bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Aspects of Labour Use in Southern Africa – Problems and Policies
Authors: Colclough Christopher
Published: August 2010

SUMMARY The 10 Southern African countries, excluding South Africa, which are the subject of this article are at very different stages of transition from colonial to independent rule. Yet there are common problems which all these countries face. This article focuses upon two of these: migrant labour and skill shortages, particularly in the formal sector. It is argued that these problems may best be tackled by a combined approach which aims to reduce the present heavy dependence of individual countries on South Africa, and to exploit the complementary strengths and opportunities by other countries in the region.

RÉSUMÉ Quelques aspects de l'utilisation de la main‐d'oeuvre dans le sud de l'Afrique – Problèmes et mesures prises pour les résoudre

Les dix pays du sud de l'Afrique examinés ici, Afrique du Sud non comprise, sont à des étapes de transition très différentes, du régime colonial à l'état d'indépendance. Et pourtant tous ces pays ont des problèmes communs. Cet article traite de deux de ces problèmes: la main‐d'oeuvre migrante et le manque de main‐d'oeuvre qualifiée, surtout dans le secteur formel. L'auteur soutient que la meilleure façon de résoudre ces problèmes est d'adopter une approche double qui tende à réduire la lourde dépendance de chaque pays vis‐à‐vis de l'Afrique du Sud et à exploiter les forces et possibilités complémentaires fournies par les autres pays de la région.

RESUMEN Algunos aspectos de la utilización de mano de obra en Africa Meridional : problemas y políticas

Los diez países de Africa Meridional, excluida Sudáfrica, que son objeto de este artículo se hallan en fases muy distintas de transición del gobierno colonial a la independencia. Sin embargo existen problemas comunes con los que tienen que enfrentarse todos estos países. El presente artículo se enfoca hacia dos de estos problemas, a saber, las escaseces de mano de obra emigratoria y de pericia, especialmente en el sector oficial. Se alega que estos problemas pueden plantearse mediante una actitud combinada que pretenda reducir la enorme dependencia actual de los distintos países en Sudáfrica, y tratar de explotar la fuerza y oportunidades complementarias que proveen otros países de la región.
Zimbabwe : a New Nation with Old Problems
Authors: Riddell Roger
Published: August 2010

SUMMARY As the euphoria surrounding the achievement of independence and the ending of eight years of war dies down, the new Government of Zimbabwe is faced with a whole range of social and economic problems, some directly related to the war, some resulting from decades of economic policies which in practice neglected the needs of the black majority. Critical issues include land reform, employment, the distribution of wealth and income and the need to expand basic social services to the rural poor. Already tensions and conflicts are surfacing in relation to the speed with which change can be effected and in the difficult task of policy implementation.

RÉSUMÉ Zimbabwe : Une nation neuve et de vieux problèmes

Tandis que se dissipe l'euphorie qui a fait suite à l'accession à l'indépendance et à la fin de huit ans de guerre, le nouveau gouvernement du Zimbabwe est confronté à toute une série de problèmes sociaux et économiques, dont certains ont pour cause directe la guerre et dont d'autres résultent de plusieurs décennies de politiques économiques ayant négligé dans la pratique les besoins de la majorité noire. Les points critiques sont la réforme agraire, l'emploi, la redistribution des richesses et des revenus et la nécessité d'apporter aux populations pauvres des campagnes les services sociaux de base. Déjà apparaissent des tensions et des conflits en relation avec la rapidité avec laquelle des changements peuvent être effectués et la tache difficile de la mise en oeuvre des mesures adoptées.

RESUMEN Zimbabwe: una nación nueva con antiguos problemas

A media que se desvanece la euforia que envuelve el éxito de la independencia y el fin de una guerra de ocho años, el nuevo gobierno de Zimbabwe se tiene que enfrentar con toda una gama de problemas sociales y económicos, algunos directamente vinculados con la guerra y otros resultantes de decenios de políticas económicas que en la práctica descuidaron las necesidades de la mayoría negra. Los temas críticos incluyen la reforma agraria, el empleo, la distribución de la riqueza y los ingresos y la necesidad de ampliar los servicios sociales básicos para que incluya a los pobres rurales. Ya empiezan a emerger tensiones y conflictos en relación con la velocidad con que se puede efectuar el cambio y con la difícil tarea de ejecutar la política.
Precision Grindability of Granite in Relation to Discrete Distribution Parameters of Microhardness and Microbrittleness
Authors: Xie J.
Published: August 2010

