| 1. |
|
|
| 2. |
- Andersson, John, 1979-
(författare)
-
Air pollution and dementia in a low exposure setting : the role of noise, olfaction, and theapoe gene
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Previous research indicates an association between air pollution exposure, and risk of dementia. Still, a number of factors that may play a role in this association remain to be explored. In addition, while most studies on air pollution and brain health have taken place in highly exposed large urban areas, the studies included in this thesis are conducted in an area with relatively low levels of air pollution and road traffic noise.The overall aim of this thesis is to investigate possible mechanisms - more specifically the role of noise, olfaction and the APOE-ε4 allele - in the association between air pollution and dementia, in a low exposure area. Because olfactory deficits have been linked to air pollution, and can be an early sign of dementia, an additional aim is to examine associations between exposure to air pollution and olfactory function.Methods: Participants were drawn from the Betula project – a prospective cohort study – in Umeå, Sweden. Modelled data on concentrations of nitrogenoxides (NOx), fine particle matter (PM2.5) and levels of road traffic noise, were matched with participants residential address at baseline. PM2.5 levels at the day of testing were obtained from a measuring station in the vicinity of the test location. Data on dementia diagnoses, APOE status, olfactory functions, and covariates, were drawn from the Betula project. Dementia assessment was primarily based on medical records, and conducted by a geropsychiatrist. Odor identification was assessed using the Scandinavian Odor Identification Test, and odor detection threshold by “sniffin’ sticks”. APOE genotype was determined by DNA analyses of blood samples.Study I. Where there is pollution, there is also often noise. In addition, exposure to noise can increase the risk of dementia. The aim of study I was to investigate the individual and combined effect of noise and air pollution on risk of dementia. The results showed an association between NOx and dementia. However, noise from road traffic did not contribute to this association.Study II. Olfactory deficits can be an early sign of dementia and might also becaused by air pollution. Olfactory receptor cells in the nasal cavity are exposed to inhaled air, and the olfactory bulb is one of the areas of the brain most affectedby air pollution. The APOE-ε4 allele is important to consider, as it is a risk factor for both dementia and declining olfactory functions. The aim of study II was to investigate the role of olfaction and the APOE-ε4 allele in the association between air pollution and dementia. Stratified analyses showed that associations between PM2.5 and dementia persisted only among APOE-ε4 carriers, and those with poor odor identification ability.Study III. The olfactory system may be vulnerable to air pollution, and olfactory dysfunction is an early sign of dementia. In addition, the moderating effect of odor identification ability found in study II, could be explained by air pollution increasing the risk of olfactory functions and dementia independent of each other. Thus, the aim of study III was to investigate the associations between PM2.5 (both long term exposure, and concentrations on the day of testing), and odor identification and detection. A positive association was observed between longterm air pollution exposure and odor identification ability. No association was found between long term air pollution exposure and odor detection, or between short term exposure and either olfactory outcome.Conclusion: Low levels of long-term exposure to air pollution increases the risk of dementia. APOE-ε4 carriers, and those with poor odor identification ability, seem particularly vulnerable. No residual confounding from road traffic noisewas found, suggesting that air pollution is the main component in the association between traffic related exposures and dementia in low-exposure areas. The positive association between air pollution and odor identification might be explained by socioeconomic status, and the links between olfaction and semantic memory.
|
|
| 3. |
- Bellm, Eric C., et al.
(författare)
-
The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
-
Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
-
Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
|
|
| 4. |
- Chatterjee, Saion, et al.
(författare)
-
Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia
- 2016
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:2, s. 300-307
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.
|
|
| 5. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 6. |
|
|
| 7. |
- Nichols, Emma, et al.
(författare)
-
Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
-
Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:1, s. 88-106
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.Methods: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugarsweetened beverages).Findings: In 2016, the global number of individuals who lived with dementia was 43.8 million (95% uncertainty interval [UI] 3 7. 8-51.0), increased from 20.2 million (17. 4-23 5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1.7% (1.0-2.4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27.0 million, 95% UI 23 .3-31. 4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2.4 million (95% UI 2.1-2.8) deaths. Overall, 28.8 million (95% UI 24. 5-34. 0) DALYs were attributed to dementia; 6.4 million (95% UI 3 .4-10. 5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.Interpretation: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.
|
|
| 8. |
- Silberzahn, Raphael, et al.
(författare)
-
Many analysts, one dataset : Making transparent how variations in analytical choices affect results
- 2018
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 337-356
-
Tidskriftsartikel (refereegranskat)abstract
- Twenty-nine teams involving 61 analysts used the same dataset to address the same research question: whether soccer referees are more likely to give red cards to dark skin toned players than light skin toned players. Analytic approaches varied widely across teams, and estimated effect sizes ranged from 0.89 to 2.93 in odds ratio units, with a median of 1.31. Twenty teams (69%) found a statistically significant positive effect and nine teams (31%) observed a non-significant relationship. Overall 29 differentanalyses used 21 unique combinations of covariates. We found that neither analysts' prior beliefs about the effect, nor their level of expertise, nor peer-reviewed quality of analysis readily explained variation in analysis outcomes. This suggests that significant variation in the results of analyses of complex data may be difficult to avoid, even by experts with honest intentions. Crowdsourcing data analysis, a strategy by which numerous research teams are recruited to simultaneously investigate the same research question, makes transparent how defensible, yet subjective analytic choices influence research results.
|
|
| 9. |
|
|
