Response to: Use of prior odds for missing persons identifications - authors' reply

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Use of prior odds for missing persons identifications

Identification of missing persons from mass disasters is based on evaluation of a number of variables and observations regarding the combination of features derived from these variables. DNA typing now is playing a more prominent role in the identification of human remains, and particularly so for highly decomposed and fragmented remains. The strength of genetic associations, by either direct or kinship analyses, is often quantified by calculating a likelihood ratio. The likelihood ratio can be multiplied by prior odds based on nongenetic evidence to calculate the posterior odds, that is, by applying Bayes' Theorem, to arrive at a probability of identity. For the identification of human remains, the path creating the set and intersection of variables that contribute to the prior odds needs to be appreciated and well defined. Other than considering the total number of missing persons, the forensic DNA community has been silent on specifying the elements of prior odds computations. The variables include the number of missing individuals, eyewitness accounts, anthropological features, demographics and other identifying characteristics. The assumptions, supporting data and reasoning that are used to establish a prior probability that will be combined with the genetic data need to be considered and justified. Otherwise, data may be unintentionally or intentionally manipulated to achieve a probability of identity that cannot be supported and can thus misrepresent the uncertainty with associations. The forensic DNA community needs to develop guidelines for objectively computing prior odds

Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains

Forensic and ancient DNA samples often are damaged and in limited quantity as a result of exposure to harsh environments and the passage of time. Several strategies have been proposed to address the challenges posed by degraded and low copy templates, including a PCR based whole genome amplification method called degenerate oligonucleotide-primed PCR (DOP-PCR). This study assessed the efficacy of four modified versions of the original DOP-PCR primer that retain at least a portion of the 5' defined sequence and alter the number of bases on the 3' end. The use of each of the four modified primers resulted in improved STR profiles from environmentally-damaged bloodstains, contemporary human skeletal remains, American Civil War era bone samples, and skeletal remains of WWII soldiers over those obtained by previously described DOP-PCR methods and routine STR typing. Additionally, the modified DOP-PCR procedure allows for a larger volume of DNA extract to be used, reducing the need to concentrate the sample and thus mitigating the effects of concurrent concentration of inhibitors. Published by Elsevier Ireland Ltd.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

One-Year Mortality After Hip Fracture: Development and Validation of a Prognostic Index

OBJECTIVES: To develop a prediction index for one year mortality after hip fracture in older adults that includes predictors from wide range of domains. DESIGN: Retrospective cohort study. SETTINGS: Health and Retirement Study (HRS) PARTICIPANTS: 857 HRS participants who experienced hip fracture between 1992 and 2010, as identified by Medicare claims data. MEASUREMENTS: Outcome measure was death within one year of hip fracture. Predictor measures were participants’ demographics, socio-economic status, social support health, geriatrics symptoms and function. We identified variables independently associated with one year mortality and used best subsets regression to identify the final model. The selected variables were weighted to create a risk index. The index was internally validated by using bootstrapping to estimate model optimism. RESULTS: Mean age at time of hip fracture was 84, and 76% of the participants were women. There were 235 deaths (27%) during the one year follow up. Five predictors of mortality were included in the final model: age over 90 (2 points); male (2 points); CHF (2 points); difficulty preparing meals (2 points); and not being able to drive (1 point). The point scores of the index were associated with one year mortality, with 0 points predicting 10% risk and 7–9 points predicting 66% risk. The c-statistic for the final model was 0.73, with an estimated optimism penalty of 0.01 indicating very little evidence of overfitting. CONCLUSION: The prognostic index combines variables about demographics, comorbidities and function, and can be used to differentiate between patients at low and high risk of one year mortality after hip fracture

Erratum to: More Comprehensive Forensic Genetic Marker Analyses for Accurate Human Remains Identification Using Massively Parallel DNA Sequencing

This article provides erratum for the article "More Comprehensive Forensic Genetic Marker Analyses for Accurate Human Remains Identification Using Massively Parallel DNA Sequencing," which incorrectly deleted an author from the author list

A survey of the occurrence of motion sickness amongst passengers at sea

A questionnaire survey of motion sickness occurrence on board passenger ferries has been conducted. Data were collected from 20,029 passengers on 114 voyages on 9 vessels: 6 ships, 2 hovercraft, and 1 jetfoil. Information was obtained about feelings of illness, the occurrence of vomiting, the taking of anti-seasickness tablets, the consumption of alcoholic drinks, regularity of travel by sea, age, and sex. overall, 7% of passengers reported vomiting at some time during the journey, 21% said they felt 'slightly unwell', 4% felt 'quite ill', and a further 4% felt 'absolutely dreadful'. Both vomiting incidence and illness rating were greater in females than in males, and there was a slight decrease in sickness occurrence with increasing age. The incidence of vomiting was related to the taking of tablets and the drinking of alcohol; there were also some interaction effects with other variables. Anecdotal information from passengers is reported and consideration is given to the effects of environmental variables.</p