. To reduce this variability, representatives from each research group agreed an integrated Visual Hallucination Framework that is consistent with current theories of veridical and hallucinatory vision. The Framework delineates cognitive systems relevant to hallucinations. It allows a systematic, consistent, investigation of relationships between the phenomenology of visual hallucinations and changes in underpinning cognitive structures. The episodic nature of hallucinations highlights separate factors associated with the onset, persistence, and end of specific hallucinations suggesting a complex relationship between state and trait markers of hallucination risk. In addition to a harmonised interpretation of existing evidence, the Framework highlights new avenues of research, and potentially, new approaches to treating distressing hallucinations
The 'Fed Model' and the Changing Correlation of Stock and Bond Returns: An Equilibrium Approach
Tackling barriers to COVID-19 vaccine uptake in London: a mixed-methods evaluation
BACKGROUND: In response to the COVID-19 pandemic, the first vaccine was administered in December 2020 in England. However, vaccination uptake has historically been lower in London than in other English regions. METHODS: Mixed-methods: This comprised an analysis of cumulative percentage uptake across London between 8 December 2020 and 6 June 2021 by vaccine priority cohorts and ethnicity. We also undertook thematic analyses of uptake barriers, interventions to tackle these and key learning from a qualitative survey of 27 London local authority representatives, vaccine plans from London's five Integrated Care Systems and interviews with 38 London system representatives. RESULTS: Vaccine uptake was lower in Black ethnic (57-65% uptake) compared with the White British group (90% uptake). Trust was a critical issue, including mistrust in the vaccine itself and in authorities administering or promoting it. The balance between putative costs and benefits of vaccination created uptake barriers for zero-hour and shift workers. Intensive, targeted and 'hyper-local' initiatives, which sustained community relationships and were not constrained by administrative boundaries, helped tackle these barriers. CONCLUSIONS: The success of the national vaccination programme depended on conceding local autonomy, investing in responsive and long-term partnerships to engender trust through in-depth understanding of communities' beliefs
NRP/Optineurin Cooperates with TAX1BP1 to Potentiate the Activation of NF-ÎşB by Human T-Lymphotropic Virus Type 1 Tax Protein
Nuclear factor (NF)-ÎşB is a major survival pathway engaged by the Human T-Lymphotropic Virus type 1 (HTLV-1) Tax protein. Tax1 activation of NF-ÎşB occurs predominantly in the cytoplasm, where Tax1 binds NF-ÎşB Essential Modulator (NEMO/IKKÎł) and triggers the activation of IÎşB kinases. Several independent studies have shown that Tax1-mediated NF-ÎşB activation is dependent on Tax1 ubiquitination. Here, we identify by co-immunoprecipitation assays NEMO-Related Protein (NRP/Optineurin) as a binding partner for Tax1 in HTLV-1 infected and Tax1/NRP co-expressing cells. Immunofluorescence studies reveal that Tax1, NRP and NEMO colocalize in Golgi-associated structures. The interaction between Tax1 and NRP requires the ubiquitin-binding activity of NRP and the ubiquitination sites of Tax1. In addition, we observe that NRP increases the ubiquitination of Tax1 along with Tax1-dependent NF-ÎşB signaling. Surprisingly, we find that in addition to Tax1, NRP interacts cooperatively with the Tax1 binding protein TAX1BP1, and that NRP and TAX1BP1 cooperate to modulate Tax1 ubiquitination and NF-ÎşB activation. Our data strongly suggest for the first time that NRP is a critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-ÎşB activation
RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus
Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson’s disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia
- …