Dosing strategies for switching from oral risperidone to paliperidone palmitate: Effects on clinical outcomes.

IntroductionThere are currently no guidelines for switching patients from oral risperidone to paliperidone palmitate (Invega Sustenna®). Furthermore, the paliperidone long-acting injectable (LAI) package insert does not recommend bridging with oral antipsychotics, which may result in inadequate serum concentrations in patients on ≥4 mg/d risperidone.MethodsThis study evaluated the effects of suboptimal dosing and bridging in patients switched from oral risperidone to paliperidone LAI on hospitalization days, emergency department (ED)/mental health urgent care visits, and no-shows/cancellations to mental health appointments. Patients were categorized into optimal or suboptimal dosing based on their loading and maintenance paliperidone doses. Patients on risperidone ≥4 mg/d were categorized as bridged if they received risperidone for ≥7 days after the first paliperidone injection.ResultsThere were no significant differences in outcomes between optimally and suboptimally dosed patients. There were statistically significant reductions in hospitalization days in patients who were bridged compared with patients who were not bridged. There were statistically significant reductions in hospitalization days and ED/mental health urgent care visits after switching to paliperidone LAI.DiscussionThe results of this study indicate that bridging patients who are on ≥4 mg/d risperidone, when converting to paliperidone LAI, is associated with reductions in hospitalization days. However, more research is required to determine the optimal dose and duration of the bridge. The results also indicate that switching patients from oral risperidone to paliperidone LAI, even if the dose is suboptimal, is associated with reductions in hospitalization days and ED/mental health urgent care visits

Thermal Dissipation and Variability in Electrical Breakdown of Carbon Nanotube Devices

We study high-field electrical breakdown and heat dissipation from carbon nanotube (CNT) devices on SiO2 substrates. The thermal "footprint" of a CNT caused by van der Waals interactions with the substrate is revealed through molecular dynamics (MD) simulations. Experiments and modeling find the CNT-substrate thermal coupling scales proportionally to CNT diameter and inversely with SiO2 surface roughness (~d/{\Delta}). Comparison of diffuse mismatch modeling (DMM) and data reveals the upper limit of thermal coupling ~0.4 W/K/m per unit length at room temperature, and ~0.7 W/K/m at 600 C for the largest diameter (3-4 nm) CNTs. We also find semiconducting CNTs can break down prematurely, and display more breakdown variability due to dynamic shifts in threshold voltage, which metallic CNTs are immune to; this poses a fundamental challenge for selective electrical breakdowns in CNT electronics

Transformations of Progesterone by Subcellular Fractions of Human Skin

Homogenates of human skin metabolize progesterone-4-14C to the same products as whole skin. Studies with subcellular fractions obtained by differential centrifugation indicate the presence in skin of a membrane-bound 5α-reductase and a soluble 20α-hydroxysteroid dehydrogenase (20α-HSD), both of which utilize TPNH as cofactor. The 20α-HSD has a pH optimum of 6.2 and a Km of approximately 7 μM. Unlike placental preparations, the 105,000 × g supernatant fraction prepared from human skin has more 20α-HSD than 17β-hydroxy-steroid dehydrogenase activity. This soluble skin enzyme acting on steroid hormones is distinct from previously reported particulate enzymes

A survey of compiler development aids

A theoretical background was established for the compilation process by dividing it into five phases and explaining the concepts and algorithms that underpin each. The five selected phases were lexical analysis, syntax analysis, semantic analysis, optimization, and code generation. Graph theoretical optimization techniques were presented, and approaches to code generation were described for both one-pass and multipass compilation environments. Following the initial tutorial sections, more than 20 tools that were developed to aid in the process of writing compilers were surveyed. Eight of the more recent compiler development aids were selected for special attention - SIMCMP/STAGE2, LANG-PAK, COGENT, XPL, AED, CWIC, LIS, and JOCIT. The impact of compiler development aids were assessed some of their shortcomings and some of the areas of research currently in progress were inspected

A Novel Survey Tool to Quantify the Degree and Duration of STEMI Regionalization Across California.

IntroductionCalifornia has been a global leader in regionalization efforts for time-critical medical conditions. A total of 33 local emergency medical service agencies (LEMSAs) exist, providing an organized EMS framework across the state for almost 40 years. We sought to develop a survey tool to quantify the degree and duration of ST-elevation myocardial infarction (STEMI) regionalization over the last decade in California.MethodsThe project started with the development of an 8-question survey tool via a multi-disciplinary expert consensus process. Next, the survey tool was distributed at the annual meeting of administrators and medical directors of California LEMSAs to get responses valid through December, 2014. The first scoring approach was the Total Regionalization Score (TRS) and used answers from all 8 questions. The second approach was called the Core Score, and it focused on only 4 survey questions by assuming that the designation of STEMI Receiving Centers must have occurred at the beginning of any LEMSA's regionalization effort. Scores were ranked and grouped into tertiles.ResultsAll 33 LEMSAs in California participated in this survey. The TRS ranged from 15 to 162. The Core Score range was much narrower, from 2 to 30. In comparing TRS and Core Score rankings, the top-tertiles were quite similar. More rank variation occurred between mid- and low-tertiles.ConclusionThis study evaluated the degree and duration of STEMI network regionalization from 2004 to 2014 in California, and ranked 33 LEMSAs into tertiles based upon their TRS and their Core Score. Successful application of the 8-item survey and ranking strategies across California suggests that this approach can be used to assess regionalization in other states or countries around the world

Variation in charges for 10 common blood tests in California hospitals: A cross-sectional analysis

Objectives: To determine the variation in charges for 10 common blood tests across California hospitals in 2011, and to analyse the hospital and market-level factors that may explain any observed variation. Design setting and participants: We conducted a cross-sectional analysis of the degree of charge variation between hospitals for 10 common blood tests using charge data reported by all non-federal California hospitals to the California Office of Statewide Health Planning and Development in 2011. Outcome measures: Charges for 10 common blood tests at California hospitals during 2011. Results: We found that charges for blood tests varied significantly between California hospitals. For example, charges for a lipid panel ranged from US$10 to US$10 169, a thousand-fold difference. Although government hospitals and teaching hospitals were found to charge significantly less than their counterparts for many blood tests, few other hospital characteristics and no market-level predictors significantly predicted charges for blood tests. Our models explained, at most, 21% of the variation between hospitals in charges for the blood test in question. Conclusions: These findings demonstrate the seemingly arbitrary nature of the charge setting process, making it difficult for patients to act as true consumers in this era of ‘consumer-directed healthcare.

Mortality Of The Veined Rapa Whelk, Rapana Venosa, In Relation To A Bloom Of Alexandrium Monilatum In The York River, United States

Veined rapa whelks (Rapana venosa), carnivorous marine gastropods experienced significant mortality during an Alexandrium monilatum bloom in the lower York River, VA in September 2007. Rapa whelks stopped feeding as dissolved oxygen and chlorophyll concentrations increased with the development of the bloom. Whelk mortality was preceded by external signs of stress including reduced ventilation, inability to attach to hard Substrates, periodic Pumping of the opercular plate, and increased mucus production over a period of 24-48 h prior to death. High concentrations (2-7 mu g g(-1) tissue) of goniodimum A, a toxin produced by A. monilatum, were observed in bivalves attached to the shells of rapa whelks. Concentrations of goniodimum A in whelk foot tissue ranged from 0.02-8.39 mu g g(-1). Mortality of rapa whelks was 100%. Mortality of oysters (Crassostrea virginica) and northern quahogs (Mercenaria mercenaria) in the same flow through system was 0%. The symptoms displayed by the rapa whelks in the 24-48 h prior to death were indicative of paralysis and followed a similar time Course documented for other molluscs exposed to toxic A. monilatum

Estimating global trends in total and childhood antibiotic consumption, 2011-2015

Introduction Understanding patterns of antibiotic consumption is essential to ensure access to appropriate antibiotics when needed and to minimise overuse, which can lead to antibiotic resistance. We aimed to describe changes in global antibiotic consumption between 2011 and 2015. Methods We analysed wholesale data on total antibiotic sales and antibiotics sold as child-appropriate formulations (CAFs), stratified by country income level (low/middle-income and high-income countries (LMICs and HICs)). The volume of antibiotics sold per year was recorded for 36 LMICs and 39 HICs, measured in standard units (SU: 1 SU is equivalent to a single tablet, capsule or 5 mL ampoule/vial/oral suspension) and SU per person, overall and as CAFs. Changes over time were quantified as percentage changes and compound annual growth rates in consumption per person. Analyses were conducted separately for total sales, sales of antibiotics in the Access and Watch groups of the WHO’s Essential Medicines List for children 2017, for amoxicillin and amoxicillin with clavulanic acid. Results Antibiotic consumption increased slightly between 2011 and 2015, from 6.85×1010 SU to 7.44×1010 SU overall and from 1.66×1010 SU to 1.78×1010 SU for CAFs. However, trends differed between countries and for specific antibiotics; for example, consumption of amoxicillin as CAFs changed little in LMICs and HICs, but that of amoxicillin with clavulanic acid increased by 6.8% per year in LMICs and decreased by 1.0% per year in HICs. Conclusions As measured in standard units in sales data, the rate of increase in global antibiotic consumption may be slowing. However, the trends appear to differ between countries and drugs. In the absence of routine surveillance of antibiotic use in many countries, these data provide important indicators of trends in consumption which should be confirmed in national and local studies of prescribing

Identification of H3K4me1-associated proteins at mammalian enhancers.

Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators