Detection, Determination of Chemical Composition and Chemical Profiling of Counterfeit Medicines by Raman Spectroscopy.

Raman spectroscopy has become a widespread technique for the analysis ofpharmaceutical solid forms. The application proposed here is the investigationof counterfeit medicines. This serious global issue requires quick and accurateidentification methods to fight against this phenomenon. Thanks to its chemicalselectivity, rapidity of analysis and potential of generating repeatable spectralprofiles, Raman spectroscopy presents distinct advantages for the analysis ofcounterfeits. Combined with chemometric tools, the technique enablesthe detection, the determination of chemical composition and the profiling ofmedicine counterfeits.

Detection of possible variant forms of hemoglobin in HbA1c measurements by chromatography liquid ion exchange high resolution (HPLC)

Background: The glycosylated hemoglobin (HbA1c) is used to help monitor the degree of a diabetic’s hyperglycemia. Security and accuracy of the methods used in its detection are affected by variants forms of Hb or elevations in levels of Fetal Hb (HbF). These interference are the result of a change in the haemoglobin total net charge of the variant due of a substitution of one amino acid in the remaining amino terminal of the beta chain. International Standardization for HbA1c values (NGSP) not include interference assessment as part of the certification program. Therefore, the effect of each variant or the lifting of the HbF on HbA1c result should be examined in each sample depending on the detected variant and the method used for the detection of the same. The objectives were: to describe the possible variants of Hb and their interference in HbA1c measurement by our method, after the implementation of a computer program for their detection. To identify some variants detected by chromatography liquid ion exchange high resolution (HPLC) with DNA molecular sequencing.

Ganciclovir exposure under a 450mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study.

Manuel O, Pascual M, Perrottet N, Lamoth F, Venetz J-P, Decosterd LA, Buclin T, Meylan PR. Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study. 
Clin Transplant 2010: 24: 794-800. Abstract:  This prospective study aimed at determining the ganciclovir exposure observed under a daily dosage of 450 mg valganciclovir routinely applied to kidney transplant recipients with a GFR above 25 mL/min at risk for cytomegalovirus (CMV) disease. Ganciclovir levels at trough (C(trough) ) and at peak (C(3 h) ) were measured monthly. Ganciclovir exposure (area under the curve [AUC(0-24) ]) was estimated using Bayesian non-linear mixed-effect modeling (NONMEM). Thirty-six patients received 450 mg of valganciclovir daily for three months. Median ganciclovir C(3 h) was 3.9 mg/L (range: 1.3-7.1), and C(trough) was 0.4 mg/L (range 0.1-2.7). Median AUC(0-24) of ganciclovir was 59.3 mg h/L (39.0-85.3) in patients with GFR(MDRD) 26-39 mL/min, 35.8 mg h/L (24.9-55.8) in patients with GFR(MDRD) 40-59 mL/min, and 29.6 mg h/L (22.0-43.2) in patients with GFR(MDRD)  ≥ 60 mL/min. No major differences in adverse events according to ganciclovir exposure were observed. CMV viremia was not detected during prophylaxis. After discontinuing prophylaxis, CMV viremia was seen in 8/36 patients (22%), and 4/36 patients (11%) developed CMV disease. Ganciclovir exposure after administration of valganciclovir 450 mg daily in recipients with GFR ≥60 mL/min was comparable to those previously reported with oral ganciclovir. A routine daily dose of 450 mg valganciclovir appears to be acceptable for CMV prophylaxis in most kidney transplant recipients.

Normal forms, stability and splitting of invariant manifolds I. Gevrey Hamiltonians

In this paper, we give a new construction of resonant normal forms with a small remainder for near-integrable Hamiltonians at a quasi-periodic frequency. The construction is based on the special case of a periodic frequency, a Diophantine result concerning the approximation of a vector by independent periodic vectors and a technique of composition of periodic averaging. It enables us to deal with non-analytic Hamiltonians, and in this first part we will focus on Gevrey Hamiltonians and derive normal forms with an exponentially small remainder. This extends a result which was known for analytic Hamiltonians, and only in the periodic case for Gevrey Hamiltonians. As applications, we obtain an exponentially large upper bound on the stability time for the evolution of the action variables and an exponentially small upper bound on the splitting of invariant manifolds for hyperbolic tori, generalizing corresponding results for analytic Hamiltonians.

Normal forms, stability and splitting of invariant manifolds II. Finitely differentiable Hamiltonians

This paper is a sequel to ``Normal forms, stability and splitting of invariant manifolds I. Gevrey Hamiltonians", in which we gave a new construction of resonant normal forms with an exponentially small remainder for near-integrable Gevrey Hamiltonians at a quasi-periodic frequency, using a method of periodic approximations. In this second part we focus on finitely differentiable Hamiltonians, and we derive normal forms with a polynomially small remainder. As applications, we obtain a polynomially large upper bound on the stability time for the evolution of the action variables and a polynomially small upper bound on the splitting of invariant manifolds for hyperbolic tori.

Power and selection of contract terms: The case from the Brazilian orange juice sector

ABSTRACT We propose a model to explain how contract terms are selected in the presence of a form of economic power: contract power. The orange juice sector is used to illustrate an analysis that demonstrates the effects of contract power on the economic organization of the sector. We define contract power as the ability to exploit contractual gaps or failures of contractual provisions, which are strategically left incomplete. Empirical evidence from content analysis of antitrust documents supports the logic of contract power in the orange juice sector in three forms: avoiding changes to payment methods from weight to solid contents (quality); using information asymmetries to manipulate indexes that calculate the formula of orange prices; and deliberately harvesting oranges late in order to dehydrate the fruit, which consequently reduces weight and price. The paper contributes to understanding the selection of contract terms and the debate about how antitrust offices can deal with this issue.

Conflict resolution and evolution of social structures in insect societies

In colonies of social Hymenoptera (which include all ants, as well as some wasp and bee species), only queens reproduce whereas workers generally perform other tasks. The evolution of worker's reproductive altruism can be explained by kin selection, which states that workers can indirectly transmit copies of their genes by helping the reproduction of relatives. The relatedness between queens and workers may however be low, particularly when there are multiple queens per colony, which limits the transmission of copies of workers genes and increases potential conflicts between colony members. In this thesis, we investigated the link between social structure variations and conflicts, and explored the mechanisms involved in variation of colony queen number in ants. According to kin selection, workers should rear the brood they are most related to. In social Hymenoptera, males are haploid whereas females (workers and queens) are diploid. As a result, workers can be up to three times more related to females than males in some colonies, where they should consequently favour the production of females. In contrast, queens are equally related to daughters and sons in all types of colonies and therefore should favour a balanced sex ratio. In a meta-analysis across all studies of social Hymenoptera, we showed that colony sex ratio is generally largely influenced by workers. Hence, the evolution of social structures where queens and workers are equally related to males and females may contribute to decrease the conflict between the two castes over colony sex ratio. Another conflict between queens and workers can occur over male production. Many species contain workers that still have the ability to lay haploid eggs. In some social structures, workers are on average more related to sons of queens than to sons of other workers. As a result, workers should eliminate worker-laid eggs to favour queen-laid eggs. We showed that in the ant Formica selysi, workers eliminate more worker-laid than queen-laid eggs, independently of colony social structure. These results therefore suggest that worker policing can evolve independently from relatedness, potentially because of costs of worker reproduction at the colony-level. Colony queen number is a key parameter that influences relatedness between group members. Queen body size is generally linked to the success of independent colony foundation by single queens and may influence the number of queens in the new colony. In the ant F. selysi, single-queen colonies produce larger queens than multiple-queen colonies. We showed that this association results from genes or maternal effects transmitted to the eggs. However, we also found that queens produced in colonies of the two social forms did not differ in their general ability to found new colonies independently. Queen body size may also influence queen dispersal ability and constrain small queens to be re-adopted in their original nest after mating at proximity. We tested the acceptance of new queens in another ant species, Formica paralugubris, which has numerous queens per colony. Our results show that workers do not discriminate between nestmate and foreign queens, and more generally accept new queens at a limited rate. To conclude, this thesis shows that mechanisms influencing variation in colony queen number and the influence of these changes on conflict resolution are complex. Data gathered in this thesis therefore constitute a solid background for further research on the evolution and the maintenance of complex organisations in insect societies.

Energy dispersive X-Ray fluorescence : measuring elements in solid and liquid matrices

The subject of this project is about “Energy Dispersive X-Ray Fluorescence ” (EDXRF).This technique can be used for a tremendous variety of elemental analysis applications.It provides one of the simplest, most accurate and most economic analytical methods for thedetermination of the chemical composition of many types of materials.The purposes of this project are:- To give some basic information about Energy Dispersive X-ray Fluorescence.- To perform qualitative and quantitative analysis of different samples (water-dissolutions,powders, oils,..) in order to define the sensitivity and detection limits of the equipment.- To make a comprehensive and easy-to-use manual of the ‘ARL QUANT’X EnergyDispersive X-Ray Fluorescence’ apparatus

Analytical expressions for the flame front speed in the downward combustion of thin solid fuels and comparison to experiments

We derive analytical expressions for the propagation speed of downward combustion fronts of thin solid fuels with a background flow initially at rest. The classical combustion model for thin solid fuels that consists of five coupled reaction-convection-diffusion equations is here reduced into a single equation with the gas temperature as the single variable. For doing so we apply a two-zone combustion model that divides the system into a preheating region and a pyrolyzing region. The speed of the combustion front is obtained after matching the temperature and its derivative at the location that separates both regions.We also derive a simplified version of this analytical expression expected to be valid for a wide range of cases. Flame front velocities predicted by our analyticalexpressions agree well with experimental data found in the literature for a large variety of cases and substantially improve the results obtained from a previous well-known analytical expression

Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.

PURPOSE: To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. METHODS: Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy. RESULTS: Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a- and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer. CONCLUSIONS: HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD.

Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients.

Epstein-Barr virus (EBV) contributes to the pathogenesis of post-transplant lymphoproliferative disease (PTLD) in more than 70% of cases. EBV DNAemia surveillance has been reported to assist in the prevention and treatment of PTLD in hematopoietic stem-cell transplantation (HSCT) recipients. Derived from experience in HSCT and taking into account that PCR-based EBV monitoring techniques are currently available in most solid organ transplant (SOT) centres, there is a great interest in EBV surveillance and prevention of PTLD in SOT recipients. In the present document we have tried to address from a practical perspective different important topics regarding the prevention and management of EBV-related PTLD in SOT. To this end, available information on SOT was analysed and combined with potentially useful data from HSCT and expert observations. The document is therefore structured according to different specific questions, each of them culminating in a consensus opinion of the panel of European experts, grading the answers according to internationally recognized levels of evidence. The addressed issues were grouped under the following topics. (i) Timing and epidemiological data of PTLD. Prophylaxis guided by clinical risk factors of early and late PTLD in SOT. (ii) Relationship of EBV DNAemia load monitoring and the development of PTLD in solid organ transplant recipients. (iii) Monitoring of EBV DNAemia after SOT. Which population should be monitored? What is the optimal timing of the monitoring? (iv) Management of SOT recipients with persistent and/or increasing EBV DNAemia.

Wayne-Ringgold-Decatur County Solid Waste Management Commission, June 30, 2001 & June 30, 2002

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Pocahontas County Solid Waste Commission, June 30, 2001 & June 30, 2002

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