bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Forcing of End-Tidal Carbon Dioxide and Oxygen Applied to Functional Magnetic Resonance Imaging
Authors: Wise Richard G , Pattinson Kyle TS , Bulte Daniel P , Chiarelli Peter A , Mayhew Stephen D , Balanos George M , O'Connor David F , Pragnell Timothy R , Robbins Peter A , Tracey Irene , Jezzard Peter
Published: April 2007

Investigations into the blood oxygenation level-dependent (BOLD) functional MRI signal have used respiratory challenges with the aim of probing cerebrovascular physiology. Such challenges have altered the inspired partial pressures of either carbon dioxide or oxygen, typically to a fixed and constant level (fixed inspired challenge (FIC)). The resulting end-tidal gas partial pressures then depend on the subject's metabolism and ventilatory responses. In contrast, dynamic end-tidal forcing (DEF) rapidly and independently sets end-tidal oxygen and carbon dioxide to desired levels by altering the inspired gas partial pressures on a breath-by-breath basis using computer-controlled feedback. This study implements DEF in the MRI environment to map BOLD signal reactivity to CO2. We performed BOLD (T2*) contrast FMRI in four healthy male volunteers, while using DEF to provide a cyclic normocapnichypercapnic challenge, with each cycle lasting 4 mins (PetCO2 mean±s.d., from 40.9 ± 1.8 to 46.4 ± 1.6 mm Hg). This was compared with a traditional fixed-inspired (FiCO2 = 5%) hypercapnic challenge (PetCO2 mean±s.d., from 38.2 ± 2.1 to 45.6 ± 1.4 mm Hg). Dynamic end-tidal forcing achieved the desired target PetCO2 for each subject while maintaining PetCO2 constant. As a result of CO2-induced increases in ventilation, the FIC showed a greater cyclic fluctuation in PetCO2. These were associated with spatially widespread fluctuations in BOLD signal that were eliminated largely by the control of PetCO2 during DEF. The DEF system can provide flexible, convenient, and physiologically well-controlled respiratory challenges in the MRI environment for mapping dynamic responses of the cerebrovasculature.
Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5-phenylmorphans. Synthesis of a µ-agonist δ-antagonist and δ-inverse agonists
Authors: Cheng Kejun , Kim In Jong , Lee Mei-Jing , Adah Steven A. , Raymond Tyler J. , Bilsky Edward J. , Aceto Mario D. , May Everette L. , Harris Louis S. , Coop Andrew , Dersch Christina M. , Rothman Richard B. , Jacobson Arthur E. , Rice Kenner C.
Published: April 2007

A novel potent non-peptide morphine-like antinociceptive with μ-agonist and δ-antagonist properties represents a lead towards non-dependence producing analgesics.
Ferromagnetic relaxation in (Ni81Fe19)1−xCux thin films: Band filling at high Z
Authors: Guan Y. , Bailey W. E.
Published: April 2007

We measure the compositional dependence of ferromagnetic relaxation (damping) in (Ni81Fe19)1−xCux magnetic thin films. The compositions tested (0⩽x⩽0.30) cover the decreasing, high-Z (27.6⩽Z⩽28.0) branch of the Slater-Pauling curve. Broadband (0–18GHz) ferromagnetic resonance measurements in parallel (in-plane) and perpendicular (out-of-plane) resonance configurations reveal purely intrinsic, Gilbert-type damping, increasing with Cu content, from α=0.0081±0.0003 (no Cu) to α=0.0242±0.0006 (30% Cu). Despite the marked decrease in saturation magnetization μ0Ms, in good agreement with Slater-Pauling values, the relaxation rate G also increases, from G=112±4MHz (no Cu) to G=150±4MHz (30% Cu). The results are similar in variation with Z to those found on the low-Z branch of the Slater-Pauling curve, in epitaxial Fe1−xVx.
Spin-orbit relativistic calculations of the core excitation spectra of SO2
Authors: Fronzoni G. , De Francesco R. , Stener M. , Decleva P.
Published: April 2007

The time dependent density functional theory approach within the two-component zero-order relativistic approximation has been applied to the calculation of the core excitation spectra of SO2 molecule. The results obtained reproduce correctly the high resolution experimental spectra and allow the assignment of the spectral features both of the valence and Rydberg regions in the S 1s and O 1s spectra. For the S 2p threshold a correct description of the spin-orbit coupling as well as of the molecular field splitting appears mandatory for a reliable description of the spectrum and a detailed attribution of the complex Rydberg manifold of core excited states.
Synthesis and spectroscopy of CdS nanoparticles in amphiphilic diblock copolymer micelles
Authors: Mandal Debabrata , Chatterjee Uma
Published: April 2007

Amphiphilic diblock copolymers with the same hydrophilic but different hydrophobic blocks were used as stabilizing agents to prepare cadmium sulfide nanoparticles in aqueous solutions containing 5% of different nonaqueous solvents: methanol, THF, and acetone. Nearly spherical nanoparticles with a fair degree of monodispersity and quantum yields of 1.5%–2% were obtained. Optical absorption band edge of the CdS nanoparticles shows a >0.5eV blueshift compared to that of bulk CdS, indicating a high degree of quantum confinement. The absorption spectra, while insensitive to the nature of the hydrophobic blocks, exhibited a clear dependence on the nature of the minor, nonaqueous solvents. The photoluminescence in all cases was broad and redshifted, indicating a predominance of surface trap-state emission. Time-resolved photoluminescence demonstrates that the trap states are populated within the first 500fs, followed by decay with a broad range of time constants from 0.1to>10ns, low energy traps decaying at a slower rate than high-energy ones. Time-resolved photoluminescence anisotropy revealed that the nanoparticles experience a local microviscosity very similar to that of bulk water. The experimental observations suggest that nanoparticle formation takes place predominantly in the hydrophilic corona region of the micelles, around specific points with high local concentration of the Cd+2-coordinating basic amine groups of hydrophilic block and/or the minor, nonaqueous solvent component.
Simulation and theory of flexible equilibrium polymers under poor solvent conditions
Authors: Pam LaKedra S. , Spell Larissa L. , Kindt James T.
Published: April 2007

Grand canonical Monte Carlo simulation and simple statistical thermodynamic theory are used to model the aggregation and phase separation of systems of reversibly polymerizing monomers, capable of forming chains with or without the ability to cyclize into rings, with isotropic square-well attractions between nonbonded pairs of monomers. The general trend observed in simulation of chain-only systems, as predicted in a number of published theoretical works, is that the critical temperature for phase separation increases and the critical monomer density decreases with rising polymer bond strength. Introduction of the equilibrium between chains and rings into the theory lowers the predicted critical temperature and increases the predicted critical density. While the chain-only theories predict a vanishing critical density in the limit of complete polymerization, when ring formation is taken into account the predicted critical density in the same limit approaches the density of the onset of the ring-chain transition. The theoretically predicted effect of cyclization on chemical potential is in good qualitative agreement with a subset of simulation results in which chain-only systems were compared with equilibrium mixtures of rings and chains. The influence of attractions on the aggregation number and radius of gyration of chains and rings observed in simulations is also discussed.
Path integral formulation for quantum nonadiabatic dynamics and the mixed quantum classical limit
Authors: Krishna Vinod
Published: April 2007

This work identifies geometric effects on dynamics due to nonadiabatic couplings in Born-Oppenheimer systems and provides a systematic method for deriving corrections to mixed quantum classical methods. Specifically, an exact path integral formulation of the quantum nonadiabatic dynamics of Born-Oppenheimer systems is described. Stationary phase approximations to the propagator for full quantum dynamics are derived. It is shown that quantum corrections to mixed quantum classical methods can be obtained through stationary phase approximations to the full quantum dynamics. A rigorous description of the quantum corrections due to electronic nonadiabatic coupling on the nuclear dynamics within the Ehrenfest framework is obtained. The fewest switches surface hopping method is shown to be obtained as a quasiclassical approximation to the dynamics, and natural semiclassical extensions to include classically forbidden nonadiabatic transitions are suggested.
The influence of compressive stress on shallow-donor impurity states in symmetric GaAs-Ga1−xAlxAs double quantum dots
Authors: Liu Jian-Jun , Shen Man , Wang Shao-Wei
Published: April 2007

The effects of compressive stress on the binding energy of shallow-donor impurity states in symmetrical GaAs-Ga1−xAlxAs double quantum dots are calculated variationally using a parameterized wave function within the effective-mass approximation. Results are obtained for different dot and barrier widths, donor ion positions, and compressive stresses along the growth direction of the structure. In the direct-gap regime (for stress values up to 13.5 kbar) the binding energy increases linearly with the stress. In the indirect-gap regime (for stress values greater than 13.5 kbar) and with the donor ion at the center of the dot, the binding energy increases up to a maximum and then decreases. For all donor ion positions, the binding energy shows nonlinear behavior in the indirect-gap regime due to the Γ-X crossing effect. In the limit of single quantum wells, the results we obtain are in good agreement with those previously obtained for the case in which the donor ion is at the center of the well.
Relaxation of photoinduced spins and carriers in ferromagnetic InMnSb films
Authors: Nontapot K. , Kini R. N. , Gifford A. , Merritt T. R. , Khodaparast G. A. , Wojtowicz T. , Liu X. , Furdyna J. K.
Published: April 2007

The authors report time resolved measurements and control of photoinduced spin and carrier relaxations in InMnSb ferromagnetic films with 2% Mn content (grown by low-temperature molecular beam epitaxy) using femtosecond laser pulses, and compare them to analogous measurements on InBeSb and InSb films. In this work, magneto-optical Kerr effect and standard pump-probe techniques provided a direct measure of the photoexcited spin and carrier lifetimes, respectively. They observe decrease in relaxations times in the high laser fluence regime and an absence of temperature dependence of the relaxation times.
Pair diffusion in quasi-one- and quasi-two-dimensional binary colloid suspensions
Authors: Valley David T. , Rice Smart A. , Cui Bianxiao , Ho Hau My , Diamant Haim , Lin Binhua
Published: April 2007

