Mitochondrial donation--how many women could benefit?
Ontology highlight
ABSTRACT:
SUBMITTER: Gorman GS
PROVIDER: S-EPMC4481295 | biostudies-literature | 2015 Feb
REPOSITORIES: biostudies-literature
Publications
Mitochondrial donation--how many women could benefit?
Gorman Gráinne S GS Grady John P JP Turnbull Doug M DM
The New England journal of medicine 20150128 9
Mitochondrial disease is maternally inherited and refractory to treatment, but assisted reproduction methods can result in unaffected pregnancies. The authors provide estimates of the number of affected pregnancies per year in the United Kingdom and the United States. ...[more]
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Project description:Children created through mitochondrial replacement techniques (MRTs) are commonly presented as possessing 50% of their mother's nuclear DNA, 50% of their father's nuclear DNA and the mitochondrial DNA of an egg donor. This lab-engineered genetic composition has prompted two questions: Do children who are the product of an MRT procedure have three genetic parents? And, do MRT egg donors have parental responsibilities for the children created? In this paper, I address the second question and in doing so I also address the first one. First, I present a brief account of mitochondrial diseases and MRTs. Second, I examine how MRTs affect the numerical identity of eggs and zygotes. Third, I investigate two genetic accounts of parenthood and MRT egg donation. Fourth, I explore three causal accounts of parenthood and MRT egg donation. My conclusion is that, under the appropriate circumstances, MRT egg donors are parentally responsible for the children created under genetic accounts of parenthood and under causal accounts of parenthood.
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Project description:Small regulatory RNAs are central players in the regulation of many cellular processes across all kingdoms of life. Experiments in mouse and human have shown that a typical small RNA may regulate the expression of many different genes, suggesting that small RNAs act as global regulators. It is noted though that most targets respond only weakly to the presence of the small RNA. At the same time, evidence in bacteria and animals suggest that the phenotypes associated with small RNA mutants are only due to a few of their targets. Here we assume that targets regulated by a small RNA to control function is in fact small, and propose that the role of the many other weak targets is to confer robustness to the regulation of these few principal targets. Through mathematical modeling we show that auxiliary targets may significantly buffer both number and kinetic fluctuations of the principal targets, with only minor slowdown in the kinetics of response. Analysis of genomic data suggests that auxiliary targets experience a nonspecific evolutionary pressure, playing a role at the system level. Our work is of importance for studies on small RNA functions, and impacts on the understanding of small RNA evolution.
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| S-EPMC5243113 | biostudies-literature
Project description:Study questionDoes an informed group of citizens endorse the clinical use of mitochondrial donation in a country where this is not currently permitted?Summary answerAfter hearing balanced expert evidence and having opportunity for deliberation, a majority (11/14) of participants in a citizens' jury believed that children should be able to be born using mitochondrial donation.What is known alreadyResearch suggests that patients, oocyte donors and health professionals support mitochondrial donation to prevent transmission of mitochondrial disease. Less is known about public acceptability of this novel reproductive technology, especially from evidence using deliberative methods.Study design, size, durationThis study comprised a citizens' jury, an established method for determining the views of a well-informed group of community members. The jury had 14 participants, and ran over one and a half days in 2017.Participants/materials, setting, methodsJurors were members of the public with no experience of mitochondrial disease. They heard and engaged with relevant evidence and were asked to answer the question: 'Should Australia allow children to be born following mitochondrial donation?'Main results and the role of chanceEleven jurors decided that Australia should allow children to be born following mitochondrial donation; 7 of whom added conditions such as the need to limit who can access the intervention. Three jurors decided that children should not (or not yet) be born using this intervention. All jurors were particularly interested in the reliability of evidence, licensing/regulatory mechanisms and the rights of children to access information about their oocyte donors.Limitations, reasons for cautionJurors' views were well informed and reflected critical deliberation and discussion, but are not intended to be representative of the whole population.Wider implications of the findingsWhen presented with high quality evidence, combined with opportunities to undertake structured deliberation of novel reproductive technologies, members of the public are able to engage in detailed discussions. This is the first study to use an established deliberative method to gauge public views towards mitochondrial donation.Study funding/competing interest(s)This study was funded by a University of Sydney Industry and Community Collaboration Seed Award (2017), which was awarded contingent on additional funding from the Mito Foundation. Additional funding was provided by the Mito Foundation. The Foundation was not involved in jury facilitation or deliberation, nor analysis of research data.Trial registration numberNot applicable.
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Project description:BackgroundSince 2007, Medicare has provided one-time abdominal aortic aneurysm (AAA) screening for men with smoking history, and men and women with a family history of AAA as part of its Welcome to Medicare visit.ObjectiveWe examined utilization of the new AAA screening benefit and estimated how increased utilization could influence population health as measured by life years gained. Additionally, we explored the impact of expanding screening to women with smoking history.DesignAnalysis of Medicare claims and a simulation model to estimate the effects of screening, using published data for parameter estimates.SettingAAA screening in the primary care setting.PatientsNewly-enrolled Medicare beneficiaries aged 65 years, with smoking history or family history of AAA.Main measuresLife expectancy, 10-year survival rates.Key resultsMedicare data revealed low utilization of AAA screening, under 1% among those eligible. We estimate that screening could increase life expectancy per individual invited to screening for men with smoking history (0.11 years), with family history of AAA (0.17 years), and women with family history (0.08 years), and smoking history (0.09 years). Average gains of 131 life years per 1,000 persons screened for AAA compare favorably with the grade B United States Preventive Services Task Force (USPSTF) recommendation for breast cancer screening, which yields 95-128 life years per 1,000 women screened. These findings were robust over a range of scenarios.LimitationsThe simulation results reflect assumptions regarding AAA prevalence, treatment, and outcomes in specific populations based on published research and US survey data. Published data on women were limited.ConclusionsThe Welcome to Medicare and AAA screening benefits have been underutilized. Increasing utilization of AAA screening would yield substantial gains in life expectancy. Expanding screening to women with smoking history also has the potential for substantial health benefits.
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Project description:ImportanceLiving-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC).ObjectiveTo investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription.Design, setting, and participantsThis multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020.Main outcomes and measuresIntention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created.ResultsA total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated.Conclusions and relevanceThis study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.
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