Mitochondrial DNA Haplogroup Analysis Reveals no Association between the Common Genetic Lineages and Prostate Cancer in the Korean Population

Mitochondrial DNA (mtDNA) variation has recently been suggested to have an association with various cancers, including prostate cancer risk, in human populations. Since mtDNA is haploid and lacks recombination, specific mutations in the mtDNA genome associated with human diseases arise and remain in particular genetic backgrounds referred to as haplogroups. To assess the possible contribution of mtDNA haplogroup-specific mutations to the occurrence of prostate cancer, we have therefore performed a population-based study of a prostate cancer cases and corresponding controls from the Korean population. No statistically significant difference in the distribution of mtDNA haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that specific mtDNA mutations/lineages did not appear to have a significant effect on a predisposition to prostate cancer in the Korean population, although larger sample sizes are necessary to validate our results

Globally convergent evolution strategies for constrained optimization

International audienceIn this paper we propose, analyze, and test algorithms for constrained optimization when no use of derivatives of the objective function is made. The proposed methodology is built upon the globally convergent evolution strategies previously introduced by the authors for unconstrained optimization. Two approaches are encompassed to handle the constraints. In a first approach, feasibility is first enforced by a barrier function and the objective function is then evaluated directly at the feasible generated points. A second approach projects first all the generated points onto the feasible domain before evaluating the objective function.The resulting algorithms enjoy favorable global convergence properties (convergence to stationarity from arbitrary starting points), regardless of the linearity of the constraints.The algorithmic implementation (i) includes a step where previously evaluated points are used to accelerate the search (by minimizing quadratic models) and (ii) addresses the particular cases of bounds on the variables and linear constraints. Our solver is compared to others, and the numerical results confirm its competitiveness in terms of efficiency and robustness

Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas.</p> <p>Methods</p> <p>We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (<it>MT-ATP6, MT-CO1, MT-CYB, MT-ND1</it>, <it>MT-ND6</it>, and <it>MT-RNR1</it>) were quantified in 62 cancer tissues by real-time RT-PCR.</p> <p>Results</p> <p>Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene <it>RNR1 </it>might be used as a predictor of tumour sensitivity to chemotherapy.</p> <p>Conclusion</p> <p>In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.</p

Performance of mitochondrial DNA mutations detecting early stage cancer

<p>Abstract</p> <p>Background</p> <p>Mutations in the mitochondrial genome (mtgenome) have been associated with cancer and many other disorders. These mutations can be point mutations or deletions, or admixtures (heteroplasmy). The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites.</p> <p>Methods</p> <p>We determined the mtDNA mutation load in the entire mitochondrial genome of 26 individuals with different early stage cancers (lung, bladder, kidney) and 12 heavy smokers without cancer. MtDNA was sequenced from three matched specimens (blood, tumor and body fluid) from each cancer patient and two matched specimens (blood and sputum) from smokers without cancer. The inherited wildtype sequence in the blood was compared to the sequences present in the tumor and body fluid, detected using the Affymetrix Genechip^®Human Mitochondrial Resequencing Array 1.0 and supplemented by capillary sequencing for noncoding region.</p> <p>Results</p> <p>Using this high-throughput method, 75% of the tumors were found to contain mtDNA mutations, higher than in our previous studies, and 36% of the body fluids from these cancer patients contained mtDNA mutations. Most of the mutations detected were heteroplasmic. A statistically significantly higher heteroplasmy rate occurred in tumor specimens when compared to both body fluid of cancer patients and sputum of controls, and in patient blood compared to blood of controls. Only 2 of the 12 sputum specimens from heavy smokers without cancer (17%) contained mtDNA mutations. Although patient mutations were spread throughout the mtDNA genome in the lung, bladder and kidney series, a statistically significant elevation of tRNA and ND complex mutations was detected in tumors.</p> <p>Conclusion</p> <p>Our findings indicate comprehensive mtDNA resequencing can be a high-throughput tool for detecting mutations in clinical samples with potential applications for cancer detection, but it is unclear the biological relevance of these detected mitochondrial mutations. Whether the detection of tumor-specific mtDNA mutations in body fluidsy this method will be useful for diagnosis and monitoring applications requires further investigation.</p

A systematic review of the effect of retention methods in population-based cohort studies

