Investigation of fullerene cluster growth mechanisms by carbon atom addition using classical molecular dynamics.

The mechanisms of carbon sticking reactions to C36 and C-C80 fullerenes were investigated with molecular dynamics simulations (MD) using the Second-generation Reactive Empirical Bond Order (SREBO) and Adaptive Intermolecular Reactive Empirical Bond Order (AIREBO) potentials that were specifically optimized for carbon-carbon interactions. Results showed the existence of three possible sticking configurations where the projectile atom can stick either to one, two or three atoms of the target fullerene. They also showed that although the two potentials give similar magnitudes for the sticking cross-sections, they yield fairly different results as far as sticking mechanisms and configurations at thermal collision-energies, i.e., in the range 0.05-0.5 eV, are concerned. While AIREBO, that takes into account the long-range Lennard-Jones interaction, essentially results in a surface-sticking configuration with a single atom of the target fullerene, SREBO potential yields both surface- and two neighbors-sticking (2N-sticking) configurations. The fullerene structure is preserved in the last configuration while it can be recovered by a 2000 K annealing in the former configuration. Results obtained with SREBO eventually showed larger sticking probabilities for C36 as compared with C80. In spite of this, the sticking cross-sections obtained for C80 are similar to or even larger than those obtained for C36 due to the larger size of C80 that compensates for its smaller sticking probabilities.

Theoretical and Experimental Elucidation of the Adsorption Process of a Bioinspired Peptide on Mineral Surfaces.

Inorganic materials used for biomedical applications such as implants generally induce the adsorption of proteins on their surface. To control this phenomenon, the bioinspired peptidomimetic polymer 1 (PMP1), which aims to reproduce the adhesion of mussel foot proteins, is commonly used to graft specific proteins on various surfaces and to regulate the interfacial mechanism. To date and despite its wide application, the elucidation at the atomic scale of the PMP1 mechanism of adsorption on surfaces is still unknown. The purpose of the present work was thus to unravel this process through experimental and computational investigations of adsorption of PMP1 on gold, TiO2, and SiO2 surfaces. A common mechanism of adsorption is identified for the adsorption of PMP1 which emphasizes the role of electrostatics to approach the peptide onto the surface followed by a full adhesion process where the entropic desolvation step plays a key role. Besides, according to the fact that mussel naturally controls the oxidation states of its proteins, further investigations were performed for two distinct redox states of PMP1, and we conclude that even if both states are able to allow interaction of PMP1 with the surfaces, the oxidation of PMP1 leads to a stronger interaction.

Patterns of use of oral anticancer treatments in France: a Retrospective Analysis of Cancer Treatments given ORally from 2004 to 2012 (Re-ACTOR study).

BACKGROUNDS AND OBJECTIVES: Increasing use of oral anticancer treatments (OATs) in oncology is modifying the treatment paradigm for cancer. Nonetheless, available data on the pattern of use of OATs and its evolution over time are limited. The objective of this study was to describe the patterns of use of OATs in France from 2004 to 2012. METHODS: A retrospective analysis was performed using Oncology Analyzer, a physician survey database. All patients actively treated by an oral or an intravenous anticancer treatment between October 2004 and September 2012 were enrolled in the database. Descriptive analyses were performed by treatment category with a focus on the last year of collection and the evolution across the study period. RESULTS: From October 2011 to September 2012, a sample of 7426 patients treated by oral or intravenous active anticancer treatments was analyzed: 74% of patients receiving an OAT were diagnosed with a solid tumor, 52% of whom had a stage IV cancer. The use of OATs increased with age and was the highest in patients over 80 years. From 2004 to 2012, the proportion of cancer patients receiving OATs increased by four percentage points (from 28.4% to 32.5%). Additionally, for treatments available in both forms, a marked preference for oral formulations was observed. LIMITATIONS: The patterns and trend of use prior to 2004 were not addressed due to lack of information in the database. The use of a market research database is relevant for highly prevalent cancers but for rare cancers the sample size is limited, underlining the utility of using other data sources such as cancer registries. CONCLUSIONS: The Re-ACTOR study provides an overview of OAT use in France, which was prescribed to 32% of cancer patients in France in 2012, principally to older patients and to those with solid tumors and with metastatic disease.

[Cost of systemic lupus erythematosus for adult patients with active and treated disease in France (LUCIE study)]. / Coût du lupus systémique en France des patients adultes avec une maladie active et traitée (étude LUCIE).

PURPOSE: To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare. METHODS: A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models. RESULTS: Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P<0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was €4660 versus €3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (€3214 vs €1856; P<0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of €1330 (P<0.05). CONCLUSION: Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.

Patterns of systemic lupus erythematosus expression in Europe.

OBJECTIVES: To analyse the differences in disease expression of European SLE patients based on gender, age at diagnosis, and ethnicity. METHODS: A two-year, retrospective, multicentre, observational study was carried out in five countries (France, Germany, Italy, Spain and the UK). Patients' clinical manifestations including disease activity, organ involvement, organ damage and flares were analysed. RESULTS: Thirty-one centres enrolled 412 consecutive eligible patients (90.5% of women), with active disease, stratified by disease severity (half severe and half non-severe). Baseline characteristics included; mean (SD) age: 43.3 (13.6) years, SLE duration: 10.7 (8.0) years and age at disease diagnosis: 32.6 (13.0) years old. The mean (SD) SELENA-SLEDAI and SLICC/ACR scores were: 8.1 (6.7) and 0.82 (1.36), respectively. Over half of patients experienced flares (54.9%). The average number of annual flares was 1.01 (0.71) flares/year. In males compared to females, the renal system was more frequently active (53.8% vs 30.0%, p=0.002), the mean SLICC/ACR score was higher (1.15 vs 0.79, p=0.039) and the pulmonary system was more likely to be damaged (12.8% vs 3.8%, p=0.010). Furthermore, patients diagnosed at younger age displayed more renal system activity (young: 56.3% vs adult: 33.4% vs elder: 8.9%, p<0.001) and renal damage (25.0% vs 6.9% vs 2.2%, p=0.018) compared to the others. The annual number of flares (1.13 vs 1.05 vs 0.81 flares/year, p<0.0001), including the occurrence of severe flares (0.58 vs 0.51 vs 0.20, p<0.0001), was also higher in these patients. Conversely, greater organ damage was observed in patients diagnosed at an older age compared to the others. The mean SLICC/ACR score was higher (1.31 vs young: 0.88 and adult: 0.78, p<0.001) in patients diagnosed in the older age groups. The pulmonary (13.3% vs younger: 0% vs adult: 3.7%, p=0.030) and cardiovascular (17.8% vs younger: 0% vs adult: 2.9%, p<0.001) systems were more frequently damaged in these patients. Black African descents showed greater disease activity compared to Caucasian patients. They flared more often (77.1% vs 48.6%, p=0.001) and experienced a greater number of annual flares (1.57 vs 0.89 flares/year, p<0.0001), mainly more severe flares (0.89 vs 0.38/year, p<0.0001). They also were more likely to experience renal system damage. CONCLUSION: The study showed clearly two patient subsets. The disease was the most active in Black African descents, and this phenomenon has never been described before in continental Europe. The disease was also more active in patients diagnosed at a younger or adult. Greater disease damage was observed in males and in patients diagnosed at an older age.

Experimental demonstration of surface selection rules for SERS on flat metallic surfaces.

We have measured the polarization and incident angle dependence of the Surface-Enhanced Raman Scattering (SERS) signal of a nile blue monolayer adsorbed on a flat gold surface. Comparisons with predictions of electromagnetic (EM) theory indicate that the molecules are predominantly adsorbed flat on the surface. These results provide the most direct demonstration of the concept of surface selection rules in SERS, and further confirm the validity of the SERS-EM model beyond the |E|(4)-approximation.

Docking and 3D-QSAR studies of BMS-806 analogs as HIV-1 gp120 entry inhibitors.

BMS-378806 (BMS-806) is a small molecule that blocks the binding of host-cell CD4 with viral gp120 protein and therefore inhibits the first steps of HIV-1 infection. Recently, 36 analogs compounds of BMS-806 were synthesized and their biological activity evaluated. Based on these compounds, a molecular docking was firstly performed with BMS-806 to the gp120 cavity in order to get a representative ligand conformation for the 3D-QSAR process. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were then conducted for these 36 compounds. CoMFA and CoMSIA models give reliable correlative and predictive abilities but the CoMFA model performance was slightly better than CoMSIA. CoMFA contours were analysed and have been correlated to the gp120 viral protein. The discussion indicates several key fragment positions on the ligands and their implications on the gp120 protein binding. The computational approach used in this paper provides reliable clues for further design of small molecules gp120/CD4 inhibitors based on the BMS-806.

STM observation of a single diarylethene flickering.

We report the STM observation of single diarylethene derivatives (DD) embedded into alkylthiol self-assembled monolayers (SAM) on Au(111). Telegraph noise in the data shows that the molecular conductance oscillates between two states. Comparing our results to the ones obtained by other teams observing conductance flickering with systems in the same geometry, we relate the two observed states to the two isomeric configurations of the molecule under study.

Quantum chemical study of the photocoloration reaction in the napthoxazine series.

Ab initio and semiempirical quantum mechanical calculations were performed to study the electronic spectra of spiroxazine photochromic compounds as well as the corresponding photoisomers. Ground-state geometries were optimized based on density functional theory (DFT). Excitation energies of the different forms were calculated using the time-dependent density functional theory (TD-DFT) method. Semiempirical calculations including configuration interactions were performed to detail the mechanism of ring opening in excited states. On the basis of the obtained potential energy profile, a complete mechanism of photocoloration able to clarify some experimental findings is provided. A correlation of the experimental quantum yield of photocoloration with the calculated properties as a function of substituent effects is proposed.

Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease.

BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.

The burden cost of French patients suffering from irritable bowel syndrome.

BACKGROUND: The impact of irritable bowel syndrome (IBS) on health-care resource use in France is evaluated, and explanatory variables determined. METHODS: A questionnaire comprising socio-demographic characteristics, symptoms, consumption of resources, quality of life and impact of IBS on productivity was administered by telephone to a sample of 253 French adults with IBS recruited from the general population, and diagnosed with IBS using several well-known diagnostic criteria. The medical costs were estimated on a monthly basis and included medication(s), physicians' consultations, investigations and hospitalizations. RESULTS: Mean age was 48.3 years and 75% of subjects were women (192). Thirty-six percent of subjects had suffered from IBS for more than 10 years; 77% had consulted a general practitioner and 43% a gastroenterologist. Twenty-nine percent of subjects had undergone an investigation and 25% reported hospitalization; 61% of patients reported that they were taking medication. The average monthly medical costs was 71.8 euros (95% CI = [57.6-86.0]) with an asymmetric distribution (median = 28.1 euros) because of a high proportion of subjects (27%) who reported receiving no care at all. The two principal cost components were investigations (39%), and hospitalizations (22%). The highest medical costs were associated with subjects who were very elderly or suffered from severe symptoms (very severe pain), and were correlated with the lowest quality of life scores. CONCLUSION: IBS has a major impact on resource consumption and the productivity of patients. Determination of the variables to explain medical costs showed that advanced age, severe pain and deterioration in quality of life could be predictive of high medical costs.

[A cost-effectiveness analysis of changes in therapeutic strategies in the treatment of HIV since 1996]. / Une analyse coût-efficacité du changement des schémas thérapeutiques dans le VIH depuis 1996.

The objective was to assess the cost-effectiveness ratio of HAART in the treatment of HIV infection. Two random samples were extracted from the database of the Rothschild Public Hospital, and patients were matched for age, sex and T4 cell counts: a first sample selected in 1996/97 of HAART treated patients (CAS group) and a second sample selected in 1994/95 of non-HAART treated patients (CONTROL group). Immune recovery and use of resources data were extracted and analyzed over two years for 196 included patients. Mean T4 cell count after two years was higher among CAS patients (344/mm3 vs. 234/mm3; p < 0.0001). CAS patients recorded a supplementary cost of antiretroviral treatments (+171%; p < 0.0001) balanced by savings in other drugs expenses (-62%; p = 0.0560) and in hospitalizations (-25%; NS). Overall, CAS patients presented a 15% (NS) lower medical cost than CONTROL patients.

Effect of HAART on health status and hospital costs of severe HIV-infected patients: a modeling approach.

PURPOSE: The purpose of this study was to assess the impact of highly active antiretroviral therapy (HAART) on health status and hospital costs in severe HIV-infected patients who were followed in a French hospital. METHOD: The first 500 patients who received HAART, with CD4 + cell count below 250/mm(3), were considered. Evolution of the distribution of patients among different health states, including death, was modeled through a continuous time Markov model. Hospital financial charges and antiretroviral treatment costs were computed. Health states defined by both CD4 counts and viral load were used to show clinical changes in the patient population over a 14-month period after HAART initiation. The economic impact of HAART initiation was assessed using a simplified model based on CD4 counts only over two 14-month periods, before and after initiation. RESULTS: Between day 0 and month 14, the proportion of patients in the least severe state (CD4 + >100/mm(3) and viral load<500 copies/mL) increased from 1% to 50%, and the proportion with more than 100 CD4 + cells/mm(3) increased from 17% to 80%. Antiretroviral treatments amounted to Fr 2,141 per patient-month before HAART initiation and to Fr 3,093 after. Conversely, hospital charges fell from Fr 5,138 per patient-month to Fr 3,136. CONCLUSION: Our model gives a representation of the effect of HAART on (1) the improvement of patients' health status, (2) the increase of treatment costs, and (3) the reduction of hospital financial charge. Important savings in hospital charges can compensate for the extra cost associated with the initiation of HAART.

[Social and economic cost of L-Dopa-induced dyskinesias in patients with Parkinson's disease]. / Le coût socio-économique des dyskinésies associées au traitement par la L-Dopa chez des patients atteints de maladie de Parkinson.

Long term L-Dopa medication mainly induces two complications in Parkinson's Disease (PD) patients, i.e. motor fluctuations and dyskinesias. Both of these complications can significantly impair the patient's quality of life. At a high degree of severity, dyskinesias can interfere with everyday tasks, balance, speech, etc. From a clinical point of view, they lead to complicated L-Dopa dose adjustments or to the use of sustained release forms. For these reasons, L-Dopa-induced dyskinesias may have a significant human and financial impact. We have designed a retrospective study to explore two aspects of PD, i.e. the impact of dyskinesias on patient's social life and their economic cost. Ten French neurologists were randomly selected from a national file to participate in this study. They were asked to include 4 patients with PD currently under L-Dopa medication and showing 4 different levels of dyskinesia severity, i.e. absent, moderate, mild and severe dyskinesia, according to the Unified Parkinson Disease Rating Scale, with no other specific inclusion criteria. Two specific scales were to be completed, Hoehn & Yahr on disease severity and Schwab & England on degree of independence. Clinical profiles of patients, demographics and use of medical resources were also recorded. Investigators were interviewed about their practice. This study showed that patients with dyskinesias had an earlier onset of the disease (11.2 years vs. 3.7 years). They also had a higher level of disease severity, according to the Hoehn & Yahr scale (40p. cent vs. 0p. cent presenting a level of 4). The mean monthly cost was significantly higher for patients with dyskinesias (FF 3 733 versus FF 1 109, p=0.0005). Particularly, the presence of dyskinesias had a significant impact on treatment costs and medical visits. A positive gradient of the medical cost with level of dyskinesia severity was also underlined. In the same way, the more severe the dyskinesia status the greater the need for caregivers. Finally, based on these results, the total annual medical cost of dyskinesias in France was estimated between 588 and 812 million francs.

Oligomer-oligomer versus oligomer-monomer C(2)-C(2)' coupling reactions in polypyrrole growth.

The C(2)-C(2)' coupling reactions of oligopyrrole radical-cations of increasing length generated by electrochemical oxidation have been modeled by transition state calculations. The modeling approach takes into account solvent effects and (i) shows that the coupling distance in the transition state decreases with oligomer length, (ii) demonstrates that dimerization rates in the gas phase decrease with oligomer length but increase in water, (iii) suggests that in a less solvating medium the dimerization rates could be equivalent, (iv) indicates that in all solvents quaterpyrrole and sexipyrrole formation is faster through a coupling reaction between oligomer and monomer radical-cations than two oligomer radical-cations, and (v) suggests that for the formation of a long oligopyrrole from oligopyrrole-pyrrole reactions the mechanism might involve the coupling of the oligopyrrole dication with a non-oxidized pyrrole unit instead of the coupling of two radical-cations or that of the oligopyrrole dication with a pyrrole radical-cation.

The long-term effectiveness of preventive strategies for osteoporosis in postmenopausal women: a modeling approach.

Based on data from the literature, we have developed a computer-based simulation model to compare the long-term effectiveness of different preventive strategies of osteoporotic fractures. The Markov model comprises 25 states, including states which describe women distributed according to three levels of fracture risk, fractures states, post-fracture states and a death state. We chose eight standard preventive strategies, which we compare with the 'No Treatment' reference strategy. The first two strategies consist in treating all 50-year-old women for 5 or 10 years with hormone replacement therapy (HRT). Strategies 3 and 4 aim at assessing a 5-year course of treatment with bisphosphonates in osteopenic and osteoporotic 65- or 75-year-old women. Strategies 5 and 6 combine 5 years of HRT in all 50-year-old women with 5 years of bisphosphonates in osteopenic and osteoporotic women at 65 or 75 years. The last two strategies simulate 10 years of HRT in all 50-year-old women, followed by strategy 3 or strategy 4. Simulated life expectancy and mean ages of fracture occurrence fit well with the observed data. All the preventive strategies tested reduced the number of fractures. Early 10-year HRT in all women, plus 5 years of bisphosphonates in women at risk of fractures at 65 or 75 years, are the most effective strategies, with an 18.4-19.0% reduction in all fractures, and a 25.6-26.1% reduction in the number of hip fractures. Strategy 2 has a similar outcome, thus demonstrating the value of treatment started early and sustained over a long period. The strategies implemented later, S3 and S4, only concern women at risk (i.e., osteopenic or osteoporotic), and are less effective, with a 1.5-2.1% decrease in all fractures. The combined strategies, S5 and S6, produce intermediate results: a 12.9-13.5% reduction in the number of all fractures and a 17.5-17.9% reduction in hip fractures.

[Prenatal diagnosis of a placenta praevia percreta with color Doppler. A case report. Review of the literature]. / Diagnostic anténatal d'un placenta praevia percreta grâce au Doppler couleur. A propos d'un cas. Revue de la littérature.

Placenta praevia percreta, with bladder invasion, was diagnosed at 29 weeks of amenorrhoea with colour Doppler which visualized vascular bundles leaving the placenta and reaching the lower part of the bladder. These bundles were identified as including arterial elements with pulsed Doppler. The criteria for the diagnosis of placenta accreta with ultrasonography and colour Doppler have been presented in the literature. This prenatal diagnosis allowed adapted preoperative management and intensive care, however air embolism could not be avoided and the patient died at the end of the operation.