Eastern Mediterranean water outflow during the Younger Dryas was twice that of the present day

Eastern Mediterranean deep-intermediate convection was highly sensitive to varying inputs of fresh water fluxes associated with increased rainfall during the African Humid period (15-6 kyr Before Present). Here we investigate changes in the water-outflow from the Eastern Mediterranean Sea since the last deglaciation using neodymium isotope ratios. Our results indicate enhanced outflow during the Younger Dryas, two times higher than present-day outflow and about three times higher than during the last Sapropel. We propose that the increased outflow into the western Mediterranean over the Younger Dryas was the result of the combined effect of 1) enhanced climate-driven convection in the Aegean Sea and 2) reduced convection of western deep water during this period. Our results provide solid evidence for an enhanced Younger Dryas westward flow of Eastern Mediterranean sourced waters in consonance with an intensification of Mediterranean water-outflow during a weakened state of the Atlantic circulatio

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

Rare earth elements and Nd isotopes as tracers of modern ocean circulation in the central Mediterranean Sea

Seawater rare earth element (REE) concentrations and Nd isotopic composition (εNd) are increasingly applied as valuable tracers of oceanographic processes such as water mass mixing and lithogenic inputs to seawater. However, their measurements are basically lacking in the Mediterranean Sea water column. This study analyzes 9 seawater stations around the central Mediterranean Sea to clarify the relative importance of external sources, vertical (biogeochemical) processes and lateral water mass transport in controlling REE and εNd distributions. Concentrations of REE do not show nutrient-like profiles with depth, likely indicative of relatively young waters with limited accumulation of remineralized REE. Light REE (LREE) present a non-conservative behavior, which largely peak at surface waters and rapidly decrease with depth. The negative correlation of surface LREE enrichment with offshore distance highlights the influence of continental input from the western Italian coast to the Tyrrhenian surface waters. In contrast to other regions with reported boundary exchange, this process does not modify the εNd values here. On the other side, distributions of dissolved heavy REE (HREE) and εNd display a conservative behavior that can be explained by mixing of western- (MAW and WMDW) and eastern- (LIW and EMDW) originated waters. We test this hypothesis with an Optimum Multi-Parameter Analysis (OMPA) including HREE and εNd parameters. Even though the limited data set, consistent results of water mass fractions are obtained for the four main water masses although with some particularities. While LIW takes on major importance when considering HREE in the model, EMDW fractions are preferentially detected with εNd. This latter finding implies a noticeable deep water flux across the Sicily Strait into the Western Mediterranean that was not clearly evidenced before

Eastern Mediterranean water outflow during the Younger Dryas was twice that of the present day

Eastern Mediterranean deep-intermediate convection was highly sensitive to varying inputs of fresh water fluxes associated with increased rainfall during the African Humid period (15-6 kyr Before Present). Here we investigate changes in the water-outflow from the Eastern Mediterranean Sea since the last deglaciation using neodymium isotope ratios. Our results indicate enhanced outflow during the Younger Dryas, two times higher than present-day outflow and about three times higher than during the last Sapropel. We propose that the increased outflow into the western Mediterranean over the Younger Dryas was the result of the combined effect of 1) enhanced climate-driven convection in the Aegean Sea and 2) reduced convection of western deep water during this period. Our results provide solid evidence for an enhanced Younger Dryas westward flow of Eastern Mediterranean sourced waters in consonance with an intensification of Mediterranean water-outflow during a weakened state of the Atlantic circulation

Differences in pathogenicity of three animal isolates of Mycobacterium species in a mouse model.

Animal mycobacterioses are among the most important zoonoses worldwide. These are generally caused by either Mycobacterium tuberculosis (MTB), M. bovis (MBO) or M. avium (MAV). To test the hypothesis that different species of pathogenic mycobacteria isolated from varied anatomic locations or animal species differ in virulence and pathogenicity, we performed experiments with three mycobacteria strains (NTSE-3(MTB), NTSE-4(MBO) and NTSE-5 (MAV)) obtained from animal species. Spoligotyping analysis was used to confirm both MTB and MBO strains while the MAV strain was confirmed by 16s rDNA sequencing. BALB/c mice were intranasally infected with the three strains at low and high CFU doses to evaluate variations in pathogenicity. Clinical and pathological parameters were assessed. Infected mice were euthanized at 80 days post-inoculation (dpi). Measures of lung and body weights indicated that the MBO infected group had higher mortality, more weight loss, higher bacterial burden and more severe lesions in lungs than the other two groups. Cytokine profiles showed higher levels of TNF-α for MBO versus MTB, while MAV had the highest amounts of IFN-β in vitro and in vivo. In vitro levels of other cytokines such as IL-1β, IL-10, IL-12, IL-17, and IFN-β showed that Th1 cells had the strongest response in MBO infected mice and that Th2 cells were inhibited. We found that the level of virulence among the three isolates decreased in the following order MBO>MTB>MAV

Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0\u20137 [low mortality score] vs 8\u201315 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38\ub75%] of 343 patients died vs 57 [60\ub76%] of 94; absolute difference 22\ub71% [95% CI 11\ub70\u201333\ub73]; adjusted hazard ratio [HR] 0\ub745 [95% CI 0\ub733\u20130\ub762]; p<0\ub70001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1\ub763 [95% CI 0\ub767\u20133\ub791]; p=0\ub728). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0\ub756 [0\ub734\u20130\ub791]; p=0\ub702), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1\ub721 [0\ub756\u20132\ub756]; p=0\ub762). Interpretation Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. Funding Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative