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OBJECTIVE: The self-administered version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is used to monitor function and disease progression in individuals with amyotrophic lateral sclerosis (ALS). However, the performance of the self-administered ALSFRS-R has not been assessed using Rasch Measurement Theory. Therefore, the purpose of this study was to examine the psychometric properties of the self-administered ALSFRS-R using Rasch analysis. METHODS: Rasch analysis was performed on self-administered ALSFRS-R data from individuals with ALS across Canada. The following 6 aspects of Rasch analysis were examined using RUMM2030: fit via residuals and chi-square statistics, targeting via person-item threshold maps, dependency via item residual correlations, unidimensionality through principal components analysis of residuals, reliability via person separation index, and stability through differential item functioning analyses for sex, age, and language. RESULTS: Analysis was performed on 122 participants (mean age: 52.9 years; 62.8% men). The overall scale demonstrated good fit, reliability, and stability; however, multidimensionality was found. To address this issue, items were divided into 3 subscales (bulbar, motor, and respiratory function), and Rasch analysis was performed for each subscale. The subscales demonstrated good fit, reliability, stability, and unidimensionality. However, there were still issues with item dependency for all subscale and targeting for bulbar and respiratory subscales. CONCLUSIONS: The self-administered ALSFRS-R is reliable, internally valid, and stable across sex, age, and language subgroups; however, it is recommended that the ALSFRS-R be scored by subscale. Future studies can look at revising and/or adding items to tackle misfit, redundancy, and ceiling effects. IMPACT: Self-administered measures are simple to administer and inexpensive. The self-administered ALSFRS-R was found to be psychometrically sound and can be used as a tool to monitor disease progression and function in ALS.
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Esclerose Lateral Amiotrófica , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Reprodutibilidade dos Testes , Idioma , Psicometria , Progressão da DoençaRESUMO
BACKGROUND: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. METHODS: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory - Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. RESULTS: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. CONCLUSIONS: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.
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Transtornos Cerebrovasculares , Disfunção Cognitiva , Demência Frontotemporal , Doença de Parkinson , Substância Branca , Humanos , Feminino , Substância Branca/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.
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Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/genética , Doenças de Pequenos Vasos Cerebrais/patologia , Imageamento por Ressonância MagnéticaRESUMO
Human society is dependent on nature1,2, but whether our ecological foundations are at risk remains unknown in the absence of systematic monitoring of species' populations3. Knowledge of species fluctuations is particularly inadequate in the marine realm4. Here we assess the population trends of 1,057 common shallow reef species from multiple phyla at 1,636 sites around Australia over the past decade. Most populations decreased over this period, including many tropical fishes, temperate invertebrates (particularly echinoderms) and southwestern Australian macroalgae, whereas coral populations remained relatively stable. Population declines typically followed heatwave years, when local water temperatures were more than 0.5 °C above temperatures in 2008. Following heatwaves5,6, species abundances generally tended to decline near warm range edges, and increase near cool range edges. More than 30% of shallow invertebrate species in cool latitudes exhibited high extinction risk, with rapidly declining populations trapped by deep ocean barriers, preventing poleward retreat as temperatures rise. Greater conservation effort is needed to safeguard temperate marine ecosystems, which are disproportionately threatened and include species with deep evolutionary roots. Fundamental among such efforts, and broader societal needs to efficiently adapt to interacting anthropogenic and natural pressures, is greatly expanded monitoring of species' population trends7,8.
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Antozoários , Recifes de Corais , Calor Extremo , Peixes , Aquecimento Global , Invertebrados , Oceanos e Mares , Água do Mar , Alga Marinha , Animais , Austrália , Peixes/classificação , Invertebrados/classificação , Aquecimento Global/estatística & dados numéricos , Alga Marinha/classificação , Dinâmica Populacional , Densidade Demográfica , Água do Mar/análise , Extinção Biológica , Conservação dos Recursos Naturais/tendências , Equinodermos/classificaçãoRESUMO
Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and cerebrovascular disease; n = 391, age 40-87) and healthy controls (n = 149, age 42-87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer's disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.
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OBJECTIVE: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. METHODS: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. RESULTS: Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. CONCLUSIONS: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.
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Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doenças Cardiovasculares , Demência Frontotemporal , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/epidemiologia , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/psicologia , Doença de Alzheimer/epidemiologiaRESUMO
Warming seas, marine heatwaves, and habitat degradation are increasingly widespread phenomena affecting marine biodiversity, yet our understanding of their broader impacts is largely derived from collective insights from independent localized studies. Insufficient systematic broadscale monitoring limits our understanding of the true extent of these impacts and our capacity to track these at scales relevant to national policies and international agreements. Using an extensive time series of co-located reef fish community structure and habitat data spanning 12 years and the entire Australian continent, we found that reef fish community responses to changing temperatures and habitats are dynamic and widespread but regionally patchy. Shifts in composition and abundance of the fish community often occurred within 2 years of environmental or habitat change, although the relative importance of these two mechanisms of climate impact tended to differ between tropical and temperate zones. The clearest of these changes on temperate and subtropical reefs were temperature related, with responses measured by the reef fish thermal index indicating reshuffling according to the thermal affinities of species present. On low latitude coral reefs, the community generalization index indicated shifting dominance of habitat generalist fishes through time, concurrent with changing coral cover. Our results emphasize the importance of maintaining local ecological detail when scaling up datasets to inform national policies and global biodiversity targets. Scaled-up ecological monitoring is needed to discriminate among increasingly diverse drivers of large-scale biodiversity change and better connect presently disjointed systems of biodiversity observation, indicator research, and governance.
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Antozoários , Recifes de Corais , Animais , Antozoários/fisiologia , Austrália , Biodiversidade , Mudança Climática , Ecossistema , Peixes/fisiologiaRESUMO
BACKGROUND: Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. METHODS: Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). RESULTS: In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer's disease participant; (2) a duplication of exons 1-5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of >3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7-11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. CONCLUSION: The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.
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Variações do Número de Cópias de DNA , Doenças Neurodegenerativas , Éxons , Heterozigoto , Humanos , Doenças Neurodegenerativas/genética , FenótipoRESUMO
OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.
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Transtornos Cerebrovasculares , Demência Frontotemporal , Doenças Neurodegenerativas , Atividades Cotidianas , Cuidadores/psicologia , Humanos , OntárioRESUMO
Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Five hundred thirteen participants with Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), Parkinson's disease, or cerebrovascular disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex (female), global cognition, and right parietal and occipital WMH. Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.
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Transtornos Cerebrovasculares , Demência Frontotemporal , Substância Branca , Atrofia , Transtornos Cerebrovasculares/patologia , Empatia , Feminino , Demência Frontotemporal/patologia , Humanos , Substância Branca/diagnóstico por imagemRESUMO
Objective: The aim of this study was to refine the items of a preference-based amyotrophic lateral sclerosis health-related quality of life scale (PB-ALS HRQL scale) based on domains generated in a previous study. Methods: Survey methodology was used to assess item importance rating (IR) and independence. Median importance was calculated for each item and a rating of "very important" was required for the item to remain. Correlations were used to examine item independence. Highly correlated items (rs > 0.7) were considered for removal. Cognitive debriefing (CD) interviews, conducted by Zoom, telephone, or email based on participant preference and communication needs, were used to identify potential issues. Participants provided feedback about wording, clarity, response options, and recall period on randomly selected items. Items were considered finalized when three sequential CD participants approved the item with no revisions. Results: Thirty-four people with ALS (PALS, n = 16 females; age range 44-78 years; ALS Functional Rating Scale-Revised [ALSFRS-R] range 0-48) in Canada completed the survey; a subset of 18 PALS completed CD interviews (n = 8 female; age range 44-71 years; ALSFRS-R range 0-48). Four items were highly correlated with one or more items, were not rated as very important, or were not approved via CD and were removed. Conclusions: The final four-response option PB-ALS Scale includes eight items: recreation and leisure, mobility, interpersonal interactions and relationships, eating and swallowing, handling objects, communicating, routine activities, and mood. The next step is to translate the PB-ALS Scale into French and develop a scoring algorithm based on PALS' preferences.
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Esclerose Lateral Amiotrófica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Esclerose Lateral Amiotrófica/psicologia , Qualidade de Vida , Inquéritos e Questionários , Deglutição/fisiologia , IdiomaRESUMO
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective action by various mechanisms: inhibition of proinflammatory cytokines and macrophage migration inhibitory factor, phosphodiesterase inhibition, and attenuation of glial cell activation in models of ALS. Early-phase studies suggest that MN-166 may improve survival outcomes and slow disease progression in patients with ALS. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study in ALS. This study is designed to evaluate the pharmacokinetics, safety and tolerability and assess the efficacy of MN-166 on function, muscle strength, quality of life and survival in ALS.
Lay abstract Amyotrophic lateral sclerosis (ALS) is a neurological disease defined by the loss of the nerve cells going to the muscles. Despite significant effort, we still do not have good treatments for ALS. MN-166 (ibudilast) can protect nerve cells by calming inflammation in several ways in models of ALS. Early human studies suggest that MN-166 may extend life and slow disease progression in ALS patients. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study. This study will show the drug's safety and tolerability and its effects on physical function, muscle strength, quality of life and survival in people living with ALS. Trial registration number: NCT04057898 (ClinicalTrial.gov).
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Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Esclerose Lateral Amiotrófica/tratamento farmacológico , Método Duplo-Cego , Humanos , Piridinas , Qualidade de VidaRESUMO
Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson's disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.
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OBJECTIVE: The objectives of this study were to 1) assess the content validity of generic preference-based measures (GPBMs), and (2) examine the convergent validity of the EuroQol 5 Dimension 5 Level (EQ-5D-5L), against the Patient Generated Index (PGI) in Amyotrophic Lateral Sclerosis (ALS). METHODS: Participants were recruited from 3 clinical sites across Canada. The PGI, EQ-5D-5L and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) were administered through an online or hardcopy survey and scores compared for convergent validation. Domains nominated by participants as important to their health-related quality of life were generated using the PGI, classified using the International Classification of Functioning, Disability and Health (ICF) and mapped onto GPBMs to determine content coverage. RESULTS: Fifty-two participants (N=28 female; 61.3 ± 11.6 mean age ± standard deviation (SD); 3.5 ± 2.9 mean ± SD years since diagnosis) completed this study. The top three ICF domains identified by participants were recreation and leisure, lower limb mobility, and interpersonal relationships. The Quality of Well-Being Self-Administered (QWB-SA) scale had the highest content coverage (87%) and the Health Utilities Index 3 (HUI3) had the lowest (33%). Two domains were covered by all GPBMs and no GPBM included all domains identified as important by participants. A moderate correlation coefficient of 0.52 between the PGI and EQ-5D-5L was found. CONCLUSION: The majority of GPBMs covered only approximately half of the domains important to individuals with ALS suggesting the need for an ALS specific preference-based measure to better reflect the health-related quality of life of this population.
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For many years there has been uncertainty regarding how apolipoprotein E (APOE) E2 and E4 variants may influence overlapping features of neurodegeneration, such as cognitive impairment. We aimed to identify whether the APOE variants are associated with cognitive function across various neurodegenerative and cerebrovascular diagnoses (n = 513). Utilizing a comprehensive neuropsychology battery, multivariate multiple regression was used to assess the influence of APOE carrier status and disease cohort on performance across five cognitive domains. Irrespective of disease cohort, E4 carriers had significantly lower performance in verbal memory and visuospatial domains than those with E3/3, while E2 carriers' cognitive performance was not significantly different. However, E2 carriers with frontotemporal dementia (FTD) performed significantly worse than those with E3/3 in the attention/working memory, executive function, and visuospatial domains. Our results highlight that the influence of APOE variation on cognition is complex, in some cases varying based on diagnosis and possibly underlying disease pathology.
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Apolipoproteína E2/genética , Apolipoproteína E4/genética , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Estudos de Associação Genética , Variação Genética/genética , Doenças Neurodegenerativas/complicações , Idoso , Atenção , Disfunção Cognitiva/psicologia , Estudos de Coortes , Função Executiva , Feminino , Heterozigoto , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Doenças Neurodegenerativas/psicologia , Testes NeuropsicológicosRESUMO
Marine protected areas (MPAs) are a primary tool for the stewardship, conservation, and restoration of marine ecosystems, yet 69% of global MPAs are only partially protected (i.e., are open to some form of fishing). Although fully protected areas have well-documented outcomes, including increased fish diversity and biomass, the effectiveness of partially protected areas is contested. Partially protected areas may provide benefits in some contexts and may be warranted for social reasons, yet social outcomes often depend on MPAs achieving their ecological goals to distinguish them from open areas and justify the cost of protection. We assessed the social perceptions and ecological effectiveness of 18 partially protected areas and 19 fully protected areas compared with 19 open areas along 7000 km of coast of southern Australia. We used mixed methods, gathering data via semistructured interviews, site surveys, and Reef Life (underwater visual census) surveys. We analyzed qualitative data in accordance with grounded theory and quantitative data with multivariate and univariate linear mixed-effects models. We found no social or ecological benefits for partially protected areas relative to open areas in our study. Partially protected areas had no more fish, invertebrates, or algae than open areas; were poorly understood by coastal users; were not more attractive than open areas; and were not perceived to have better marine life than open areas. These findings provide an important counterpoint to some large-scale meta-analyses that conclude partially protected areas can be ecologically effective but that draw this conclusion based on narrower measures. We argue that partially protected areas act as red herrings in marine conservation because they create an illusion of protection and consume scarce conservation resources yet provide little or no social or ecological gain over open areas. Fully protected areas, by contrast, have more fish species and biomass and are well understood, supported, and valued by the public. They are perceived to have better marine life and be improving over time in keeping with actual ecological results. Conservation outcomes can be improved by upgrading partially protected areas to higher levels of protection including conversion to fully protected areas.
Análisis de la Efectividad Social y Ecológica de las Áreas Marinas Parcialmente Protegidas Resumen Las áreas marinas protegidas (AMPs) son una herramienta importante para la administración, conservación y restauración de los ecosistemas marinos; sin embargo, el 69% de las AMPs mundiales solamente están parcialmente protegidas (es decir, están abiertas a alguna forma de pesca). Aunque las áreas completamente protegidas tienen resultados bien documentados, incluyendo el incremento en la diversidad de peces y la biomasa, la efectividad de las áreas parcialmente protegidas está en disputa. Puede que las áreas parcialmente protegidas se justifiquen por razones sociales, aunque los resultados sociales con frecuencia dependen de que las AMPs alcancen sus metas ecológicas para distinguirlas de las áreas abiertas y justificar el costo de la protección. Analizamos las percepciones sociales y la efectividad ecológica de 18 áreas parcialmente protegidas y 19 áreas completamente protegidas a lo largo de 7000 km de costa en el sur de Australia. Usamos métodos mixtos, recopilando información por medio de entrevistas semiestructuradas, encuestas en sitio y censos Reef Life (censos visuales submarinos). Analizamos los datos cualitativos de acuerdo con la teoría fundamentada y los datos cuantitativos con modelos lineales de efectos mixtos multivariados y univariados. No encontramos beneficios sociales o ecológicos para las áreas parcialmente protegidas en relación con las áreas abiertas en nuestro estudio. Las áreas parcialmente protegidas no tuvieron más peces, invertebrados o algas que las áreas abiertas; los usuarios de la costa tenían poco entendimiento de ellas; no eran más atractivas que las áreas abiertas; y no eran percibidas como albergues de mejor vida marina que las áreas abiertas. Estos hallazgos proporcionan un contrapunto importante a algunos metaanálisis a gran escala que concluyen que las áreas parcialmente protegidas pueden ser ecológicamente efectivas, pero llegan a esta conclusión con base en medidas más reducidas. Discutimos que las áreas parcialmente protegidas funcionan como pistas falsas para la conservación marina pues crean una ilusión de estar protegidas y consumen pocos recursos para la conservación, pero proporcionan poca o ninguna ganancia ecológica o social en comparación con las áreas abiertas. Las áreas completamente protegidas, al contrario, tienen más especies de peces y biomasa y están bien comprendidas, respaldadas y valoradas por el público. Este tipo de AMPs son percibidas como albergues de mejor vida marina y como en constante mejora con el tiempo al mantenerse en regla con los resultados ecológicos actuales. Los resultados de la conservación pueden mejorarse si se eleva a las áreas parcialmente protegidas a niveles más altos de protección incluyendo la conversión a áreas completamente protegidas.
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Ecossistema , Pesqueiros , Animais , Biomassa , Conservação dos Recursos Naturais , Peixes , Austrália do SulRESUMO
This method develops a local environmental stewardship indicator (LESI), which represents the level of stewardship action of a person at a place. The goal of the indicator is to quantify stewardship activity and allow it to be compared and modelled. LESI requires a brief interview to ascertain an individual's past and current stewardship activities, which are scored on a frequency scale for each of seven action categories. Scores are then combined using the LESI equation to: ⢠Quantify reported stewardship behaviour (as opposed to attitudes or intentions) as a single number. ⢠Enable comparisons of stewardship between individuals and places. ⢠Allow development of models to understand the predictors of stewardship, and ⢠Inform evidence-based strategies for stewardship improvement.
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The common or weedy seadragon, Phyllopteryx taeniolatus, is an iconic and endemic fish found across temperate reefs of southern Australia. Despite its charismatic nature, few studies have been published, and the extent of population sub-structuring remains poorly resolved. Here we used 7462 single nucleotide polymorphisms (SNPs) to identify the extent of population structure in the weedy seadragon along the temperate southeast coast of Australia. We identified four populations, with strong genetic structure (FST = 0.562) between them. Both Discriminant Analysis of Principle Components (DAPC) and Bayesian clustering analyses support four distinct genetic clusters (north to south: central New South Wales, southern NSW, Victoria and Tasmania). In addition to these genetic differences, geographical variation in external morphology was recorded, with individuals from New South Wales shaped differently for a few measurements to those from the Mornington Peninsula (Victoria). We posit that these genetic and morphological differences suggest that the Victorian population of P. taeniolatus was historically isolated by the Bassian Isthmus during the last glacial maximum and should now be considered at least a distinct population. We also recorded high levels of genetic structure among the other locations. Based on the genomic and to a degree morphological evidence presented in this study, we recommend that the Victorian population be managed separately from the eastern populations (New South Wales and Tasmania).