| 1. |
- Brockmann, K., et al.
(författare)
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Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson's disease and dementia with Lewy bodies
- 2021
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The clinicopathological heterogeneity in Lewy-body diseases (LBD) highlights the need for pathology-driven biomarkers in-vivo. Misfolded alpha-synuclein (alpha-Syn) is a lead candidate based on its crucial role in disease pathophysiology. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has recently shown high sensitivity and specificity for the detection of misfolded alpha-Syn in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this study we performed the CSF RT-QuIC assay in 236 PD and 49 DLB patients enriched for different genetic forms with mutations in GBA, parkin, PINK1, DJ1, and LRRK2. A subgroup of 100 PD patients was also analysed longitudinally. We correlated kinetic seeding parameters of RT-QuIC with genetic status and CSF protein levels of molecular pathways linked to alpha-Syn proteostasis. Overall, 85% of PD and 86% of DLB patients showed positive RT-QuIC alpha-Syn seeding activity. Seeding profiles were significantly associated with mutation status across the spectrum of genetic LBD. In PD patients, we detected positive alpha-Syn seeding in 93% of patients carrying severe GBA mutations, in 78% with LRRK2 mutations, in 59% carrying heterozygous mutations in recessive genes, and in none of those with bi-allelic mutations in recessive genes. Among PD patients, those with severe GBA mutations showed the highest seeding activity based on RT-QuIC kinetic parameters and the highest proportion of samples with 4 out of 4 positive replicates. In DLB patients, 100% with GBA mutations showed positive alpha-Syn seeding compared to 79% of wildtype DLB. Moreover, we found an association between alpha-Syn seeding activity and reduced CSF levels of proteins linked to alpha-Syn proteostasis, specifically lysosome-associated membrane glycoprotein 2 and neurosecretory protein VGF. These findings highlight the value of alpha-Syn seeding activity as an in-vivo marker of Lewy-body pathology and support its use for patient stratification in clinical trials targeting alpha-Syn.
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| 2. |
- Brännström, Åke, 1975-, et al.
(författare)
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A Method for Estimating the Number of Infections From the Reported Number of Deaths
- 2022
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- At the outset of an epidemic, available case data typically underestimate the total number of infections due to insufficient testing, potentially hampering public responses. Here, we present a method for statistically estimating the true number of cases with confidence intervals from the reported number of deaths and estimates of the infection fatality ratio; assuming that the time from infection to death follows a known distribution. While the method is applicable to any epidemic with a significant mortality rate, we exemplify the method by applying it to COVID-19. Our findings indicate that the number of unreported COVID-19 infections in March 2020 was likely to be at least one order of magnitude higher than the reported cases, with the degree of underestimation among the countries considered being particularly high in the United Kingdom.
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| 3. |
- Colon-Gonzalez, J. Felipe, et al.
(författare)
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Projecting the risk of mosquito-borne diseases in a warmer and more populated world : a multi-model, multi-scenario intercomparison modelling study
- 2021
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Ingår i: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:7, s. E404-E414
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mosquito-borne diseases are expanding their range, and re-emerging in areas where they had subsided for decades. The extent to which climate change influences the transmission suitability and population at risk of mosquito-borne diseases across different altitudes and population densities has not been investigated. The aim of this study was to quantify the extent to which climate change will influence the length of the transmission season and estimate the population at risk of mosquito-borne diseases in the future, given different population densities across an altitudinal gradient.Methods: Using a multi-model multi-scenario framework, we estimated changes in the length of the transmission season and global population at risk of malaria and dengue for different altitudes and population densities for the period 1951-99. We generated projections from six mosquito-borne disease models, driven by four global circulation models, using four representative concentration pathways, and three shared socioeconomic pathways.Findings: We show that malaria suitability will increase by 1·6 additional months (mean 0·5, SE 0·03) in tropical highlands in the African region, the Eastern Mediterranean region, and the region of the Americas. Dengue suitability will increase in lowlands in the Western Pacific region and the Eastern Mediterranean region by 4·0 additional months (mean 1·7, SE 0·2). Increases in the climatic suitability of both diseases will be greater in rural areas than in urban areas. The epidemic belt for both diseases will expand towards temperate areas. The population at risk of both diseases might increase by up to 4·7 additional billion people by 2070 relative to 1970-99, particularly in lowlands and urban areas.Interpretation: Rising global mean temperature will increase the climatic suitability of both diseases particularly in already endemic areas. The predicted expansion towards higher altitudes and temperate regions suggests that outbreaks can occur in areas where people might be immunologically naive and public health systems unprepared. The population at risk of malaria and dengue will be higher in densely populated urban areas in the WHO African region, South-East Asia region, and the region of the Americas, although we did not account for urban-heat island effects, which can further alter the risk of disease transmission.
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| 4. |
- Danielsson, Henrik, et al.
(författare)
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A Systematic Review of Longitudinal Trajectories of Mental Health Problems in Children with Neurodevelopmental Disabilities
- 2024
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Ingår i: Journal of Developmental and Physical Disabilities. - : Springer. - 1056-263X .- 1573-3580. ; 36, s. 203-242
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Forskningsöversikt (refereegranskat)abstract
- To review the longitudinal trajectories - and the factors influencing their development - of mental health problems in children with neurodevelopmental disabilities. Systematic review methods were employed. Searches of six databases used keywords and MeSH terms related to children with neurodevelopmental disabilities, mental health problems, and longitudinal research. After the removal of duplicates, reviewers independently screened records for inclusion, extracted data (outcomes and influencing factors), and evaluated the risk of bias. Findings were tabulated and synthesized using graphs and a narrative. Searches identified 94,662 unique records, from which 49 publications were included. The median publication year was 2015. Children with attention deficit hyperactivity disorder were the most commonly included population in retrieved studies. In almost 50% of studies, trajectories of mental health problems changed by < 10% between the first and last time point. Despite multiple studies reporting longitudinal trajectories of mental health problems, greater conceptual clarity and consideration of the measures included in research is needed, along with the inclusion of a more diverse range of populations of children with neurodevelopmental disabilities.
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| 5. |
- DiSera, Laurel, et al.
(författare)
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The Mosquito, the Virus, the Climate : An Unforeseen Réunion in 2018
- 2020
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Ingår i: GeoHealth. - : John Wiley & Sons. - 2471-1403. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- The 2018 outbreak of dengue in the French overseas department of Réunion was unprecedented in size and spread across the island. This research focuses on the cause of the outbreak, asserting that climate played a large role in the proliferation of the Aedes albopictus mosquitoes, which transmitted the disease, and led to the dengue outbreak in early 2018. A stage‐structured model was run using observed temperature and rainfall data to simulate the life cycle and abundance of the Ae. albopictus mosquito. Further, the model was forced with bias‐corrected subseasonal forecasts to determine if the event could have been forecast up to 4 weeks in advance. With unseasonably warm temperatures remaining above 25°C, along with large tropical‐cyclone‐related rainfall events accumulating 10–15 mm per event, the modeled Ae. albopictus mosquito abundance did not decrease during the second half of 2017, contrary to the normal behavior, likely contributing to the large dengue outbreak in early 2018. Although subseasonal forecasts of rainfall for the December–January period in Réunion are skillful up to 4 weeks in advance, the outbreak could only have been forecast 2 weeks in advance, which along with seasonal forecast information could have provided enough time to enhance preparedness measures. Our research demonstrates the potential of using state‐of‐the‐art subseasonal climate forecasts to produce actionable subseasonal dengue predictions. To the best of the authors' knowledge, this is the first time subseasonal forecasts have been used this way.
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| 6. |
- Farooq, Zia, et al.
(författare)
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Artificial intelligence to predict West Nile virus outbreaks with eco-climatic drivers
- 2022
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Ingår i: The Lancet Regional Health - Europe. - : Elsevier BV. - 2666-7762. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Europe, the frequency, intensity, and geographic range of West Nile virus (WNV)-outbreaks have increased over the past decade, with a 7.2-fold increase in 2018 compared to 2017, and a markedly expanded geographic area compared to 2010. The reasons for this increase and range expansion remain largely unknown due to the complexity of the transmission pathways and underlying disease drivers. In a first, we use advanced artificial intelligence to disentangle the contribution of eco-climatic drivers to WNV-outbreaks across Europe using decade-long (2010-2019) data at high spatial resolution. Methods: We use a high-performance machine learning classifier, XGBoost (eXtreme gradient boosting) combined with state-of-the-art XAI (eXplainable artificial intelligence) methodology to describe the predictive ability and contribution of different drivers of the emergence and transmission of WNV-outbreaks in Europe, respectively. Findings: Our model, trained on 2010-2017 data achieved an AUC (area under the receiver operating characteristic curve) score of 0.97 and 0.93 when tested with 2018 and 2019 data, respectively, showing a high discriminatory power to classify a WNV-endemic area. Overall, positive summer/spring temperatures anomalies, lower water availability index (NDWI), and drier winter conditions were found to be the main determinants of WNV-outbreaks across Europe. The climate trends of the preceding year in combination with eco-climatic predictors of the first half of the year provided a robust predictive ability of the entire transmission season ahead of time. For the extraordinary 2018 outbreak year, relatively higher spring temperatures and the abundance of Culex mosquitoes were the strongest predictors, in addition to past climatic trends. Interpretation: Our AI-based framework can be deployed to trigger rapid and timely alerts for active surveillance and vector control measures in order to intercept an imminent WNV-outbreak in Europe. Funding: The work was partially funded by the Swedish Research Council FORMAS for the project ARBOPREVENT (grant agreement 2018-05973).
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| 7. |
- Farooq, Zia, et al.
(författare)
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European projections of West Nile virus transmission under climate change scenarios
- 2023
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Ingår i: One Health. - : Elsevier. - 2352-7714. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- West Nile virus (WNV), a mosquito-borne zoonosis, has emerged as a disease of public health concern in Europe. Recent outbreaks have been attributed to suitable climatic conditions for its vectors favoring transmission. However, to date, projections of the risk for WNV expansion under climate change scenarios is lacking. Here, we estimate the WNV-outbreaks risk for a set of climate change and socioeconomic scenarios. We delineate the potential risk-areas and estimate the growth in the population at risk (PAR). We used supervised machine learning classifier, XGBoost, to estimate the WNV-outbreak risk using an ensemble climate model and multi-scenario approach. The model was trained by collating climatic, socioeconomic, and reported WNV-infections data (2010−22) and the out-of-sample results (1950–2009, 2023–99) were validated using a novel Confidence-Based Performance Estimation (CBPE) method. Projections of area specific outbreak risk trends, and corresponding population at risk were estimated and compared across scenarios. Our results show up to 5-fold increase in West Nile virus (WNV) risk for 2040-60 in Europe, depending on geographical region and climate scenario, compared to 2000-20. The proportion of disease-reported European land areas could increase from 15% to 23-30%, putting 161 to 244 million people at risk. Across scenarios, Western Europe appears to be facing the largest increase in the outbreak risk of WNV. The increase in the risk is not linear but undergoes periods of sharp changes governed by climatic thresholds associated with ideal conditions for WNV vectors. The increased risk will require a targeted public health response to manage the expansion of WNV with climate change in Europe.
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| 8. |
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| 9. |
- Farooq, Zia, 1986-
(författare)
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Navigating epidemics : by leveraging data science and data-driven modelling
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ours is an era of global change—including climate change, land-use change, urbanization, increased mobility of humans, species and goods, and environmental shifts. Concurrently, we are witnessing a tangible increase in the rate of (re)emerging infectious diseases, mostly driven by global change factors. This complex landscape of infectious diseases necessitates strategies underpinned by computational tools such as data-driven models to enhance our understanding, response, and predictions of potential epidemics.In this thesis, I leveraged data science algorithms and developed data-driven models that extend beyond specific pathogens, providing insights to prepare for future epidemics, with a focus on Europe. I delved into three temporal contexts: 1) retrospective analyses to understand the contribution of global change factors—specifically climate change and human mobility—fuelling the disease outbreaks and expansion (papers I & IV), 2) develop model to improve disease severity estimation during an outbreak for immediate response (paper III), and 3) future disease transmission risk trajectories under various projected scenarios of global change (paper II)—each playing a crucial role in proactive public health planning and response.In paper I, we assessed the predictive ability and the influence of eco-climatic factors on West Nile virus (WNV)—a pathogen with multiple hosts and mosqutio-vectors, and of public health concern in Europe. Utilizing an advanced machine learning classifier XGBoost, trained on a diverse dataset encompassing eco-climatic, sociodemographic predictors to the WNV presence/absence data, the model accurately predicted the WNV risk a season ahead. Furthermore, by employing an explainable AI algorithm, we uncovered both local and European-level drivers of WNV transmission. Higher temperatures in summer and spring, along with drier winters, were pivotal in the escalated frequency of WNV outbreaks in Europe from 2010 to 2019.In paper II, we projected the WNV risk under climate change and socioeconomics scenarios by integrating augmenting the outputs of climate ensemble into machine learning algorithms. We projected transmission risk trends and maps at local, national, regional and European scale. We predicted a three to five fold increase in WNV transmission risk during the next few decades (2040-60) compared 2000-2020 under extreme climate change scenarios. The proportion of diseasereported European land areas could increase from 15% to 23-30%, putting 161 to 244 million people at risk. Western Europe remains at largest relative risk of WNV increase under all scenarios, and Northern Europe under extreme scenarios. With the current rate of spread and in the absence of intervention or vaccines the virus will have sustained suitability even under low carbon emission scenarios in currently endemic European regions.In paper III, we developed a method to quantify an important epidemiological parameter-case fatality ratio (CFR)— commonly used measure to assess the disease severity during novel outbreaks. In our model, we accounted for the time lags between the reporting of a cases and that of the case fatalities and the probability distribution of time lags and derived the CFR and distribution parameters using an optimization algorithm. The method provided more accurate CFR estimations earlier than the widely used estimators under various simulation scenarios. The method also performed well on empirical COVID-19 data from 34 countries. In paper IV, we modelled annual dengue importations in Europe and the United States driven by human mobility and climate. Travel rates were modelled using a radiation model based on population density, geographic distance, and travel volumes. Dengue viraemic travellers were computed considering local mosquito bite risk, travel-associated bite probability, and visit duration. A dynamic vector life-stage model quantified the climatic suitability of transmissionpermissive local areas. Dengue importations linearly increased in Europe and the U.S. from 2015-2019, rising by 588% and 390%, respectively, compared to 1996-2000 estimates, driven by increased travel volumes (373%) and dengue incidence rates (30%) from endemic countries. Transmission seasons lengthened by 53% and 15% in Europe and the U.S., respectively, indicating increasingly permissive climates for local outbreaks. These findings apply to other diseases such as chikungunya, Zika, and yellow fever, sharing common intermediate host vectors, namely Aedes mosquitoes.This thesis highlights Europe's increasing vulnerability to infectious diseases due to global change factors, putting millions at risk. It emphasizes the significance of advanced modelling and innovative data streams in anticipating epidemic risks. Developing digital early warning systems to track disease drivers and taking urgent climate change mitigation and adaptation measures are crucial to anticipate and reduce future epidemic risks. The outcomes of this research can be used to develop technology-driven decision support tools to aid public health authorities and policymakers in making evidence-based decisions during and inter-epidemic periods.
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| 10. |
- Gama, Fábio, Ass. Professor, 1980-, et al.
(författare)
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Artificial Intelligence Capabilities as Enablers for Digital Innovation Processes : A Systematic Literature Review
- 2021
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Konferensbidrag (refereegranskat)abstract
- Firms increasingly use artificial intelligence (AI) to innovate. Yet, the current literature offers fragmented guidance regarding its use in innovation processes. This study argues that the exponential use of AI has resulted in a mass of disorganised knowledge, creating confusion and frustration surrounding how managers navigate from conventional to digital innovation processes. A systematic literature review was carried out to examine studies investigating AI innovation published over the last decade (2011–2021). The results suggest that AI is present across all innovation phases and that firms have created three unique capabilities: AI-enabled ideation, AI-enabled development, and AI-enabled commercialisation. This article enriches the innovation management literature, and it equips managers with practical guidance in the use of AI.
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| 11. |
- Gebre-Medhin, Maria, et al.
(författare)
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ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
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| 12. |
- Lerche, S., et al.
(författare)
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CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:11, s. 2595-2604
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Tidskriftsartikel (refereegranskat)abstract
- Background Molecular pathways associated with alpha-synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin-proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids. Objective The objective of this study was to evaluate CSF protein profiles of pathways related to alpha-synuclein proteostasis. Methods We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with alpha-synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated alpha-synuclein pathology with pronounced clinical trajectories. Results (1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by GBA variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total alpha-synuclein, with lower levels of proteostasis proteins related to lower levels of total alpha-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of alpha-synuclein longitudinally compared with PD patients with a normal proteostasis profile. Conclusion CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to alpha-synuclein proteostasis in PD and DLB. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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| 13. |
- Lowe, A. J., et al.
(författare)
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Cerebrospinal fluid endo-lysosomal proteins as potential biomarkers for Huntington's disease
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- Molecular markers derived from cerebrospinal fluid (CSF) represent an accessible means of exploring the pathobiology of Huntington's disease (HD) in vivo. The endo-lysosomal/autophagy system is dysfunctional in HD, potentially contributing to disease pathogenesis and representing a potential target for therapeutic intervention. Several endo-lysosomal proteins have shown promise as biomarkers in other neurodegenerative diseases; however, they have yet to be fully explored in HD. We performed parallel reaction monitoring mass spectrometry analysis (PRM-MS) of multiple endo-lysosomal proteins in the CSF of 60 HD mutation carriers and 20 healthy controls. Using generalised linear models controlling for age and CAG, none of the 18 proteins measured displayed significant differences in concentration between HD patients and controls. This was affirmed by principal component analysis, in which no significant difference across disease stage was found in any of the three components representing lysosomal hydrolases, binding/transfer proteins and innate immune system/peripheral proteins. However, several proteins were associated with measures of disease severity and cognition: most notably amyloid precursor protein, which displayed strong correlations with composite Unified Huntington's Disease Rating Scale, UHDRS Total Functional Capacity, UHDRS Total Motor Score, Symbol Digit Modalities Test and Stroop Word Reading. We conclude that although endo-lysosomal proteins are unlikely to have value as disease state CSF biomarkers for Huntington's disease, several proteins demonstrate associations with clinical severity, thus warranting further, targeted exploration and validation in larger, longitudinal samples.
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| 14. |
- Minta, Karolina, et al.
(författare)
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Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background The human APOE gene, which codes for apolipoprotein E (apoE), has three major polymorphic alleles: epsilon 2, epsilon 3, and epsilon 4 that give rise to amino acid substitutions. APOE-epsilon 4 is a strong risk factor of sporadic Alzheimer's disease (AD) but the reason why is still unknown despite intense research for more than 20 years. The aim of the study was to investigate if the concentrations of total apoE and the specific apoE isoforms in cerebrospinal fluid (CSF) differ between various neurodegenerative diseases and control individuals, as well as among the APOE genotypes. Methods Quantification of total apoE and specific apoE isoforms (E2, E3, and E4) in CSF was performed using high-resolution parallel reaction monitoring mass spectrometry. In total, 1820 individuals were involved in the study including clinically diagnosed AD patients (n = 228), cognitively unimpaired (CU) patients (n = 896), and patients with other neurodegenerative disorders (n = 696). Follow-up data was available for 100 individuals, assessed at two time points. Subjects were dichotomized based on an A beta(42/40) CSF concentration ratio cut-off into A beta positive (A beta+, < 0.091) and A beta negative (A beta-, > 0.091) groups. Results Even though there was a significant increase of total apoE in the amyloid beta-positive (A beta+) group compared with amyloid beta-negative (A beta-) individuals (p < 0.001), the magnitude of the effect was very small (AUC = 0.55). Moreover, CSF total apoE concentrations did not differ between A beta- CU controls and clinically diagnosed AD patients. There was a difference in concentration between isoforms in heterozygous individuals in an isoform-dependent manner (E2 < E3 < E4) (p < 0.001, AUC = 0.64-0.69), and these associations remained when dichotomizing the samples into A beta+ and A beta- groups (p < 0.01, AUC = 0.63-0.74). In the cohort with follow-up samples, neither total apoE nor isoform-specific apoE concentrations differed between the two time points (p > 0.05). Conclusions The results indicate that neither the concentrations of total apoE nor the different apoE isoforms in CSF are associated with APOE-epsilon 4 carrier status, A beta status, or clinical dementia diagnoses.
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| 15. |
- Nilsson, Johanna, 1993, et al.
(författare)
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Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer's disease
- 2021
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed. Method Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross-sectional studies including AD (n = 52) and controls (n = 37). Results Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, phosphatidylethanolamine-binding protein 1, and 14-3-3 proteins were observed in AD patients compared to controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased. Discussion We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.
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| 16. |
- Ranlund, Åsa, et al.
(författare)
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Metodbeskrivning : 2020 års inventeringar av gräsmarker och lövskogar
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En generell stickprovsdesign, inom vilken det går att inventera både vanliga och ovanliga fenomen på såväl nationell som regional nivå, utvecklades under 2019 och 2020. Under 2020 har den nya stickprovsdesignen använts för inventeringar av gräsmarker och lövskogar med syfte att förbättra nationella data på naturtyper med höga naturvärden, dvs. naturtyper som uppfyller kriterierna för EU:s art- och habitatdirektivs annex 1, samtidigt som vanligare naturtyper följdes där behov funnits för att komplettera befintliga data. I den här rapporten redovisar vi metodiken vi utvecklat för flygbilds- och fältinventeringarna samt hur urval av trakter till stickprov och provytor för fältbesök gått till.För gräsmarks- och lövskogsinventeringarna gjordes först ett gemensamt så kallat balanserat urval för att slumpmässigt välja ut trakter ur urvalsramen till stickprov. Sedan klassades alla provytor inom de utvalda trakterna i en flygbildsinventering till både lövskogs- och gräsmarksklasser. Utifrån de flygbildsinventerade klasserna skapades urvalsklasser separat för gräsmarks- respektive lövskogsinventeringen. Urvalsklasserna användes sedan för att välja ut provytor för fältbesök, ett urval som gjordes för gräsmarks- respektive lövskogsinventeringen oberoende av varandra.Metodiken för flygbildsinventering utvecklades för att gräsmarks- och lövskogsinventeringarna skulle kunna använda stora stickprov, i linje med den nya stickprovsdesignen. En viktig princip vid flygbildsinveteringen var överklassning, dvs att provytor inkluderades där klassningen var osäker. Detta för att säkerställa att alla gräsmarker och lövskogar inom inventeringarnas respektive ramverk hade möjlighet att ingå så att det statistiska kravet för stickprovsdesignen var uppfyllda. Provytor som utifrån flygbildsinventeringen helt säkert inte innehöll eftersökta naturtyper behövde inte besökas i fält vilket gjorde att fältbesöken fokuserades till provytor av intresse för gräsmarks- eller lövskogsinventeringarna. Det minskade kostnaden för fältbesök och vi kunde använda större stickprov. Sammantaget flygbildsinventerades över 137 000 provytor fördelat på 701 trakter inför fältinventeringen 2020.För fältinventeringen inom gräsmarks- och lövskogsinventeringarna introducerades flera nyheter jämfört med tidigare inventeringar för att samla in mer data på bl.a. naturtypers kvalitet. Varje delyta klassades t.ex. till en naturtyp oavsett om den uppfyller kravet för att bli klassad som en annex 1-naturtyp. Utöver det registrerades ett antal kvalitetsvariabler som visar vilka kriterier för annex 1 som är uppfyllda eller inte. Det gör att det går att jämföra areal och statusvariabler för en annex 1-naturtyp) med areal och statusvariabler av motsvarande naturtyp med låga naturvärden (dvs. där annex 1-kriterierna inte är uppfyllda). 1763 provytor fördelat på 187 trakter slumpades ut för att inventeras i fält 2020. Av dem inventerades 64 provytor 2021 eftersom de inte hanns med säsongen 2020.Eftersom antalet trakter är den viktigaste faktorn i att bestämma precisionen i skattningarna så vill vi inte minska antalet trakter eftersom det ökar osäkerheten i skattningarna. För att effektivisera inventeringarna arbetar vi därför med två olika angreppssätt för en viss stickprovstäthet. Dels vill vi förbättra möjligheten att korrekt kunna utesluta provytor, och ibland hela trakter, från fältbesök genom att förbättra flygbildsinventeringen. Det kan t.ex. handla om att minska överklassningen, genom att göra kriterierna för klasserna snävare . Under det första inventeringsåret 2020 tog det lite längre tid att inventera en trakt i fält än vad som var önskvärt. För att minska fälttiden kan vi därför behöva minska antalet provytor som vi inventerar per trakt alternativt förenkla fältmetodiken per provyta. Fältinsatsen kan också bli effektivare genom att inventering av smala linjära objekt, som åker- och vägrenar, görs genom en linjekorsningsinventering istället för via gräsmarks- och lövskogsinventeringarnas provytor. För lövskogsinventeringen 2020 var ålderskriteriet >30 år . Ett sätt att fokusera denna inventering mot naturtyper av större intresse är att höja ålderskriteriet så att inventeringen riktas mer mot äldre lövskogar. Utöver färre provytor skulle det antagligen också leda till att vi behöver besöka färre trakter inom lövskogsinventeringen. Nackdelen blir förstås att inventeringen inte inkluderar yngre skogar, så det är ett beslut som bör tas utifrån vilka frågeställningar som ska besvaras och hur prioriteringen ser ut för vilka data som ska samlas in.För att kunna ta tillvara de möjligheter som den nya stickprovsdesignen ger har vi utvecklat ny metodik för flygbildsinventering av stora stickprov inom gräsmarks- och lövskogsinventeringarna. Det förbättrar våra möjligheter att möta kraven på tillfredställande data även för mer ovanliga naturtyper. För att möta de ökade kraven på data till artikel 17-rapporteringen har vi också utvecklat och omprioriterat fältinventeringen. 2020 var det första året för gräsmarks- och lövskogsinventeringarna. Redan då fanns allt på plats men många delar behöver utvecklas vidare för att ytterligare effektivisera dem.
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| 17. |
- Rocklöv, Joacim, Professor, 1979-, et al.
(författare)
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COVID-19 outbreak on the Diamond Princess cruise ship : estimating the epidemic potential and effectiveness of public health countermeasures
- 2020
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Ingår i: Journal of Travel Medicine. - : Oxford University Press. - 1195-1982 .- 1708-8305. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cruise ships carry a large number of people in confined spaces with relative homogeneous mixing. On 3 February, 2020, an outbreak of COVID-19 on cruise ship Diamond Princess was reported with 10 initial cases, following an index case on board around 21-25 January. By 4 February, public health measures such as removal and isolation of ill passengers and quarantine of non-ill passengers were implemented. By 20 February, 619 of 3,700 passengers and crew (17%) were tested positive.METHODS: We estimated the basic reproduction number from the initial period of the outbreak using (SEIR) models. We calibrated the models with transient functions of countermeasures to incidence data. We additionally estimated a counterfactual scenario in absence of countermeasures, and established a model stratified by crew and guests to study the impact of differential contact rates among the groups. We also compared scenarios of an earlier versus later evacuation of the ship.RESULTS: The basic reproduction rate was initially 4 times higher on-board compared to the ${R}_0$ in the epicentre in Wuhan, but the countermeasures lowered it substantially. Based on the modeled initial ${R}_0$ of 14.8, we estimated that without any interventions within the time period of 21 January to 19 February, 2920 out of the 3700 (79%) would have been infected. Isolation and quarantine therefore prevented 2307 cases, and lowered the ${R}_0$ to 1.78. We showed that an early evacuation of all passengers on 3 February would have been associated with 76 infected persons in their incubation time.CONCLUSIONS: The cruise ship conditions clearly amplified an already highly transmissible disease. The public health measures prevented more than 2000 additional cases compared to no interventions. However, evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew from infection.
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| 18. |
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| 19. |
- Sjödin, Henrik, et al.
(författare)
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COVID-19 healthcare demand and mortality in Sweden in response to non-pharmaceutical mitigation and suppression scenarios
- 2020
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:5, s. 1443-1453
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: While the COVID-19 outbreak in China now appears suppressed, Europe and the USA have become the epicentres, both reporting many more deaths than China. Responding to the pandemic, Sweden has taken a different approach aiming to mitigate, not suppress, community transmission, by using physical distancing without lockdowns. Here we contrast the consequences of different responses to COVID-19 within Sweden, the resulting demand for care, intensive care, the death tolls and the associated direct healthcare related costs.METHODS: We used an age-stratified health-care demand extended SEIR (susceptible, exposed, infectious, recovered) compartmental model for all municipalities in Sweden, and a radiation model for describing inter-municipality mobility. The model was calibrated against data from municipalities in the Stockholm healthcare region.RESULTS: Our scenario with moderate to strong physical distancing describes well the observed health demand and deaths in Sweden up to the end of May 2020. In this scenario, the intensive care unit (ICU) demand reaches the pre-pandemic maximum capacity just above 500 beds. In the counterfactual scenario, the ICU demand is estimated to reach ∼20 times higher than the pre-pandemic ICU capacity. The different scenarios show quite different death tolls up to 1 September, ranging from 5000 to 41 000, excluding deaths potentially caused by ICU shortage. Additionally, our statistical analysis of all causes excess mortality indicates that the number of deaths attributable to COVID-19 could be increased by 40% (95% confidence interval: 0.24, 0.57).CONCLUSION: The results of this study highlight the impact of different combinations of non-pharmaceutical interventions, especially moderate physical distancing in combination with more effective isolation of infectious individuals, on reducing deaths, health demands and lowering healthcare costs. In less effective mitigation scenarios, the demand on ICU beds would rapidly exceed capacity, showing the tight interconnection between the healthcare demand and physical distancing in the society. These findings have relevance for Swedish policy and response to the COVID-19 pandemic and illustrate the importance of maintaining the level of physical distancing for a longer period beyond the study period to suppress or mitigate the impacts from the pandemic.
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| 20. |
- Sjödin, Henrik, et al.
(författare)
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Only strict quarantine measures can curb the coronavirus disease (COVID-19) outbreak in Italy, 2020
- 2020
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 25:13
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Tidskriftsartikel (refereegranskat)abstract
- Several Italian towns are under lockdown to contain the COVID-19 outbreak. The level of transmission reduction required for physical distancing interventions to mitigate the epidemic is a crucial question. We show that very high adherence to community quarantine (total stay-home policy) and a small household size is necessary for curbing the outbreak in a locked-down town. The larger the household size and amount of time in the public, the longer the lockdown period needed.