Background: Longitudinal studies are of aetiological and public health relevance but can be undermined by attrition. The aim of this paper was to identify effective retention strategies to increase participation in population-based cohort studies. Methods: Systematic review of the literature to identify prospective population-based cohort studies with health outcomes in which retention strategies had been evaluated. Results: Twenty-eight studies published up to January 2011 were included. Eleven of which were randomized controlled trials of retention strategies (RCT). Fifty-seven percent of the studies were postal, 21% in-person, 14% telephone and 7% had mixed data collection methods. A total of 45 different retention strategies were used, categorised as 1) incentives, 2) reminder methods, repeat visits or repeat questionnaires, alternative modes of data collection or 3) other methods. Incentives were associated with an increase in retention rates, which improved with greater incentive value. Whether cash was the most effective incentive was not clear from studies that compared cash and gifts of similar value. The average increase in retention rate was 12% for reminder letters, 5% for reminder calls and 12% for repeat questionnaires. Ten studies used alternative data collection methods, mainly as a last resort. All postal studies offered telephone interviews to non-responders, which increased retention rates by 3%. Studies that used face-to-face interviews increased their retention rates by 24% by offering alternative locations and modes of data collection. Conclusions: Incentives boosted retention rates in prospective cohort studies. Other methods appeared to have a beneficial effect but there was a general lack of a systematic approach to their evaluation

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering

Maximizing and stabilizing luminescence from halide perovskites with potassium passivation

Metal halide perovskites are of great interest for various high-performance optoelectronic applications. The ability to tune the perovskite bandgap continuously by modifying the chemical composition opens up applications for perovskites as coloured emitters, in building-integrated photovoltaics, and as components of tandem photovoltaics to increase the power conversion efficiency. Nevertheless, performance is limited by non-radiative losses, with luminescence yields in state-of-the-art perovskite solar cells still far from 100 per cent under standard solar illumination conditions. Furthermore, in mixed halide perovskite systems designed for continuous bandgap tunability2 (bandgaps of approximately 1.7 to 1.9 electronvolts), photoinduced ion segregation leads to bandgap instabilities. Here we demonstrate substantial mitigation of both non-radiative losses and photoinduced ion migration in perovskite films and interfaces by decorating the surfaces and grain boundaries with passivating potassium halide layers. We demonstrate external photoluminescence quantum yields of 66 per cent, which translate to internal yields that exceed 95 per cent. The high luminescence yields are achieved while maintaining high mobilities of more than 40 square centimetres per volt per second, providing the elusive combination of both high luminescence and excellent charge transport. When interfaced with electrodes in a solar cell device stack, the external luminescence yield—a quantity that must be maximized to obtain high efficiency—remains as high as 15 per cent, indicating very clean interfaces. We also demonstrate the inhibition of transient photoinduced ion-migration processes across a wide range of mixed halide perovskite bandgaps in materials that exhibit bandgap instabilities when unpassivated. We validate these results in fully operating solar cells. Our work represents an important advance in the construction of tunable metal halide perovskite films and interfaces that can approach the efficiency limits in tandem solar cells, coloured-light-emitting diodes and other optoelectronic applications.M.A.-J. thanks Nava Technology Limited and Nyak Technology Limited for their funding and technical support. Z.A.-G. acknowledges funding from a Winton Studentship, and ICON Studentship from the Lloyd’s Register Foundation. This project has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement number PIOF-GA-2013-622630, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 756962), and the Royal Society and Tata Group (UF150033). We thank the Engineering and Physical Sciences Research Council (EPSRC) for support. XMaS is a mid-range facility at the European Synchrotron Radiation Facility supported by the EPSRC and we are grateful to the XMaS beamline team staff for their support. We thank Diamond Light Source for access to beamline I09 and staff member T.-L. Lee as well as U. Cappel for assistance during the HAXPES measurements. S.C., C.D. and G.D. acknowledge funding from the ERC under grant number 25961976 PHOTO EM and financial support from the European Union under grant number 77 312483 ESTEEM2. M.A. thanks the president of the UAE’s Distinguished Student Scholarship Program, granted by the Ministry of Presidential Affairs. H.R. and B.P. acknowledge support from the Swedish research council (2014-6019) and the Swedish foundation for strategic research. E.M.H. and T.J.S. were supported by the Netherlands Organization for Scientific Research under the Echo grant number 712.014.007