Intrapartum Antibiotic Prophylaxis and Early-Onset Neonatal Sepsis Patterns

Objective: To compare the relative effects of intrapartum antibiotic prophylaxis regimens on patterns of early-onset neonatal sepsis. Methods: We performed an historical cohort study of 17 187 infants born at our center from September 1993 to February 2000. A risk-based strategy was employed prior to July 1996 and a screening-based strategy was utilized thereafter. Ampicillin was utilized prior to March 1995 and penicillin was used thereafter. Results: There were 75 cases of neonatal sepsis, 34 (4.10/1000) in the risk-based era and 41 (4.63/1000) in the screening-based era (p = 0.62). There were fewer ampicillin-resistant isolates during the risk-based than the screening-based era (32 versus 61%; p = 0.014). The only significant change in organism-specific sepsis rates was an increase in the rate of infection caused by coagulase-negative staphylococci in the screening-based era (0.36 versus 1.46/1000; p = 0.018), but 75% of infants infected with these organisms were not exposed to ß-lactam antibiotics within 72 h prior to delivery. For the risk- and screening-based eras, respectively, the rates of Gram-negative sepsis (1.21 versus 1.46/1000; p = 0.65) and the proportions of Gram-negative pathogens that were ampicillin-resistant (70 versus 77%; p = 1.0) were similar. The drug employed for prophylaxis did not appear to affect the pattern of sepsis cases. Conclusion: In our patient population, coagulase-negative staphylococci have become the most common cause of early-onset neonatal sepsis. The cause of this shift in pathogen prevalence is uncertain and seemingly unrelated to intrapartum antibiotic exposure

Networks of High Mutual Information Define the Structural Proximity of Catalytic Sites: Implications for Catalytic Residue Identification

Identification of catalytic residues (CR) is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI), and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA) database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL) conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI) was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC) was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls), combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution

Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells

Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+) prostate cancer cells. ALDH+ subpopulations were detected and isolated from the human prostate cancer cell lines DU145 and long-term IL-6 stimulated LNCaP cells using ALDEFLUOR® assay and flow cytometry. In contrast to ALDH− cells, ALDH+ prostate cancer cells showed cancer stem cell-like characteristics such as increased self-renewing and colony forming capacity and tumorigenicity. In addition, ALDH+ cells showed an increased expression of putative prostate cancer stem cell markers (CD44 and integrin α2β1). Furthermore, ALDH+ cells expressed phosphorylated STAT3. Galiellalactone treatment decreased the proportion of ALDH+ prostate cancer cells and induced apoptosis of ALDH+ cells. The gene expression of ALDH1A1 was downregulated in vivo in galiellalactone treated DU145 xenografts. These findings emphasize that targeting the STAT3 pathway in prostate cancer cells, including prostate cancer stem cell-like cells, is a promising therapeutic approach and that galiellalactone is an interesting compound for the development of future prostate cancer drugs

Wildlife collisions with aircraft: A missing component of land-use planning for airports

Projecting risks posed to aviation safety by wildlife populations is often overlooked in airport land-use planning. However, the growing dependency on civil aviation for global commerce can require increases in capacity at airports which affect land use, wildlife populations, and perspectives on aviation safety. Our objectives were to (1) review legislation that affects airports and surrounding communities relative to managing and reducing wildlife hazards to aviation; (2) identify information gaps and future research needs relative to regulated land uses on and near airports, and the effects on wildlife populations; and (3) demonstrate how information regarding wildlife responses to land-use practices can be incorporated into wildlife-strike risk assessments.We show that guidelines for land-use practices on and near airports with regard to wildlife hazards to aviation can be vague, conflicting, and scientifically ill-supported. We discuss research needs with regard to management of storm water runoff; wildlife use of agricultural crops and tillage regimens relative to revenue and safety; the role of an airport in the landscape matrix with regard to its effects on wildlife species richness and abundance; and spatial and temporal requirements of wildlife species that use airports, relative to implementing current and novel management techniques. We also encourage the development and maintenance of data sets that will allow realistic assessment of wildlife-strike risk relative to current airport conditions and anticipated changes to capacity. Land uses at airports influence wildlife populations, and understanding and incorporating these effects into planning will reduce risks posed to both aviation safety and wildlife species

