| 1. |
- Hudson, Thomas J., et al.
(författare)
-
International network of cancer genome projects
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
|
|
| 2. |
- vom Saal, Frederick S., et al.
(författare)
-
The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA)
- 2024
-
Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 132:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2 ng/kg body weight (BW)/day. BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA’s revision of the TDI for BPA.Objectives: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government–academic program model.Discussion: We strongly endorse EFSA’s revised TDI for BPA and support the European Commission’s (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Mahjani, B, et al.
(författare)
-
Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders
- 2022
-
Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies report an important—and previously underestimated—role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. Method: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. Results: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). Conclusions: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.
|
|
| 6. |
- Nilsson, Kjell, et al.
(författare)
-
A General Method for the Immobilization of Cells with Preserved Viability
- 1983
-
Ingår i: Applied Microbiology and Biotechnology. ; 17, s. 319-326
-
Tidskriftsartikel (refereegranskat)abstract
- Microbial, algal, plant and animal cells have been immobilized, with preserved viability, by entrapment in various matrices according to a new bead polymerization technique. The cell polymer/monomer mixture is kept suspended in a hydrophobic phase such as soy, paraffin, or silicon oil, tri-n-butylphosphate, or dibutyphtalate, which is compatible with the cells. The various monomers or polymers tested include agarose, agar, carrageenan, alginate, fibrin, and polyacrylamide. Furthermore, by adjustment of the stirring speed of the suspension, beads of desired diameter can easily be obtained. The entrapped cells are fully viable and biosynthetically active.
|
|
| 7. |
- Nilsson, S, et al.
(författare)
-
Real-time Fluorescence Imaging of Capillary Electrophoresis
- 1995
-
Ingår i: Journal of Capillary Electrophoresis. - 1079-5383. ; 2:1, s. 46-52
-
Tidskriftsartikel (refereegranskat)abstract
- An arrangement for real-time fluorescence imaging of capillary electrophoretic separations is described. A decoated capillary was excited along a substantial part of its length by a dye laser pumped with an XeCl excimer laser tuned to match the fluorophors in the sample. Light emitted from the migrating, fluorescent molecules was detected by an image-intensified, thermoelectrically cooled charge-coupled device camera. The camera signals were processed by a computer and displayed as moving peaks on a screen in real-time, thus allowing the progress of the separation to be monitored continuously. Basic characteristics of the imaging arrangement such as sensitivity (signal-to-noise ratio) and resolution were checked with fluorescein samples. The imaging principle was also illustrated with a separation of a mixture of DNA fragments on a commercially available capillary designated for DNA separations. The benefits of real-time imaging for separation processes, in particular for capillary electrophoresis, are discussed.
|
|
| 8. |
- Pearce, Neil E, et al.
(författare)
-
IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
|
|
| 9. |
- van den Berg, Martin, et al.
(författare)
-
Polybrominated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls : Inclusion in the Toxicity Equivalency Factor Concept for Dioxin-Like Compounds
- 2013
-
Ingår i: Toxicological Sciences. - Oxfors, United Kingdom : Oxford University Press. - 1096-6080 .- 1096-0929. ; 133:2, s. 197-208
-
Forskningsöversikt (refereegranskat)abstract
- In 2011 a joint World Health Organization (WHO) and United Nations Environment Programme (UNEP) expert consultation took place, during which the possible inclusion of brominated analogues of the dioxin-like compounds in the WHO Toxicity Equivalency Factor (TEF) scheme were evaluated. The expert panel concluded that polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), and some dioxin-like biphenyls (dl-PBBs) may contribute significantly in daily human background exposure to the total dioxin toxic equivalencies (TEQs). These compounds are also commonly found in the aquatic environment. Available data for fish toxicity were evaluated for possible inclusion in the WHO-UNEP TEF scheme (Van den Berg et al., 1998). Because of the limited database it was decided not to derive specific WHO-UNEP TEFs for fish, but for ecotoxicological risk assessment the use of specific relative effect potencies (REPs) from fish embryo assays is recommended. Based on the limited mammalian REP database for these brominated compounds, it was concluded that sufficient differentiation from the present TEF values of the chlorinated analogues (Van den Berg et al., 2005) was not possible. However, the REPs for PBDDs, PBDFs, and non-ortho dl-PBBs in mammals closely follow those of the chlorinated analogues, at least within one order of magnitude. Therefore, the use of similar interim TEF values for brominated and chlorinated congeners for human risk assessment is recommended, pending more detailed information in the future.
|
|
| 10. |
- Zoeller, R. Thomas, 1952-, et al.
(författare)
-
European Medicines Agency Conflicts With the European Food Safety Authority (EFSA) on Bisphenol A Regulation
- 2023
-
Ingår i: Journal of the Endocrine Society. - : Oxford University Press. - 2472-1972. ; 7:9
-
Tidskriftsartikel (refereegranskat)abstract
- The European Food Safety Authority (EFSA) has revised their estimate of the toxicity of bisphenol A (BPA) and, as a result, have recommended reducing the tolerable daily intake (TDI) by 20 000-fold. This would essentially ban the use of BPA in food packaging such as can liners, plastic food containers, and in consumer products. To come to this conclusion, EFSA used a systematic approach according to a pre-established protocol and included all guideline and nonguideline studies in their analysis. They found that Th-17 immune cells increased with very low exposure to BPA and used this endpoint to revise the TDI to be human health protective. A number of regulatory agencies including the European Medicines Agency (EMA) have written formal disagreements with several elements of EFSA's proposal. The European Commission will now decide whether to accept EFSA's recommendation over the objections of EMA. If the Commission accepts EFSA's recommendation, it will be a landmark action using knowledge acquired through independent scientific studies focused on biomarkers of chronic disease to protect human health. The goal of this Perspective is to clearly articulate the monumental nature of this debate and decision and to explain what is at stake. Our perspective is that the weight of evidence clearly supports EFSA's proposal to reduce the TDI by 20 000-fold.
|
|
