bluuebunny/crossref_metadata_2025 huggingface dataset:
A tale of two clades: monkeypox viruses
Authors: Likos Anna M. , Sammons Scott A. , Olson Victoria A. , Frace A. Michael , Li Yu , Olsen-Rasmussen Melissa , Davidson Whitni , Galloway Renee , Khristova Marina L. , Reynolds Mary G. , Zhao Hui , Carroll Darin S. , Curns Aaron , Formenty Pierre , Esposito Joseph J. , Regnery Russell L. , Damon Inger K.
Published: September 2005

Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.
Open reading frame 73 is required for herpesvirus saimiri A11-S4 episomal persistence
Authors: Calderwood Michael , White Robert E. , Griffiths Rhoswyn A. , Whitehouse Adrian
Published: September 2005

Herpesvirus saimiri (HVS) establishes a latent infection in which the viral genome persists as a non-integrated episome. Analysis has shown that only open reading frames (ORFs) 71–73 are transcribed in an in vitro model of HVS latency. ORF73 also colocalizes with HVS genomic DNA on host mitotic chromosomes and maintains the stability of HVS terminal-repeat-containing plasmids. However, it is not known whether ORF73 is the only HVS-encoded protein required for episomal maintenance. In this study, the elements required for episomal maintenance in the context of a full-length HVS genome were examined by mutational analysis. A recombinant virus, HVS-BACΔ71-73, lacking the latency-associated genes was unable to persist in a dividing cell population. However, retrofitting an ORF73 expression cassette into the recombinant virus rescued episomal maintenance. This indicates that ORF73 is the key trans-acting factor for episomal persistence and efficient establishment of a latent infection.
Representing structural databases in a self-organizing map
Authors: Wehrens Ron , Melssen Willem , Buydens Lutgarde , de Gelder René
Published: September 2005

This paper presents a way to accomodate large numbers of crystal structures, as present in e.g. the Cambridge Structural Database (CSD), in a self-organizing map. The structures are represented by their calculated powder diffraction patterns. The use of a recently introduced similarity criterion is essential: the weighted cross-correlation. This accurately reflects the similarities of the powder patterns and therefore, indirectly measures the resemblance of crystal packings. It will be shown that good results are obtained, even if the network is trained with a small subset of a complete database. This makes it possible to construct the map on common hardware in a few hours. Such a map provides several possibilities for two-dimensional visualization, but additionally has a number of important applications. Two such applications are fast and easy screening of a database, and providing an overview of the contents of a database in terms of structural diversity of specific chemical classes of compounds, e.g. steroids or peptides. A third is the selection of archetypical structures, covering the complete structural space.
A structural study of new potent and selective antagonists to the A2B adenosine receptor
Authors: Ferretti Valeria , Pretto Loretta , Tabrizi Mojgan Aghazadeh , Bertolasi Valerio
Published: September 2005

Xanthines, including the natural derivatives theophylline and caffeine, are non-selective antagonists of adenosine. They are able to bind with good affinity to all four adenosine-receptor subtypes A1, A2A, A2B and A3. In order to develop new drugs with few side effects, over the last few years many efforts have been devoted to the discovery of new adenosine antagonists with enhanced selectivity properties. The present paper reports the crystal structures of five new xanthinic derivatives, which display different affinities and selectivity properties towards the A2B receptor. Besides the crystallographic study, a structural comparison has been made with the calculated geometry of other xanthinic derivatives which are reported to have similar biological characteristics to understand the structural features controlling their affinity capabilities and selectivity. This structural comparison has been interpreted in the light of a recently published study on the binding of N-benzo[1,3]-dioxol-5-yl-2-[5-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)-1-methyl-1-H-pyrazol-3-iloxy]-acetamide to a model of the A2B receptor, which shows the most interesting affinity and selectivity properties.
Diffuse scattering and ordering in the short-range modulated paraelectric phase of sodium nitrite, NaNO2
Authors: Łukaszewicz K. , Pietraszko A. , Kucharska M.
Published: September 2005

The incommensurately modulated antiferroelectric phase of sodium nitrite, NaNO2, transforms at TN
= 437.7 K to the short-range modulated paraelectric phase. The apparently discontinuous phase transition is accompanied by characteristic changes in the diffraction pattern. Contrary to the well known modulated structures with sharp satellite reflections, the diffraction pattern of a short-range modulated structure contains diffuse satellite reflections. The short-range modulated crystal structure of the paraelectric phase of sodium nitrite has been analysed by the Reverse Monte Carlo (RMC) simulation of X-ray diffuse scattering. The crystal structure of sodium nitrite may be regarded as consisting of [Na+NO_2^{-}]∞ rows running along the polar b axis. One can expect long fragments of rows with uniform polarity The assumption that single [Na+NO_2^-]∞ rows are polar with uniform polarity proved to be a convenient approximation which is in good agreement with the observed diffraction pattern. The distribution of (+)- and (−)-[Na+NO_2^-]∞ polar rows crossing the (010) plane of short-range modulated NaNO2 revealed by RMC shows nanodomains consisting of distorted fragments of a sinusoidally modulated crystal structure. The size of the nanodomains and the degree of order in paraelectric NaNO2 decreases with temperature.
Bayesian methods for the conformational classification of eight-membered rings
Authors: Pérez J. , Nolsøe K. , Kessler M. , García L. , Pérez E. , Serrano J. L.
Published: September 2005

Two methods for the classification of eight-membered rings based on a Bayesian analysis are presented. The two methods share the same probabilistic model for the measurement of torsion angles, but while the first method uses the canonical forms of cyclooctane and, given an empirical sequence of eight torsion angles, yields the probability that the associated structure corresponds to each of the ten canonical conformations, the second method does not assume previous knowledge of existing conformations and yields a clustering classification of a data set, allowing new conformations to be detected. Both methods have been tested using the conformational classification of Csp
3 eight-membered rings described in the literature. The methods have also been employed to classify the solid-state conformation in Csp
3 eight-membered rings using data retrieved from an updated version of the Cambridge Structural Database (CSD).
Elimination of CD4+CD25+ T cell accelerates the development of glomerulonephritis during the preactive phase in autoimmune‐prone female NZB × NZW F1 mice
Authors: Hayashi Toshiharu , Hasegawa Keiko , Adachi Chie
Published: September 2005

The role of CD4+CD25+ T cell in glomerulonephritis (GN) development during the preactive phase was investigated in autoimmune‐prone female NZB × NZW F1 (B/WF1) mice. The administration of anti‐mouse CD25+ T‐cell monoclonal antibody (PC61.5) 3 days after birth induced the development of GN with an increase in IgG2a antinuclear antibody, productions of IL‐6 and IFN‐γ, whereas TGF‐β1 production decreased, compared to untreated control mice. The present study results suggest that CD4+CD25+ T cells may, at least in part, downregulate the development of GN during the preactive phase in B/WF1 mice.
Cyclic Fatigue in Ceramics: A Balance between Crack Shielding Accumulation and Degradation
Authors: Jacobs David S. , Chen I‐W.
Published: September 2005

Cyclic fatigue growth rates in R‐curve ceramics have been observed to depend very strongly on the maximum applied stress intensity, Kmax, and only weakly on the stress intensity range, Δ This behavior is rationalized through measurement of crack wake shielding characteristics as a function of these fatigue parameters in a gas‐pressure‐sintered silicon nitride. In particular, evidence for a mechanical equilibrium between shielding accumulation by crack growth and shielding degradation by frictional wear of sliding interfaces is found for steady‐state cyclic fatigue. This equilibrium gives rise to a rate law for cyclic fatigue. The data suggest that the accumulation process is the origin of the strong Kmax dependence, and that the degradation process is the origin of the weak Δ dependence. These features are shown to be related to the “cyclic”R‐curve and to the cyclic crack opening displacement, respectively.
Solidification Behavior of Undercooled Liquid Aluminum Oxide
Authors: Weber J. K. Richard , Anderson Collin D. , Merkley Dennis R. , Nordine Paul C.
Published: September 2005

Solidification of aluminum oxide from undercooled melts was investigated in containerless experiments. Specimens were levitated in a gas jet, stabilized with an acoustic positioning device, and melted with cw CO2 laser beams. Cooling curves were obtained by optical pyrometry when the laser intensity was reduced. The materials examined were high‐purity Verneuil sapphire, 99.5% polycrystalline alumina, and oxide materials recovered from the effluent of an aluminum‐fueled rocket motor. The degree of undercooling, the apparent temperature behavior during the thermal arrest on solidification, and the structure of the materials formed were different in argon and oxygen atmospheres. Undercooling of the sapphire and alumina materials was 360 ± 10 K in an oxygen atmosphere and approximately 450 K in argon. Melting and solidification of high‐purity sapphire resulted in a dendritic and porous polycrystalline material in oxygen. Dense, larger crystals were obtained in argon. Products formed from 99.5% alumina were discolored and the cores were white, indicating impurity segregation effects. More reproducible behavior was observed for the sapphire and 99.5% alumina than for the tungstencontaminated rocket motor effluent materials.
Subcritical Growth of Indentation Median Cracks in Soda‐Lime‐Silica Glass
Authors: Sglavo Vincenzo M. , Green David J.
Published: September 2005

The influence of load and dwell time on the subcritical growth of indentation cracks was investigated. The behavior of soda‐lime‐silica glass in both active and inert environments was considered. Vickers indentations were obtained.using loads ranging from 1.96 to 39.2 N and the dwell time.at maximum load was varied between 5 s and 30 min. Indented samples were broken and the fracture surfaces.observed using optical microscopy. Anomalous crack shapes were obtained in air and water for long dwell times, particularly at higher indentation loads. The cracks were markedly circular in shape and substantially deeper than conventional median/radial indentation cracks, evidencing a time‐dependent growth. Comparison of the measured crack depth with a theoretical analysis demonstrated that the appearance of the “circular” cracks was related to the subcritical growth of median cracks.
High‐Temperature Fracture Mechanism of Low‐Ca‐Doped Silicon Nitride
Authors: Tanaka Isao , Igashira Ken'ichiro , Okamoto Taira , Niihara Koichi , Cannon Rowland M.
Published: September 2005

