Efficacy of doripenem against Escherichia coli and Klebsiella pneumoniae in experimental meningitis

Objectives In this study the efficacy of doripenem, a new broad-spectrum carbapenem, was tested against an Escherichia coli strain and a Klebsiella pneumoniae strain in an experimental animal model. The comparator was cefepime monotherapy. Methods The rabbit meningitis model was used in this study and the penetration of doripenem through uninflamed and inflamed meninges was determined. Results Doripenem, injected three times (75 mg/kg), led to serum peak levels around 100 mg/L and trough levels around 5 mg/L, resulting in a penetration rate of 14% through inflamed meninges and 7% through uninflamed meninges. Against K. pneumoniae, doripenem was slightly but not significantly more efficacious than cefepime over 8 h (5.40 ± 1.37 log10 cfu/mL versus 3.59 ± 0.89 log10 cfu/mL for cefepime). Also against the E. coli strain doripenem was slightly superior to the comparator (5.55 ± 0.87 log10 cfu/mL versus 3.80 ± 1.10 log10 cfu/mL for cefepime), although the difference was not significant. Conclusions Doripenem is a potential monotherapy for the treatment of meningitis due to Gram-negative microorganism

The Development of Stacked Core for the Fabrication of Deep Lightweight UV-Quality Space Mirrors

The 2010 Decadal Survey stated that an advanced large-aperture ultraviolet, optical, near-infrared (UVOIR) telescope is required to enable the next generation of compelling astrophysics and exoplanet science; and, that present technology is not mature enough to affordably build and launch any potential UVOIR mission concept. Under Science and Technology funding, NASA's Marshall Space Flight Center (MSFC) and Exelis have developed a more cost effective process to make 4m class or larger monolithic spaceflight UV quality, low areal density, thermally and dynamically stable primary mirrors. A proof of concept 0.43m mirror was completed at Exelis optically tested at 250K at MSFC which demonstrated the ability for imaging out to 2.5 microns. The parameters and test results of this concept mirror are shown. The next phase of the program includes a 1.5m subscale mirror that will be optically and dynamically tested. The scale-up process will be discussed and the technology development path to a 4m mirror system by 2018 will be outlined

Status of the Advanced Mirror Technology Development (AMTD) Phase 2, 1.5m ULE(Registered Trademark) Mirror

The Decadal Survey stated that an advanced large-aperture ultraviolet, optical, near-infrared (UVOIR) telescope is required to enable the next generation of compelling astrophysics and exoplanet science; and, that present technology is not mature enough to affordably build and launch any potential UVOIR mission concept. Under Science and Technology funding, NASA's Marshall Space Flight Center (MSFC) and Exelis have developed a more cost effective process to make up to 4m monolithic spaceflight UV quality, low areal density, thermally and dynamically stable primary mirrors. Under a Phase I program, a proof of concept mirror was completed at Exelis and tested down to 250K at MSFC which would allow imaging out to 2.5 microns. In 2014, Exelis and NASA started a Phase II program to design and build a 1.5m mirror to demonstrate lateral scalability to a 4m monolithic primary mirror. The current status of the Phase II development program will be provided along with a Phase II program summary

Combining Adverse Pregnancy and Perinatal Outcomes for Women Exposed to Antiepileptic Drugs During Pregnancy, Using a Latent Trait Model

Background Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity. Methods This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome. Results The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P \u3c .0001), and the valproate only subgroup (19.6% vs. 10.5%, P  \u3c .0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho = 0.24, P \u3c .0001) and the valproate only subgroup (Rho = 0.16, P = .01). The mean score for the combined outcome in the total AED group was significantly higher (2.04 ± 0.02 vs. 1.88 ± 0.01, P \u3c .0001) than AED unexposed group, whereas the valproate only subgroup was not. Conclusions Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome

Removing Orbital Debris with Lasers

Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.Comment: 37 pages, 15 figures, in preparation for submission to Advances in Space Researc

Wide-field Infrared Survey Telescope (WFIRST): Composite Structure Verification for Operational Temperatures

The Wide-Field Infrared Survey Telescope (WFIRST) mission is the next large astrophysics observatory for NASA after the James Webb Space Telescope and is the top priority mission from the 2010 National Academy of Sciences' decadal survey. The WFIRST Optical Telescope Assembly (OTA) includes inherited composite support structures that were originally designed and tested for room temperature operation; however, the WFIRST mission will require operation at colder temperatures to achieve sufficient sensitivity for the infrared wavelengths. We will present the results and conclusions of testing completed at the coupon and engineering model level to verify that the inherited composite structures will maintain mechanical integrity and performance over the required temperature range. The testing included: (1) characterization testing of constituent material coupons, (2) thermal cycling and static load testing of a representative aft metering structure (AMS) and forward metering structure (FMS), and (3) thermal cycling and dynamic testing of a representative secondary mirror assembly (SMA)

Activin subfamily peptides predict chronological age in humans

Loss of muscle mass and function are a well‐defined aspect of human aging from the 3rd decade of life, which result in reduced independence and increased mortality. The activin family of peptides contains several endocrine factors (activin A, myostatin, growth and differentiation factor 11 [GDF11]) that may play roles in changes in muscle mass and the aging process, however, it may be simplistic to consider aging as a result of a single peptides changes. Thus, we aimed to examine changes in activin family members across a cohort of healthy individuals of various ages, hypothesizing that these would aid predictive models of age and functional measures of age. Healthy participants (n = 88) were recruited and resting metabolic rate, body composition, grip strength, walking speed, and circulating plasma concentrations of myostatin (total and free), activin A, follistatin‐like binding protein (FLRG), and GDF11 quantified. Simple regressions between circulating factors and chronological age, grip strength, and walking speed were examined. Multiple stepwise regressions for age, grip strength, and walking speed are also reported. Age negatively correlated with total myostatin (P = 0.032, r2 = 0.053), grip strength positively with activin A (P = 0.046, r2 = 0.048), whereas walking speed showed no simple regression relationships. Stepwise regressions suggested a role of total myostatin and activin A in models of age, whereas GDF11 contributed to the model of grip strength. Here we suggest a role for myostatin, activin A, and GDF11 in normal human aging that mirrors animal studies to date. Further interventional studies are required to elicitate the physiological role of these changes in the normal human aging process, and indeed if offsetting these changes can promote successful aging

New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss

BACKGROUND: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/− computerized tomography‐defined LSMI. We also explored whether the transcription in muscle of identified genes was altered according to such cachexia phenotype METHODS: A retrospective cohort study design was used. Analysis explored associations of candidate SNPs with WL (n = 1276) and WL + LSMI (n = 943). Human muscle transcriptome (n = 134) was analysed using an Agilent platform. RESULTS: Single nucleotide polymorphisms in the following genes showed association with WL alone: GCKR, LEPR, SELP, ACVR2B, TLR4, FOXO3, IGF1, CPN1, APOE, FOXO1, and GHRL. SNPs in LEPR, ACVR2B, TNF, and ACE were associated with concurrent WL + LSMI. There was concordance between muscle‐specific expression for ACVR2B, FOXO1 and 3, LEPR, GCKR, and TLR4 genes and LSMI and/or WL (P < 0.05). CONCLUSIONS: The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI. These findings focus attention on pro‐inflammatory cytokines and the renin–angiotensin system as biomarkers/mediators of muscle wasting in cachexia