bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallization of Amorphous Precursors in the Calcia–Alumina System: A Differential Scanning Calorimetry Study
Authors: Douy André , Gervais Monique
Published: July 2008

Amorphous powders were synthesized by spray‐drying aqueous solutions of calcium and aluminum nitrates, followed by calcination in order to completely decompose the salts. The formation of pure calcium aluminates—C3A, C5A3, C12A7, CA, CA2, and CA6 (C = CaO and A = Al2O3)—has been studied by DSC and XRD. A number of compositions first crystallized to metastable structures without partitioning, i.e., without phase separation. This is the case for orthorhombic C5A3, orthorhombic CA, and γ‐Al2O3 solid solution which may incorporate up to about 25 mol% CaO. o‐C5A3 ultimately partitioned into a mixture of C12A7 and CA according to the equilibrium diagram. o ‐CA transformed partitionless into the stable monoclinic m ‐CA, and the stable CA6 compound was obtained pure at low temperature from γ‐Al2O3 solid solution through a second exotherm. Among all the calcium aluminates studied, C3A was the only one for which an intermediary amorphous precursor could not be obtained, CaO crystallizing as the nitrates were decomposed. Phase transitions involving metastable materials are often fast and release heat over a narrow temperature range leading to steep exothermal DSC signals even at a relatively low heating rate (5°C/min). The present results are consistent with current understanding of partitionless crystallization. They clearly show the ability of the synthesis used to achieve homogeneous mixing at the molecular level. Amorphous precursors formed in a large composition range may be advantageously used as glass models.
Nanocrystalline γ‐Alumina Synthesized by Sonohydrolysis of Alkoxide Precursor in the Presence of Organic Acids: Structure and Morphological Properties
Authors: Ramesh Sivarajan , Sominska Elena , Cina Baruch , Chaim Rachman , Gedanken Aharon
Published: July 2008

γ‐Al2O3 nanoparticles with an average size of 5 nm were synthesized by the hydrolysis of aluminum triisopropoxide under the influence of power ultrasound (100 W/cm2) and in the presence of formic or oxalic acids as peptizers, followed by calcination. The structural and morphological properties of the as‐prepared precursor hydroxides and calcined nanocrystalline powders were characterized by XRD, SEM, TEM, TGA, IR, and BET. The ultrasound‐driven cavitation process has been shown to affect the agglomeration of the precursor nanoparticles by condensation of interparticle hydroxyls. The oxalate anions were strongly adsorbed on the surface of the precursor nanoparticles and thus retarded the ultrasound‐driven condensation of interparticle hydroxyls. Formic acid showed a lesser degree of adsorption on the surface of the precursor particles. The ultrasound‐driven agglomeration of the primary particles as well as the role of organic modifiers on the microstructural properties of the precursor and the target alumina phases have been discussed.
Microwave Dielectric Loss of Titanium Oxide
Authors: Templeton Alan , Wang Xiaoru , Penn Stuart J. , Webb Stephen J. , Cohen Lesley F. , Alford Neil McN.
Published: July 2008

The dielectric loss (tan δ) of titanium dioxide (TiO2) disks has been measured at a frequency of 3 GHz. High‐purity TiO2 sintered to almost‐full density exhibits a very high tan δ, which is interpreted to be due to oxygen deficiency. To counter this, doping with stable divalent and trivalent cations, such as Mg and Al, leads to a low tan δ, probably by preventing Ti4+ reduction. The tan δ of polycrystalline TiO2 doped with divalent and trivalent ions with ionic radii in the range of 0.5–0.95 Å at 3 GHz can be very low: 6 × 10−5 (Q∼ 17 000) at a temperature of 300 K. The tan δ of undoped pure TiO2 disks increases when the disks are cooled from 300 K to ∼100 K. At temperatures <100 K, the tan δ decreases rapidly, which is interpreted as carrier freeze‐out. The tan δ for all the high‐Q doped TiO2 polycrystalline samples smoothly decrease to ∼5 × 10−6 (Q∼ 200 000) at 15 K, comparable to that of single crystals.
Dielectric and Electromechanical Properties of Textured Niobium‐Doped Bismuth Titanate Ceramics
Authors: Hong Seong‐Hyeon , Trolier‐McKinstry Susan , Messing Gary L.
Published: July 2008

Textured Nb‐doped bismuth titanate ceramics (Bi4Ti3−x/5‐ Nbx/5O12, where x= 0.02) were fabricated by templated grain growth. It was found that the use of a fine precursor powder led to enhanced densification of the ceramic, while Nb doping reduced electrical conduction and dielectric loss, which enabled poling at high temperatures and high electric fields. Sintered tapes showed anisotropic dielectric and piezoelectric properties when measured parallel and perpendicular to the casting plane (e.g., the remanent polarization differed by more than a factor of 15 in the two directions). The piezoelectric constant parallel to the casting plane of the tape was ∼30 pC/N, or ∼77% of the single‐crystal value. Thermal depoling studies demonstrated that high‐temperature piezoelectric applications are possible up to ∼450°C in textured, doped bismuth titanate.
Fabrication of Piezoelectric Ceramic/Polymer Composite Transducers Using Fused Deposition of Ceramics
Authors: Lous Gwenaëlle M. , Cornejo Iván A. , McNulty Thomas F. , Safari Ahmad , Danforth Stephen C.
Published: July 2008

