Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO 3- and NO2- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 μM N2O (range 1.4-157.9 μM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention. © 2014 Kolpen et al

Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

Oceanography : plankton in a warmer world

Author Posting. © Nature Publishing Group, 2006. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 444 (2006): 695-696, doi:10.1038/444695a.Satellite data show that phytoplankton biomass and growth generally decline as the oceans’ surface waters warm up. Is this trend, seen over the past decade, a harbinger of the future for marine ecosystems

Microstructural control suppresses thermal activation of electron transport at room temperature in polymer transistors

Recent demonstrations of inverted thermal activation of charge mobility in polymer field- effect transistors have excited the interest in transport regimes not limited by thermal bar- riers. However, rationalization of the limiting factors to access such regimes is still lacking. An improved understanding in this area is critical for development of new materials, establishing processing guidelines, and broadening of the range of applications. Here we show that precise processing of a diketopyrrolopyrrole-tetrafluorobenzene-based electron transporting copo- lymer results in single crystal-like and voltage-independent mobility with vanishing activation energy above 280 K. Key factors are uniaxial chain alignment and thermal annealing at temperatures within the melting endotherm of films. Experimental and computational evi- dences converge toward a picture of electrons being delocalized within crystalline domains of increased size. Residual energy barriers introduced by disordered regions are bypassed in the direction of molecular alignment by a more efficient interconnection of the ordered domains following the annealing process

Low-grade pelvic masses with spindle cell and fibroblastic proliferation: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Land of Addicts? An Empirical Investigation of Habit-Based Asset Pricing Models

A popular explanation of aggregate stock market behavior suggests that assets are priced as if there were a representative investor whose utility is a power function of the difference between aggregate consumption and a “habit” level, where the habit is some function of lagged and (possibly) contemporaneous consumption. But theory does not provide precise guidelines about the parametric functional relationship between the habit and aggregate consumption. This makes for- mal estimation and testing challenging; at the same time, it raises an empirical question about the functional form of the habit that best explains asset pricing data. This paper studies the ability of a general class of habit-based asset pricing models to match the conditional moment restrictions implied by asset pricing theory. Our approach is to treat the functional form of the habit as unknown, and to estimate it along with the rest of the model’s finite dimensional parameters. This semiparametric approach allows us to empirically evaluate a number of interesting hypotheses about the specification of habit-based asset pricing models. Using stationary quarterly data on consumption growth, assets returns and instruments, our empirical results indicate that the estimated habit function is nonlinear, the habit formation is internal, and the estimated time-preference parameter and the power utility parameter are sensible. In addition, our estimated habit function generates a positive stochastic discount factor (SDF) proxy and performs well in explaining cross-sectional stock return data. We find that an internal habit SDF proxy can explain a cross-section of size and book-market sorted portfolio equity returns better than (i) the Fama and French (1993) three-factor model, (ii) the Lettau and Ludvigson (2001b) scaled consumption CAPM model, (iii) an external habit SDF proxy, (iv) the classic CAPM, and (v) the classic consumption CAPM

A Canadian approach to the regionalization of testis cancer: A review.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine

Radiating Shear-Free Gravitational Collapse with Charge

We present a new shear free model for the gravitational collapse of a spherically symmetric charged body. We propose a dissipative contraction with radiation emitted outwards. The Einstein field equations, using the junction conditions and an ansatz, are integrated numerically. A check of the energy conditions is also performed. We obtain that the charge delays the black hole formation and it can even halt the collapse.Comment: 22 pages, 9 figures. It has been corrected several typos and included several references. Accepted for publication in GR

Patients with shoulder impingement remain satisfied 6 years after arthroscopic subacromial decompression: A prospective study of 46 patients

Background Although arthroscopic subacromial decompression (ASD) is a common procedure for treatment of shoulder impingement, few long term results have been published. In this prospective study, we determined whether the high degree of patient satisfaction at 6 months postoperatively reported by us earlier remained at the 6-year follow-up. Patients and methods We originally reported high patient satisfaction 6 months after ASD for shoulder impingement in 50 prospectively studied patients using the Disability of the Arm Shoulder and Hand questionnaire (DASH) and the Visual Analog Scale (VAS). Patients with associated shoulder disorders were excluded. The surgeons were experienced shoulder arthroscopists. 6 years after surgery, the DASH questionnaire and the VAS were sent to these 50 patients. 2 patients had other medical problems of the upper extremity that affected the DASH and VAS scores, 1 patient was lost to follow-up, and another refused to participate. Thus, 46 patients with a mean age of 55 (33-78) years were included in this 6-year evaluation. Results The considerable improvement in both the DASH score and the VAS that was observed 6 months after surgery persisted or had even improved 6 years after surgery. Interpretation Properly selected patients with shoulder impingement treated with ASD remain satisfied 6 years after surgery

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions