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| 4. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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- Scott, G. D., et al.
(författare)
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Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.
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| 8. |
- Laabei, M., et al.
(författare)
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Predicting the virulence of MRSA from its genome sequence
- 2014
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 24:5, s. 839-849
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Tidskriftsartikel (refereegranskat)abstract
- Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen's evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate's toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.
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| 9. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 10. |
- Reed, Mark S., et al.
(författare)
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The future of the uplands
- 2009
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Ingår i: Land use policy. - : Elsevier Limited. - 0264-8377 .- 1873-5754. ; 26:Supplement 1
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Tidskriftsartikel (refereegranskat)abstract
- Upland areas provide UK society with many important functions, goods and services, but have experienced a number of disturbing trends and face an uncertain future. This paper outlines historic, current and future drivers of environmental, economic, socio-cultural and policy change in UK uplands, and assesses how these have affected or are likely to affect ways in which land is used and the provision of ecosystem services. Information is synthesised into scenarios summarising a range of possible futures anticipated for UK uplands to 2060 and beyond. Finally, innovations in science, technology, governance and policy are evaluated that could enable uplands to continue providing key ecosystem services under a range of scenarios. The paper concludes that many upland areas will need to be prepared for significant reductions in grazing and prescribed burning. Conversely, other areas could experience agricultural intensification, for example significant increases in grazing or an expansion of arable or bioenergy crops into upland valleys, due to anticipated increases in global demand for food and energy. These scenarios will take place in the context of climate change. Many may take place together and may interact with each other, with complex and unpredictable implications for the upland environment, economy and society. In this context, a number of advances are needed in science, technology and policy to maintain viable uplandcommunities and the future provision of ecosystem services. These may include funding for ecological and hydrological restoration via carbon offsetting or other means. It may also involve advances in ecosystem service modelling, mapping and valuation, which through stakeholder participation could facilitate more integrated rural planning. New forms of environmental governance need to be explored that can empower those interested in developing upland economies to maintain thriving upland communities, while managing the ecosystem services they provide as efficiently as possible.
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- Clase, CM, et al.
(författare)
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Can Peer Review Be Kinder? Supportive Peer Review: A Re-Commitment to Kindness and a Call to Action
- 2022
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Ingår i: Canadian journal of kidney health and disease. - : SAGE Publications. - 2054-3581. ; 9, s. 20543581221080327-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology “supportive review.”
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| 13. |
- Colbourne, JK, et al.
(författare)
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The Precision Toxicology initiative
- 2023
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Ingår i: Toxicology letters. - 1879-3169. ; 383, s. 33-42
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Allen, K. D., et al.
(författare)
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Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative
- 2023
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Ingår i: Osteoarthritis and Cartilage. - : ELSEVIER SCI LTD. - 1063-4584 .- 1522-9653. ; 31:7, s. 954-965
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by & GE;80% of participants were retained, and participants could suggest addi-tional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if & GE;80% rated it & GE;6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if & GE;80% of participants rated it & GE;9 and as "optional" if & GE;80% rated it & GE;7. Results: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. Conclusion: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
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| 17. |
- Barocchi, M A, et al.
(författare)
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A pneumococcal pilus influences virulence and host inflammatory responses
- 2006
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:8, s. 2857-2862
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
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| 20. |
- Eyles, J.P., et al.
(författare)
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Clinical Outcomes Of Osteoarthritis Management Programs: A Project Of The Oa Trial Bank And Oarsi Joint Effort Initiative Using Individual Participant Data
- 2023
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 31, s. S385-S386
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: People living with osteoarthritis (OA) often do not receive best evidence care. Coordinated OA management programs (OAMPs) have been implemented to address this global evidence-practice gap. An OAMP is defined as a package of care with the following: i) a personalized management plan; ii) with reassessment and progression; iii) using a minimum of 2 core treatments (education, exercise, weight control), and; iv) optional adjunctive therapies. Existing OAMP models differ in treatment mode, intensity, duration, the health professionals delivering care, and the healthcare systems and settings they operate within. Randomized trials (RCTs) and cohort studies assess the outcomes of different OAMPs, however, these models are unlikely to ever be compared in RCTs due to the huge expense and complicated logistics required. Prognosis research provides another method of comparing outcomes of different OAMP models. This study aimed to estimate the pain and self-reported function outcomes (at 12-, 26- and 52-weeks) of people with hip and/or knee OA who participated in international OAMPs. It also aimed to describe the characteristics of OAMP participants.Methods: This study was undertaken by members of the OARSI Joint Effort Initiative (JEI), in collaboration with the OA Trial Bank (Erasmus MC, Netherlands). RCTs and clinical cohorts assessing OAMPs were identified through the JEI membership and literature searches. Eligible studies included data from an ongoing OAMP, in any real-world setting, with participants who were diagnosed with hip or knee OA, and longitudinal measures of patient-reported pain and function. The investigators of eligible studies were invited to complete data delivery agreements with the OA Trial Bank, share individual participant data (IPD), contribute to study design and authorship. Investigators ensured they had local ethics review board approval to contribute IPD to the OA Trial bank. Each dataset was converted to a common format to enable merging into one dataset. The IPD were evaluated to convert pain and function variables to standardized scales as appropriate. Pain scores were converted to a 0-100 point scale (100 worst). Function scores were converted to a 0-100 point scale (100 best). A generalized estimating equations (GEE) model analysis was performed to assess the change in pain and function from baseline across weeks 12, 26, and 52. The model specification was based on an unstructured correlation structure and robust standard errors. Pain and function estimates were adjusted by age, sex and body mass index (BMI). Data analyses were carried out using Stata 15 (StataCorp 2015) and SPSS 17.Results: The investigators of 13 international OAMPs were invited to take part. IPD from 9 OAMPs were delivered: the OA Chronic Care Program, Ramsay Health OA Management Program, Joint Health Program, University of Wisconsin Health Knee and Hip Comprehensive Non-Surgical OA Management Clinic, Improved Management of Patients With Hip and Knee OA in Primary Health Care, Joint Academy, Amsterdam OA cohort, Management of OA In Consultations, and Collaborative model of care between Orthopaedics and allied healthcare professionals in knee OA. The characteristics of the OAMPs are summarised in table 1. The OAMPs were conducted in-person except for the Joint Academy that was implemented as an online OAMP. Individual participant data from 9819 participants were analyzed. The cohort studies were missing large amounts of data, as expected in clinical practice. The characteristics of OAMP participants are summarised in Table 2. The majority of OAMP participants reported the knee as their index joint, their mean age ranged between 62- 67 years, 58-74% were female, 25-48% were working and mean BMI indicated they were overweight at baseline. Pain was most commonly assessed using a Numeric Rating Scale or validated questionnaires e.g. the Knee Injury and OA Outcome Scale (KOOS). Function was mostly assessed using validated questionnaires such as the KOOS. The pain and fuction measured in the original datasets are reported in Table 1. The changes in pain and function of the OAMP participants from baseline across weeks 12, 26, and 52 are summarised in Table 3. There were reductions in pain scores and improvements in function scores seen across all programs at the majority of timepoints.Conclusions: We established the first data bank of IPD from different international OAMPs. Analysis of the IPD demonstrated modest improvements in pain and function across the programs at all timepoints. The most rapid improvements were made by week-12, however, these gains were maintained at week-52. In future work this project will use IPD meta-analysis to identify prognostic factors of people with OA who participate in OAMPs.
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| 26. |
- Guerendiain, D, et al.
(författare)
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Mapping HPV 16 Sub-Lineages in Anal Cancer and Implications for Disease Outcomes
- 2022
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Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of anal cancer is rising worldwide. As identified in cervical cancer management, an improvement in the early detection and management of anal pre-cancer is essential. In other cancers associated with human papillomavirus (HPV), HPV 16 sub-lineages have been shown to be associated with disease status and prognosis. However, in anal cancer, they have been under-explored. A total of 119 HPV 16-positive anal cancer lesions diagnosed between 2009 and 2018 in Scotland and 134 HPV 16-positive residual rectal swabs from asymptomatic men collected in 2016/7 were whole genome sequenced. The association of HPV 16 sub-lineages with underlying disease status (cancer vs. asymptomatic) and overall survival in anal cancer samples was assessed (comparing A1 vs non-A1 sub-lineages). A1 was the dominant sub-lineage present in the anal cancer (76.5%) and the asymptomatic (76.1%) cohorts. A2 was the second most dominant sub-lineage in both groups (16.8% and 17.2%, respectively). We did not observe significant associations of sub-lineage with demographics, clinical variables or survival (A1 vs. non-A1 sub-lineages (HR 0.83, 0.28–2.46 p = 0.743)). HPV 16 sub-lineages do to not appear to cluster with disease vs asymptomatic carriage or be independently associated with outcomes in anal cancer patients. Further international studies on anal HPV sub-lineage mapping will help to determine whether this is a consistent observation.
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| 27. |
- Gössling, Stefan, et al.
(författare)
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Climate Policy and Tourism
- 2012
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Ingår i: A Handbook of Tourism and the Environment. - London : Routledge. - 9780415582070 - 0415582075 ; , s. 421-434
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Bokkapitel (refereegranskat)
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| 30. |
- Kazakos, K., et al.
(författare)
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A real-time IVR platform for community radio
- 2016
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Ingår i: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : ACM.
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Konferensbidrag (refereegranskat)abstract
- Interactive Voice Response (IVR) platforms have been widely deployed in resource-limited settings. These systems tend to afford asynchronous push interactions, and within the context of health, provide medication reminders, descriptions of symptoms and tips on self-management. Here, we present the development of an IVR system for resource-limited settings that enables real-time, synchronous interaction. Inspired by community radio, and calls for health systems that are truly local, we developed ’Sehat ki Vaani’. Sehat ki Vaani is a real-time IVR platform that enables hosting and participation in radio chat shows on community-led topics. We deployed Sehat ki Vaani with two communities in North India on topics related to the management of Type 2 diabetes and maternal health. Our deployments highlight the potential for synchronous IVR systems to offer community connection and localised sharing of experience, while also highlighting the complexity of producing, hosting and participating in radio shows in real time through IVR. We discuss the relative strengths and weaknesses of synchronous IVR systems, and highlight lessons learnt for interaction design in this area.
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| 31. |
- McNaney, R., et al.
(författare)
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Designing for and with people with Parkinson’s : A focus on exergaming
- 2015
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Ingår i: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : ACM.
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Konferensbidrag (refereegranskat)abstract
- Parkinson’s is a complex and multifaceted condition with a myriad of symptoms, thus, designing for and with this user group requires careful consideration. We reflect upon two studies, employing different design methodologies, relating to the design of rehabilitative exergames in Parkinson’s. The first explored the concept of designing ’for’ People with Parkinson’s (PwP) and focused on specifications outlined by clinical stakeholders. The second used a designing ’with’ approach and modified a pre-established participatory design method for use with PwP. We call attention to the importance of carrying out design work with PwP and contribute; an empathic understanding of living with Parkinson’s, a set of recommendations for how to design with PwP and a set of wider considerations for developing rehabilitative exergames for PwP.
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| 33. |
- Pelak, Victoria S., et al.
(författare)
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Consensus recommendations for clinical assessment tools for the diagnosis of posterior cortical atrophy syndrome from the Atypical AD PIA of ISTAART
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Delay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed. METHODS: Recommendations were developed using results from a web-based survey of members of Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Atypical Alzheimer's Disease Professional Interest Area (PIA), literature review, and consensus by the PCA assessment working party of the Atypical Alzheimer's Disease PIA. RESULTS: Survey results revealed robust agreement for assessment tool preferences for PCA features, and many respondents indicated that they reserve assessment tools for use only when PCA is suspected. For some PCA features, curated tools were preferred over validated battery tools, particularly for the office visit. Consensus recommendations superseded survey preferences for two core cognitive features within the 2017 PCA diagnostic criteria. DISCUSSION: These consensus recommendations provide an evaluation framework for PCA clinical features and can facilitate timely and accurate recognition and diagnosis of PCA. Broader use of these tools should be sought, and development and validation of novel PCA clinical outcome assessments are needed to improve our understanding of atypical AD and other dementias and support the inclusion of those with PCA in treatment trials.
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| 34. |
- Qiu, Chunjing, et al.
(författare)
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A strong mitigation scenario maintains climate neutrality of northern peatlands
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:1, s. 86-97
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Tidskriftsartikel (refereegranskat)abstract
- Northern peatlands store 300–600 Pg C, of which approximately half are underlain by permafrost. Climate warming and, in some regions, soil drying from enhanced evaporation are progressively threatening this large carbon stock. Here, we assess future CO2 and CH4 fluxes from northern peatlands using five land surface models that explicitly include representation of peatland processes. Under Representative Concentration Pathways (RCP) 2.6, northern peatlands are projected to remain a net sink of CO2 and climate neutral for the next three centuries. A shift to a net CO2 source and a substantial increase in CH4 emissions are projected under RCP8.5, which could exacerbate global warming by 0.21°C (range, 0.09–0.49°C) by the year 2300. The true warming impact of peatlands might be higher owing to processes not simulated by the models and direct anthropogenic disturbance. Our study highlights the importance of understanding how future warming might trigger high carbon losses from northern peatlands.
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| 37. |
- Zou, J. Y., et al.
(författare)
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Rewetting global wetlands effectively reduces major greenhouse gas emissions
- 2022
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- Carbon and nitrogen losses from degraded wetlands and methane emissions from flooded wetlands are both important sources of greenhouse gas emissions. However, the net-exchange dependence on hydrothermal conditions and wetland integrity remains unclear. Using a global-scale in situ database on net greenhouse gas exchanges, we show diverse hydrology-influenced emission patterns in CO2, CH4 and N2O. We find that total CO2-equivalent emissions from wetlands are kept to a minimum when the water table is near the surface. By contrast, greenhouse gas exchange rates peak in flooded and drained conditions. By extrapolating the current trajectory of degradation, we estimate that between 2021 and 2100, wetlands could result in greenhouse gas emissions equivalent to around 408 gigatons of CO2. However, rewetting wetlands could reduce these emissions such that the radiative forcing caused by CH4 and N2O is fully compensated by CO2 uptake. As wetland greenhouse gas budgets are highly sensitive to changes in wetland area, the resulting impact on climate from wetlands will depend on the balance between future degradation and restoration. Global in situ observations show greenhouse gas emissions from wetlands are lowest when the water table is near the surface, and therefore rewetting wetlands could substantially reduce future emissions.
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