Measuring the Berry phase of graphene from wavefront dislocations in Friedel oscillations.

Electronic band structures dictate the mechanical, optical and electrical properties of crystalline solids. Their experimental determination is therefore crucial for technological applications. Although the spectral distribution in energy bands is routinely measured by various techniques1, it is more difficult to access the topological properties of band structures such as the quantized Berry phase, γ, which is a gauge-invariant geometrical phase accumulated by the wavefunction along an adiabatic cycle2. In graphene, the quantized Berry phase γ = π accumulated by massless relativistic electrons along cyclotron orbits is evidenced by the anomalous quantum Hall effect4,5. It is usually thought that measuring the Berry phase requires the application of external electromagnetic fields to force the charged particles along closed trajectories3. Contradicting this belief, here we demonstrate that the Berry phase of graphene can be measured in the absence of any external magnetic field. We observe edge dislocations in oscillations of the charge density ρ (Friedel oscillations) that are formed at hydrogen atoms chemisorbed on graphene. Following Nye and Berry6 in describing these topological defects as phase singularities of complex fields, we show that the number of additional wavefronts in the dislocation is a real-space measure of the Berry phase of graphene. Because the electronic dispersion relation can also be determined from Friedel oscillations7, our study establishes the charge density as a powerful observable with which to determine both the dispersion relation and topological properties of wavefunctions. This could have profound consequences for the study of the band-structure topology of relativistic and gapped phases in solids.

[At-risk drinking screening by general practitioners: A survey of patients in primary care]. / Repérage de la consommation d'alcool à risque par les médecins généralistes : enquête auprès de patients en soins premiers.

BACKGROUND: The screening of patients who are at-risk drinkers, which means exceeding the thresholds defined by health authorities or associated with a specific situation (taking psychotropic drugs, having an organic pathology, driving a vehicle, drinking during pregnancy), represents a major issue in primary care. Few studies have offered perspective from the patients' standpoint. The main purpose of this study was to describe general practitioners at-risk drinking screening from their patients point of view. The secondary objective was to identify the factors associated with perception of satisfactory general practitioner knowledge about alcohol consumption. METHODS: A quantitative cross-sectional study was launched in 9 general practitioner offices over 6 months. Patients older than 18 were recruited to answer a questionnaire blinded from their general practitioner, indicating the level of their alcohol consumption and their perception regarding their general practitioner's screening methods. Descriptive, univariate and multivariate logistic regression analyses were performed. RESULTS: All in all, 445 patients were analyzed. Sixty-two at-risk drinkers were screened (13.9 %). Most of the patients declared they had not been interviewed about their alcohol consumption by their general practitioner either during initial consultations (86.1 %) or over time (83.3 %). Only 4.2 % of patients had previously initiated discussion about their consumption. Patients were not ashamed to talk about alcohol (99.2 %) and found their general practitioner to be competent on this topic (100 %). In multivariate analysis, independent factors associated with a good general practitioner knowledge about their patients' current consumption were the questions put forward by their general practitioner about alcohol consumption during their first visit (P<0.001) and during subsequent visits (P<0.001). CONCLUSION: This study showed a low general practitioner screening rate of their patients' at-risk drinking. Only a minority of patients, including at-risk drinkers, declared that their general practitioner was aware of their level of alcohol consumption. Screening could be improved by being systematized during initial consultations and regularly scheduled during subsequent visits, especially in at-risk situations.

Effects 4.5 years after an interactive GP educational seminar on antibiotic therapy for respiratory tract infections: a randomized controlled trial.

BACKGROUND: The few studies assessing long-term effects of educational interventions on antibiotic prescription have produced conflicting results. OBJECTIVES: Our aim was to assess the effects after 4.5 years of an interactive educational seminar designed for GPs and focused on antibiotic therapy in respiratory tract infections (RTIs). The seminar was expected to decrease antibiotic prescriptions for any diagnosis. METHODS: We conducted a randomized controlled parallel-group trial in a Paris suburb (France), with GPs as the randomization unit and prescriptions as the analysis unit. The intervention occurred in September 2004 and the final assessment in March 2009. Among 203 randomized GPs, 168 completed the study, 70 in the intervention group and 98 in the control group. Intervention GPs were randomized to attending only a 2-day interactive educational seminar on evidence-based guidelines about managing RTIs or also 1 day of problem-solving training. The primary outcome was the percentage of change in the proportion of prescriptions containing an antibiotic for any diagnosis in 2009 versus 2004. An intention-to-treat sensitivity analysis was performed using multiple imputation. RESULTS: After 4.5 years, absolute changes in the primary outcome measure were -1.1% (95% confidence interval: -2.2 to 0.0) in the intervention group and +1.4% (0.3-2.6) in the control group, yielding an adjusted between-group difference of -2.2% (-2.7 to -1.7; P < 0.001). Both intervention modalities had significant effects, and multiple imputation produced similar results. CONCLUSIONS: A single, standardized and interactive educational seminar targeting GPs significantly decreased antibiotic use for RTIs after 4.5 years.

Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer.

BACKGROUND: To evaluate capecitabine-docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC). PATIENTS AND METHODS: Patients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m(2) twice daily, days 1-14, plus docetaxel 36 mg/m(2), days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The primary end point was pathologic complete response (pCR) rate, evaluated separately in HER2-negative and HER2-positive cohorts. Secondary end points included clinical response rates and tolerability. RESULTS: The pCR rate was 15% [95% confidence interval (CI) 7-28] in 53 patients receiving XT and 40% (95% CI 26-55) in 50 patients receiving HXT. After neoadjuvant therapy, 50 patients receiving XT and 45 receiving HXT underwent surgery. No unexpected toxicity was observed: the most common grade ≥3 adverse events were diarrhea/mucositis (30% and 20%, respectively) and grade 3 hand-foot syndrome (11% and 6%, respectively). Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort. CONCLUSION: Neoadjuvant XT (HXT in HER2-positive disease) is highly effective in inoperable LABC, demonstrating pCR rates of 15% and 40%, respectively. This non-anthracycline-containing regimen offers obvious benefits in early disease, where avoidance of long-term cardiotoxicity is particularly important.

Impact of valley polarization on the resistivity in two dimensions.

We examine the temperature dependence of resistivity in a two-dimensional electron system formed in a silicon-on-insulator quantum well. The device allows us to tune the valley splitting continuously in addition to the electron density. Our data provide a global picture of how the resistivity and its temperature dependence change with valley polarization. At the boundary between valley-polarized and partially polarized regions, we demonstrate that there is an insulating contribution from spin-degenerate electrons occupying the upper valley-subband edge.

CD8 beta increases CD8 coreceptor function and participation in TCR-ligand binding.

To study the role of CD8 beta in T cell function, we derived a CD8 alpha/beta-(CD8-/-) T cell hybridoma of the H-2Kd-restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8 alpha alone or together with CD8 beta. All three hybridomas released interleukin 2 upon incubation with L cells expressing Kd-peptide derivative complexes, though CD8 alpha/beta cells did so more efficiently than CD8 alpha/alpha and especially CD8-/- cells. More strikingly, only CD8 alpha/beta cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab' fragments of the anti-Kd alpha 3 monoclonal antibody SF1-1.1.1 or substitution of Kd D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR-ligand binding on CD8 alpha/beta cells was approximately 5- and 20-fold more avid than on CD8 alpha/a and CD8-/- cells, respectively. SF1-1.1.1 Fab' or Kd mutation D227K reduced the TCR photoaffinity labeling on CD8 alpha/beta cells to approximately the same low levels observed on CD8-/- cells. These results indicate that CD8 alpha/beta is a more efficient coreceptor than CD8alpha/alpha, because it more avidly strengthens TCR-ligand binding.

Different roles for the Fc epsilon RI gamma chain as a function of the receptor context.

The high affinity immunoglobulin E receptor (Fc epsilon RI) and the B and T cell antigen receptors (TCR) are multimeric complexes containing subunits with cytoplasmic antigen recognition activation motifs (ARAMs). The presence of multiple motifs may be a way to amplify a single signal or provide independent activation modules. Here we have compared the signaling capacity of the same Fc epsilon RI gamma motif in the context of two different receptors, Fc epsilon RI and TCR/CD3, simultaneously reconstituted on the surface of the same zeta-deficient T cell line. Both reconstituted receptors mediate early (phosphorylation) and late (interleukin [IL]-2 release) signals. Mutation of the two tyrosine residues of ARAM gamma alters early signaling by both receptors, but the set of substrates phosphorylated via ARAM gamma is different for each receptor and is thus dependent on the receptor context. Furthermore, the mutations prevent Fc epsilon RI- but not TCR/CD3-mediated IL-2 release. These data demonstrate that ARAM gamma is necessary for allowing both receptors to phosphorylate the complete set of substrates, and that the CD3 complex, unlike the Fc epsilon RI beta chain, contains activation modules capable of compensating for the absence of a functional ARAM gamma in generating late signals such as IL-2 release.

Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study.

OBJECTS: Technical aspects of local chemotherapy in inoperable brainstem gliomas by convection-enhanced delivery (CED) are still under experimental considerations. In this study, we characterize the feasibility of multiple cannula placements in the rat brainstem. MATERIALS AND METHODS: In 38 male Fisher rats, up to three guided screws were positioned in burr holes paramedian at 2.5 mm anterior and posterior to as well as at the lambdoid suture. Using Alzettrade mark pumps (1 microl/h flow rate over 7 days) either vehicle (5% dextrose) or 0.1 mg carboplatin was delivered via one, two, or three cannulas, respectively. During cannula insertion, electrocardiogram and respiratory rate was monitored. All rats were subsequently evaluated neurologically for 8 days. For drug distribution in coronal sections, the brain tissue concentration of platinum was measured. HE staining was used to evaluate the local site of drug delivery. Heart and respiratory rate remained within normal range during surgical procedure. Neurological scoring showed only mild neurological impairment in the groups receiving two or three cannulas, which resolved after vehicle delivery. However, after carboplatin delivery, this deficit remained unchanged. Drug distribution was more homogeneous in the three cannula group. Histological slices visualized edematous changes at the sight of cannula placement. CONCLUSION: The unilateral application of up to three cannulas in the brainstem of rats for local drug delivery studies is feasible. The remaining neurological deficit in carboplatin-treated animals underlines the need of low toxicity drugs for CED in the brainstem.

Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model.

OBJECTIVE: Convection-enhanced delivery using carboplatin in brainstem glioma models was reported to prolong survival. Functional impairment is of additional importance to evaluate the value of local chemotherapy. We established a neurological scoring system for the rat brainstem glioma model. MATERIAL AND METHODS: In 46 male Fisher rats stereotactically 10(5) F-98 cells were implanted at 1.4-mm lateral to midline and at the lambdoid suture using guided screws. Following 4 days local delivery was performed using Alzet pumps (1 microl/h over 7 days) with either vehicle (5% dextrose) or carboplatin via one or two cannulas, respectively. All rats were subsequently tested neurologically using a specified neurological score. In 38 animals survival time was recorded. Representative MR imaging were acquired in eight rats, respectively, at day 12 after implantation. HE staining was used to evaluate tumor extension. RESULTS: Neurological scoring showed significantly higher impairment in the high dose carboplatin group during the treatment period. Survival was significantly prolonged compared to control animals in the high dose carboplatin-one cannula group as well as in both low dose carboplatin groups (18.6 +/- 3 versus 26.3 +/- 9, 22.8 +/- 2, 23.6 +/- 2 days; p < 0.05). Overall neurological grading correlated with survival time. MR imaging showed a focal contrast enhancing mass in the pontine brainstem, which was less exaggerated after local chemotherapy. Histological slices visualized decreased cellular density in treatment animals versus controls. CONCLUSION: Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival. Our neurological grading enables quantification of drug and tumor-related morbidity as an important factor for functional performance during therapy.

Valley polarization assisted spin polarization in two dimensions.

Valleytronics is rapidly emerging as an exciting area of basic and applied research. In two-dimensional systems, valley polarization can dramatically modify physical properties through electron-electron interactions as demonstrated by such phenomena as the fractional quantum Hall effect and the metal-insulator transition. Here, we address the electrons' spin alignment in a magnetic field in silicon-on-insulator quantum wells under valley polarization. In stark contrast to expectations from a non-interacting model, we show experimentally that less magnetic field can be required to fully spin polarize a valley-polarized system than a valley-degenerate one. Furthermore, we show that these observations are quantitatively described by parameter-free ab initio quantum Monte Carlo simulations. We interpret the results as a manifestation of the greater stability of the spin- and valley-degenerate system against ferromagnetic instability and Wigner crystalization, which in turn suggests the existence of a new strongly correlated electron liquid at low electron densities.

Metallic behaviour in SOI quantum wells with strong intervalley scattering.

The fundamental properties of valleys are recently attracting growing attention due to electrons in new and topical materials possessing this degree-of-freedom and recent proposals for valleytronics devices. In silicon MOSFETs, the interest has a longer history since the valley degree of freedom had been identified as a key parameter in the observation of the controversial "metallic behaviour" in two dimensions. However, while it has been recently demonstrated that lifting valley degeneracy can destroy the metallic behaviour, little is known about the role of intervalley scattering. Here, we show that the metallic behaviour can be observed in the presence of strong intervalley scattering in silicon on insulator (SOI) quantum wells. Analysis of the conductivity in terms of quantum corrections reveals that interactions are much stronger in SOI than in conventional MOSFETs, leading to the metallic behaviour despite the strong intervalley scattering.

Boundary-mediated electron-electron interactions in quantum point contacts.

An unusual increase of the conductance with temperature is observed in clean quantum point contacts for conductances larger than 2(e2/h). At the same time, a positive magnetoresistance arises at high temperatures. A model accounting for electron-electron interactions mediated by boundaries (scattering on Friedel oscillations) qualitatively describes the observation. It is supported by a numerical simulation at zero magnetic field.

Iodine-123-interleukin-2 scintigraphy in metastatic hypernephroma: a pilot study.

AIM: This pilot study reports on the uptake of (123)I-interleukin 2 (IL-2) in metastatic renal cell carcinoma (MRCC) patients and its relationship to prognostic factors of response or failure of MRCC to cytokines treatment. METHODS: Nine consecutive patients with MRCC underwent an (123)I-IL-2 scan (6 male and 3 female; mean age 64 years; range 51-78). Uptake in metastases was related to a summed score of 4 independent factors, predictive of rapid progression under cytokine treatment as defined by Negrier et al. RESULTS: Four patients presented with metastases at one site, 4 at 2 sites and one patient at 3 different sites. Summed scores were: 5 patients had a summed score of 1; 3 a summed score of 2 and 1 patient a summed score of 3. Uptake of (123)I-IL-2 by tumor tissue was found in only 2 patients. Uptake occurred in 1 patient with a summed score of 3 and in 1 with a summed score of 2. CONCLUSION: In this small series of patients with MRCC, (123)I-IL-2 uptake was found in tumors of 2 patients who less likely will benefit from cytokine treatment. Additional studies are needed to assess the relationship between the pretreatment uptake of (123)/I-IL2 in MRCC and the response to IL-2 therapy.

A Belgian registry of interleukin-2 administration for treatment of metastatic renal cell cancer and confrontation with literature data.

In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease.

Femtosecond time resolved coherent anti-Stokes Raman spectroscopy: experiment and modelization of speed memory effects on H2-N2 mixtures in the collision regime.

With the aim of temperature diagnostic, femtosecond time-resolved CARS (coherent anti-Stokes Raman spectroscopy) is applied to probe H2 in H2-N2 mixtures. In a first part, a Lorentzian profile is used to model the femtosecond CARS response. A difference between the experimental broadening and the expected one is observed in the collision regime. The observed broadening increases strongly in an inhomogeneous way with respect to the perturber concentration. This is of considerable importance for temperature measurements. In a second part, we show that in the collision regime, this inhomogeneous broadening is due to the speed dependence of the collisional parameters and the memory effects of the radiator speed. A new modelization of the time-resolved CARS response taking into account the speed memory effects is presented and applied to the temperature diagnostic in H2-N2 mixtures. The numerical results are in good agreement with experiments.

Tobacco and occupation as risk factors in bladder cancer: a case-control study in southern Belgium.

A pilot case-control study on bladder cancer, with population-based controls matched for each of 74 cases, has been conducted in two industrial areas of Southern Belgium in order to analyze the influence of tobacco use and occupation. Observed bladder cancer risk for smokers is more than 5 times higher than that for non-smokers, and the risk for people having an a priori hazardous occupation is about 3.5 times higher than that of other subjects. A dose-response relationship was found for tobacco exposure and duration of employment. It seems that the risk is increased in a log-linear way by these variables. Population attributable risks show that in 20 cases of bladder cancer, 17 could be explained by the two factors combined. This study also reveals an increased risk for metal workers, truck and engine drivers, coal-miners, and rubber and coal-tar workers. The risk for metal workers is specially high in the case of turners, metal fitters, blacksmiths, stokers and workers exposed to hot metal.

Complete degradation of tetrachloroethene by combining anaerobic dechlorinating and aerobic methanotrophic enrichment cultures.

Degradation of tetrachloroethene (perchloroethylene, PCE) was investigated by combining the metabolic abilities of anaerobic bacteria, capable of reductive dechlorination of PCE, with those of aerobic methanotrophic bacteria, capable of co-metabolic degradation of the less-chlorinated ethenes formed by reductive dechlorination of PCE. Anaerobic communities reductively dechlorinating PCE, trichloroethene (TCE) and dichloroethenes were enriched from various sources. The maximum rates of dechlorination observed for various chloroethenes in these batch enrichments were: PCE to TCE (341 mumol l-1 day-1), TCE to cis-dichloroethene (159 mumol l-1 day-1), cis-dichloroethene to chloroethene (99 mumol l-1 day-1) and trans-dichloroethene to chloroethene (22 mumol l-1 day-1). A mixture of these enrichments was inoculated into an anoxic fixed-bed upflow column. In this column PCE was converted mainly into cis-1,2-dichloroethene, small amounts of TCE and chloroethene, and chloride. Enrichments of aerobic methanotrophic bacteria were grown in an oxic fixed-bed downflow column. Less-chlorinated ethenes, formed in the anoxic column, were further metabolized in this oxic methanotrophic column. On the basis of analysis of chloride production and the disappearance of chlorinated ethenes it was demonstrated that complete degradation of PCE was possible by combining these two columns. Operation of the two-column system under various process conditions indicated that the sensitivity of the methanotrophic bacteria to chlorinated intermediates represented the bottle-neck in the sequential anoxic/oxic degradation process of PCE.

The CD8 beta polypeptide is required for the recognition of an altered peptide ligand as an agonist.

T cell activation is triggered by the specific recognition of cognate peptides presented by MHC molecules. Altered peptide ligands are analogs of cognate peptides which have a high affinity for MHC molecules. Some of them induce complete T cell responses, i.e. they act as agonists, whereas others behave as partial agonists or even as antagonists. Here, we analyzed both early (intracellular Ca2+ mobilization), and late (interleukin-2 production) signal transduction events induced by a cognate peptide or a corresponding altered peptide ligand using T cell hybridomas expressing or not the CD8 alpha and beta chains. With a video imaging system, we showed that the intracellular Ca2+ response to an altered peptide ligand induces the appearance of a characteristic sustained intracellular Ca2+ concentration gradient which can be detected shortly after T cell interaction with antigen-presenting cells. We also provide evidence that the same altered peptide ligand can be seen either as an agonist or a partial agonist, depending on the presence of CD8beta in the CD8 co-receptor dimers expressed at the T cell surface.