| 31. |
- Kelly, Rachel S, et al.
(författare)
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Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers : a nested case-control study
- 2017
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Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence suggests a largely environmental component to non-Hodgkin's lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined.METHODS: The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers.RESULTS: The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (p < 0.05) in median exposure levels between cases and controls for any of the investigated exposures. However under a multivariate model PCB138, PCB153, HCB and DDE displayed significant inverse trends (Wald test p-value <0.05). Under stratified analyses these were determined to be driven by males and by the Diffuse Large B-Cell Lymphoma subtype. When considering those in the highest levels of exposure (>90(th) percentile) the association was null for all POPs CONCLUSION: We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL.
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| 32. |
- Kelly, Rachel, et al.
(författare)
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The Small Molecule Alpha-Synuclein Aggregator, FN075, Enhances Alpha-Synuclein Pathology in Subclinical AAV Rat Models
- 2021
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Animal models of Parkinson’s disease, in which the human α-synuclein transgene is overexpressed in the nigrostriatal pathway using viral vectors, are widely considered to be the most relevant models of the human condition. However, although highly valid, these models have major limitations related to reliability and variability, with many animals exhibiting pronounced α-synuclein expression failing to demonstrate nigrostriatal neurodegeneration or motor dysfunction. Therefore, the aim of this study was to determine if sequential intra-nigral administration of AAV-α-synuclein followed by the small α-synuclein aggregating molecule, FN075, would enhance or precipitate the associated α-synucleinopathy, nigrostriatal pathology and motor dysfunction in subclinical models. Rats were given unilateral intra-nigral injections of AAV-α-synuclein (either wild-type or A53T mutant) followed four weeks later by a unilateral intra-nigral injection of FN075, after which they underwent behavioral testing for lateralized motor functionality until they were sacrificed for immunohistological assessment at 20 weeks after AAV administration. In line with expectations, both of the AAV vectors induced widespread overexpression of human α-synuclein in the substantia nigra and striatum. Sequential administration of FN075 significantly enhanced the α-synuclein pathology with increased density and accumulation of the pathological form of the protein phosphorylated at serine 129 (pS129-α-synuclein). However, despite this enhanced α-synuclein pathology, FN075 did not precipitate nigrostriatal degeneration or motor dysfunction in these subclinical AAV models. In conclusion, FN075 holds significant promise as an approach to enhancing the α-synuclein pathology in viral overexpression models, but further studies are required to determine if alternative administration regimes for this molecule could improve the reliability and variability in these models.
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| 33. |
- Machiela, Mitchell J., et al.
(författare)
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:8, s. 1663-1676
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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| 34. |
- Nieters, Alexandra, et al.
(författare)
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Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition.
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:12, s. 2716-2722
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Tidskriftsartikel (refereegranskat)abstract
- Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (low: <20; intermediate: 20-100; high >100 kU/l) and specific IgE (negative: <0.35; positive ≥0.35 kU/I) concentrations against inhalant antigens and lymphoma risk in a study nested within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 1021 incident cases and matched controls of NHL, multiple myeloma (MM) and Hodgkin lymphoma with a mean follow-up time of 7 years were investigated. Multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated by conditional logistic regression. Specific IgE was not associated with the risk of MM, B-cell NHL and B-cell NHL subtypes. In contrast, total IgE levels were inversely associated with the risk of MM [high level: OR = 0.40 (95% CI = 0.21-0.79)] and B-cell NHL [intermediate level: OR = 0.68 (95% CI = 0.53-0.88); high level: OR = 0.62 (95% CI = 0.44-0.86)], largely on the basis of a strong inverse association with chronic lymphocytic leukemia [CLL; intermediate level: OR = 0.49 (95% CI = 0.30-0.80); high level: OR = 0.13 (95% CI = 0.05-0.35)] risk. The inverse relationship for CLL remained significant for those diagnosed 5 years after baseline. The findings of this large prospective study demonstrated significantly lower prediagnostic total IgE levels among CLL and MM cases compared with matched controls. This corresponds to the clinical immunodeficiency state often observed in CLL patients prior to diagnosis. No support for an inverse association between prediagnostic levels of specific IgE and NHL risk was found.
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| 35. |
- Pecl, Gretta T., et al.
(författare)
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Climate-driven 'species-on-the-move' provide tangible anchors to engage the public on climate change
- 2023
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Ingår i: People and Nature. - : John Wiley & Sons. - 2575-8314. ; 5:5, s. 1384-1402
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Tidskriftsartikel (refereegranskat)abstract
- Over recent decades, our understanding of climate change has accelerated greatly, but unfortunately, observable impacts have increased in tandem. Both mitigation and adaptation have not progressed at the level or scale warranted by our collective knowledge on climate change. More effective approaches to engage people on current and future anthropogenic climate change effects are urgently needed. Here, we show how species whose distributions are shifting in response to climate change, that is, ‘species-on-the-move’, present an opportunity to engage people with climate change by linking to human values, and our deep connections with the places in which we live, in a locally relevant yet globally coherent narrative. Species-on-the-move can impact ecosystem structure and function, food security, human health, livelihoods, culture and even the climate itself through feedback to the climate system, presenting a wide variety of potential pathways for people to understand that climate change affects them personally as individuals. Citizen science focussed on documenting changes in biodiversity is one approach to foster a deeper engagement on climate change. However, other possible avenues, which may offer potential to engage people currently unconnected with nature, include arts, games or collaborations with rural agriculture (e.g. new occurrences of pest species) or fisheries organisations (e.g. shifting stocks) or healthcare providers (e.g. changing distributions of disease vectors). Through the importance we place on the aspects of life impacted by the redistribution of species around us, species-on-the-move offer emotional pathways to connect with people on the complex issue of climate change in profound ways that have the potential to engender interest and action on climate change. Read the free Plain Language Summary for this article on the Journal blog.
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| 36. |
- Phillips, John B., et al.
(författare)
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Rapid Learning of Magnetic Compass Direction by C57BL/6 Mice in a 4-Armed 'Plus' Water Maze
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naive mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180 degrees so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.
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| 37. |
- Phillips, John, et al.
(författare)
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Why is it so difficult to study magnetic compass orientation in murine rodents?
- 2022
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Ingår i: Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology. - : Springer Science and Business Media LLC. - 0340-7594. ; 208:1, s. 197-212
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Forskningsöversikt (refereegranskat)abstract
- A magnetic compass sense has been demonstrated in all major classes of vertebrates, as well as in many invertebrates. In mammals, controlled laboratory studies of mice have provided evidence for a robust magnetic compass that is comparable to, or exceeds, the performance of that in other animals. Nevertheless, the vast majority of laboratory studies of spatial behavior and cognition in murine rodents have failed to produce evidence of sensitivity to magnetic cues. Given the central role that a magnetic compass sense plays in the spatial ecology and cognition of non-mammalian vertebrates, and the potential utility that a global/universal reference frame derived from the magnetic field would have in mammals, the question of why responses to magnetic cues have been so difficult to demonstrate reliably is of considerable importance. In this paper, we review evidence that the magnetic compass of murine rodents shares a number of properties with light-dependent compasses in a wide variety of other animals generally believed to be mediated by a radical pair mechanism (RPM) or related quantum process. Consistent with the RPM, we summarize both published and previously unpublished findings suggesting that the murine rodent compass is sensitive to low-level radio frequency (RF) fields. Finally, we argue that the presence of anthropogenic RF fields in laboratory settings, may be an important source of variability in responses of murine rodents to magnetic cues.
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| 38. |
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| 39. |
- Reitsma, Marissa B., et al.
(författare)
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Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015
- 2017
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 389:10082, s. 1885-1906
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Tidskriftsartikel (refereegranskat)abstract
- Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.
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| 40. |
- Roulland, Sandrine, et al.
(författare)
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t(14;18) Translocation: A Predictive Blood Biomarker for Follicular Lymphoma
- 2014
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Ingår i: Journal of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 32:13, s. 1347-1347
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. Participants and Methods Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. Results Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P < .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency > 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P < .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis. Conclusion High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.
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