Verifying likelihoods for low template DNA profiles using multiple replicates

AbstractTo date there is no generally accepted method to test the validity of algorithms used to compute likelihood ratios (LR) evaluating forensic DNA profiles from low-template and/or degraded samples. An upper bound on the LR is provided by the inverse of the match probability, which is the usual measure of weight of evidence for standard DNA profiles not subject to the stochastic effects that are the hallmark of low-template profiles. However, even for low-template profiles the LR in favour of a true prosecution hypothesis should approach this bound as the number of profiling replicates increases, provided that the queried contributor is the major contributor. Moreover, for sufficiently many replicates the standard LR for mixtures is often surpassed by the low-template LR. It follows that multiple LTDNA replicates can provide stronger evidence for a contributor to a mixture than a standard analysis of a good-quality profile. Here, we examine the performance of the likeLTD software for up to eight replicate profiling runs. We consider simulated and laboratory-generated replicates as well as resampling replicates from a real crime case. We show that LRs generated by likeLTD usually do exceed the mixture LR given sufficient replicates, are bounded above by the inverse match probability and do approach this bound closely when this is expected. We also show good performance of likeLTD even when a large majority of alleles are designated as uncertain, and suggest that there can be advantages to using different profiling sensitivities for different replicates. Overall, our results support both the validity of the underlying mathematical model and its correct implementation in the likeLTD software

An overview of mutational and copy number signatures in human cancer

The genome of each cell in the human body is constantly under assault from a plethora of exogenous and endogenous processes that can damage DNA. If not successfully repaired, DNA damage generally becomes permanently imprinted in cells, and all their progenies, as somatic mutations. In most cases, the patterns of these somatic mutations contain the tell-tale signs of the mutagenic processes that have imprinted and are termed mutational signatures. Recent pan-cancer genomic analyses have elucidated the compendium of mutational signatures for all types of small mutational events, including: (i) single base substitutions; (ii) doublet base substitutions; and (iii) small insertions/deletions. In contrast to small mutational events, where, in most cases, DNA damage is a prerequisite, aneuploidy, which refers to the abnormal number of chromosomes in a cell, usually develops from mistakes during DNA replication. Such mistakes include DNA replication stress, mitotic errors caused by faulty microtubule dynamics, or cohesion defects that contribute to chromosomal breakage and can lead to copy number alterations or even to structural rearrangements. These aberrations also leave behind genomic scars which can be inferred from sequencing as copy number signatures and rearrangement signatures. The analyses of mutational signatures of small mutational events have been extensively reviewed [1-3], so we will not comprehensively re-examine them here. Rather, our focus will be on summarizing the existing knowledge for mutational signatures of copy number alterations. As studying copy number signatures is an emerging field, we briefly summarize the utility that mutational signatures of small mutational events have provided in basic science, cancer treatment, and cancer prevention and we emphasize the future role that copy number signatures may play in each of these fields

Digital Orthopaedics: A Glimpse Into the Future in the Midst of a Pandemic.

BackgroundThe response to COVID-19 catalyzed the adoption and integration of digital health tools into the health care delivery model for musculoskeletal patients. The change, suspension, or relaxation of Medicare and federal guidelines enabled the rapid implementation of these technologies. The expansion of payment models for virtual care facilitated its rapid adoption. The authors aim to provide several examples of digital health solutions utilized to manage orthopedic patients during the pandemic and discuss what features of these technologies are likely to continue to provide value to patients and clinicians following its resolution.ConclusionThe widespread adoption of new technologies enabling providers to care for patients remotely has the potential to permanently change the expectations of all stakeholders about the way care is provided in orthopedics. The new era of Digital Orthopaedics will see a gradual and nondisruptive integration of technologies that support the patient's journey through the successful management of their musculoskeletal disease

Statistical bias in isotope ratios

Dr. Coath is supported in this work by STFC grant ref. ST/F002734/1.This paper presents the mathematics of the systematic bias in the expected value of the ratio of two noise- corrected Poisson-distributed variables, such as ion counting measurements. Such bias can lead to the reporting of incorrect ratios and, in some cases, systematic correlations with other measurements which can impact the scientific interpretation. We describe a novel method of treating such measurements which results in a negligible, exponentially small bias. We also re-examine the conventional approach deriving an exact expression for the bias including the noise correction explicitly.PostprintPeer reviewe