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| 21. |
- Swift, I. J., et al.
(författare)
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Differential patterns of lysosomal dysfunction are seen in the clinicopathological forms of primary progressive aphasia
- 2024
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Ingår i: Journal of Neurology. - 0340-5354. ; 271:3, s. 1277-1285
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence implicates endo-lysosomal dysfunction in frontotemporal dementia (FTD). 18 proteins were quantified using a mass spectrometry assay panel in the cerebrospinal fluid of 36 people with the language variant of FTD, primary progressive aphasia (PPA) (including 13 with non-fluent variant (nfvPPA), 11 with semantic variant (svPPA), and 12 with logopenic variant (lvPPA)) and 19 healthy controls. The concentrations of the cathepsins (B, D, F, L1, and Z) as well as AP-2 complex subunit beta, ganglioside GM2 activator, beta-hexosaminidase subunit beta, tissue alpha l-fucosidase, and ubiquitin were decreased in nfvPPA compared with controls. In contrast, the concentrations of amyloid beta A4 protein, cathepsin Z, and dipeptidyl peptidase 2 were decreased in svPPA compared with controls. No proteins were abnormal in lvPPA. These results indicate a differential alteration of lysosomal proteins in the PPA variants, suggesting those with non-Alzheimer's pathologies are more likely to show abnormal lysosomal function.
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| 22. |
- Tozan, Yesim, et al.
(författare)
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Transmission dynamics of dengue and chikungunya in a changing climate : do we understand the eco-evolutionary response?
- 2020
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Ingår i: Expert Review of Anti-Infective Therapy. - : Taylor & Francis. - 1478-7210 .- 1744-8336. ; 18:12, s. 1187-1193
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We are witnessing an alarming increase in the burden and range of mosquito-borne arboviral diseases. The transmission dynamics of arboviral diseases is highly sensitive to climate and weather and is further affected by non-climatic factors such as human mobility, urbanization, and disease control. As evidence also suggests, climate-driven changes in species interactions may trigger evolutionary responses in both vectors and pathogens with important consequences for disease transmission patterns.Areas covered: Focusing on dengue and chikungunya, we review the current knowledge and challenges in our understanding of disease risk in a rapidly changing climate. We identify the most critical research gaps that limit the predictive skill of arbovirus risk models and the development of early warning systems, and conclude by highlighting the potentially important research directions to stimulate progress in this field.Expert opinion: Future studies that aim to predict the risk of arboviral diseases need to consider the interactions between climate modes at different timescales, the effects of the many non-climatic drivers, as well as the potential for climate-driven adaptation and evolution in vectors and pathogens. An important outcome of such studies would be an enhanced ability to promulgate early warning information, initiate adequate response, and enhance preparedness capacity.
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| 23. |
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| 24. |
- van Daalen, Kim R., et al.
(författare)
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The 2024 Europe report of the lancet countdown on health and climate change : unprecedented warming demands unprecedented action
- 2024
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 9:7, s. e495-e522
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Forskningsöversikt (refereegranskat)abstract
- Record-breaking temperatures were recorded across the globe in 2023. Without climate action, adverse climate-related health impacts are expected to worsen worldwide, affecting billions of people. Temperatures in Europe are warming at twice the rate of the global average, threatening the health of populations across the continent and leading to unnecessary loss of life. The Lancet Countdown in Europe was established in 2021, to assess the health profile of climate change aiming to stimulate European social and political will to implement rapid health-responsive climate mitigation and adaptation actions. In 2022, the collaboration published its indicator report, tracking progress on health and climate change via 33 indicators and across five domains.This new report tracks 42 indicators highlighting the negative impacts of climate change on human health, the delayed climate action of European countries, and the missed opportunities to protect or improve health with health-responsive climate action. The methods behind indicators presented in the 2022 report have been improved, and nine new indicators have been added, covering leishmaniasis, ticks, food security, health-care emissions, production and consumption-based emissions, clean energy investment, and scientific, political, and media engagement with climate and health. Considering that negative climate-related health impacts and the responsibility for climate change are not equal at the regional and global levels, this report also endeavours to reflect on aspects of inequality and justice by highlighting at-risk groups within Europe and Europe's responsibility for the climate crisis.
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