Comparison of hospitalization rates in patients with community-acquired pneumonia treated with telithromycin for 5 or 7 days or clarithromycin for 10 days.

Journal ArticleAIMS: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP). METHODS: A total of 581 patients with CAP were enrolled in this randomized, double-blind, parallel group, multinational study, of whom 575 were evaluated for healthcare resource utilization from a payer perspective (intent to treat [ITT] population). Patients received telithromycin 800 mg once daily for 5 (n = 193) or 7 (n = 195)days, or clarithromycin 500 mg once daily for 10 days (n = 187). The primary efficacy endpoint was clinical outcome at test of cure (Days 17-24) in the per-protocol population. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (ITT) up to late post- for clarithromycin vs dollars 37930 (difference: -26446; therapy (Days 31-36). Study investigators blinded to treatment assessed whether hospital admissions were CAP-related or not. CAP-related hospitalization costs (USdollars) for telithromycin and clarithromycin were compared. RESULTS: Clinical cure rates were similar in patients who received clarithromycin for 10 days and telithromycin for 5 or 7 days: 91.8% (134/146), 89.3% (142/159), and 88.8% (143/161), respectively, and both 5- and 7-day telithromycin were statistically equivalent to clarithromycin (difference: -2.5 and -3.0%, respectively; 95% CI: -9.7, 4.7 and -10.2, 4.3, respectively). There were 7 CAP-related hospital admissions among clarithromycin patients vs 3 (p = 0.283) and 1 (p = 0.021) admissions among 5- and 7-day telithromycin patients, respectively. The number of hospital days/100 patients was 40.1 for clarithromycin vs 17.1 and 7.2 for 5- and 7-day telithromycin, respectively. Projected hospitalization costs/100 patients were dollars 86205 95% CI: -66 654; 13 762) and dollars 16 091 (difference: -37 847; 95% CI: -77953; 2259) for 5- and 7-day telithromycin, respectively. CONCLUSIONS: Data from this study demonstrate that telithromycin 800 mg once daily for 5 or 7 days with fewer hospital days and potentially lower is an effective treatment for CAP,and that telithromycin treatment of CAP may be associated hospitalization costs than clarithromycin treatment

Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

<p>Abstract</p> <p>Background</p> <p>HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper.</p> <p>Methods</p> <p>A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR) of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit.</p> <p>Results</p> <p>HPV loads were consistently higher among women <25 years old, and those who had multiple sex partners, multiple HPV type infections and smokers. HPV-16 integration was encountered only in one sample. Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8, 95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI: 1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and infection clearance followed a clear dose-response pattern, after adjusting for age and number of sexual partners. GEE Odds Ratios for HPV persistence of the middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV-16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between HPV-31 or -45 DNA loads and persistence.</p> <p>Conclusions</p> <p>The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.</p

The J-2X Fuel Turbopump - Design, Development, and Test

Pratt and Whitney Rocketdyne (PWR), a NASA subcontractor, is executing the design, development, test, and evaluation (DDT&E) of a liquid oxygen, liquid hydrogen two hundred ninety four thousand pound thrust rocket engine initially intended for the Upper Stage (US) and Earth Departure Stage (EDS) of the Constellation Program Ares-I Crew Launch Vehicle (CLV). A key element of the design approach was to base the new J-2X engine on the heritage J-2S engine with the intent of uprating the engine and incorporating SSME and RS-68 lessons learned. The J-2S engine was a design upgrade of the flight proven J-2 configuration used to put American astronauts on the moon. The J-2S Fuel Turbopump (FTP) was the first Rocketdyne-designed liquid hydrogen centrifugal pump and provided many of the early lessons learned for the Space Shuttle Main Engine High Pressure Fuel Turbopumps. This paper will discuss the design trades and analyses performed for the current J-2X FTP to increase turbine life; increase structural margins, facilitate component fabrication; expedite turbopump assembly; and increase rotordynamic stability margins. Risk mitigation tests including inducer water tests, whirligig turbine blade tests, turbine air rig tests, and workhorse gas generator tests characterized operating environments, drove design modifications, or identified performance impact. Engineering design, fabrication, analysis, and assembly activities support FTP readiness for the first J-2X engine test scheduled for July 2011

A new method to quantify and compare the multiple components of fitness-A study case with kelp niche partition by divergent microstage adaptations to Temperature

Point 1 Management of crops, commercialized or protected species, plagues or life-cycle evolution are subjects requiring comparisons among different demographic strategies. The simpler methods fail in relating changes in vital rates with changes in population viability whereas more complex methods lack accuracy by neglecting interactions among vital rates. Point 2 The difference between the fitness (evaluated by the population growth rate.) of two alternative demographies is decomposed into the contributions of the differences between the pair-wised vital rates and their interactions. This is achieved through a full Taylor expansion (i.e. remainder = 0) of the demographic model. The significance of each term is determined by permutation tests under the null hypothesis that all demographies come from the same pool. Point 3 An example is given with periodic demographic matrices of the microscopic haploid phase of two kelp cryptic species observed to partition their niche occupation along the Chilean coast. The method provided clear and synthetic results showing conditional differentiation of reproduction is an important driver for their differences in fitness along the latitudinal temperature gradient. But it also demonstrated that interactions among vital rates cannot be neglected as they compose a significant part of the differences between demographies. Point 4 This method allows researchers to access the effects of multiple effective changes in a life-cycle from only two experiments. Evolutionists can determine with confidence the effective causes for changes in fitness whereas population managers can determine best strategies from simpler experimental designs.CONICYT-FRENCH EMBASSADY Ph.D. gran

A new scab-like disease on apple caused by the formerly saprotrophic fungus Venturia asperata

Atypical scab-like symptoms were reported for the first time in 2007 in the south of France on fruits of apple cultivars carrying the Rvi6 (=Vf) major resistance gene to Venturia inaequalis. With microscopic observations, nucleotide sequence data and pathological tests, it was shown that the causal agent was Venturia asperata. Scanning electron microscopy was used to compare its infection process and conidiogenesis to those of Venturia inaequalis on apple and Venturia pirina on pear. Venturia asperata produced fewer hyphae and fewer spores than the two other Venturia species, and resulted in weaker symptoms. This fungal species was previously described as a saprotroph on apple leaf litter. This is the first report of damage on apple fruits caused by V. asperata. Changes in host and cultural practices may have created a new context favourable for the emergence of this pathogen. It was also detected on symptomless leaves and on overwintered leaves on the ground. Pseudothecia developed on overwintered leaves and released ascospores over a 2-month period from the end of March until the end of May, suggesting that the fungus is able to survive from season to season. However, it is not yet known if this new disease will establish over coming years and become an emergent disease

Forging strategic partnerships with industry: The Industrial Fellows Program

Science, technology, and industrial policy are at an important nexus due to long developing trends in the national and international economy and recent events in national security affairs. The research and development assets built by the American taxpayer in response to the Cold War face a quest for relevance in the new era. National competitiveness in international markets has emerged as an important new priority. To better understand the perspective of US industry the management of the Los Alamos National Laboratory has initiated an Industrial Fellows Program which has placed six individuals at US corporations. Their goal is to create strategic partnerships through increased understanding of technical needs of industry and the technical capabilities of the Laboratory

Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis

Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator

A functional triazine framework based on N-heterocyclic building blocks

Covalent organic frameworks constitute a subclass of polymeric materials offering enhanced porosity, functionality and stability. In this work a covalent triazine framework based on bipyridine building blocks is presented, along with a comprehensive elucidation of its local structure, porosity, and capacity for metal uptake. A typical synthesis was carried out under ionothermal conditions at 400-700 degrees C using ZnCl2 as a Lewis acidic trimerization catalyst. A high degree of local order and the presence of triazine and bipyridine moieties are ascertained at a synthesis temperature of 400 degrees C, along with micropores and specific surface areas of up to 1100 m(2) g(-1). Mesopores are increasingly formed at synthesis temperatures above 450 degrees C, yielding highly porous frameworks with hierarchical porosity and exceptionally large surface areas in excess of 3200 m(2) g(-1) at 700 degrees C. We demonstrate the capability of the bipyridine unit to provide specific and strong binding sites for a large variety of transition metal ions, including Co, Ni, Pt and Pd. The degree of metal loading (up to 38 wt%) can be tuned by the metal concentration in solution and is dependent on both the type of metal as well as the temperature at which the CTF was synthesized. Evidence for site-specific metal coordination bodes well for the use of metal-loaded CTFs as heterogeneous catalysts carrying homogeneous-type active sites

CHARGE syndrome

CHARGE syndrome was initially defined as a non-random association of anomalies (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness). In 1998, an expert group defined the major (the classical 4C's: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) and minor criteria of CHARGE syndrome. Individuals with all four major characteristics or three major and three minor characteristics are highly likely to have CHARGE syndrome. However, there have been individuals genetically identified with CHARGE syndrome without the classical choanal atresia and coloboma. The reported incidence of CHARGE syndrome ranges from 0.1–1.2/10,000 and depends on professional recognition. Coloboma mainly affects the retina. Major and minor congenital heart defects (the commonest cyanotic heart defect is tetralogy of Fallot) occur in 75–80% of patients. Choanal atresia may be membranous or bony; bilateral or unilateral. Mental retardation is variable with intelligence quotients (IQ) ranging from normal to profound retardation. Under-development of the external genitalia is a common finding in males but it is less apparent in females. Ear abnormalities include a classical finding of unusually shaped ears and hearing loss (conductive and/or nerve deafness that ranges from mild to severe deafness). Multiple cranial nerve dysfunctions are common. A behavioral phenotype for CHARGE syndrome is emerging. Mutations in the CHD7 gene (member of the chromodomain helicase DNA protein family) are detected in over 75% of patients with CHARGE syndrome. Children with CHARGE syndrome require intensive medical management as well as numerous surgical interventions. They also need multidisciplinary follow up. Some of the hidden issues of CHARGE syndrome are often forgotten, one being the feeding adaptation of these children, which needs an early aggressive approach from a feeding team. As the child develops, challenging behaviors become more common and require adaptation of educational and therapeutic services, including behavioral and pharmacological interventions

Transmission of Aerosolized Seasonal H1N1 Influenza A to Ferrets

Influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. Recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. In order to measure the aerosol infectious dose for 50% (aID50) of seronegative ferrets, seasonal influenza virus was nebulized into an exposure chamber with controlled airflow limiting inhalation to airborne particles less than 5 µm diameter. Airborne virus was collected by liquid impinger and Teflon filters during nebulization of varying doses of aerosolized virus. Since culturable virus was accurately captured on filters only up to 20 minutes, airborne viral RNA collected during 1-hour exposures was quantified by two assays, a high-throughput RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000™ Biosensor system) and a standard real time RT-qPCR assay. Using the more sensitive T5000 assay, the aID50 for A/New Caledonia/20/99 (H1N1) was approximately 4 infectious virus particles under the exposure conditions used. Although seroconversion and sustained levels of viral RNA in upper airway secretions suggested established mucosal infection, viral cultures were almost always negative. Thus after inhalation, this seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure