| 1. |
- Idavain, Jane, et al.
(author)
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Cancer Incidence Trends in the Oil Shale Industrial Region in Estonia
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:11
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Journal article (peer-reviewed)abstract
- Large oil shale resources are found in Eastern Estonia, where the mineral resource is mined, excavated, and used for electricity generation and shale oil extraction. During industrial activities in the last 100 years, pollutants have been emitted in large amounts, some of which are toxic and carcinogenic. The current study aims to analyse time trends in cancer incidence in the oil shale industry-affected areas and compare them with overall cancer incidence rates and trends in Estonia. We analysed Estonian Cancer Registry data on selected cancer sites that have been previously indicated to have relationships with industrial activities like oil shale extraction. We included lung cancer, kidney cancer, urinary bladder cancer, leukaemia, breast cancer, and non-Hodgkin's lymphoma. A statistically significantly higher lung cancer age-standardized incidence rate (ASIR) was found during the study period (1992-2015) only in males in the oil shale areas as compared to males in Estonia overall: 133.6 and 95.5 per 100,000, respectively. However, there appeared to be a statistically significant (p < 0.05) decrease in the lung cancer ASIR in males in the oil shale areas (overall decrease 28.9%), whereas at the same time, there was a significant increase (p < 0.05) in non-oil shale areas (13.3%) and in Estonia overall (1.5%). Other cancer sites did not show higher ASIRs in the oil shale industrial areas compared to other areas in Estonia. Possible explanations could be improved environmental quality, socio-economic factors, and other morbidities.
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| 2. |
- Amare, Azmeraw, et al.
(author)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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In: Research square. - : Research Square Platform LLC.
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Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 3. |
- Fuerst, Johannes J., et al.
(author)
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The Ice-Free Topography of Svalbard
- 2018
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 45:21, s. 11760-11769
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Journal article (peer-reviewed)abstract
- We present a first version of the Svalbard ice-free topography (SVIFT1.0) using a mass conserving approach for mapping glacier ice thickness. SVIFT1.0 is informed by more than 1 million point measurements, totalling more than 8,700 km of thickness profiles. SVIFT1.0 is publicly available and represents the geometric state around the year 2010. Our estimate for the total ice volume is 6,199 km(3), equivalent to 1.5-cm sea level rise. The thickness map suggests that 13% of the glacierized area is grounded below sea level. A complementary map of error estimates comprises uncertainties in the thickness surveys as well as in other input variables. Aggregated error estimates are used to define a likely ice-volume range of 5,200-7,300 km(3). The ice front thickness of marine-terminating glaciers is a key quantity for ice loss attribution because it controls the potential ice discharge by iceberg calving into the ocean. We find a mean ice front thickness of 135 m for the archipelago (likely range 123-158 m). Plain Language Summary Svalbard is an archipelago in the Arctic, north of Norway, which is comparable in size to the New York metropolitan area. Roughly half of it is covered by glacier ice. Yet to this day, the ice volume stored in the many glaciers on Svalbard is not well known. Many attempts have been made to infer a total volume estimate, but results differ substantially. This surprises because of the long research activity in this area. A large record of more than 1 million thickness measurements exists, making Svalbard an ideal study area for the application of a state-of-the-art mapping approach for glacier ice thickness. The mapping approach computes an ice volume that will raise global sea level by more than half an inch if instantaneously melted. If spread over the metropolitan area, New York would be buried beneath a 100-m ice cover. The asset of this approach is that it provides not only a thickness map for each glacier on the archipelago but also an error map that defines the likely local thickness range. Finally, we provide the first well-informed estimate of the ice front thickness of all marine-terminating glaciers that loose icebergs to the ocean. The archipelago-wide mean ice front cliff is 135 m.
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| 4. |
- Hoffmann, Rasmus, et al.
(author)
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Innovations in health care and mortality trends from five cancers in seven European countries between 1970 and 2005
- 2014
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In: International Journal of Public Health. - : Springer Science and Business Media LLC. - 1661-8556 .- 1661-8564. ; 59:2, s. 341-350
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Journal article (peer-reviewed)abstract
- Although the contribution of health care to survival from cancer has been studied extensively, much less is known about its contribution to population health. We examine how medical innovations have influenced trends in cause-specific mortality at the national level. Based on literature reviews, we selected six innovations with proven effectiveness against cervical cancer, Hodgkin's disease, breast cancer, testicular cancer, and leukaemia. With data on the timing of innovations and cause-specific mortality (1970-2005) from seven European countries we identified associations between innovations and favourable changes in mortality. For none of the five specific cancers, sufficient evidence for an association between introduction of innovations and a positive change in mortality could be found. The highest association was found between the introduction of Tamoxifen and breast cancer mortality. The lack of evidence of health care effectiveness may be due to gradual improvements in treatment, to effects limited to certain age groups or cancer subtypes, and to contemporaneous changes in cancer incidence. Research on the impact of health care innovations on population health is limited by unreliable data on their introduction.
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| 5. |
- Hoffmann, Rasmus, et al.
(author)
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Innovations in medical care and mortality trends from four circulatory diseases between 1970 and 2005
- 2013
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In: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 23:5, s. 852-857
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Journal article (peer-reviewed)abstract
- Background:Governments have identified innovation in pharmaceuticals and medical technology as a priority for health policy. Although the contribution of medical care to health has been studied extensively in clinical settings, much less is known about its contribution to population health. We examine how innovations in the management of four circulatory disorders have influenced trends in cause-specific mortality at the population level.Methods:Based on literature reviews, we selected six medical innovations with proven effectiveness against hypertension, ischaemic heart disease, heart failure and cerebrovascular disease. We combined data on the timing of these innovations and cause-specific mortality trends (1970-2005) from seven European countries. We sought to identify associations between the introduction of innovations and favourable changes in mortality, using Joinpoint-models based on linear spline regression.Results:For both ischaemic heart disease and cerebrovascular disease, the timing of medical innovations was associated with improved mortality in four out of five countries and five out of seven countries, respectively, depending on the innovation. This suggests that innovation has impacted positively on mortality at the population level. For hypertension and heart failure, such associations could not be identified.Conclusion:Although improvements in cause-specific mortality coincide with the introduction of some innovations, this is not invariably true. This is likely to reflect the incremental effects of many interventions, the time taken for them to be adopted fully and the presence of contemporaneous changes in disease incidence. Research on the impact of medical innovations on population health is limited by unreliable data on their introduction.
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| 6. |
- Kalman, Janos L, et al.
(author)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 7. |
- Niedzielska, Magdalena, et al.
(author)
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Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
- 2015
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In: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 195:4, s. 1753-1762
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Journal article (peer-reviewed)abstract
- Plasmacytoid dendritic cells (pDCs) efficiently produce large amounts of type I IFN in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDCs) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. In this study, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDCs, but not cDCs. We confirmed the constitutive expression of Dusp9 at the protein level in pDCs generated in vitro by culture with Flt3 ligand and ex vivo in sorted splenic pDCs. Dusp9 expression was low in B220(-) bone marrow precursors and was upregulated during pDC differentiation, concomitant with established pDC markers. Higher expression of Dusp9 in pDCs correlated with impaired phosphorylation of the MAPK ERK1/2 upon TLR9 stimulation. Notably, Dusp9 was not expressed at detectable levels in human pDCs, although these displayed similarly impaired activation of ERK1/2 MAPK compared with cDCs. Enforced retroviral expression of Dusp9 in mouse GM-CSF-induced cDCs increased the expression of TLR9-induced IL-12p40 and IFN-β, but not of IL-10. Conditional deletion of Dusp9 in pDCs was effectively achieved in Dusp9(flox/flox); CD11c-Cre mice at the mRNA and protein levels. However, the lack of Dusp9 in pDC did not restore ERK1/2 activation after TLR9 stimulation and only weakly affected IFN-β and IL-12p40 production. Taken together, our results suggest that expression of Dusp9 is sufficient to impair ERK1/2 activation and enhance IFN-β expression. However, despite selective expression in pDCs, Dusp9 is not essential for high-level IFN-β production by these cells.
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| 8. |
- Veber, Triin, et al.
(author)
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Industrial Air Pollution Leads to Adverse Birth Outcomes : A Systematized Review of Different Exposure Metrics and Health Effects in Newborns
- 2022
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In: Public Health Reviews. - : Frontiers Media S.A.. - 0301-0422 .- 2107-6952. ; 43
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Journal article (peer-reviewed)abstract
- Objectives: To review the evidence of associations between adverse birth outcomes (ABO) and industrial air pollution.Methods: Searches were conducted in PubMed, and Scopus databases, and additional articles were found from snowball search techniques. The included studies feature a study population of mothers with live-born babies exposed to industrial air pollutants, and they examine the effects of industrial pollutants on adverse birth outcomes-namely, low birth weight, term low birth weight, preterm birth, and small for gestational age.Results: Altogether, 45 studies were included in this review. Exposure to PM2.5, PAHs, benzene, cadmium, and mixtures of industrial air pollutants and living near an industrial area affect birth outcomes.Conclusion: This study concludes that industrial air pollution is an important risk factor for ABO, especially low birth weight and preterm birth. The strongest evidence is associations between ABO and air pollution from power plants and petrochemical industries. Understanding of specific chemicals that are critical to birth outcomes is still vague. However, the evidence is strongest for more specific air pollutants from the industry, such as PAH, benzene, BTEX, and cadmium.
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| 9. |
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| 10. |
- Westerling, Ragnar, et al.
(author)
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The timing of introduction of pharmaceutical innovations in seven European countries
- 2014
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In: Journal of Evaluation In Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 20:4, s. 301-310
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Journal article (peer-reviewed)abstract
- Rationale, aims and objectives Differences in the performance of medical care may be due to variation in the introduction and diffusion of medical innovations. The objective of this paper is to compare seven European countries (United Kingdom, the Netherlands, West Germany, France, Spain, Estonia and Sweden) with regard to the year of introduction of six specific pharmaceutical innovations (antiretroviral drugs, cimetidine, tamoxifen, cisplatin, oxalaplatin and cyclosporin) that may have had important population health impacts. Methods We collected information on introduction and further diffusion of drugs using searches in the national and international literature, and questionnaires to national informants. We combined various sources of information, both official years of registration and other indicators of introduction (clinical trials, guidelines, evaluation reports, sales statistics). Results and conclusions The total length of the period between first and last introduction varied between 8 years for antiretroviral drugs and 22 years for cisplatin. Introduction in Estonia was generally delayed until the 1990s. The average time lags were smallest in France (2.2 years), United Kingdom (2.8 years) and the Netherlands (3.5 years). Similar rank orders were seen for year of registration suggesting that introduction lags are not only explained by differences in the process of registration. We discuss possible reasons for these between-country differences and implications for the evaluation of medical care.
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