Studies in the handling and absorption of biopterin derivatives in man

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Performance management in the United States and France:four case studies in the retail and airline industries

The profusion of performance measurement models suggested by Management Accounting literature in the 1990’s is one illustration of the substantial changes in Management Accounting teaching materials since the publication of “Relevance Lost” in 1987. At the same time, in the general context of increasing competition and globalisation it is widely thought that national cultural differences are tending to disappear, meaning that management techniques used in large companies, including performance measurement and management instruments (PMS), tend to be the same, irrespective of the company nationality or location. North American management practice is traditionally described as a contractually based model, mainly focused on financial performance information and measures (FPMs), more shareholder-focused than French companies. Within France, literature historically defined performance as being broadly multidimensional, driven by the idea that there are no universal rules of management and that efficient management takes into account local culture and traditions. As opposed to their North American brethren, French companies are pressured more by the financial institutions that fund them rather than by capital markets. Therefore, they pay greater attention to the long-term because they are not subject to quarterly capital market objectives. Hence, management in France should rely more on long-term qualitative information, less financial, and more multidimensional data to assess performance than their North American counterparts. The objective of this research is to investigate whether large French and US companies’ practices have changed in the way the textbooks have changed with regards to performance measurement and management, or whether cultural differences are still driving differences in performance measurement and management between them. The research findings support the idea that large US and French companies share the same PMS features, influenced by ‘universal’ PM models.

G-protein-coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent

G-protein coupled receptors (GPCRs) constitute the largest class of membrane proteins and are a major drug target. A serious obstacle to studying GPCR structure/function characteristics is the requirement to extract the receptors from their native environment in the plasma membrane, coupled with the inherent instability of GPCRs in the detergents required for their solubilization. In the present study, we report the first solubilization and purification of a functional GPCR [human adenosine A<inf>2Ainf> receptor (A<inf>2Ainf>R)], in the total absence of detergent at any stage, by exploiting spontaneous encapsulation by styrene maleic acid (SMA) co-polymer direct from the membrane into a nanoscale SMA lipid particle (SMALP). Furthermore, the A<inf>2Ainf>R-SMALP, generated from yeast (Pichia pastoris) or mammalian cells, exhibited increased thermostability (∼5°C) compared with detergent [DDM (n-dodecyl-β-D-maltopyranoside)]-solubilized A<inf>2Ainf>R controls. The A<inf>2Ainf>R-SMALP was also stable when stored for prolonged periods at 4°C and was resistant to multiple freeze-thaw cycles, in marked contrast with the detergent-solubilized receptor. These properties establish the potential for using GPCR-SMALP in receptor-based drug discovery assays. Moreover, in contrast with nanodiscs stabilized by scaffold proteins, the non-proteinaceous nature of the SMA polymer allowed unobscured biophysical characterization of the embedded receptor. Consequently, CD spectroscopy was used to relate changes in secondary structure to loss of ligand binding ([³H]ZM241385) capability. SMALP-solubilization of GPCRs, retaining the annular lipid environment, will enable a wide range of therapeutic targets to be prepared in native-like state to aid drug discovery and understanding of GPCR molecular mechanisms.

Where did we come from? The emergence and early development of voluntary sector studies in the UK

This article considers how the field of voluntary sector studies (VSS) in the UK emerged. Drawing on published and unpublished documents as well as on semi-structured interviews with people involved in the early development of VSS, a timeline of key events is suggested. The analysis reveals both social and cognitive elements in the field's development and considers the broader policy and institutional context within which key events of the VSS field occurred.

The origin of vertebrate steroids in molluscs: uptake, metabolism and depuration studies in the common mussel

No abstract available.

Trammel net selectivity studies in the Algarve (southern Portugal), gulf of cadiz (Spain), Basque coutry (Spain) and cyclades islands (Greece)

Trammel net fisheries were studied in four areas: the Cantabrian Sea (Basque Country, Spain), the Algarve (Southern Portugal), the Gulf of Cádiz (Spain) and the Cyclades Islands (Greece). Surveys were carried out in order to identify trammel net métiers and to characterise the gear used. Trammel nets were among the most important gears used in the small-scale fisheries, with up to 9 different métiers identified in each area. The most important métiers in the Algarve and the Gulf of Cádiz were those for cuttlefish (Sepia officinalis) and soles (Solea senegalensis, Microchirus azevia, Synaptura lusitanica). In the Cantabrian Sea, sole (Solea vulgaris), shellfish (several species) and scorpion fish (Scorpaena spp.) métiers dominated while a variety of species where targeted in the multi-species trammel net fishery in the Cyclades. In each area, experimental trammel nets of six different types (combinations of 2 large mesh outer panel sizes and 3 small mesh outer panels) corresponding to the most common métier, were constructed and fishing trials carried out on a seasonal basis (4 seasons in the Cantabrian Sea, Algarve and Cyclades and 2 in the Gulf of Cádiz) using chartered commercial fishing vessels. Overall, 271, 360, 185 and 185 km of trammel nets were fished in the experimental fishing trials in the Cantabrian Sea, Algarve, Gulf of Cádiz and Cyclades Islands respectively.

Comparative fixed gear studies in the Cyclades (Aegean Sea): size selectivity of small-hook longlines and monofilament gill nets

Fishing trials with monofilament gill nets and longlines using small hooks were carried out at the same fishing grounds in Cyclades (Aegean Sea) over 1 year. Four sizes of MUSTAD brand, round bent, flatted sea hooks (Quality 2316 DT, numbers 15, 13, 12 and 11) and four mesh sizes of 22, 24, 26 and 28 turn nominal bar length monofilament gill nets were used. Significant differences in the catch size frequency distributions of the two gears were found for four out of five of the most important species caught by both the gears (Diplodus annularis, Diplodus vulgaris, Pagellus erythrinus, Scorpaena porcus and Serranus cabrilla), with longlines catching larger fish and a wider size range than gill nets. Whereas longline catch size frequency distributions for most species for the different hook sizes were generally highly overlapped, suggesting little or no differences in size selectivity, gill net catch size frequency distributions clearly showed size selection, with larger mesh sizes catching larger fish. A variety of models were fitted to the gill net data, with the lognormal providing the best fit in most cases. A maximum likelihood method was also used to estimate the parameters of the logistic model for the longline data. Because of the highly overlapped longline catch size frequency distributions parameters could only be estimated for two species. This study shows that the two static gears have different impacts in terms of size selection. This information will be useful for the more effective management of these small-scale, multi-species and multi-gear fisheries. (C) 2002 Elsevier Science B.V. All rights reserved.

Validation of reference genes for gene expression studies in the honey bee, Apis mellifera, by quantitative real-time RT-PCR

For obtaining accurate and reliable gene expression results it is essential that quantitative real-time RT-PCR (qRT-PCR) data are normalized with appropriate reference genes. The current exponential increase in postgenomic studies on the honey bee, Apis mellifera, makes the standardization of qRT-PCR results an important task for ongoing community efforts. For this aim we selected four candidate reference genes (actin, ribosomal protein 49, elongation factor 1-alpha, tbp-association factor) and used three software-based approaches (geNorm, BestKeeper and NormFinder) to evaluate the suitability of these genes as endogenous controls. Their expression was examined during honey bee development, in different tissues, and after juvenile hormone exposure. Furthermore, the importance of choosing an appropriate reference gene was investigated for two developmentally regulated target genes. The results led us to consider all four candidate genes as suitable genes for normalization in A. mellifera. However, each condition evaluated in this study revealed a specific set of genes as the most appropriated ones.

Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.

Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium

Background Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). Methods We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. Results Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). Conclusions Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.

Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases < 45 years, 73% for cases > 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541-50)

Family history of cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology consortium

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR = 1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR = 2.2, 95% CI 1.6-3.1) rather than a parent (OR = 1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR = 1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR = 1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR = 1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC. (C) 2008 Wiley-Liss, Inc,