The natural granite includes various hard and brittle minerals with different material behaviors. In this paper, the discrete distribution parameters of microhardness and microbrittleness are proposed to describe its micron-scale material behavior. The objective is to evaluate and predict the precision grindability of various granites by using its microhardness and microbrittleness. First, the relative values of microhardness and microbrittleness were defined by measuring diagonal length and crack spreading length of micron-scale indentation in a micro-indentation experiment; then the microhardness, the microbrittleness, and their average deviations were introduced as discrete distribution parameters with regard to the weighted coefficients of various minerals in granite; finally, a precision grinding experiment was carried out to investigate the grinding force and surface roughness with regard to different grinding variables. It is found that grinding force and surface roughness have good and very good correlations with the microhardness and its average deviation, respectively, but they have no obvious relations with the microbrittleness. The ground surface can be improved when grinding the granite with high microhardness and its uniform distribution even if leading to large grinding force. For grinding variables, the grinding force increases with the decrease in the depth of cut and the work speed in brittle-mode grinding, but it has little correlation with work speed when approaching ductile-mode grinding. It is concluded that the precision grindability of granite may be evaluated and predicated by the relative microhardness and its average deviation.
A Model for Bending, Torsional, and Axial Vibrations of Micro- and Macro-Drills Including Actual Drill Geometry—Part I: Model Development and Numerical Solution
Authors: Filiz Sinan , Burak Ozdoganlar O.
Published: August 2010

Part I of this work presents a combined one-dimensional/three-dimensional approach for obtaining a unified model for the dynamics of micro- and macro-drills. To increase the numerical efficiency of the model, portions of the drill with circular cross-section (shank, extension, and tapered sections) are modeled using one-dimensional beam models without compromising model accuracy. A three-dimensional model is used for an accurate representation of the fluted section, considering the actual geometry with the pretwisted shape and axially varying (nonaxisymmetric) cross-section. The actual cross-section of the drills is incorporated to the model through a polynomial mapping while the pretwist effect is captured by defining a rotating reference frame. The boundary-value problem for both one- and three-dimensional models are derived using a variational approach, based on the extended Hamilton’s principle, and are subsequently solved by applying the spectral-Tchebychev technique. A component-mode synthesis is used for connecting the individual sections to obtain the dynamic model for the entire drill. Convergence of the model is studied by varying the number of polynomials for each section. The experimental validation of the model is included in Part II for both macro- and micro-drills. Also included in Part II is an analysis of drill dynamics for varying drill-geometry parameters and axial (thrust) force.
Further Evidence for Acoustic Resonance in Full Size Steam Generator and Tubular Heat Exchanger Tube Banks
Authors: Eisinger Frantisek L. , Sullivan Robert E.
Published: August 2010

Acoustic resonance or acoustic vibration, which develops in flow channels containing a tube bank, is caused by vortex shedding generated by crossflow over the tube bank. Transverse acoustic modes are excited, which are perpendicular to the direction of flow and of the tube axes. For the excitation of the acoustic modes resulting in acoustic resonance, two conditions must be met: (a) The frequency of vortex shedding must coincide with the frequency of the particular acoustic mode to be excited, and (b) there must be sufficient energy available to initiate the vibration. If the frequency coincidence is not satisfied or if the excitation energy is insufficient, the acoustic resonance will not be possible. It is important to define the criteria, which need to be met for the initiation of the acoustic resonance. In this paper, new criteria are developed on the basis of the acoustic particle velocity for the onset of acoustic resonance in steam generator and tubular heat exchanger tube banks.
Numerical Estimation of Fluidelastic Instability in Tube Arrays
Authors: Hassan Marwan , Gerber Andrew , Omar Hossin
Published: August 2010

This study investigates unsteady flow in tube bundles and fluid forces, which can lead to large tube vibration amplitudes, in particular, amplitudes associated with fluidelastic instability (FEI). The fluidelastic forces are approximated by the coupling of the unsteady flow model (UFM) with computational fluid dynamics (CFD). The CFD model employed solves the Reynolds averaged Navier–Stokes equations for unsteady turbulent flow and is cast in an arbitrary Lagrangian–Eulerian form to handle any motion associated with tubes. The CFD solution provides time domain forces that are used to calculate added damping and stiffness coefficients employed with the UFM. The investigation demonstrates that the UFM utilized in conjunction with CFD is a viable approach for calculating the stability map for a given tube array. The FEI was predicted for in-line square and normal triangle tube arrays over a mass damping parameter range of 0.1– 100. The effect of the P/d ratio and the Reynolds number on the FEI threshold was also investigated.
The Chlorine Isotope Composition of the Moon and Implications for an Anhydrous Mantle
Authors: Sharp Z. D. , Shearer C. K. , McKeegan K. D. , Barnes J. D. , Wang Y. Q.
Published: August 2010

Over the Moon

Based on recent analyses of lunar rocks, it has been argued that the lunar interior contained much more water than previously thought.

Sharp
et al.

(p.
1050
, published online 5 August) measured the chlorine isotope content of lunar samples returned by the Apollo missions and found that the spread in their chlorine isotope composition is 25-fold greater than for rocks and minerals that have been measured from Earth and meteorites. This result implies that the hydrogen content of the Moon (and therefore its water content) is much lower than suggested by recent studies.
Nuclear expression of interleukin-33 in pancreatic stellate cells
Authors: Masamune Atsushi , Watanabe Takashi , Kikuta Kazuhiro , Satoh Kennichi , Kanno Atsushi , Shimosegawa Tooru
Published: August 2010

Activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have suggested a role of IL-33, a newly identified IL-1 family member, in fibrosis. We here examined the expression of IL-33 and the IL-33-mediated regulation of cell functions in PSCs. PSCs were isolated from human and rat pancreas tissues. The expression of IL-33 was examined by Western blotting, PCR, ELISA, and immunostaining. The roles of IL-33 in the regulation of PSC functions were examined by using recombinant IL-33 and small interfering RNA. Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1β, TNF-α, PDGF-BB, and IFN-γ, but not TGF-β1. Nuclear IL-33 expression was also observed in the pancreatic acinar and ductal cells. IL-1β induced IL-33 expression mainly through the activation of NF-κB and ERK pathways and partially through that of p38 MAP kinase, whereas PDGF-BB induced IL-33 expression mainly through the activation of ERK pathway. PSCs expressed soluble ST2, ST2L, and IL-1RAcP, but the expression level of ST2L was relatively low. Recombinant IL-33 did not stimulate key cell functions of PSCs. Decreased IL-33 expression by small interfering RNA resulted in decreased proliferation in response to PDGF-BB. In conclusion, activated PSCs expressed IL-33 in the nucleus. IL-33 might regulate the PDGF-induced proliferation in PSCs.
Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats
Authors: Zheng Jun , Babygirija Reji , Bülbül Mehmet , Cerjak Diana , Ludwig Kirk , Takahashi Toku
Published: August 2010

Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression.
Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus)
Authors: Sakahara Satoshi , Xie Zuoyun , Koike Kanako , Hoshino Satoya , Sakata Ichiro , Oda Sen-ichi , Takahashi Toku , Sakai Takafumi
Published: August 2010

Although many studies have demonstrated the physiological action of motilin on the migrating motor complex, the precise mechanisms remain obscure. To obtain new insights into the mechanisms, we focused on the house musk shrew ( Suncus murinus, suncus used as a laboratory name) as a small model animal for in vivo motilin study, and we studied the physiological characteristics of suncus gastrointestinal motility. Strain gauge transducers were implanted on the serosa of the gastric body and duodenum, and we recorded gastrointestinal contractions in the free-moving conscious suncus and also examined the effects of intravenous infusion of various agents on gastrointestinal motility. During the fasted state, the suncus stomach and duodenum showed clear migrating phase III contractions (intervals of 80–150 min) as found in humans and dogs. Motilin (bolus injection, 100–300 ng/kg; continuous infusion, 10–100 ng·kg−1·min−1) and erythromycin (80 μg·kg−1·min−1) induced gastric phase III contractions, and motilin injection also increased the gastric motility index in a dose-dependent manner ( P < 0.05, vs. saline). Pretreatment with atropine completely abolished the motilin-induced gastric phase III contractions. On the other hand, in the free-feeding condition, the suncus showed a relatively long fasting period in the light phase followed by spontaneous gastric phase III contractions. The results suggest that the suncus has almost the same gastrointestinal motility and motilin response as those found in humans and dogs, and we propose the suncus as a new small model animal for studying gastrointestinal motility and motilin in vivo.
Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis
Authors: Olfert I. Mark , Howlett Richard A. , Wagner Peter D. , Breen Ellen C.
Published: August 2010

We have previously shown, using a Cre-LoxP strategy, that vascular endothelial growth factor (VEGF) is required for the development and maintenance of skeletal muscle capillarity in sedentary adult mice. To determine whether VEGF expression is required for skeletal muscle capillary adaptation to exercise training, gastrocnemius muscle capillarity was measured in myocyte-specific VEGF gene-deleted (mVEGF−/−) and wild-type (WT) littermate mice following 6 wk of treadmill running (1 h/day, 5 days/wk) at the same running speed. The effect of training on metabolic enzyme activity levels and whole body running performance was also evaluated in mVEGF−/−and WT mice. Posttraining capillary density was significantly increased by 59% ( P < 0.05) in the deep muscle region of the gastrocnemius in WT mice but did not change in mVEGF−/−mice. Maximal running speed and time to exhaustion during submaximal running increased by 20 and 13% ( P < 0.05), respectively, in WT mice after training but were unchanged in mVEGF−/−mice. Training led to increases in skeletal muscle citrate synthase (CS) and phosphofructokinase (PFK) activities in both WT and mVEGF−/−mice ( P < 0.05), whereas β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity was increased only in WT mice. These data demonstrate that skeletal muscle capillary adaptation to physical training does not occur in the absence of myocyte-expressed VEGF. However, skeletal muscle metabolic adaptation to exercise training takes place independent of myocyte VEGF expression.
Early right ventriculo-arterial uncoupling in borderline pulmonary hypertension on experimental heart failure
Authors: Pagnamenta Alberto , Dewachter Céline , McEntee Kathleen , Fesler Pierre , Brimioulle Serge , Naeije Robert
Published: August 2010

Pulmonary hypertension on heart failure (HF) limits exercise capacity and survival probably because of associated right ventricular (RV) failure. This study investigated the mechanisms of RV function adaptation to early pulmonary hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six dogs induced a HF characterized by cardiomegaly and decreased left ventricular ejection fraction. Compared with eight control dogs, pulmonary hypertension was borderline, with a mean pulmonary artery pressure increased to only 23 ± 2 (means ± SE) mmHg. However, the pulmonary vascular impedance spectrum was globally shifted to higher pressures, with an increase in 0 Hz impedance (resistance) to 662 ± 69 vs. 455 ± 41 dynes·cm−5·m2 in controls ( P < 0.01) and in characteristic impedance to 183 ± 20 vs. 104 ± 7 dynes·cm−5·m2 in controls ( P < 0.01). There was no change in RV end-systolic elastance (Ees), but arterial elastance (Ea) was increased to 1.8 ± 0.3 vs. 0.9 ± 0.1 mmHg/ml in controls so that RV-arterial coupling defined by the Ees-to-Ea ratio (Ees/Ea) was decreased to 0.8 ± 0.1 vs. 1.5 ± 0.1 in controls ( P < 0.01). Inhaled nitric oxide, 40 ppm or 5 μg·kg−1·min−1 nitroprusside iv, did not affect Ees/Ea. Fifty milligrams (iv) of milrinone increased Ees/Ea to 1.6 ± 0.2 by an isolated increase in Ees. We conclude that overpacing-induced HF is accompanied by a borderline pulmonary hypertension but profound RV-arterial uncoupling explained by the failure of RV systolic function to adapt combined effects of increased pulmonary arterial resistance and elastance.
Protein and carbohydrate supplementation during 5-day aerobic training enhanced plasma volume expansion and thermoregulatory adaptation in young men
Authors: Goto Masaki , Okazaki Kazunobu , Kamijo Yoshi-ichiro , Ikegawa Shigeki , Masuki Shizue , Miyagawa Ken , Nose Hiroshi
Published: August 2010

We examined whether protein and carbohydrate (CHO) supplementation during 5-day training enhanced plasma volume (PV) expansion and thermoregulatory and cardiovascular adaptations in young men. Eighteen men [age 23 ± 4 (SD) yr] were divided into two groups according to supplements: placebo (CNT: 0.93 kcal/kg, 0.00 g protein/kg, n = 9) and protein and CHO (Pro-CHO: 3.6 kcal/kg, 0.36 protein/kg, n = 9). Subjects in both groups performed a cycling exercise at 70% peak oxygen consumption rate (V̇o2peak), 30 min/day, for 5 consecutive days at 30°C ambient temperature and 50% relative humidity and took either a placebo or Pro-CHO within 10 min after exercise for each day. Before and after training, PV at rest, heart rate (HR), and esophageal temperature (Tes) during 30-min exercise at 65% of pretraining V̇o2peak in the same condition as training were determined. Also, the sensitivity of the chest sweat rate (ΔSR/ΔTes) and forearm vascular conductance (ΔFVC/ΔTes) in response to increased Tes were determined. After training, PV and cardiac stroke volume (SV) at rest increased in both groups ( P < 0.001) but the increases were twofold higher in Pro-CHO than CNT ( P = 0.007 and P = 0.078, respectively). The increases in HR from 5 to 30 min and Tes from 0 to 30 min of exercise were attenuated after training in both groups with greater attenuation in Pro-CHO than CNT ( P = 0.002 and P = 0.072, respectively). ΔSR/ΔTes increased in CNT ( P = 0.052) and Pro-CHO ( P < 0.001) and the increases were higher in Pro-CHO than CNT ( P = 0.018). ΔFVC/ΔTes increased in Pro-CHO ( P < 0.001), whereas not in CNT ( P = 0.16). Thus protein-CHO supplementation during 5-day training enhanced PV expansion and thermoregulatory adaptation and, thereby, the reduction in heat and cardiovascular strain in young men.
Wnt/β-Catenin Signaling in T-Cell Immunity and Cancer Immunotherapy
Authors: Gattinoni Luca , Ji Yun , Restifo Nicholas P.
Published: August 2010

Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic development, cell fate specification, and the homeostasis of self-renewing adult tissues. In addition to its well-established role in thymocyte development, recent studies have indicated that Wnt/β-catenin signaling is critical for the differentiation, polarization, and survival of mature T lymphocytes. Here, we describe our current understanding of Wnt signaling in the biology of post-thymic T cells, and discuss how harnessing the Wnt/β-catenin pathway might improve the efficacy of vaccines, T-cell–based therapies, and allogeneic stem cell transplantation for the treatment of patients with cancer. Clin Cancer Res; 16(19); 4695–701. ©2010 AACR.
Transforming Growth Factor-β1–Mediated Activation of NF-κB Contributes to Enhanced ADAM-12 Expression in Mammary Carcinoma Cells
Authors: Ray Alpana , Dhar Srijita , Ray Bimal K.
Published: August 2010

A disintegrin and metalloproteinase-12 (ADAM-12), a member of multifunctional family of proteins, is upregulated in many cancers, including breast, lung, liver, prostate, gastric, and bladder. The multidomain structure, composed of a prodomain, a metalloproteinase, disintegrin-like, epidermal growth factor–like, cysteine-rich and transmembrane domains, and a cytoplasmic tail, allows ADAM-12 to promote matrix degradation, cell-cell adhesion, and intracellular signaling capacities and thereby to play a critical role in cancer growth and metastasis. Despite ample evidence linking increased ADAM-12 expression with cancer, the mechanisms controlling its upregulation are still unknown. In the present study, transforming growth factor-β1 (TGF-β1) is shown to increase ADAM-12 mRNA expression in MDA-MB-231 breast carcinoma cells. We have identified a promoter element responsible for TGF-β1–mediated ADAM-12 induction. We show interaction of NF-κB with ADAM-12 promoter and that high level of NF-κB activity in breast carcinoma cells results in the upregulation of ADAM-12 expression. Site-directed mutagenesis of the NF-κB element in ADAM-12 promoter and inhibition of NF-κB activity by Bay-11-7085 and MG-132 significantly reduced TGF-β1–mediated increase of ADAM-12 promoter-driven gene expression. Transfection of cells with a dominant-negative mutant form of IκBα (IκBαΔN), which inhibits activation of NF-κB, significantly reduced transcription from ADAM-12 promoter-reporter in TGF-β1–stimulated MDA-MB-231 cancer cells. In correlation, overexpression of NF-κB induced ADAM-12 expression in a dose-dependent manner. DNA-binding and ChIP assays indicated that p65 subunit of NF-κB binds to ADAM-12 promoter. Together, our study identified a cellular mechanism for induction of ADAM-12, which involves NF-κB and its activation by TGF-β1. Mol Cancer Res; 8(9); 1261–70. ©2010 AACR.
Basal Ganglia Volume Is Associated with Aerobic Fitness in Preadolescent Children
Authors: Chaddock Laura , Erickson Kirk I. , Prakash Ruchika Shaurya , VanPatter Matt , Voss Michelle W. , Pontifex Matthew B. , Raine Lauren B. , Hillman Charles H. , Kramer Arthur F.
Published: August 2010

The present investigation is the first to explore the association between childhood aerobic fitness and basal ganglia structure and function. Rodent research has revealed that exercise influences the striatum by increasing dopamine signaling and angiogenesis. In children, higher aerobic fitness levels are associated with greater hippocampal volumes, superior performance on tasks of attentional and interference control, and elevated event-related brain potential indices of executive function. The present study used magnetic resonance imaging to investigate if higher-fit and lower-fit 9- and 10-year-old children exhibited differential volumes of other subcortical brain regions, specifically the basal ganglia involved in attentional control. The relationship between aerobic fitness, dorsal and ventral striatum volumes and performance on an attention and inhibition Eriksen flanker task was also examined. The results indicated that higher-fit children showed superior flanker task performance compared to lower-fit children. Higher-fit children also showed greater volumes of the dorsal striatum, and dorsal striatum volume was negatively associated with behavioral interference. The results support the claim that the dorsal striatum is involved in cognitive control and response resolution and that these cognitive processes vary as a function of aerobic fitness. No relationship was found between aerobic fitness, the volume of the ventral striatum and flanker performance. The findings suggest that increased childhood aerobic fitness is associated with greater dorsal striatal volumes and that this is related to enhanced cognitive control. Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle during childhood has important public health and educational implications.
Effect of Sevelamer Hydrochloride Exposure on Carotid Intima Media Thickness in Hemodialysis Patients
Authors: Boaz M. , Katzir Z. , Schwartz D. , Gafter U. , Biro A. , Shtendik L. , Kon V. , Chernin G. , Weinstein T.
Published: August 2010

Background: Elevated phosphorus (P) and calcium (Ca)-P product (Ca × P) are associated with vascular calcification and cardiovascular disease (CVD) morbidity and CVD and all-cause mortality. Objectives: This study examined the effect of sevelamer hydrochloride exposure (regardless of calcium carbonate exposure) on carotid and femoral intima media thickness (IMT), reliable surrogate measures of prospective intimal thickening, in end-stage renal disease patients on maintenance hemodialysis. Methods: The present cross-sectional study is nested in the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima media thickness progression in end-stage renal disease (SUMMER) clinical trial. Carotid and femoral arteries were visualized in B-mode ultrasonography. Log-transformed IMT was compared by sevelamer hydrochloride exposure and modeled using multiple linear regression. Results: Forty-five subjects were exposed to sevelamer hydrochloride and 130 were not. Exposed subjects had significantly lower carotid IMT, an association which persisted in the multiple linear regression model even after controlling for potentially confounding variables including serum Ca, history of CVD and body weight. Exposed subjects had lower low-density lipoprotein cholesterol levels and significantly higher parathyroid hormone, but no differences in P, Ca and Ca × P. Conclusions: Sevelamer hydrochloride was associated with lower carotid IMT. This association may be mediated through reduction in Ca load, low-density lipoprotein cholesterol lowering or some other pleiotropic effect.
Addition of Infliximab to Standard Therapy for ANCA-Associated Vasculitis
Authors: Morgan Matthew D. , Drayson Mark T. , Savage Caroline O.S. , Harper Lorraine
Published: August 2010

Background: Tumour necrosis factor-α (TNF) is implicated in the pathogenesis of anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). Current immunosuppressive therapy is associated with considerable morbidity and mortality. Anti-TNF antibody therapy (infliximab) may help control AAV by providing more targeted immunosuppression and allow reductions in the use of corticosteroids and cyclophosphamide, thereby reducing the burden of immunosuppression with its associated morbidity and mortality. Methods: 33 patients with active AAV participated in this cohort study. Patients were treated with standard therapy (corticosteroids and cyclophosphamide with additional plasma exchange in the case of life- or organ-threatening disease) or standard therapy + infliximab at weeks 0, 2, 6 and 10. The primary outcome measure was time to remission. Other outcome measures were adverse events, cumulative damage scores and relapse, as well as biomarkers for circulating activated and regulatory T cells. Follow-up was for 12 months. Results: 17 patients received standard therapy alone; 16 patients received additional infliximab. The addition of infliximab to standard therapy did not influence remission rates, adverse events, damage index scores, relapse rates or biomarker levels in this cohort study. Conclusion: The addition of infliximab to standard therapy did not confer clinical benefit for patients with active AAV.
Gamma-glutamyl carboxylase and its influence on warfarin dose
Authors: King Cristi , Deych Elena , Milligan Paul , Eby Charles , Lenzini Petra , Grice Gloria , Porche-Sorbet Rhonda , Ridker Paul , Gage Brian
Published: August 2010

Via generation of vitamin K-dependent proteins, gamma-glutamyl carboxylase (GGCX) plays a critical role in the vitamin K cycle. Single nucleotide polymorphisms (SNPs) in GGCX, therefore, may affect dosing of the vitamin K antagonist, warfarin. In a multi-centered, cross-sectional study of 985 patients prescribed warfarin therapy, we genotyped for two GGCX SNPs (rs11676382 and rs12714145) and quantified their relationship to therapeutic dose. GGCX rs11676382 was a significant (p=0.03) predictor of residual dosing error and was associated with a 6.1% reduction in warfarin dose (95% CI: 0.6%-11.4%) per G allele. The prevalence was 14.1% in our predominantly (78%) Caucasian cohort, but the overall contribution to dosing accuracy was modest (partial R2 = 0.2%). GGCX rs12714145 was not a significant predictor of therapeutic dose (p = 0.26). GGCX rs11676382 is a statistically significant predictor of warfarin dose, but the clinical relevance is modest. Given the potentially low marginal cost of adding this SNP to existing geno-typing platforms, we have modified our non-profit website (www.WarfarinDosing.org) to accommodate knowledge of this variant.
Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation
Authors: Connolly Stuart , Patel Indravadan , Salazar Daniel , Rohatagi Shashank , Mendell Jeanne , Kastrissios Helen , Jin Jianqing , Kunitada Satoshi , Weitz Jeffrey
Published: August 2010

The primary objective of this study was to compare the safety of four fixed-dose regimens of edoxaban with warfarin in patients with nonvalvular atrial fibrillation (AF). In this 12-week, parallel-group, multi-centre, multinational study, 1,146 patients with AF and risk of stroke were randomised to edoxaban 30 mg qd, 30 mg bid, 60 mg qd, or 60 mg bid or warfarin dose-adjusted to a target international normalised ratio of 2.0–3.0. The study was double-blind to edoxaban dose, but open-label to warfarin. Primary outcomes were occurrence of major and/or clinically relevant non-major bleeding and elevated hepatic enzymes and/or bilirubin. Mean age was 65 ± 8.7 years and 64.4% were warfarin-naïve. Whereas major plus clinically relevant non-major bleeding occurred in 3.2% of patients randomised to warfarin, the incidence of bleeding was significantly higher with the edoxaban 60 mg bid (10.6%; p=0.002) and 30 mg bid regimens (7.8%; p=0.029), but not with the edoxaban 60 mg qd (3.8%) or 30 mg qd regimens (3.0%). For the same total daily dose of 60 mg, both bleeding frequency and trough edoxaban concentrations were higher in the 30-mg bid group than in the 60-mg qd group. There were no significant differences in hepatic enzyme elevations or bilirubin values among the groups. The safety profiles of edoxaban 30 and 60 mg qd in patients with AF were similar to warfarin. In contrast, the edoxaban bid regimens were associated with more bleeding than warfarin. These results suggest that in this three-month study, edoxaban 30 or 60 mg qd are safe and well-tolerated.

ClinicalTrials.gov Registration Number: NCT00504556
Enoxaparin for the secondary prevention of placental vascular complications in women with abruptio placentae
Authors: Chauleur Céline , Faillie Jean-Luc , Baer Guillaume , Marès Pierre , Fabbro-Peray Pascale , Quéré Isabelle , Lefrant Jean-Yves , Haddad Bassam , Dauzat Michel , Gris Jean-Christophe
Published: August 2010

Administration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18–0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.
The vessel wall: A forgotten player in post thrombotic syndrome
Authors: DeRoo Scott , Deatrick K. Barry , Henke Peter
Published: August 2010

Much research in venous thrombotic diseases focuses on the acute thrombotic process such as anticoagulation and risk factors. Deep-vein thrombosis directly leads to post thrombotic syndrome, and this can cause significant patient disability. Little research has focused on the vein wall injury response to the thrombotic inflammatory insult. Herein, we review what is currently known about this process with emphasis on the matrix, mediators, and vascular medial smooth muscle response after thrombotic injury. Translational therapies and potential future agents are reviewed.
Phosphorylation of G Protein–Coupled Receptor Kinase 2–Interacting Protein 1 Tyrosine 392 Is Required for Phospholipase C-γ Activation and Podosome Formation in Vascular Smooth Muscle Cells
Authors: Wang Jing , Yin Guoyong , Menon Prashanthi , Pang Jinjiang , Smolock Elaine M. , Yan Chen , Berk Bradford C.
Published: August 2010

Objective—

Podosomes, which are actin-rich structures, contribute to cell motility, matrix remodeling, and tissue remodeling. We have shown that G protein–coupled receptor kinase 2–interacting protein 1 (GIT1) colocalizes with podosomes and is important in podosome formation in endothelial cells. Src stimulates GIT1 tyrosine phosphorylation, which is critical for phospholipase C-γ (PLCγ) activation. In this study, we identified specific GIT1 tyrosines required for PLCγ activation and podosome formation in vascular smooth muscle cells (VSMC).

Methods and Results—

We used phorbol 12,13-dibutyrate (PDBU) to induce podosomes in A7r5 VSMC. GIT1 colocalized with podosomes and GIT1 knockdown using short interfering RNA significantly reduced podosome formation. PDBU stimulated GIT1 tyrosine phosphorylation. GIT1 tyrosine phosphorylation was dramatically decreased in SYF−/− cells, and it was also reduced by pretreatment with the protein kinase C (PKC) and Src inhibitors, suggesting that GIT1 phosphorylation was dependent on PKC and Src. By mutation analysis of multiple tyrosines, we found that PDBU specifically increased GIT1-Y392 phosphorylation. Overexpression of GIT1 (Y392F) but not of GIT1 (Y321F) decreased PDBU-mediated PLCγ activation and podosome formation without effect on extracellular signal–regulated kinase 1/2 activation. Additionally, we provide evidence that GIT1 knockout VSMC have markedly fewer podosomes on PDBU treatment compared with wild-type VSMC. These data show that GIT1 is a key regulator of podosome formation in VSMC.

Conclusion—

In conclusion, our data suggest that GIT1-Y392 phosphorylation is critical for PDBU-induced podosome formation by regulating PLCγ activation. We propose that specific signaling modules are assembled in a GIT1 phosphotyrosine-dependent manner as exemplified by PLCγ activation versus extracellular signal–regulated kinase 1/2 activation.
Ischemic Stroke Subtypes in a Japanese Population
Authors: Turin Tanvir Chowdhury , Kita Yoshikuni , Rumana Nahid , Nakamura Yasuyuki , Takashima Naoyuki , Ichikawa Masaharu , Sugihara Hideki , Morita Yutaka , Hirose Kunihiko , Okayama Akira , Miura Katsuyuki , Ueshima Hirotsugu
Published: August 2010

Background and Purpose—

Population-based information on the epidemiology of ischemic stroke (IS) subtypes is scant. In this study, we characterized IS subtypes in terms of incidence, time trend, and risk factor profiles in a community-based population.

Methods—

We obtained data from the Takashima Stroke Registry on approximately 55 000 residents of Takashima County in central Japan and calculated age-adjusted stroke incidence rates for different IS subtypes. We determined the incidence time trend by calculating the average annual change across years and also compared risk factors between subtypes.

Results—

There were 1389 first-ever ischemic strokes registered during 1988 to 2004. Lacunar infarction was the most frequent etiology (54.1%) followed by cardioembolic infarction (22.9%). Age-adjusted incidence rates for different IS subtypes were lacunar, 77.1; cardioembolic, 31.5; and nonlacunar, 29.7/10
5
person-years. The average annual change was not significant for the IS subtypes except for nonlacunar infarction, which showed a decreasing trend. Risk factor analysis showed that patients with lacunar infarctions were younger and less likely to have a history of transient ischemic attack or a drinking habit than patients with nonlacunar infarctions.

Conclusion—

Lacunar infarct was the most common IS subtype in our population. We found no significant change in the incidence of subtypes during the study, except a decrease in nonlacunar infarction.
Lack of Association Between Pretreatment Neurology Consultation and Subsequent Protocol Deviation in Tissue Plasminogen Activator-Treated Patients With Stroke
Authors: Meurer William J. , Caveney Angela F. , Lo Alex , Zhang Lingling , Frederiksen Shirley M. , Sandretto Annette M. , Silbergleit Robert , Scott Phillip A.
Published: August 2010

Background and Purpose—

We evaluated the hypothesis that consultation with neurology would be associated with fewer protocol deviations in tissue plasminogen activator-treated patients with stroke.

Methods—

A retrospective analysis of consecutive tissue plasminogen activator-treated patients with acute patients was performed. Using χ
2
tests, the proportion of patients with a protocol deviation was calculated and compared between those with evidence of a neurology consultation and those without. Logistic regression was then used to determine the OR for protocol deviation at the same time as controlling for clinical presentation covariates.

Results—

Two hundred seventy-three subjects were included. Protocol deviation rates did not significantly differ between those with (44%) and those without (41%) a consultation. The adjusted OR for deviation comparing any consultation versus nonconsultation was 1.25 (95% CI: 0.58 to 2.68). There was no statistically significant difference between symptomatic intracranial hemorrhage and in-hospital mortality rates between the groups. The proportion of patients with pretreatment deviations not related to timing was low in both the consultation (9.7%) and nonconsultation groups (8.1%).

Conclusions—

Neurological consultation was not found to be associated with decreased protocol deviations in this cohort, although the high proportion of deviations with and without consultation suggests that quality improvement is needed. Most observed pretreatment deviations were attributable to timing. As acute stroke care becomes more efficient and additional methods in reducing door-to-treatment times are sought, models in which emergency physicians direct the initial phase of treatment may merit further consideration.
Side Differences of Carotid Intima-Media Thickness in Predicting Cardiovascular Events Among Patients With Coronary Artery Disease
Authors: Lee Stephen Wai-luen , Siu Han Hai Jo Jo , Kong Shun-ling , Lam Yui-ming , Lam Simon , Chan Pak-hei , Chan Ki-wan , Wong Ka-lam , Tam Chor-cheung , Chan Raymond Hon-wah
Published: August 2010

Population-based studies have demonstrated differences in intima—media thickness (IMT) measured from the left and right common carotid arteries (CCAs). However, its prognostic implications among patients with established coronary artery disease (CAD) remain unknown. Correlations between the left and right CCAs and the composite end point of cardiac death or nonfatal acute coronary syndrome among 149 patients with angiographically confirmed stable CAD were studied. A total of 22 patients had cardiovascular events during the 32.1 ± 10.9 months follow-up. Multivariate analysis revealed that prior ischemic stroke (hazard ratio [HR]: 15.36, 95% confidence interval [CI]: 4.49-52.59, P < .001), extent of CAD (HR: 1.56, 95%CI: 1.01-2.42, P = .046), and right CCA IMT (HR: 17.07, 95%CI: 2.16-134.69, P = .007) but not the left CCA IMT, independently predicted cardiovascular events. The right CCA IMT independently predicted event-free survival among patients with established CAD, suggesting that the left and right CCA may exhibit different prognostic values in our population.
Cognitive Defusion Versus Thought Distraction: A Clinical Rationale, Training, and Experiential Exercise in Altering Psychological Impacts of Negative Self-Referential Thoughts
Authors: Masuda Akihiko , Feinstein Amanda B. , Wendell Johanna W. , Sheehan Shawn T.
Published: August 2010

Using two modes of intervention delivery, the present study compared the effects of a cognitive defusion strategy with a thought distraction strategy on the emotional discomfort and believability of negative self-referential thoughts. One mode of intervention delivery consisted of a clinical rationale and training (i.e., Partial condition). The other mode contained a condition-specific experiential exercise with the negative self-referential thought in addition to the clinical rationale and training (i.e., Full condition). Nonclinical undergraduates were randomly assigned to one of five protocols: Partial-Defusion, Full-Defusion, Partial-Distraction, Full-Distraction, and a distraction-based experimental control task. The Full-Defusion condition reduced the emotional discomfort and believability of negative self-referential thoughts significantly more than other comparison conditions. The positive results of the Full-Defusion condition were also found among participants with elevated depressive symptoms.
Having the Power to Forgive: When the Experience of Power Increases Interpersonal Forgiveness
Authors: Karremans Johan C. , Smith Pamela K.
Published: August 2010

The present research examined the association between power, defined in terms of experienced control over outcomes and resources in a relationship, and interpersonal forgiveness. Based on recent findings in the literature suggesting that power is associated with goal directedness, it was hypothesized that high levels of experienced power should facilitate forgiveness, in particular in relationships of strong commitment. The results of three studies, using both correlational and experimental designs, supported this prediction: Power was positively associated with forgiveness, but this effect was stronger in relationships of strong (rather than weak) commitment. This pattern of results was observed for both the inclination to forgive hypothetical offenses and actual forgiveness regarding a past offense. Study 3 provided some preliminary evidence for the role of rumination in the link between power and forgiveness. Implications of these findings for the literature on forgiveness and the literature on social power are discussed.
Reliability and Validity of the Dementia Quality of Life Measure in Nursing Home Residents
Authors: Adler Efrat , Resnick Barbara
Published: August 2010

The purpose of this study was to test the reliability and validity of the Dementia Quality of Life (DQOL) in a sample of 486 residents from 12 nursing homes in the greater Baltimore area. There was some evidence of validity of the DQOL based on confirmatory factor analysis and Rasch model testing and criterion-related validity. Reliability of the DQOL was somewhat supported in this study based on internal consistency and test—retest reliability. Alpha coefficients and R2 estimations were generally low across all of the subscales. Despite these findings, the subscale scores remained consistent over a 12-month period. The use of the single-item question about QOL may not be an accurate reflection of QOL among nursing home residents. These findings provide additional information about the psychometric properties of the DQOL and offer some recommendations for revisions in the measure to optimally measure QOL in nursing home residents.