MLVA-16 typing of 295 marine mammal <i>Brucella</i> isolates from different animal and geographic origins identifies 7 major groups within <i>Brucella ceti</i> and <i>Brucella pinnipedialis</i>

BackgroundSince 1994, Brucella strains have been isolated from a wide range of marine mammals. They are currently recognized as two new Brucella species, B. pinnipedialis for the pinniped isolates and B. ceti for the cetacean isolates in agreement with host preference and specific phenotypic and molecular markers. In order to investigate the genetic relationships within the marine mammal Brucella isolates and with reference to terrestrial mammal Brucella isolates, we applied in this study the Multiple Loci VNTR (Variable Number of Tandem Repeats) Analysis (MLVA) approach. A previously published assay comprising 16 loci (MLVA-16) that has been shown to be highly relevant and efficient for typing and clustering Brucella strains from animal and human origin was used.Results294 marine mammal Brucella strains collected in European waters from 173 animals and a human isolate from New Zealand presumably from marine origin were investigated by MLVA-16. Marine mammal Brucella isolates were shown to be different from the recognized terrestrial mammal Brucella species and biovars and corresponded to 3 major related groups, one specific of the B. ceti strains, one of the B. pinnipedialis strains and the last composed of the human isolate. In the B. ceti group, 3 subclusters were identified, distinguishing a cluster of dolphin, minke whale and porpoise isolates and two clusters mostly composed of dolphin isolates. These results were in accordance with published analyses using other phenotypic or molecular approaches, or different panels of VNTR loci. The B. pinnipedialis group could be similarly subdivided in 3 subclusters, one composed exclusively of isolates from hooded seals (Cystophora cristata) and the two others comprising other seal species isolates.ConclusionThe clustering analysis of a large collection of marine mammal Brucella isolates from European waters significantly strengthens the current view of the population structure of these two species, and their relative position with respect to the rest of the Brucella genus. MLVA-16 is confirmed as being a rapid, highly discriminatory and reproducible method to classify Brucella strains including the marine mammal isolates. The Brucella2009 MLVA-16 genotyping database available at http://mlva.u-psud.fr is providing a detailed coverage of all 9 currently recognized Brucella species

Small business economics: A perspective from The Netherlands

In the analysis of economic phenomena either within or across industries there is room for integrating the role of small business. This contribution can be made by aggregation or generalization of the findings at the meso level, which again are partly based upon analyses at the micro level. The Netherlands has a long history in macro model building. A recent discussion among Dutch macro-economists considered the future of econometric model building at the macro level, and considered how best to improve this model building. The explicit integration of scale effects, however, was not mentioned. I am convinced that improvements in this respect are possible. In particular, I have in mind the role which small businesses play in certain areas such as wage structure, employment or investments. The dissection of macro prognoses into a small business component and a remaining component is a traditional practice in The Netherlands.1 Finally, there is much concern in The Netherlands for the calculation of regulatory effects, decomposed into effects for small and large businesses. If anywhere in the world there is a solid foundation for studying scale effects in both macro and sectoral models, it most certainly has been in The Netherlands. There is a strong tradition of macro-econometric model building; groups of econometricians specialized in small business research exist; Dutch policymakers show concern and the required research apparatus is available

Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children.

OBJECTIVES: The objectives of this study were to investigate the population pharmacokinetics of posaconazole in immunocompromised children, evaluate the influence of patient characteristics on posaconazole exposure and perform simulations to recommend optimal starting doses. METHODS: Posaconazole plasma concentrations from paediatric patients undergoing therapeutic drug monitoring were extracted from a tertiary paediatric hospital database. These were merged with covariates collected from electronic sources and case-note reviews. An allometrically scaled population-pharmacokinetic model was developed to investigate the effect of tablet and suspension relative bioavailability, nonlinear bioavailability of suspension, followed by a step-wise covariate model building exercise to identify other important sources of variability. RESULTS: A total of 338 posaconazole plasma concentrations samples were taken from 117 children aged 5 months to 18 years. A one-compartment model was used, with tablet apparent clearance standardised to a 70-kg individual of 15 L/h. Suspension was found to have decreasing bioavailability with increasing dose; the estimated suspension dose to yield half the tablet bioavailability was 99 mg/m2. Diarrhoea and proton pump inhibitors were also associated with reduced suspension bioavailability. CONCLUSIONS: In the largest population-pharmacokinetic study to date in children, we have found similar covariate effects to those seen in adults, but low bioavailability of suspension in patients with diarrhoea or those taking concurrent proton pump inhibitors, which may in particular limit the use of posaconazole in these patients

Infantile zinc deficiency: Association with autism spectrum disorders

Elucidation of the pathogenesis and effective treatment of autism spectrum disorders is one of the challenges today. In this study, we examine hair zinc concentrations for 1,967 children with autistic disorders (1,553 males and 414 females), and show considerable association with zinc deficiency. Histogram of hair zinc concentration was non-symmetric with tailing in lower range, and 584 subjects were found to have lower zinc concentrations than −2 standard deviation level of its reference range (86.3–193ppm). The incidence rate of zinc deficiency in infant group aged 0–3 year-old was estimated 43.5 % in male and 52.5 % in female. The lowest zinc concentration of 10.7 ppm was detected in a 2-year-old boy, corresponding to about 1/12 of the control mean level. These findings suggest that infantile zinc deficiency may epigenetically contribute to the pathogenesis of autism and nutritional approach may yield a novel hope for its treatment and prevention

How Smart Cities Transform Operations Models: A New Research Agenda for Operations Management in the Digital Economy

The notion of smart cities is growing in prominence in the digital economy. The integration of urban infrastructures with information and communication technologies (ICT) enables the development of new operations models. Digitised infrastructures offer opportunities for public and private organisations to design and deliver more customer-centric products or services, particularly for those that require geographical proximity with consumers in the O2O (online to offline) context. A framework is developed and used to analyse three case examples. These cases illustrate the emergence of new operations models and, demonstrate how smart cities are re-defining the characteristics of operations models around their scalability, analytical output and, connectivity. We also explore the feasibility, vulnerability and acceptability of each new operation. This paper contributes to our understanding of how smart cities can potentially transform operational models, and sets out a research agenda for operations management in smart cities in the digital economy

Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

Final adult height and its relationship to blood glucose control and microvascular complications in IDDM.

The effect of longitudinal blood glucose control on final adult height was evaluated in 181 subjects (94 women and 87 men) with IDDM. Diabetes onset was at a median age of 6.9 years with an interquartile range of 4.7 years. Longitudinal glycated haemoglobin values were determined over a mean period of 6.6 +/- 2.6 years during their growth phase. Serial eye and joint examinations and urinary albumin excretion rates were performed with final assessment being carried out at a mean age of 21.1 +/- 3.0 years. The mean adult height standard deviation score of the whole group was -0.22 +/- 1.15 and was reduced compared to the mean height of the general population and to the mean height of the subjects' parents and siblings. There was an inverse correlation with mean longitudinal glycated haemoglobin and final adult height (p &lt; 0.01). There was also an inverse relationship between adult height and the severity of eye, kidney, and joint complications, but when controlled by glycated haemoglobin, this relationship only remained significant for eye complications. Final adult height is reduced in subjects with early onset IDDM who remain in poor blood glucose control during their growth period