bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dissemination and uptake of competency frameworks
Authors: Hendry Charles , Lauder William , Roxburgh Michelle 
Published: October 2007

Clinical competencies are increasingly being used to structure career and clinical progression in post-registration nursing. Competency framework documents have been proposed as a way of supporting competence development. One major national initiative in this respect is the NHS Education for Scotland (NES) competency frameworks which have seen development of over 26 such frameworks dealing with a wide range of nursing specialties. Utilising an initial scoping study followed by a stakeholder evaluation the dissemination and uptake of a selected number of competency frameworks was investigated. Participants in the scoping study ( n = 18) and in the main stakeholder survey ( n = 24) from a sample of Health Boards and Higher Education Institutions were recruited. Data were collected by telephone and face-to-face interviews. Within the NHS and HEI's the specified framework documents have a variable penetration. Documents are used to support CPD at the individual and organisational levels. They also inform, albeit in a very limited way, curricular developments in HEIs. The success of framework documents is linked to their timeliness in relation to local and national developments such as service redesign and to whether or not documents were `championed' by committed practitioners or professional groups. Competency framework documents are recognised and utilised by clinicians, NHS managers and Education providers. Information providers and users need to co-ordinate their initiatives in order that staff development links with service redesign.
Incorporation of Fe3+ in phase-X, A2–xM2Si2O7Hx, a potential high-pressure K-rich hydrous silicate in the mantle
Authors: Bindi L. , Bobrov A. , Litvin Y. A. 
Published: October 2007

AbstractPhase-X, a potential sink for K in the mantle, is a synthetic hydrous K-rich silicate formed by the breakdown of K-amphibole at high pressure. It has the general formula A2–xM2Si2O7Hx where A = K, Na, Ca, □ (vacancy), and M = Mg, Al, or Cr. No other isomorphic substitutions, either for the A or the M site, were reported for such a synthetic compound. Here we report the crystal structure and chemical composition of a crystal of phase-X containinglarg e amounts of trivalent Fe. This crystal was synthesized in the model system garnet lherzolite–K2CO3 at lower pressure (P = 7 GPa) and higher temperature (T = 1450–1650°C) with respect to the stability range reported in the literature (i.e. P = 9–17 GPa and T = 1150–1400°C). Quantitative analysis led to the following formula: . The lattice parameters (hexagonal setting) are: a = 5.005(1), c = 13.148(2) Å, V = 285.23(9) Å3, and Z = 2. The structure was refined in space group P63cm to R = 5.06% using199 independent reflections and consists of MO6 octahedra layers stacked alongthe c axis and linked together by Si2O7 groups. The Si2O7 groups form pillars in the layer that contains A atoms in the cavities between the pillars. The Raman spectrum in the OH-stretching region indicates the existence of two different OH environments. However, the position of H could not be determined. The substitution of Fe3+ for Mg shortens octahedral bond distances. In addition, the entry of Fe3+ in M induces geometrical changes to the adjacent A site. The crystal-chemical characteristics are compared with published data on synthetic Fe-free phase-X.
Zeolitic alteration in the Tertiary Feres volcano-sedimentary basin, Thrace, NE Greece
Authors: Marantos I. , Markopoulos T. , Christidis G. E. 
Published: October 2007

AbstractThe Tertiary volcano-sedimentary sequence of the Feres basin (Thrace, NE Greece), includes lavas of andesitic–rhyolitic composition as well as volcaniclastic rocks, pyroclastic flows and pyroclastic fall deposits principally of dacitic–rhyodacitic composition. The pyroclastic flow deposits frequently show intense devitrification, vapour-phase crystallization and evidence of fumarolic activity, which involves deposition of scapolite in pore spaces. The Feres basin can be subdivided on the basis of mineral alteration assemblages: (1) the Pefka region; characterized by intense hydrothermal alteration of the volcanic rocks and mineral zoning(silicic, argillic, sericitic and propylitic zones) with polymetallic mineralization, and (2) the remainder of the basin; where the volcaniclastic rocks are characterized by the alteration of volcanic glass to zeolites (clinoptilolite, heulandite, mordenite, analcime), clay minerals (smectite, illite, celadonite, chlorite), SiO2polymorphs (cristobalite, opal-CT, quartz), K-feldspar and calcite. Laumontite is also present as an alteration product of plagioclase, with stilbite sporadically occurringin veinlets. Locally, rhyolites are also altered to zeolites (clinoptilolite and/or mordenite). The zeolitization process has occurred rapidly with the depositional environment, temperature, rate of cooling(of the volcanic rocks), nature and temperature of the mineral-forming fluids and composition of the parent material controllingthe formation of zeolites.
Cesium kupletskite renamed kupletskite-(Cs)
Authors: Bayliss P. 
Published: October 2007

AbstractCesium kupletskite has been renamed kupletskite-(Cs) with the approval of the IMA Commission on New Minerals, Nomenclature and Classification, because the name of a mineral species should be a single word and the International Union of Pure and Applied Chemistry spelling is caesium. The presence or absence of parentheses around the suffix chemical-element is discussed. The advantages of the chemical-element suffix nomenclature are stated.
FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia
Authors: Kim Hyung-Gyoon , Kojima Kyoko , Swindle C. Scott , Cotta Claudiu V. , Huo Yongliang , Reddy Vishnu , Klug Christopher A. 
Published: October 2007

Abstract
The inversion of chromosome 16 in the inv(16)(p13q22) is one of the most frequent cytogenetic abnormalities observed in acute myeloid leukemia (AML). The inv(16) fuses the core binding factor (CBF) beta subunit with the coiled-coil rod domain of smooth muscle myosin heavy chain (SMMHC). Expression of CBFβ-SMMHC in mice does not promote AML in the absence of secondary mutations. Patient samples with the inv(16) also possess mutually exclusive activating mutations in either N-RAS, K-RAS, or the receptor tyrosine kinases, c-KIT and FLT3, in almost 70% of cases. To test whether an activating mutation of FLT3 (FLT3-ITD) would cooperate with CBFβ-SMMHC to promote AML, we coexpressed both mutations in hematopoietic progenitor cells used to reconstitute lethally irradiated mice. Analysis of transplanted animals showed strong selection for CBFβ-SMMHC/FLT3-ITD–expressing cells in bone marrow and peripheral blood. Compared with animals transplanted with only CBFβ-SMMHC–expressing cells, FLT3-ITD further restricted early myeloid differentiation and promoted peripheralization of primitive myeloblasts as early as 2.5 weeks after transplantation. FLT3-ITD also accelerated disease progression in all CBFβ-SMMHC/FLT3-ITD–reconstituted animals, which died of a highly aggressive and transplantable AML within 3 to 5 months. These results indicate that FLT3-activating mutations can cooperate with CBFβ-SMMHC in an animal model of inv(16)-associated AML.
Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice
Authors: Guillot Pascale V. , Abass Oyebode , Bassett J. H. Duncan , Shefelbine Sandra J. , Bou-Gharios George , Chan Jerry , Kurata Hitoshi , Williams Graham R. , Polak Julia , Fisk Nicholas M. 
Published: October 2007

Abstract
The inherited skeletal dysplasia osteogenesis imperfecta (OI) results in multiple fractures and is currently treated empirically. We transplanted human first-trimester fetal blood mesenchymal stem cells (MSCs) into homozygous oim mice in utero. This resulted in a two-thirds reduction in long bone fractures (P < .01), with fewer fractures per mouse (median 1, range 0-2 in mice that received transplants vs median 3, range 1-5 in mice that did not receive transplants by 12 weeks, P < .01). Nearly all mice that did not receive transplants had fractures (47 [97.9%] of 48), in contrast to 17 (58.6%) of 29 4- to 12-week-old mice that received transplants (P < .01). Transplantation was associated with increased bone strength (P < .01), thickness (P < .01), and length (P < .01), and normalization/reduction of growth plate height in 4- to 12-week-old oim was reduced in mice that underwent transplantion (P < .001). More donor cells were found in bone tissues compared with other organs (P < .001), with cells clustered in areas of active bone formation and remodeling, and at sites of fracture healing. Donor cells found in the bone expressed osteoblast lineage genes, and produced the extracellular bone structural protein osteopontin. Finally, MSC transplantation decreased bone hydroxyproline content. In conclusion, intrauterine transplantation of fetal MSCs markedly reduced fracture rates and skeletal abnormalities in a mouse model of the intermediate severity type III OI, suggesting a scientific basis for MSC treatment of affected human fetuses.
Impact of imatinib on the pharmacokinetics and in vivo efficacy of etoposide and/or ifosfamide
Authors: Rezaï Keyvan , Lokiec François , Grandjean Isabelle , Weill Sophie , de Cremoux Patricia , Bordier Vincent , Ekue Richard , Garcia Mickael , Poupon Marie-France , Decaudin Didier 
Published: October 2007

Abstract

Background
Using a human small cell lung cancer (SCLC) xenografted in nude mice, we have previously reported enhanced tumor growth inhibition following chemotherapy in combination with imatinib (STI571). We therefore investigated the in vivo impact of imatinib on the pharmacokinetics and efficacy of chemotherapy.

Methods
Two different human tumors were used: SCLC6 small cell lung cancer xenografted in nude mice, and LY-3 EBV-associated human B-cell lymphoma xenografted in SCID mice. Plasma, urine, and fecal concentrations of etoposide (VP16) were determined by a validated high performance liquid chromatography method. Plasma concentrations of ifosfamidewere determined by a validated gas chromatography assay with nitrogen-phosphorus detection.

Results
Slight tumor growth inhibition was induced by imatinib administered alone in one in vivo EBV-associated B-cell lymphomatous xenograft. In contrast, an increase of the chemotherapy-induced antitumor effect was observed in the lymphoma model but not in a small cell lung cancer model when mice bearing human xenografted tumors were treated concomitantly by imatinib and chemotherapy. This antitumor effect was not influenced by concomitant administration of fluconazole. The AUC0-3 h (Area Under the concentration-time Curve) of etoposide was increased when mice were treated with etoposide + imatinib due to decreased fecal excretion. In contrast, imatinib did not appear to influence the urinary excretion of etoposide, and concomitant administration of the CYP3A4 inhibitor, fluconazole, with imatinib did not modify the pharmacokinetics of etoposide plus imatinib alone.

Conclusion
Altogether, these results therefore justify further prospective phase I and II clinical trials with combinations of etoposide-based chemotherapy and imatinib in patients with certain cancers, such as malignant lymphoma, with careful toxicologic monitoring.
Mutation Status of the Residual ATM Allele Is an Important Determinant of the Cellular Response to Chemotherapy and Survival in Patients With Chronic Lymphocytic Leukemia Containing an 11q Deletion
Authors: Austen Belinda , Skowronska Anna , Baker Claire , Powell Judith E. , Gardiner Anne , Oscier David , Majid Aneela , Dyer Martin , Siebert Reiner , Taylor A. Malcolm , Moss Paul A. , Stankovic Tatjana 
Published: October 2007

Purpose The ataxia telangiectasia mutated (ATM) gene is located on chromosome 11q and loss of this region is common in B-cell chronic lymphocytic leukemia (CLL). Our aim was to determine if CLL tumors with a chromosome 11q deletion might be divided into two subgroups based on the status of the remaining ATM allele. Methods The sequence of the residual ATM allele was determined in 72 CLLs with an 11q deletion. This was related to the cellular response to irradiation or cytotoxic drug exposure in vitro and clinical outcome. Results We show that the residual ATM allele is mutated in 36% of CLLs with an 11q deletion and that these leukemias demonstrate an impaired cellular response to irradiation or cytotoxic drug exposure in vitro. Inactivation of the second ATM allele was associated with a reduction in patient survival beyond that already dictated by the presence of an 11q deletion (P = .0283). Furthermore, we demonstrate that ATM mutations may arise during the evolution of an 11q deleted subclone and are associated with its expansion. Conclusion CLL with 11q deletion can be divided into two subgroups based on the integrity of the residual ATM allele. Patients with complete loss of ATM function, due to biallelic ATM defects, have defective responses to cytotoxic chemotherapeutics in vitro and a poorer clinical outcome. ATM mutant subclones can develop during an individual's disease course and give rise to additional expansion of the 11q deleted subclone.
VCAP-AMP-VECP Compared With Biweekly CHOP for Adult T-Cell Leukemia-Lymphoma: Japan Clinical Oncology Group Study JCOG9801
Authors: Tsukasaki Kunihiro , Utsunomiya Atae , Fukuda Haruhiko , Shibata Taro , Fukushima Takuya , Takatsuka Yoshifusa , Ikeda Shuichi , Masuda Masato , Nagoshi Haruhisa , Ueda Ryuzo , Tamura Kazuo , Sano Masayuki , Momita Saburo , Yamaguchi Kazunari , Kawano Fumio , Hanada Shuichi , Tobinai Kensei , Shimoyama Masanori , Hotta Tomomitsu , Tomonaga Masao 
Published: October 2007

Purpose Our previous phase II trial for treating human T-lymphotropic virus type I–associated adult T-cell leukemia-lymphoma (ATLL) with vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP), doxorubicin, ranimustine, and prednisone (AMP), and vindesine, etoposide, carboplatin, and prednisone (VECP) showed promising results. To test the superiority of VCAP-AMP-VECP over biweekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), we conducted a randomized controlled trial exclusively for ATLL. Patients and Methods Previously untreated patients with aggressive ATLL were assigned to receive either six courses of VCAP-AMP-VECP every 4 weeks or eight courses of biweekly CHOP. Both treatments were supported with granulocyte colony-stimulating factor and intrathecal prophylaxis. Results A total of 118 patients were enrolled. The complete response (CR) rate was higher in the VCAP-AMP-VECP arm than in biweekly CHOP arm (40% v 25%, respectively; P = .020). Progression-free survival rate at 1 year was 28% in the VCAP-AMP-VECP arm compared with 16% in the CHOP arm (P = .100, two-sided P = .200). Overall survival (OS) at 3 years was 24% in the VCAP-AMP-VECP arm and 13% in the CHOP arm (P = .085, two-sided P = .169). For VCAP-AMP-VECP versus biweekly CHOP, grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 or 4 infection rates were 98% v 83%, 74% v 17%, and 32% v 15%, respectively. There were three toxic deaths in the VCAP-AMP-VECP arm. Conclusion The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
Prediction of human pharmacokinetics — renal metabolic and excretion clearance
Authors: Fagerholm Urban 
Published: October 2007

AbstractThe kidneys have the capability to both excrete and metabolise drugs. An understanding of mechanisms that determine these processes is required for the prediction of pharmacokinetics, exposures, doses and interactions of candidate drugs. This is particularly important for compounds predicted to have low or negligible non-renal clearance (CL). Clinically significant interactions in drug transport occur mostly in the kidneys. The main objective was to evaluate methods for prediction of excretion and metabolic renal CL (CLR) in humans. CLR is difficult to predict because of the involvement of bi-directional passive and active tubular transport, differences in uptake capacity, pH and residence time on luminal and blood sides of tubular cells, and limited knowledge about regional tubular residence time, permeability (Pe) and metabolic capacity. Allometry provides poor predictions of excretion CLR because of species differences in unbound fraction, urine pH and active transport. The correlation between fraction excreted unchanged in urine (fe) in humans and animals is also poor, except for compounds with high passive Pe (extensive/complete tubular reabsorption; zero/negligible fe) and/or high non-renal CL. Physiologically based in-vitro/in-vivo methods could potentially be useful for predicting CLR. Filtration could easily be predicted. Prediction of tubular secretion CL requires an in-vitro transport model and establishment of an in-vitro/in-vivo relationship, and does not appear to have been attempted. The relationship between passive Pe and tubular fraction reabsorbed (freabs) for compounds with and without apparent secretion has recently been established and useful equations and limits for prediction were developed. The suggestion that reabsorption has a lipophilicity cut-off does not seem to hold. Instead, compounds with passive Pe that is less than or equal to that of atenolol are expected to have negligible passive freabs. Compounds with passive Pe that is equal to or higher than that of carbamazepine are expected to have complete freabs. For compounds with intermediate Pe the relationship is irregular and freabs is difficult to predict. Tubular cells are comparably impermeable (for passive diffusion), and show regional differences in enzymatic and transporter activities. This limits the usefulness of microsome data and makes microsome-based predictions of metabolic CLR questionable. Renal concentrations and activities of CYP450s are comparably low, suggesting that CYP450 substrates have negligible metabolic CLR. The metabolic CLR of high-Pe UDP-glucuronyltransferase substrates could contribute to the total CL.
Laser-ablated nanofunctional polymers for the formulation of slow-release powders for dry powder inhalers: physicochemical characterization and slow-release characteristics
Authors: Coowanitwong Intira , Arya Vikram , Patel Gina , Kim Won-Seok , Craciun Valentin , Rocca James R , Singh Rajiv , Hochhaus Günther 
Published: October 2007

Abstract
Recently, dry powder inhalation (DPI) powders coated with nanometre-thin layers of biodegradable polymers, prepared using pulse laser deposition (PLD), have been evaluated as a slow-release formulation for DPI use, with the goal of improving pulmonary selectivity. This paper describes evaluation of the chemical stability of one potential polymer, poly lactic acid (PLA), during the ablation process, the resulting respirable properties and potential cytotoxicity of coated glucocorticoid powders, and the resulting sustained-release characteristics of PLA-coated glucocorticoids creating using PLD. Triamcinolone acetonide (TA) and budesonide (BUD) were used as two model glucocorticoids to determine pulmonary targeting (PT) in-vivo.
The chemical stability of PLA was determined at various laser energy densities. The respirable fraction and the cytotoxicity of the micronized particles of TA and BUD, coated using optimum laser energy density, were determined. In-vitro dissolution profiles were generated for the coated/uncoated formulations and an ex-vivo receptor binding assay was used to determine PT in rats.
Increasing laser energy density led to decreases in molecular weight and film density, and increases in degradation products, roughness and thickness of the film. The mean dissolution time of coated formulations of BUD was longer (4 h) than with the less lipophilic TA (2 h). This correlated well with a more pronounced pulmonary selectivity observed for coated BUD ex-vivo.
Stability and the physical properties of the film correlated with the laser energy density. We observed a direct relationship between the dissolution rate of the uncoated and coated formulation and the degree of PT; however, physiochemical properties of the drug (e.g. lipophilicity) may also contribute to the improved PT.
Determination of calcium salt solubility with changes in pH and PCO2, simulating varying gastrointestinal environments
Authors: Goss Sandra L , Lemons Karen A , Kerstetter Jane E , Bogner Robin H 
Published: October 2007

Abstract
The amount of calcium available for absorption is dependent, in part, on its sustained solubility in the gastrointestinal (GI) tract. Many calcium salts, which are the calcium sources in supplements and food, have pH-dependent solubility and may have limited availability in the small intestine, the major site of absorption. The equilibrium solubility of four calcium salts (calcium oxalate hydrate, calcium citrate tetrahydrate, calcium phosphate, calcium glycerophosphate) were determined at controlled pH values (7.5, 6.0, 4.5 and ≤ 3.0) and in distilled water. The solubility of calcium carbonate was also measured at pH 7.5, 6.0 and 4.5 with two CO2 environments (0.3 and 152 mmHg) above the solution. The precipitation profile of CaCO3 was calculated using in-vivo data for bicarbonate and pH from literature and equilibrium calculations. As pH increased, the solubility of each calcium salt increased. However, in distilled water each salt produced a different pH, affecting its solubility value. Although calcium citrate does have a higher solubility than CaCO3 in water, there is little difference when the pH is controlled at pH 7.5. The partial pressure of CO2 also played a role in calcium carbonate solubility, depressing the solubility at pH 7.5. The calculations of soluble calcium resulted in profiles of available calcium, which agreed with previously published in-vivo data on absorbed calcium. The experimental data illustrate the impact of pH and CO2 on the solubility of many calcium salts in the presence of bicarbonate secretions in the intestine. Calculated profiles using in-vivo calcium and bicarbonate concentrations demonstrate that large calcium doses may not further increase intestinal calcium absorption once the calcium carbonate solubility product has been reached.