The authors report the results of measurements of the center of mass and relative pair diffusion coefficients in quasi-one-dimensional (q1D) and quasi-two-dimensional (q2D) binary colloid suspensions. The new results extend the findings of similar studies of one-component quasi-one-dimensional and quasi-two-dimensional colloid suspensions. Our principal new finding is that the presence of the smaller diameter component can destroy the oscillatory structure of the separation dependence of the q2D relative pair diffusion coefficient of the large particles even though the oscillatory character of the large particle equilibrium pair correlation function remains prominent, and that no such effect occurs with the q1D suspension. An interpretation of these results is proposed.
Dehydrogenation from 3d-transition-metal-doped NaAlH4: Prediction of catalysts
Authors: Blomqvist A. , Moysés Araújo C. , Jena P. , Ahuja R.
Published: April 2007

A fundamental understanding of the role of catalysts in improving the kinetics and thermodynamics of hydrogen sorption in NaAlH4 is the key for using this material in hydrogen storage. The authors present a systematic theoretical study of energies needed to desorb hydrogen in 3d transition metal (Sc–Cu)-doped NaAlH4. They show that Cr and Fe atoms can be far more effective catalysts than Ti in desorbing hydrogen. The role of the 3d metal atoms in improving the thermodynamics of dehydrogenation is attributed to a significant shortening of the bond length with neighboring Al atoms.
Effect of the thermal expansion matching on the dielectric tunability of (100)-one-axis-oriented (Ba0.5Sr0.5)TiO3 thin films
Authors: Ito Shinichi , Funakubo Hiroshi , Koutsaroff Ivoyl P. , Zelner Marina , Cervin-Lawry Andrew
Published: April 2007

The impact of the residual strain induced by the thermal strain on the dielectric tunability was systematically studied for rf sputtered (100)-one-axis-oriented polycrystalline (Ba0.5Sr0.5)TiO3 films. These films were grown on various substrates with different thermal expansion coefficients [α(sub)] covered with a stack of (100)cSrRuO3∕(100)cLaNiO3∕(111)Pt layers. The residual strain was ascertained to linearly increase with the increase in α(sub) by enhancement of the surface-normal lattice spacing of (Ba0.5Sr0.5)TiO3 and Pt. Dielectric tunability of the films also linearly increased with the increase in α(sub). These results clearly demonstrate that dielectric tunability tailoring of the (Ba0.5Sr0.5)TiO3 films can be achieved by using residual thermal strain.
Localized steady-state domain wall oscillators
Authors: He J. , Zhang S.
Published: April 2007

The authors predict a spatially localized magnetic domain wall oscillator upon the application of an external magnetic field and a dc electric current. The amplitude and frequency of the oscillator can be controlled by the field and/or the current. The resulting oscillator could be used as an effective microwave source for information storage application.
Negative differential resistance of electrons in graphene barrier
Authors: Dragoman D. , Dragoman M.
Published: April 2007

The graphene is a native two-dimensional crystal material consisting of a single sheet of carbon atoms. In this unique one-atom-thick material, the electron transport is ballistic and is described by a quantum relativisticlike Dirac equation rather than by the Schrödinger equation. As a result, a graphene barrier behaves very differently compared to a common semiconductor barrier. The authors show that a single graphene barrier acts as a switch with a very high on-off ratio and displays a significant differential negative resistance, which promotes graphene as a key material in nanoelectronics.
On the path to extinction
Authors: Jagers Peter , Klebaner Fima C. , Sagitov Serik
Published: April 2007

Populations can die out in many ways. We investigate one basic form of extinction, stable or intrinsic extinction, caused by individuals on the average not being able to replace themselves through reproduction. The archetypical such population is a subcritical branching process, i.e., a population of independent, asexually reproducing individuals, for which the expected number of progeny per individual is less than one. The main purpose is to uncover a fundamental pattern of nature. Mathematically, this emerges in large systems, in our case subcritical populations, starting from a large number,
x
, of individuals. First we describe the behavior of the time to extinction
T
: as
x
grows to infinity, it behaves like the logarithm of
x
, divided by
r
, where
r
is the absolute value of the Malthusian parameter. We give a more precise description in terms of extreme value distributions. Then we study population size partway (or
u
-way) to extinction, i.e., at times
uT
, for 0 <
u
< 1, e.g.,
u
= 1/2 gives halfway to extinction. (Note that mathematically this is no stopping time.) If the population starts from
x
individuals, then for large
x
, the proper scaling for the population size at time
uT
is
x
into the power
u
− 1. Normed by this factor, the population
u
-way to extinction approaches a process, which involves constants that are determined by life span and reproduction distributions, and a random variable that follows the classical Gumbel distribution in the continuous time case. In the Markov case, where an explicit representation can be deduced, we also find a description of the behavior immediately before extinction.
I. EC Maritime Transport Law and Policy
Authors: McMahon Joe , Greaves Rosa
Published: April 2007

The EC maritime transport policy was slow to develop. Although the EC Treaty requires the Member States to create a Common Transport Policy,1the focus of the Treaty transport provisions2is on inland modes of transport (road, rail and inland waterways).3However, the EU Council is expressly given competence to decide what ‘appropriate provisions’ may be adopted for maritime and air transport.4

Maritime transport is by its very nature an international mode of transport regulated by a large number of international treaties and conventions, most of them negotiated and concluded within the International Maritime Organization (IMO). Members of the international community, including some EU Member States themselves, were initially reluctant to transfer their sovereignty in this field of transport to the Community. However, two main events gradually changed the attitude of the Member States to the Community's competence to regulate this mode of transport. First, the mid-1980s impetus to establish an internal market by 1992 placed all modes of transport at the centre of the project. It was not feasible to establish a geographical market, stretching from the Atlantic to the Eastern European countries and from the North Sea to the Mediterranean, where goods, people, services and capital would be able to circulate freely,5and in a competitive manner, without the Community seriously addressing transport issues. Thus, unsurprisingly, a number of important legislative proposals affecting the provisions of maritime transport services were adopted and implemented during that period.6The second significant factor in the development of a maritime transport policy was the number of serious marine accidents which took place in the Community's coastal waters during the last 20 years.7
II. Competition Law
Authors: McMahon Joe , Lane Robert
Published: April 2007

The period under review (Autumn 2003–December 2006) saw in not only the expansion of the Union from 15 to 25 Member States, but also the attendant ‘big bang’, on 1 May 2004, in competition rules with the entry into operation of Regulations 1/2003 and 139/2004. The changes introduced by Regulation 1/20031—primarily abandoning the notification/authorization procedure which had obtained since 1962 in favour of a directly effective Article 81(3) andexception légale, and including further measures enabling/compelling the decentralized enforcement of Articles 81 and 82—are discussed in previous notes2and (copiously) elsewhere, and it is not proposed to rerehearse them here. Rather, the concern is the manner in which the dust has settled, in what is, after the frenetic legislative change and the absorption of 10 new Member States into a new culture of competition, a time of consolidation.
II. Regression and Reform in the Law of Domicile
Authors: McEleavy Peter , McEleavy Peter
Published: April 2007

In the United Kingdom the law pertaining to domicile has the rather dubious distinction that, although subjected to concerted criticism from commentators and law reformers alike for over half a century, it has largely remained unchanged.1 Common law jurisdictions around the world have succeeded in passing legislation which, to varying degrees, has modernized the concept,2 yet in Britain a series of initiatives have either failed to complete the legislative process or not even made it to Parliament.3 The reason in each instance was less the substance of the proposals, but rather political expediency in the face of pressure from the overseas business community resident in the United Kingdom, who feared extended fiscal liability if the connecting factors were attributed with a less legalistic interpretation.4
Customer choice of a car maintenance service provider
Authors: Pereira Zamith Brito Eliane , Luís Beneduzzi Aguilar Ricardo , Artur L. Brito Luiz
Published: April 2007

Purpose

This paper investigates the determinants of customer choice of a car maintenance service provider after the warranty period. It focuses on the alternative of using branded car dealers, who provide this service during the warranty period, or independent garages.

Design/methodology/approach

A comprehensive list of 30 service attributes is developed drawing on the service quality literature, specific previous studies on car maintenance services, and including other purchase behaviour determinants such as perceived value. Simple random sampling with replacement is used to collect data from 400 car owners using the actual choice of a service provider as the dependent variable. A quantitative analysis using a set of logistic regressions links directly customer choice to the service attributes.

Findings

Service attributes that determine customer choice are the ones consumers simultaneously consider important and perceive differences in performance between the service providers. The branded dealers service operation proved to be relatively weak, having only one of these attributes, while being better evaluated in less important ones. Independent garages have a much better offer justifying their gain in market share.

Research limitations/implications

Only economic cars (1,000 cc) were analysed. Convenience and location were only partially controlled and could play a more significant role in some decision settings. Logistic regressions could effectively predict customer choice in close to 90 per cent of the cases demonstrating the adequacy of including other service attributes beyond the ones covered in the service quality literature.

Practical implications

Directions for improvement in the operations of both branded dealers and independent garages could be derived and some recent moves by both types of players could be supported by the results.

Originality/value

Investigation of the Brazilian setting and the methodological approach of linking actual customer choice to the extended set of service attributes by the combination of logistic regressions and the importance rating of the attributes.
Building interoperable Canadian architecture collections: initial metadata assessment
Authors: Park Eun G.
Published: April 2007

Purpose

The purpose of this research is to assess the current descriptions of architecture collections housed at the McGill University Library in preparation for building an interoperable metadata and search interface for Canadian architecture collections.

Design/methodology/approach

The names and frequencies of tables and fields of 11 architecture databases were analyzed and summarized into the most commonly used groups. In addition, typologies of buildings by purpose of construction were presented as subject headings.

Findings

Current metadata schemes are diverse and heterogeneous across the 11 databases.

Research limitations/implications

This study is at the pilot stage and is limited to Canadian architecture collections at McGill University. The observations provide insights into metadata normalization that can be used as a basis for building architecture collections or image collections.

Originality/value

This is the first metadata assessment of architecture collections for the purpose of building a single uniform access.
Syntectonic subaqueous mass flows of the Neoproterozoic Otavi Group, Namibia: where is the evidence of global glaciation?
Authors: Eyles Nick , Januszczak Nicole
Published: April 2007

The thick (>1 km) Neoproterozoic Otavi Group of Namibia accumulated after ca. 760 Ma along >700 km of the faulted margin of the Congo Craton. The margin shows a north to south, downbasin transition from a shallow‐water carbonate shelf (Otavi Platform) to offshore deepwater slope (Outjo Basin). Within the latter, the Abenab and Tsumeb Subgroups contain large volumes of poorly sorted breccias, conglomerates and diamictites composed principally of locally derived carbonate. Diamictite facies were reported in the 1930s as tillites left by an ice sheet (although the absence of striated clasts and other key glacial indicators was viewed as problematic). Later workers rejected a glacial origin concluding that Outjo basin facies were deposited as parts of prograding submarine wedges built by mass flows during active rifting. Recently, the Snowball Earth hypothesis has returned to the earlier glacial interpretation; arguing that these strata represent a record of extraordinary late Neoproterozoic glacial and interglacial climates when global temperatures fluctuated by up to 100°C. Facies analysis of breccias, diamictites, conglomerates and sandstone strata of the Otavi Group identifies them as genetically related, subaqueously deposited sediment gravity flows. They lack diagnostic indicators of any one specific climate in source areas. These facies were all deposited in deepwater at the foot of landslide‐prone scarp blocks where debris flows and turbidity currents moved large volumes of coarse, freshly broken carbonate debris produced by faulting. Breccias, diamictites, conglomerates and sandstones occur in composite fining‐ and thinning‐upward bundles that are directly analogous to those reported from many other faulted margins in the Phanerozoic stratigraphic record. These rocks provide no clear sedimentological signature of a glacial source or catastrophic Snowball Earth‐type temperature fluctuations. Instead, they point to a dominant tectonic control on sedimentation related to faulting along the margin of the Congo Craton.
World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes
Authors: Bernasconi Paolo , Klersy Catherine , Boni Marina , Cavigliano Paola M. , Calatroni Silvia , Giardini Ilaria , Rocca Barbara , Zappatore Rita , Caresana Marilena , Dambruoso Irene , Lazzarino Mario , Bernasconi Carlo
Published: April 2007

This study correlated chromosomal defects with French–American–British (FAB)/World Health Organization (WHO) classification subtypes, proposed a revised International Prognostic Scoring System (IPSS) cytogenetic grouping; and established which classification, when used with the IPSS cytogenetic categories, best predicted clinical outcome in the myelodysplastic syndromes (MDS). A higher prevalence of chromosomal defects and distinct defects were observed in patients with multi‐lineage dysplasia and a blast cell percentage >10%. Abnormalities of the long arm of chromosome 3, del(7)(q31q35), trisomy 8, del(11)(q14q23), del(12p) and 20q‐ could be segregated from their respective IPSS cytogenetic categories and used to develop new cytogenetic subgroups. Clinical parameters, FAB/WHO classification, IPSS score and standard or revised cytogenetic categories were statistically relevant for overall survival (OS) and progression‐free intervals (PFI) and were included within five distinct multivariate models compared by the Akaike Information Criterion. To predict OS, the best models included age, WHO classification and standard or revised IPSS cytogenetic categories; to predict PFI, the best model included the same variables and revised cytogenetic categories. In conclusion, (i) the WHO classification was associated with a more homogeneous cytogenetic pattern than the FAB classification, (ii) WHO classification and standard/revised IPSS cytogenetic categories were much more effective than IPSS for predicting MDS clinical outcome, (iii) revised cytogenetic subgroups predicted PFI more effectively than standard categories.
Stage I/II follicular lymphoma: spread of bcl‐2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy
Authors: Pulsoni Alessandro , Starza Irene Della , Frattarelli Natalia , Ghia Emanuela , Carlotti Emanuela , Cavalieri Elena , Matturro Angela , Tempera Settimio , Rambaldi Alessandro , Foà Robin
Published: April 2007

Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl‐2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66·6%). After treatment, in 9/15 Bcl‐2/IgH positive evaluable patients, a disappearance of Bcl‐2/IgH+ cells was observed, which persisted after a median follow‐up of 43·5 months (range 11–70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl‐2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl‐2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl‐2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR.
Vaccination with autologous non‐irradiated dendritic cells in patients with bcr/abl+ chronic myeloid leukaemia
Authors: Westermann Jörg , Kopp Joachim , Van Lessen Antje , Hecker Ann‐Christine , Baskaynak Gökben , Le Coutre Philipp , Döhner Konstanze , Döhner Hartmut , Dörken Bernd , Pezzutto Antonio
Published: April 2007

