National Authority for Health: France

Provides an overview of France's National Authority for Health, which defines best-care standards and assesses the benefit and effectiveness of new technologies for inclusion on benefits lists. Examines its use of comparative effectiveness research

Mid- and Far-Infrared Marker Bands of the Metal Coordination Sites of the Histidine Side Chains in the Protein Cu,Zn-Superoxide Dismutase

International audienceVibrational spectroscopy gives important information on the properties of ligand and metal–ligand bonds in metalloenzymes. Infrared spectroscopy is appealing for the study of metal active sites that are not amenable to Raman spectroscopy. We present a combined experimental and theoretical approach to analyze the mid- and far-IR spectra of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as a probe of the histidine ligands. This metalloenzyme provides a unique model to identify specific IR signatures of metal–histidine coordination and to study their alterations as a function of the metal (copper/zinc), the copper valence state (+I/+II), the histidine coordination mode (Nτ and Nπ) and the histidine protonation state. DFT calculations combined with normal mode descriptions from potential energy distribution calculations were performed on two slightly different cluster models. Differences in the constraints at the side chain of one histidine Cu ligand sensibly modify the geometric parameters and vibrational properties. Electrochemically induced FTIR difference spectroscopy provided mid- and far-IR fingerprint spectra of the Cu protein in aqueous media that are sensitive to the redox state of the Cu centre at the active site. Comparisons of the DFT predictions with the experimental IR modes of the histidine ligands at the Cu,Zn-SOD active site showed that useful mid-IR markers of histidine Nτ and Nπ coordination were predicted with good accuracy. The DFT analysis further demonstrated a link between the ν(C4–C5) mode frequency of His46 and the specific properties of the His46–Cu bond in Cu,Zn-SOD. A combined theoretical and experimental approach on samples in H2O and 2H2O or 15N-labelled samples identified the contributions from the histidine side chain modes in the 669–629 cm–1 region

Contiguous follicular lymphoma and follicular lymphoma in situ harboring N-glycosylated sites

International audienceFollicular lymphoma in situ (FLIS) is composed of a clonal B-cell population harboring the typical t(14;18) hallmark of follicular lymphoma (FL), forming unconventional BCL2 Bright CD10 + cell foci in an otherwise normal reactive lymph node (LN). The diagnosis of FLIS is made on the fortuitous discovery of unconventional BCL2 Bright CD10 + cell foci. 1 Several studies recently demonstrated that FLIS are already advanced precursors in follicular lymphomagene-sis, but not necessarily committed to malignant transformation. 2,3 However, the relationship between FLIS and FL still remains unclear, as only a minority (<5%) of FLIS patients eventually develop FL. This is in line with the usually indolent progression of the disease, and the genomic instability observed in FLIS cells, which can engage FL precursor cells either in an evolutionary malignant process, or to an evolutionary dead end. 4 We report the case of a 35-year old male patient who presented with a cervical adenopathy. Histological examination of the excised LN displayed an altered architecture suggestive of FL, consisting of high number of monomorphic large follicles, uniformly spread in the cortical and medullary areas. Most follicles contained a predominant population of small cleaved cells with scant macrophages and mitoses. The mantle zone was reduced or absent. However, in a minor cortical area, a few follicles showed features mimicking residual classical germ cells (GC), including a smaller size, higher cell polymorphism, and a preserved mantle zone (Figure 1A). The BCL2 immunostaining (clone 100) was negative in follicles displaying a typical FL pattern. In contrast, follicles located in the pseudo-residual area were BCL2bright, i.e. more strongly stained than the surrounding mantle zone and reactive T cells (Figure 1B). Most follicles were only slightly positive for Ki67 (Online Supplementary Figure S1A). Both BCL2 – and BCL2 + follicles were CD10 positive (Online Supplementary Figure S1B) and contained a BCL2/JH break-point evidenced by fluorescence in situ hybridization (FISH) (Figure 1C). Taken together these results suggested the diagnosis of simultaneous occurrence of BCL2 – FL (grade I/II) and of BCL2 + FLIS in the same LN. We decided to further analyze those two lesions independently, and performed macrodissection in order to proceed with individual molecular analyses when required. Sanger sequenc-ing revealed that both FLIS and FL shared the same BCL2/JH sequence at the t(14;18)+ breakpoint, and thus originated from the same clone (Figure 1D). We tested two other anti-BCL2 antibodies (E17, SP66) directed against other epitopes, but the staining remained BCL2-in the FL area of the LN, similar to the anti-BCL2 antibody (clone 100) staining (Figure 1E and F). We thus sequenced exons 1 to 3 of the BCL2 gene (B-cell CLL/lym-phoma 2, NG_009361.1). Punctual mutations, resulting in amino acid substitutions, were found in the FL component (Online Supplementary Table S1), and were indeed located in the targeted aa41 to aa54 epitope of clone 100 (mutation

Etude des propriétés vibrationnelles dans l'IR lointain d'une superoxyde dismutase à cuivre et zinc dans son état oxydé et réduit et d'analogues par des méthodes de la chimie quantique

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Des indicateurs consensuels concernant les démarches de maintien en emploi dans les Contrats pluriannuels d’objectifs et de moyens (CPOM) ?

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Toward a fast evaluation of g-tensor of Cu containing systems: A DFT parametrized approach

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Molecular structures and thermodynamic properties of 12 gaseous cesium-containing species of nuclear safety interest: Cs2, CsH, CsO, Cs2O, CsX, and Cs2X2 (X=OH, Cl, Br, and I)

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Vibrational Modeling of Copper−Histamine Complexes: Metal−Ligand IR Modes Investigation

International audienceRecent reports on proteins and related models show that vibrational spectroscopy in the far-infrared domain is a promising technique to characterize metal sphere coordination in proteins. The low-frequency modes are however complex, and there is a need to develop the analysis of metal sites by means of quantum chemical calculations as a support for useful interpretation of the far-IR data. In this study, we determined vibrational properties for systems containing CuII−N(Imidazole) interactions present in many biological complexes by means of quantum chemical calculations and confronted the normal mode description with available experimental data. Analysis of the [Cu(histamine)]2+ complex led us to conclude that the anharmonic contributions are negligible in the far-IR domain. Geometry optimizations and vibrational frequency calculations of [Cu(hm)]2+ and [Cu(hm)2(ClO4)2] complexes were compared using various hybrid DFT functionals and basis sets. These investigations stressed the need of potential energy distribution calculations (PED) to assign the vibrational modes, to obtain an overall description of the vibration modes, and to efficiently compare the methods. Comparison of calculation methods with the B3LYP/6-31+G(d,p) and B3LYP/6-311+G(2d,2p) methods and with available experimental data showed that the B3LYP/6-31G(d,p) level of theory provides accurate predictions of the normal mode frequencies and assignments. These comparisons also enlighten that theoretical investigations of 2H- and 65Cu-labeled [Cu(hm)2(ClO4)2] complexes give with a very good accuracy the band shifts of the labeled copper−histamine derivatives. The theoretical calculations combined with experimental data allowed us to predict and calculate with good accuracy the values and assignments of the low-frequency IR modes, notably those involving metal contribution

Comparative effectiveness research and evidence-based health policy: experience from four countries.

CONTEXT: The discussion about improving the efficiency, quality, and long-term sustainability of the U.S. health care system is increasingly focusing on the need to provide better evidence for decision making through comparative effectiveness research (CER). In recent years, several other countries have established agencies to evaluate health technologies and broader management strategies to inform health care policy decisions. This article reviews experiences from Britain, France, Australia, and Germany. METHODS: This article draws on the experience of senior technical and administrative staff in setting up and running the CER entities studied. Besides reviewing the agencies' websites, legal framework documents, and informal interviews with key stakeholders, this analysis was informed by a workshop bringing together U.S. and international experts. FINDINGS: This article builds a matrix of features identified from the international models studied that offer insights into near-term decisions about the location, design, and function of a U.S.-based CER entity. While each country has developed a CER capacity unique to its health system, elements such as the inclusiveness of relevant stakeholders, transparency in operation, independence of the central government and other interests, and adaptability to a changing environment are prerequisites for these entities' successful operation. CONCLUSIONS: While the CER entities evolved separately and have different responsibilities, they have adopted a set of core structural, technical, and procedural principles, including mechanisms for engaging with stakeholders, governance and oversight arrangements, and explicit methodologies for analyzing evidence, to ensure a high-quality product that is relevant to their system

Health Policy: Experience from Four Countries

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