bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordant Cellular Response to Presurgical Letrozole in Bilateral Synchronous ER+ Breast Cancers with aKRASMutation orFGFR1Gene Amplification
Authors: Balko Justin M. , Mayer Ingrid A. , Sanders Melinda E. , Miller Todd W. , Kuba Maria G. , Meszoely Ingrid M. , Wagle Nikhil , Garraway Levi A. , Arteaga Carlos L.
Published: August 2012

We describe herein a patient presenting with bilateral estrogen-receptor–positive (ER+) breast tumors who was enrolled in a clinical trial exploring molecular aberrations associated with hormone-refractory tumor cell proliferation. Short-term (two week) hormonal therapy with the aromatase inhibitor letrozole substantially reduced proliferation as measured by Ki67 immunohistochemistry in one tumor, whereas the second was essentially unchanged. Extensive molecular and genetic work-up of the two tumors yielded divergent lesions in the two tumors: an activating KRAS mutation in the responsive tumor and an amplification of the fibroblast growth factor receptor-1 (FGFR1) locus in the treatment-refractory tumor. These findings provide an insight to possible mechanisms of resistance to antiestrogen therapy in ER+ breast cancers. First, they illustrate the necessity of clinically approved assays to identify FGFR1 gene amplification, which occur in approximately 5% of breast tumors and have been linked to antiestrogen resistance. It is quite possible that the addition of FGFR inhibitors to ER-targeted therapy will yield a superior antitumor effect and improved patient outcome. Second, they suggest that the role of activating mutations in RAS, although rare in breast cancer, may need to be explored in the context of ER+ breast tumors. Mol Cancer Ther; 11(10); 2301–5. ©2012 AACR.
Turn Off the IDO: Will Clinical Trials Be Successful?
Authors: Novitskiy Sergey V. , Moses Harold L.
Published: August 2012

Summary: Indoleamine 2,3-dioxygenase (IDO) is overexpressed in many human cancers and is believed to play a role in tumor immune evasion, but a requirement for IDO in tumor progression has not been formally shown. The study by Smith and colleagues in this issue of Cancer Discovery provides genetic evidence for the importance of IDO in tumorigenesis, which supports the use of IDO inhibitors in clinical trials in humans. Cancer Discov; 2(8); 673–5. ©2012 AACR.

Commentary on Smith et al., p. 722.
No Evidence for JAK2V617F Mutation in Monoclonal B Cells in 2 Patients with Polycythaemia Vera and Concurrent Monoclonal B Cell Disorder
Authors: Stijnis C. , Kroes W.G.M. , Balkassmi S. , Marijt E.W.A. , van Rossum A.P. , Bakker E. , Vlasveld L.T.
Published: August 2012

Occurrence of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph– MPN) and lymphoproliferative disorders, like B cell chronic lymphocytic leukaemia (B-CLL), in the same patient is rare. JAK2V617F mutation was recently introduced as a powerful diagnostic tool for Ph– MPN. JAK2V617F mutation is not present in B-CLL. In 4 previously reported patients with JAK2V617F-positive Ph– MPN and B-CLL there was no definitive proof of JAK2V617F mutation in B-CLL cells, although this was suggested in 1 patient. We present 2 patients with JAK2V617F-positive polycythaemia vera who subsequently developed a monoclonal B cell disorder. The granulocytes were separated from the mononuclear cells by centrifugation on density gradient. Using an ARIA-SORP sorter, the CD20+/CD5+ B cells were separated from the CD20+/CD5– B cells, T cells, NK cells and monocytes. On each of the fractions JAK2V617F mutation was analysed by allele-specific competitive blocker-PCR. In both patients JAK2V617F mutation was present in granulocytes confirming the clinical diagnosis of polycythaemia vera. We did not detect the JAK2V617F mutation in the CD20+/CD5+ B cells but detected it in CD20+/CD5– B cells, T and NK cells, indicating a lymphoid subdifferentiation of the JAK2V617F MPN clonality. JAK2V617F MPN and monoclonal B cell disorder can coexist but there is no evidence that the proliferative behaviour of these B cells is mediated through the JAK2V617F mutation.
In vitro Assessment of Gentian Violet Anti-Candida Activity
Authors: Gomes-de-Elvas A.R. , Palmeira-de-Oliveira A. , Gaspar C. , Gouveia P. , Palmeira-de-Oliveira R. , Pina-Vaz C. , Rodrigues A.G. , Martinez-de-Oliveira J.
Published: August 2012

