130 research outputs found
Estimating selection pressures on HIV-1 using phylogenetic likelihood models
Human immunodeficiency virus (HIV-1) can rapidly evolve due to selection pressures exerted by HIV-specific immune responses, antiviral agents, and to allow the virus to establish infection in different compartments in the body. Statistical models applied to HIV-1 sequence data can help to elucidate the nature of these selection pressures through comparisons of non-synonymous (or amino acid changing) and synonymous (or amino acid preserving) substitution rates. These models also need to take into account the non-independence of sequences due to their shared evolutionary history. We review how we have developed these methods and have applied them to characterize the evolution of HIV-1 in vivo. To illustrate our methods, we present an analysis of compartment-specific evolution of HIV-1 em) in blood and cerebrospinal fluid and of site-to-site variation in the gag gene of subtype C HIV-1. Copyright (C) 2008 John Wiley & Sons, Ltd
Who wrote the Ladino Siddur for Women [French National Library, Hebr. 668]?
Lazar published Siddur Tefillot: A Woman's Ladino Prayer Book in 1995, based on a manuscript found in the French National Library [Hebr. 668]. He claimed that the text originated in 15th century Spain. Minervini reviewed the publication in 1998 and argued that the manuscript must have been written later, most likely in the latter years of the sixteenth or beginning of the seventeenth century. Both researchers agree that the Siddur is a literal, non-normative translation of a Hebrew Siddur written by an amateur author. The bibliographical description of the manuscript gives its origin as “Maroc?.” The manuscript is extremely interesting because it features linguistic characteristics of the languages spoken in Andalusia, Aragon, Portugal, Italy, and Judeo-Spanish from the Ottoman Empire. This paper examines various linguistic and textual aspects of the Siddur to determine the origin of the author. Even if the manuscript did reach Paris via Morocco, the linguistic data prove that the author's background is from Italy, probably of Portuguese ex-converso origin
Internet Media in Technological Risk Amplification: Plutonium on Board the Cassini-Huygens Spacecraft
The author discusses how the Cassini controversy demonstrates the power of the Internet, particularly listservs and Usenet groups, and how this resource offers political activists an opportunity to affect the agendas of risk management policy decision-makers
Risk of subsequent primary leukaemias among 69,460 five-year survivors of childhood cancer diagnosed from 1940 to 2008 in Europe: A cohort study within PanCareSurFup
Background: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. Methods: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Results: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. Conclusions: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL. © 2019 Elsevier Lt
Wild bird influenza survey, Canada, 2005
Of 4,268 wild ducks sampled in Canada in 2005, real-time reverse transcriptase-PCR detected influenza A matrix protein (M1) gene sequence in 37% and H5 gene sequence in 5%. Mallards accounted for 61% of samples, 73% of M1-positive ducks, and 90% of H5-positive ducks. Ducks hatched in 2005 accounted for 80% of the sample.LR: 20090115; JID: 9508155; OID: NLM: PMC2600159; ppublishSource type: Electronic(1
Risk Factors for Primary Bone Cancer After Childhood Cancer:A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans. </p
Correction: Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals
Corrección de: Molecular Psychiatry https://doi-org.udd.idm.oclc.org/10.1038/s41380-022-01616-5 , publicado en línea el 14 de junio de 2022
El nombre de uno de los coautores (Javier Vázquez-Bourgon) había sido escrito incorrectamente en el pasado, lo que ya ha sido corregido.
The article “Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals”, written by Sean R. McWhinney, Katharina Brosch, Vince D. Calhoun, Benedicto Crespo-Facorro, Nicolas A. Crossley, Udo Dannlowski, Erin Dickie, Lorielle M. F. Dietze, Gary Donohoe, Stefan Plessis, Stefan Ehrlich, Robin Emsley, Petra Furstova, David C. Glahn, Alfonso Gonzalez- Valderrama, Dominik Grotegerd, Laurena Holleran, Tilo T. J. Kircher, Pavel Knytl, Marian Kolenic, Rebekka Lencer, Igor Nenadić, Nils Opel, JuliaKatharina Pfarr, Amanda L. Rodrigue, Kelly Rootes-Murdy, Alex J. Ross, Kang Sim, Antonín Škoch, Filip Spaniel, Frederike Stein, Patrik Švancer, Diana Tordesillas-Gutiérrez, Juan Undurraga, Javier Váquez-Bourgon, Aristotle Voineskos, Esther Walton, Thomas W. Weickert, Cynthia Shannon Weickert, Paul M. Thompson, Theo G. M. Erp, Jessica A. Turner, Tomas Hajek, was originally published electronically on the publisher’s internet portal on 14 June 2022 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 20 May 2022 to © The Author(s) 2022 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.Versión Publicad
Nonadaptive Amino Acid Convergence Rates Decrease over Time.
Convergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, nonadaptive convergence is much more common than expected in closely related organisms, falling off as organisms diverge. The extent of the convergent drop-off in mitochondrial proteins is well predicted by epistatic or coevolutionary effects in our "evolutionary Stokes shift" models and poorly predicted by conventional evolutionary models. Convergence probabilities decrease dramatically if the ancestral amino acids of branches being compared have diverged, but also drop slowly over evolutionary time even if the ancestral amino acids have not substituted. Convergence probabilities drop-off rapidly for quickly evolving sites, but much more slowly for slowly evolving sites. Furthermore, once sites have diverged their convergence probabilities are extremely low and indistinguishable from convergence levels at randomized sites. These results indicate that we cannot assume that excessive convergence early on is necessarily adaptive. This new understanding should help us to better discriminate adaptive from nonadaptive convergence and develop more relevant evolutionary models with improved validity for phylogenetic inference
Risk Factors for Heart Failure Among Pan-European Childhood Cancer Survivors: A PanCareSurFup and ProCardio Cohort and Nested Case-Control Study.
PURPOSE
Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines.
METHODS
This study includes the PanCareSurFup and ProCardio cohort of ≥ 5-year childhood cancer survivors diagnosed between 1940 and 2009 in seven European countries (N = 42,361). We calculated the cumulative incidence of HF and conducted a nested case-control study to evaluate detailed treatment-related risk factors.
RESULTS
The cumulative incidence of HF was 2% (95% CI, 1.7 to 2.2) by age 50 years. The case-control study (n = 1,000) showed that survivors who received a mean heart radiation therapy (RT) dose of 5 to < 15 Gy have an increased risk of HF (odds ratio, 5.5; 95% CI, 2.5 to 12.3), when compared with no heart RT. The risk associated with doses 5 to < 15 Gy increased with exposure of a larger heart volume. In addition, the HF risk increased in a linear fashion with higher mean heart RT doses. Regarding total cumulative anthracycline dose, survivors who received ≥ 100 mg/m2 had a substantially increased risk of HF and survivors treated with a lower dose showed no significantly increased risk of HF. The dose-response relationship appeared quadratic with higher anthracycline doses.
CONCLUSION
Survivors who received a mean heart RT dose of ≥ 5 Gy have an increased risk of HF. The risk associated with RT increases with larger volumes exposed. Survivors treated with < 100 mg/m2 total cumulative anthracycline dose have no significantly increased risk of HF. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines
Impact of measurement error in radon exposure on the estimated excess relative risk of lung cancer death in a simulated study based on the French Uranium Miners' Cohort
International audienceMeasurement error (ME) can lead to bias in the analysis of epidemiologic studies. Here a simulation study is described that is based on data from the French Uranium Miners' Cohort and that was conducted to assess the effect of ME on the estimated excess relative risk (ERR) of lung cancer death associated with radon exposure. Starting from a scenario without any ME, data were generated containing successively Berkson or classical ME depending on time periods, to reflect changes in the measurement of exposure to radon ( 222Rn) and its decay products over time in this cohort. Results indicate that ME attenuated the level of association with radon exposure, with a negative bias percentage on the order of 60% on the ERR estimate. Sensitivity analyses showed the consequences of specific ME characteristics (type, size, structure, and distribution) on the ERR estimates. In the future, it appears important to correct for ME upon analyzing cohorts such as this one to decrease bias in estimates of the ERR of adverse events associated with exposure to ionizing radiation. © Springer-Verlag 2012
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