Superconductivity in a Quasi One Dimensional Spin Liquid

The single rung t-J ladder is analyzed in a mean field theory using Gutzwiller renormalization of the matrix elements to account for strong correlation. The spin liquid (RVB) state at half-filling evolves into a superconducting state upon doping. The order parameter has a modified d-wave character. A lattice of weakly coupled ladders should show a superconducting phase transition.Comment: 9 pages + 4 postscript files appende

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

High Resolution Discrimination of Clinical Mycobacterium tuberculosis Complex Strains Based on Single Nucleotide Polymorphisms

Recently, the diversity of the Mycobacterium tuberculosis complex (MTBC) population structure has been described in detail. Based on geographical separation and specific host pathogen co-evolution shaping MTBC virulence traits, at least 20 major lineages/genotypes have evolved finally leading to a clear influence of strain genetic background on transmissibility, clinical presentation/outcome, and resistance development. Therefore, high resolution genotyping for characterization of strains in larger studies is mandatory for understanding mechanisms of host-pathogen-interaction and to improve tuberculosis (TB) control. Single nucleotide polymorphisms (SNPs) represent the most reliable markers for lineage classification of clinical isolates due to the low levels of homoplasy, however their use is hampered either by low discriminatory power or by the need to analyze a large number of genes to achieve higher resolution. Therefore, we carried out de novo sequencing of 26 genes (approx. 20000 bp per strain) in a reference collection of MTBC strains including all major genotypes to define a highly discriminatory gene set. Overall, 161 polymorphisms were detected of which 59 are genotype-specific, while 13 define deeper branches such as the Euro-American lineage. Unbiased investigation of the most variable set of 11 genes in a population based strain collection (one year, city of Hamburg, Germany) confirmed the validity of SNP analysis as all strains were classified with high accuracy. Taken together, we defined a diagnostic algorithm which allows the identification of 17 MTBC phylogenetic lineages with high confidence for the first time by sequencing analysis of just five genes. In conclusion, the diagnostic algorithm developed in our study is likely to open the door for a low cost high resolution sequence/SNP based differentiation of the MTBC with a very high specificity. High throughput assays can be established which will be needed for large association studies that are mandatory for detailed investigation of host-pathogen-interaction during TB infection

Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population.</p> <p>Methods</p> <p>Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated <it>P. falciparum </it>malaria in infants and children in Africa were analysed according to body weight group.</p> <p>Results</p> <p>The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively.</p> <p>Conclusion</p> <p>Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.</p

Dihydroartemisinin-Piperaquine and Artemether-Lumefantrine for Treating Uncomplicated Malaria in African Children: A Randomised, Non-Inferiority Trial

BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443

Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation

Cardiolog

Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis.

There are currently several recommended drug regimens for uncomplicated falciparum malaria in Africa. Each has different properties that determine its impact on disease burden. Two major antimalarial policy options are artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQP). Clinical trial data show that DHA-PQP provides longer protection against reinfection, while AL is better at reducing patient infectiousness. Here we incorporate pharmacokinetic-pharmacodynamic factors, transmission-reducing effects and cost into a mathematical model and simulate malaria transmission and treatment in Africa, using geographically explicit data on transmission intensity and seasonality, population density, treatment access and outpatient costs. DHA-PQP has a modestly higher estimated impact than AL in 64% of the population at risk. Given current higher cost estimates for DHA-PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large. We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden