Gift Tax Returns as a Planning Strategy

Timely filing of a properly prepared gift tax return will begin the statute of limitations period for revaluing the gift for gift tax purposes, but not necessarily for estate tax purposes. Walsh describes how the Taxpayer Relief Act of 1997 (TRA\u2797) can provide a taxpayer with potential solutions and describes how the final regulations provide planning opportunities for attorneys to assist their clients

Integrated survival analysis using an event-time approach in a Bayesian framework

Event-time or continuous-time statistical approaches have been applied throughout the bio-statistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. this has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed in integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. this provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest \u3c5 days old and were lower for chicks with larger birth weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data

Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

© 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities. Methods: People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups. Results: DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode. Conclusion: Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.Peer reviewedFinal Published versio

Statistics of Solar Wind Electron Breakpoint Energies Using Machine Learning Techniques

Solar wind electron velocity distributions at 1 au consist of a thermal "core" population and two suprathermal populations: "halo" and "strahl". The core and halo are quasi-isotropic, whereas the strahl typically travels radially outwards along the parallel and/or anti-parallel direction with respect to the interplanetary magnetic field. With Cluster-PEACE data, we analyse energy and pitch angle distributions and use machine learning techniques to provide robust classifications of these solar wind populations. Initially, we use unsupervised algorithms to classify halo and strahl differential energy flux distributions to allow us to calculate relative number densities, which are of the same order as previous results. Subsequently, we apply unsupervised algorithms to phase space density distributions over ten years to study the variation of halo and strahl breakpoint energies with solar wind parameters. In our statistical study, we find both halo and strahl suprathermal breakpoint energies display a significant increase with core temperature, with the halo exhibiting a more positive correlation than the strahl. We conclude low energy strahl electrons are scattering into the core at perpendicular pitch angles. This increases the number of Coulomb collisions and extends the perpendicular core population to higher energies, resulting in a larger difference between halo and strahl breakpoint energies at higher core temperatures. Statistically, the locations of both suprathermal breakpoint energies decrease with increasing solar wind speed. In the case of halo breakpoint energy, we observe two distinct profiles above and below 500 km/s. We relate this to the difference in origin of fast and slow solar wind.Comment: Published in Astronomy & Astrophysics, 11 pages, 10 figure

Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase

Hepatitis C (HCV) is a virus characterized by an RNA-dependent RNA polymerase that lacks a proofreading mechanism and, as a result, generates a quasispecies. There is emerging evidence that this RNA-dependent RNA polymerase may in fact have variable fidelity. Here, we review the relevant concepts, including fitness landscapes, clonal interference, robustness, selection, adaptation, mutation rates, and their optimization, and provide a unique interpretation of a number of relevant theoretical models, evolving the theory of replicative homeostasis in light of their findings. We suggest that a variable fidelity polymerase can find its own optimal mutation rate, which is governed by the sequence itself and certain population dynamics. We propose that this concept can explain features of viral kinetics and clearance, both spontaneously and following treatment of chronic HCV. We point to evidence that supports this theory and explain how it refines replicative homeostasis and conclude by discussing particular areas of potential research that might augment our understanding of viral host interactions at an individual cellular level

Composing Efficient, Robust Tests for Policy Selection

Modern reinforcement learning systems produce many high-quality policies throughout the learning process. However, to choose which policy to actually deploy in the real world, they must be tested under an intractable number of environmental conditions. We introduce RPOSST, an algorithm to select a small set of test cases from a larger pool based on a relatively small number of sample evaluations. RPOSST treats the test case selection problem as a two-player game and optimizes a solution with provable $k$-of-$N$ robustness, bounding the error relative to a test that used all the test cases in the pool. Empirical results demonstrate that RPOSST finds a small set of test cases that identify high quality policies in a toy one-shot game, poker datasets, and a high-fidelity racing simulator.Comment: 26 pages, 13 figures. To appear in Proceedings of the Thirty-Ninth Conference on Uncertainty in Artificial Intelligence (UAI 2023

Mechanistic Characterization and Molecular Modeling of Hepatitis B Virus Polymerase Resistance to Entecavir

BACKGROUND: Entecavir (ETV) is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV) polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr) is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT) domain involve lamivudine-resistance (LVDr) substitutions in the conserved YMDD motif (M204V/I +/- L180M), plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. METHODS/PRINCIPAL FINDINGS: To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M) and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i)) for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat)) in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP) binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of comprehensive substitutions of each ETVr position. CONCLUSIONS: Altogether, ETVr occurred through exclusion of ETV-TP from the dNTP-binding site, through different, novel mechanisms that involved lamivudine-resistance, ETV-specific substitutions, and the primer-template

The Ray Bundle method for calculating weak magnification by gravitational lenses

We present here an alternative method for calculating magnifications in gravitational lensing calculations -- the Ray Bundle method. We provide a detailed comparison between the distribution of magnifications obtained compared with analytic results and conventional ray-shooting methods. The Ray Bundle method provides high accuracy in the weak lensing limit, and is computationally much faster than (non-hierarchical) ray shooting methods to a comparable accuracy. The Ray Bundle method is a powerful and efficient technique with which to study gravitational lensing within realistic cosmological models, particularly in the weak lensing limit.Comment: 9 pages Latex, 8 figures, submitted to MNRA

Genetic aspects of conservation and management of the Eurasian Curlew Numenius arquata

Decades of decline have triggered an AEWA action plan and numerous conservation and management projects across the range of Eurasian Curlew Numenius arquata. Several projects include DNA studies, but more have an untapped potential to collect and analyse DNA. This document intends to promote DNA studies in Eurasian Curlew projects, in particular through pointing out the broad array of useful DNA samples that projects can collect for current and future use, often at low costs and without negatively affecting the birds. The document also provides an overview of DNA analysis methods, and advice on how to fit DNA studies sustainably into socio-economical and ethical frameworks. Additionally, the document contains numerous hands-on practical advice and an extensive reference list. The result is a long text, but we hope its structure helps you to navigate smoothly to the parts of your interest, whatever role you have or plan to play in Eurasian Curlew conservation and management projects