The fused deposition of ceramics (FDC) technique was used to fabricate piezoelectric ceramic skeletons for the development of piezoelectric composite transducers with 2–2 connectivity for medical imaging. The green parts were designed to have 30 vol% lead zirconate titanate ceramic (PZT‐5H) in the final composites. Physical characterization of the sintered samples revealed that 96% of the theoretical density was achieved. Optical microscopy showed that defects due to the FDC mode of deposition, such as small roads and bubbles, were eliminated, because of improvements in powder processing. The electromechanical properties of the final composites were similar to the properties that were obtained for conventionally made composites. A matching layer and a backing layer, as well as wires and an inductor, were added to each FDC composite to fabricate a functional medical imaging transducer. The devices were tested in water using a steel target 3.5 cm thick. Echoes from the target could be detected with all the transducers that were fabricated using FDC. The sensitivities of the transducers were similar to that of a commercial transducer. However, the ringing was much longer than that for a commercial transducer, because the backing layer was not optimized in the transducers that were fabricated using FDC.
Hysteresis in theI–VTunneling Characteristics ofn‐Type BaTiO3Ceramics
Authors: Kolodiazhnyi Taras V. , Thomas Daniel F.
Published: July 2008

Scanning tunneling microscopy (STM) and spectroscopy (STS) have been applied to study the surface electronic properties ofn‐type BaTiO3ceramics under ultrahigh vacuum and at various oxygen partial pressures.I–Vtunneling characteristics of vacuum‐annealed BaTiO3do not exhibit rectifying behavior, implying that the Fermi level is pinned at the surface. The surface band gap of BaTiO3annealed under vacuum at 540°C is equal to 1 eV. The top edge of the surface valence band is located 0.7 eV below the Fermi level. Hysteresis in theI–Vcharacteristics has been observed at high oxygen partial pressures. Dosing of the BaTiO3with oxygen increases the surface band gap and unpins the Fermi level. As a result, theI–Vcharacteristics acquire rectifying features similar to those observed for BaTiO3Schottky‐type diodes. Hysteresis in theI–Vspectra observed at high oxygen partial pressures is attributed to the changes of the surface potential barrier due to adsorption/desorption of oxygen modulated by the tip‐sample potential difference.
Dielectric‐State Analysis in Solid‐Solution Pb(Yb1/2Ta1/2)O3–Pb(Lu1/2Nb1/2)O3
Authors: Park Yung , Cho Kurn
Published: July 2008

The structure and temperature dependence of complex lead perovskite dielectrics were investigated for the system (1 −x)Pb(Yb1/2Ta1/2)O3–x Pb(Lu1/2Nb1/2)O3. Superlattice reflections for the compositions 0.8 < x < 1.0 were observed by X‐ray diffractometry, and the temperature‐composition dielectric‐state diagram was determined. In the present study, the disordered middle composition, with 0.2 < x < 0.8, showed a diffuse paraelectric–ferroelectric phase transition, whereas the ordered end compositions, with 0 ≤x < 0.2 and 0.8 < x≤ 1.0, revealed successive sharp paraelectric–antiferroelectric and weak antiferroelectric–ferroelectric phase transitions. The dielectric state was confirmed by examining the variation of polarization (P) with electric field (E).
Crystal Chemistry and Dielectric Properties of Chemically Substituted (Bi1.5Zn1.0Nb1.5)O7 and Bi2(Zn2/3Nb4/3)O7 Pyrochlores
Authors: Valant Matjaz , Davies Peter K.
Published: July 2008

The effect of the chemical substitution of Ti, Zr, and Gd cations on the structure and properties of bismuth‐based pyrochlores was investigated for (Bi1.5Zn1.0Nb1.5)O7 and Bi2(Zn2/3Nb4/3)O7. Broad ranges of solid solutions based on cubic (Bi1.5Zn1.0Nb1.5)O7 were observed for Ti and Zr cations: (Bi1.5Zn1−(x/3)Nb1.5−(2 x/3)Zrx)O7 (0.0 ≤x≤ 1.5) and (Bi1.5Zn1−(x/3)Nb1.5−(2 x/3)Tix)O7 (0.0 ≤x≤ 2.25). For Gd cations, the range of solid solution was quite limited in (Bi1.5−xGdxZn1.0Nb1.5)O7 (0.0 ≤x≤ 0.2); however, the range of solid solution is more extensive in the system that contains Ti and Gd cations ((Bi1.5−xGdxZn0.5Ti1.5Nb0.5)O7 (0.0 ≤x≤ 0.6)). The stability fields of the solid solutions could be interpreted by using the ratio of the ionic sizes of the A‐ and B‐site ions in the pyrochlore structure (RA/RB). The substituted phases exhibited permittivities (κ′) in the range of ∼100–200 and relatively low dielectric losses (tan δ < 7 × 10−4) at 1 MHz. The temperature coefficients of permittivity (τκ) varied in accordance with the RA/RB value and could be tuned from −88 ppm/K to −1300 ppm/K. For the orthorhombic Bi2(Zn2/3Nb4/3)O7 pyrochlore, the ranges of solid solution were very limited and the dielectric properties remained similar to those of the undoped phase (κ′= 90, τκ= 150 ppm/K).
Direct Imaging of Atomic Ordering in Undoped and La‐Doped Pb(Mg1/3Nb2/3)O3
Authors: Xu Zhengkui , Gupta Surya M. , Viehland Dwight , Yan Yanfa , Pennycook Stephen J.
Published: July 2008

In this paper, we report the first direct observations of local ordering in undoped and La‐doped Pb(Mg1/3Nb2/3)O3 (PMN) on an atomic scale by high‐resolution (∼1.26 Å) Z‐contrast imaging. The 1:1 ordering occurs by a variation in the occupancy of Mg and Nb cations between BI and BII sublattices. In ordered regions, the BII sublattice is dominantly occupied by Nb cations, but a small Mg occupancy cannot be excluded. The Mg cations were found to dominantly occupy the BI sublattice. Within the BI sublattice, the local Mg/Nb ratio was found to vary among the various BI sublattices. The results show that the random‐site model, rather than the space‐charge model, is a better structural model for the 1:1 ordering observed in PMN. A random distribution of Mg and Nb cations on the BI sublattice within 1:1 ordered regions is believed to be responsible for the relaxor behavior of mixed B‐site cation relaxors, such as PMN.
Sintering of Industrial Mullites in the Presence of Magnesia as a Sintering Aid
Authors: Montanaro Laura , Perrot Christophe , Esnouf Claude , Thollet Gilbert , Fantozzi Gilbert , Negro Alfredo
Published: July 2008

The sinterability of two industrial mullite powders, in the presence of MgO as a sintering aid, was investigated. A glassy phase, which was generated during preparation, was present in both powders; this glassy phase had a strong influence on sintering, depending on its content, composition, and spatial distribution. MgO promoted sintering in the presence of a liquid phase, both in the as‐received materials and in samples washed with HF, in which most of the pre‐existing glassy phase was eliminated. Investigations using transmission electron microscopy, coupled with energy‐dispersive spectroscopy, as well as dilatometric measurements and X‐ray diffraction data, on washed and unwashed materials and on quenched and slow‐cooled samples allowed a better understanding of the influence of MgO and the glassy phase on the sintering behavior and the formation of new phases. Most of the phases, in fact, can be explained by using the MgO–Al2O3–SiO2 phase diagram, even in such complex systems.
Experimental Investigation and Thermodynamic Calculation of the Titanium–Silicon–Carbon System
Authors: Du Yong , Schuster Julius C. , Seifert Hans J. , Aldinger Fritz
Published: July 2008

The 1100°C isothermal section and the isopleths at 5, 10, and 15 at.% C in the Ti–Si–C system were determined by DTA and XRD methods. Five invariant reactions (L (liquid) = Si + SiC + TiSi2 at 1330°C, L = TiSi + TiSi2+ Ti5Si3Cx at 1485°C, L + Ti5Si3Cx= Ti3SiC2+ TiSi2 at 1485°C, L + Ti3SiC2= TiSi2+ SiC at 1473°C, and L + TiC = bcc‐(Ti) + Ti5Si3Cx at 1341°C) were observed. The transition temperature for L + TiC = Ti3SiC2+ SiC was measured by the Pirani technique. Optimized thermodynamic parameters for the Ti–Si–C system were then obtained by means of the CALPHAD (calculation of phase diagrams) method applied to the present experimental results and reliable literature data. The calculations satisfactorily account for most of the experimental data.
Anisotropic Grain Growth and Microstructural Evolution of Dense Mullite above 1550°C
Authors: Huang Tieshu , Rahaman Mohamed N. , Mah Tai‐Il , Parthasarathay Triplicane A.
Published: July 2008

Mullite powder with a nearly stoichiometric composition was hot‐pressed at 1550°C to produce an almost fully dense microstructure of fine, nearly uniaxial grains. The grain growth of the dense mullite was investigated during subsequent annealing at temperatures in the range of 1550–1750°C. Grain growth was relatively slow at 1550°C and the microstructure remained nearly equiaxial. Annealing at temperatures above the eutectic temperature (∼1590°C) produced fairly rapid anisotropic grain growth. At 1750°C, the anisotropic grain growth can be divided into two stages. In the first stage, the initial microstructure with an anisometric shape factor of 1.7 evolved rapidly into a microstructure with a shape factor of 2.7, consisting of a significant fraction of highly elongated grains. In the second stage, the microstructure evolved slowly into a system consisting of somewhat “blocky” grains with a shape factor of 2.2. The Al2O3 content of the mullite grains increased slightly and reached an equilibrium value during the first stage of anisotropic grain growth. For the samples annealed at 1750°C, the indentation fracture toughness (2.5 ± 0.2 MPa · m1/2) was almost independent of the anisometric shape factor. The interaction between the indentation cracks and the microstructure showed a predominantly transgranular mode of crack propagation. The data indicate that while a network of highly elongated grains can be developed by the present approach, some further manipulation of the grain boundary chemistry is required for an improvement of the fracture toughness.
Observations of Accelerated Silicon Carbide Recession by Oxidation at High Water‐Vapor Pressures
Authors: More Karren L. , Tortorelli Peter F. , Ferber Mattison K. , Keiser James R.
Published: July 2008

A study of the exposure of SiC at 1200°C and high water‐vapor pressures (1.5 atm) has shown SiC recession rates that exceed what is predicted based on parabolic oxidation at water‐vapor pressures of less than or equal to ∼1 atm. After exposure to these conditions, distinct silica‐scale structures are observed; thick, porous, nonprotective cristobalite scales form above a thin, dense silica layer. The porous cristobalite thickens with exposure time, while the thickness of the underlying dense layer remains constant. These observations suggest a moving‐boundary phenomenon that is controlled by the rapid conversion of dense vitreous silica to a porous, nonprotective crystalline SiO2.
Nucleation Barrier for Volume‐Conserving Shape Changes of Faceted Crystals
Authors: Mullins William W. , Rohrer Gregory S.
Published: July 2008

