Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis

The original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa toward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

A multi-proxy approach for revealing recent climatic changes in the Russian Altai

For the first time we present a multi-proxy data set for the Russian Altai, consisting of Siberian larch tree-ring width (TRW), latewood density (MXD), δ13C and δ18O in cellulose chronologies obtained for the period 1779–2007 and cell wall thickness (CWT) for 1900–2008. All of these parameters agree well between each other in the high-frequency variability, while the low-frequency climate information shows systematic differences. The correlation analysis with temperature and precipitation data from the closest weather station and gridded data revealed that annual TRW, MXD, CWT, and δ13C data contain a strong summer temperature signal, while δ18O in cellulose represents a mixed summer and winter temperature and precipitation signal. The temperature and precipitation reconstructions from the Belukha ice core and Teletskoe lake sediments were used to investigate the correspondence of different independent proxies. Low frequency patterns in TRW and δ13C chronologies are consistent with temperature reconstructions from nearby Belukha ice core and Teletskoe lake sediments showing a pronounced warming trend in the last century. Their combination could be used for the regional temperature reconstruction. The long-term δ18O trend agrees with the precipitation reconstruction from the Teletskoe lake sediment indicating more humid conditions during the twentieth century. Therefore, these two proxies could be combined for the precipitation reconstruction.

Fingerprints of changes in the terrestrial carbon cycle in response to large reorganizations in ocean circulation

CO2 and carbon cycle changes in the land, ocean and atmosphere are investigated using the comprehensive carbon cycle-climate model NCAR CSM1.4-carbon. Ensemble simulations are forced with freshwater perturbations applied at the North Atlantic and Southern Ocean deep water formation sites under pre-industrial climate conditions. As a result, the Atlantic Meridional Overturning Circulation reduces in each experiment to varying degrees. The physical climate fields show changes qualitatively in agreement with results documented in the literature, but there is a clear distinction between northern and southern perturbations. Changes in the physical variables, in turn, affect the land and ocean biogeochemical cycles and cause a reduction, or an increase, in the atmospheric CO2 concentration by up to 20 ppmv, depending on the location of the perturbation. In the case of a North Atlantic perturbation, the land biosphere reacts with a strong reduction in carbon stocks in some tropical locations and in high northern latitudes. In contrast, land carbon stocks tend to increase in response to a southern perturbation. The ocean is generally a sink of carbon although large reorganizations occur throughout various basins. The response of the land biosphere is strongest in the tropical regions due to a shift of the Intertropical Convergence Zone. The carbon fingerprints of this shift, either to the south or to the north depending on where the freshwater is applied, can be found most clearly in South America. For this reason, a compilation of various paleoclimate proxy records of Younger Dryas precipitation changes are compared with our model results. The proxy records, in general, show good agreement with the model's response to a North Atlantic freshwater perturbation.

Proteomic changes in the rat brain induced by homogenous irradiation and by the bystander effect resulting from high energy synchrotron X-ray microbeams

Abstract Purpose: To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue. Methods: Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry. Results: HI resulted in proteomic responses indicative of tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI), and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect proteomic changes were indicative of reactive oxygen species mediated apoptosis; reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also associated with neurodegeneration. However the bystander effect also increased heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of the neurological disorders characterized by the bystander effect proteome changes. Conclusions: These results indicate that the collective interaction of these MBI-induced bystander effect proteins and their mediation by HSP 71, may confer a protective effect which now warrants additional experimental attention.

Postoperative changes in the superficial temporal artery and the external carotid artery duplex sonography after extra-intracranial bypass surgery in European Moyamoya disease

Despite Duplex ultrasonography being a noninvasive, easily repeatable, readily available and economical tool, this examination and its normal ranges are rarely described in Moyamoya disease (MMD).