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Background: Within the last decades, there has been increasing research on the occurrence of chemicals of emerging concern (CECs) in aquatic ecosystems due to their potential adverse effects on freshwater organisms and risk to human health. However, information on CECs in freshwater environments in sub-Saharan countries is very limited. Here, we investigated the occurrence of CECs in snails and sediments collected from 48 sites within the Lake Victoria South Basin, Kenya, which have been previously investigated for water contamination. Samples were analyzed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) with a target list of 429 compounds.
Results: In total, 30 compounds have been detected in snails and 78 in sediment samples, compared to 79 previously identified compounds in water. By extending the monitoring of CECs to snails and sediments, we found 68 compounds that were not previously detected in water. These compounds include the anti-cancer drug anastrozole, detected for the first time in the Kenyan environment. Individual compound concentrations were detected up to 480 ng/g wet weight (N-ethyl-o-toluenesulfonamide) in snails and 110 ng/g organic carbon (pirimiphos-methyl) in sediments. Higher contaminant concentrations were found in agricultural sites than in areas not impacted by anthropogenic activities. Crustaceans were the organisms at greatest toxic risk from sediment contamination [toxic unit (TU) up to 0.99] with diazinon and pirimiphos-methyl driving this risk. Acute and chronic risks to algae were driven by diuron (TU up to 0.24), whereas fish were found to be at low-to-no acute risk (TU up to 0.007).
Conclusions: The compound classes present at the highest frequencies in all matrices were pesticides and biocides. This study shows substantial contamination of surface water in rural western Kenya. By filling data gaps on contamination of sediments and aquatic biota, our study reveals that CECs pose a substantial risk to environmental health in Kenya demanding for monitoring and mitigation.
Is free speech in danger on university campus? Some preliminary evidence from a most likely case
(2020)
Although universities play a key role in questions of free speech and political viewpoint diversity, they are often associated with the opposite of a free exchange of ideas: a proliferation of restrictive campus speech codes, violent protests against controversial speakers and even the firing of inconvenient professors. For some observers these trends on university campuses are a clear indicator of the dire future for freedom of speech. Others view these incidents as scandalized singular events and regard campus intolerance as a mere myth. We take an empirical look at some of the claims in the debate and present original survey evidence from a most likely case: the leftist social science studentship at Goethe University Frankfurt. Our results show that taking offense is a common experience and that a sizable number of students are in favor of restricting speech on campus. We also find evidence for conformity pressures on campus and that both the desire to restrict speech and the reluctance to speak openly differ significantly across political ideology. Left-leaning students are less likely to tolerate controversial viewpoints and right-leaning students are more likely to self-censor on politically sensitive issues such as gender, immigration, or sexual and ethnic minorities. Although preliminary, these findings may have implications for the social sciences and academia more broadly.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Hepatocyte nuclear factor 4α (HNF4α) is a ligand-sensing transcription factor and presents as a potential drug target in metabolic diseases and cancer. In humans, mutations in the HNF4α gene cause maturity-onset diabetes of the young (MODY), and the elevated activity of this protein has been associated with gastrointestinal cancers. Despite the high therapeutic potential, available ligands and structure–activity relationship knowledge for this nuclear receptor are scarce. Here, we disclose a chemically diverse collection of orthogonally validated fragment-like activators as well as inverse agonists, which modulate HNF4α activity in a low micromolar range. These compounds demonstrate the druggability of HNF4α and thus provide a starting point for medicinal chemistry as well as an early tool for chemogenomics.
leporello #7
(2021)