Background/Aim: Recurrent vulvovaginal candidosis (RVVC) needs alternative therapeutic approaches. Gentian violet (GeV) has been traditionally used to treat mucocutaneous candidosis. The aim of the present study was to evaluate the in vitro activity of GeV against Candida spp. and contribute to clarify the mechanism of action, supporting its clinical therapeutic use. Methods: Seventeen clinical Candida isolates from RVVC and one C. albicans type collection (ATCC 10231) were studied; the antifungal activity of GeV was evaluated according to the CLSI M27-A3 protocol. To elucidate its mechanism of action, cells were stained with propidium iodide and afterwards analyzed by flow cytometer. Results: GeV showed a fungicidal activity against most Candida spp. C. albicans and C. tropicalis were the most susceptible species. Minimal lethal concentrations were similar to minimal inhibitory concentrations for most tested strains. The fungicidal effect was not related to a primary lesion of the cytoplasmic membrane. Conclusion: In accordance with our findings, GeV is a valuable potent fungicidal drug to be used topically, isolated or in combination with oral antifungal drugs, particularly in RVVC cases.
Systematic Review of Randomized Controlled Trials: Fiber Supplements for Abdominal Pain-Related Functional Gastrointestinal Disorders in Childhood
Authors: Horvath Andrea , Dziechciarz Piotr , Szajewska Hania
Published: August 2012

Background: A lack of safe and reliable treatments for abdominal pain-related functional gastrointestinal disorders (FGIDs) has prompted interest in new therapies. Aim: To systematically evaluate the effect of dietary fibers for treating abdominal pain-related FGIDs in children. Methods: In December 2011, MEDLINE, EMBASE and the Cochrane Library were searched for randomized controlled trials (RCTs) evaluating fiber supplementation in children with FGIDs. Results: Only 3 RCTs were identified, which enrolled a total of 167 children and adolescents (5–17 years old) with recurrent abdominal pain. Only 1 study used the Rome III criteria. Patients were supplemented with different dietary fiber types for 4–6 weeks. The use of dietary fibers did not influence the proportion of responders to treatment, and improvement did not occur in reported clinically relevant outcomes such as no pain or a significant decrease in pain intensity (risk ratio 1.17, 95% confidence interval 0.75–1.81). Conclusion: There is no evidence that supplementation with fiber as a dietary manipulation may be useful for treating children with FGIDs. However, one should not overlook the fact that the main limitation for recommendation of the routine fiber use in clinical practice derives from the weak quality and paucity of available studies.
Successful Treatment of γ-Heavy-Chain Disease with Rituximab and Fludarabine
Authors: Inoue Daichi , Matsushita Akiko , Kiuchi Mineyo , Takiuchi Yoko , Nagano Seiji , Arima Hiroshi , Mori Minako , Tabata Sumie , Yamashiro Akiko , Maruoka Hayato , Oita Tatsuo , Imai Yukihiro , Takahashi Takayuki
Published: August 2012

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ĸ-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgMĸ monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.
Discordant Diagnoses of Acute Myocardial Infarction due to the Different Use of Assays and Cut-Off Points of Cardiac Troponins
Authors: Lyck Hansen Maria , Saaby Lotte , Nybo Mads , Rasmussen Lars Melholt , Thygesen Kristian , Mickley Hans , Svenstrup Poulsen Tina
Published: August 2012

Objectives: Several assays for the measurement of cardiac troponin (cTn) are available, but differences in their analytical performances may affect the diagnosis of acute myocardial infarction (MI). Methods: A survey was conducted at all Danish departments of clinical biochemistry at hospitals receiving patients with suspected acute MI to gather information about the assay and cut-off value used. cTn was measured in blood samples from 574 patients enrolled into the Odense Chest Pain Biobank with 3 different assays: the 4th generation cTnT (cTnT4th), high-sensitivity cTnT (cTnThs; Roche Diagnostics) and cTnI (Abbott Diagnostics). To evaluate concordance, patients were dichotomised according to the 99th percentile value for each assay. Additionally, a cut-off at 50 ng/l for cTnThs was used, as this is the currently employed cut-off point in Denmark. Results: Using a cTnT4th cut-off value of >0.03 µg/l, 130 patients (23%) had potential MI. With the cTnThs assay and cut-off values at 50 versus 14 ng/l, respectively, 136 (24%) versus 301 (52%) patients had potential MI. With the cTnI cut-off point, 205 patients (36%) should be considered as having had an acute MI. Conclusions: The use of different cTn assays and cut-off values may result in a discordant frequency of MI diagnoses. This makes efforts to harmonize cTn assays and cut-off levels mandatory.
Bufalin Induces the Apoptosis of Acute Promyelocytic Leukemia Cells via the Downregulation of Survivin Expression
Authors: Zhu Zhitu , Li Enze , Liu Yangyang , Gao Yu , Sun Hongzhi , Wang Ying , Wang Zhenghua , Liu Xiaomei , Wang Qingjun , Liu Yunpeng
Published: August 2012

Background and Aims: Bufalin is a cardiotonic steroid isolated from the Chinese toad venom preparation Chan’su and has been shown to induce leukemia cell differentiation and apoptosis under certain experimental conditions. However, the detailed mechanism by which bufalin induces the apoptosis of acute promyelocytic leukemia cells is largely unexplored. Methods: The acute promyelocytic leukemia cell line NB4 was treated with bufalin, then the proliferation was evaluated by cell viability assay and apoptosis was detected by flow cytometry analysis. In addition, NB4 cells were treated by MEK inhibitor PD98059 in combination with bufalin, and the expression of survivin and activation of caspase-3 were detected by Western blot analysis. Results: Bufalin inhibited the proliferation and induced the apoptosis of NB4 cells in a dose- and time-dependent manner. Moreover, bufalin synergized with PD98059 to inhibit the proliferation and induce the apoptosis of NB4 cells, which was associated with the downregulation of survivin expression and the upregulation of caspase-3 activation. Conclusions: Bufalin is a potential regimen to be used in combination with conventional chemotherapeutic drugs to improve acute promyelocytic leukemia therapy.
von Willebrand Factor: More Than a Regulator of Hemostasis and Thrombosis
Authors: Luo Gui-Ping , Ni Bing , Yang Xia , Wu Yu-Zhang
Published: August 2012

von Willebrand factor (vWF) was first identified as an adhesive glycoprotein involved in hemostasis by Zimmermann in 1971. Since then, vWF has been shown to play a vital role in platelet adhesion, platelet binding to collagen and factor VIII protection. Recent studies have implicated vWF as a regulator of angiogenesis, smooth muscle cell proliferation, tumor cell metastasis and crosstalk in the immune system. In this review, we will discuss the aspects of vWF structure that facilitate its biological effects and speculate on its newly discovered and hypothesized roles in the pathogenesis of several diseases.
Bone Marrow Mesenchymal Stem Cells in Myelodysplastic Syndromes: Cytogenetic Characterization
Authors: Song Lu-Xi , Guo Juan , He Qi , Yang Lian-Ping , Gu Shu-Cheng , Zhang Xi , Wu Ling-Yun , Li Xiao , Chang Chun-Kang
Published: August 2012

Aim: This study compared genetic aberrations in hematopoietic cells (HCs) and mesenchymal stem cells of myelodysplastic syndrome (MDS-MSCs) patients. Methods: We obtained chromosomes with aberrations from 22 patients with MDS and chromosomes from 7 healthy individuals. Chromosomal aberrations in both HCs and MSCs were identified using G-banding. We then performed DNA content analysis of the HCs and MSCs. Results: Cytogenetic aberrations were detected in HCs from 13 of the 22 MDS patients (59%). Chromosomal aberrations in MSCs were detected in 15 of the 22 MDS patients (68%). No chromosomal abnormalities were identified in MSCs of the 7 healthy volunteers. We demonstrate herein that MSCs have distinct genetic abnormalities compared to HCs from the same individual. We observed a random loss of chromosomal material in significant proportions of MSCs. A high proportion of random loss may be a marker of chromosomal instability of MDS-MSCs. However, two case results showed that HCs and MSCs have different altered structural changes. Conclusion: Our results suggest enhanced genetic susceptibility of these cells in MDS patients. Our data indicates that the genetic alterations in MSCs may constitute a particular biological mechanism of MDS pathogenesis.
Patients with Early-Stage Myelodysplastic Syndromes Show Increased Frequency of CD4+CD25high+CD127low Regulatory T Cells
Authors: Fozza Claudio , Longu Francesco , Contini Salvatore , Galleu Antonio , Virdis Patrizia , Bonfigli Silvana , Murineddu Marco , Gabbas Attilio , Longinotti Maurizio
Published: August 2012

Regulatory T cells (Treg) have often been ascribed a role in the pathophysiology of several neoplastic diseases considering their potential ability to suppress anti-tumor immunity. This is particularly the case in myelodysplastic syndromes (MDS), which are clonal hematologic disorders characterized by marked immune dysregulation. We analyzed Treg frequencies in a cohort of 36 patients with early-stage MDS using a flow-cytometric approach based on the concomitant expression of CD25 and CD127. MDS patients showed a higher frequency of CD4+CD25high+CD127low Treg than healthy controls (1.51 vs. 1.14%), with no specific effect of patient- and disease-related factors. Our data point to impaired anti-tumor immunity in patients with MDS, even in the early stage, which has already been noted in other clonal disorders.
A Linear Karyotypic Association between PB-I, PB-II and Blastomere Using Sequentially Performed Comparative Genome Hybridization with No Association Established between Karyotype, Morphologic, Biochemical (sHLA-G Expression) Characteristics, Blastocyst Formation and Subsequent Pregnancy Outcome
Authors: Kotze Dirk , Keskintepe Levent , Sher Geoffrey , Kruger Thinus , Lombard Carl
Published: August 2012

Background: The importance of oocyte/embryo ploidy to achieve implantation and a subsequent pregnancy. Aim: To correlate first and second polar bodies and day-3 blastomere ploidy, embryo morphology and biochemical (sHLA-G) characteristics with blastocyst development and in vitro pregnancy outcome. Materials and Methods: All oocytes/zygotes and embryos were individually cultured to the blastocyst stage. PB-I, PB-II and blastomeres underwent complete karyotyping and sHLA-G expression was measured on day 2. Results: 57 mature (MII) donor oocytes were obtained, 33/57 (57.9%) were aneuploid, 21/57 (36.8%) were euploid, and 3/57 (5%) were ‘inconclusive’. No correlation was found between comparative genomic hybridization (CGH) status of PB-I, PB-II and the graduated embryo score. Furthermore, no correlation was established between PB-I CGH results and blastocyst morphology grade. There was a significant correlation between PB-I CGH and blastomere CGH results. Euploid and aneuploid PB-I developed into 58 and 67% blastocysts, respectively. ĸ statistics (>0.7) revealed a positive correlation between the ploidy of PB-I, PB-II and the blastomeres. Conclusion: Following ICSI and sequential genetic karyotyping of the oocyte/zygote and subsequent blastomeres, the majority of oocytes fertilized and subsequent zygotes developed into blastocysts, despite their ploidy status. We therefore conclude that blastocyst development is not associated with ploidy.
Morphometric Analysis of Telencephalic Structure in a Variety of Neognath and Paleognath Bird Species Reveals Regional Differences Associated with Specific Behavioral Traits
Authors: Corfield Jeremy R. , Wild J. Martin , Parsons Stuart , Kubke M. Fabiana
Published: August 2012

Birds exhibit a huge array of behavior, ecology and physiology, and occupy nearly every environment on earth, ranging from the desert outback of Australia to the tropical rain forests of Panama. Some birds have adopted a fully nocturnal lifestyle, such as the barn owl and kiwi, while others, such as the albatross, spend nearly their entire life flying over the ocean. Each species has evolved unique adaptations over millions of years to function in their respective niche. In order to increase processing power or network efficiency, many of these adaptations require enlargements and/or specializations of the brain as a whole or of specific brain regions. In this study, we examine the relative size and morphology of 9 telencephalic regions in a number of Paleognath and Neognath birds and relate the findings to differences in behavior and sensory ecology. We pay particular attention to those species that have undergone a relative enlargement of the telencephalon to determine whether this relative increase in telencephalic size is homogeneous across different brain regions or whether particular regions have become differentially enlarged. The analysis indicates that changes in the relative size of telencephalic regions are not homogeneous, with every species showing hypertrophy or hypotrophy of at least one of them. The three-dimensional structure of these regions in different species was also variable, in particular that of the mesopallium in kiwi. The findings from this study provide further evidence that the changes in relative brain size in birds reflect a process of mosaic evolution.
Wide Clinical Variability in Cat Eye Syndrome Patients: Four Non-Related Patients and Three Patients from the Same Family
Authors: Belangero S.I. , Pacanaro A.N.X. , Bellucco F.T. , Christofolini D.M. , Kulikowski L.D. , Guilherme R.S. , Bortolai A. , Dutra A.R.N. , Piazzon F.B. , Cernach M.C. , Melaragno M.I.
Published: August 2012

A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common cytogenetic finding. This sSMC typically results in tetrasomy for a chromosomal region that spans the chromosome 22p arm and the proximal 2 Mb of 22q11.21. Using classical cytogenetics, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and array techniques, 7 patients with sSMCs derived from chromosome 22 were studied: 4 non-related and 3 from the same family (mother, daughter, and son). The sSMCs in all patients were dicentric and bisatellited chromosomes with breakpoints in the chromosome 22 low-copy repeat A region, resulting in cat eye syndrome (CES) due to chromosome 22 partial tetrasomy 22pter→q11.2 including the cat eye chromosome region. Although all subjects presented the same chromosomal abnormality, they showed a wide range of phenotypic differences, even in the 3 patients from the same family. There are no previous reports of CES occurring within 3 patients in the same family. Thus, the clinical and follow-up data presented here contribute to a better delineation of the phenotypes and outcomes of CES patients and will be useful for genetic counseling.
Visualization of Vascular Inflammation in the Atherosclerotic Mouse by Ultrasmall Superparamagnetic Iron Oxide Vascular Cell Adhesion Molecule-1–Specific Nanoparticles
Authors: Michalska Marta , Machtoub Lina , Manthey Helga D. , Bauer Elisabeth , Herold Volker , Krohne Georg , Lykowsky Gunthard , Hildenbrand Markus , Kampf Thomas , Jakob Peter , Zernecke Alma , Bauer Wolfgang R.
Published: August 2012

Objective—

Noninvasive imaging of atherosclerosis remains challenging in clinical applications. Here, we applied noninvasive molecular imaging to detect vascular cell adhesion molecule-1 in early and advanced atherosclerotic lesions of apolipoprotein E–deficient mice.

