The effect of health care expenditures on survival in locally advanced and metastatic Non Small Cell Lung Cancer

Context: The significant survival benefit of chemotherapy over best supportive care for locally advanced and metastatic NSCLC has been amply demonstrated in the literature. However, there is no clear evidence of the impact of the type of chemotherapy or of a superiority of combination chemotherapy over single-agent chemotherapy.Objective: The present study empirically examines, in real-life practise and using multiple proxies, the impact of health care expenditures on overall survival in locally advanced and metastatic NSCLC in order to guide medical decision-making.Methods: Disease characteristics, the resources used, the costs of treatment and survival data were retrospectively collected from the records of 175 patients treated between 2000 and 2004 at Léon Bérard Regional Cancer Center (Lyon, France). Survival data were modelled using multivariate Cox models and controlled for endogeneity with the instrumental variable method.Results: The median survival for the whole cohort was 289 days. The average total cost of treatment reached €35,160. Survival was significantly shorter for patients with stage IV disease, poor performance status, and past or concomitant cardiovascular disease and/or diabetes, for current smokers, and for patients with adenocarcinoma compared to large cell carcinoma. Survival duration was not significantly associated with the total cost of treatment per day of hospitalisation, the number of chemotherapy drugs administered, nor inpatient length of stay.Conclusion: Higher care expenditures do not appear to improve survival for patients with locally advanced or metastatic NSCLC. Hence, maintaining patient quality of life and tailoring therapy to stage, histology and comorbidities appears to be the less bad choice.Cost; NSCLC; Oncology; Survival

The influence of N-terminal acetylation on micelle-induced conformational changes and aggregation of α-Synuclein

The biological function of α-Synuclein has been related to binding to lipids and membranes but these interactions can also mediate α-Synuclein aggregation, which is associated to Parkinson's disease and other neuropathologies. In brain tissue α-Synuclein is constitutively N-acetylated, a modification that plays an important role in its conformational propensity, lipid and membrane binding, and aggregation propensity. We studied the interactions of the lipid-mimetic SDS with N-acetylated and non-acetylated α-Synuclein, as well as their early-onset Parkinson's disease variants A30P, E46K and A53T. At low SDS/protein ratios α-Synuclein forms oligomeric complexes with SDS micelles with relatively low α-helical structure. These micellar oligomers can efficiently nucleate aggregation of monomeric α-Synuclein, with successive formation of oligomers, protofibrils, curly fibrils and mature amyloid fibrils. N-acetylation reduces considerably the rate of aggregation of WT α-Synuclein. However, in presence of any of the early-onset Parkinson's disease mutations the protective effect of N-acetylation against micelle-induced aggregation becomes impaired. At higher SDS/protein ratios, N-acetylation favors another conformational transition, in which a second type of α-helix-rich, non-aggregating oligomers become stabilized. Once again, the Parkinson's disease mutations disconnect the influence of N-acetylation in promoting this transition. These results suggest a cooperative link between the N-terminus and the region of the mutations that may be important for α-Synuclein function

The effect of health care expenditures on survival in locally advanced and metastatic Non Small Cell Lung Cancer

Working Paper GATE 2009-03Context: The significant survival benefit of chemotherapy over best supportive care for locally advanced and metastatic NSCLC has been amply demonstrated in the literature. However, there is no clear evidence of the impact of the type of chemotherapy or of a superiority of combination chemotherapy over single-agent chemotherapy.Objective: The present study empirically examines, in real-life practise and using multiple proxies, the impact of health care expenditures on overall survival in locally advanced and metastatic NSCLC in order to guide medical decision-making.Methods: Disease characteristics, the resources used, the costs of treatment and survival data were retrospectively collected from the records of 175 patients treated between 2000 and 2004 at Léon Bérard Regional Cancer Center (Lyon, France). Survival data were modelled using multivariate Cox models and controlled for endogeneity with the instrumental variable method.Results: The median survival for the whole cohort was 289 days. The average total cost of treatment reached €35,160. Survival was significantly shorter for patients with stage IV disease, poor performance status, and past or concomitant cardiovascular disease and/or diabetes, for current smokers, and for patients with adenocarcinoma compared to large cell carcinoma. Survival duration was not significantly associated with the total cost of treatment per day of hospitalisation, the number of chemotherapy drugs administered, nor inpatient length of stay.Conclusion: Higher care expenditures do not appear to improve survival for patients with locally advanced or metastatic NSCLC. Hence, maintaining patient quality of life and tailoring therapy to stage, histology and comorbidities appears to be the less bad choice

Genetic regulation of amphioxus somitogenesis informs the evolution of the vertebrate head mesoderm

The evolution of vertebrates from an ancestral chordate was accompanied by the acquisition of a predatory lifestyle closely associated to the origin of a novel anterior structure, the highly specialized head. While the vertebrate head mesoderm is unsegmented, the paraxial mesoderm of the earliest divergent chordate clade, the cephalochordates (amphioxus), is fully segmented in somites. We have previously shown that fibroblast growth factor signalling controls the formation of the most anterior somites in amphioxus; therefore, unravelling the fibroblast growth factor signalling downstream effectors is of crucial importance to shed light on the evolutionary origin of vertebrate head muscles. By using a comparative RNA sequencing approach and genetic functional analyses, we show that several transcription factors, such as Six1/2, Pax3/7 and Zic, act in combination to ensure the formation of three different somite populations. Interestingly, these proteins are orthologous to key regulators of trunk, and not head, muscle formation in vertebrates. Contrary to prevailing thinking, our results suggest that the vertebrate head mesoderm is of visceral and not paraxial origin and support a multistep evolutionary scenario for the appearance of the unsegmented mesoderm of the vertebrates new 'head'

In Vivo Anti-Inflammatory Effect of a New Steroidal Saponin, Mannioside A, and Its Derivatives Isolated from Dracaena mannii

A new steroidal saponin, mannioside A (1), was isolated from the stem bark of Dracaena mannii, together with the known pennogenin (2), pennogenin-3-O-β-D-glucopyranoside (3) and pennogenin-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranoside (4). Their structures were determined using 1D-and 2D-NMR spectroscopy and mass spectrometry. Compounds 1 and 3 significantly inhibited carrageenan-induced paw edema in the rat; compound 4 was moderately active whereas 2 showed very weak activity

Parvovirus 4 in French in-patients: a study of haemodialysis and lung transplant cohorts

International audienceThe epidemiology and the clinical implication of human parvovirus 4 (PARV4) in human populations is still under evaluation. The distribution of PARV4 DNA was determined in cohorts of French haemodialysis and lung transplant patients. Plasma samples (n=289) were tested for PARV4 by real-time PCR assay (ORF2), and amplification products selected at random were sequenced. Analysis of available serological and biological markers was also undertaken. Fifty-seven samples out of 185 (30.8%) were positive for PARV4 DNA in the cohort of haemodialysis patients. A higher prevalence of the virus was identified in individuals with markers of HBV infection. PARV4 was also identified in 14 out of 104 samples (13.5%) from lung transplant recipients, with no clear-cut association with available clinical markers. Point mutations located on the zone of real-time detection were identified for some amplification products. This study describes the detection of PARV4 in the blood of haemodialysis and lung transplanted patients with significant difference in prevalence in these two cohorts. Further studies will be needed in order to understand better both the potential implication in host health and the natural history of this virus

A quantum dot-based frequency multiplier

Silicon offers the enticing opportunity to integrate hybrid quantum-classical computing systems on a single platform. For qubit control and readout, high-frequency signals are required. Therefore, devices that can facilitate its generation are needed. Here, we present a quantum dot-based radiofrequency multiplier operated at cryogenic temperatures. The device is based on the non-linear capacitance-voltage characteristics of quantum dot systems arising from their low-dimensional density of states. We implement the multiplier in a multi-gate silicon nanowire transistor using two complementary device configurations: a single quantum dot coupled to a charge reservoir and a coupled double quantum dot. We study the harmonic voltage conversion as a function of energy detuning, multiplication factor and harmonic phase noise and find near ideal performance up to a multiplication factor of 10. Our results demonstrate a method for high-frequency conversion that could be readily integrated into silicon-based quantum computing systems and be applied to other semiconductors.Comment: 17 pages, 16 figure

Sexual risk among Colombian adolescents: knowledge, attitudes, normative beliefs, perceived control, intention, and sexual behavior

Background: Colombia has one of the highest rates of the human immunodeficiency virus (HIV) and pregnancies - both of which are influenced by lack of condom use -, among adolescent population in Latin America; however, the mechanisms underlying the inconsistent use of condoms in this population are poorly understood. This descriptive and cross-sectional study’s purpose was to examine sexual behavior and its precursors using the theory of planned behavior (TPB) and considering gender-based differences. Another objective was to study the mediating effect of intention in the relationship between behavior precursors and condom use based on the TPB. Methods: We recruited 1100 adolescents aged between 14 and 19 years old (M = 15.94, SD = 1.30, 54.4% female) from Bogotá and Barranquilla, two of the cities with highest adolescent birth rates among adolescents in Colombia. Sociodemographic variables, knowledge on HIV and other sexually transmitted infections (STIs), HIV/AIDS-related attitudes, including attitudes toward the use of condoms, normative beliefs, perceived behavioral control, behavioral intention, and sexual behavior were assessed using self-reports. All analyses were run using SPSS v25. The indirect effect of intention to explain the relationship between precursors and the use of condoms during sexual intercourse was estimated using the PROCESS v3 macro. Results: Descriptive analyses suggest a high risk of contracting sexually transmitted infections and unplanned pregnancies associated to inconsistent condom use, medium-low level of knowledge about sexual health, low normative beliefs regarding peers’ condom use, and a certain perceived difficulty for using condoms. Condoms are used 71% of the times they have sex, but only 22% of the participants use them consistently; girls use condoms more consistently than boys. Sexual risk characteristics differed significantly by gender. Mediation analyses indicated that condom use intention mediates the relationship between behavioral precursors and frequency of condom use, according to the TPB. Conclusions: Findings provide a better understanding of sexual risk and highlight important implications for the sexual and reproductive health of adolescents. There is a need of designing and implementing protocolized sexual health promotion programs in schools with the aim of reducing sexual risk behaviors in Colombian adolescents