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The impact of endocrine disrupting chemicals on adrenal corticosteroids – A systematic review of epidemiological studies
Full text linkBackground
The role of endocrine disrupting chemicals (EDCs) in the development of metabolic syndrome has gained increasing recognition in recent years. The underlying mechanisms are largely unresolved. Disruption of corticosteroid action and hypothalamic-pituitary-adrenal (HPA) axis are considered possible mechanisms.
Objective
To summarise epidemiological studies investigating an association between EDC concentration and altered levels of corticosteroids and the adrenocorticotropic hormone (ACTH).
Methods
Following the PRISMA guidelines, we searched PubMed and the Cochrane Library for epidemiological studies published from database inception until April 1st, 2024. Various groups of EDCs were evaluated with the prerequisite of direct measurement of the chemical, a metabolite, or biomarker.
Results
We identified 2094 articles. After removing duplicates and screening, 27 studies were included. Studies focused predominantly on glucocorticoids (n = 26) compared to mineralocorticoids (n = 5) and ACTH (n = 2). The most studied EDCs were pesticides (n = 9) and phthalates (n = 8). Significant associations between the concentrations of specific EDCs and hormone levels were found in all but three studies. Only one study described an association between EDCs, and hormone concentration and metabolic features.
Conclusion
There is clear evidence for the impact of specific EDCs on plasma corticosteroid concentrations in different age groups worldwide, however, results varied according to EDC class, study population and study methodology. Further research combining EDC and hormone concentrations, and clinical features, complemented by experimental investigations to study cell mechanisms, is needed to gain holistic knowledge of EDCs’ influence on glucocorticoid- and mineralocorticoid-related disorders
Molecular hyperselection for optimal choice of first-line targeted therapy independent of primary tumor sidedness: An exploratory analysis of the randomized FIRE-3 study performed in RAS wild-type metastatic colorectal cancer
No full textIntroduction
Molecular diagnostics play a pivotal role in guiding therapy for metastatic colorectal cancer (mCRC). Current guidelines recommend stratification based on biomarkers such as RAS, BRAF, and DNA mismatch-repair (MMR) status to select between anti-EGFR (epidermal growth factor receptor) and anti-VEGF (vascular endothelial growth factor) therapies.
Materials and methods
This retrospective analysis evaluated the randomized FIRE-3 study that compared first-line treatment with FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in RAS wild-type patients. The present analysis included 199 patients with RAS/BRAF wild-type MMR proficient tumors. Next-generation sequencing (NGS) was successfully performed in all patients and allowed stratification into hyperselected (no predefined genetic alterations) or gene altered subgroups using the previously published approach of the PRESSING-studies.
Results
Hyperselection according to PRESSING-3 was associated with a survival benefit from anti-EGFR-based therapy compared to bevacizumab (38.5 months vs. 27.5 months; HR 0.68; 95 % CI, 0.44–1.05; P = 0.08). This benefit was observed in both, right- and left-sided tumors, (HR 0.58 and HR 0.70). Patients with gene alterations showed inferior survival compared to hyperselected patients across all subgroups. In this unfavorable subgroup, application of cetuximab and bevacizumab were associated with comparable OS (total cohort: HR 1.04; 95 % CI, 0.61–1.79). Again, this finding was independent of primary tumor sidedness (left-sided tumors: HR 1.10; 95 % CI, 0.59–2.07; right-sided tumors: HR 1.05; 95 % CI, 0.31–3.55).
Conclusion
Molecular hyperselection facilitated by next generation sequencing could replace primary tumor sidedness as a tool of decision making for optimal choice of targeted therapy in first-line treatment of RAS wild-type mCR
Cellular responses to RNA damage
No full textRNA plays a central role in protein biosynthesis and performs diverse regulatory and catalytic functions, making it essential for all processes of life. Like DNA, RNA is constantly subjected to damage from endogenous and environmental sources. However, while the DNA damage response has been extensively studied, it was long assumed that RNA lesions are relatively inconsequential due to the transient nature of most RNA molecules. Here, we review recent studies that challenge this view by revealing complex RNA damage responses that determine survival when cells are exposed to nucleic acid-damaging agents and promote the resolution of RNA lesions
Therapeutic strategies for adrenocortical carcinoma: integrating genomic insights, molecular targeting, and immunotherapy
No full textAugmented Reality and Spatial Fit Uncertainty in Online Retailing
No full textAugmented Reality (AR) is an emerging technology in e-commerce that facilitates online product evaluation. It enables consumers to project virtual product models into their real-world surroundings in real time using their mobile devices. By improving online product evaluation, AR has the potential to reduce online consumer product uncertainty and thereby increase e-commerce sales. This paper investigates the effectiveness of AR enablement in reducing spatial product fit uncertainty by analyzing a unique dataset of online purchases of AR-enabled and non-AR-enabled products from a multi-channel home interior retailer. The authors' identification strategy exploits a pandemic-related shutdown of offline retail stores to isolate the effect of AR enablement on online sales when the offline channel is unavailable for product evaluation. The authors find that AR enablement can be particularly effective for evaluating and selling larger products, which are associated with higher spatial fit uncertainty. The authors derive channel-related implications for retailers deploying AR and contribute to retail and consumer research by enhancing the nuanced understanding of online consumer behavior when interacting with a new digital technology
Occupations and retirement across countries
No full textWe study the role of occupations for individual and aggregate retirement behavior. First, we document large differences in individual retirement ages across occupations in U.S. data. We then show that retirement behavior among European workers is strongly correlated with U.S. occupational retirement ages, indicating an inherent association between occupations and retirement that is present across institutional settings. Finally, we find that occupational composition is an important predictor of aggregate retirement behavior across 45 countries. Our findings suggest that events affecting occupational structure, such as skill-biased technological change or international trade, can have consequences for aggregate retirement behavior and social security systems
Finite- and large-sample inference for ranks using multinomial data with an application to ranking political parties
No full textIt is common to rank different categories by means of preferences that are revealed through data on choices. A prominent example is the ranking of political candidates or parties using the estimated share of support each one receives in surveys or polls about political attitudes. Since these rankings are computed using estimates of the share of support rather than the true share of support, there may be considerable uncertainty concerning the true ranking of the political candidates or parties. In this paper, we consider the problem of accounting for such uncertainty by constructing confidence sets for the rank of each category. We consider both the problem of constructing marginal confidence sets for the rank of a particular category as well as simultaneous confidence sets for the ranks of all categories. A distinguishing feature of our analysis is that we exploit the multinomial structure of the data to develop confidence sets that are valid in finite samples. We additionally develop confidence sets using the bootstrap that are valid only approximately in large samples. We use our methodology to rank political parties in Australia using data from the 2019 Australian Election Survey. We find that our finite-sample confidence sets are informative across the entire ranking of political parties, even in Australian territories with few survey respondents and/or with parties that are chosen by only a small share of the survey respondents. In contrast, the bootstrap-based confidence sets may sometimes be considerably less informative. These findings motivate us to compare these methods in an empirically-driven simulation study, in which we conclude that our finite-sample confidence sets often perform better than their large-sample, bootstrap-based counterparts, especially in settings that resemble our empirical application
Analysis of change in health-related quality of life in patients with COPD over 6 years, including information on dropouts: Results from the German COSYCONET cohort
Full text linkIntroduction
Long-term studies as well as adequate methods accounting for attrition are necessary to measure the longitudinal change in health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). The aim of this analysis was to evaluate the change in HRQoL, measured by the EQ-5D-3L, over 6 years, while adequately accounting for dropouts.
Methods
We examined 6-year mean changes in HRQoL for 2701 COPD patients from the COSYCONET cohort study, based on data from baseline and follow-up visits after 1.5, 3, 4.5, and 6 years. Patients who dropped out during the 6-year follow-up were included in the analysis by imputing missing values using multiple imputation. We incorporated information on dropout reason in the imputation model and used additional information on HRQoL for dropouts to assess the imputation model.
Results
Average EQ-5D-3L deteriorated significantly by −0.121 (95 %-CI: 0.125; −0.117) over 6 years for all patients and by −0.047 (95 %-CI: 0.049; −0.045) when patients who dropped out because of death were excluded. Patients with impaired forced expiratory volume in 1 s (FEV1) in percent of predicted normal values at baseline had a more pronounced 6-year mean decline in HRQoL. Inclusion of dropout information in the imputation model was informative. Assessment of the imputed data revealed that performing multiple imputation produced less biased results compared to complete case analysis.
Conclusion
The HRQoL decreased significantly over time for COPD patients. We propose a method to include all dropouts as well as additional information on dropouts to reduce bias in the results
Enjoyable for some, stressful for others? Physiological and subjective indicators of achievement emotions during adaptive versus fixed-item testing
No full textIn light of the increasing use of computerized adaptive testing, we investigated how adaptive testing impacts test-takers’ subjective emotional experiences and their psychophysiological arousal. Applying a within-person design (N = 89), we compared participants’ affective states while working on an adaptive and a fixed-item test of numerical reasoning ability. During both tests, we continuously recorded participants’ skin conductance response. In addition, they filled in a self-report questionnaire after each of the three item blocks per test, assessing discrete achievement emotions (joy, pride, anger, boredom, frustration, and anxiety) and perceived level of task difficulty. As expected, participants showed higher levels of psychophysiological arousal in the adaptive compared to the fixed-item test, indicating that the adaptive test was more stimulating, independent of emotional valence. For subjective achievement emotions, we expected disordinal interaction effects between test type and ability (objective control experience) and between test type and relative perceived difficulty of the two tests (subjective control experience). This was supported for relative perceived difficulty, as participants indeed reported more joy and pride, and less frustration, anxiety, and anger on whichever test they subjectively perceived as easier. Meanwhile, no main effects of test type and no interaction between test type and ability were found. This is in line with the control-value theory and shows that it is not the adaptivity of a test that influences subjective emotional experience, but rather how difficult the adaptive test is perceived by test-takers compared to a fixed-item test. Directions for future research and implications for practice are discussed
Fixing sustainability through technoscience and diversity: The case of EU agriculture policy
Full text linkSustainability is a conveniently vague boundary term with which a variety of interest groups can identify. Over time, it has grown together with a technoscientific paradigm which demands a closer look at how actors envision science, technology, digitization, and innovation to foster said sustainability, and how the latter has shifted as a result. Sustainability also continues to hold strong value and political weight in the EU, where technoscientific optimism has had a binding effect, particularly in efforts of environmental protection in agriculture (in light of the Green Deal), in an increasingly decentralized political union. This paper discusses these processes in the recent reform of the Common Agriculture Policy (CAP; 2023–2027) by focusing on the one hand on how sustainability’s three pillars – the environmental, the social, and the economic – are ‘reconciled,’ and on the other, on the new ‘eco-schemes’ as an instrument to achieve a more sustainable agriculture. Empirical data gleaned from participant observation, expert interviews and policy document analysis show how in EU agriculture policy science, digitization/technology and innovation are imagined as fixtures that cohere these pillars, thereby maintaining a growth paradigm imminent to dominant sustainability discourses. This technoscientific sustainability is also evident in agriculture measures on the ground, in the new eco-schemes, which offer a diversity of farming approaches for EU's member states, ranging from agroforestry to precision farming. In this technocratic instrument, holistic systems, like agroecology, are rendered technical ‘tools’ that member states can combine at will, fostering a politics of toolkit diversity that accommodates diverse farming approaches and philosophies while evading environmental compliance. Scientific epistemology, technical quantification, digital tools and innovation thus act as wider discursive fixture that not only hold together the holy trinity of sustainability, but also accommodates diverse landscapes and member states, and through that the political union of an increasingly decentralized EU