The development of multiple reaction monitoring assays for liver-derived plasma proteins

There is wide interpatient variability in toxicity to chemotherapeutic drugs and a lack of routine clinical tests for prospectively identifying patients at risk of developing toxicity from chemotherapy. An empirically driven MS strategy has been developed to monitor liver-derived plasma proteins as potential biomarkers of early toxicity. Multiple reaction monitoring (MRM) has been used to assess 46 candidate peptides from 18 liver-derived proteins. Following an iterative process of assay design, optimisation and assessment we selected 29 MRM assays (median CV 4.6%, range 1.2-11.6%) and monitored changes in levels of plasma proteins from a small number of colorectal cancer (CRC) patients undergoing chemotherapy. We demonstrated MRM assay robustness, and show that patients undergo minor elevation in plasma proteins when profiled on Day 3 of the chemotherapeutic regime. The MRM assays were in general agreement with 2-D DIGE-based quantitation from the same patient samples. The data supports the application of MRM-based methods as facile, highly reproducible, medium-throughput techniques that warrant expanded investigation for clinical utility in identifying patients at risk of developing chemotoxicity.     

The Effectiveness of Telephone-Based Continuing Care in the Clinical Management of Alcohol and Cocaine Use Disorders: 12-Month Outcomes.

This study of continuing care for substance dependent patients compared a telephone-based monitoring and brief counseling intervention (TEL) with 2 face-to-face interventions, relapse prevention (RP) and standard 12-step group counseling (STND). The participants were graduates of intensive outpatient programs who had current dependence on alcohol and/or cocaine. Self-report, collateral, and biological measures of alcohol and cocaine use were obtained over a 12-month follow-up. The treatment groups did not differ on abstinence-related outcomes in the complete sample (N = 359) or on cocaine use outcomes in participants with cocaine dependence (n = 268). However, in participants with alcohol dependence only (n = 91), TEL produced better alcohol use outcomes than STND on all measures examined and better outcomes than RP on some of the measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chitosan amphiphiles provide new drug delivery opportunities

Chitosan, an acid soluble and renewable biopolymer, was first studied as a drug delivery agent in 1990. This review focuses on the relatively newer self‐assembling chitosan amphiphiles and their use as drug delivery agents. Chitosan amphiphiles, first introduced in the late 1990s, are prepared by conjugating hydrophobic and sometimes additional hydrophilic units to chitosan. These amphiphiles self‐assemble in aqueous media at neutral pH to form micelles, with critical micellar concentrations (CMCs) ranging from 0.09 to 700 µg mL^?1. The CMCs depend on the actual molecular architecture, molecular weight and hydrophobic character, but are typically lower than the values reported for block copolymer amphiphiles. As well as linear amphiphiles in which chitosan is derivatised with hydrophobic pendant groups, new claw amphiphiles have been prepared in which chitosan amphiphiles radiate geometrically from a dendrimer core. These chitosan amphiphiles (linear and claw) have been exploited as drug delivery agents and they increase the oral bioavailability of hydrophobic drugs up to sixfold, deliver hydrophobic drugs to tumours, genes to the liver via the intravenous route, genes to the muscle via the intramuscular routes and small interfering RNAs to tumours via the intratumoural route. Chitosan amphiphile nanoparticles also deliver peptides to the brain via the intravenous and oral routes. © 2014 Society of Chemical Industry     

Domestic exposure to fungal allergenic particles determined by halogen immunoassay using subject's serum versus particles carrying three non‐fungal allergens determined by allergen‐specific HIA

Studies that estimate indoor aeroallergen exposure typically measure a pre‐selected limited range of allergens. In this study, inhalable aeroallergen particles were quantified using the halogen immunoassay (HIA) to determine the contribution of fungal and non‐fungal aeroallergens to total allergen exposure. Bioaerosols from 39 homes of fungal‐allergic subjects were sampled using inhalable fraction samplers and immunostained by HIA using resident subject's immunoglobulin E (IgE) to detect allergen‐laden particles. Fungal aerosols as well as particles carrying mite, cat, and cockroach allergens were identified and enumerated by HIA. Reservoir dust‐mite (Der p 1), cat (Fel d 1), and cockroach (Bla g 1) allergen concentrations were quantified by ELISA. Fungal particles that bound subject's IgE in the HIA were 1.7 (bedroom)‐ and 1.4 (living room)‐fold more concentrated than Der p 1, Fel d 1, and Bla g 1 allergen particles combined. Predominant fungal conidia that bound IgE were derived from common environmental genera including Cladosporium and other fungi that produce amerospores. Airborne mite, cat, and cockroach allergen particle counts were not associated with reservoir concentrations determined by ELISA. This study demonstrates that inhalable fungal aerosols are the predominant aeroallergen sources in Sydney homes and should be considered in future exposure assessments.     

HPLC determination of polycyclic aromatic hydrocarbons (PAHs) in the littoral urban sewage area of cortiou (Marseille,France)

A selective method for determining polycyclic aromatic hydrocarbons (PAHs) in sediments using solid‐phase extraction and RP‐HPLC with fluorescence and UV detection is described. The complete analytical method is used to surface sediments from the creek of Cortiou (France). Sewage from the urban area of Marseille is delivered to the creek. PAH levels in sediments (µg/g) range between 2.251 µg/g (for the benzo(a)anthracene) and 相似文献   

Building human agency: a timely manifesto

The 2009 Passive and Low Energy Architecture Conference (PLEA), held in Québec City, Canada, was themed ‘Architecture, Energy and the Occupant's Perspective’, with the ambition of positioning building inhabitants as key ‘active’ determinants of energy performance in ‘passive’ design through adaptive opportunities. Conference delegates committed to a Manifesto that embodied both the key longstanding priorities of PLEA and explicitly conveyed the priorities of the conference hosts. The Manifesto is examined in terms of how it captures and represents a shift in thinking that has occurred over the past few years, away from technological and technocratic solutions to comfort provisioning and towards reframing building energy consumption as a social and ethical challenge in which comfort plays a key role.

La Conférence 2009 sur l'Architecture Passive et Basse Energie (PLEA), qui s'est tenue à Québec, au Canada, avait pour thème « Architecture, Energie et la Perspective de l'Occupant », avec pour ambition de positionner les habitants d'immeubles comme principaux déterminants « actifs » de la performance énergétique dans un design « passif » par des opportunités d'adaptation. Les délégués de la conférence se sont engagés en faveur d'un Manifeste qui, tout à la fois, incarne les principales priorités qui sont depuis longtemps celles des Conférences PLEA et traduit explicitement les priorités des hôtes de la conférence. Cet article examine le Manifeste quant à la manière dont il appréhende et reflète le changement intervenu au cours de ces dernières années dans la manière de voir les choses, consistant à se détourner d'un confort fourni par des solutions technologiques et technocratiques et à aller dans le sens d'un recadrage de la consommation énergétique des immeubles considérée comme un défi social et éthique dans lequel le confort joue un rôle clé.

Mots clés: comportement adaptatif, agence, confort, fourniture du confort, qualité environnementale intérieure, habitants, manifeste, Conférence sur l'Architecture Passive et Basse Energie (PLEA)     

Plasmid-mediated reduced phage sensitivity in Streptococcus lactis KR5

The phage insensitivity of Streptococcus lactis KR5 was evaluated for its possible linkage to plasmid DNA. This strain possessed plasmids of 40, 29, 26, 21, 16.5, 10.5, 7.8, and 1.5 Mdal. Plasmid curing using novobiocin resulted in derivatives with increased sensitivity to prolate-headed phage, suggesting the involvement of plasmid DNA in phage insensitivity. Transformation of S. lactis LM0230 protoplasts with the KR5 plasmid DNA pool produced transformants containing a plasmid of about 27 Mdal. These erythromycin-resistant transformants were lactose-positive phage-sensitive or were lactose-negative and exhibited a reduced sensitivity to phage. Agarose gel electrophoresis and restriction endonuclease digestion analysis showed the 27-Mdal plasmid band to be composed of two distinct plasmids of 26 Mdal (pBF61) and 29 Mdal (pBF62), which coded for reduced phage sensitivity and lactose-positive phenotypes, respectively. The mechanisms of reduced phage sensitivity encoded by pBF61 included a restriction/modification system and a mechanism that resulted in reduced plaque size independent of incubation temperature. These results further support the involvement of plasmid DNA in the mechanisms for reduced phage sensitivity in dairy streptococci.     

Towards van der Waals Epitaxial Growth of GaAs on Si using a Graphene Buffer Layer

Van der Waals growth of GaAs on silicon using a two‐dimensional layered material, graphene, as a lattice mismatch/thermal expansion coefficient mismatch relieving buffer layer is presented. Two‐dimensional growth of GaAs thin films on graphene is a potential route towards heteroepitaxial integration of GaAs on silicon in the developing field of silicon photonics. Hetero‐layered GaAs is deposited by molecular beam epitaxy on graphene/silicon at growth temperatures ranging from 350 °C to 600 °C under a constant arsenic flux. Samples are characterized by plan‐view scanning electron microscopy, atomic force microscopy, Raman microscopy, and X‐ray diffraction. The low energy of the graphene surface and the GaAs/graphene interface is overcome through an optimized growth technique to obtain an atomically smooth low­ temperature GaAs nucleation layer. However, the low adsorption and migration energies of gallium and arsenic atoms on graphene result in cluster‐growth mode during crystallization of GaAs films at an elevated temperature. In this paper, we present the first example of an ultrasmooth morphology for GaAs films with a strong (111) oriented fiber‐texture on graphene/silicon using quasi van der Waals epitaxy, making it a remarkable step towards an eventual demonstration of the epitaxial growth of GaAs by this approach for heterogeneous integration.     

A practical clinical trial of coordinated care management to treat substance use disorders among public assistance beneficiaries.

This study tested whether coordinated care management (CCM), a continuity of care intervention for substance use disorders (SUD), improved rates of abstinence when compared with usual welfare management for substance-using single adults and adults with dependent children applying for public assistance. The study was designed as a practical clinical trial and was implemented in partnership with a large city welfare agency. Participants were 421 welfare applicants identified via SUD screening and assigned via an unbiased computerized allocation program to a site that provided either CCM (n = 232) or usual care (UC; n = 189). Outcomes were assessed for 1 year postbaseline with self-reports and biological measures of substance use. As hypothesized, for participants not enrolled in methadone maintenance programs (n = 313), CCM clients received significantly more services than did UC clients. Nonmethadone CCM also showed significantly higher abstinence rates (odds ratio = 1.75; 95% confidence interval = 1.12, 2.76; d = 0.31) that emerged early in treatment and were sustained throughout follow-up. In contrast, no treatment services or outcome effects were found for methadone maintenance clients (n = 108). Findings suggest that CCM is promising as a wraparound to SUD treatment for welfare recipients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)