A quorum sensing regulated small volatile molecule reduces acute virulence and promotes chronic infection phenotypes.

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections.

Muscle moment-arms: a key element in muscle-force estimation.

A clear and rigorous definition of muscle moment-arms in the context of musculoskeletal systems modelling is presented, using classical mechanics and screw theory. The definition provides an alternative to the tendon excursion method, which can lead to incorrect moment-arms if used inappropriately due to its dependency on the choice of joint coordinates. The definition of moment-arms, and the presented construction method, apply to musculoskeletal models in which the bones are modelled as rigid bodies, the joints are modelled as ideal mechanical joints and the muscles are modelled as massless, frictionless cables wrapping over the bony protrusions, approximated using geometric surfaces. In this context, the definition is independent of any coordinate choice. It is then used to solve a muscle-force estimation problem for a simple 2D conceptual model and compared with an incorrect application of the tendon excursion method. The relative errors between the two solutions vary between 0% and 100%.

Determination of Flood Dischard Characteristics of Small Drainage Areas, HR-3, Progress Report, 1960

Project HR-3 of the Iowa Highway Research Board has been active since October 1, 1950. The project objective is the determination of flood discharge characteristics of small drainage areas. Funds for the project amount to $10,000 per year of which, by cooperative agreement, the Highway Commission and the U. S. Geological Survey each furnish $5,000. Previous reports have explained the set-up of the project and these explanations will not be repeated in this report.

Transverse Joint Sealing with Various Sealants, HR-203, 1983

Iowa's first portland cement concrete pavement was constructed in 1904 in the City of LeMars. A portion of that pavement served traffic until 1974 at which time it was resurfaced. The first rural Iowa pee pavement (16' wide, 6" to 7" thick) was constructed under the direction of the Iowa State Highway Commission in 1913. Some of Iowa's early pavements had transverse joints at 25-foot spacings. At that time, joint spacings across the nation ranged from 24 to 100 ft. There have been many changes in joint design over the years with some pavements being constructed without transverse joints. Joint spacing on Iowa primary pavements has generally remained around 20 feet with this spacing having been adopted as an Iowa standard in 1954. Until 1978 it was common to specify a 40-foot joint spacing on secondary pavements. The performance of the pavements with joint spacings greater than 20 feet, and in some cases no contraction joints, generated a 1955 research project on joint spacing. This project was 16 miles long containing sections without contraction joints and sections with joints sawed at intervals of 20, 50 and 80 feet. Approximately half of the sawed joints were left unsealed. The results of this research supported the 20-foot spacing, but were inconclusive regarding the benefits of sealing. One of the desired characteristics of joint sealing material is that it should act as a moisture barrier and prevent the intrusion of surface water. It was generally accepted from past experience that the hot poured type joint seals did not provide this effective moisture barrier.

Transverse Joint Sealing with Improved Sealers, HR-276, 1991

Concern about premature joint sealant failures occurring in portland cement concrete (PCC) pavements gave impetus to initiating this research project. Eight sealants, including three silicone sealants, were evaluated and tested in the lab as well as incorporated in approximately 700 joints in the field and evaluated over a six-year period. The preliminary data show that among the silicone sealants, Dow Corning 888 rated the highest. However, this was rated third overall behind the W. R. Meadows cold-applied Sof Seal and Crafco #231 hot pour sealants. The W. R. Meadows and Crafco sealants cost approximately 30 percent and 50 percent less to furnish and place than the Dow Corning product. All joint sealants will continue to be evaluated.

Nullification of small knots

in the paper we consider the nullification number of small knots with at most 9 crossings. We establish two inequalities (Corollary 2.1) relating the nullification number to other knot invariants and properties of the knot diagram. We show that these inequalities allow us to settle the nullification number for all of the 84 prime knots with at most 9 crossings.

Therapeutic advances in non-small cell lung cancer.

Despite decades of research, therapeutic advances in non-small cell lung cancer (NSCLC) have progressed at a painstaking slow rate with few improvements in standard surgical resection for early stage disease and chemotherapy or radiotherapy for patients with advanced disease. In the past 18 months, however, we seemed to have reached an inflexion point: therapeutic advances that are centred on improvements in the understanding of patient selection, surgery that is undertaken through smaller incisions, identification of candidate mutations accompanied by the development of targeted anticancer treatments with a focus on personalised medicine, improvements to radiotherapy technology, emergence of radiofrequency ablation (RFA), and last but by no means least, the recognition of palliative care as a therapeutic modality in its own right. The contributors to this review are a distinguished international panel of experts who highlight recent advances in each of the major disciplines.

Transverse Cracking Study of Asphalt Pavement, HR-1020, 1981

At a pavement management study meeting in Omaha, Nebraska, September 12 and 13, 1979, the states of Iowa, Kansas and Nebraska agreed on the need for an in-depth engineering study of thermal cracking of bituminous pavement. In addition, the states of Oklahoma and North Dakota agreed to participate in the study. The scope of the study was to analyze all functions relating to the thermal cracking problem to determine how different uses of preventative materials, mix design measures, maintenance repairs, and design of bituminous pavements and overlays might be contributing to the problem and to determine what improvements might be made in these procedures to reduce the problem of thermal cracking. This publication describes the study and its conclusions. One of the conclusions is that the study did not address what the authors believe to be the major contributor to transverse cracking - the subgrade and subbase.

Transverse Cracking of Asphalt Pavements, HR-1040, Summary Report, 1982

This report summarizes the analysis of transverse cracking in asphalt pavement by a five state study team from Iowa, Kansas, Nebraska, North Dakota, and Oklahoma. The study was initiated under the sponsorship of the Federal Highway Administration and four evaluation conferences were held during the course of the study. Each state conducted a crack inventory on their asphalt pavement. An effort was made to correlate this inventory with numerous factors that were considered to be pertinent to the cracking problem. One state did indicate that there was a correlation between transverse cracking severity and the subsurface geology. The other states were unable to identify any significant factors as being the primary contributors. The analysis of the problem was divided into, (1) mix design, (2) maintenance, and (3) 3R rehabilitation. Many potential factors to be considered were identified under each of these three study divisions. There were many conclusions as to good and bad practices. One major conclusions was that a more effective crack maintenance program with early sealing was essential. Some new practices were suggested as potentially more cost effective in design, construction and maintenance. The interchange of methods and procedures by individual states yielded benefits in that other states selected practices that would be an improvement to their program.

Longitudinal Joint Forming in PCC Pavements, MLR-00-05, Construction Report, 2003

In conventional construction practices, a longitudinal joint is sawed in a PCC (Portland Cement Concrete) pavement to control concrete shrinkage cracking between two lanes of traffic. Sawing a joint in hardened concrete is an expensive and time consuming operation. The longitudinal joint is not a working joint (in comparison to a transverse joint) as it is typically tied with a tie bar at 30 inch spacing. The open joint reservoir, left by the saw blade, typically is filled or sealed with a durable crack sealant to keep incompressibles and water from getting into the joint reservoir. An experimental joint forming knife has been developed. It is installed under the paving machine to form the longitudinal joint in the wet concrete as a part of the paving process. Through this research method, forming a very narrow longitudinal joint during the paving process, two conventional paving operations can be eliminated. Joint forming eliminates the need of the joint sawing operation in the hard concrete, and as the joint that is formed does not leave a wide-open reservoir, but only a hairline crack, it does not need the joint filling or sealing operation. Therefore, the two conventional longitudinal joint sawing and sealing operations are both being eliminated by this innovation. A laboratory scale prototype joint forming knife was built and tested, initially forming joints in small concrete beams. The results were positive so the method was proposed for field testing. Initial field tests were done in the construction season of 2001, limited to one paving contractor. A number of modifications were made to the knife throughout the field tests. About 3000 feet of longitudinal joint was formed in 2001. Additional testing was done in the 2002 construction season, working with the same contractor. About 150,000 feet of longitudinal joint was formed in 2002. Evaluations of the formed joints were done to determine longitudinal joint hairline crack development rate and appearance. Additional tests will be done in the next construction season to improve or perfect the longitudinal joint forming technique.

A propos des "small area variations": opérations pour fracture de hanche dans le canton de Vaud. [Small area variations: surgery for hip fractures in the canton of Vaud].

OBJECTIVES: Studies of small area variations of health care utilization are more and more frequent. Such variations are often considered to be an indication of variations in the quality of medical care. The variations in the rate of operations for hip fractures are among the lowest studied to date, due to the fact that a consensus exists concerning this surgery. Our objective is to examine these variations within the context of relatively small and heterogeneous districts. METHOD: Based on anonymous computerized data on public hospital stays, this study describes the variations in population rates (crude and standardized) of operations for hip fracture among the health districts of the Canton of Vaud for the period from 1986 to 1991. District populations vary from 22,000 to 164,000. Using the extremal quotient (EQ), the importance of these variations was determined. RESULTS: The study population consists of 2363 cases, of which 78% are women. Mean age is 80.4 for women and 70.6 for men. Standardized rates of operation for hip fracture per 100,000 in the Canton Vaud for the years 1986 to 1991 are, respectively: 56; 67; 86; 91; 89 and 94. The EQ for the years 1986 to 1991 are respectively: 8.2; 4.0; 3.5; 2.7; 1.9 and 1.9. The high EQ, especially for the earlier years, are contrary to the initial premise of absence of variation. The progressive implementation in the Canton Vaud of VESKA medical statistics could play a role, as could the small size of many of the districts, with resultant instability of rates. CONCLUSIONS: Considering the wide variations shown here for an operation hardly regarded as subject to variations, it is important to exercise caution in interpreting published data of small area variations.

Impact of lung function changes after induction radiochemotherapy on resected T4 non-small cell lung cancer outcome.

BACKGROUND: Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. METHODS: A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. RESULTS: The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. CONCLUSIONS: In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.