Kinetic energy choice in Hamiltonian/hybrid Monte Carlo

We consider how different choices of kinetic energy in Hamiltonian Monte Carlo affect algorithm performance. To this end, we introduce two quantities which can be easily evaluated, the composite gradient and the implicit noise. Results are established on integrator stability and geometric convergence, and we show that choices of kinetic energy that result in heavy-tailed momentum distributions can exhibit an undesirable negligible moves property, which we define. A general efficiency-robustness trade off is outlined, and implementations which rely on approximate gradients are also discussed. Two numerical studies illustrate our theoretical findings, showing that the standard choice which results in a Gaussian momentum distribution is not always optimal in terms of either robustness or efficiency.Comment: 15 pages (+7 page supplement, included here as an appendix), 2 figures (+1 in supplement

Modeling the Disappearance of the Neanderthals Using Concepts of Population Dynamics and Ecology

Current hypotheses regarding the disappearance of Neanderthals (NEA) in Europe fall into two main categories: climate change, and competition. Here we review current research and existing mathematical models that deal with this question, and we propose an approach that incorporates and permits the investigation of the current hypotheses. We have developed a set of differential equations that model population dynamics of anatomically modern humans (AMH) and NEA, their ecological relations to prey species, and their mutual interactions. The model allows investigators to explore each of the two main categories or combinations of both, as well as various forms of competition and/or interference within the context of competition. The model is designed to include a wide variety of hypotheses and associated archaeological evidence, not focused on a particular hypothesis regarding NEA extinction. It therefore provides investigators with a model to impartially examine various hypotheses (individually or in combination) regarding climatic effects, differential resource use, differences in birth/death rates and carrying capacities, competition, interference, disease, interbreeding, and cultural distinctions that might have led to the extinction of NEA. Moreover, the model accommodates the design of scenarios concerning—for example—population growth, hunting, competitive interactions, cultural differences, and climatic influences to investigate which concepts best explain the rapid disappearance of NEA. In addition, our model is a modification of the classical Lotka-Volterra model for a wide range of any two populations competing for a common resource. Specifically, our model explicitly includes the resource as an additional variable, a dependence of important population parameters on resource, as well as accommodates treating one of the populations as invasive

HIV Screening via Fourth-Generation Immunoassay or Nucleic Acid Amplification Test in the United States: A Cost-Effectiveness Analysis

BACKGROUND: At least 10% of the 56,000 annual new HIV infections in the United States are caused by individuals with acute HIV infection (AHI). It unknown whether the health benefits and costs of routine nucleic acid amplification testing (NAAT) are justified, given the availability of newer fourth-generation immunoassay tests. METHODS: Using a dynamic HIV transmission model instantiated with U.S. epidemiologic, demographic, and behavioral data, I estimated the number of acute infections identified, HIV infections prevented, quality-adjusted life years (QALYs) gained, and the cost-effectiveness of alternative screening strategies. I varied the target population (everyone aged 15-64, injection drug users [IDUs] and men who have sex with men [MSM], or MSM only), screening frequency (annually, or every six months), and test(s) utilized (fourth-generation immunoassay only, or immunoassay followed by pooled NAAT). RESULTS: Annual immunoassay testing of MSM reduces incidence by 9.5% and costs <$10,000 per QALY gained. Adding pooled NAAT identifies 410 AHI per year, prevents 9.6$92,000 per QALY gained, and remains <$100,000 per QALY gained in settings where undiagnosed HIV prevalence exceeds 4$10,000 per QALY gained. Increasing the screening frequency to every six months reduces incidence by 11% (MSM only) or 16% (MSM and IDUs) and costs <$20,000 per QALY gained. CONCLUSIONS: Pooled NAAT testing every 12 months of MSM and IDUs in the United States prevents a modest number of infections, but may be cost-effective given sufficiently high HIV prevalence levels. However, testing via fourth-generation immunoassay every six months prevents a greater number of infections, is more economically efficient, and may obviate the benefits of acute HIV screening via NAAT

Two Middle Holocene Marker Beds in Vertically Accreted Floodplain Deposits, Lower Fraser River, British Columbia

Drill cores obtained from the eastern Fraser Delta and adjoining Fraser River floodplain reveal two middle Holocene marker beds—a peat with an age of about 6000 14C yr BP and a tephra bed, identified as Mazama (6800 yr BP). These marker beds, in conjunction with 14C dates from the flood-plain sediments, indicate that the Fraser River floodplain aggraded in response to a rise in sea-level, between about 8000 and 2250 yr BP, and that aggradation kept pace with sea-level rise. The aggradational deposits form a sediment wedge consisting mainly of organic-rich silts and fine sands of overbank origin. The wedge extends at least 20 km into the lower Fraser River Valley. Preservation of the marker beds indicates considerable channel stability in the lower reaches of the Fraser River over about the last 7000 years.Des carottes recueillies dans la partie est du delta du Fraser et de la plaine d'inondation adjacente montrent deux lits repères datant du milieu de l'Holocène, un lit de tourbe datant d'à peu près 6000 BP et un lit de tephra, correspondant à l'éruption du mont Mazama (6800 BP). Ces lits repères, ainsi que les datations au radiocarbone obtenues dans les sédiments de crue, montrent que la plaine d'inondation du Fraser a progressé en réponse à une hausse du niveau marin survenue entre environ 8000 et 2250 BP et que l'aggradation suivait la hausse du niveau marin. L'accumulation de sédiments, de forme triangulaire, est composée principalement de limons riches en matière organique et de sables fins d'origine alluviale. Le triangle s'étend jusqu'à au moins 20 km dans la vallée inférieure du Fraser. La conservation des lits repères démontre la grande stabilité des biefs du Fraser inférieur depuis environ 7000 ans.Bohrkerne von dem ôstlichen Fraser-Delta und der angrenzenden Hochflutebene lassen zwei Betten aus dem mittleren Holozân erkennen, die als Anhalt dienen: ein Torfbett das auf etwa 6000 "1C Jahre v.u.Z. datiert wird und ein Tephra-Bett, das aus der Zeit des Ausbruchs des Mazamabergs stammt (6800 Jahre v.u.Z.). Die als Anhaltspunkt dienenden Betten weisen zusammen mit den von den Hochflutsedimenten gewonnenen 14C-Daten darauf hin, dass die Hochflut des Fraser-Flusses als Reaktion auf eine Anhebung des Meeresspiegels zwischen etwa 8000 und 2250 Jahren v.u.Z. zugenommen hat. und dass diese Zunahme der Hebung des Meeresspiegels entsprach. Die Akkumulationssedimente bilden einen Sedimentkeil, der vor allem aus organisch reichem Schlamm und feinem Sand alluvialer Herkunft besteht. Der Keil erstreckt sich mindestens 20 km in das TaI des unteren Fraser. Die Erhaltung der als Anhaltspunkte dienenden Betten beweist eine beachtliche Kanalstabilitât in den unteren Stillen des Fraser wâhrend ungefàhr 7000 Jahren

Military Voting and the Law: Procedural and Technological Solutions to the Ballot Transit Problem

During the 2000 presidential election controversy in Florida, the ballots submitted by individuals living overseas—especially military voters—were seen as crucial to the election outcome as the margin of potential victory was so small that these ballots could turn the election from one candidate to the other. Headlines at the time noted that “Odds Against Gore Absentee Gains: Republican-Leaning Counties Appear to Have More Uncounted Overseas Ballots,” “Bush Lead Swells with Overseas Votes,” “Military Ballot Review is Urged,” and “How Bush Took Florida: Mining the Overseas Absentee Vote.” For many Americans, however, the controversy surrounding the votes of military personnel and overseas voters, despite its importance, may have seemed both bewildering and esoteric. The debate centered on minute details; whether or not certain overseas absentee ballots were valid and could therefore be counted if they lacked postmarks, were received within given time periods, had missing signature or were deficient in other statutorily required characteristics, that are beyond the interest of the typical individual. However, several key legal skirmishes were fought within the broader context of the recount battle concerning whether certain absentee ballots could be counted, the resolution of which could have swayed the outcome of the 2000 presidential election. Issues of equal protection, federalism and statutory interpretation played large roles in this litigation. The tension between allowing overseas votes to be counted and ensuring a fair election that complied with state law was at the heart of the debate and related litigation

