Analysis of forensic DNA mixtures with artefacts

DNA is now routinely used in criminal investigations and court cases, although DNA samples taken at crime scenes are of varying quality and therefore present challenging problems for their interpretation. We present a statistical model for the quantitative peak information obtained from an electropherogram of a forensic DNA sample and illustrate its potential use for the analysis of criminal cases. In contrast with most previously used methods, we directly model the peak height information and incorporate important artefacts that are associated with the production of the electropherogram. Our model has a number of unknown parameters, and we show that these can be estimated by the method of maximum likelihood in the presence of multiple unknown individuals contributing to the sample, and their approximate standard errors calculated; the computations exploit a Bayesian network representation of the model. A case example from a UK trial, as reported in the literature, is used to illustrate the efficacy and use of the model, both in finding likelihood ratios to quantify the strength of evidence, and in the deconvolution of mixtures for finding likely profiles of the individuals contributing to the sample. Our model is readily extended to simultaneous analysis of more than one mixture as illustrated in a case example. We show that the combination of evidence from several samples may give an evidential strength which is close to that of a single-source trace and thus modelling of peak height information provides a potentially very efficient mixture analysis

Melt onset over Arctic sea ice controlled by atmospheric moisture transport

The timing of melt onset affects the surface energy uptake throughout the melt season. Yet the processes triggering melt and causing its large interannual variability are not well understood. Here we show that melt onset over Arctic sea ice is initiated by positive anomalies of water vapor, clouds, and air temperatures that increase the downwelling longwave radiation (LWD) to the surface. The earlier melt onset occurs; the stronger are these anomalies. Downwelling shortwave radiation (SWD) is smaller than usual at melt onset, indicating that melt is not triggered by SWD. When melt occurs early, an anomalously opaque atmosphere with positive LWD anomalies preconditions the surface for weeks preceding melt. In contrast, when melt begins late, clearer than usual conditions are evident prior to melt. Hence, atmospheric processes are imperative for melt onset. It is also found that spring LWD increased during recent decades, consistent with trends toward an earlier melt onset. ©2016. American Geophysical Union. All Rights Reserved

The global atmospheric energy transport analysed by a wavelength-based scale separation

The atmosphere transports energy polewards by circulation cells and eddies. To the present day, there has been a knowledge gap regarding the preferred spatial scales and physical mechanisms of eddy energy transport. To fill the gap, we separate the meridional atmospheric energy transport in the ERA5 reanalysis by spatial scales and into quasi-stationary and transient flow patterns and latent and dry components. Baroclinic instability is the major instability mechanism in the transient synoptic scales and is responsible for forming cyclones, anticyclones, and small-scale Rossby waves. At the planetary scales, circulation patterns are often induced by other mechanisms such as flow interaction with orography and land–sea heating contrasts. However, a separation between circulation patterns at the synoptic and planetary scales has yet to be established. We find that both baroclinically induced and transient energy transport is predominantly associated with eddies at wavelengths between 2000 and 8000 km. The maxima in both types of transport occur at wavelengths around 5000 km, in good agreement with linear baroclinic theory. Since these results are independent of latitude, we adapt the scale separation of the energy transport to be based on the wavelength instead of the previously used wavenumber. We define the synoptic transport by the wavelength band between 2000 and 8000 km. We analyse the annual and seasonal mean in the energy transport components and their inter-annual variability. The scale-separated transport components are fairly similar in both hemispheres. Transport by synoptic waves is the largest contributor to extra-tropical energy and moisture transport, mainly of a transient character, and is influenced little by seasonality. In contrast, transport by planetary waves depends highly on the season and has two distinct characteristics. (1) In the extra-tropical winter, planetary waves are important due to a large transport of dry energy. This planetary transport features the largest inter-annual variability of all components and is mainly quasi-stationary in the Northern Hemisphere but transient in its southern counterpart. (2) In the sub-tropical summer, quasi-stationary planetary waves are the most important transport component, mainly due to moisture transport, presumably associated with monsoons. In contrast to transport by planetary and synoptic waves, only a negligible amount of energy is transported by mesoscale eddies (&lt; 2000 km).</p

Estimation of Parameters in DNA Mixture Analysis

In Cowell et al. (2007), a Bayesian network for analysis of mixed traces of DNA was presented using gamma distributions for modelling peak sizes in the electropherogram. It was demonstrated that the analysis was sensitive to the choice of a variance factor and hence this should be adapted to any new trace analysed. In the present paper we discuss how the variance parameter can be estimated by maximum likelihood to achieve this. The unknown proportions of DNA from each contributor can similarly be estimated by maximum likelihood jointly with the variance parameter. Furthermore we discuss how to incorporate prior knowledge about the parameters in a Bayesian analysis. The proposed estimation methods are illustrated through a few examples of applications for calculating evidential value in casework and for mixture deconvolution

Body mass index trajectories from 2 to 18 years - exploring differences between European cohorts.

