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AbstractBackground: A previously developed monoclonal/polyclonal ELISA (Mono/Poly) to detect plasma concentrations of osteopontin (OPN) was shown to provide prognostic information in breast, prostate, and other cancers. Here we describe the clinical validation of a new dual monoclonal (Dual Mono) assay. We compared both assays with 4 assays that recognize defined regions of OPN protein (dual polyclonal systems 5-1, 4-1, 4-3 and polyclonal-monoclonal system 1-3).Methods: OPN sequences recognized by the monoclonal antibodies that make up the Dual Mono ELISA were identified by Pepscan CLIPS™ analysis. Using the 6 ELISAs, we measured OPN in plasma from 66 patients with castration-resistant prostate cancer, and we assessed the ability of each assay to predict patient survival.Results: The assays varied in measured plasma OPN concentrations, with median values ranging from 112 to 1740 μg/L, and ability to predict patient survival. By Cox univariable regression of survival by tertiles of OPN, the Mono/Poly and Dual Mono ELISAs had the highest log-rank χ2 values. After adjustment for risk factors independently associated with survival in our samples, OPN remained associated with survival only for the Mono/Poly and Dual Mono systems.Conclusions: OPN plasma values varied significantly depending on the assay used. Only the Mono/Poly and Dual Mono systems were independently associated with survival in a population of men with castration-resistant prostate cancer. The availability of a clinically validated, dual monoclonal–based ELISA will provide consistent reagents for studies of OPN plasma concentrations in cancer and other pathologies.

We thank Barra and Agarwal for their interest in our examination of implantable cardioverter-defibrillator (ICD) outcomes and therapies in different age groups, focusing on the elderly.1 We agree that rates of device therapies with conventional programming may overestimate the potential benefit of ICD implantation. Barra and Agarwal suggest that device programming approaches that were used in the Primary Prevention Parameters Evaluation (PREPARE),2 Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy (MADIT-RIT),3 and Avoid Delivering Therapies for Non-sustained Arrhythmias in ICD Patients III (ADVANCE III)4 trials would lead to rates of appropriate shock and therapy that better reflect the occurrence of ventricular tachyarrhythmia episodes that would more likely have been associated with an arrhythmic death. Early after the initiation of the Ontario ICD Database, the PREPARE study was published, the potential benefits of delaying ICD-delivered therapies were recognized, and participating sites adapted …

What would be a genuinely caring approach to the provision of procedures of so-called artificial reproduction such as in vitro fertilization (IVF)? What are appropriate and justified social policies with respect to attempting to enable infertile persons to have offspring? These urgent questions have provoked significant disagreements among theologians, sociologists, healthcare providers, philosophers and even — or especially — among feminists. In the existing literature and in developing social policy, three different kinds of answers can be discerned. (1) Some have suggested that access to IVF should be provided as a matter of right. (2) Some existing social policies and practices imply that access to IVF is a privilege. (3) Some theorists have argued that, because of its alleged violation of family values and marital security, or because of its risks, costs, and low success rate, IVF should not be available at all. After evaluating each of these views, I shall offer a feminist alternative, describing what I think would constitute the caring provision of in vitro fertilization.

Ligation of the B cell Ag receptor (BCR) activates a protein-tyrosine kinase (PTK) and CD45 protein-tyrosine phosphatase (PTPase)-dependent signaling cascade that results in the activation of Ras. This pathway of Ras activation can operate independently of protein kinase C (PKC) activity. Activation of Ras may lead to two distinct Ras-dependent pathways involving either a Raf1/MEK/MAPK module or a MEKK/SEK/SAPK module; however, it is unclear as to how Ras controls the independent activation of either of these pathways. We have used genistein and phenylarsine oxide (PAO) as inhibitors of PTK and PTPase, respectively, to investigate whether they regulate the BCR- and Ca2+/PKC-dependent activation of the Ras/Raf1/MEK/MAPK module. Assays of phosphotransferase activities conducted with Ag (TNP6-OVA)-specific 7.9 murine B lymphoma cells demonstrated that BCR-mediated stimulation of the Raf1/MEK/MAPK module is controlled by PTK and PTPase activities. An elevation in [Ca2+]i was required to optimally activate Raf1 and MEK through the BCR. However, when signaling through the BCR was bypassed by direct stimulation of the Raf1/MEK/MAPK module via a rise in [Ca2+]i and phorbol ester-induced PKC activation, the phosphotransferase activities of Raf1, MEK and MAPK were still regulated in a PTK-dependent manner that was also partially sensitive to the PTPase inhibitor PAO. Thus, at least two alternate routes, i.e. a BCR/PTK/Ras-dependent route and another PKC/Ca(2+)-dependent route, may converge at the level of Raf1 for activation of the Raf1/MEK/MAPK module in B cells.

SH2 domains are phosphotyrosine specific interaction modules with largely overlapping sequence specificities. A recent structure by Bae et al. revealed that SH2 domain specificity can be mediated by secondary binding sites located outside the phosphotyrosine binding pocket.

ABSTRACTTraining protocols designed to improve dual-task performance of an obstacle crossing and auditory Stroop task (OBS+Stroop) were tested. In Experiment 1, following baseline collection of OBS+Stroop trials, proximally related walking training was performed, and participants were then retested on the OBS+Stroop test. After training, participants adopted a more cautious obstacle crossing strategy, indicating a potentially safer navigation strategy. Transfer effects from distally related training were then examined (Experiment 2); a computer game training paradigm was examined using the same testing protocol as Experiment 1. Computer training demonstrated improved dual-task performance on some measures, but did not induce a more cautious stepping strategy. Results indicate that dual-task training needs to be similar to targeted tasks to yield reliable, positive training outcomes.

The present investigation deals with the facile synthesis and characterization of chitosan (CTS)-based zinc oxide (ZnO) nanoparticles (NPs) and their antimicrobial activities against pathogenic microorganisms. ZnO–CTS NPs were synthesized through two different methods: nano spray drying and precipitation, using various organic compounds (citric acid, glycerol, starch and whey powder) as stabilizers. Both the synthesis methods were simple and were devoid of any chemical usage. The detailed characterization of the NPs was carried out using UV–Vis spectroscopy, dynamic light scattering particle size analysis, zeta potential measurements and scanning electron microscopy, which confirmed the fabrication of NPs with different shapes and sizes. Antimicrobial assay of synthesized ZnO–CTS NPs was carried out against different pathogenic microbial strains (Candida albicans, Micrococcus luteus and Staphylococcus aureus). The significant (p < 0.05) inhibition of growth was observed for both M. luteus and S. aureus with ZnO–CTS NPs (with a concentration ranging from 0.625 to 0.156 mg/ml) as compared to control treatment. ZnO–CTS NPs also showed significant biofilm inhibition activity (p < 0.05) against M. luteus and S. aureus. The study demonstrated the potential of ZnO–CTS NPs as antimicrobial and antibiofilm agents.

To compare the cost-effectiveness of different imaging strategies in the diagnosis of pediatric appendicitis by using a decision analytic model.Approval for this retrospective study based on literature review was not required by the institutional Research Ethics Board. A Markov decision model was constructed by using costs, utilities, and probabilities from the literature. The risk of radiation-induced cancer was modeled by using the Biological Effects of Ionizing Radiation VII report, which is based primarily on data from atomic bomb survivors. The three imaging strategies were ultrasonography (US), computed tomography (CT), and US followed by CT if the initial US study was negative. The model simulated the short-term and long-term outcomes of the patients, calculating the average quality-adjusted life span and health care costs.For a single abdominal CT study in a 5-year-old child, the lifetime risk of radiation-induced cancer would be 26.1 per 100,000 in female and 20.4 per 100,000 in male patients. In the base-case analysis, US followed by CT was the most costly and most effective strategy, CT was the second-most costly and second-most effective strategy, and US was the least costly and least effective strategy. The incremental cost-effectiveness ratios (ICERs) of CT to US and of US followed by CT to US were both well below the societal willingness-to-pay threshold of $50,000 (in U.S. dollars). The ICER of US followed by CT to CT was less than $10,000 in both male and female patients.In a Markov-based decision model of pediatric appendicitis, the most cost-effective method of imaging pediatric appendicitis was to start with a US study and follow each negative US study with a CT examination.

AbstractObjectiveTo evaluate trends in organisms causing early-onset neonatal sepsis (EONS). Congruent with recent reports, we hypothesized there would be an increase in EONS caused by Escherichia coli.Study DesignNational data on infants admitted to neonatal intensive care units from 2009 to 2014 were compared to previously reported data from 2003 to 2008. We report 430 cases of EONS from 2009 to 2014. Bivariate analyses were used to analyze the distribution of causative organisms over time and differences by gestational age. Linear regression was used to estimate trends in causative organisms.ResultsSince 2003, there has been a trend of increasing numbers of cases caused by E coli (P&lt;0.01). The predominant organism was E coli in preterm infants and Group B Streptococcus in term infants.ConclusionsWith the majority of EONS cases now caused by E coli, our findings emphasize the importance of continued surveillance of causative organism patterns and developing approaches to reduce cases caused by E coli.

Objective: Research has highlighted several negative consequences for individuals born in the later part of the academic year, including increased likelihood of being diagnosed with learning disabilities. In this study, we considered whether birthdate predicted ADHD symptomatology using two well known mechanisms, the relative age effect (RAE) and the season of birth effect (SOBE). Methods: Study participants completed two ADHD measures: Conners Adult ADHD Rating Scales (CAARS) and the Wender Utah Rating Scale (WURS). Results: There were gender effects in the WURS data indicating that males scored higher than females on ADHD symptoms as well as a significant interaction in the CAARS data to support differential patterns among males and females. Conclusion: Overall, results did not support a RAE or SOBE among males or females. Possible reasons for these findings and their implications are discussed.