bluuebunny/crossref_metadata_2025 huggingface dataset:
Ankle morphology amplifies calcaneus movement relative to triceps surae muscle shortening
Authors: Csapo R. , Hodgson J. , Kinugasa R. , Edgerton V. R. , Sinha S.
Published: June 2013

The present study investigated the mechanical role of the dorsoventral curvature of the Achilles tendon in the conversion of the shortening of the plantarflexor muscles into ankle joint rotation. Dynamic, sagittal-plane magnetic resonance spin-tagged images of the ankle joint were acquired in six healthy subjects during both passive and active plantarflexion movements driven by a magnetic resonance compatible servomotor-controlled foot-pedal device. Several points on these images were tracked to determine the 1) path and deformation of the Achilles tendon, 2) ankle's center of rotation, and 3) tendon moment arms. The degree of mechanical amplification of joint movement was calculated as the ratio of the displacements of the calcaneus and myotendinous junction. In plantarflexion, significant deflection of the Achilles tendon was evident in both the passive (165.7 ± 7.4°; 180° representing a straight tendon) and active trials (166.9 ± 8.8°). This bend in the dorsoventral direction acts to move the Achilles tendon closer to the ankle's center of rotation, resulting in an ∼5% reduction of moment arm length. Over the entire range of movement, the overall displacement of the calcaneus exceeded the displacement of the myotendinous junction by ∼37%, with the mechanical gains being smaller in dorsi- and larger in plantarflexed joint positions. This is the first study to assess noninvasively and in vivo using MRI the curvature of the Achilles tendon during both passive and active plantarflexion movements. The dorsoventral tendon curvature amplifies the shortening of the plantarflexor muscles, resulting in a greater displacement of the tendon's insertion into the calcaneus compared with its origin.
Shunt volume dynamics in stroke patients with patent foramen ovale
Authors: Reichenberger F. , Kaps M. , Seeger W. , Tanislav C.
Published: June 2013

A variation in right atrial and pulmonary arterial pressure might result in a shunt dynamic across a patent foramen ovale (PFO). In the present study we tested if peak exercise facilitates a restoration of right to left shunt (RLS) in stroke patients who demonstrated a functional PFO closure (no evidence of RLS across an initially demonstrated PFO). In stroke patients with PFO demonstrating a functional closure, the RLS was reassessed on peak exercise using contrast-enhanced transcranial Doppler sonography. The exercise procedure consisted of a cardiopulmonary exercise test with supplementary stress echocardiography for assessment of pulmonary circulation. Four stroke patients with initially PFO curtain pattern and a subsequent functional PFO closure (no evidence for RLS) underwent the procedure. In all four patients a RLS could be resurrected during peak physical exercise after a Valsalva strain. While in two patients peak exercise led to an RLS in a countable range of microembolic signals, in two patients a curtain pattern was obtained. One patient showed evidence for reoccurrence of RLS on peak exercise without a Valsalva strain. The patients with curtain pattern had a better peak exercise performance. Although the systolic pulmonary arterial pressure increased during exercise in all patients, there was no direct correlation with the detected RLS. After a functional PFO closure peak exercise combined with a Valsalva strain facilitates the reoccurrence of RLS in stroke patients.
Removal of sedimentation decreases relative deposition of coarse particles in the lung periphery
Authors: Darquenne C. , Zeman K. L. , Sá R. C. , Cooper T. K. , Fine J. M. , Bennett W. D. , Prisk G. K.
Published: June 2013

Lung deposition of >0.5-μm particles is strongly influenced by gravitational sedimentation, with deposition being reduced in microgravity (μG) compared with normal gravity (1G). Gravity not only affects total deposition, but may also alter regional deposition. Using gamma scintigraphy, we measured the distribution of regional deposition and retention of radiolabeled particles (99mTc-labeled sulfur colloid, 5-μm diameter) in five healthy volunteers. Particles were inhaled in a controlled fashion (0.5 l/s, 15 breaths/min) during multiple periods of μG aboard the National Aeronautics and Space Administration Microgravity Research Aircraft and in 1G. In both cases, deposition scans were obtained immediately postinhalation and at 1 h 30 min, 4 h, and 22 h postinhalation. Regional deposition was characterized by the central-to-peripheral ratio and by the skew of the distribution of deposited particles on scans acquired directly postinhalation. Relative distribution of deposition between the airways and the alveolar region was derived from data acquired at the various time points. Compared with inhalation in 1G, subjects show an increase in central-to-peripheral ratio ( P = 0.043), skew ( P = 0.043), and tracheobronchial deposition ( P < 0.001) when particles were inhaled in μG. The absence of gravity caused fewer particles to deposit in the lung periphery than in the central region where deposition occurred mainly in the airways in μG. Furthermore, the increased skew observed in μG likely illustrates the presence of localized areas of deposition, i.e., “hot spots”, resulting from inertial impaction. In conclusion, gravity has a significant effect on deposition patterns of coarse particles, with most of deposition occurring in the alveolar region in 1G but in the large airways in μG.
Progesterone Receptor Signaling in the Microenvironment of Endometrial Cancer Influences Its Response to Hormonal Therapy
Authors: Janzen Deanna M. , Rosales Miguel A. , Paik Daniel Y. , Lee Daniel S. , Smith Daniel A. , Witte Owen N. , Iruela-Arispe M. Luisa , Memarzadeh Sanaz
Published: June 2013

Progesterone, an agonist for the progesterone receptor (PR), can be an efficacious and well-tolerated treatment in endometrial cancer. The clinical use of progesterone is limited because of the lack of biomarkers that predict hormone sensitivity. Despite its efficacy in cancer therapy, mechanisms and site of action for progesterone remain unknown. Using an in vivo endometrial cancer mouse model driven by clinically relevant genetic changes but dichotomous responses to hormonal therapy, we show that signaling through stromal PR is necessary and sufficient for progesterone antitumor effects. Endometrial cancers resulting from epithelial loss of PTEN (PTENKO) were hormone sensitive and had abundant expression of stromal PR. Stromal deletion of PR as a single genetic change in these tumors induced progesterone resistance indicating that paracrine signaling through the stroma is essential for the progesterone therapeutic effects. A hormone-refractory endometrial tumor with low levels of stromal PR developed when activation of KRAS was coupled with PTEN-loss (PTENKO/Kras). The innate progesterone resistance in PTENKO/Kras tumors stemmed from methylation of PR in the tumor microenvironment. Add-back of stromal PR expressed from a constitutively active promoter sensitized these tumors to progesterone therapy. Results show that signaling through stromal PR is sufficient for inducing hormone responsiveness. Our findings suggest that epigenetic derepression of stromal PR could be a potential therapeutic target for sensitizing hormone-refractory endometrial tumors to progesterone therapy. On the basis of these results, stromal expression of PR may emerge as a reliable biomarker in predicting response to hormonal therapy. Cancer Res; 73(15); 4697–710. ©2013 AACR.
Ketogenic Diets Enhance Oxidative Stress and Radio-Chemo-Therapy Responses in Lung Cancer Xenografts
Authors: Allen Bryan G. , Bhatia Sudershan K. , Buatti John M. , Brandt Kristin E. , Lindholm Kaleigh E. , Button Anna M. , Szweda Luke I. , Smith Brian J. , Spitz Douglas R. , Fath Melissa A.
Published: June 2013

Purpose: Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress.

Experimental Design: Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8–2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)–modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and γH2AX as indices of proliferation and DNA damage, respectively.

Results: The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA.

Conclusions: These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress. Clin Cancer Res; 19(14); 3905–13. ©2013 AACR.
Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution
Authors: Semino-Mora Cristina , Testerman Traci L. , Liu Hui , Whitmire Jeannette M. , Studeman Kimberley , Jia Yali , McAvoy Thomas J. , Francis Jennifer , Nieroda Carol , Sardi Armando , Merrell D. Scott , Dubois Andre
Published: June 2013

Purpose: Pseudomyxoma peritonei is an understudied cancer in which an appendiceal neoplasm invades the peritoneum and forms tumor foci on abdominal organs. Previous studies have shown that bacteria reside within pseudomyxoma peritonei tumors and mucin. Thus, we sought to analyze the effect of antibiotics on bacterial density and β-catenin expression within pseudomyxoma peritonei samples.

Experimental Design: The study included 48 patients: 19 with disseminated peritoneal adenomucinosis (DPAM) and 29 with peritoneal mucinous carcinomatosis (PMCA). Fourteen patients were given antibiotics (30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin) twice a day for 14 days. One week after completion of therapy, surgery was conducted and specimens were harvested for pathology, bacterial culture, ISH, and immunohistochemistry.

Results: ISH showed the presence of bacteria in 83% of the patient samples, with a higher Helicobacter pylori density observed in PMCA versus DPAM. PMCA patients treated with antibiotics had a significantly lower bacterial density and decreased β-catenin levels in the cytoplasm, the cell nuclei, and mucin-associated cells. Although not significant, similar trends were observed in DPAM patients. Cell membrane β-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics.

Conclusions: Bacteria play an important role in pseudomyxoma peritonei. Antibiotic treatment improved the histopathology of tissue, particularly in PMCA patients. In PMCA, antibiotics decreased bacterial density and were associated with a significant β-catenin decrease in the cytoplasm, cell nuclei, and mucin along with a small membrane increase. These results suggest that antibiotics offer potential protection against cell detachment, cellular invasion, and metastasis. Clin Cancer Res; 19(14); 3966–76. ©2013 AACR.
The New Kid on the Block: RET in Lung Cancer
Authors: Gainor Justin F. , Shaw Alice T.
Published: June 2013

Summary: RET has recently been identified as a potential new oncogenic driver in a subset of patients with non–small cell lung cancer (NSCLC). In this issue of Cancer Discovery, Drilon and colleagues report preliminary trial data with a RET inhibitor in RET fusion-positive NSCLC, validating RET as a therapeutic target in lung cancer. Cancer Discov; 3(6); 604–6. ©2013 AACR.

See related article by Drilon et al., p. 630
FGFR Fusions in the Driver's Seat
Authors: Sabnis Amit J. , Bivona Trever G.
Published: June 2013

Summary: Through a clinical deep sequencing protocol, Wu and colleagues have identified multiple FGFR fusion proteins in diverse cancers. Pharmacologic inhibition of FGFR suppressed the growth of FGFR fusion–positive tumor models, suggesting that these FGFR fusions are oncogenic drivers and highlighting the use of streamlined clinical sequencing efforts to identify novel, actionable driver oncoproteins in human tumors. Cancer Discov; 3(6); 607–9. ©2013 AACR.

See related article by Wu et al., p. 636
Patterns of Family Identification and Self-Congruence in Childhood Separation Anxiety Disorder
Authors: Blatter-Meunier Judith C. , Lavallee Kristen L. , Schneider Silvia
Published: June 2013

Background: Patterns of identification among family members may differ in families with children with separation anxiety disorder (SAD) as compared with healthy children. However, this has not been explored to date. Method: The present study examines identification processes in 199 families: 100 families of children with SAD, 43 families of children with other anxiety disorders, and 56 families of nondisordered children, using the Family Identification Test. Results: Children with SAD and their parents generally identify significantly less with each other and report less desire to be similar to each other than nondisordered children and their parents. Further, children with SAD are less self-congruent than healthy children. There were no significant differences between children with SAD and with other anxiety disorders. Conclusions: Identification and self-congruence distinguish families of children with SAD from families of healthy children. Future studies should aim to determine the direction of effects over time, as well as to determine the contribution of identification and coherence in explaining SAD after accounting for other factors such as attachment and self-esteem.
Beta Amyloid Suppresses the Expression of the Vitamin D Receptor Gene and Induces the Expression of the Vitamin D Catabolic Enzyme Gene in Hippocampal Neurons
Authors: Dursun Erdinç , Gezen-Ak Duygu , Yilmazer Selma
Published: June 2013

Background/Aims: The beta amyloid aggregations present in Alzheimer's disease affect neurons through various toxic alterations. The aim of this study was to determine the expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D3 24-hydroxylase (an accelerator of vitamin D catabolism), and the L-type voltage-sensitive calcium channel A1C (LVSCC-A1C) in hippocampal neurons in response to beta amyloid and vitamin D treatments to test the protective effects of vitamin D and the probable effects of beta amyloid on vitamin D catabolism. Methods: The expression of the VDR, 24-hydroxylase (24OHase) and LVSCC-A1C mRNAs were studied using quantitative real-time polymerase chain reaction, and the cytotoxicity levels were determined by an ELISA in primary hippocampal neuron cultures prepared from Sprague-Dawley rat embryos. Results: Our results demonstrated that beta amyloid suppressed the expression of VDR mRNA and induced the expression of 24OHase and LVSCC-A1C mRNAs. Conclusion: Beta amyloid may disrupt the vitamin D-VDR pathway and cause defective utilization of vitamin D by suppressing the level of the VDR and elevating the level of 24OHase.
Apoptotic Signaling Pathways in Uteri of Rats with Endometrial Hyperplasia Induced by Ovariectomy Combined with Estrogen
Authors: He Fengjie , Zhang Wenting , Zhang Hong
Published: June 2013

Aims: To explore a new reliable method inducing an animal model similar to the morphology and apoptotic signaling pathways in endometrial hyperplasia patients. Methods: After the rats were ovariectomized, estradiol benzoate (60 µg/​100 g) was intramuscularly injected on alternate days for 4 weeks. The morphology in the uterus was observed under a light microscope and by electron microscopy. The expression levels of survivin/caspase-3 and Fas/FasL were checked by immunohistochemistry, Western blotting and real-time polymerase chain reaction. Results: After the models were induced, the edema and hypertrophy in uteri were observed 4 weeks later. The glands in the endometrium had increased, indented hyperplasia of glandular cells appeared, and a pseudo-stratified phenomenon occurred. Under a transmission electron microscope, free ribosomes had markedly increased and the nucleus was enlarged in the cytoplasm. Compared with the control group, the expression of survivin increased (p < 0.05) while that of caspase-3 and Fas/FasL declined (p < 0.05). Conclusions: In the rat model of endometrial hyperplasia induced by ovariectomy with pharmacological estrogen add-back treatment, survivin, caspase-3 and Fas/FasL signaling pathways play an important role in regulating the apoptosis of glandular cells in uteri.
Differences between ACC/AHA and ESC Guidelines on antiplatelet therapy in patients with acute coronary syndromes
Authors: Lip Gregory , Huber Kurt
Published: June 2013

Note: The review process for this Editorial was fully handled by Christian Weber, Editor in Chief.
Rapid Estrogen Receptor Signaling Mediates Estrogen-Induced Inhibition of Vascular Smooth Muscle Cell Proliferation
Authors: Ueda Kazutaka , Lu Qing , Baur Wendy , Aronovitz Mark J. , Karas Richard H.
Published: June 2013

Objective—

The proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in vascular diseases, such as atherosclerosis and restenosis, after percutaneous coronary intervention. Many studies have shown that estrogen inhibits VSMC proliferation in response to vascular injury in the mouse carotid injury model. However, the mechanisms that mediate these effects remain unclear. Here, we investigated the mechanisms by which estrogen inhibits VSMC proliferation.

Approach and Results—

We established a novel transgenic mouse line, referred to as the disrupting peptide mice, in which rapid estrogen receptor (ER)–mediated signaling is abolished by overexpression of a peptide that prevents the ER from forming a signaling complex necessary for rapid signaling. Carotid artery VSMCs from disrupting peptide mice or littermate wild-type female mice were obtained by the explant method. In VSMCs derived from wild-type mice, estrogen significantly inhibited VSMC proliferation. Phosphorylation levels of Akt and extracellular regulated kinase induced by platelet derived growth factor were significantly inhibited by estrogen pretreatment. Estrogen enhanced complex formation between ERα and protein phosphatase 2A (PP2), and enhanced PP2A activity. The blockade of PP2A activity abolished the estrogen-induced antiproliferative effect on VSMCs. In contrast, none of these effects of estrogen observed in the wild-type VSMCs were observed in VSMCs derived from disrupting peptide mice. These results support that rapid, non-nuclear ER signaling is required for estrogen-induced inhibition of VSMC proliferation, and further that PP2A activation by estrogen mediates estrogen-induced antiproliferative effects.

Conclusions—

These findings support that PP2A activation via rapid, non-nuclear ER signaling may be a novel target for therapeutic approaches to inhibit VSMC proliferation, which plays a central role in atherosclerosis and restenosis.
Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation
Authors: Chen Yikuan , Wong Mei Mei , Campagnolo Paola , Simpson Russell , Winkler Bernhard , Margariti Andriani , Hu Yanhua , Xu Qingbo
Published: June 2013

Objective—

This study was designed to carry out the characterization of stem cells within the adventitia and to elucidate their functional role in the pathogenesis of vein graft atherosclerosis.

Approach and Results—

A mouse vein graft model was used to investigate the functional role of adventitial stem/progenitor cells on atherosclerosis. The adventitia of vein grafts underwent significant remodeling during early stages of vessel grafting and displayed markedly heterogeneous cell compositions. Immunofluorescence staining indicated a significant number of stem cell antigen-1–positive cells that were closely located to vasa vasorum. In vitro clonogenic assays demonstrated 1% to 11% of growing rates from adventitial cell cultures, most of which could be differentiated into smooth muscle cells (SMCs). These stem cell antigen-1–positive cells also displayed a potential to differentiate into adipogenic, osteogenic, or chondrogenic lineages in vitro. In light of the proatherogenic roles of SMCs in atherosclerosis, we focused on the functional roles of progenitor-SMC differentiation, in which we subsequently demonstrated that it was driven by direct interaction of the integrin/collagen IV axis. The ex vivo bioreactor system revealed the migratory capacity of stem cell antigen-1–positive progenitor cells into the vessel wall in response to stromal cell-derived factor-1. Stem cell antigen-1–positive cells that were applied to the outer layer of vein grafts showed enhanced atherosclerosis in apolipoprotein E–deficient mice, which contributed to ≈30% of neointimal SMCs.

Conclusions—

We demonstrate that during pathological conditions in vein grafting, the adventitia harbors stem/progenitor cells that can actively participate in the pathogenesis of vascular disease via differentiation into SMCs.
Flt-1 (Vascular Endothelial Growth Factor Receptor-1) Is Essential for the Vascular Endothelial Growth Factor–Notch Feedback Loop During Angiogenesis
Authors: Chappell John C. , Mouillesseaux Kevin P. , Bautch Victoria L.
Published: June 2013

Objective—

Vascular endothelial growth factor (VEGF) signaling induces Notch signaling during angiogenesis. Flt-1/VEGF receptor-1 negatively modulates VEGF signaling. Therefore, we tested the hypothesis that disrupted Flt-1 regulation of VEGF signaling causes Notch pathway defects that contribute to dysmorphogenesis of Flt-1 mutant vessels.

Approach and Results—

Wild-type and
flt-1
−/−
mouse embryonic stem cell–derived vessels were exposed to pharmacological and protein-based Notch inhibitors with and without added VEGF. Vessel morphology, endothelial cell proliferation, and Notch target gene expression levels were assessed. Similar pathway manipulations were performed in developing vessels of zebrafish embryos. Notch inhibition reduced
flt-1
−/−
embryonic stem cell–derived vessel branching dysmorphogenesis and endothelial hyperproliferation, and rescue of
flt-1
−/−
vessels was accompanied by a reduction in elevated Notch targets. Surprisingly, wild-type vessel morphogenesis and proliferation were unaffected by Notch suppression, Notch targets in wild-type endothelium were unchanged, and Notch suppression perturbed zebrafish intersegmental vessels but not caudal vein plexuses. In contrast, exogenous VEGF caused wild-type embryonic stem cell–derived vessel and zebrafish intersegmental vessel dysmorphogenesis that was rescued by Notch blockade.

Conclusions—

Elevated Notch signaling downstream of perturbed VEGF signaling contributes to aberrant
flt-1
−/−
blood vessel formation. Notch signaling may be dispensable for blood vessel formation when VEGF signaling is below a critical threshold.
The Insufficiency of Left Anterior Oblique and the Usefulness of Right Anterior Oblique Projection for Correct Localization of a Computed Tomography–Verified Right Ventricular Lead Into the Midseptum
Authors: Osmancik Pavel , Stros Petr , Herman Dalibor , Curila Karol , Petr Robert
Published: June 2013

Background—

The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac computed tomography and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the midseptum.

Methods and Results—

Patients indicated to pacemaker implantation were prospectively enrolled. The right ventricular lead was implanted into the midseptum according to standard criteria in left anterior oblique 40 view. The cardiac shadow on the right anterior oblique 30 was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using computed tomography. Of 51 patients, the right ventricular lead was anchored midseptum in 21 (41.2%; MS group). In 30 patients (58.8%; non-MS group), the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the left anterior oblique was similar in both groups. The non-MS group was associated with shorter distances between the tip and the cardiac contours in the right anterior oblique 30 (96.7% of leads in the non-MS group were in the outer quadrant versus 9.6% in the MS group;
P
<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct midseptum placement with positive predictive value of 94.7%.

Conclusions—

Despite the optimal shape of the left anterior oblique, substantial numbers of leads were not anchored in the midseptum. Knowing the right anterior oblique 30 lead position can ensure proper midseptal placement.
Ultra-Sensitive Molecular MRI of Vascular Cell Adhesion Molecule-1 Reveals a Dynamic Inflammatory Penumbra After Strokes
Authors: Gauberti Maxime , Montagne Axel , Marcos-Contreras Oscar A. , Le Béhot Audrey , Maubert Eric , Vivien Denis
Published: June 2013

Background and Purpose—

Our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular MRI method.

Methods—

We first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using MRI after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1). Thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke.

Results—

Using multiparametric MRI, we demonstrated that the level and the kinetics of cerebrovascular VCAM-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. Interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, VCAM-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. In contrast, after permanent middle cerebral artery occlusion, VCAM-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. Our results suggest that these perilesional areas expressing VCAM-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. Using MPIOs-αVCAM-1–enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate VCAM-1 overexpression after stroke and prevent formation of the inflammatory penumbra.

Conclusions—

MPIOs-αVCAM-1–enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.
Dabigatran Versus Warfarin
Authors: Hori Masatsugu , Connolly Stuart J. , Zhu Jun , Liu Li Sheng , Lau Chu-Pak , Pais Prem , Xavier Denis , Kim Sung Soon , Omar Razali , Dans Antonio L. , Tan Ru San , Chen Jyh-Hong , Tanomsup Supachai , Watanabe Mitsunori , Koyanagi Masahide , Ezekowitz Michael D. , Reilly Paul A. , Wallentin Lars , Yusuf Salim
Published: June 2013

Background and Purpose—

Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries.

Methods—

There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used.

Results—

Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3–4.7;
P
=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03–0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06–0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19–0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13–0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year).

Conclusions—

Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00262600.
Modulating the Motor System by Action Observation After Stroke
Authors: Garrison Kathleen Alice , Aziz-Zadeh Lisa , Wong Savio Waiho , Liew Sook-Lei , Winstein Carolee Joyce
Published: June 2013

Background and Purpose—

Much recent interest surrounds the use of action observation, which is observing another individual performing a motor task, in stroke rehabilitation, to promote motor recovery by engaging similar brain regions to action execution. This may be especially useful in individuals with limited mobility. Here, we assess how cortical motor activity during action observation is affected by stroke and by stroke-related motor deficits.

Methods—

We used functional MRI to compare brain activity during right and left hand action observation in right-handed nondisabled participants and participants who were right-handed before left hemisphere stroke. All participants performed the same actions after their functional MRI.

Results—

Nondisabled participants show greater bilateral cortical motor activity when observing actions made using the left hand, whereas participants with stroke show greater ipsilesional cortical motor activity when observing actions made using the right (paretic) hand (
P
<0.05; corrected). For both groups, action processing is modulated by motor capability: cortical motor activity is greater when observing the hand with lower motor scores (
P
<0.05; corrected). Furthermore, for stroke, the extent of ipsilesional activity correlates with lesion volume (
P
=0.049), in a pattern that suggests adaptive plasticity.

Conclusions—

We found that action observation activates specific motor plans in damaged motor circuits after stroke, and this activity is related to motor capability to perform the same actions. Cortical motor activity during action observation may be relevant to motor learning, and to motor relearning in stroke rehabilitation.
Filtering Sensory Information with XCSF: Improving Learning Robustness and Robot Arm Control Performance
Authors: Kneissler Jan , Stalph Patrick O. , Drugowitsch Jan , Butz Martin V.
Published: June 2013

It has been shown previously that the control of a robot arm can be efficiently learned using the XCSF learning classifier system, which is a nonlinear regression system based on evolutionary computation. So far, however, the predictive knowledge about how actual motor activity changes the state of the arm system has not been exploited. In this paper, we utilize the forward velocity kinematics knowledge of XCSF to alleviate the negative effect of noisy sensors for successful learning and control. We incorporate Kalman filtering for estimating successive arm positions, iteratively combining sensory readings with XCSF-based predictions of hand position changes over time. The filtered arm position is used to improve both trajectory planning and further learning of the forward velocity kinematics. We test the approach on a simulated kinematic robot arm model. The results show that the combination can improve learning and control performance significantly. However, it also shows that variance estimates of XCSF prediction may be underestimated, in which case self-delusional spiraling effects can hinder effective learning. Thus, we introduce a heuristic parameter, which can be motivated by theory, and which limits the influence of XCSF's predictions on its own further learning input. As a result, we obtain drastic improvements in noise tolerance, allowing the system to cope with more than 10 times higher noise levels.
Miscellaneous New species of Brazilian Bromeliaceae
Authors: LEME ELTON M.C. , KOLLMANN LUDOVIC J.C.
Published: June 2013

We describe and illustrate 14 miscellaneous new Bromeliaceae species from the Brazilian states of Bahia, Espírito Santo, Minas Gerais, Rio de Janeiro and São Paulo: Aechmea ituberaensis, A. pendulispica, Alcantarea acuminatifolia, A. occulta, Cryptanthus aracruzensis, C. ilhanus, C. rigidifolius, C. tabuleiricola, C. viridipetalus, Neoregelia desenganensis, N. insulana, N. watersiana, Vriesea saltensis, and V. sanctaparecidae. The morphological affinities of the new taxa are also discussed.
A new species of Eriotheca (Malvaceae: Bombacoideae) from Espírito Santo, eastern Brazil
Authors: DE CARVALHO-SOBRINHO JEFFERSON GUEDES
Published: June 2013

A new species of Eriotheca (Malvaceae: Bombacoideae) from a granitic rock outcrop in the state of Espírito Santo, eastern Brazil, is described and illustrated. Eriotheca saxicola represents the first reference of a xylopodium-like organ for the genus. The new species is compared to its putative closest relatives and notes on its distribution, ecology, and phenology are provided.
Global Identification of Previously Undetected Pre-Satellite-Era Tropical Cyclone Candidates in NOAA/CIRES Twentieth-Century Reanalysis Data
Authors: Truchelut Ryan E. , Hart Robert E. , Luthman Briana
Published: June 2013

Prior to the satellite era, limited synoptic observation networks led to an indefinite number of tropical cyclones (TCs) remaining undetected. This period of decreased confidence in the TC climatological record includes the first two-thirds of the twentieth century. While prior studies found that this undersampling exists, disagreement regarding its magnitude has caused difficulties in interpreting multidecadal changes in TC activity. Previous research also demonstrated that reanalyses can be used to extend TC climatology, utilizing the NOAA/Cooperative Institute for Research in Environmental Sciences (CIRES) Twentieth-Century Reanalysis to manually identify previously unknown Atlantic Ocean basin potential TCs. This study expands the spatiotemporal scope of the earlier work by presenting a filtering algorithm that dramatically improves the efficiency with which candidate events are identified in the reanalysis. This algorithm was applied to all tropical basins for the years 1871–1979, resulting in the first quantitative and objective global TC candidate event counts for the decades prior to formal recordkeeping. Observational verification performed on a subset of these events indicates that the algorithm identifies potential missing TCs at a success rate approximating that of earlier work with a significant decrease in the amount of time required. Extrapolating these proportions to all of the candidate events identified suggests that this method may help to locate hundreds of previously unknown TCs worldwide for future study and cataloging. As such, the dataset produced by this research is a source of independent guidance for use in ongoing and future TC climatology revision efforts to produce a more complete historical record more quickly than with current methods.
Atmospheric Forcing of Debris Flows in the Southern Swiss Alps
Authors: Toreti Andrea , Schneuwly-Bollschweiler Michelle , Stoffel Markus , Luterbacher Jürg
Published: June 2013

This article addresses the role of large-scale circulation and thermodynamical features in the release of past debris flows in the Swiss Alps by using classification algorithms, potential instability, and convective time scale. The study is based on a uniquely dense dendrogeomorphic time series of debris flows covering the period 1872–2008, reanalysis data, instrumental time series, and gridded hourly precipitation series (1992–2006) over the area. Results highlight the crucial role of synoptic and mesoscale forcing as well as of convective equilibrium on triggering rainfalls. Two midtropospheric synoptic patterns favor anomalous southwesterly flow toward the area and high potential instability. These findings imply a certain degree of predictability of debris-flow events and can therefore be used to improve existing alert systems.
Applications of Bivariate Fourier Series for Solving the Poisson Equation in Limited-Area Modeling of the Atmosphere: Higher Accuracy with a Boundary Buffer Strip Discarded and an Improved Order-Raising Procedure
Authors: Boyd John P. , Deng Difei , Chen Qiu-Shi , Gao Shouting
Published: June 2013

Bivariate Fourier series have many benefits in limited-area modeling (LAM), weather forecasting, and meteorological data analysis. However, atmospheric data are not spatially periodic on the LAM domain (“window”), which can be normalized to the unit square (x, y) ∈ [0, 1] ⊗ [0, 1] by rescaling the coordinates. Most Fourier LAM meteorology has employed rather low-order methods that have been quite successful in spite of Gibbs phenomenon at the boundaries of the artificial periodicity window. In this article, the authors explain why. Because data near the boundary between the high-resolution LAM window and the low-resolution global model are necessarily suspect, corrupted by the discontinuity in resolution, meteorologists routinely ignore LAM results in a buffer strip of nondimensional width D, and analyze only the Fourier sums in the smaller domain (x, y) ∈ [D, 1 − D] ⊗ [D, 1 − D]. It is shown that the error in a one-dimensional Fourier series with N terms or in a two-dimensional series with N2 terms, is smaller by a factor of N on a boundary-buffer-discarded domain than on the full unit square. A variety of procedures for raising the order of Fourier series convergence are described, and it is explained how the deletion of the boundary strip greatly simplifies and improves these enhancements. The prime exemplar is solving the Poisson equation with homogeneous boundary conditions by sine series, but the authors also discuss the Laplace equation with inhomogeneous boundary conditions.
Familial lipoprotein lipase deficiency: a case of compound heterozygosity of a novel duplication (R44Kfs*4) and a common mutation (N291S) in the lipoprotein lipase gene
Authors: Overgaard Martin , Brasen Claus Lohman , Svaneby Dea , Feddersen Søren , Nybo Mads
Published: June 2013

Familial lipoprotein lipase (LPL) deficiency (FLLD) is a rare autosomal recessive genetic disorder caused by homozygous or compound heterozygous mutations in the LPL gene. FLLD individuals usually express an impaired or non-functional LPL enzyme with low or absent triglyceride (TG) hydrolysis activity causing severe hypertriglyceridaemia. Here we report a case of FLLD in a 29-year-old man, who initially presented with eruptive cutaneous xanthomata, elevated plasma TG concentration but no other co-morbidities. Subsequent genetic testing of the patient revealed compound heterozygosity of a novel duplication (p.R44Kfs*4) leading to a premature stop codon in exon 2 and a known mutation (N291S) in exon 5 of the LPL gene. Further biochemical analysis of the patient's postheparin plasma confirmed a reduction of total lipase activity compared with his heterozygous father carrying the common N291S mutation and to a healthy control. Also the patient showed increased (1.85-fold) activity of hepatic lipase (HL), indicating a functional link between HL and LPL. In summary, we report a case of FLLD caused by compound heterozygosity of a new duplication and a common mutation in the LPL gene, resulting in residual LPL activity. With such mutations, individuals may not receive a diagnosis before classical FLLD symptoms appear later in adulthood. Nevertheless, early diagnosis and lipid-lowering treatment may favour a reduced risk of premature cardiovascular disease or acute pancreatitis in such individuals.
A Review of the Neurological and Neurosurgical Implications of Down Syndrome in Children
Authors: Hwang Steven W. , Jea Andrew
Published: June 2013

Down syndrome is the most commonly encountered chromosomal translation and has been associated with significant congenital abnormalities in various organ systems. Along with classic facial findings, it may involve the gastroenterologic, cardiac, ophthalmologic, endocrine, immunologic, orthopedic, or neurologic systems. With respect to the neurological system, a higher incidence of moyamoya, seizure disorders, strokes, and spinal ligamentous laxity has been described in these children. We have summarized the current available literature with respect to children who have Down syndrome and the varying neurological pathologic entities associated to help health care providers better understand these patients.
Advice for Families Traveling to Developing Countries With Young Children
Authors: Doan Sylvia , Steele Russell W.
Published: June 2013

Young children are most likely to travel to developing countries with their parents to visit relatives. Preparation for such travel must include careful counseling and optimal use of preventive vaccines and chemoprophylaxis. For infants and very young children, data defining safety and efficacy of these agents are often limited. However, accumulated experience suggests that young travelers may be managed similarly to older children and adults.
The Aid for Trade Charade
Authors: Langan Mark , Scott James
Published: June 2013

Aid for Trade (AfT) has gained prominence as an innovative form of donor support in the ‘post’-Washington Consensus. AfT mechanisms have been praised as a means of aligning trade liberalisation deals (whether in the Doha Round or within bilaterals) to poverty reduction objectives. This article, through critical analysis of AfT discourse within the ‘moral economies’ of multilateral World Trade Organization and bilateral European Union–African, Caribbean and Pacific negotiations, points to the strategic purposes of donor language in rationalising asymmetric North–South trade systems. Moreover, it questions the ‘development’ credentials of AfT assistance by examining some of the ensuing private sector activities and the impact on the supposed beneficiaries, and the tying of AfT disbursements to the implementation of inappropriate policies.
Constructing differences in a cross-cultural context: National distance, social differentiation or functional distinction
Authors: Belhoste Nathalie , Monin Philippe
Published: June 2013

This article develops theory about the perspectives through which expatriate managers and their employees socially construct differences in a cross-cultural context. On the basis of qualitative research on three kinds of organizations – multinational corporations, small and medium-sized enterprises and start-up companies – we identify three perspectives on differences in a cross-cultural context: the national distance perspective, the social differentiation perspective and the functional distinction perspective. Each perspective relates to a specific basis for categorization (nationality, status and function), focus of attention (values, attitudes and expertise) and definition of diversity (separation, disparity and variety). We find that international experience and country experience on one side, and the purpose of business (business development, business creation or business turnaround) on the other side, explain why some expatriate managers and their employees adopt one perspective or another, sometimes as default. The passing of time, as reflected in growing country experience, growing work experience and growing company tenure, can be the motor of transition from one perspective to another. Our findings contribute to cross-cultural and diversity studies, to social constructionism, and have consequences for international human resource management research and practices.
Labour markets and wages in Australia in 2012
Authors: Jefferson Therese , Preston Alison
Published: June 2013

During 2012, the labour market continued to show considerable diversity in outcomes for different labour market groups. Employment growth was slower and the number of employees searching for full-time work rose alongside falling participation rates compared with the previous year. Overall, the employment situation for men was not looking as strong as for women, although women continued to exhibit higher levels of labour underutilisation. Earnings indicators suggest increased wages in low-paid sectors, although this was coming off a low base and may be indicative of catch-up for slow growth in recent years. The relative value of the minimum wage is now at its lowest level in six years, suggesting some evidence of growing earnings inequality. Recent debates in the mass media about labour productivity and industrial relations regulation appear to have limited grounding in national accounting and labour market data.
Major tribunal decisions in Australia in 2012
Authors: Catanzariti Joseph , Kane Christopher
Published: June 2013

This article examines a number of decisions of Fair Work Australia, the High Court of Australia and the Federal Court of Australia from 2012 regarding the application of the Fair Work Act 2009. In the decision of Bendigo v Barclay, the High Court considered how the courts should approach a determination as to whether an employer has engaged in adverse action for a prohibited reason. The Endeavour Coal decisions of Fair Work Australia and the Federal Court have addressed the good-faith bargaining provisions of the Fair Work Act 2009. Further, Fair Work Australia has resolved conflicting authority regarding the approval of enterprise agreements containing ‘opt-out’ clauses. In other decisions, Fair Work Australia has considered an appeal from unfair dismissal proceedings regarding an employee who was terminated on the basis of an offensive Facebook page, and the Federal Court has confirmed the existence of an implied term of mutual trust and confidence in an employee's contract.
Temporary labour migration and care work: The Japanese experience
Authors: Ford Michele , Kawashima Kumiko
Published: June 2013

Around the world, advanced industrial societies are facing a demographic time bomb that has enormous implications for the workforce in general, but for workforce planning and industrial relations in the health sector and related industries in particular. Japan, which has traditionally resisted structured forms of labour migration, has responded by establishing labour migration schemes for nurses and other care workers from selected South and Southeast Asian countries. This article examines the responses of different industrial relations actors to the first of these schemes. It begins by describing the opening up of hospitals and residential care facilities to temporary labour migrants from the Philippines and Indonesia, before turning to a discussion of the roles played by trade unions and employers and an evaluation of the outcomes of the programme to date. The article demonstrates the potential pitfalls of trade-driven labour migration schemes and their implications for the sector and the migrant workers concerned.