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

THE PESTICIDE REREGISTRATION PROCESS: COLLECTIONS OF HUMAN HEALTH HAZARDS DATA FOR 3-CHLORO-P-TOLUIDINE HYDROCHLORIDE (DRC-1339)

The 1988 Amendments to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) accelerated the reregistration schedule for pesticide products registered with the Environmental Protection Agency (EPA) prior to 1984. The compound 3-chloro-p-toluidine hydrochloride (DRC-1339), an avicide registered to control 14 pest bird species, was included on Pesticide List B published by EPA. For the reregistration of DRC-1339,44 studies were required — 22 product chemistry, 7 wildlife/aquatic hazards, 8 human/domestic animal hazards, 5 environmental fate, and 2 residue chemistry studies. In 5 acute human-health-hazards studies, DRC-1339 was found to: (1) have an oral LD50 of 330 (272-401) mg/kg in rats, (2) have a dermal LD50 of \u3e2.0 g/kg in rabbits, (3) cause corrosive effects to the eyes of rabbits, (4) cause corrosive effects to the skin of rabbits, and (5) induce dermal sensitization in guinea pigs. Results support the current precautionary statements on the “use labels” warning of harmful ingestion, inhalation, dermal absorption and eye irritation effects to users of the active ingredient

CONTRACTS AND REGISTRATION STUDIES

Public and governmental concerns about the health, safety, and environmental impacts of pesticides have led to increased regulatory requirements to determine the hazards and risks associated with their manufacture, distribution, and use. Vertebrate pesticides are regulated by the U.S. Environmental Protection Agency (EPA) under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended. Much of the data required for registration of these pesticides will be generated by commercial testing laboratories under contract to the product registrants or sponsors. In this paper, we address aspects of the contract research process including: 1) an overview of FIFRA requirements, 2) the nature of the contract research process, 3) guidelines for setting up and administering a contract for this type of work, and 4) several case studies to illustrate some of the pitfalls that may be encountered. The information presented is based on the collective experience of the authors\u27 involvement with 49 contracted studies over a three-year period

Good Moments in Gestalt Therapy: A Descriptive Analysis of two Perls Sessions

Two Gestalt therapy sessions conducted by Fritz Perls were analyzed using a category system that was recently developed for identifying in-session client behaviours that are valued by Gestalt therapists. Two hundred and ten client statements were independently rated by four judges. Descriptive analysis of the combined data revealed a common pattern of therapeutic movement. In both sessions, an initial phase dominated by building block good moments (focusing on client awareness, and expressing feeling directly to other) was followed by a phase characterized by combinations of good moments. Sustained bursts of these complex good moments led to the presence of outcome good moments in therapy. Differences between the two sessions were explored with respect to client characteristics, therapeutic alliance, and therapist interventions. The form and content of therapeutic interventions leading to good moments were examined.L'analyse descriptive des données des deux entrevues a permis de constater la présence d'un processus thérapeutique similaire. Le début des deux sessions, soit la première phase, était composée principalement par différents "bons moments" isolés. Ceux-ci constituent la pierre angulaire de la thérapie gestalt (prise de conscience, expression directe des sentiments). Dans la deuxième phase, on retrouvait des "bons moments" en combinaison. La présence continue de cette combinaison de "bons moments" reflétant l'aboutissement d'un processus thérapeutique (outcome good moments). Une analyse des différences entre les deux sessions fut effectuée en tenant compte des facteurs suivants: caractéristiques des clients, l'alliance thérapeutique et l'intervention particulière du thérapeute. La nature et la forme des interventions thérapeutiques donnant lieu à des "bons moments" furent également examinées