How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements

Natural handicaps in Dutch agricultural areas : assessment of less favoured areas based on economic criteria

Smit en Brouwer (2009) hebben bodems met een landbouwkundige handicap geselecteerd aan de hand van biofysische criteria. De relevante biofysische criteria waren gerelateerd aan bodemeigenschappen: drainage, textuur, aanwezigheid van stenen en chemische eigenschappen. Textuur en aanwezigheid van stenen zijn onderverdeeld in verschillende klassen: grof materiaal, grof en middelgrof zand, zware klei, veengronden, zwel en krimpverschijnselen en het opkomen van stenen uit de ondergrond. Verzilting is de enige chemische eigenschap die relevant is voor Nederland. Naast een selectie van gebieden op grond van biofysische eigenschappen, moet ook een verfijnde selectie worden uitgevoerd. Deze verfijnde selectie is gebaseerd op de verschillen in saldo per hectare tussen gebieden met en zonder de landbouwkundige gevolgen van de biofysische eigenschappen. De belangrijkste landbouwkundige gevolgen voor de verschillende categorieën waren de gevoeligheid voor winderosie bij grof en middelgrof zand; de beperkingen van de bewerkbaarheid van de grond en de beperkingen in het bouwplan op de zware kleigronden en lagere netto productie en de onmogelijkheid om maïs te verbouwen op veengronde

Physical properties of the Schur complement of local covariance matrices

General properties of global covariance matrices representing bipartite Gaussian states can be decomposed into properties of local covariance matrices and their Schur complements. We demonstrate that given a bipartite Gaussian state $\rho_{12}$ described by a $4\times 4$ covariance matrix \textbf{V}, the Schur complement of a local covariance submatrix $\textbf{V}_1$ of it can be interpreted as a new covariance matrix representing a Gaussian operator of party 1 conditioned to local parity measurements on party 2. The connection with a partial parity measurement over a bipartite quantum state and the determination of the reduced Wigner function is given and an operational process of parity measurement is developed. Generalization of this procedure to a $n$-partite Gaussian state is given and it is demonstrated that the $n-1$ system state conditioned to a partial parity projection is given by a covariance matrix such as its $2 \times 2$ block elements are Schur complements of special local matrices.Comment: 10 pages. Replaced with final published versio

Eta Carinae: Binarity Confirmed

We report the recovery of a spectroscopic event in eta Carinae in 1997/98 after a prediction by Damineli (1996). A true periodicity with P = 2020+-5 days (0.2% uncertainty) is obtained. The line intensities and the radial-velocity curve display a phase-locked behavior implying that the energy and dynamics of the event repeat from cycle to cycle. This rules out S Doradus oscillation or multiple shell ejection by an unstable star as the explanation of the spectroscopic events. A colliding-wind binary scenario is supported by our spectroscopic data and by X-ray observations. Although deviations from a simple case exist around periastron, intensive monitoring during the next event (mid 2003) will be crucial to the understanding of the system.Comment: 13 pages, accepted by ApJ Letters (January 2000

Exponential Separation of Quantum and Classical Online Space Complexity

Although quantum algorithms realizing an exponential time speed-up over the best known classical algorithms exist, no quantum algorithm is known performing computation using less space resources than classical algorithms. In this paper, we study, for the first time explicitly, space-bounded quantum algorithms for computational problems where the input is given not as a whole, but bit by bit. We show that there exist such problems that a quantum computer can solve using exponentially less work space than a classical computer. More precisely, we introduce a very natural and simple model of a space-bounded quantum online machine and prove an exponential separation of classical and quantum online space complexity, in the bounded-error setting and for a total language. The language we consider is inspired by a communication problem (the set intersection function) that Buhrman, Cleve and Wigderson used to show an almost quadratic separation of quantum and classical bounded-error communication complexity. We prove that, in the framework of online space complexity, the separation becomes exponential.Comment: 13 pages. v3: minor change

