Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

Humanized Mice Recapitulate Key Features of HIV-1 Infection: A Novel Concept Using Long-Acting Anti-Retroviral Drugs for Treating HIV-1

BACKGROUND: Humanized mice generate a lymphoid system of human origin subsequent to transplantation of human CD34+ cells and thus are highly susceptible to HIV infection. Here we examined the efficacy of antiretroviral treatment (ART) when added to food pellets, and of long-acting (LA) antiretroviral compounds, either as monotherapy or in combination. These studies shall be inspiring for establishing a gold standard of ART, which is easy to administer and well supported by the mice, and for subsequent studies such as latency. Furthermore, they should disclose whether viral breakthrough and emergence of resistance occurs similar as in HIV-infected patients when ART is insufficient. METHODS/PRINCIPAL FINDINGS: NOD/shi-scid/γ(c)null (NOG) mice were used in all experimentations. We first performed pharmacokinetic studies of the drugs used, either added to food pellets (AZT, TDF, 3TC, RTV) or in a LA formulation that permitted once weekly subcutaneous administration (TMC278: non-nucleoside reverse transcriptase inhibitor, TMC181: protease inhibitor). A combination of 3TC, TDF and TMC278-LA or 3TC, TDF, TMC278-LA and TMC181-LA suppressed the viral load to undetectable levels in 15/19 (79%) and 14/14 (100%) mice, respectively. In successfully treated mice, subsequent monotherapy with TMC278-LA resulted in viral breakthrough; in contrast, the two LA compounds together prevented viral breakthrough. Resistance mutations matched the mutations most commonly observed in HIV patients failing therapy. Importantly, viral rebound after interruption of ART, presence of HIV DNA in successfully treated mice and in vitro reactivation of early HIV transcripts point to an existing latent HIV reservoir. CONCLUSIONS/SIGNIFICANCE: This report is a unique description of multiple aspects of HIV infection in humanized mice that comprised efficacy testing of various treatment regimens, including LA compounds, resistance mutation analysis as well as viral rebound after treatment interruption. Humanized mice will be highly valuable for exploring the antiviral potency of new compounds or compounds targeting the latent HIV reservoir

Overview of the coordinated ground-based observations of Titan during the Huygens mission

Coordinated ground-based observations of Titan were performed around or during the Huygens atmospheric probe mission at Titan on 14 January 2005, connecting the momentary in situ observations by the probe with the synoptic coverage provided by continuing ground-based programs. These observations consisted of three different categories: (1) radio telescope tracking of the Huygens signal at 2040 MHz, (2) observations of the atmosphere and surface of Titan, and (3) attempts to observe radiation emitted during the Huygens Probe entry into Titan's atmosphere. The Probe radio signal was successfully acquired by a network of terrestrial telescopes, recovering a vertical profile of wind speed in Titan's atmosphere from 140 km altitude down to the surface. Ground-based observations brought new information on atmosphere and surface properties of the largest Satumian moon. No positive detection of phenomena associated with the Probe entry was reported. This paper reviews all these measurements and highlights the achieved results. The ground-based observations, both radio and optical, are of fundamental imnortance for the interpretatinn of results from the Huygens mission

The continuous performance test revisited with neuroelectric mapping : impaired orienting in children with attention deficits

A total of 11 children with attention deficit disorder (ADD) and nine control children performed a continuous performance test (CPT) of the A-X type with concurrent neuroelectric brain mapping to assess preparatory processing, purportedly mediated by the frontal lobes. This cued CPT task proved to be a highly specific task. The groups could be clearly differentiated both at the behavioral and electrophysiological level. ADD children detected fewer signals and made more false alarms. There were no major group differences in topographical distribution of the event-related potential microstates, but ADD children displayed reduced global field power (GFP) in an early CNV/P3 microstate to cues. This indicated that impaired orienting to cues, rather than impaired executive target processing, determines the initial processing stages in ADD. In comparison with data from the same task run in Utrecht, the same orienting deficit in clinically diagnosed ADHD children was demonstrated. Low resolution electromagnetic tomography (LORETA) estimated posterior sources underlying these orienting processes and the orienting deficit. This argued against frontal lobe involvement at this stage and suggested involvement of a posterior attention system