The GALAXIES inelastic hard X-ray scattering end-station at Synchrotron SOLEIL.

GALAXIES is an in-vacuum undulator hard X-ray micro-focused beamline dedicated to the study of the electronic structure of materials with high energy resolution using both photoelectron spectroscopy and inelastic X-ray scattering and under both non-resonant (NR-IXS) and resonant (RIXS) conditions. Due to the penetrating power of hard X-rays and the `photon-in/photon-out' technique, the sample environment is not a limitation. Materials under extreme conditions, for example in diamond anvil cells or catalysis chambers, thus constitute a major research direction. Here, the design and performance of the inelastic X-ray scattering end-station that operates in the energy range from ∼4 keV up to 12 keV is reported, and its capabilities are highlighted using a selection of data taken from recently performed experiments. The ability to scan `on the fly' the incident and scattered/emitted X-ray energies, and the sample position enables fast data collection and high experimental throughput. A diamond X-ray transmission phase retarder, which can be used to generate circularly polarized light, will also be discussed in the light of the recent RIXS-MCD approach.

Equation of state of liquid mercury to 520 K and 7 GPa from acoustic velocity measurements.

Ultrafast acoustics measurements on liquid mercury have been performed at high pressure and temperature in a diamond anvil cell using picosecond acoustic interferometry. We extract the density of mercury from adiabatic sound velocities using a numerical iterative procedure. We also report the pressure and temperature dependence of the thermal expansion, isothermal and adiabatic compressibility, bulk modulus, and pressure derivative of the latter up to 7 GPa and 520 K. We finally show that the sound velocity follows a scaling law as a function of density in the overall measured metallic state.

Impact of UV Radiation on the Raman Signal of Cystine: Implications for the Detection of S-rich Organics on Mars.

Traces of life may have been preserved in ancient martian rocks in the form of molecular fossils. Yet the surface of Mars is continuously exposed to intense UV radiation detrimental to the preservation of organics. Because the payload of the next rovers going to Mars to seek traces of life will comprise Raman spectroscopy tools, laboratory simulations that document the effect of UV radiation on the Raman signal of organics appear critically needed. The experiments conducted here evidence that UV radiation is directly responsible for the increase of disorder and for the creation of electronic defects and radicals within the molecular structure of S-rich organics such as cystine, enhancing the contribution of light diffusion processes to the Raman signal. The present results suggest that long exposure to UV radiation would ultimately be responsible for the total degradation of the Raman signal of cystine. Yet because the degradation induced by UV is not instantaneous, it should be possible to detect freshly excavated S-rich organics with the Raman instruments on board the rovers. Alternatively, given the very short lifetime of organic fluorescence (nanoseconds) compared to most mineral luminescence (micro- to milliseconds), exploiting fluorescence signals might allow the detection of S-rich organics on Mars. In any case, as illustrated here, we should not expect to detect pristine S-rich organic compounds on Mars, but rather by-products of their degradation.

All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial.

BACKGROUND: This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC). METHODS: Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m(-2) (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m(-2) (750 if >or=65 years of age) twice daily, on days 1-14. Treatment was continued until progression or unacceptable toxicity. RESULTS: A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36-66), including complete response in 4%. The clinical benefit rate (response or stable disease for >or=6 months) was 63% (95% CI, 48-77). The median duration of response was 7.2 months (95% CI, 6.4-10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8-9.7) and median overall survival was 29.2 months (95% CI, 18.2-40.1). Treatment-related adverse events were manageable, the main grade 3-4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed. CONCLUSION: These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MBC.

Assessing the unmet supportive care needs of newly diagnosed patients with cancer.

Adequate monitoring in cancer control needs to include measures of psychosocial outcomes so as to take account of the totality of the felt cancer experience. There is a need to know whether the experience of cancer is changing, as well as a need for tools to identify where supportive care interventions or services could be targeted to good effect. The aim of this study was to investigate the utility of using a telephone-administered survey to identify the unmet needs of cancer patients. Participants were identified from a statewide population-based cancer registry following an episode of hospitalized care in Victoria (Australia). Of the 506 eligible patients, 236 completed a telephone adaptation of the Supportive Care Needs Survey-Short Form (SCNS-SF31). Sampling from the cancer registry was shown to provide timely contact with patients. Results from the survey indicated that perceived needs for this newly diagnosed group of cancer patients were mostly in the area of information provision. Results also showed that some socio-demographic and disease-specific variables affected the level of perceived unmet needs. Overall, this study indicated that registry-based sampling was practical and the telephone adaptation of the SCNS-SF31 provided a reliable method to explore the unmet needs of newly diagnosed patients with cancer.

Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.

Congenital hyperinsulinism, or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is a glucose metabolism disorder characterized by unregulated secretion of insulin and profound hypoglycemia. From a morphological standpoint, there are two types of histopathological lesions, a focal adenomatous hyperplasia of islet cells of the pancreas in approximately 30% of operated sporadic cases, and a diffuse form. In sporadic focal forms, specific losses of maternal alleles (LOH) of the imprinted chromosomal region 11p15, restricted to the hyperplastic area of the pancreas, were observed. Similar mechanisms are observed in embryonal tumors and in the Beckwith-Wiedemann syndrome (BWS), also associated with neonatal but transient hyperinsulinism. However, this region also contains the sulfonylurea receptor (SUR1) gene and the inward rectifying potassium channel subunit (KIR6.2) gene, involved in recessive familial forms of PHHI, but not known to be imprinted. Although the parental bias in loss of maternal alleles did not argue in favor of their direct involvement, the LOH may also unmask a recessive mutation leading to persistent hyperinsulinism. We now report somatic reduction to hemizygosity or homozygosity of a paternal SUR1 constitutional heterozygous mutation in four patients with a focal form of PHHI. Thus, this somatic event which leads both to beta cell proliferation and to hyperinsulinism can be considered as the somatic equivalent, restricted to a microscopic focal lesion, of constitutional uniparental disomy associated with unmasking of a heterozygous parental mutation leading to a somatic recessive disorder.

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.

Detection of Echinococcus multilocularis in wild boars in France using PCR techniques against larval form.

Recently, new data have been collected on the distribution and ecology of Echinococcus multilocularis in European countries. Different ungulates species such as pig, goat, sheep, cattle and horse are known to host incomplete development of larval E. multilocularis. We report a case of E. multilocularis portage in two wild boars from a high endemic area in France (Department of Jura). Histological examination was performed and the DNA was isolated from hepatic lesions then amplified by using three PCR methods in two distinct institutes. Molecular characterisation of PCR products revealed 99% nucleotide sequence homology with the specific sequence of the U1 sn RNA gene of E. multilocularis, 99 and 99.9% nucleotide sequence homology with the specific sequence of the cytochrome oxydase gene of Echinococcus genus and 99.9% nucleotide sequence homology with a genomic DNA sequence of Echinococcus genus for the first and the second wild boar, respectively.

Thermodynamic properties of liquid gallium from picosecond acoustic velocity measurements.

Due to discrepancies in the literature data the thermodynamic properties of liquid gallium are still in debate. Accurate measurements of adiabatic sound velocities as a function of pressure and temperature have been obtained by the combination of laser picosecond acoustics and surface imaging on sample loaded in diamond anvil cell. From these results the thermodynamic parameters of gallium have been extracted by a numerical procedure up to 10 GPa and 570 K. It is demonstrated that a Murnaghan equation of state accounts well for the whole data set since the isothermal bulk modulus BT has been shown to vary linearly with pressure in the whole temperature range. No evidence for a previously reported liquid-liquid transition has been found in the whole pressure and temperature range explored.

Picosecond acoustics method for measuring the thermodynamical properties of solids and liquids at high pressure and high temperature.

Based on the original combination of picosecond acoustics and diamond anvils cell, recent improvements to accurately measure hypersonic sound velocities of liquids and solids under extreme conditions are described. To illustrate the capability of this technique, results are given on the pressure and temperature dependence of acoustic properties for three prototypical cases: polycrystal (iron), single-crystal (silicon) and liquid (mercury) samples. It is shown that such technique also enables the determination of the density as a function of pressure for liquids, of the complete set of elastic constants for single crystals, and of the melting curve for any kind of material. High pressure ultrafast acoustic spectroscopy technique clearly opens opportunities to measure thermodynamical properties under previously unattainable extreme conditions. Beyond physics, this state-of-the-art experiment would thus be useful in many other fields such as nonlinear acoustics, oceanography, petrology, in of view. A brief description of new developments and future directions of works conclude the article.

cDNA cloning, tissue distribution and chromosomal localization of the human ID4 gene.

A cDNA e encoding the human Id4 protein has been isolated from an astrocytoma library. The predicted protein product shares 98% identity with the mouse Id4 protein and is markedly different from that already reported. By FISH analysis, the human ID4 gene was more precisely mapped to chromosome 6p22.3-p23. Northern blot analysis showed that ID4 is mainly expressed in thyroid, brain and fetal tissue and in some nervous system tumor cell lines.

Effects of iridovirus-like agent on the cell-mediated immunity in sheatfish (Silurus glanis)--an in vitro study.

An iridovirus-like agent was tested for the first time in vitro on cell-mediated immunity in sheatfish (Silurus glanis). The influence of the iridovirus-like agent on pronephric macrophage metabolism was examined at two temperatures, 20 and 30 degrees C, by studying the respiratory burst activity stimulated by phorbol myristate acetate as well as the proliferative ability of lymphocytes stimulated by concanavalin A (ConA) and lipopolysaccharide (LPS) measured by MTT assay. The results showed that the iridovirus-like agent decreased the macrophage activity at incubation temperatures of 20 and 30 degrees C. The highest inhibitory effect was observed at 30 degrees C. The proliferative ability of pronephric lymphocytes had a similar pattern. The results showed that applying a virus at the same time or after the mitogen at 20 and 30 degrees C decreased the lymphocyte proliferation that was stimulated by either ConA or LPS. The highest suppressive effect was observed when virus was applied 14 h after the mitogen. This preliminary in vitro study demonstrated a strong suppressive influence of the iridovirus-like agent on pronephric macrophage and lymphocyte activity in sheatfish.

Immunostimulatory effects of dimerized lysozyme (KLP-602) on the nonspecific defense mechanisms and protection against furunculosis in salmonids.

Utilization of natural immunostimulants in fish culture offers a wide range of attractive methods for inducing and building protection against diseases. Lysozyme is an enzyme with bacteriolytic properties and is ubiquitous in its distribution among living organisms. This enzyme has antiviral, antibacterial and anti-inflammatory properties. In nature, lysozyme is found as a monomer. Lysozyme dimer is significantly less toxic than its monomer, and its high biological activity has been ascertained in cases of both viral and bacterial infections. In our study, we examined the influence of dimerized lysozyme (KLP-602) on the nonspecific cellular and humoral defense mechanisms and protection against furunculosis in rainbow trout (Oncorhynchus mykiss). We have analyzed the immunomodulatory effects of KLP-602 after experimental infection by Aeromonas salmonicida. Application of dimerized lysozyme (KLP-602) by injection stimulated the cellular and humoral defense mechanisms and provided protection against furunculosis. By contrast, mortality rate was reduced to 45% (one injection) and 25% (three injections) using 10 or 100 microg/kg KLP-602. Mortality in the untreated control group was 85%.

Prevalence of workplace smoking bans in Victoria.

Restrictions on smoking in the Victorian workplace have been measured since 1988. This paper investigates whether the trend of increasing prevalence of total bans found between 1988 and 1992 has continued. Estimates are based on workers' reports of the restrictions on smoking that apply at their workplaces. For indoor workers a total ban on smoking restrictions in the workplace has increased from 58% in 1992 to 66% in 1995. White collar workers continue to enjoy a higher rate of protection than blue collar workers. Factories, warehouses, hotels and restaurants are the worksites least likely to have restrictions. Bans result in considerable exiled smoking: half the smokers reported going out to smoke during working hours on their last work day.

[Detection of the eggs of Echinococcus multilocularis Leuckart, 1863, in the feces of the fox (Vulpes vulpes Linnaeus, 1758) by the polymerase chain reaction]. / Détection des oeufs d'Echinococcus multilocularis Leuckart, 1863 dans les fèces de renard (Vulpes vulpes Linnaeus, 1758) par amplification en chaîne par polymérase.

The polymerase chain reaction (PCR) was applied to the identification of eggs of Echinococcus multilocularis in faeces from foxes. The test was positive in three of six faeces samples from foxes which were harbouring adult worms, and in one of four samples from foxes in which no adult E. multilocularis was found in the intestines. These initial results show that it is possible to use PCR to identify E. multilocularis eggs in faeces. PCR can be used to complement examination of intestinal contents, showing that the distribution of eggs in faeces is uneven. The sensitivity of the test was estimated to be 50 eggs in 5 g of faeces. Further work is needed to confirm these initial results before the test can be used more widely.

In vitro immunomodulating influence of methisoprinol on the head kidney phagocyte and lymphocyte activity after suppression induced by VHSV in rainbow trout (Oncorhynchus mykiss).

The aim of this study was to evaluate the in vitro influence of methisoprinol on head kidney phagocyte and lymphocyte activity after suppression induced by VHSV. The VHSV statistically significantly decreased the respiratory burst activity of head kidney phagocytes and the proliferative response of lymphocytes stimulated by ConA. The results of our study showed that methisoprinol at a concentration of 100 microl/ml modulated and restored the phagocyte and lymphocyte activity suppressed by VHSV.

Influence of methisoprinol on the replication of rhabdoviruses isolated from carp (Cyprinus carpio) and catfish (Ictalurus melas): in vitro study.

Rhabdoviruses constitute one of the most pathogenic viruses isolated from rainbow trout and carp culture. Several viruses were also isolated from other species of fish. These viruses are mostly associated with epizootics and heavy losses. Spring viraemia of carp virus (SVCV) and pike fry rhabdovirus (PFRV) have been the most extensively studied, due to their significant economic impact. Significant progress has been made towards controlling the major bacterial fish diseases using vaccines, but this approach has not yet been successful in preventing viral diseases in fish culture. However, for an effective therapeutic approach, specific drugs should be developed to selectively inhibit virus replication and/or stimulate antiviral protection. In this investigation we examined the in vitro influence of methisoprinol on the SVCV and virus isolated from catfish (Ictalurus melas) replication by measuring their RNA synthesis. The viruses were propagated in EPC cells and cell cultures containing methisoprinol were followed by infection with SVCV or catfish rhabdovirus suspension containing 10(7) TCID50/ml. Methisoprinol (Polfa, Poland) at concentrations of 0, 100, 200, 300, 400 and 500 microg/ml of medium (Glasgow MEM) was used in this study. The results of this study show the strong inhibition of incorporation (cpm) of [3H]-uridine into SVCV and catfish rhabdovirus RNA in cell culture exposed to methisoprinol at various concentrations. The highest percent of inhibition of viral RNA at 72 h after infection with two rhabdoviruses were observed in doses of 400 and 500 microg/ml of methisoprinol in medium. The results of this in vitro study showed that methisoprinol inhibits the rhabdoviruses isolated from carp and catfish.

How surface composition of high milk proteins powders is influenced by spray-drying temperature.

High milk proteins powders are common ingredients in many food products. The surface composition of these powders is expected to play an essential role during their storage, handling and/or final application. Therefore, an eventual control of the surface composition by modifying the spray-drying temperature could be very useful in the improvement of powder quality and the development of new applications. For this purpose, the influence of five spray-drying temperatures upon the surface composition of the powders was investigated by X-ray photoelectron spectroscopy. The major milk proteins were studied: native micellar casein and native whey, both more or less enriched in lactose. The results show a surface enrichment in lipids for all the powders and in proteins for many powders. Whatever the drying temperature, lipids and proteins are preferentially located near the surface whereas lactose is found in the core. This surface enrichment is also highly affected by the spray-drying temperature. More lipids, more proteins and less lactose are systematically observed at the surface of powders spray-dried at lower outlet air temperatures. The nature of proteins is also found essential; surface enrichment in lipids being much stronger for whey proteins containing powders than for casein containing powders. Additionally, we found a direct correlation between the lipids surface concentration and the wetting ability for the 25 powders studied.