Internal representation of movement in children with developmental coordination disorder : a mental rotation task

Recent studies show that children with developmental coordination disorder (DCD) have difficulties in generating an accurate visuospatial representation of an intended action, which are shown by deficits in motor imagery. This study sought to test this hypothesis further using a mental rotation paradigm. It was predicted that children with DCD would not conform to the typical pattern of responding when required to imagine movement of their limbs. Participants included 16 children with DCD and 18 control children; mean age for the DCD group was 10 years 4 months, and for controls 10 years. The task required children to judge the handedness of single-hand images that were presented at angles between 0° and 180° at 45° intervals in either direction. Results were broadly consistent with the hypothesis above. Responses of the control children conformed to the typical pattern of mental rotation: a moderate trade-off between response time and angle of rotation. The response pattern for the DCD group was less typical, with a small trade-off function. Response accuracy did not differ between groups. It was suggested that children with DCD, unlike controls, do not automatically enlist motor imagery when performing mental rotation, but rely on an alternative object-based strategy that preserves speed and accuracy. This occurs because these children manifest a reduced ability to make imagined transformations from an egocentric or first-person perspective.

Procedural learning in children with developmental coordination disorder

Despite the fact that developmental coordination disorder (DCD) is characterised by a deficit in the ability to learn or automate motor skills, few studies have examined motor learning over repeated trials. In this study we examined procedural learning in a group of 10 children with DCD (aged 8–12 years) and age-matched controls without DCD. The learning task was modelled on that of Nissen and Bullemer [Cognitive Psychology 19 (1987) 1]. Children performed a serial reaction time (SRT) task in which they were required to learn a spatial sequence that repeated itself every 10 trials. Children were not aware of the repetition. Spatial targets were four (horizontal) locations presented on a computer monitor. Children responded using four response keys with the same horizontal mapping as the stimulus. They were tested over five blocks of 100 trials each. The first four blocks presented the same repeating sequence, while the fifth block was randomised. Procedural learning was indexed by the slope of the regression of RT on blocks 1–4. Results showed that most children displayed strong procedural learning of the sequence, despite having no explicit knowledge about it. Overall, there was no group difference in the magnitude of learning over blocks of trials – most children performed within the normal range. Procedural learning for simple sequential movements appears to be intact in children with DCD. This suggests that cortico-striatal circuits that are strongly implicated in the sequencing of simple movements appear to be function normally in DCD.

Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer

We and others have shown that the copper transporters ATP7A and ATP7B play a role in cellular resistance to cisdiaminedichloroplatinum (II) (CDDP).  In this study, we found that ATP7A transfection of Chinese hamster ovary  cells (CHOK1) and fibroblasts isolated from Menkes disease patients  enhanced resistance not only to CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7-ethyl-10- hydroxy-camptothecin (SN-38),  etoposide, doxorubicin, mitoxantron, and 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A preferentially localized
doxorubicin fluorescence to the Golgi apparatus in contrast to the more intense nuclear staining of doxorubicin in the parental cells. Brefeldin A   partially and monensin completely altered the distribution of doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the uptake of SN-38 in membrane vesicles. These findings strongly suggested that   ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi network has an important role of ATP7A-related drug resistance. ATP7A was expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the adjacent normal epithelium. Using the histoculture drug response assay that is useful for the prediction of drug sensitivity of clinical cancers, ATP7A-expressing colon cancer cells were significantly more  resistant to SN-38 than ATP7Anegative cells. Thus, ATP7A confers  resistance to various anticancer agents on cancer cells and might be a good index of drug resistance in clinical colon cancers.

Microstructure evolution of TI-SN-NB alloy prepared by mechanical alloying

In the present study, Ti-16Sn-4Nb alloy was prepared by mechanical alloying (MA). Optical microscopy, scanning electron microscopy combined with energy dispersive X-ray analysis (SEM-EDX), and X-ray diffraction analysis (XRD) were used to characterise the phase transformation and the microstructure evolution. Results indicated that ball milling to 8 h led to the formation of a supersaturated hcp α-Ti and partial amorphous phase due to the solid solution of Sn and Nb into Ti lattice. The microstructure of the bulk sintered Ti-16Sn-4Nb alloy samples made from the powders at shorter ball milling times, i.e. 20 min- 2 h, exhibited a primary α surrounded by a Widmanstätten structure (transformed β); while in the samples made from the powders at longer ball milling times, i.e. 5- 10 h, the alloy evolved to a microstructure with a disordered and fine β phase dispersed homogeneously within the α matrix. These results contribute to the understanding of the microstructure evolution in alloys of this type prepared by powder metallurgy.

Simultaneous determination of irinotecan (CPT-11) and SN-38 in tissue culture media and cancer cells by high performance liquid chromatography: Application to cellular metabolism and accumulation studies

A simple and sensitive HPLC method was developed to simultaneously determine CPT-11 and its major metabolite SN-38 in culture media and cell lysates. Camptothecin (CPT) was used as internal standard (I.S.). Compounds were eluted with acetonitrile–50 mM disodium hydrogen phosphate buffer containing 10 mM sodium 1-heptane-sulfonate, with the pH adjusted to 3.0 using 85% (w/v) orthophosphoric acid (27/73, v/v) by a Hyperclon ODS (C18) column (200 mm × 4.6 mm i.d.), with detection at excitation and emission wavelengths of 380 and 540 nm, respectively. The average extraction efficiencies were 96.9–108.3% for CPT-11 in culture media and 94.3–107.2% for CPT-11 in cell lysates; and 87.7–106.8% for SN-38 in culture media and 90.1–105.6% for SN-38 in cell lysates. Within- and between-day precision and accuracy varied from 0.1 to 10.3%. The limit of quantitation (precision and accuracy <20%) was 5.0 and 2.0 ng/ml for CPT-11 and 1.0 and 0.5 ng/ml for SN-38 in culture media and cell lysates, respectively. This method was successfully applied to quantitate the cellular accumulation and metabolism of CPT-11 and SN-38 in H4-II-E, a rat hepatoma cell line.

Trimethylene-bridged tetraorganodistannoxanes{[Me3SiCH2(RCOO)Sn(CH2)3Sn(OOCR)CH2SiMe3]O}n(R=Ph,2,4-Me2C6H3): control of structure by variation of R*

The synthesis of trimethylene-bridged carboxylate-substituted tetraorganodistannoxanes {[Me_3SiCH_2(RCOO)Sn(CH_2)_3Sn(OOCR)CH_2SiMe_3]O}_n (1, R = Ph; 2, R = 2,4-Me_2C_6H_3) is reported. Depending on the structure of R, in the solid state these compounds are either dimers (1, n = 2, cis-isomer) with a ladder-type structure or tetramers (2, n = 4) with a double ladder-type structure.

The first dimeric trioganotin fluoride : stabilization by unsymmetrically oriented menthyl substituents

In the solid state, (-)-tris([1R,2S,5R]-menthyl)tin fluoride, Men₃SnF (6), exhibits a dimeric structure in which one tin atom is four-coordinate and the other five-coordinate. This novel dimeric association mode is attributed to the orientation of the unsymmetrical menthyl groups, which are arranged to allow a minimum Sn···Sn separation of 4.84 Å within the dimer. The exocyclic isopropyl groups of the menthyl groups point in opposite directions on each tin atom of the dimer, thus preventing further association (Sn···Sn separation outside the dimer 10.49 Å). ¹¹⁹Sn and ¹⁹F MAS NMR spectroscopy were utilized to probe the diverse coordination numbers found by X-ray crystallography for the geometries of the two tin and fluorine sites. In solution, 6 is a monomer at both room temperature and -100 °C. However, upon addition of Bu₄NF, 6 is in equilibrium with [(Men₃SnF)₂F]- (6a), [Men₃SnF₂]^- (6b), and noncoordinating fluoride anions.

The interplay of secondary Te···N, Te···O, Te···I and I···I interactions, Te···π contacts and π-stacking in the supramolecular structures of [{2-(4-nitrobenzylideneamino)-5-methyl}phenyl](4-methoxyphenyl)tellurium dihalides

The unsymmetrical1y substituted diorganotellurium dihalides [2-(4,4'-N0₂C₆H₄CHNC₆H₃Me]RTeX₂ (R = 4-MeOC₆H₄, X = Cl,
1a; Br, 1b; I, 1c; R =4-MeC₆H₄ ; X = Cl, 2; R =C₆H₅, X = Cl, 3) were prepared in good yields and characterized by solution and solid-state ¹²⁵Te NMR spectroscopy, IR spectroscopy and X-ray crystallography. In the solid-state, molecular structures of 1a and 1c possess scarcely observed 1,4-type intramolecular Te···N secondary interaction. Crystal packing of these compounds show an unusually rich diversity of intermolecular secondary, Te·· ·0, Te· .. \ and 1···1 interactions, Te·· ·π contacts as well as extensive
π-stacking of the organic substituents.

Rules and resources: a structuration approach to understanding the coordination of childrens`s inpatient health care

Aim. This paper presents findings from a multi-method study exploring the process of care coordination in children's inpatient health care.

Background. Existing work on care coordination is typified by 'black-box' type studies that measure inputs to and outcomes of care coordination roles and practices, without addressing the process of coordination.

Method. Using questionnaires, interviews and observation to collect data in multiple sites in the United Kingdom and Denmark between 1999 and 2005, the study gathered the perceptions of staff and compared these with observed practice. Giddens' structuration theory was used to provide an analytical and explanatory framework.

Findings. Current care coordination practice is diverse and inconsistent. It involves a wide range of clinical and non-clinical staff, many of whom perceive a lack of clarity about who should perform specific coordination activities. Staff draw upon a wide range of different material and non-material resources in coordinating care, the use of which is governed by largely tacit and informal rules.

Conclusions. Care coordination can be usefully conceptualized as a 'structurated' process – one that is continually produced and reproduced by staff using rules and resources to 'instantiate' or bring about care coordination through action. Potentially negative implications of this are manifested in diversity and inconsistency in care coordination practice. However, positive aspects such as the opportunity this provides to tailor care to the needs of the individual patient can be realized.

Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat.

Irinotecan (CPT-11) and its main metabolite SN-38 are potent anticancer derivatives of camptothecin (CPT), with active lactone and inactive carboxylate forms coexisting. A simple and sensitive HPLC method using the ion-pairing reagent tetrabutylammonium hydrogen sulfate (TBAHS) was developed to simultaneously determine all four analytes in rat plasma samples. Camptothecin (CPT) was used as internal standard. The mobile phase was 0.1 M potassium dihydrogen phosphate containing 0.01 M TBAHS (pH 6.4)–acetonitrile (75:25, v/v). Separation of the compounds was carried out on a Hypersil C18 column, monitored at 540 nm (excitation wavelength at 380 nm). All four compounds gave linear response as a function of concentration over 0.01–10 μM. The limit of quantitation in rat plasma was 0.01, 0.008, 0.005 and 0.005 μM for CPT-11 lactone, CPT-11 carboxylate, SN-38 lactone and SN-38 carboxylate, respectively. The method was successfully used in the study on the effect of coadministered thalidomide on the plasma pharmacokinetics of CPT-11 and SN-38 in rats. Coadministered thalidomide (100 mg/kg body weight by intraperitoneal injection) significantly increased the AUC_0–10h values of CPT-11 lactone and CPT-11 carboxylate by 32.6% and 30.3 %, respectively, (P < 0.01), but decreased the values by 19.2% and 32.4% for SN-38 lactone and carboxylate, respectively, (P < 0.05). Accordingly, the value of total body clearance (CL) of CPT-11 lactone was significantly lower in combination group compared to the control (1.329 versus 1.837 L/h/kg, P = 0.0002). Plasma t_1/2β values for SN-38 lactone and carboxylate were significantly (P < 0.01) smaller in rats with coadministered thalidomide, as compared to rats receiving CPT-11 alone. Further studies are needed to explore the underlying mechanisms for the observed kinetic interaction between CPT-11 and thalidomide.

Photochemical Generation and Intramolecular Chemistry of β-Alkoxycarbenes

The photolytic phenanthrene-based precursors for both β-methoxycarbene and β-ethoxycarbene were synthesized with and without a deuterium label attached to the a carbon. The incorporation of this deuterium label allowed distinction between a 1, 2-H shift and a 1, 2-O shift pathway to the respective alkyl vinyl ether, without the influence of a primary kinetic isotope effect. Photolyses of these precursors gave rearrangement products of the expected β-alkoxycarbenes. In the case of β-methoxycarbene, no methyl vinyl ether was observed due to its volatility. However, the appearance of aldehyde peaks in the NMR spectra, from an apparent further rearrangement to acetaldehyde through an enol intermediate, indicated that a 1,2-H shift had occurred. Ethyl vinyl ether was isolated following the photolysis of the β-ethoxycarbene precursor. Quantification of the two pathways showed less than 2% undergoing an ethoxy shift to the ethyl vinyl ether. Yield experiments on this photolysis demonstrated a maximum yield of β-ethoxycarbene as 43%, though this decreased as the experiment continued. Computational work on the β-ethoxycarbene system indicates that the triplet scate is more stable than the singlet. In addition, the activation energy to the 1.2-H shift pathway is remarkably low and is clearly consistent with the observed overwhelming preference for this pathway in the experiment.

T-Shaped equi-channel angular pressing of Pb-Sn eutectic and its tensile properties

Equi-channel angular pressing (ECAP) of a Pb–Sn eutectic alloy up to six passes in a T-shaped die, rather than a conventional L-shaped die, was studied for grain refinement. The effect of ECAP on the hardness and tensile properties was studied. Microstructure predominately changed in the early part of the ECAP process and became equiaxed and uniformly distributed in both the longitudinal and the transverse sections after four passes. There occurred substantial softening over the first two passes—hardness of 10 Hv, yield strength of 14.2 MPa and tensile strength of 16.3 MPa in the as-cast condition decreased upon two passes to 6 Hv, 9.7 MPa and 13.0 MPa, respectively. The ductility (% elongation) increased drastically from <50% in the as-cast condition to 150% upon two passes, and further increased to 230% after four passes. Various tensile properties and concurrent microstructural evolution were used to develop a mutual relationship among them.