High‐purity Si3N4 (with 2.5 wt% glassy SiO2) doped with 0 to 450 at.ppm of Ca was prepared as a model system to investigate the effects of grain‐boundary segregants on fracture phenomenology at 1400°C. Subcritical crack‐growth (SCG) resistance as well as creep resistance was degraded significantly by the presence of a small amount of Ca. The internal friction of the doped materials exhibited the superposition of a grain‐boundary relaxation peak and a high‐temperature background, and the apparent viscosity of the grain‐boundary film was determined from the peak. Based on these experimental data, the fracture mechanism at 1400°C was divided into three regions: “brittle,” SCG, and creep failure as a function of both external strain rate and Ca concentration, CCa. From the investigation of the CCa dependence of the critical strain rate for the transition from “brittle” to SCG fractures, the SCG phenomenon is suggested to be triggered by small‐scale, grain‐boundary sliding. The CCa dependence of “steady‐state” creep rate was far from the theoretical dependence of diffusional creep via a solution‐precipitation mechanism. The discrepancy was interpreted to be due to the presence of an impurity‐insensitive creep component. This component may correspond to the lowest limit of the tensile creep rate in Si3N4 polycrystalline materials containing intergranular glassy‐SiO2 film.
Fracture Resistance of SiC‐Fiber‐Reinforced Si3N4 Composites at Ambient and Elevated Temperatures
Authors: Xu Hockin H. K. , Ostertag Claudia P. , Fuller Edwin R. , Braun Linda M. , Lloyd Isabel K.
Published: September 2005

The crack growth behavior in unidirectional SiC‐fiber‐rein‐forced Si3N4‐matrix composites fabricated in our laboratories was investigated as a function of fiber volume fraction and temperature. Both the stress‐intensity factor and an energy approach were adopted in the characterization of the crack growth behavior. Crack resistance increased with crack extension (R‐curve or T‐curve) as a result of bridging effects associated with the intact fibers. Large‐scale bridging was observed, and was considered in the determination of the R‐curves. Temperature and fiber volume fraction affected the crack propagation behavior. At room temperature a single crack was initiated at the notch tip; it then branched and delaminated upon further loading. In contrast, at 1200°C, little crack branching was observed. Increasing fiber volume fraction increased the degree of crack branching. Temperature and fiber volume fraction also affected the R‐curve behavior. Raising the temperature to 1200°C did not significantly degrade the room‐temperature R‐curve effect. Increasing the fiber volume fraction from 14% to 29% substantially enhanced the toughening effect and the R‐curve behavior.
New Generation of Plasma‐Sprayed Mullite Coatings on Silicon Carbide
Authors: Lee Kang N. , Miller Robert A. , Jacobson Nathan S.
Published: September 2005

Mullite is promising as a protective coating for silicon‐based ceramics in aggressive high‐temperature environments. Conventionally plasma‐sprayed mullite on SiC tends to crack and debond on thermal cycling. It is shown that this behavior is due to the presence of amorphous mullite in the conventionally sprayed mullite. Heating the SiC substrate during the plasma spraying eliminated the amorphous phase and produced coatings with dramatically improved properties. The new coating exhibits excellent adherence and crack resistance under thermal cycling between room temperature and 1000–1400°C. Preliminary tests showed good resistance to Na2CO3‐induced hot corrosion.
Influence of Processing Conditions on the Microstructure and Mechanical Properties of Sintered Yttrium Oxides
Authors: Desmaison‐Brut M. , Montintin J. , Valin F. , Boncoeur M.
Published: September 2005

High‐purity (99.9%) yttrium oxide (Y2O3) powder has been consolidated, either by vacuum sintering (VS) or by hot isostatic pressing (HIP). As the dense polycrystalline ceramics contained point defects, mainly oxygen vacancies, oxidation treatment was applied at 1500°C for 2 h. The two materials were compared with respect to mechanical, elastic, and thermal properties, and this work demonstrated that the HIPed oxide had the best performance. The beneficial effect of the HIP technique was mainly due to the achievement of a slightly higher densiflcation at a much lower applied temperature. This technique prevented any grain coarsening and allowed us to obtain a more homogeneous structure. Consequently, improvements in microhardness, flexural strength, and thermal shock parameters were significant. Nevertheless, the elastic parameters and the toughness values of the two grades were very close to each other.
Subsolidus Phase Equilibria of the CaO‐B2O3‐BaO System
Authors: Ji Yangyang , Liang Jingkui , Xie Sishen , Yu Yude
Published: September 2005

The “subsolidus” phase relations at room temperature in the system CaO‐B2O3‐BaO are investigated. Specimens of various compositions were prepared from appropriate ratios of CaCO3, B2O3, and BaCO3, and fired from 780° to 1040°C according to their melting points. There are three ternary compounds in this system. The crystal structures of these compounds were determined by X‐ray diffraction (XRD). CaBa2(BO3)2 and Ca5Ba2B10O22 are monoclinic structures. The lattice constants a= 14.221 Å, b= 4.569 Å, c= 11.926 A, β= 99.947°, and V= 763.4 å3 for CaBa2(BO3)2 and a= 15.714 å, b= 6.184 å, c= 10.204 å, β= 93.954°, and V= 989.29 å3 for Ca5Ba2B10O22 are obtained. The third compound, CaBa2(B3O6)2, is isostructural with the high form of BaB2O4 with lattice constants a= 7.167 å and c= 35.298 å. Powder second harmonic generation efficiencies of these ternary compounds were measured using a homemade apparatus.
Low‐Temperature Sintering of Pb(Zr,Ti)O3 Ceramics with the Aid of Oxyfluoride Additive: X‐ray Diffraction and Dielectric Studies
Authors: Ohtaka Osamu , Von Der Mühll Régnault , Ravez Jean
Published: September 2005

Low‐temperature sintering of Pb(Zr,Ti)O3 (PZT) ceramics has been performed with the aid of oxyfluoride additives in order to compensate the volatilization of PbO, which results in the degradation of electric properties. An additive of a mixture of PbO and PbF2 (eutectic composition) realizes a liquid‐phase sintering and allows high densification at low temperature. The densification of more than 98% of theoretical density was achieved by sintering at 900°C. The characterization of these PZT ceramics was carried out with XRD, TG, SEM, and dielectric measurements. The thermal variation of dielectric constant showed ferroelectric behavior. The highest permittivity value was obtained in the specimen fired at 900°C for 3 or 5 h with 3 wt% additive.
Particle Crowding Analysis of Slip Casting
Authors: Smith Peter A. , Haerle Andrew G.
Published: September 2005

The particle crowding index and interparticle spacing terms were calculated for seven alumina suspensions. The particle crowding index was used to interpret the casting rate for the tested alumina suspensions; the index was successfully correlated with the casting rate for cakes that produced the same modes of porosity. Unfortunately, this index could not be correlated with the casting rate for the particle system that produced varied porosity as a function of composition. The interparticle spacing term was correlated with viscosity for particle size distributions between 31 and 0.1 μm. For particle size distributions extended to 44 μm, the viscosity could not be correlated with interparticle spacing, because the quantity of fine particles, rather than the particle packing, controlled the viscosity.
Ultrasonic Real‐Time Monitoring of Cake Structure during Slip Casting
Authors: Haerle Andrew G. , Haber Richard A.
Published: September 2005

An ultrasonic monitoring system was developed which utilizes two longitudinal transducers configured in a pulse‐echo mode to monitor the structure of a growing slip cast cake. By applying appropriate volume conservation equations to the planar, uniaxial casting apparatus, it is shown that the cake permeability and local volume fraction of voids in a cake can be measured while casting is taking place. Values obtained from the ultrasound measurements were compared to traditional methods of measuring cake permeability and cake porosity. Reasonable agreement was found. Advantages of the ultrasound technique over traditional methods, as well as limitations of the technique, are discussed.
Structure of Na‐ and Ca‐β″‐Al2O3 Coatings on α‐Al2O3 Single‐Crystal Platelets
Authors: Kuo Chu Kun , Huang Xue‐Ning , Nicholson Patrick S.
Published: September 2005

The structure of Na‐ and Ca‐β″‐Al2O3 coatings on α‐Al2O3 single‐crystal platelets has been studied by optical and electron microscopy and X‐ray and electron diffraction. The growth features and potential interface weakening effects of the modified platelets in dispersed‐particle reinforced composites are discussed.
Determination of Fictive Temperature of Soda‐Lime Silicate Glass
Authors: Agarwal Anand , Tomozawa Minoru
Published: September 2005

Peak positions of silica structural bands, both in infrared absorption and reflection modes, were used earlier to measure the fictive temperature of silica glass. In the present study, the method was applied to determine the fictive temperatures of a soda‐lime silicate glass. For the silicate glass, the IR absorption spectra produced a broad structural band which made the precise determination of peak position difficult, and only the IR reflection band was used. Equilibrium peak positions of ∼1056 cm−1 IR band, due to Si‐O stretching, were found to be directly correlated with the fictive temperature of the soda‐lime silicate glass. The soda‐lime glass exhibited an opposite dependence of the IR band position on the glass fictive temperature as compared to silica glass.
The role of alcohol‐specific socialization in adolescents’ drinking behaviour
Authors: Van Der Vorst Haske , Engels Rutger C. M. E. , Meeus Wim , Deković Maja , Van Leeuwe Jan
Published: September 2005

Aims  To determine which alcohol‐specific socialization practices are related to adolescents’ alcohol use, and to investigate whether parents differ in their alcohol‐specific socialization towards their children.

Design  In a sample of 428 families, both parents and two adolescents (aged 13–16 years) completed a questionnaire at home about alcohol‐specific parenting and their own alcohol use. Based on the reports of each family member, three different models of alcohol‐specific socialization were formulated: from the perspective of the siblings, the mother and the father.

Findings  Results of structural equation modelling generally showed the same associations between alcohol‐specific socialization and drinking of younger and older adolescents. The strongest association was found for providing alcohol‐specific rules. Applying strict rules about alcohol use was negatively related to adolescents’ alcohol use; this was also the case for having confidence in the effectiveness of alcohol‐specific socialization. Unexpectedly, frequency of communication about alcohol issues was positively associated with alcohol consumption of adolescents.

Conclusions  This study is one of the first to examine associations between alcohol‐specific socialization and adolescents’ drinking using a between‐ and a within‐family design. Results showed strong associations between alcohol‐specific socialization (particularly of enforcing rules) and adolescent alcohol use. Although parents strongly differentiated their socialization practices between children, no differences in associations between alcohol‐specific socialization and drinking were found between older and younger adolescents.
Reducing bias in telephone survey estimates of the prevalence of drug use: a randomized trial of telephone audio‐CASI
Authors: Turner Charles F. , Villarroel Maria A. , Rogers Susan M. , Eggleston Elizabeth , Ganapathi Laxminarayana , Roman Anthony M. , Al‐Tayyib Alia
Published: September 2005

Aim  To assess the impact of telephone audio computer‐assisted self‐interviewing (T‐ACASI) on reporting of alcohol use, alcohol problems and illicit drug use in telephone surveys of the general population. Prior research suggests that illicit drug use is underreported in traditional, interviewer‐administered, telephone surveys.

Design  Randomized experiment embedded in telephone survey of probability samples of populations of USA and Baltimore, MD. Survey respondents were randomly assigned to be interviewed either by human telephone interviewers or by T‐ACASI after household screening, recruitment, and informed consent procedures were completed.

Setting  Respondents were interviewed by telephone in their homes.

Participants  Probability samples of 1543 English‐speaking adults ages 18–45 residing in telephone‐accessible households in USA and 744 similarly defined adults residing in Baltimore, MD, USA.

Measurements  Nine questions on alcohol, marijuana, cocaine, and injection drug use adapted from 1994 NHSDA and four CAGE questions on alcohol problems. Crude odds ratios and odds ratios controlling for demographic factors calculated to test for differences between responses obtained by T‐ACASI and human interviewers.

Findings  T‐ACASI had mixed effects on reporting of alcohol use, but it did increase reporting of one of four CAGE alcohol problems: feeling guilty about drinking (23.0% in T‐ACASI vs. 17.6% in T‐IAQ, OR = 1.4, P < 0.01). T‐ACASI also obtained significantly more frequent reporting of marijuana, cocaine, and injection drug use. The impact of T‐ACASI was most pronounced for reporting of recent use of ‘harder’ drugs. Thus T‐ACASI respondents were more likely to report marijuana use in the past month (10.0% vs. 5.7%, crude OR = 1.9, P < 0.001), cocaine use in the past month (2.1% vs. 0.7%, crude 3.2, P < 0.001) and injection drug use in the past five years (1.6% vs. 0.3%, crude OR = 4.8, P < 0.01).

Conclusions  Telephone survey respondents were more likely to report illicit drug use and one alcohol problem when interviewed by T‐ACASI rather than by human telephone interviews.
Validity of carbohydrate‐deficient transferrin (%CDT), γ‐glutamyltransferase (γ‐GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non‐alcoholic and alcoholic origin
Authors: Hock B. , Schwarz M. , Domke I. , Grunert V. P. , Wuertemberger M. , Schiemann U. , Horster S. , Limmer C. , Stecker G. , Soyka M.
Published: September 2005

Aim  To test the clinical performance of carbohydrate‐deficient transferrin (%CDT), γ‐glutamyltransferase (γ‐GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases.

Design  Well‐characterized collectives of alcohol‐dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased γ‐GT, 51 hepatitis patients and 20/31 patients with non‐alcohol/alcohol‐dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD‐10)/Diagnostic and Statistical Manual version IV (DSM‐IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified.

Findings  Median AUDIT scores of patients without/with regular heavy drinking were 1–3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased γ‐GT 2.1/3.0, hepatitis 2.0/4.4, non‐alcohol‐dependent liver cirrhosis 2.4/4.8, alcohol‐dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, γ‐GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut‐off for the test used (Tina‐quant®%CDT 2nd‐generation). At this cut‐off, the sensitivity for ALC patients was 73.3%, whereas γ‐GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with γ‐GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, γ‐GT and MCV. The diagnostic specificity of %CDT calculated at the cut‐off of 3% was 93.5% in patients with unspecifically increased γ‐GT, 88.2% in hepatitis patients and 70.0% in patients with non‐alcohol‐dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than γ‐GT (specificity in hepatitis 52.9%, and 35.0% in non‐alcohol‐dependent liver cirrhosis).

Conclusion  %CDT is of high diagnostic value to support diagnosis of alcohol‐use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers γ‐GT and MCV.
Excessive alcohol consumption and dependence on amphetamine are associated with parallel increases in subjective ratings of both ‘wanting’ and ‘liking’
Authors: Willner Paul , James Darren , Morgan Michael
Published: September 2005

Aim  One of the tenets of the incentive sensitization theory of drug addiction is that ‘as drugs come to be wanted more and more, they often come to be liked less and less’. The aim of this study was to test whether this assumption holds true. Specifically, the study aimed to test the hypothesis that in non‐clinical samples, dependence on amphetamines and excessive alcohol use are associated with increased ‘wanting’ but decreased ‘liking’ for the drug.

Design, setting and participants  In two studies, the Desires for Alcohol Questionnaire (DAQ) was administered to 380 recreational drinkers, and the Desires for Speed Questionnaire (DSQ) and the Leeds Dependence Questionnaire (LDQ) were administered to 174 amphetamine users. Scales were derived from the DAQ and DSQ representing craving, on one hand, and positive and negative reinforcement on the other hand. Craving and positive reinforcement were taken as measures of alcohol or amphetamine ‘wanting’ and ‘liking’, respectively.

Findings  Scores on all three DAQ scales increased monotonically as a function of the extent of alcohol consumption. Scores on all three DSQ scales increased monotonically as a function of dependence, as measured by the LDQ. ‘Liking’ for amphetamine was unrelated to time since the drug was last taken. (These data were not available for alcohol.)

Conclusions  The finding that ‘wanting’ increased as a function of dependence on amphetamine or level of consumption in the case of alcohol is as predicted by the incentive sensitization theory, but the finding that ‘liking’ also increased as a function of dependence or excess is the opposite of the predicted effects While not refuting the incentive sensitization theory directly, the study questions the validity of one of the tenets of the theory.
Allele and genotype frequencies of CYP2C9 in a Korean population
Authors: Bae Jung‐Woo , Kim Hyun‐Kyung , Kim Ji‐Hong , Yang Sang‐In , Kim Mi‐Jeong , Jang Choon‐Gon , Park Young‐Seo , Lee Seok‐Yong
Published: September 2005

Aims

To determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population.

Methods

Three hundred and fifty‐eight healthy Korean subjects were studied. CYP2C9 alleles were detected by polymerase chain reaction‐restriction fragment length polymorphism assays and direct sequencing assays.

Results

The allele frequencies were 0.934 for CYP2C9*1, 0.060 for CYP2C9*3 and 0.006 for CYP2C9*13. The CYP2C9*2,*4,*5 and *11 alleles were not detected. The frequencies of the CYP2C9*1/*1, *1/*3 and *1/*13 genotypes were 0.869, 0.120 and 0.011, respectively.

Conclusion

The frequency of the CYP2C9*3 allele in the Korean population studied was significantly higher than reported elsewhere, and a novel allele, CYP2C9*13, was found at a frequency of 0.006 (95% confidence interval 0, 0.012). Only three genotypes of CYP2C9, CYP2C9*1/*1,*1/*3 and *1/*13 were observed in this Korean population.
Anti‐factor Xa kinetics after intravenous enoxaparin in patients undergoing percutaneous coronary intervention: a population model analysis
Authors: Sanchez‐Pena Paola , Hulot Jean‐Sébastien , Urien Saïk , Ankri Annick , Collet Jean‐Philippe , Choussat Rémi , Lechat Philippe , Montalescot Gilles
Published: September 2005

Aim

Recent studies have suggested that intravenous (i.v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti‐Xa pharmacokinetics following different i.v. dosing regimens is not clearly established.

Methods

A population pharmacokinetic analysis was developed using anti‐Xa activities measured in 546 patients who received a single 0.5 mg kg−1 i.v. dose of enoxaparin immediately before PCI. Effects of higher doses (0.75 mg kg−1 and 1 mg kg−1) and/or additional bolus after the initial administration were similarly simulated.

Results

Enoxaparin anti‐Xa time profiles were best described by a one‐compartment model with zero‐order kinetics. Mean population parameters (intersubject variability, %) were CL 1.2 l h−1 (33), V 2.9 l (30) and zero‐order input 0.25 h (24). With a single bolus of 0.5 mg kg−1, the totality of the patients reached an effective anticoagulation level (anti‐Xa >0.5 IU ml−1) and only 2.5% reached levels above 1.5 IU ml−1. Simulations showed that greater doses (0.75 mg kg−1 and 1 mg kg−1) prolonged the duration of anticoagulation (3.4 and 4.1 h, respectively) compared with the 0.5 mg kg−1 bolus (2.7 h) and markedly increased the proportion (48% and 79%, respectively) of patients with anti‐Xa levels >1.5 IU ml−1. For delayed and/or prolonged procedures, patients could be administered a second bolus of half the initial dose in a time interval between 90 min to 2 h after in order to maintain similar anticoagulation profile levels.

Conclusions

A single 0.5 mg kg−1 i.v. dose of enoxaparin reached anticoagulation levels adequately and should be safer compared with greater doses for anticoagulation in patients undergoing an elective PCI. An additional second bolus could be proposed in patients with delayed or prolonged procedures.
Population pharmacokinetic analysis for nelfinavir and its metabolite M8 in virologically controlled HIV‐infected patients on HAART
Authors: Panhard X. , Goujard C. , Legrand M. , Taburet A. M. , Diquet B. , Mentré F. ,   COPHAR 1‐ANRS study group
Published: September 2005

Aims

To describe the pharmacokinetics of nelfinavir and its main metabolite M8 in HIV‐infected patients with a sustained virological response, to characterize the effect of covariates and to estimate inter‐ and intra‐individual variability in the pharmacokinetics.

Methods

Three hundred and twenty concentrations of both nelfinavir and M8 were measured in 46 patients enrolled in the COPHAR 1‐ANRS 102 study. Blood samples were taken at a first visit (one sample before drug administration and four samples at fixed times after) and at a second visit 1 to 3 months later (one before and one 3 h after drug administration). The data from both visits on nelfinavir and M8 were modelled jointly in all patients using a population approach.

Results

A one‐compartment model with first‐order absorption and elimination best described nelfinavir data, with an additional compartment incorporating a first order rate‐constant describing the metabolism of the drug to M8. For nelfinavir, the apparent volume of distribution (V/F ) (95% confidence interval for the mean), was 309 l (185, 516), the absorption rate constant (ka) was 0.4 h−1 (0.2, 0.8), and the apparent clearance (CL/F ) was 37.3 l h−1 (32, 44). For M8, Vm /(Fkm) and CLm/(Fkm) were 866 l h−1 (351, 2161) and 1670 l (965, 2894), respectively. The interindividual variabilities were 34.9%, 34.3% and 62.2% for V/F, CL/F and CLm/(Fkm), respectively. The interoccasion variability was 27.8% for CL/F. The mean half‐lives were 05.38 h and 00.44 h for nelfinavir and M8, respectively. Significant but opposite effects of comedication with zidovudine were found on nelfinavir CL/F and M8 CLm/(Fkm), but they were not considered to be clinically relevant.

Conclusions

A joint model was found to describe adequately nelfinavir and M8 concentrations and was used to estimate pharmacokinetic parameters for M8. The model can be used to build reference pharmacokinetic profiles for therapeutic drug monitoring of the drug.
Co‐proxamol overdose is associated with a 10‐fold excess mortality compared with other paracetamol combination analgesics
Authors: Afshari R. , Good A.M. , Maxwell S.R.J. , Bateman D.N.
Published: September 2005

Aims

To assess the relative toxicity of co‐proxamol in overdose in comparison to the 2 other paracetamol‐opioid combination products, co‐codamol and co‐dydramol.

Methods

Data collected over a 2‐year period (July 2000–June 2002) was used to estimate the frequency of overdose and death for the three most popular paracetamol‐opioid compound analgesics. Prescription data for Scotland and Edinburgh, the number of overdoses (derived from overdose admissions in Edinburgh) or Poisons Information Service contacts in Scotland, and national death records were used to calculate a series of indicators relating morbidity (admissions), surrogates of morbidity (poisons enquiries by telephone or internet) and mortality to prescriptions.

Results

When related to prescription volume overdoses involving co‐proxamol in Scotland were 10 times more likely to be fatal (24.6 (19.7, 30.4)) when compared with co‐codamol (2.0 (0.88, 4.0)) or co‐dydramol (2.4 (0.5, 7.2)). In contrast there was no difference in the presentation rate or enquiry rates for these analgesics when corrected for prescriptions.

Conclusions

The excess hazard from co‐proxamol is due to inherent toxicity rather than increased use in overdose. We estimate from this study that withdrawal of co‐proxamol would prevent 39 excess deaths per annum in Scotland alone.
Amplified‐fragment length polymorphism analysis of Propionibacterium isolates implicated in contamination of blood products
Authors: Mohammadi T. , Reesink H. W. , Pietersz R. N. I. , Vandenbroucke‐Grauls C. M. J. E. , Savelkoul P. H. M.
Published: September 2005

Propionibacterium acnes is implicated in most cases of bacterial contamination of platelet concentrates (PCs). To determine the source of contamination, amplified‐fragment length polymorphism (AFLP) analysis was applied. This DNA fingerprinting technique was used to study the molecular relationship of 44 isolates derived from 22 PCs and 22 corresponding red blood cells concentrates (RBCs) from the same whole blood donations. The AFLP results together with sequencing analysis of the 1200 bp of the 16S ribosomal RNA gene revealed the existence of three main groups: two groups (groups 2 and 3) (55%) consisted of isolates that did not originate from skin flora and another group (group 1) (45%) comprised bacteria belonging to the skin flora. This latter group showed complete homology with reference strains of P. acnes. Therefore these isolates can be considered as P. acnes strains. In contrast, contaminants from groups 2 and 3 were shown to be molecularly unrelated to the P. acnes found on the skin surface. The AFLP is reproducible and gave invaluable information about the nature of Propionibacteria contaminating PCs. To gain more insights into the source of contamination, this technique could be exploited in further studies to determine the molecular relationship of different bacteria commonly found in blood products.
Activity and safety of combined rituximab with chlorambucil in patients with mantle cell lymphoma
Authors: Bauwens Deborah , Maerevoet Marie , Michaux Lucienne , Théate Ivan , Hagemeijer Anne , Stul Michel , Danse Etienne , Costantini Sabrina , Vannuffel Pascal , Straetmans Nicole , Vekemans Marie‐Christiane , Deneys Véronique , Ferrant Augustin , Van Den Neste Eric
Published: September 2005

We evaluated the combination of rituximab with chlorambucil in patients with mantle cell lymphoma (MCL) not eligible for aggressive therapy. Fourteen patients (male/female: 9/5) were included (two newly diagnosed, 12 relapsed/refractory). The toxicities were neutropenia, thrombopenia and infection. Nine (64%) patients responded; five (36%) achieved complete remission and four (29%) achieved partial remission. The median progression‐free survival for responders was 26 months (95% CI, 4–48). Marrow polymerase chain reaction negativity was attained in seven responders. These results suggest that this schedule may have notable antitumour activity in patients with MCL, including patients in relapse after autologous stem cell transplantation.
Diagnosis of red cell G6PD deficiency in rural Burkina Faso. Comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotyping
Authors: Meissner Peter E. , Coulibaly Boubacar , Mandi Germain , Mansmann Ulrich , Witte Steffen , Schiek Wolfgang , Müller Olaf , Heiner Schirmer R. , Mockenhaupt Frank P. , Bienzle Ulrich
Published: September 2005

Glucose‐6‐phosphate dehydrogenase (G6PD) deficient individuals are at increased risk of developing haemolysis following treatment with various antimalarial drugs. Reliable field tests for G6PD deficiency are thus needed in chemotherapy studies and their validity has to be assessed. In two phase II clinical trials on methylene blue (MB) antimalarial therapy in rural Burkina Faso, paediatric and adult participants were tested for G6PD deficiency. The results of a haemoglobin‐adjusted nicotinamide adenine dinucleotide phosphate (NADPH) fluorescence test on paper (NFP test) were compared with polymerase chain reaction (PCR)‐based G6PD genotyping also using blood samples on filter papers. This is the first study comparing sensitivity and specificity of the two methods. There was good agreement between the NFP test results and the PCR findings. The estimate of the sensitivity of the NFP test was 98·2% (95·8–99·6%) and the specificity was 97·1% (94·2–99·2%). In conclusion, the NFP assay is a reliable and inexpensive method for large‐scale G6PD deficiency screening in rural West Africa.
Immune responses following experimental human hookworm infection
Authors: Wright V , Bickle Q
Published: September 2005

To characterize the immune response following primary human hookworm infection, an adult volunteer was infected with 50 L3 larvae of Necator americanus, reinfected 27 months later and followed for a further 6 months. Clinical signs, blood picture, ex-vivo peripheral blood cytokine production (IFN-γ, IL-5, IL-13, IL-10 to mitogen and hookworm antigen), acute phase proteins (APP) (C-reactive protein, CRP and α1-antitrypsin, α1-AT) and antibody levels were determined. Dermatitis, oedema, mild nausea and abdominal discomfort followed the primary infection. Eosinophil counts peaked early during both infections but remained elevated (∼18%) throughout. Transient production of IL-5, IL-13 and APP also followed infection but there were negligible levels of IFN-γ or IL-10. The onset of nausea, oedema and the initial rise in CRP, α1-AT, eosinophilia and IL-5 coincided (days 13–27) with the late larval migration and early establishment of the preadult worms in the intestine. Apart from the eosinophilia these responses declined to baseline levels within 4 months and were less pronounced on re-infection.
Adrenocortical insufficiency after pituitary surgery: an audit of the reliability of the conventional short synacthen test
Authors: Klose M. , Lange M. , Kosteljanetz M. , Poulsgaard L. , Feldt‐Rasmussen U.
Published: September 2005

Background  Assessment of the hypothalamic–pituitary–adrenal (HPA) axis after pituitary surgery is important for appropriate decision making regarding replacement therapy. The synacthen test is often used but is questioned, as time has to elapse for adrenal atrophy to develop.

Objective  To audit the use of the 250 µg synacthen test after transsphenoidal adenomectomy.

Methods  A retrospective study of 110 patients submitted to first‐time transsphenoidal adenomectomy. Anterior pituitary testing was performed preoperatively, 1 week and 1, 3, 6 and 12 months postoperatively. The adrenocortical function was tested by a synacthen test (250 µg synacthen i.v.).

Results  Thirty‐two out of 71 patients with normal HPA function before surgery developed insufficiency postoperatively, seven patients presenting an insufficient test response after 1 week, 16 after 1 month and nine after 3 months, whereas none became insufficient during the remaining follow‐up. Three patients presented symptomatic adrenal insufficiency during the first postoperative week despite a normal test. All of these developed an insufficient test 1 month postoperatively. A 1‐week basal plasma cortisol > 400 nmol/l indicated HPA sufficiency, whereas a basal cortisol ≤ 100 nmol/l indicated insufficiency when related to the diagnosis based on the 3‐month synacthen test.

Conclusion  This study confirms that the synacthen test is of limited use in the early postoperative phase, because out of 62 patients with normal 1‐week postoperative synacthen responses, 23 patients developed a test that was indicative of adrenal insufficiency over 1–3 months. Our results indicate that a large proportion of patients should be considered for hydrocortisone replacement therapy up to 3 months postoperatively followed by reassessment of the HPA axis.