The Optical Potential on the Lattice

The extraction of hadron-hadron scattering parameters from lattice data by using the L\"uscher approach becomes increasingly complicated in the presence of inelastic channels. We propose a method for the direct extraction of the complex hadron-hadron optical potential on the lattice, which does not require the use of the multi-channel L\"uscher formalism. Moreover, this method is applicable without modifications if some inelastic channels contain three or more particles.Comment: 26 pages, 12 figure

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients

Rationale For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. Objectives To compare the safety and efficacy of a 28-day course of treatment with LIS 240 mg or placebo BID in persons ≥ 12 years old with CF and chronic P. aeruginosa infection. Methods A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28 days in CF patients ≥ 12 years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported quality of life were among secondary endpoints. Main results Baseline demographics for 330 subjects (LIS = 220) were similar although significantly more patients randomized to LIS had experienced multiple exacerbations in the year prior to study entry. There was no statistically significant difference in protocol-defined pulmonary exacerbations between treatment arms. Relative change in FEV1% predicted from baseline was significantly greater for patients randomized to LIS compared to those randomized to placebo (mean difference 1.31%, p = 0.01 [95% CI 0.27, 2.34%]). LIS was well-tolerated, with dysguesia the most frequent adverse event. Conclusions LIS did not demonstrate a difference in time to next exacerbation when compared to placebo. Reasons for this result are discussed but may be due to an imbalance in the frequency of prior pulmonary exacerbations between the two groups. An improvement in FEV1 (% predicted) at 28 days was observed and LIS was well tolerated. LIS is safe and has a potential role in the management of CF patients with chronic P. aeruginosa

A phase 3, open-label, randomized trial to evaluate the safety and efficacy of levofloxacin inhalation solution (APT-1026) versus tobramycin inhalation solution in stable cystic fibrosis patients

Background: Inhaled antibiotics are standard of care for persons with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa airway infection. APT-1026 (levofloxacin inhalation solution, LIS) is fluoroquinolone in development. We compared the safety and efficacy of LIS to tobramycin inhalation solution (TIS) in persons ≥12 years old with CF and chronic P. aeruginosa infection. Methods: This multinational, randomized (2:1), non-inferiority study compared LIS and TIS over three 28-day on/off cycles. Day 28 FEV1 % predicted change was the primary endpoint. Time to exacerbation and patient-reported quality of life superiority were among secondary endpoints. Results: Baseline demographics for 282 subjects were comparable. Non-inferiority was demonstrated (1.86% predicted mean FEV1 difference [95% CI −0.66 to 4.39%]). LIS was well-tolerated, with dysguesia (taste distortion) the most frequent adverse event. Conclusions: LIS is a safe and effective therapy for the management of CF patients with chronic P. aeruginosa

Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

Objective and designCystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.Materials and methodsCFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.ResultsPharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.ConclusionsLack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury

Multiple FadD Acyl-CoA Synthetases Contribute to Differential Fatty Acid Degradation and Virulence in Pseudomonas aeruginosa

A close interconnection between nutrient metabolism and virulence factor expression contributes to the pathophysiology of Pseudomonas aeruginosa as a successful pathogen. P. aeruginosa fatty acid (FA) degradation is complicated with multiple acyl-CoA synthetase homologs (FadDs) expressed in vivo in lung tissue during cystic fibrosis infections. The promoters of two genetically linked P. aeruginosa fadD genes (fadD1 and fadD2) were mapped and northern blot analysis indicated they could exist on two different transcripts. These FadDs contain ATP/AMP signature and FA-binding motifs highly homologous to those of the Escherichia coli FadD. Upon introduction into an E. coli fadD-/fadR- double mutant, both P. aeruginosa fadDs functionally complemented the E. coli fadD-/fadR- mutant, allowing degradation of different chain-length FAs. Chromosomal mutagenesis, growth analysis, induction studies, and determination of kinetic parameters suggested that FadD1 has a substrate preference for long-chain FAs while FadD2 prefers shorter-chain FAs. When compared to the wild type strain, the fadD2 mutant exhibited decreased production of lipase, protease, rhamnolipid and phospholipase, and retardation of both swimming and swarming motilities. Interestingly, fadD1 mutant showed only increased swarming motility. Growth analysis of the fadD mutants showed noticeable deficiencies in utilizing FAs and phosphatidylcholine (major components of lung surfactant) as the sole carbon source. This defect translated into decreased in vivo fitness of P. aeruginosa in a BALB/c mouse lung infection model, supporting the role of lipids as a significant nutrient source for this bacterium in vivo

Bacterial Gut Symbionts Contribute to Seed Digestion in an Omnivorous Beetle

Obligate bacterial symbionts alter the diets of host animals in numerous ways, but the ecological roles of facultative bacterial residents that colonize insect guts remain unclear. Carabid beetles are a common group of beneficial insects appreciated for their ability to consume insect prey and seeds, but the contributions of microbes to diet diversification in this and similar groups of facultative granivores are largely unknown.Using 16S rRNA gene clone libraries and terminal restriction fragment (tRF) length polymorphism analyses of these genes, we examined the bacterial communities within the guts of facultatively granivorous, adult Harpalus pensylvanicus (Carabidae), fed one of five dietary treatments: 1) an untreated Field population, 2) Seeds with antibiotics (seeds were from Chenopodium album), 3) Seeds without antibiotics, 4) Prey with antibiotics (prey were Acheta domesticus eggs), and 5) Prey without antibiotics. The number of seeds and prey consumed by each beetle were recorded following treatment. Harpalus pensylvanicus possessed a fairly simple gut community of approximately 3-4 bacterial operational taxonomic units (OTU) per beetle that were affiliated with the Gammaproteobacteria, Bacilli, Alphaproteobacteria, and Mollicutes. Bacterial communities of the host varied among the diet and antibiotic treatments. The field population and beetles fed seeds without antibiotics had the closest matching bacterial communities, and the communities in the beetles fed antibiotics were more closely related to each other than to those of the beetles that did not receive antibiotics. Antibiotics reduced and altered the bacterial communities found in the beetle guts. Moreover, beetles fed antibiotics ate fewer seeds, and those beetles that harbored the bacterium Enterococcus faecalis consumed more seeds on average than those lacking this symbiont.We conclude that the relationships between the bacterium E. faecalis and this factultative granivore's ability to consume seeds merit further investigation, and that facultative associations with symbiotic bacteria have important implications for the nutritional ecology of their hosts

Gout. Epidemiology of gout

Gout is the most prevalent form of inflammatory arthropathy. Several studies suggest that its prevalence and incidence have risen in recent decades. Numerous risk factors for the development of gout have been established, including hyperuricaemia, genetic factors, dietary factors, alcohol consumption, metabolic syndrome, hypertension, obesity, diuretic use and chronic renal disease. Osteoarthritis predisposes to local crystal deposition. Gout appears to be an independent risk factor for all-cause mortality and cardiovascular mortality and morbidity, additional to the risk conferred by its association with traditional cardiovascular risk factors

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe