| 1. |
- Lima Ramos, Pedro, et al.
(författare)
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A review of capture-recapture methods and its possibilities in ophthalmology and vision sciences
- 2020
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Ingår i: Ophthalmic Epidemiology. - : Taylor & Francis. - 0928-6586 .- 1744-5086. ; 27:4, s. 310-324
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Forskningsöversikt (refereegranskat)abstract
- Epidemiological information is expected to be used to develop key aspects of eye care such as to control and minimise the impact of diseases, to allocate resources, to monitor public health actions, to determine the best treatment options and to forecast the consequence of diseases in populations. Epidemiological studies are expected to provide information about the prevalence and/or incidence of eye diseases or conditions. To determine prevalence is necessary to perform a cross-sectional screening of the population at risk to ascertain the number of cases.The aim of this review is to describe and evaluate capture-recapture methods (or models) to ascertaining the number of individuals with a disease (e.g. diabetic retinopathy) or condition (e.g. vision impairment) in the population.The review covers the fundamental aspects of capture-recapture methods that would enable non-experts in epidemiology to use it in ophthalmic studies. The review provides information about theoretical aspects of the method with examples of studies in ophthalmology in which it has been used. We also provide a problem/solution approach for limitations arising from the lists obtained from registers or other reliable sources.We concluded that capture-recapture models can be considered reliable to estimate the total number of cases with eye conditions using incomplete information from registers. Accordingly, the method may be used to maintain updated epidemiological information about eye conditions helping to tackle the lack of surveillance information in many regions of the globe.
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| 2. |
- Lima Ramos, Pedro, et al.
(författare)
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Cross-sectional study investigating the prevalence and causes of vision impairment in Northwest Portugal using capture–recapture: [SV] Tvärsnittsstudie som undersöker prevalensen och orsakerna till synnedsättning i nordvästra Portugal med hjälp av infångning-återfångst[PT] Estudo transversal que investiga a prevalência e as causas da deficiência visual no Noroeste de Portugal utilizando captura-recaptura
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to estimate the prevalence and causes of vision impairment (VI) in Portugal.Setting Information about people with VI was obtained from primary care centres, blind association (ACAPO) and from hospitals (the PCVIP study) in the Northwest of Portugal during a period spanning years 2014–2015. Causes of VI were obtained from hospitals.Participants Administrative and medical records of people with visual acuity in the better seeing eye of 0.5 decimal (0.30logMAR) or worse and/or visual field less than 20° were investigated. Capture–recapture with log-linear models was applied to estimate the number of individuals missing from lists of cases obtained from available sources.Primary and secondary outcome measures Log-linear models were used to estimate the crude prevalence and the category specific prevalence of VI.Results Crude prevalence of VI was 1.97% (95% CI 1.56% to 2.54%), and standardised prevalence was 1% (95% CI 0.78% to 1.27%). The age-specific prevalence was 3.27% (95% CI 2.36% to 4.90%), older than 64 years, 0.64% (95% CI 0.49% to 0.88%), aged 25–64 years, and 0.07% (95% CI 0.045% to 0.13%), aged less than 25 years. The female-to-male ratio was 1.3, that is, higher prevalence among females. The five leading causes of VI were diabetic retinopathy, cataract, age-related macular degeneration, glaucoma and disorders of the globe.Conclusions The prevalence of VI in Portugal was within the expected range and in line with other European countries. A significant number of cases of VI might be due to preventable cases and, therefore, a reduction of the prevalence of VI in Portugal seems possible. Women and old people were more likely to have VI and, therefore, these groups require extra attention. Future studies are necessary to characterise temporal changes in prevalence of VI in Portugal.No data are available. Raw data can be requested from the first author.
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| 3. |
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| 4. |
- Lima Ramos, Pedro
(författare)
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Studying prevalence using capture-recapture methods : visual impairment in Portugal
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Visual impairment (VI) due to eye diseases remains a significant healthproblem worldwide and, also, in Europe. There are an estimated 15 million peoplesuffering from moderate or severe visual impairment in Western Europe. VI has asignificant impact on the quality of life by reducing functional status and interferingwith the ability of the subject to maintain independence in a safe manner. Prevalenceof VI needs to be estimated regularly so that the progress of the vision health of apopulation can be evaluated and monitored. In addition, it is important to ascertainthe causes behind VI so that health programs can be designed to lower itsprevalence. There is currently a lack of epidemiological information about theprevalence and causes of VI in Portugal. Therefore, the aim of this thesis was todetermine the prevalence of VI in a large region Portugal using data from lists ofcases of VI.Capture-recapture models have been applied in several disciplines, asbiomedical sciences, epidemiology or ecology, to estimate the size of populations. Inparticular, they have been used to estimate the prevalence of several diseases orconditions. Developing these inferential models is of great importance to avoid thehigh costs and unreasonable time spending of cross-sectional studies. However,applying capture-recapture models is challenging, as they are very sensitive to listdependence and possible capture rates heterogeneity among subgroups of thepopulation. In particular, applying these models to human population samples isadditionally challenging, as in most epidemiologic studies only a small number oflists are available. There are two main differences between human and wildlifepopulations. First, human population lists generally have not a well-defined timeorder. Second, in wildlife studies there are often more trapping samples than inhuman population studies. In most epidemiologic surveys, only two to four lists areavailable. This can be problematic and is an additional difficulty when applyingcapture-recapture models in the context of human populations.The main objective of this work was to estimate the prevalence of VI usingcapture-recapture models. We estimated a crude prevalence of1.97%,95%CI=[1.56,2.54] to the Northwest of Portugal in the time period between2014 and 2015, specifically at the regions of Minho and Douro Litoral. Almost 2 ofevery 100 inhabitants of the Portuguese Northwest suffer from visual impairment.This prevalence value is in line with the values in some countries, particularly withSpain. Diabetic Retinopathy was the main cause (31%), followed by Cataract (15%),Age-related Macular Degeneration (14%) and Glaucoma (10%). This thesis provides asignificant contribution to the understanding of the CR methodology in human populations and for the knowledge of the epidemiological information about VI inPortugal.
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| 5. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 6. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 7. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 8. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 9. |
- Domanovic, Dragoslav, et al.
(författare)
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Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union : an expert opinion from the European Centre for Disease Prevention and Control consultation meeting
- 2019
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Ingår i: Blood Transfusion. - : SIMTIPRO SRL. - 1723-2007. ; 17:6, s. 433-448
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Tidskriftsartikel (refereegranskat)abstract
- Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease.
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| 10. |
- Fanouriakis, Antonis, et al.
(författare)
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EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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| 11. |
- Ferreira, Marisa Borges, et al.
(författare)
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Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients
- 2018
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Ingår i: PeerJ. - : PeerJ, Inc. - 2167-8359. ; 6, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop.ObjectivesThe aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task.MethodsWe measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group.ResultsPatients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits.ConclusionsOur findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS.
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| 12. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 13. |
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| 14. |
- Lim, Eric, et al.
(författare)
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Longitudinal study of the profile and predictors of left ventricular mass regression after stentless aortic valve replacement
- 2008
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 85:6, s. 2026-2029
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to evaluate the long-term profile and determine the factors that would influence the effect and rate of ventricular mass regression with time after aortic valve replacement with a stentless or a homograft valve.METHODS: We studied 300 patients during a 10-year period with at least a year of follow-up with a total of 1,273 serial echocardiographic measurements. Left ventricular mass was calculated from M-mode recordings and indexed to body surface area. Longitudinal data analysis was performed using a linear mixed effects model.RESULTS: The mean age (+/- standard deviation) was 65 (+/-14) years, consisting of 216 (72%) males. A stentless valve was implanted in 156 (52%), and a homograft in 144 (48%). The median time (interquartile range) to follow-up was 4.7 (2.8 to 6.6) years. The greatest rate of left ventricular mass regression occurred in the first year after surgery. On multivariable modeling, independent predictors of left ventricular mass were valve size (p = 0.011), left ventricular function (moderate impairment, p = 0.418; severe impairment, p = 0.011), and baseline left ventricular mass (middle tercile, p < 0.001; highest tercile, p < 0.001). Only baseline ventricular mass influenced the rate of subsequent left ventricular mass regression; the greatest rate of regression occurred in patients with the highest baseline values of ventricular mass (p < 0.001).CONCLUSIONS: The greatest rate of left ventricular mass regression occurs in the first year with baseline left ventricular mass as the strongest predictor and the only identified variable that influenced the rate of left ventricular mass regression.
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| 15. |
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| 16. |
- Macedo, António Filipe, et al.
(författare)
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Anti-saccades in early stages of multiple sclerosis
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Eye movements disability is common finding in multiple sclerosis (MS) but the exact stage at which changes are visible is not clear. The aim of study was to assess if anti-saccade (AS) planning and execution are altered at early stages of the disease.Methods: A total of 48 participants with MS selected by a neurologist (JJC) at Hospital de Braga and 52 controls participated in this study. Inclusion criteria: relapsing-remitting course, EDSS≤3, 1 month or more without MS crisis, and normal or corrected visual acuity. Exclusion criteria (MS and Control): cognitive impairment, traumatic brain injury or stroke. The mean age in the MS group was 37y and 33y in the control group. Eye movements were monitored using a binocular infrared eyetracker running at 250Hz(RED250, SMI Gmb Germany), precision <0.4deg, stimuli were presented in a 22 monitor (Dell P2210). Code for running the experiment and data analysis was written using the Matlab (Mathworks Inc). Participants were seated in a room dim light at 74cm from the monitor and head movements were minimized by a headband. The task was to fixate, after a variable period between steady fixation and the stimulus of 1250ms or 1600ms, participants looked as quickly as possible for the opposite direction where the target (a 30x30mm cross) was presented (anti-saccade movement). Each subject performed 40 trails.Results: The main results were the proportion of the directional errors (wherein the participant voluntarily looked for the wrong side), and latencies for: i) anti-saccades, ii) pro-saccades (movement in the same direction of the stimulus) and iii) correction (reaction time that the participant takes from the error fixation until to start the movement). The mean number of errors was 28%(SD=19) in MS group and 16%(SD=11) in the control group, mean difference 12%, t(74)=3.83, p<.001. Anti-saccades latency was 330msec (SD=61) in the MS group and 294ms(SD=59) in the control group, mean difference 36ms, F(1,98)=10.99, p<.05. The mean of the correction latency value was 178ms(SD=111) in the MS group and 129ms(SD=107) in the control group with a mean difference of 49ms, F(1,98)=6, p<.05. No statistically significant differences were found in accuracy and pro-saccade latency between groups.Conclusions: This study shows that anti-saccades latency and errors are increased at early stages of multiple sclerosis. Anti-saccades might be a sensitive tool to assess functional status in people with this condition.
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| 17. |
- Marisa, Ferreira, 1992-, et al.
(författare)
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Using endogenous saccades to characterize fatigue in multiple sclerosis
- 2017
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 14, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- PurposeMultiple Sclerosis (MS) is likely to cause dysfunction of neural circuits between brain regions increasing brain working load or a subjective overestimation of such working load leading to fatigue symptoms. The aim of this study was to investigate if saccades can reveal the effect of fatigue in patients with MS.MethodsPatients diagnosed with MS (EDSS<=3) and age matched controls were recruited. Eye movements were monitored using an infrared eyetracker. Each participant performed 40 trials in an endogenous generated saccade paradigm (valid and invalid trials). The fatigue severity scale (FSS) was used to assess the severity of fatigue. FSS scores were used to define two subgroups, the MS fatigue group (score above normal range) and the MS non-fatigue. Differences between groups were tested using linear mixed models.ResultsThirty-one MS patients and equal number of controls participated in this study. FSS scores were above the normal range in 11 patients. Differences in saccade latency were found according to group (p<0.001) and trial validity (p=0.023). Differences were 16.9 ms, between MS fatigue and MS non-fatigue, 15.5 ms between MS fatigue and control. The mean difference between valid and invalid trials was 7.5 ms. Differences in saccade peak velocity were found according to group (p<0.001), the difference between MS fatigue and control was 22.3°/s and between MS fatigue and non-fatigue was 12.3°/s. Group was a statistically significant predictor for amplitude (p<0.001). FSS scores were correlated with peak velocity (p=0.028) and amplitude (p=0.019).ConclusionConsistent with the initial hypothesis, our study revealed altered saccade latency, peak velocity and amplitude in patients with fatigue symptoms. Eye movement testing can complement the standard inventories when investigating fatigue because they do not share similar limitations. Our findings contribute to the understanding of functional changes induced by MS and might be useful for clinical trials and treatment decisions.
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| 18. |
- Menjivar, Ana, et al.
(författare)
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Psychosocial risk factors for impaired health-related quality of life in living kidney donors: results from the ELIPSY prospective study
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, The Author(s). Living kidney donors’ follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors’ psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient’s medical outcomes on their donor’s psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors’ 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering.
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| 19. |
- Pádua, Diana, et al.
(författare)
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A SOX2 reporter system identifies gastric cancer stem-like cells sensitive to monensin
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6– cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs.
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| 20. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 21. |
- Sousa, João M., et al.
(författare)
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Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
- 2020
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Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.METHODS: Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE2I BPND and R1 estimates, and [11C]PE2I time-activity curves. BPND was examined for striatal regions and R1 in clusters of regions across the brain.RESULTS: For BPND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (- 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R1 estimates had a marginal bias for all MRAC methods (- 1.0-3.2%). MaxProb-MRAC showed the largest intersubject variability for both R1 and BPND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to - 10%), followed by MaxProb-MRAC (+5 to - 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.CONCLUSIONS: Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a 68Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [11C]PE2I PET analysis with use of kinetic modelling.
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| 22. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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