Structure and Magnetic Fields in the Precessing Jet System SS 433 II. Intrinsic Brightness of the Jets

Deep Very Large Array imaging of the binary X-ray source SS 433, sometimes classified as a microquasar, has been used to study the intrinsic brightness distribution and evolution of its radio jets. The intrinsic brightness of the jets as a function of age at emission of the jet material tau is recovered by removal of the Doppler boosting and projection effects. We find that intrinsically the two jets are remarkably similar when compared for equal tau, and that they are best described by Doppler boosting of the form D^{2+alpha}, as expected for continuous jets. The intrinsic brightnesses of the jets as functions of age behave in complex ways. In the age range 60 < tau < 150 days, the jet decays are best represented by exponential functions of tau, but linear or power law functions are not statistically excluded. This is followed by a region out to tau ~ 250 days during which the intrinsic brightness is essentially constant. At later times the jet decay can be fit roughly as exponential or power law functions of tau.Comment: 30 Pages, 11 Figures, Submitted to Ap

In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immuno-biology of Allogeneic Transplantation

Donor T cell mediated graft vs. host effects may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA in each donor-recipient pair (DRP) undergoing stem cell transplantation (SCT). Whole exome sequencing has demonstrated extensive nucleotide sequence variation in HLA-matched DRP. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the GVH direction (polymorphisms present in recipient and absent in donor) were identified in 4 HLA-matched related and 5 unrelated DRP. The nucleotide sequence flanking each SNP was obtained utilizing the ANNOVAR software package. All possible nonameric-peptides encoded by the non-synonymous SNP were then interrogated in-silico for their likelihood to be presented by the HLA class I molecules in individual DRP, using the Immune-Epitope Database (IEDB) SMM algorithm. The IEDB-SMM algorithm predicted a median 18,396 peptides/DRP which bound HLA with an IC50 of <500nM, and 2254 peptides/DRP with an IC50 of <50nM. Unrelated donors generally had higher numbers of peptides presented by the HLA. A similarly large library of presented peptides was identified when the data was interrogated using the Net MHCPan algorithm. These peptides were uniformly distributed in the various organ systems. The bioinformatic algorithm presented here demonstrates that there may be a high level of minor histocompatibility antigen variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential. These data provide a possible explanation for how relatively minor adjustments in GVHD prophylaxis yield relatively similar outcomes in HLA matched and mismatched SCT recipients.Comment: Abstract: 235, Words: 6422, Figures: 7, Tables: 3, Supplementary figures: 2, Supplementary tables:

Internal Carotid Artery Stenosis: A Novel Surgical Model for Moyamoya Syndrome

Moyamoya is a cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries. There are two forms: Disease and Syndrome, with each characterized by the sub-population it affects. Moyamoya syndrome (MMS) is more prominent in adults in their 20’s-40’s, and is often associated with autoimmune diseases. Currently, there are no surgical models for inducing moyamoya syndrome, so our aim was to develop a new animal model to study this relatively unknown cerebrovascular disease. Here, we demonstrate a new surgical technique termed internal carotid artery stenosis (ICAS), to mimic MMS using micro-coils on the proximal ICA. We tested for Moyamoya-like vasculopathies by fluorescently labelling the mouse cerebrovasculature with Di I for visualization and analysis of vessel diameter at the distal ICA and anastomoses on the cortical surface. Results show a significant narrowing of the distal ICA and anterior cerebral artery (ACA) in the Circle of Willis, as observed in humans. There is also a significant decrease in the number of anastomoses between the middle cerebral artery (MCA) and the ACA in the watershed region of the cortex. While further characterization is needed, this ICAS model can be applied to transgenic mice displaying co-morbidities as observed within the Moyamoya syndrome population, allowing a better understanding of the disease and development of novel treatments