Safety and Pharmacokinetics of Dapivirine Delivery From Matrix and Reservoir Intravaginal Rings to HIV-Negative Women

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twentyfour
healthy HIV-negative women 18–35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma
and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were ,2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

Radiocarbon dating of bulk peat samples from raised bogs: nonexistence of a previously reported 'reservoir effect'?

In 1995. an unexpected reservoir effect was reported in sequences of bulk C-14 dates of raised bog peat. In most peat Studies bulk C-14 dates are used for obtaining chronologies. Therefore it is important to confirm and quantify such a C-14 reservoir effect. Five bulk peat samples from the raised bog Engbertsdijksveen were conventionally C-14 dated. The same core had previously been precisely dated by C-14 AMS dates of carefully selected above-ground plant remains. The existence of a reservoir effect in bulk peat C-14 samples could not be confirmed. Other explanations for the reported reservoir effect are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

Marine reservoir corrections: St Helena, South Atlantic Ocean

We present the first marine reservoir age and Delta R determination for the island of St. Helena using marine mollusk radiocarbon dates obtained from an historical context of known age. This represents the first marine reservoir a.-c and Delta R determination in the southern Atlantic Ocean within thousands of kilometers of the island. The depletion of C-14 in the shells indicates a rather larger reservoir age for that portion of the surface Atlantic than models indicate. The implication is that upwelling old water along the Namibian coast is transported for a considerable distance, although it is likely to be variable on a decadal timescale. An artilleryman's button, together with other artifacts found in a midden, demonstrate association of the mollusk shells with a narrow historic period of AD 1815-1835.

Entangling two distant oscillators with a quantum reservoir

The generation of entanglement between two oscillators that interact via a common reservoir is theoretically studied. The reservoir is modeled by a one-dimensional harmonic crystal initially in thermal equilibrium. Starting from a separable state, the oscillators can become entangled after a transient time, that is of the order of the thermalization time scale. This behaviour is observed at finite temperature even when the oscillators are at a distance significantly larger than the crystal's interparticle spacing. The underlying physical mechanisms can be explained by the dynamical properties of the collective variables of the two oscillators which may decouple from or be squeezed by the reservoir. Our predictions can be tested with an ion chain in a linear Paul trap. Copyright (C) EPLA, 2011

Cowpox: reservoir hosts and geographic range

It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although direct evidence for this is lacking for much of the virus's geographic range. Here, through a combination of serology and PCR, we demonstrate conclusively that the main hosts in Great Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that wood mice may not be able to maintain infection alone, explaining the absence of cowpox from Ireland where voles are generally not found. Infection in wild rodents varies seasonally, and this variation probably underlies the marked seasonal incidence of infection in accidental hosts such as humans and domestic cats.

Understanding the variability in freshwater radiocarbon reservoir offsets: a cautionary tale

Freshwater resources in past diets can lead to inaccuracies when attempts are made to ascertain their radiocarbon ages or those of the consumers. Radiocarbon reservoir effects may lead to significant age offsets when the bones or other tissues of these consumers are radiocarbon dated. A number of recent studies have investigated freshwater reservoir offsets. However no study thus far has satisfactorily obtained a ubiquitous freshwater reservoir correction due to variability in the ecosystems analysed. This study tests the possibility of predicting freshwater reservoir effects from the carbonate alkalinity of the water with measurements on modern fish bone and water samples. A predictive capability would be especially valuable in the absence of well-preserved archaeological fish bone. We surveyed samples from lakes and rivers in varying geological settings in Britain and Ireland. Modern fish bone and water samples were analysed to investigate modern radiocarbon offsets from the atmosphere. Archaeological fish bone was also analysed to examine past reservoir offsets at selected sites. Stable carbon and nitrogen isotope values were measured to aid in interpretation of any variability in the offsets. Large freshwater reservoir offsets were measured in some modern and archaeological samples (maximum offset = 1638 14C years). The freshwater reservoir offsets in the fish bone were highly correlated with alkalinity of water in modern lake sites analysed. However, a high amount of variation within and between fish species was also evident in the results, precluding the possibility of providing regional corrections for freshwater reservoir offsets from alkalinity although this still may provide a general guideline. The variability is thought to be due to differences in the diet of individual fish.

Late-Holocene marine radiocarbon reservoir correction (Delta R) for the west coast of South Africa

In order to calibrate radiocarbon ages based on samples with a marine carbon component it is important to know the marine carbon reservoir correction or Delta R value. This study measured the Delta R on both known-age pre-bomb marine shells and paired marine and terrestrial samples from two regions on the west coast of South Africa: the southwestern Cape and Namaqualand. Pooling the data by region produces Delta R values that are similar enough to use a west coast weighted mean Delta R of 146 +/- 85 C-14 years to correctly calibrate marine shell or mixed marine and terrestrial C-14 ages. There are however temporal differences in Delta R throughout the Holocene, which we compare with proxy data for upwelling and sea surface temperatures.