Publications

The aim of the study was to determine whether or not primary care EPR-based data can be used to measure specific process parameters that can then, in turn, be used to assess the quality of care provided to chronic patients. We analysed data from a large research network that collects data from all Belgian GP practices through both manual and automatic extraction procedures. We built a number of quality-related process parameters and observed the concordance of our results with two external databases: a nationwide reimbursement database and a regional EPR-based network. We found that only the automatic data extraction method was suitable for building process parameters. The current research network may lead to an underestimation of the quality of care processes. We suggested ways to improve this network.

Abstract Depending on the target enzyme with which they interact, nucleoside analogues exhibit marked differences in their antiviral activity spectrum. The activity spectrum of those nucleoside analogues that interact with cellular enzymes involved in the biosynthesis of the RNA and DNA precursor nucleotides encompasses virtually all RNA and DNA viruses. In contrast, the activity spectrum of those nucleoside analogues that are targeted at a specific viral enzyme will be limited to those specific virus types whose enzyme(s) they interact with. For a given compound, the antiviral activity spectrum can often be predicted from identification of the target enzyme, and, vice versa, the mode of action can be deduced from the activity spectrum.1 This concordance between antiviral activity spectrum and mode (target) of antiviral action will be scrutinized for the following categories of nucleoside analogues: AKAR analogues (i.e. ribavirin) that are targeted at IMP dehydrogenase; carbocyclic adenosine analogues (i.e. neplanocin A) that are targeted at AdoHcy hydrolase; OMP decarboxylase inhibitors such as pyrazofurin; CTP synthetase inhibitors such as cyclopentenylcytosine; acyclic guanosine analogues (i.e. acyclovir, ganciclovir) which act as viral DNA chain terminators following initial phosphorylation by the virus-encoded thymidine kinase (TK) or protein kinase; thymidine analogues (ie. BVDU) whose antiviral action (at the viral DNA polymerase level) also depends on a preferential phosphorylation by the viral TK; acyclic nucleoside phosphonates which can be divided into different subcategories depending on whether their activity spectrum includes all major DNA viruses (herpes, adeno, pox, papova and hepadna, or herpes-, hepadna-, and retroviruses, or only hepadna- and retroviruses); 2′,3′-dideoxynucleoside analogues which, following phosphorylation to the 5′-triphosphate form by cellular enzymes, act as chain terminators of the retro- and hepadnaviral reverse transcriptase; and certain nucleoside derivatives (i.e. HEPT, TSAO) which act as highly specific inhibitors of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) (Table 1).

Virtually all the compounds that are currently used (or have been the subject of advanced clinical trials) for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine and nucleotide reverse transcriptase inhibitors (NtRTIs) (i.e., tenofovir disoproxil fumarate); (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. In addition to the reverse transcriptase and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 (i.e., bicyclam (AMD3100) derivatives) and CCR5 (i.e., TAK-779 derivatives); (iii) virus-cell fusion, through binding to the viral envelope glycoprotein gp41 (T-20, T-1249); (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents (2,2′-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)); (v) proviral DNA integration, through integrase inhibitors such as 4-aryl-2,4-dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e., phosphoramidate and cyclosaligenyl pronucleotides by-passing the first phosphorylation step of the NRTIs), (ii) increased activity (“second” generation NNRTIs (i.e., TMC-125, DPC-083)) against those HIV strains that are resistant to the “first” generation NNRTIs, or (iii), as in the case of PIs, a different, modified peptidic (i.e., azapeptidic (atazanavir)) or non-peptidic scaffold (i.e., cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)). Non-peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs.

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Poly(xanthylic acid) [X)n] abolished the ability of (A)n-(U)n to induce interferon in "superinduced" (actinomycin D and cycloheximide) primary rabbit kidney cells. Under the same conditions, (X)n had a relatively minor effect on the interferon inducing capacity of (I)n-(C)n. Evidence based on mixing curves, melting profiles, pancreatic ribonuclease resistance and sucrose gradient ultracentrifugation pointed to the conclusion that the following three reactions occur depending on stoichiometry: (1) 2(A)n-(U)n + (X)n leads to (A)n-2(U)n + (A)n-(X)n; (2) (A)n-(U)n + (X)n leads to (A)n-(U)n-(X)n; (3) (A)n-(U)n + 2(X)n + (X)n-(U)n. The second reaction represents the formation of a new triple helix which can also be formed according to the following reactions: (X)n-(U)n + (A)n leads to (A)n-(X)n-(U)n; (A)n-(X)n + (U)n leads to (A)n-(X)n-(U)n.

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International audience

Advanced engineering ceramics are more and more employed in modern industries because of their excellent mechanical properties such as high hardness, high compressive strength, chemical and abrasive resistance.This paper investigates the Wire EDM of ShN 4 -based, ZrOz-based, and Ah03-based ceramics, provided that the ceramics have sufficiently high electrical conductivity.First, this paper investigates the cutting rate, the surface quality and surface integrity of Si3N4-TiN, Zr0 2 -TiN and Ah03-SiCw-TiC by Wire EDM.Furthermore, it is pointed out that besides typical material removal mechanisms like melting and evaporation, other mechanisms such as decomposition and oxidation have been identified.The latter mechanism results in a remarkable increase of the cutting rate, but a poorer surface quality.