BACKGROUND: In recent decades, there has been an increase in the prevalence of childhood overweight in most high-income countries. Within northern Europe, prevalence tends to be higher in the UK compared with the Scandinavian countries. We aimed to study differences in body mass index (BMI) trajectories between large cohorts of children from UK and Scandinavian populations. METHODS: We compared BMI trajectories in participants from the English Avon Longitudinal Study of Parents and Children born in 1991-1993 (ALSPAC) (N = 6517), the Northern Finland Birth Cohorts born in 1966 (NFBC1966) (N = 3321) and 1986 (NFBC1986) (N = 4764), and the Danish Aarhus Birth Cohort born in 1990-1992 (ABC) (N = 1920). We used multilevel models to estimate BMI trajectories from 2 to 18 years. We explored whether cohort differences were explained by maternal BMI, height, education or smoking during pregnancy and whether differences were attributable to changes in the degree of skew in the BMI distribution. RESULTS: Differences in mean BMI between the cohorts were small but emerged early and persisted in most cases across childhood. Girls in ALSPAC had a higher BMI than all other cohorts throughout childhood, e.g. compared with the NFBC1986 BMI was 2.2-3.5% higher. For boys, the difference emerging over time (comparing the two NFBC's) exceeded the differences across populations (comparing NFBC1986, ABC and ALSPAC). BMI distribution demonstrated increasing right skew with age. CONCLUSION: Population-level differences between cohorts were small, tended to emerge very early, persisted across childhood, and demonstrated an increase in the right-hand tail of the BMI distribution

Impact of assimilating sea ice concentration, sea ice thickness and snow depth in a coupled ocean–sea ice modelling system

The accuracy of the initial state is very important for the quality of a forecast, and data assimilation is crucial for obtaining the best-possible initial state. For many years, sea-ice concentration was the only parameter used for assimilation into numerical sea-ice models. Sea-ice concentration can easily be observed by satellites, and satellite observations provide a full Arctic coverage. During the last decade, an increasing number of sea-ice related variables have become available, which include sea-ice thickness and snow depth, which are both important parameters in the numerical sea-ice models. In the present study, a coupled ocean–sea-ice model is used to assess the assimilation impact of sea-ice thickness and snow depth on the model. The model system with the assimilation of these parameters is verified by comparison with a system assimilating only ice concentration and a system having no assimilation. The observations assimilated are sea ice concentration from the Ocean and Sea Ice Satellite Application Facility, thin sea ice from the European Space Agency's (ESA) Soil Moisture and Ocean Salinity mission, thick sea ice from ESA's CryoSat-2 satellite, and a new snow-depth product derived from the National Space Agency's Advanced Microwave Scanning Radiometer (AMSR-E/AMSR-2) satellites. The model results are verified by comparing assimilated observations and independent observations of ice concentration from AMSR-E/AMSR-2, and ice thickness and snow depth from the IceBridge campaign. It is found that the assimilation of ice thickness strongly improves ice concentration, ice thickness and snow depth, while the snow observations have a smaller but still positive short-term effect on snow depth and sea-ice concentration. In our study, the seasonal forecast showed that assimilating snow depth led to a less accurate long-term estimation of sea-ice extent compared to the other assimilation systems. The other three gave similar results. The improvements due to assimilation were found to last for at least 3–4 months, but possibly even longer.</p

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

UNLABELLED: Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7-7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4-5.0; p = 0.03). Plasma HIV-1 RNA increased from &lt;20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46-103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1-2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION: clinicaltrials.gov NTC02092116

Event structures for the reversible early internal pi-calculus

The pi-calculus is a widely used process calculus, which models com-munications between processes and allows the passing of communication links.Various operational semantics of the pi-calculus have been proposed, which canbe classified according to whether transitions are unlabelled (so-called reductions)or labelled. With labelled transitions, we can distinguish early and late semantics.The early version allows a process to receive names it already knows from the en-vironment, while the late semantics and reduction semantics do not. All existingreversible versions of the pi-calculus use reduction or late semantics, despite theearly semantics of the (forward-only) pi-calculus being more widely used than thelate. We define piIH, the first reversible early pi-calculus, and give it a denotationalsemantics in terms of reversible bundle event structures. The new calculus is a re-versible form of the internal pi-calculus, which is a subset of the pi-calculus whereevery link sent by an output is private, yielding greater symmetry between inputsand outputs

Clinical, Pathologic, and Functional Outcomes After Nephron-Sparing Surgery in Patients with a Solitary Kidney: A Multicenter Experience

Abstract Background and Purpose: Surgical management of a renal neoplasm in a solitary kidney is a balance between oncologic control and preservation of renal function. We analyzed patients with a renal mass in a solitary kidney undergoing nephron-sparing procedures to determine perioperative, oncologic, and renal functional outcomes. Patients and Methods: A multicenter study was performed from 12 institutions. All patients with a functional or anatomic solitary kidney who underwent nephron-sparing surgery for one or more renal masses were included. Tumor size, complications, and recurrence rates were recorded. Renal function was assessed with serum creatinine level and estimated glomerular filtration rate. Results: Ninety-eight patients underwent 105 ablations, and 100 patients underwent partial nephrectomy (PN). Preoperative estimated glomerular filtration rate (eGFR) was similar between the groups. Tumors managed with PN were significantly larger than those managed with ablation (P<0.001). Ablations were associated with a lower overall complication rate (9.5% vs 24%, P=0.01) and higher local recurrence rate (6.7% vs 3%, P=0.04). Eighty-four patients had a preoperative eGFR ≥60?mL/min/1.73?m2. Among these patients, 19 (23%) fell below this threshold after 3 months and 15 (18%) at 12 months. Postoperatively, there was no significant difference in eGFR between the groups. Conclusions: Extirpation and ablation are both reasonable options for treatment. Ablation is more minimally invasive, albeit with higher recurrence rates compared with PN. Postoperative renal function is similar in both groups and is not affected by surgical approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98449/1/end%2E2012%2E0114.pd