Evolution of cassava brown streak disease-associated viruses

Cassava brown streak disease (CBSD) has occurred in the Indian Ocean coastal lowlands and some areas of Malawi in East Africa for decades, and makes the storage roots of cassava unsuitable for consumption. CBSD is associated with Cassava brown streak virus (CBSV) and the recently described Ugandan cassava brown streak virus (UCBSV) [picorna-like (+)ssRNA viruses; genus Ipomovirus; family Potyviridae]. This study reports the first comprehensive analysis on how evolution is shaping the populations of CBSV and UCBSV. The complete genomes of CBSV and UCBSV (four and eight isolates, respectively) were 69.0–70.3 and 73.6–74.4% identical at the nucleotide and polyprotein amino acid sequence levels, respectively. They contained predictable sites of homologous recombination, mostly in the 39-proximal part (NIb-HAM1h-CP-39-UTR) of the genome, but no evidence of recombination between the two viruses was found. The CP-encoding sequences of 22 and 45 isolates of CBSV and UCBSV analysed, respectively, were mainly under purifying selection; however, several sites in the central part of CBSV CP were subjected to positive selection. HAM1h (putative nucleoside triphosphate pyrophosphatase) was the least similar protein between CBSV and UCBSV (aa identity approx. 55 %). Both termini of HAM1h contained sites under positive selection in UCBSV. The data imply an on-going but somewhat different evolution of CBSV and UCBSV, which is congruent with the recent widespread outbreak of UCBSV in cassava crops in the highland areas (.1000 m above sea level) of East Africa where CBSD has not caused significant problems in the past

The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: data from the multinational Sampling Antibiotics in Renal Replacement Therapy Study

Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and to relate observed trough antibiotic concentrations to optimal targets. Methods: We performed a prospective, observational, multi-national, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam and vancomycin and related them to high and low target trough concentrations. Results: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8 fold) in antibiotic dosing regimens; RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/min (interquartile range [IQR] 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (p<0.05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin 78.6 mg/L (49.5-127.3), tazobactam 9.5 mg/L (6.3-14.2) and vancomycin 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, 72%, and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin and vancomycin respectively. Conclusions: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.Jason A. Roberts … Sandra L. Peake … Michael S. Roberts … Mahipal Sinnollareddy … John Turnidge … Tricia Williams … et al. on behalf of the SMARRT Study Collaborators and the ANZICS Clinical Trials Grou

Factors explaining the geographical differences in Disability Free Life Expectancy in Spain

OBJECTIVE—To study the geographical variations in Disability Free Life Expectancy (DFLE) at birth (DFLEb) and at 65 years (DFLE65) in Spain and to identify the main factors that explain these variations.
DESIGN—Ecological study with the 50 provinces of Spain as the units of analysis. Sullivan's method is used to calculate DFLE for each province based on information from the death registry and the survey on disabilities, impairments and handicaps. Information on the independent variables—socioeconomic level, factors related with the health system and risk factors—was taken from various sources.
MAIN OUTCOME MEASURE—Simple correlation coefficients were obtained between each dependent variable (DFLEb and DLFE65) and the independent variables. Two multiple linear regression models were fit to obtain the best set of factors that explain the geographical distribution of DFLEb and DLFE65.
RESULTS—Both DFLEb and DLFE65 vary widely among provinces. The multiple linear regression analysis shows that the illiteracy rate, the percentage of the unemployed and the percentage of smokers in the population were the main factors associated with the geographical variation of DFLE. The models explained approximately 40% of the variance for DFLEb and 30% for DLFE65.
CONCLUSIONS—The results obtained show the influence of education, the unemployment rate and smoking on the geographical differences of DFLE. The DFLE indicators are shown to be valid for use in health policy.


Keywords: Disability Free Life Expectancy; geographical difference

The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: data from the multinational sampling antibiotics in renal replacement therapy study

Background: the optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets.Methods: we performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.Results: we studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P &lt; .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.Conclusions: in critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients