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

Electric field control of multiferroic domains in Ni3_3V2_2O8_8 imaged by X-ray polarization enhanced topography

The magnetic structure of multiferroic Ni$_3$V$_2$O$_8$ has been investigated using non-resonant X-ray magnetic scattering. Incident circularly polarized X-rays combined with full polarization analysis of the scattered beam is shown to yield high sensitivity to the components of the cycloidal magnetic order, including their relative phases. New information on the magnetic structure in the ferroelectric phase is obtained, where it is found that the magnetic moments on the "cross-tie" sites are quenched relative to those on the "spine" sites. This implies that the onset of ferroelectricity is associated mainly with spine site magnetic order. We also demonstrate that our technique enables the imaging of multiferroic domains through polarization enhanced topography. This approach is used to image the domains as the sample is cycled by an electric field through its hysteresis loop, revealing the gradual switching of domains without nucleation.Comment: 9 pages, 6 figure

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

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

The development of a stochastic mathematical model of Alzheimer's disease to help improve the design of clinical trials of potential treatments

Alzheimer’s disease (AD) is a neurodegenerativ e disorder characterised by a slow progres- sive deterioration of cognitive capacity. Drugs are urgently needed for the treatment of AD and unfortunately almost all clinical trials of AD drug candidates have failed or been discon- tinued to date. Mathematical, computational and statistical tools can be employed in the construction of clinical trial simulators to assist in the improvement of trial design and enhance the chances of success of potential new therapies. Based on the analysis of a set of clinical data provided by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) we developed a simple stochastic mathematical model to simulate the development and pro- gression of Alzheimer’s in a longitudinal cohort study. We show how this modelling frame- work could be used to assess the effect and the chances of success of hypothetical treatments that are administered at different stages and delay disease development. We demonstrate that the detection of the true efficacy of an AD treatment can be very challeng- ing, even if the treatment is highly effective. An important reason behind the inability to detect signals of efficacy in a clinical trial in this therapy area could be the high between- and within-individual variability in the measuremen t of diagnostic markers and endpoints, which consequently results in the misdiagno sis of an individual’s disease state

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