Macro-quantitative vs. macro-qualitative methods in the social sciences: an example from empirical democratic theory employing new software

'Es gibt einige neue Versuche, die Kluft zwischen quantitativen und qualitativen Methoden in den Sozialwissenschaften zu überbrücken (vgl. auch Berg-Schlosser & Quenter 1996). Dieser Beitrag illustriert und testet einerseits ausschließlich einige dieser Methoden wie etwa Regressions-, Cluster- oder Diskriminanzanalyse und andererseits neuere Fall- und Diversität-orientierte Methoden wie QCA, MultiValue QCA (MVQCA) und Fuzzy-Set QCA (fs/ QCA). Dazu werden Daten genutzt, um Lipsets Theorie der sozio-ökonomischen 'Anforderungen' von Demokratie auf der Basis von 18 Fällen in Europa in der Zeit zwischen den Kriegen zu testen. Dadurch werden die spezifischen Stärken und Schwächen der jeweiligen Methoden gezeigt.' (Autorenreferat)'There are some new attempts to bridge the divide between quantitative and qualitative methods in the social sciences (see also Berg-Schlosser & Quenter 1996). This paper explicitly illustrates and tests some of these methods like regression, cluster, or discriminant analysis, on the one hand, and more recent case- and diversity-oriented methods like QCA, Multi-Value QCA (MVQCA), and Fuzzy-Set QCA (fs/ QCA) on the other. This is done by using data to test Lipset's theory of socio-economic 'requisites' of democracy on the basis of 18 cases in Europe in the interwar period. In this way, the specific strengths and weaknesses of the respective methods are demonstrated.' (author's abstract

Risk understanding and risk acknowledgement: a new approach to environmental risk assessment in marine aquaculture

publishedVersio

Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events

AIMS: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechanisms linked to TLR7 expression in atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and subjected to gene array expression analysis (n = 123). Increased levels of TLR7 transcript in the plaques were associated with better outcome in a follow-up study over a maximum of 8 years. Patients with higher TLR7 transcript levels had a lower risk of experiencing major cardiovascular and cerebrovascular events (MACCE) during the follow-up period after CEA (hazard ratio: 2.38, P = 0.012, 95% CI 1.21–4.67). TLR7 was expressed in all plaques by T cells, macrophages and endothelial cells in capillaries, as shown by immunohistochemistry. In short-term tissue cultures, ex vivo treatment of plaques with the TLR7 ligand imiquimod elicited dose-dependent secretion of IL-10, TNF-α, GM-CSF, and IL-12/IL-23p40. This secretion was blocked with a TLR7 inhibitor. Immunofluorescent tissue analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated with IL-10 receptor (r = 0.4031, P < 0.0001) and GM-CSF receptor A (r = 0.4354, P < 0.0001) transcripts. CONCLUSION: These findings demonstrate that TLR7 is abundantly expressed in human atherosclerotic plaques. TLR7 ligation elicits the secretion of pro-inflammatory and anti-inflammatory cytokines, and high TLR7 expression in plaques is associated with better patient outcome, suggesting that TLR7 is a potential therapeutic target for prevention of complications of atherosclerosis

Cause of Death, Mortality and Occult Blood in Colorectal Cancer Screening

SIMPLE SUMMARY: Colorectal cancer (CRC) screening participants with significant traces of hemoglobin in their stool have been reported to have higher mortality and different causes of death (other than CRC) compared to those without. We aimed to investigate these differences among screening participants after 33 years of follow-up. We confirmed that participants with detectable fecal hemoglobin were more likely to die in the study period and to die from different causes, such as cardiovascular and endocrine and hematological diseases, compared to those without detectable fecal hemoglobin. This confirms that fecal hemoglobin may have potential as a marker for diseases not directly related to the colon and rectum and may represent a target for future preventive measures. ABSTRACT: Fecal hemoglobin (f-Hb) detected by the guaiac fecal occult blood test (gFOBT) may be associated with mortality and cause of death in colorectal cancer (CRC) screening participants. We investigated this association in a randomly selected population of 20,694 participants followed for 33 years. We followed participants from the start of the Hemoccult-II CRC trial in 1985–1986 until December 2018. Data on mortality, cause of death and covariates were retrieved using Danish national registers. We conducted multivariable Cox regressions with time-varying exposure, reporting results as crude and adjusted hazard ratios (aHRs). We identified 1766 patients with at least one positive gFOBT, 946 of whom died in the study period. Most gFOBT-positive participants (93.23%) died of diseases unrelated to CRC and showed higher non-CRC mortality than gFOBT-negative participants (aHR: 1.20, 95% CI 1.10–1.30). Positive gFOBT participants displayed a modest increase in all-cause (aHR: 1.28, 95% CI: 1.18–1.38), CRC (aHR: 4.07, 95% CI: 3.00–5.56), cardiovascular (aHR: 1.22, 95% CI: 1.07–1.39) and endocrine and hematological mortality (aHR: 1.58, 95% CI: 1.19–2.10). In conclusion, we observed an association between positive gFOBT, cause of death and mortality. The presence of f-Hb in the gFOBT might indicate the presence of systemic diseases

The future looks like the past: Introgression of domesticated Atlantic salmon escapees in a risk assessment framework

Escapes of domesticated fish from aquaculture, followed by interbreeding with wild conspecifics, represent a threat to the genetic integrity and evolutionary trajectory of natural populations. Approximately fifty years of Atlantic salmon production has left an unprecedented legacy of widespread introgression of domesticated escapees in wild Norwegian populations. A major question, however, is whether current aquaculture practice will lead to additional introgression in the near future. As part of the updated Norwegian risk assessment of fish farming, we conducted a risk assessment for further introgression of domesticated escapees in wild populations in Norway. Extensive data of reported numbers of escapees, observed proportions of escapees in rivers, removal of escapees pre‐spawning, and the resilience of wild populations through demographic and genetic status informed the risk assessment. The analysis revealed that rivers in 10 of the 13 aquaculture production zones covering Norway display a moderate or high risk of further introgression of domesticated escapees. This comes in addition to widespread introgression that is already documented. We therefore conclude that so long as aquaculture production continues at its present level and form, there is a moderate‐to‐high risk of further introgression of domesticated salmon in many native populations throughout much of Norway.publishedVersio

Faecal haemoglobin concentrations are associated with all-cause mortality and cause of death in colorectal cancer screening

BACKGROUND: Colorectal cancer (CRC) screening reduces all-cause and CRC-related mortality. New research demonstrates that the faecal haemoglobin concentration (f-Hb) may indicate the presence of other serious diseases not related to CRC. We investigated the association between f-Hb, measured by a faecal immunochemical test (FIT), and both all-cause mortality and cause of death in a population-wide cohort of screening participants. METHODS: Between 2014 and 2018, 1,262,165 participants submitted a FIT for the Danish CRC screening programme. We followed these participants, using the Danish CRC Screening Database and several other national registers on health and population, until December 31, 2018. We stratified participants by f-Hb and compared them using a Cox proportional hazards regression on all-cause mortality and cause of death reported as adjusted hazard ratios (aHRs). We adjusted for several covariates, including comorbidity, socioeconomic factors, demography and prescription medication. RESULTS: We observed 21,847 deaths in the study period. Our multivariate analyses indicated an association relationship between increasing f-Hb and the risk of dying in the study period. This risk increased steadily from aHR 1.38 (95% CI: 1.32, 1.44) in those with a f-Hb of 7.1–11.9 μg Hb/g faeces to 2.20 (95% CI: 2.10, 2.30) in those with a f-Hb ≥60.0 μg Hb/g faeces, when compared to those with a f-Hb ≤7.0 μg Hb/g faeces. The pattern remained when excluding CRC from the analysis. Similar patterns were observed between incrementally increasing f-Hb and the risk of dying from respiratory disease, cardiovascular disease and cancers other than CRC. Furthermore, we observed an increased risk of dying from CRC with increasing f-Hb. CONCLUSIONS: Our findings support the hypothesis that f-Hb may indicate an elevated risk of having chronic conditions if causes for the bleeding have not been identified. The mechanisms still need to be established, but f-Hb may be a potential biomarker for several non-CRC diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02724-3

Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology

Abstract Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2 , SFMBT2 , AKAP6 and PHYHIP . Differentially methylated probes were independent of known PD genetic risk alleles. Meta-analysis provided suggestive evidence for a differentially methylated locus within the chromosomal region affected by the PD-associated 22q11.2 deletion. Our findings elucidate novel disease pathways in PD and DLB and generate hypotheses for future molecular studies of Lewy body pathology