Efficacy and safety of ceftobiprole in patients aged 65 years or older:a post hoc analysis of three Phase III studies

Lay abstract Infections are a common cause of severe disease and death in older patients. Antibiotic treatment may also be complicated by age-related changes within the body. The present study analyzed results from three large clinical trials that assessed the benefits of the novel antibiotic ceftobiprole in the older population. In patients aged over 65 years with skin infections or with pneumonia acquired either in the community or in a hospital setting, ceftobiprole offered similar benefits to established antibiotics. There was also some preliminary evidence that older patients may respond more quickly to ceftobiprole compared with the other antibiotics used in these studies. Overall, ceftobiprole was well tolerated and will be a useful treatment option for infections in older patients. Aim: To evaluate the efficacy and safety of ceftobiprole in patients aged >= 65 years. Materials & methods: We conducted a post hoc analysis of three randomized, double-blind, Phase III studies in patients with acute bacterial skin and skin structure infections, community-acquired pneumonia and hospital-acquired pneumonia. Results: Findings for patients aged >= 65 years (n = 633) were consistent with those for the overall study populations, although a trend toward improved outcomes was reported in some subgroups, for example, patients aged >= 75 years with community-acquired pneumonia were more likely to achieve an early clinical response with ceftobiprole than comparator (treatment difference 16.3% [95% CI:1.8-30.8]). The safety profile was similar between treatment groups in all studies. Conclusion: This analysis further supports the efficacy and safety of ceftobiprole in older patients with acute bacterial skin and skin structure infections or pneumonia. Clinicaltrials.gov trial identifiers: , ,

Leveraging eco-evolutionary models for gene drive risk assessment

Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic processbased models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of biological complexity and uncertainty, and provide insights to promote responsible development and model-assisted risk assessment of gene drives. Supplemental files attached belo

NbSe3: Effect of Uniaxial Stress on the Threshold Field and Fermiology

We have measured the effect of uniaxial stress on the threshold field ET for the motion of the upper CDW in NbSe3. ET exhibits a critical behavior, ET ~ (1 - e/ec)^g, wher e is the strain, and ec is about 2.6% and g ~ 1.2. This ecpression remains valid over more than two decades of ET, up to the highest fields of about 1.5keV/m. Neither g nor ec is very sensitive to the impurity concentraction. The CDW transition temperature Tp decreases linearly with e at a rate dTp/de = -10K/%, and it does not show any anomaly near ec. Shubnikov de-Haas measurements show that the extremal area of the Fermi surface decreases with increasing strain. The results suggest that there is an intimate relationship between pinning of the upper CDW and the Fermiology of NbSe3.Comment: 4 pages, 5 figure

Beneficial Reuse and Sustainability: The Fate of Organic Compounds in the Land-Applied Waste

Land application systems, also referred to as beneficial reuse systems, are engineered systems that have defined and permitted application areas based on site and waste characteristics to determine the land area size requirement. These terrestrial systems have orders of magnitude greater microbial capability and residence time to achieve decomposition and assimilation compared with aquatic systems. In this paper we focus on current information and information needs related to terrestrial fate pathways in land treatment systems. Attention is given to conventional organic chemicals as well as new estrogenic and pharmaceutical chemicals of commerce. Specific terrestrial fate pathways addressed include: decomposition, bound residue formation, leaching, runoff, and crop uptake. Molecular decomposition and formation of bound residues provide the basis for the design and regulation of land treatment systems. These mechanisms allow for assimilation of wastes and nondegradation of the environment and accomplish the goal of sustainable land use. Bound residues that are biologically produced are relatively immobile, degrade at rates similar to natural soil materials, and should present a significantly reduced risk to the environment as opposed to parent contaminants. With regard to leaching and runoff pathways, no comprehensive summary or mathematical model of organic chemical migration from land treatment systems has been developed. For the crop uptake pathway, a critical need exists to develop information for nonagricultural chemicals and to address full-scale performance and monitoring at more land application sites. The limited technology choices for treatment of biosolids, liquids, and other wastes implies that acceptance of some risks and occurrence of some benefits will continue to characterize land application practices that contribute directly to the goal of beneficial reuse and sustainability

Associations Between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress