Search

Contains fulltext : 168280.pdf (Publisher’s version ) (Open Access) Ethics has been identified as a key element in Health Technology Assessment (HTA) since its conception. However, ethical issues are still not frequently addressed explicitly in HTA. Several valuable reasons have been identified. The basis of the article is the claim that ethics is often not part of HTA for "epistemological reasons". Hence, the main aim of the contribution is to explore in more details and emphasize them by using the fact/value dichotomy. Our conclusion is that current HTA configuration is predominantly based on the comparison among objective and empirically testable "facts", whilst ethics is not empirically testable. In this sense, there is a sort of "epistemological gap", which can explain why it is so difficult to integrate ethics in HTA. We suggest that the epistemological differences among the various domains of HTA are addressed more explicitly.

We measured the concentrations and isotopic compositions of He Ne and Ar in 14 fragments from 12 different meteorites: three carbonaceous chondrites six L chondrites (three most likely paired) one H chondrite one R chondrite and one ungrouped chondrite. The data obtained for the CV3 chondrites Ramlat as Sahmah (RaS) 221 and RaS 251 support the hypothesis of exposure age peaks for CV chondrites at approximately 9Ma and 27Ma. The exposure age for Shir 033 (CR chondrite) of 7.3Ma is also indicative of a possible CR chondrite exposure age peak. The three L chondrites Jiddat al Harasis (JaH) 091 JaH 230 and JaH 296 which are most likely paired fall together with Hallingeberg into the L chondrite exposure age peak of approximately 15Ma. The two L chondrites Shelburne and Lake Torrens fall into the peaks at approximately 40Ma and 5Ma respectively. The ages for Bassikounou (H chondrite) and RaS 201 (R chondrite) are approximately 3.5Ma and 5.8Ma respectively. Six of the studied meteorites show clear evidence for 3He diffusive losses the deficits range from approximately 17 for one Lake Torrens aliquot to approximately 45 for RaS 211. The three carbonaceous chondrites RaS 221 RaS 251 and Shir 033 all have excess 4He either of planetary or solar origin. However very high 4He/20Ne ratios occur at relatively low 20Ne/22Ne ratios which is unexpected and needs further study. The measured 40Ar ages fit well into established systematics. They are between 2.5 and 4.5Ga for the carbonaceous chondrites older than 3.6Ga for the L and H chondrites and about 2.4Ga for the R chondrite as well as for the ungrouped chondrite. Interestingly none of our studied L chondrites has been degassed in the 470Ma break up event. Using the amount of trapped 36Ar as a proxy for noble gas contamination due to terrestrial weathering we are able to demonstrate that the samples studied here are not or only very slightly affected by terrestrial weathering (at least in terms of their noble gas budget).

We describe a new high-purity germanium (HPGe) detector setup for low-background ��-ray spectrometry. The GeMSE facility (Germanium Material and meteorite Screening Experiment) is dedicated to material screening for rare event searches in astroparticle physics as well as to the characterization of meteorites. It is installed in a medium depth (~620 m.w.e.) underground laboratory in Switzerland in a multi-layer shielding and is equipped with an active muon veto. We have reached a very competitive integral background rate of (246$\pm$2) counts/day (100-2700 keV) and measured a sensitivity of $\sim$0.5-0.6 mBq/kg for long-lived isotopes from the $^{238}$U/$^{232}$Th chains in a $\sim$1\,kg sample screened for $\sim$27 days. An extrapolation to higher sample masses and measurement times suggests a maximum sensitivity in the $\mathcal{O}(50)$ ��Bq/kg range. We describe the data analysis based on Bayesian statistics, background simulations, the efficiency calibration and first sample measurements.

We tested a handheld X ray fluorescence instrument with adaptable matrix correction for its suitability in meteoritics. We report here the instrument setup precision and accuracy and present examples of applications. With a measuring time of 300 s it is possible to collect accurate data for K Ca Ti Cr Mn Fe Co Ni Sr and Ba that are needed for the identification of doubtful meteorites and the nondestructive classification of chondrites and achondrites. The factory supplied calibration curve of the instrument was fine tuned for our purposes with the use of well analyzed meteorite powders pressed pellets and meteorite hand specimens as standards. Relative errors of 10 to 20 are reached for the mentioned elements. The instrument was tested in the hot desert of Oman while searching for meteorites and also in the laboratory while doing research on meteorites. The main applications of the instrument are the identification and classification of meteorites the quantification of terrestrial elemental contamination (Sr and Ba) and detection of Mn rich desert varnish. It is possible to discriminate the major meteorite groups using Fe/Mn and Ni values. Handheld X ray fluorescence is also useful in identifying meteorites belonging to the same fall event.

A series of 10 analogues of platelet-activating factor (PAF) was evaluated for proaggregatory and inhibitory behaviour on human blood platelets in vitro. Most of the compounds did not activate platelets but inhibited the PAF-induced aggregation. The inhibition was concentration-dependent and selective for PAF. Platelet responses to ADP and collagen were not suppressed. Schild analysis of the aggregation data was consistent with a simple competitive antagonism. The pA2 of the most effective antagonist (1-O-hexadecyl-2-O-ethylglycero-3-phosphoric acid-6'-(1-chinuclidinium)-hexylester) was 5.96. There is also evidence for its ability to inhibit the high affinity binding of [3H]PAF to the platelet receptors.

An overview and status report of the new trapping facility for highly charged ions at the Gesellschaft fuer Schwerionenforschung is presented. The construction of this facility started in 2005 and is expected to be completed in 2008. Once operational, highly charged ions will be loaded from the experimental storage ring ESR into the HITRAP facility, where they are decelerated and cooled. The kinetic energy of the initially fast ions is reduced by more than fourteen orders of magnitude and their thermal energy is cooled to cryogenic temperatures. The cold ions are then delivered to a broad range of atomic physics experiments., Comment: 8 pages, 11 figures

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VII has 572 predicted open reading frames (ORFs), of which 341 are new. No correlation was found between G+C content and gene density along the chromosome, and their variations are random. Of the ORFs, 17% show high similarity to human proteins. Almost half of the ORFs could be classified in functional categories, and there is a slight increase in the number of transcription (7.0 %) and translation (5.2 %) factors when compared with the complete S. cerevisiae genome. Accurate verification procedures demonstrate that there are less than two errors per 10,000 base pairs in the published sequence

The vitamin D3 derived hormone 1.25 (OH)2 vitamin D3 (1,25 D3) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1.25 D3 reduced proliferation as measured by 3H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 4.8 nM. The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4. The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33. When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia.

The avermectins ivermectin and doramectin and the milbemycins milbemycin A4 oxime and moxidectin were tested for filaricidal activity in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi, and B. pahangi. Single subcutaneous doses of 0.005-5 mg/kg (L. carinii), 0.0005-0.5 mg/kg (A. viteae), 0.5 and 5 mg/kg (B. malayi), and 5 mg/kg (B. pahangi) were injected. Necropsies were performed 42 days after treatment. The avermectins caused a strong and rapid reduction of microfilaraemia in L. carinii and A. viteae infections within a few hours after treatment but showed only moderate efficacies on microfilariae of Brugia spp. The effects of the milbemycin derivatives on L. carinii and A. viteae microfilariae were generally weaker than those of the avermectins. However, moxidectin was comparatively active against microfilariae of Brugia spp. Subsequently the parasitaemia levels of L. carinii and A. viteae infected animals remained either almost completely depressed or tended to reincrease in a dose dependent manner whereas there was generally a continuous decrease of microfilaraemia levels in Brugia spp. infected animals. Adulticidal effects were limited to A. viteae although with neither dose of neither drug95% reductions of adult worm counts were reached. However, pathogenic influences of the drugs were observed on intrauterine embryonic stages of the parasites.

A series of 8 analogues of platelet-activating factor (PAF) in which both the acetyl group and the polar head are changed, were tested for biological activities on human and rabbit platelets in plasma. Two of these compounds, 1-0-hexadecyl-2-0-ethyl-rac-glycero-3-phosphoric acid-5′-trimethylammoniumpentyl ester and 1-0-hexadecyl-20-ethyl-rac-glycero-3-phosphoric acid-6′-trimethylammoniumhexyl ester inhibit selectively the PAF-induced aggregation response without showing any agonistic activity. Schild analysis revealed a competitive antagonism and K B , values of 4.4 and 10.5 μmol/1, respectively. These results point to a crucial role of the distance between the phosphoryl group and the polar head for expression of PAF-antagonistic properties. Moreover, the substituent at the 2-position was found to influence predominantly the agonistic behaviour.

Platelets are prepared from human native blood by a two-step procedure without use of anticoagulants. The first step involves Sephadex gel filtration of native blood to prevent clotting by the removal of plasma calcium. In a second step platelets are separated from other blood cells and plasma constituents by centrifugation of the gel filtered blood on a Ficoll density gradient. During the whole procedure a pH of 7.4 is maintained. As a first measure for the cell integrity the morphological feature of the platelets was evaluated and compared to platelet-rich plasma (PRP) which was prepared with different anticoagulants at physiological pH. Considering the extent of pseudopod formation the anticoagulant-free prepared platelets reveal a less activated state than the platelets in PRP.

The degradation of platelet-activating factor (PAF) and lipid concentrations were measured in sera from 20 patients with insulin-dependent diabetes mellitus and from 20 age- and sex-matched healthy volunteers. The PAF-degrading capacity as well as triglycerides and total and very low density and low-density lipoprotein cholesterol were found to be significantly increased in the patients group, whereas the difference observed in high-density lipoprotein cholesterol was statistically nonsignificant. There were also a series of close relationships between the degradation of PAF and some lipid variables in the control group. These results confirm the parallel changes of lipoproteins and PAF-degrading capacity described previously in serum from atherosclerotic patients and extend it to patients suffering from diabetes mellitus.

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.

The participation of blood platelets in physiological and pathological events is necessarily preceeded by an activation of the respective cells apparent In the changing of the shape, increasing adhesivenes, aggregation and release. The underlying metabolic reaction sequences, as well as the changes in structural components, are not completely understood. The results obtained previously caused us to think about the possible existence of a regulatory function played by the cellular levels of reduced glutathione (GSH) and NADPH in the activation process: During the platelet aggregation induced by arachidonic acid (AA), the cellular levels of both compounds fall rapidly off in the initial phase, being subsequently normalized by a powerful stimulation of the hexose monophosphate shunt (B.IPS) (1). Diminished capacity of the HMPS in platelets genetically deficient in glucose-6-phosphate dehydrogenase is accompanied by decreased levels of both compounds and by altered platelet aggregation (2).

Platelets appear to be involved in the development of vascular diseases in diabetic patients. In a number of studies, platelet adhesion and aggregation has been found to be enhanced in diabetic patients indicating a platelet hyperreactivity. However, contradictory results on hyperreactivity of diabetic platelets towards agonists published in the literature leading to the problem of reliability of agonist-induced aggregation as a parameter which is able to reflect an altered platelet reactivity. Therefore, we introduced the quantification of actin filaments of platelets as an early indicator of platelet hyperreactivity. In 20 patients with type I diabetes mellitus agonist-induced aggregation, spontaneous aggregation, malondialdehyde (MDA)-formation, plasma lipid status and the ability of plasma to degrade platelet activating factor (PAF) as well as the G- to F-actin equilibrium of platelets were assayed. Compared to an age- and sex-matched control group F-actin values, spontaneous aggregation and PAF-hydrolase were significantly increased in diabetic patients.

n/a

n/a

International audience

International audience

International audience

We analyzed the molybdenum (Mo) isotope compositions (IC) of 59 samples from two molybdenite mineralizations (Alpjahorn and Grimsel) and from a Mo-rich hydrothermal breccia (Grimsel) from the Aar Massif, Switzerland. The formation temperature of the Late Paleozoic Mo mineralizations (300–600 C) is much higher than that of the Pliocene breccia (100–160 C). The Mo IC of the molybdenites varies over 1.35&. Even in a single hand specimen it spans 0.45&, indicating that fractionation processes during molybdenite precipitation can vary on a cm scale. The Mo IC of most molybdenites analyzed here are significantly heavier than that of the host rock (d 98/95 Mo = (0.05 ± 0.1)&) and show a bimodal distribution centered around d 98/95 Mo � 1.1& and 0.2&. This result rules out single stage Rayleigh fractionation as the relevant formation mechanism and instead, redox variations are suggested to be a main factor controlling the Mo IC of the studied high-temperature Mo deposits. The range of the Mo IC in one single deposit, the Alpjahorn, overlaps with the variation range of almost all other published values for Mo IC in Mo deposits. Compared to the molybdenites, the breccia shows an even wider variation of 3.0& (d 98/95 Mo between � 1.6& and +1.4&). In contrast to the high-T molybdenite deposits, here the Mo was transported via oxidized surface waters into the breccia system, where it was reduced and precipitated. This indicates that oxidation and reduction of Mo complexes may lead to highly variable Mo IC in hydrothermal systems. 2011 Elsevier Ltd. All rights reserved.

Returning samples from Mars to Earth for scientific analysis has been, and continues to be, among the highest priority objectives of planetary science. Partly for this reason, the 2011 Planetary Science Decadal Survey placed high priority on a proposed 2018 rover mission that would conduct careful in situ science and use that scientific information to select and cache samples that could be returned to Earth by a potential future mission. In order to ensure that the potential contributions of the 2018 rover to the proposed MSR Campaign are properly planned, this study was undertaken to consider the science of the MSR Campaign concept from end to end. This white paper is the principal output of the Mars Sample Return (MSR) End-to-End International Science Analysis Group (E2E-iSAG): a group chartered by MEPAG (Mars Exploration Program Analysis Group).

The lunar meteorite Sayh al Uhaymir 169 consists of an impact melt breccia extremely enriched with potassium, rare earth elements, and phosphorus [thorium, 32.7 parts per million (ppm); uranium, 8.6 ppm; potassium oxide, 0.54 weight percent], and adherent regolith. The isotope systematics of the meteorite record four lunar impact events at 3909 +/- 13 million years ago (Ma), approximately 2800 Ma, approximately 200 Ma, and0.34 Ma, and collision with Earth sometime after 9.7 +/- 1.3 thousand years ago. With these data, we can link the impact-melt breccia to Imbrium and pinpoint the source region of the meteorite to the Lalande impact crater.