Confirmation of mass-independent Ni isotopic variability in iron meteorites

Funding: NERC (NE/F007329/1), STFC (ST/F002734/1) and NHM.We report high-precision analyses of internally-normalised Ni isotope ratios in 12 bulk iron meteorites. Our measurements of 60Ni/61Ni, 62Ni/61Ni and 64Ni/61Ni normalised to 58Ni/61Ni and expressed in parts per ten thousand (‱) relative to NIST SRM 986 as ε60Ni586, ε62Ni5861 and ε64Ni5861 vary by 0.146, 0.228 and 0.687, respectively. The precision on a typical analysis is 0.03, 0.05nd 0.08‱ for ε60Ni5861,  ε62Ni5861 and ε64Ni5861, respectively, which is comparable to our sample reproducibility. We show that this ‘mass-independent’ Ni isotope variability cannot be ascribed to interferences, inaccurate correction of instrumental or natural mass-dependent fractionation, fractionation controlled by nuclear field shift effects, nor the influence of cosmic ray spallation. These results thus document the presence of mass-independent Ni isotopic heterogeneity in bulk meteoritic samples, as previously proposed by Regelous et al. (2008) (EPSL 272, 330–338), but our new analyses are more precise and include determination of 64Ni. Intriguingly, we find that terrestrial materials do not yield homogenous internally-normalised Ni isotope compositions, which, as pointed out by Young et al. (2002) (GCA 66, 1095–1104), may be the expected result of using the exponential (kinetic) law and atomic masses to normalise all fractionation processes. The certified Ni isotope reference material NIST SRM 986 defines zero in this study, while appropriate ratios for the bulk silicate Earth are given by the peridotites JP-1 and DTS-2 and, relative to NIST SRM 986, yield deviations in ε60Ni5861, ε62Ni5861 and ε64Ni5861 of −0.006, 0.036 and 0.119‱, respectively. There is a strong positive correlation between ε64Ni5861 and ε62Ni5861in iron meteorites analyses, with a slope of 3.03 ± 0.71. The variations of Ni isotope anomalies in iron meteorites are consistent with heterogeneous distribution of a nucleosynthetic component from a type Ia supernova into the proto-solar nebula.PostprintPeer reviewe

Asymptotics of Relativistic Spin Networks

The stationary phase technique is used to calculate asymptotic formulae for SO(4) Relativistic Spin Networks. For the tetrahedral spin network this gives the square of the Ponzano-Regge asymptotic formula for the SU(2) 6j symbol. For the 4-simplex (10j-symbol) the asymptotic formula is compared with numerical calculations of the Spin Network evaluation. Finally we discuss the asymptotics of the SO(3,1) 10j-symbol.Comment: 31 pages, latex. v3: minor clarification

The Massive Progenitor of the Type II-Linear Supernova 2009kr

We present early-time photometric and spectroscopic observations of supernova (SN) 2009kr in NGC 1832. We find that its properties to date support its classification as Type II-linear (SN II-L), a relatively rare subclass of core-collapse supernovae (SNe). We have also identified a candidate for the SN progenitor star through comparison of pre-explosion, archival images taken with WFPC2 on board the Hubble Space Telescope with SN images obtained using adaptive optics plus NIRC2 on the 10 m Keck-II telescope. Although the host galaxy's substantial distance (similar to 26 Mpc) results in large uncertainties in the relative astrometry, we find that if this candidate is indeed the progenitor, it is a highly luminous (M(V)(0) = -7.8 mag) yellow supergiant with initial mass similar to 18-24 M(circle dot). This would be the first time that an SN II-L progenitor has been directly identified. Its mass may be a bridge between the upper initial mass limit for the more common Type II-plateau SNe and the inferred initial mass estimate for one Type II-narrow SN.Hungarian OTKA K76816NSF AST-0707769, AST-0908886Sylvia & Jim Katzman FoundationTABASGO FoundationNASA through STScI AR-11248, GO-10877Harvard UniversityUC BerkeleyUniversity of VirginiaNASA/Swift NNX09AQ66GDOEAstronom

Neutron-poor nickel isotope anomalies in meteorites

We present new, mass-independent, Ni isotope data for a range of bulk chondritic meteorites. The data are reported as ε60Ni58/61 , ε62Ni58/61 , and ε64Ni58/61 , or the parts per ten thousand deviations from a terrestrial reference, the NIST SRM 986 standard, of the 58Ni/61Ni internally normalized 60Ni/61Ni, 62Ni/61Ni, and 64Ni/61Ni ratios. The chondrites show a range of 0.15, 0.29, and 0.84 in ε60Ni58/61 , ε62Ni58/61, and ε64Ni58/61 relative to a typical sample precision of 0.03, 0.05, and 0.08 (2 s.e.), respectively. The carbonaceous chondrites show the largest positive anomalies, enstatite chondrites have approximately terrestrial ratios, though only EH match Earth's composition within uncertainty, and ordinary chondrites show negative anomalies. The meteorite data show a strong positive correlation between ε62Ni58/61 and ε64Ni58/61, an extrapolation of which is within the error of the average of previous measurements of calcium-, aluminium-rich inclusions. Moreover, the slope of this bulk meteorite array is 3.003 ± 0.166 which is within the error of that expected for an anomaly solely on 58Ni. We also determined to high precision (~10 ppm per AMU) the mass-dependent fractionation of two meteorite samples which span the range of ε62Ni58/61 and ε64Ni58/61. These analyses show that "absolute" ratios of 58Ni/61Ni vary between these two samples whereas those of 62Ni/61Ni and 64Ni/61Ni do not. Thus, Ni isotopic differences seem most likely explained by variability in the neutron-poor 58Ni, and not correlated anomalies in the neutron-rich isotopes, 62Ni and 64Ni. This contrasts with previous inferences from mass-independent measurements of Ni and other transition elements which invoked variable contributions of a neutron-rich component. We have examined different nucleosynthetic environments to determine the possible source of the anomalous material responsible for the isotopic variations observed in Ni and other transition elements within bulk samples. We find that the Ni isotopic variability of the solar system cannot be explained by mixing with a component of bulk stellar ejecta from either SN II, Wolf-Rayet or, an asymptotic giant branch source and is unlikely to result from bulk mixing of material from an SN Ia. However, variable admixture of material from the Si/S zone of an SN II can create all the characteristics of Ni isotope variations in solar system materials. Moreover, these characteristics can also be provided by an SN II with a range of masses from 15 to 40 M☉ , showing that input from SN II is a robust source for Ni isotope variations in the solar system. Correlations of Ni isotope anomalies with O, Cr, and Ti isotope ratios and Pb/Yb in bulk meteorites suggest that the heterogeneous distribution of isotopic anomalies in the early solar system likely resulted from nebular sorting of chemically or physically different materials bearing different amounts of isotopes synthesized proximally to the collapse of the protosolar nebula.PostprintPeer reviewe

Feasibility assessment on use of proximal geophysical sensors to support precision management

A study was conducted at three sites in North Dakota to strengthen understanding of the usefulness of different proximal geophysical data types in agricultural contexts of varying pedology. This study hypothesizes that electromagnetic induction (EMI), gamma-ray sensor (GRS), cosmic-ray neutron sensor (CRNS), and elevation data layers are all useful in multiple linear regression (MLR) predictions of soil properties that meet expert criteria at three agricultural sites. In addition to geophysical data collection with vehicle-mounted sensors, 15 soil samples were collected at each site and analyzed for nine soil properties of interest. A set of model training data was compiled by pairing the sampled soil property measurements with the nearest geophysical data. Eleven models passed expert-defined uncertainty criteria at Site 1, 16 passed at Site 2, and 14 passed at Site 3. Electrical conductivity (EC), organic matter (OM), available water holding capacity, silt, and clay were predicted at Site 1 with an R-squared of prediction (2 ) \u3e .50 and acceptable root mean square error of prediction (RMSEP). Bulk density (BD), OM, available water capacity, silt, and clay were predicted with 2\u3e .50 and acceptable RMSEP at Site 2. At Site 3, no soil properties were predicted with acceptable RMSEP and an 2\u3e .50. These results confirm feasibility of our method, and the authors recommend the prioritization of EMI data collection if geophysical data collection is limited to a single mapping effort and calibration soil samples are few

Lithium Depletion in Fully Convective Pre-Main Sequence Stars

We present an analytic calculation of the thermonuclear depletion of lithium in contracting, fully convective, pre-main sequence stars of mass M < 0.5 M_sun. Previous numerical work relies on still-uncertain physics (atmospheric opacities and convection, in particular) to calculate the effective temperature as a unique function of stellar mass. We assume that the star's effective temperature, T_eff, is fixed during Hayashi contraction and allow its actual value to be a free parameter constrained by observation. Using this approximation, we compute lithium burning analytically and explore the dependence of lithium depletion on T_eff, M, and composition. Our calculations yield the radius, age, and luminosity of a pre-main sequence star as a function of lithium depletion. This allows for more direct comparisons to observations of lithium depleted stars. Our results agree with those numerical calculations that explicitly determine stellar structure during Hayashi contraction. In agreement with Basri, Marcy, and Graham (1996), we show that the absence of lithium in the Pleiades star HHJ 3 implies that it is older than 100 Myr. We also suggest a generalized method for dating galactic clusters younger than 100 Myr (i.e., those with contracting stars of M > 0.08 M_sun) and for constraining the masses of lithium depleted stars.Comment: 13 pages, LaTex with 2 postscript figures, uses aaspp4.sty and epsfig.sty, to appear in the Astrophysical Journa