In chronic myeloid leukaemia (CML), dendritic cells (DC) and leukaemic cells share a common progeny, leading to constitutive expression of putative tumour antigens, such as bcr/abl, in DC. In this phase‐I/II study, autologous DC were used as a vaccine in patients with chronic phase bcr/abl+ CML, who had not achieved an adequate cytogenetic response after treatment with α‐interferon or imatinib. Ten patients were enrolled, DC were generated from peripheral blood monocytes and vaccination consisted of four subcutaneous injections of increasing numbers of DC (1–50 × 106 cells per injection) on days 1, 2, 8 and 21. Vaccination was feasible and safe. Improvement of the cytogenetic/molecular response, as detected by fluorescence in situ hybridization of peripheral blood mononuclear cells (PBMC), was possibly related to vaccination in four of 10 patients. In three of these patients, T cells recognizing leukaemia‐associated antigens became detectable. The proliferative capacity of PBMC in response to autologous DC increased after vaccination in all evaluable patients. We conclude that vaccination with autologous, non‐irradiated ‘leukaemic’ DC is feasible, safe and induces anti‐leukaemic T‐cell responses in some CML patients. DC vaccination might be useful in CML as postremission therapy, i.e. after treatment with tyrosine kinase inhibitors.
Establishment of a novel childhood acute myeloid leukaemia cell line, KOPM‐88, containing partial tandem duplication of the MLL gene and an in vivo model for childhood acute myeloid leukaemia using NOD/SCID mice
Authors: Hayashi Mutsumi , Kondoh Kensuke , Nakata Yuji , Kinoshita Akitoshi , Mori Taijiro , Takahashi Takao , Sakamoto Michi‐ie , Yamada Taketo
Published: April 2007

MLL gene rearrangement is common in both adult and childhood acute myeloid leukaemia (AML), and its role in oncogenesis has been investigated. While over 50 translocated‐partner genes have been identified so far, few studies have detailed the molecular mechanism of partial tandem duplication (PTD) of the MLL gene. The prognostic impact and contribution to leukaemogenesis of MLL‐PTD, especially in childhood cases, remain unknown. We have established a novel cell line containing MLL‐PTD derived from an 11‐year‐old patient with AML and designated as KOPM‐88. KOPM‐88 cells exhibited certain characteristics associated with the myeloid lineage including abundant primary granules in the cytoplasm and the expression of myeloperoxidase. The cell growth of KOPM‐88 was cytokine independent but was accelerated by granulocyte colony‐stimulating factor and granulocyte‐macrophage colony‐stimulating factor. MLL‐PTD of exon 2 to exon 6 and exon 2 to exon 8 was revealed using Southern blotting, fluorescence in situ hybridisation, and reverse transcription polymerase chain reaction/DNA sequencing. Furthermore, non‐obese diabetic/severe combined immunodeficient mice inoculated with KOPM‐88 cells exhibited leukaemic infiltrations in the bone marrow and hemiparalysis because of compression myelopathy. This is the first report of an in vivo animal model exhibiting the systemic involvement of childhood AML containing MLL‐PTD. KOPM‐88 cells and our murine model may be useful for investigating the pathogenesis of childhood AML associated with MLL gene rearrangement.
Genetic polymorphisms associated with priapism in sickle cell disease
Authors: Elliott Laine , Ashley‐Koch Allison E. , Castro Laura De , Jonassaint Jude , Price Jennifer , Ataga Kenneth I. , Levesque Marc C. , Brice Weinberg J. , Eckman James R. , Orringer Eugene P. , Vance Jeffery M. , Telen Marilyn J.
Published: April 2007

Priapism occurs in 30–45% of male patients with sickle cell disease (SCD), but the possible influence of genetic risk factors on the incidence of priapism is not well understood. We examined genetic polymorphisms in 199 unrelated, adult (>18 years), male patients with Hb SS and Hb Sβ0‐thalassaemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation and cell signalling. Additionally, we examined genes involved in nitric oxide biology (NOS2, NOS3, SLC4A1), as well as polymorphisms in the klotho (KL) gene, which has previously been associated with priapism. Strong evidence of association was found for single nucleotide polymorphisms in transforming growth factor‐β receptor, type III (TGFBR3) (rs7526590; P = 0·00058), aquaporin (AQP1) (rs10244884; P = 0·00068), integrin αv (ITGAV) (rs3768780; P = 0·00090), and the A1 subunit of coagulation factor XIII (F13A1) (hcv1860621; P = 0·00156). Associations with TGFBR3, AQP1, and ITGAV remained significant after adjusting for multiple testing, using the Benjamini–Hochberg procedure. Our data suggest that genes involved in the TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.
The expression of the novel cytotoxic protein granzyme M by large granular lymphocytic leukaemias of both T‐cell and NK‐cell lineage: an unexpected finding with implications regarding the pathobiology of these disorders
Authors: Morice William G. , Jevremovic Dragan , Hanson Curtis A.
Published: April 2007

Granzyme M (GrM) is a novel cytotoxic protein normally exclusively expressed by natural killer (NK)‐cells and cytotoxic T‐cells with innate immune function. As most T‐cell granular lymphocytic leukaemias (T‐LGL) are thought to be derived from the adaptive immune system it was predicted that T‐LGL would be GrM negative. Contrary to this hypothesis, bone marrow biopsy immunohistochemistry revealed that GrM was frequently expressed in both T‐LGL (16 / 18) and NK‐LGL (6 / 9). These unexpected results suggest commonality between T‐ and NK‐LGL, providing further support to the notion that T‐LGL is a disorder of dysregulated, chronically stimulated, adaptive cytotoxic T‐cells.
Anaemia characterises patients with myelofibrosis harbouring MplW515L/K mutation
Authors: Guglielmelli Paola , Pancrazzi Alessandro , Bergamaschi Gaetano , Rosti Vittorio , Villani Laura , Antonioli Elisabetta , Bosi Alberto , Barosi Giovanni , Vannucchi Alessandro M. ,   for the GIMEMA‐Italian Registry of Myelofibrosis and the MPD Research Consortium, Chicago, IL, USA
Published: April 2007

The clinical and haematological phenotype of patients with myelofibrosis harbouring MPLW515L/K mutation has not been thoroughly investigated. Of 217 myelofibrosis subjects, 18 (8·2%) had an MPL mutation, four of which (22%) co‐existed with JAK2V617F mutation. When compared with MPL wild‐type patients, irrespective of JAK2V617F status, those with MPLW515L/K, were more frequently female, were older (61 years vs. 57 years; P = 0·02), presented with more severe anaemia (haemoglobin, 101 g/l vs. 121 g/l; P = 0·002) and were more likely to require regular transfusional support (P = 0·012). These data indicate that MPL mutation in myelofibrosis characterises patients with more severe anaemic phenotype.
Benign cortisol‐secreting adrenocortical adenomas produce small amounts of androgens
Authors: Kamenicky Peter , Houdoin Laurence , Ferlicot Sophie , Salenave Sylvie , Brailly Sylvie , Droupy Stéphane , Meduri Geri , Sasano Hironobu , Suzuki Takashi , Young Jacques , Chanson Philippe
Published: April 2007

Background  Serum androgen levels are below normal in patients with benign cortisol‐secreting adrenocortical adenomas, owing to ACTH suppression. Associated androgen secretion is usually considered as indicative of malignancy. The objective of the study was to analyse the androgen‐producing ability of cortisol‐secreting adrenocortical adenomas.

Design  Retrospective data collection in a single referral hospital centre.

Methods  Dehydroepiandrosterone sulfate (DHEAS), Δ4androstenedione and testosterone concentrations were measured before and after adrenalectomy and then at 6‐month intervals in 20 women (eight cortisol‐secreting adrenocortical adenomas, six subclinical cortisol‐secreting adrenocortical adenomas, and six nonfunctional adenomas).

Results  Before adrenalectomy, serum androgen concentrations were measurable in all women with clinically apparent and subclinical cortisol‐secreting adrenocortical adenomas. DHEAS levels were either at the lower end of the normal range or below normal, but were always clearly detectable. Postoperatively, during adrenocortical insufficiency, DHEAS, Δ4androstenedione and testosterone concentrations fell to near the detection limit in all patients with cortisol‐secreting adrenocortical adenomas (P = 0·008 for each marker) and showed a similar tendency to fall in all patients with subclinical cortisol‐secreting adrenocortical adenomas. Pre‐ and post‐treatment androgen concentrations did not differ in patients with nonfunctional adenomas. Immunohistochemical analysis confirmed CYP17, HSD3B2, SULT2A1 and CYB5 expression by all cortisol‐producing tumours. The intensity of CYP17 and SULT2A1 expression was stronger in cortisol‐secreting adenomas than in their adjacent normal adrenal tissue.

Conclusion  Both clinically apparent and subclinical cortisol‐secreting adrenocortical adenomas appear to show moderate autonomous androgen production. Thus, weak androgen secretion in patients with adrenocortical tumours should not necessarily be considered as a sign of malignancy.
Oxytocin is not important for the control of gonadotrophin secretion in the late follicular phase of the cycle
Authors: Vanakara P. , Dafopoulos K. , Papastergiopoulou L. , Kallitsaris A. , Papageorgiou I. , Messinis I. E.
Published: April 2007

Objective  To study the role of oxytocin in basal and GnRH‐induced gonadotrophin secretion in normal women.

Design  Normal women were studied in three cycles. When the diameter of the leading follicle was 15–16 mm, the women were infused intravenously (i.v.) for 3 h with normal saline (cycle 1), atosiban (cycle 2) or oxytocin (cycle 3).

Patients  The study included 12 normally cycling women aged 23–38 years.

Measurements  After cessation of treatment, two injections of GnRH, 10 µg each, were administered i.v. 2 h apart and blood samples were collected every 30 min for a total of 240 min. The 30‐min pituitary response (sensitivity) to a single GnRH injection (10 µg i.v.) was investigated thereafter every 12 h from the end of the 3‐h infusion until the day of LH surge onset.

Results  No significant differences in LH and FSH response to GnRH (sensitivity and reserve) during the 240‐min experiment were found between the three cycles. The time of LH surge onset from the initiation of the infusion was similar in the three cycles. Also similar in the three cycles were oestradiol (E2) and gonadotrophin levels as well as the 30‐min response to GnRH for 48 h following the 3‐h infusion.

Conclusions  The present study demonstrates that neither exogenous oxytocin administration nor blockage of endogenous oxytocin action influences pituitary sensitivity to GnRH in cycling women.
Differential inflammatory mediator response in vitro from murine macrophages to lactobacilli and pathogenic intestinal bacteria
Authors: Marcinkiewicz J. , Ciszek M. , Bobek M. , Strus M. , Heczko P. B. , Kurnyta M. , Biedroń R. , Chmielarczyk A.
Published: April 2007

Chronic active colitis (including inflammatory bowel disease – IBD) is maintained by a variety of pro‐inflammatory mediators. Certain intestinal bacterial strains may induce colitis, whereas some strains (e.g. Lactobacillus spp.) show a protective effect in colitis owing to their anti‐inflammatory activity. In this study, we have examined the production of selected inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO) and the expression of haeme oxygenase‐1 (HO‐1) by murine peritoneal macrophages stimulated in vitro by the intestinal bacterial strains, isolated from mice with colitis. Lactobacillus strains (Lactobacillus reuteri, L. johnsonii, L. animalis/murinus) and two potentially pathogenic bacteria (Escherichia coli and Enterococcus faecalis) induced the production of substantial amounts of cytokines with a strain specific profile. Despite some interstrain differences, all lactobacilli induced production of anti‐inflammatory cytokines (IL‐10high, IL‐6low, IL‐12p70low). Conversely, E. faecalis and E. coli induced the production of proinflammatory cytokines (TNF‐α, IL‐12p70), the cytokines essential for chronic IBD. Macrophages released comparably substantial amounts of ROS in response to all Lactobacillus strains tested, while E. coli and E. faecalis ability to induce generation of ROS was negligible. In contrast to ROS, the production of NO/NO2− by macrophages activated with all bacterial strains tested was similar. Moreover, for the first time, it has been shown that intestinal bacteria differed in their ability to induce expression of HO‐1, a stress‐inducible enzyme with antioxidant and anti‐inflammatory properties. The beneficial immunoregulatory properties of candidate probiotic bacteria for the treatment of IBD are discussed.
The role and potential contribution of clinical research nurses to clinical trials
Authors: Spilsbury Karen , Petherick Emily , Cullum Nicky , Nelson Andrea , Nixon Jane , Mason Su
Published: April 2007

Aims and objectives.  This study explores the scope and potential contribution of the Clinical Research Nurse (CRN) role to clinical trials of a nursing‐specific topic.

Background.  Over the past two decades, there have been increases in the numbers of nurses working as CRNs because of the increasing global demand for clinical trials. CRNs can influence the quality of clinical trials but the scope and contribution of the role to clinical trials is not known.

Design.  Qualitative focus group study.

Methods.  A focus group interview was carried out with CRNs (n = 9) employed on a large, multi‐centre (six NHS Trusts) randomized controlled trial of pressure area care. The focus group interview was recorded, alongside field notes of participant interactions and behaviours, and transcribed verbatim. Data were analysed for thematic content and process.

Findings.  CRNs described their transition to a clinical research role. They reported a lack of confidence, role conflict as researcher and nurse, the challenges of gaining cooperation of clinical nursing staff to comply with trial protocols and difficulties maintaining their own motivation. CRNs provided their perceptions and observations of pressure area care and prevention. They identified areas of inadequate treatment, management and care, influenced by organizational and clinical aspects of care delivery.

Conclusions.  The study reveals challenges associated with training and management of CRNs. CRNs are usually associated with trial recruitment and data collection. This study highlights the additional contributions of CRNs for the study of topics specific to nursing as the result of their unique placement in the research centres as informal ‘participant observers.’ Such observations enhance understanding of the contexts being studied.

Relevance to clinical practice.  These findings are relevant to the design and conduct of research studies of nursing care and practice and present ways for investigators to optimize the skills and knowledge of nurses working as CRNs.
The Bali bombings and the evolving mental health response to disaster in Australia: lessons from Darwin
Authors: GUSCOTT W. M. , GUSCOTT A. J. , MALINGAMBI G. , PARKER R.
Published: April 2007

The Bali bombing in 2002 initiated a new phase of trauma response for public health services in Australia, and the Royal Darwin Hospital in particular. The mental health response to the initial disaster was limited to a debriefing of Royal Darwin Hospital staff some time after the disaster. Following this initial episode, a number of important developments occurred within the Royal Darwin Hospital and nationally to further develop mental health resources. A mental health consultation liaison nursing position was established within the hospital. The Director of Mental Health for the Northern Territory, along with the Director of Psychiatry, was involved with an evolving national mental health response to mass trauma through the National Planning Group of Mental Health Response to Trauma. The improved recognition of mental health in disaster response, along with increased recognition and confidence in the consultation liaison nursing staff, considerably improved the mental health services available to patients and Royal Darwin Hospital staff following the second Bali blast in October 2005.
Time geography: a model for psychiatric life charting?
Authors: SUNNQVIST C. , PERSSON U. , LENNTORP B. , TRÄSKMAN‐BENDZ L.
Published: April 2007

Since many years, life charting has been used to describe the life course and life events of psychiatric patients. The aim of the present study was to describe and evaluate time geographic life charts of 11 former psychiatric patients in order to promote systematic descriptions of their life events over time. Information on all events which was gathered from the life charts was analysed by manifest content analysis and reduced to four categories: information received by asking only about moves, social capacity, predisposing life events and/or stressful as well as precipitating life events. Our findings showed that this kind of life charts offered a comprehensive and structured picture. They describe a detailed life situation from one time period to another, where geographical sites serve as anchors. The patients expressed satisfaction with this method of combining an interview with a time geographic life line.