A silicate disk in the heart of the Ant

We aim at getting high spatial resolution information on the dusty core of bipolar planetary nebulae to directly constrain the shaping process. Methods: We present observations of the dusty core of the extreme bipolar planetary nebula Menzel 3 (Mz 3, Hen 2-154, the Ant) taken with the mid-infrared interferometer MIDI/VLTI and the adaptive optics NACO/VLT. The core of Mz 3 is clearly resolved with MIDI in the interferometric mode, whereas it is unresolved from the Ks to the N bands with single dish 8.2 m observations on a scale ranging from 60 to 250 mas. A striking dependence of the dust core size with the PA angle of the baselines is observed, that is highly suggestive of an edge-on disk whose major axis is perpendicular to the axis of the bipolar lobes. The MIDI spectrum and the visibilities of Mz 3 exhibit a clear signature of amorphous silicate, in contrast to the signatures of crystalline silicates detected in binary post-AGB systems, suggesting that the disk might be relatively young. We used radiative-transfer Monte Carlo simulations of a passive disk to constrain its geometrical and physical parameters. Its inclination (74 degrees $\pm$ 3 degrees) and position angle (5 degrees $\pm$ 5 degrees) are in accordance with the values derived from the study of the lobes. The inner radius is 9$\pm$ 1 AU and the disk is relatively flat. The dust mass stored in the disk, estimated as 1 x 10-5Msun, represents only a small fraction of the dust mass found in the lobes and might be a kind of relic of an essentially polar ejection process

New method to study stochastic growth equations: a cellular automata perspective

We introduce a new method based on cellular automata dynamics to study stochastic growth equations. The method defines an interface growth process which depends on height differences between neighbors. The growth rule assigns a probability $p_{i}(t)=\rho$ exp$[\kappa \Gamma_{i}(t)]$ for a site $i$ to receive one particle at a time $t$ and all the sites are updated simultaneously. Here $\rho$ and $\kappa$ are two parameters and $\Gamma_{i}(t)$ is a function which depends on height of the site $i$ and its neighbors. Its functional form is specified through discretization of the deterministic part of the growth equation associated to a given deposition process. In particular, we apply this method to study two linear equations - the Edwards-Wilkinson (EW) equation and the Mullins-Herring (MH) equation - and a non-linear one - the Kardar-Parisi-Zhang (KPZ) equation. Through simulations and statistical analysis of the height distributions of the profiles, we recover the values for roughening exponents, which confirm that the processes generated by the method are indeed in the universality classes of the original growth equations. In addition, a crossover from Random Deposition to the associated correlated regime is observed when the parameter $\kappa$ is varied.Comment: 6 pages, 7 figure

A dense disk of dust around the born-again Sakurai's object

In 1996, Sakurai's object (V4334 Sgr) suddenly brightened in the centre of a faint Planetary Nebula (PN). This very rare event was interpreted as the reignition of a hot white dwarf that caused a rapid evolution back to the cool giant phase. From 1998 on, a copious amount of dust has formed continuously, screening out the star which has remained embedded in this expanding high optical depth envelope. The new observations, reported here, are used to study the morphology of the circumstellar dust in order to investigate the hypothesis that Sakurai's Object is surrounded by a thick spherical envelope of dust. We have obtained unprecedented, high-angular resolution spectro-interferometric observations, taken with the mid-IR interferometer MIDI/VLTI, which resolve the dust envelope of Sakurai's object. We report the discovery of a unexpectedly compact (30 x 40 milliarcsec, 105 x 140 AU assuming a distance of 3.5 kpc), highly inclined, dust disk. We used Monte Carlo radiative-transfer simulations of a stratified disk to constrain its geometric and physical parameters, although such a model is only a rough approximation of the rapidly evolving dust structure. Even though the fits are not fully satisfactory, some useful and robust constraints can be inferred. The disk inclination is estimated to be 75+/-3 degree with a large scale height of 47+/-7 AU. The dust mass of the disk is estimated to be 6 10^{-5} solar mass. The major axis of the disk (132+/-3 degree) is aligned with an asymmetry seen in the old PN that was re-investigated as part of this study. This implies that the mechanism responsible for shaping the dust envelope surrounding Sakurai's object was already at work when the old PN formed.Comment: A&A Letter, accepte

Writhing Photons and Berry Phases in Diffusive Wave Scattering

We study theoretically the polarization state of light in multiple scattering media in the limit of weak gradients in refractive index. Linearly polarized photons are randomly rotated due to the Berry phase associated with the scattering path. For circularly polarized light independent speckle patterns are found for the two helical states. The statistics of the geometric phase is related to the writhe distribution of semiflexible polymers such as DNA.Comment: 4 pages, 1 figur

Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load.

OBJECTIVE: Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. DESIGN AND METHODS: By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. RESULTS: Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. CONCLUSION: HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted