Interaction of High Intensity Picosecond Laser Pulses with Large Pre-formed Plasmas

The interaction of short (1-2 ps) laser pulses with solid targets at irradiances of over 1016 Wcm~2 , in the presence of a substantial prepulse has been investigated. High absorption of laser energy is found even at high angles of incidence, with evidence for a resonance absorption peak being found for S, P, and circular polarizations. It is considered that this may be a result of refraction and beam filamentation, which causes loss of distinct polarization. Measurements of hard X-ray emission (~ 100 keV) confirm a resonance absorption type peak at 45-50°, again for all three cases. Typically, 5-15% of the incident light is back-reflected by stimulated Brillouin scatter, with spatially resolved spectra showing evidence of beam hot-spots at high intensity. The possibility that filamentation and refraction of the beam can explain the lack of polarization dependence in the absorption and hard X-ray emission data is discussed.

Nature as historical protagonist: environment and society in pre-industrial England

This article compares chronologies reconstructed from historical records of prices, wages, grain harvests, and population with corresponding chronologies of growing conditions and climatic variations derived from dendrochronology and Greenland ice-cores. It demonstrates that in pre-industrial, and especially late medieval, England, short-term environmental shocks and more enduring shifts in environmental conditions (sometimes acting in concert with biological agencies) exercised a powerful influence upon the balance struck between population and available resources via their effects upon the reproduction, health and life expectancy of humans, crops, and livestock. Prevailing socio-economic conditions and institutions, in turn, shaped society's susceptibility to these environmental shocks and shifts.

Pre-treatment with Depo-Provera modifies the pharmacokinetics of CMPD167 in rhesus macaques following vaginal ring administration

BACKGROUND: Vaginal ring devices are being developed to provide sustained release of HIV microbicides. To date, only limited pharmacokinetic data is available from animal or human studies. Here we report the effect of Depo-Provera (DP) pre- treatment, commonly used to thin the vaginal epithelium in challenge experiments, on the pharmacokinetic profile of CMPD167 (a small molecule CCR5 co-receptor antagonist) in rhesus macaques following vaginal ring administration.

METHODS: A single 400mg CMPD167 silicone elastomer vaginal ring was inserted into each of twelve female rhesus macaques. Six macaques were treated with (DP) 30 days before ring placement; the other six macaques were untreated. Blood, vaginal fluid and vaginal biopsies were collected prior to and at various times during 28 days of ring placement and assayed for CMPD167 levels by HPLC. Rings were assayed for residual CMPD167 at the end of the study and the calculated amount of CMPD167 released in vivo compared with in vitro release data.

RESULTS: Vaginal fluid, plasma and tissue levels of CMPD167 were detectable throughout ring placement. Significant differences were observed in mean daily vaginal fluid levels between the DP-treated (16–56 mcg/mL) and untreated groups (48–181 mcg/mL). Plasma CMPD167 levels were significantly higher peaking at 4 ng/mL and maintaining levels of 1–2 nM throughout the 14 days of testing in animals pre-treated with DP compared to non DP-treated macaques (<1 ng/mL maintained). Tissue levels were varied between 2–10 g/mL CMPD167 with no significant difference between the DP-treated and untreated macaques.

CONCLUSIONS: The study demonstrates that clinically relevant, and possibly protective doses of CMPD167 are released in the vaginal vault of rhesus macaques from vaginal rings through 28 days duration. DP is known to induce vaginal epithelial thinning and lower vaginal fluid levels, which accounts for the increased plasma levels of CMPD167. In contrast, macaques not treated with DP had minimal absorption into plasma compartments and significantly higher levels of CMPD167 in the vagina, similar to those previously shown to be protective against vaginal challenge.

Statin prescribing in Northern Ireland and England pre and post introduction of the quality and outcomes framework

Objective The objective of this research was to examine differences in patterns of statin prescribing between Northern Ireland and England both before and after the introduction of the Quality and Outcomes Framework (QOF). Setting: Primary care practices in Northern Ireland and England. Method Northern Ireland practices were matched with practices in England, statin prescribing data and QOF achievement scores (for the first year post-QOF) were obtained. Crude prescribing data from matched practices were manipulated to provide a data set of Defined Daily Doses (DDDs)/1,000 patients and cost/DDD/1,000 patients for each statin drug entity covering 1 year before and after the introduction of QOF. QOF achievements were converted into percentage scores for matched practices. Main outcome measure Cost per defined daily dose (DDD) per 1,000 patients. Results Significantly less statins (DDD/1,000 patients) were dispensed in Northern Ireland compared with the matched region in England both before and after the introduction of QOF (P