An Exploratory Study of Suboxone (Buprenorphine/ Naloxone) Film Splitting: Cutting Methods, Content Uniformity, and Stability

Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter \u3c905\u3e was used to evaluate the weight variation and content uniformity of split films. The stability of split films stored in polybags was evaluated over 7 days. A stability-indicating high-performance liquid chromatography method was used for content uniformity and stability evaluation. The weight variation results were acceptable for the half films from all four cutting methods, but this was not true for the quarter films. The method of ruler/razor cut was determined most favorable and used for the content uniformity test. Based on the high-performance liquid chromatography results, the half films from the ruler/razor cut method met the passing criteria of United States Pharmacopeia Chapter \u3c905\u3e with acceptance values of 9.8 to 10.4 for buprenorphine and 8.4 to 11.5 for naloxone (≤15 is considered passing). The stability results indicated that both actives retained \u3e97.7% of initial strength. Four cutting methods were found to be acceptable for splitting Suboxone films into half but not quarter fractions. The half films from the ruler/razor cut method also passed United States Pharmacopeia Chapter \u3c905\u3e content uniformity test. Both actives remained stable for 7 days when the half films were stored in polybags at room temperature

Semantic web data warehousing for caGrid

The National Cancer Institute (NCI) is developing caGrid as a means for sharing cancer-related data and services. As more data sets become available on caGrid, we need effective ways of accessing and integrating this information. Although the data models exposed on caGrid are semantically well annotated, it is currently up to the caGrid client to infer relationships between the different models and their classes. In this paper, we present a Semantic Web-based data warehouse (Corvus) for creating relationships among caGrid models. This is accomplished through the transformation of semantically-annotated caBIG® Unified Modeling Language (UML) information models into Web Ontology Language (OWL) ontologies that preserve those semantics. We demonstrate the validity of the approach by Semantic Extraction, Transformation and Loading (SETL) of data from two caGrid data sources, caTissue and caArray, as well as alignment and query of those sources in Corvus. We argue that semantic integration is necessary for integration of data from distributed web services and that Corvus is a useful way of accomplishing this. Our approach is generalizable and of broad utility to researchers facing similar integration challenges

The Influence of Physical Activity on Monocyte Phenotype on Circulating Platelet-Monocyte Complexes in Overweight/Obese Persons

Elevated platelet-monocyte complexes (PMC) promote atherosclerosis and are associated with cardiovascular disease. It is unknown whether consistent physical activity (PA) decreases circulating PMCs. Additionally, no one has determined the monocyte phenotype most associated with PMCs. Purposes: 1) to examine the influence of PA on PMCs and their association with inflammatory /prothrombotic markers such as C-reactive protein (CRP), L-selectin (LS), platelet factor 4 (PF4), von Willebrand Factor (vWF), and hemoglobin A1C (HbA1c) and 2) to determine the monocyte phenotype most likely to form PMCs. Methods: Thirty-one overweight/obese subjects (44±5yr, BMI 34.2±5 kg×m2) were divided into two groups: sedentary (SED, n=17) and physically active (PA, n=14) based on physical activity logs. SED participated in \u3c 1 h of formal exercise while PA participated in moderate-high intensity exercise at least 3 h per week. Flow cytometry was used to identify PMCs on the monocyte phenotypes: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14+CD16++). Platelets were identified using the marker CD42a. Results: Percentage of circulating PMCs and median fluorescence intensity of CD42a (MedFI; marker of platelet density per monocyte) were not different between groups; however, monocyte phenotype significantly impacted PMC percentage and MedFI where the lower the CD16 expression, the greater the adhesion of platelets. Classical monocytes (CD16-) had the highest % of PMC, etc. (Fig 1). HbA1c was greater (p=0.031) and LS (p=0.019) was lower in SED compared to PA (Fig. 2). There were no significant associations between any blood marker and PMC percentage, but PF4 was correlated with percent of CD16 -(r= -0.482, p=0.031) and CD16+(r= 0.473, p=0.035) monocytes. Conclusions: The absence of a separation between groups in VO2max may partially explain the lack of a difference in PMCs between groups. Regarding our second aim, classical monocytes appear to be more involved in PMC formation than do CD16+ monocytes with CD16++ having the lowest percentage of cells with platelets adhered (PMC). This observation may be due to the shedding of adhesion molecules from platelets and monocytes during activation from classical (CD16-) to a more inflammatory state (ie. CD16+)

Hypothesis: The electrochemical regulation of metabolism

Abstract -An Electrochemical model of metabolism is described that takes account of a variety of metabolic phenomena observed in our laboratory. These include a utilisation by hepatocytes of oxygen, substantially in excess of ATP requirements; energydependence of the [lactate~[pyruvate] ratio; non-equilibrium behaviour of the components of the lactate dehydrogenase reaction during ethanol oxidation, and linear relationships between cellular potentials and metabolic fluxes. In the light of these findings, we propose as an extension of the Mitchell chemiosmotic hypothesis, that metabolic pathways are under the control of opposing far-from-equilibrium chemical and electrical forces that poise the pathways in a balanced state of apparent equilibrium, allowing flux to be regulated by changes in the magnitude of cellular potentials

Content Description of Very-long-duration Recordings of the Environment

Long-duration sound recordings are an established technique to monitor terrestrial ecosystems. Acoustic sensing has several advantages over personal field-surveys, but a disadvantage is that technological advances enable collection of much more audio than can be listened to. Machine learning methods can identify individual species, but these are time-consuming to build and if the species of interest is absent, nothing is revealed about recording content. Visual methods have also been developed to interrogate long-duration recordings but ultimately, interpretation of acoustic recordings must be ground-truthed by listening to the actual sound. However, the ear is constrained to listen in real-time. Even if one listens to 10 hours of one-minute segments, selected randomly from one year of recording, this represents only a 0.11% sample of the data. For this study, we recorded 13 months of continuous audio in natural Australian woodland. We divided the audio into one-minute segments, which yields a content description at one-minute resolution. The feature set representing each segment consists of summary and/or spectral acoustic indices. Our objective in this investigation is two-fold: (1) to maximise content description of a very-long-duration recording while keeping listening to manageable levels; and (2) to determine how content description is influenced by the choice of acoustic features and other variables. We begin by clustering the acoustic feature vectors using the k-means algorithm. Given sufficient clusters (k = 60), each cluster can be interpreted as a discrete acoustic state within the year-long soundscape. We describe four findings: 1. Listening to the medoid minute of each cluster (the minute whose feature vector is closest to the cluster centroid) yields a similar content description to that obtained by listening to a random sample of ten minutes from each cluster. This represents a ten-fold reduction in listening effort. 2. Although k-means is known to produce different clustering outcomes depending on cluster initialisation, we find that content description is little affected by different runs of k-means. 3. Different feature vectors yield a slightly different content description depending on which acoustic events have been ‘targeted’ by the selected features. 4. Training a Hidden Markov Model on the year-long cluster sequence helps to identify the underlying acoustic communities and can be used to obtain a more fine-grained labelling of sound-sources of interest

Difference in Postoperative Outcomes and Perioperative Resource Utilization Between General Surgeons and Pediatric Surgeons: A Systematic Review

Background: Both general surgeons (GS) and pediatric surgeons (PS) perform a high volume of appendectomies in pediatric patients, but there is a paucity of data on these outcomes based on surgeon training. We performed a systematic review and meta-analysis to compare postoperative outcomes and perioperative resource utilization for pediatric appendectomies.Methods: We searched PubMed to identify articles examining the association between surgeon specialization and outcomes for pediatric patients undergoing appendectomies. Study selection, data extraction, risk of bias assessment, and quality assessment were performed by one reviewer, with another reviewer to resolve discrepancies.Results: We identified 4799 articles, with 98.4% (4724/2799) concordance after initial review. Following resolution of discrepancies, 16 studies met inclusion criteria. Of the studies that reported each outcome, GS and PS demonstrated similar rates of readmission within 30 days (pooled RR 1.61 95% CI 0.66, 2.55) wound infections (pooled RR 1.07, 95% CI .55, 1.60), use of laparoscopic surgery (pooled RR 1.87, 95% CI .21, 3.53), postoperative complications (pooled RR 1.40, 95% CI .83, 1.97), use of preoperative imaging (pooled RR .98,95% CI .90, 1.05), and intra-abdominal abscesses (pooled RR .80, 95% CI .03, 1.58). Patients treated by GS did have a significantly higher risk of negative appendectomies (pooled RR 1.47, 95% CI 1.10, 1.84) when compared to PS.Discussion: This is the first meta-analysis to compare outcomes for pediatric appendectomies performed by GS compared to PS. Patient outcomes and resource utilization were similar among PS and GS, except for negative appendectomies were significantly more likely with GS