This paper considers volume‐conserving shape changes of small faceted particles or cavities; these changes are driven by surface‐energy reduction. If these changes require normal motion of the facets (singular surfaces), and if the perimeter free energy σp (per unit area) of a nucleus of a new facet layer is comparable to a typical surface free energy (σ∼ 1 J/m2), the energy barrier is prohibitively large for facets larger than a limiting size of approximately a nanometer unless they are intersected by dislocations that provide a source of steps. In the absence of such dislocations, particles that contain these facets are immobilized in their initial shapes. If σp < σ, the limiting facet size is increased by a factor of approximately σ/σp.
Probing Polymeric Stabilization in Nonaqueous Media by Direct Measurements
Authors: Bergström Lennart , Blomberg Eva
Published: July 2008

The steric repulsion induced by adsorbed layers of the commercial dispersant Hypermer KD3 has been probed by direct measurements in decalin. The forces are long range (commencing at 30–40 nm) and repulsive, and the distance dependence can be modeled with a simple scaling theory expression valid for polymer brushes. We obtain layer thicknesses of ∼9–15 nm for the compressed layers, depending on KD3 concentration, whereas the undisturbed layers have a thickness of ∼23–24 nm, independent of polymer concentration. Comparison of the measured interaction lengths with previous layer thickness estimates based on rheological studies shows that the polymer layers are compressed in dense suspensions.
Influence of Silica and Aluminum Contents on Sintering of and Grain Growth in 6H‐SiC Powders
Authors: Tanaka Hidehiko , Yoshimura Humberto N. , Otani Shigeki , Zhou You , Toriyama Motohiro
Published: July 2008

To clarify the influence of impurities on the sintering of SiC powder, three 6H‐SiC powder samples—with different levels of SiO2 and aluminum impurities—were sintered with additions of boron and carbon. The densification, grain growth, and transformation of 6H‐SiC during sintering were studied qualitatively. The powder that contained the most SiO2 required the greatest amount of boron additive for complete densification. SiO2 apparently reacted with the boron additive and was consumed during sintering. The powder with the greater aluminum impurity level exhibited partial transformation of 6H‐SiC to 4H‐SiC, and the sintered SiC from this powder had elongated grains. The partial transformation in the SiC crystal accelerated non‐equiaxial grain growth.
Transparent Anatase Nanocomposite Films by the Sol–Gel Process at Low Temperatures
Authors: Matsuda Atsunori , Kotani Yoshinori , Kogure Toshihiro , Tatsumisago Masahiro , Minami Tsutomu
Published: July 2008

We have successfully prepared transparent anatase nanocomposite films on various types of substrates, including organic polymers, using the sol–gel method at temperatures <100°C under ambient pressure. This novel process is based on the findings that (i) anatase nanocrystals are uniquely formed in sol–gel‐derived SiO2–TiO2 films that have been subjected to a hot‐water treatment, and (ii) the addition of an organic polymer such as poly(ethylene glycol) in the films accelerates the formation of anatase nanocrystals. The film coating on the substrates is a promising candidate for use as a photocatalyst to decompose environmental pollutants and harmful microorganisms.
Synthesis and Characterization of MgAl2O4 Spinel Precursor from a Heterogeneous Alkoxide Solution Containing Fine MgO Powder
Authors: Shiono Takeshi , Shiono Koji , Miyamoto Kazuyo , Pezzotti Giuseppe
Published: July 2008

A precursor was synthesized from a heterogeneous alkoxide solution that contained fine MgO powder, which allowed the preparation of MgAl2O4 spinel powder with high sinterability characteristics. The precursor consisted of a mixture of boehmite (AlO(OH)) and a mixed hydroxide (Mg4Al2(OH)14· 3H2O). The spinel phase formed through two steps: (i) decomposition of the mixed hydroxide at low temperature and (ii) solid‐state reaction between MgO and γ‐Al2O3 at higher temperatures. Dense polycrystalline spinel could be obtained from the calcined powders at sintering temperatures as low as 1400°C.
A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post‐release
Authors: Gordon Michael S. , Kinlock Timothy W. , Schwartz Robert P. , O’Grady Kevin E.
Published: July 2008

Aims This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post‐release.

Design A three‐group randomized controlled trial was conducted between September 2003 and June 2005.

Setting A Baltimore pre‐release prison.

Participants Two hundred and eleven adult pre‐release inmates who were heroin‐dependent during the year prior to incarceration.

Intervention Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community‐based methadone maintenance program upon release (n = 71).

Measurements Addiction Severity Index at study entry and follow‐up. Additional assessments at 6 months post‐release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs.

Findings Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid‐positive urine specimen compared to counseling only (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self‐reported heroin use and criminal activity than counseling only participants.

Conclusions Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post‐release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.
Adolescent cannabis users at 24 years: trajectories to regular weekly use and dependence in young adulthood
Authors: Swift Wendy , Coffey Carolyn , Carlin John B. , Degenhardt Louisa , Patton George C.
Published: July 2008

Aims  To examine the association between cannabis use by 18 years and problematic cannabis use at 24 years, considering possible mediating and confounding factors.

Design  Ten‐year representative prospective study with data from six time‐points in adolescence (mean age 14.9–17.4 years) and two in young adulthood (mean age 20.7 and 24.1 years)

Setting  Victoria, Australia.

Participants  Inception cohort of 1943 secondary school students (95.6% response rate), with 1520 (78% of adolescent participants) interviewed in the final wave.

Measurements  Participants reported frequency of cannabis use for the past 6 months at each time‐point in adolescence (age 14–17 years). Cannabis exposure was defined as: maximum frequency of use (occasional, weekly, daily), number of waves of use (1 or 2; 3–6) and first wave of use (early use: first waves 1–3). Young adult (24 years) outcomes were: weekly+ cannabis use and DSM‐IV cannabis dependence, referred to collectively as problematic use.

Findings  Of those interviewed at age 24 (wave 8), 34% had reported cannabis use in adolescence (waves 1–6), 12% at a level of weekly or more frequent use; 37% of these adolescent cannabis users were using at least weekly at wave 8, with 20% exhibiting dependence. Persistent adolescent cannabis and tobacco use as well as persistent mental health problems were associated strongly with problematic cannabis use at 24 years, after adjustment for potential confounding factors.

Conclusions  Heavy, persistent and early‐onset cannabis use were all strongly predictive of later cannabis problems. Even so, occasional use was not free of later problems. Where there was co‐occurring tobacco use or persistent mental health problems, risks for later problem cannabis use was higher.
Alcohol use trajectories among adults in an urban area after a disaster: evidence from a population‐based cohort study
Authors: Cerda Magdalena , Vlahov David , Tracy Melissa , Galea Sandro
Published: July 2008

Alcohol use increased in the New York City (NYC) metropolitan area in the first months after the 11 September 2001 terrorist attacks.

Aims  To investigate alcohol use trajectories in the NYC metropolitan area in the 3 years after 11 September and examine the relative contributions of acute exposure to the attacks and ongoing stressors to these trajectories.

Design  We used a population‐based cohort of adults recruited through a random‐digit‐dial telephone survey in 2002; participants completed three follow‐up interviews over 30 months.

Setting  The NYC metropolitan area.

Participants  A total of 2752 non‐institutionalized adult residents of NYC.

Measurements  We used growth mixture models to assess trajectories in levels of total alcohol consumption and bingeing in the past 30 days, and predictors of these trajectories.

Findings  We identified five trajectories of alcohol consumption levels and three bingeing trajectories. Predictors of higher levels of use over time included ongoing stressors, traumatic events and lower income. Ongoing exposure to stressors and low income also play a central role in bingeing trajectories.

Conclusions  While point‐in‐time mass traumatic events may matter in the short term, their contribution subsides over time. Accumulated stressors and traumatic events, in contrast, lead to higher levels of consumption among respondents already vulnerable to high alcohol use. Interventions to mitigate post‐disaster stressors may have substantial benefit in reducing alcohol abuse in the medium‐ to long term.
Incentive‐elicited striatal activation in adolescent children of alcoholics
Authors: Bjork James M. , Knutson Brian , Hommer Daniel W.
Published: July 2008

Aims  Deficient recruitment of motivational circuitry by non‐drug rewards has been postulated as a pre‐morbid risk factor for substance dependence (SD). We tested whether parental alcoholism, which confers risk of SD, is correlated with altered recruitment of ventral striatum (VS) by non‐drug rewards in adolescence.

Design  During functional magnetic resonance imaging, adolescent children of alcoholics (COA; age 12–16 years) with no psychiatric disorders (including substance abuse) and similarly aged children with no risk factors responded to targets to win or avoid losing $0, $0.20, $1, $5 or a variable amount (ranging from $0.20 to $5).

Results  In general, brain activation by either reward anticipation or outcome notification did not differ between COA and age/gender‐matched controls. Cue‐elicited reward anticipation activated portions of VS in both COA and controls. In nucleus accumbens (NAcc), signal change increased with anticipated reward magnitude (with intermediate recruitment by variable incentives) but not with loss magnitudes. Reward deliveries activated the NAcc and mesofrontal cortex in both COA and controls. Losses activated anterior insula bilaterally in both groups, with more extensive right anterior insula activation by losses in controls. NAcc signal change during anticipation of maximum rewards (relative to non‐reward) correlated positively with both Brief Sensation‐Seeking Scale scores and with self‐reported excitement in response to maximum reward cues (relative to cues for non‐reward).

Conclusions  Among adolescents with no psychiatric disorders, incentive‐elicited VS activation may relate more to individual differences in sensation‐seeking personality than to presence of parental alcoholism alone. Future research could focus on adolescents with behavior disorders or additional risk factors.
Perceived safety and efficacy of nicotine replacement therapies among US smokers and ex‐smokers: relationship with use and compliance
Authors: Shiffman Saul , Ferguson Stuart G. , Rohay Jeffrey , Gitchell Joseph G.
Published: July 2008

Aim  Nicotine replacement therapy (NRT) is effective for smoking cessation, but most smokers try to quit without using it. We examined the impact of misperceptions of NRT safety and efficacy on its use.

Design and participants  A total of 3203 current and former US smokers completed a national mail‐out survey of issues and attitudes related to smoking cessation.

Findings  Two‐thirds (66%) of respondents either agreed that ‘Stop‐smoking products with nicotine are just as harmful as cigarettes’ or were unsure whether the statement was true. These respondents were less likely to have used NRT in the past [30% versus 49%; odds ratio (OR) = 0.45, 95% confidence interval (CI): 0.39–0.53] and less likely to consider using NRT during future quit attempts (40% versus 53%; OR = 0.60, 95% CI = 0.51–0.71). Additionally, of the respondents who had used nicotine gum in the past 12 months (n = 407), those who had concerns about the safety of NRT reported using fewer pieces of gum per day during treatment (six versus eight pieces/day; P < 0.05), and were less likely to report that they used the gum for greater than 4 weeks (28.5% versus 46.8%; OR = 0.45, 95% CI: 0.27–0.76). A large proportion of the respondents also stated that they did not believe NRT to be efficacious.

Conclusions  The findings suggest that many smokers are misinformed about the health risks of NRT and that these misperceptions impede not only the adoption of NRT but also compliance during treatment. Misperception of NRT safety is one barrier to effective use of NRT and probably reduces success in quitting.
Adherence to antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome among drug users: a systematic review
Authors: Malta Monica , Strathdee Steffanie A. , Magnanini Monica M. F. , Bastos Francisco I.
Published: July 2008

Aims  Adherence to highly active antiretroviral therapy (HAART) is a key predictor of survival for human immunodeficiency virus (HIV)‐infected people. Suboptimal adherence among marginalized populations such as HIV‐positive drug users could be associated with clinical failure and the emergence of viral resistance.

Objective  To conduct a systematic review of studies assessing adherence to HAART among HIV‐positive drug users (DU) and identify factors associated with non‐adherence to HIV treatment.

Data sources  Seven electronic databases were searched for peer‐reviewed papers published in English, French, Spanish or Portuguese, from 1996 to 2007.

Study selection and data abstraction  Studies were excluded if they presented only qualitative data, were reviews themselves or assessed other populations without disaggregating data on DU. Findings on adherence were extracted and summarized.

Data synthesis  Forty‐one studies were considered, which studied a total of 15 194 patients, the majority of whom were HIV‐positive DU (n = 11 628, 76.5%). Twenty‐two studies assessed adherence using patient self‐reports, eight used pharmacy records, three used electronic monitoring [i.e. Medication Event Monitoring Systems (MEMS) caps], six studies used a combination of patient self‐report, clinical data and MEMS‐caps, and two analyzed secondary data. Overall, active substance use was associated with poor adherence, as well as depression and low social support. Higher adherence was found in patents receiving care in structured settings (e.g. directly observed therapy) and/or drug addiction treatment (especially substitution therapy).

Conclusion  While lower than other populations—especially among users of stimulants, incarcerated DU and patients with psychiatric comorbidities—adherence to HAART among HIV‐positive DU can be achieved. Better adherence was identified among those engaged in comprehensive services providing HIV and addiction treatment with psychosocial support.
Extended cognitive behavior therapy for cigarette smoking cessation
Authors: Killen Joel D. , Fortmann Stephen P. , Schatzberg Alan F. , Arredondo Christina , Murphy Greer , Hayward Chris , Celio Maria , Cromp DeAnn , Fong Dalea , Pandurangi Maya
Published: July 2008

Primary aim  Examine the effectiveness of extended cognitive behavior therapy (CBT) in promoting longer‐term smoking abstinence.

Design  Open‐label treatment phase followed by extended treatment phase. Randomization conducted prior to entry into open‐label treatment phase; analysis based on intention‐to‐treat to avoid threat of selection bias.

Setting  Community smoking cessation clinic.

Participants  A total of 304 adult smokers (≥18 years of age; ≥10 cigarettes/day).

Intervention  Open‐label (8 weeks): all participants received bupropion SR, nicotine patch, CBT. Extended treatment (12 weeks): participants received either CBT + voicemail monitoring and telephone counseling or telephone‐based general support.

Measurements  Seven‐day point prevalence abstinence, expired‐air carbon monoxide.

Results  At week 20 follow‐up, CBT produced a higher 7‐day point prevalence abstinence rate: 45% versus 29%, P = 0.006; at 52 weeks the difference in abstinence rates (31% versus 27%) was not significant. History of depression was a moderator of treatment. Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy (P < 0.05).

Conclusion  The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non‐smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term. At present, the minimum duration of therapy is unknown.
Drug and Therapeutics Committees in Australia: expected and actual performance
Authors: & LYNN MARIA WEEKES , BROOKS COLLEEN
Published: July 2008

1 This study describes stakeholders’opinions on Drug and Therapeutics Committees (DTCs) and measures the composition, activities and perceived effectiveness of DTCs in Australia.

2 Focus groups explored the opinions of clinicians, consumers and administrators on the goals, objectives and strategies of DTCs.

3 A national survey was sent to 306 hospitals to collect data on the composition, committee processes, goals, objectives, educational activities, policies and decision making of DTCs.

4 Stakeholders believed the DTC should optimise therapeutic health outcomes for patients and economic outcomes for the hospital. Important objectives were availability of safe, efficacious and cost‐effective medicines, affordability of medicines and quality use of medicines.

5 The national survey of DTCs found that over 92% of respondents had a DTC in their hospital. Composition was generally representational and most commonly included members from the disciplines of internal medicine, pharmacy and nursing. More than half the DTCs had executive authority although only 21% had an appeals mechanism.

6 The most commonly cited issues for DTCs in 1994‐95 were quality drug use, drug policies and spending on high cost drugs.

7 While access to clinical pharmacologists and specialist drug utilisation evaluation (DUE) pharmacists was poor, 71% of DTCs had access to DUE data of some sort. Guidelines (61%), prescribing restrictions (60%) and pharmacist monitoring (63%) were the most commonly used strategies to implement DTC policies and decisions. Audit‐feedback activities (61%) and drug bulletins (56%) were the most commonly used interventions.

8 Available information for formulary decision making varied with small rural hospitals having access to significantly less information. The most commonly used information was availability of a therapeutic alternative (87%), efficacy (83%), cost (80%) and estimated usage (78%).

9 On average DTCs reported an ability to implement 75% of decisions (range 0‐95%) with teaching hospitals perceived to perform better than other hospital types.

10 This study reveals a high level of expectation for DTC activities and achievements. In Australia DTCs were involved in policy, education and management initiatives to promote best practice in therapeutics. Few committees appeared to have adequate resources to extend services to their wider community.
Medicine taking in Southampton: a second look
Authors: & M. J. SULLIVAN , GEORGE C. F.
Published: July 2008

1 A 1 in 200 sample of the Southampton electorate were sent a postal questionnaire in January 1993. Of the 756 adults surveyed, 400 (52.9%) returned completed questionnaires. One hundred and eighty‐eight (47.0%) of the respondents had been prescribed a medicine within the previous month.

2 Compared with a survey 9 years earlier, medicine taking had increased amongst men (44.1%vs 33.7% NS) and drugs acting on the respiratory system were in more widespread use (19 vs 7 patients P < 0.05).

3 Patterns of storage of medicines were almost identical to those found in 1984. However, methods of disposal were significantly different with 34% of the respondents stating that they would return left‐over medicines to the Doctor or Pharmacist compared with 17% in the previous study (P < 0.01).

4 Of those taking medicines 120 (63.8%) had received a manufacturers’information leaflet. Medicines used to treat disorders of the respiratory and cardiovascular systems were most likely to be accompanied by such a leaflet (74% and 70% respectively).

5 Those who received a leaflet were almost all satisfied by it. However, patient awareness of potential side effects remained poor with only 30% being aware of any which their medicine might cause.

6 Despite improvements in attitudes towards medicine taking over time patients awareness of potential adverse effects remains limited. Further research is necessary in order to determine how best to educate patients on this topic.
Pharmacokinetics and pharmacodynamics of ()‐sotalol in healthy male volunteers
Authors: KIMURA MASAHIKO , UMEMURA KAZUO , IKEDA YASUHIKO , KOSUGE KAZUHIRO , MIZUNO ATSUHIRO , NAKANOMYO HIROSHI , & KYOICHI OHASHI , NAKASHIMA MITSUYOSHI
Published: July 2008

1 We investigated the pharmacokinetics and pharmacodynamics of (±)‐sotalol administered orally to healthy male volunteers in single doses of 40, 80 and 160 mg and in multiple doses of 80 mg twice daily for 7 consecutive days.

2 In the single dose studies, the half‐life of (‐)‐sotalol (7.2‐8.5 h) was significantly (P < 0.01) shorter than that of (+)‐sotalol (9.1‐11.4 h) while the renal clearance of (‐)‐sotalol (110.6‐126.4 ml min‐1) was significantly (P < 0.01) faster than that of (+)‐sotalol (102.2‐110.1 ml min‐1). In the multiple dose studies, similar differences in the pharmacokinetics of (+)‐ and (‐)‐sotalol were observed. In addition, the pharmacokinetics of both (+)‐ and (‐)‐sotalol on day 4 were shown to be essentially the same as those on day 7.

3 In pharmacodynamic examinations, (±)‐sotalol prolonged QTc intervals on electrocardiograms dose‐dependently after single doses of 80 and 160 mg (3.81 ± 2.96%, 13.23 ± 5.66%). The correlation between the plasma concentration of (±)‐sotalol and prolongation of QTc intervals was nearly linear, and showed no hysteresis.

4 In conclusion, we demonstrated that QTc interval was prolonged with a linear correlation to the plasma concentration of (±)‐sotalol. In addition, our study suggested that differences in the pharmacokinetics of (+)‐ and (‐)‐sotalol may be attributable to faster urinary excretion of (‐)‐sotalol.
The implications of non‐linear red blood cell partitioning for the pharmacokinetics and pharmacodynamics of the nucleoside transport inhibitor draflazine
Authors: SNOECK E. , JACQMIN P. , VAN PEER A. , DANHOF M. , VER DONCK K. , VAN BELLE H. , WOESTENBORGHS R. , CRABBÉ R. , VAN GOOL R. , DUPONT A. , HEYKANTS J.
Published: July 2008

1 Draflazine, a nucleoside transport inhibitor, was administered as a 15 min i.v. infusion of 2.5 mg to eight healthy male subjects. Plasma and whole blood concentrations were measured up to 32 h post‐dose, and were related to adenosine breakdown inhibition (ABI) measured ex vivo, which served as a pharmacodynamic endpoint.

2 The red blood cell/plasma distribution of draflazine was non‐linear and characterized as a capacity‐limited specific binding to the nucleoside transporter on the red blood cells. The binding (dissociation) constant Kd was 0.87 ng ml‐1 plasma and the maximal specific binding capacity (Bmax) was 164ng ml‐1 RBC, which corresponds to about 14000 specific binding sites per erythrocyte. Non‐specific binding amounted to less than 15% of the total binding.

3 The pharmacokinetics of draflazine in blood were determined in each subject and characterized by a two‐compartment pharmacokinetic model. The pharm‐acokinetic parameters (mean ± s.d.) were: clearance 22.0 ± 8.0 ml min‐1, volume of distribution at steady‐state 39.8 ± 4.71 and terminal half‐life 24.0 ± 9.4 h. Concentrations in plasma were much lower, and could only be determined accurately in pooled plasma samples with a red blood cell binding assay. The pharmacokinetic parameters in pooled plasma were: clearance 551 ml min‐1, volume of distribution at steady‐state 3491 and terminal half‐life 10.7 h.

4 A non‐linear relationship was observed between the plasma or blood concentration of draflazine and the ABI determined ex vivo. This relationship was characterized by the sigmoidal Emax pharmacodynamic model. Based on concentrations in pooled plasma, values of the pharmacodynamic parameters were Emax 100%, IC50 10.5 ng ml‐1 and Hill factor 0.9. When using whole blood concentrations, the relationship was much steeper with values (mean ± s.d.) Emax 92.4 + 5.6%, IC50 76.0 ± 15.3 ng ml‐1 and Hill factor 3.5 ± 0.9.

5 Binding to the nucleoside transporter on red blood cells is an important determinant of the pharmacokinetics of draflazine and a high degree of occupancy of the transporter by draflazine is required to inhibit adenosine breakdown ex vivo. It is suggested that red blood cell nucleoside transporter occupancy may serve as a useful pharmacodynamic endpoint in dose ranging studies with draflazine.
Effect of intravenous magnesium sulphate on airway calibre and airway reactivity to histamine in asthmatic subjects
Authors: & JENNIFER M HILL , BRITTON JOHN
Published: July 2008

In a randomized, double‐blind, placebo controlled cross‐over study we have investigated the effect of intravenous magnesium on airway calibre and airway reactivity to histamine in 20 subjects with mild to moderate asthma. After baseline measurements of forced expiratory volume in one second (FEV1), subjects received 100 ml normal saline with or without 2 g of magnesium sulphate by infusion over 20 min. Measurements of FEV1 were repeated at 5 min intervals throughout the infusion, and the provocative dose of histamine required to drop the FEV1 by 20% from baseline (PD20FEV1) was determined at 20 min. The area under the curve (AUC) in litre minutes for change from baseline in FEV1 between 0 and 20 min was significantly higher on the magnesium study day (mean difference in AUC (95% CI) 1.71 (0.02‐3.4), P= 0.049). The increase in FEV1 from baseline with magnesium relative to saline was maximal at 20 min (mean difference (95% CI) 0.13 (0.02‐0.23) 1, P= 0.01). Log PD20FEV1 to histamine was not significantly different after magnesium and saline (mean difference in log PD20FEV1 (95% CI) 0.04 (‐0.19 to 0.27), P= 0.7). We conclude that intravenous magnesium is a weak bronchodilator but does not alter airway reactivity at this dose in stable asthmatic subjects.
A single sample saliva test to determine acetylator phenotype
Authors: & A. D. HUTCHINGS , ROUTLEDGE P. A.
Published: July 2008

A comparison was made between the results of acetylator phenotyping by determination of the acetylisoniazid to isoniazid (AcINH/INH) concentration ratio in plasma and in saliva 3 h after oral administration of isoniazid (200mg). In the 154 subjects studied, 68 (44%) were fast acetylators (AcINH/INH ratio > 1.5) using the plasma ratio. In all subjects the saliva AcINH/INH ratio was also > 1.5. Eighty‐five of the eighty‐six remaining subjects had saliva and plasma AcINH/INH ratios < 1.5 in the 3 h sample. Thus, with one exception there was complete agreement between the acetylator status determined by measurement of saliva or plasma AcINH/INH ratio in a single 3 h sample. Saliva measurement may provide a simple non‐invasive alternative to plasma collection in assessing acetylator status.
Effect of food on the comparative pharmacokinetics of modified‐release morphine tablet formulations, Oramorph SR and MST Continus
Authors: & A. J. MILLER , SMITH K J.
Published: July 2008

In their recent paper Drake et al. [1] have expressed the opinion that Oramorph SR tablets and MST CONTINUS tablets are‘readily interchangeable’in patients receiving either product for pain control. This is based on the equivalence of the extent of availability of morphine from the two preparations. However, guidelines on bioequivalence issued by the authorities of the European Community define bioavailability in terms of both the rate and extent of absorption [2]. The authors appear to have chosen to disregard the statistically significant difference in Cmax between the preparations, the mean Cmax associated with the Oramorph SR Tablet (13.9 ng ml‐1) was 30% higher than that associated with the MST CONTINUS tablet (10.7 ng ml‐1) which indicates that the rate of absorption from the two preparations was different. Therefore, we do not accept that the two products are interchangeable.
Selective factor VIII and V inactivation by iminodiacetate ion exchange resin through metal ion adsorption*
Authors: Takeyama Masahiro , Nogami Keiji , Okuda Masahiro , Sakurai Yoshihiko , Matsumoto Tomoko , Tanaka Ichiro , Yoshioka Akira , Shima Midori
Published: July 2008

The procoagulant activity of factors VIII and V depends on the presence of metal ion(s). We examined the effect of cation‐exchange resins with different functional groups on both factors, of which only reaction with iminodiacetate resin resulted in the complete loss of their activity levels in plasma. However, the antigen level of factor VIII was preserved by >95%. This resin reduced divalent cations content present in factor VIII preparations, indicating that it inactivated this factor by direct deprivation of predominant Ca2+ (>Mn2+>>Cu2+), rather than adsorption of the factor itself. The antigen level of recombinant factor VIII alone was decreased by >95% by reaction with resin, whilst that complexed with von Willebrand factor was preserved by >95%. Iminodiacetate resin‐treated plasma was evaluated by measuring factor VIII and V activity in plasma with various levels of either activity. These were significantly correlated to the values obtained using factor VIII‐ or V‐deficient plasma prepared commercially by immunodepletion. We demonstrated that iminodiacetate resin‐induced factors VIII and V inactivation is because of direct deprivation of metal ions, predominantly Ca2+, which is more essential for the functional structure of their molecules. Furthermore, iminodiacetate resin‐treated plasma would be useful as a substrate for measuring the activity of these factors.