Methods and Results—

Ultrasmall superparamagnetic iron oxide particles functionalized with (P03011) or without (P3007) vascular cell adhesion molecule-1−binding peptide were visualized by ultra high-field (17.6 T) magnetic resonance. Injection of P03011 resulted in a marked signal loss in the aortic root of apolipoprotein E–deficient mice fed a Western diet for 8 and 26 weeks in vivo and ex vivo, compared with preinjection measurements, P3007-injected mice, and P03011- or P3007-injected age-matched C57BL/6 controls. Histological analyses revealed iron accumulations in the intima, in colocalization with vascular cell adhesion molecule-1−expressing macrophages and endothelial cells. Coherent anti-Stokes Raman scattering microscopy demonstrated iron signals in the intima and media of the aortic root in the P03011-injected but not untreated apolipoprotein E–deficient mice, localized to macrophages, luminal endothelial-like cells, and medial regions containing smooth muscle cells. Electron microscopy confirmed iron particles enclosed in endothelial cells and in the vicinity of smooth muscle cells.

Conclusion—

Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying P03011 as a contrast agent for imaging of atherosclerosis.
Adverse Alterations in Mitochondrial Function Contribute to Type 2 Diabetes Mellitus–Related Endothelial Dysfunction in Humans
Authors: Kizhakekuttu Tinoy J. , Wang Jingli , Dharmashankar Kodlipet , Ying Rong , Gutterman David D. , Vita Joseph A. , Widlansky Michael E.
Published: August 2012

Objective—

Mitochondrial dysfunction plays a key pathophysiological role in type 2 diabetes mellitus (T2DM). Data delineating relationships between mitochondrial and endothelial dysfunction in humans with T2DM are lacking.

Methods and Results—

In 122 human subjects (60 with T2DM, 62 without T2DM), we measured endothelial function by brachial artery ultrasound (flow mediated dilation) and digital pulse amplitude tonometery. Endothelial function in arterioles isolated from gluteal subcutaneous adipose was measured by videomicroscopy. In arterioles and mononuclear cells, we measured inner mitochondrial membrane potential (Δψ
m
), mitochondrial mass, and mitochondrial superoxide production using fluorophores. Endothelial function was impaired in T2DM subjects versus control subjects. Δψ
m
magnitude was larger and mitochondrial mass was lower in arterioles and mononuclear cells in T2DM. Mononuclear mitochondrial mass correlated with flow-mediated dilation and pulse amplitude tonometery (
ρ
=0.38 and 0.33,
P
=0.001 and 0.02, respectively), and mononuclear mitochondrial superoxide production inversely correlated with flow-mediated dilation (
ρ
=−0.58,
P
=0.03). Low doses of 2 different mitochondrial uncoupling agents (carbonyl cyanide m-chlorophenyl hydrazone and 2,4-dinitrophenol) that reduce Δψ
m
magnitude and a mitochondrial-targeted antioxidant (MitoTEMPOL) improved endothelial function and reduced mitochondrial superoxide levels in T2DM arterioles.

Conclusion—

Mitochondrial dysfunction may play a central role in the impairment of endothelial dysfunction in T2DM.
Role of Thromboxane Receptor in C-Reactive Protein–Induced Thrombosis
Authors: Grad Etty , Pachino Rachel M. , FitzGerald Garret A. , Danenberg Haim D.
Published: August 2012

Objective—

Thromboxane A
2
and prostacyclin are thromboregulatory prostaglandins. The inflammatory C-reactive protein (CRP) promotes thrombosis after vascular injury, presumably via potentiation of thromboxane activity. Using a genetic approach, we investigated the role of thromboxane receptor (TP) pathway in CRP-induced thrombosis.

Methods and Results—

Four genetically engineered mice strains were used:
C57BL
/
6
wild-type, human CRP transgenic (
CRPtg
), thromboxane receptor–deficient (
Tp
−/−
), and CRPtgTp
−/−
mice. CRP and TP expression were correlated, and suppression of CRP expression using small interfering RNA/CRP led to reduction in TP expression. Platelet–endothelial adherence was increased in CRPtg and suppressed in CRPtgTP
−/−
and CRPtg cells that were suppressed with TP small interfering RNA. TP deficiency in both platelets and endothelial cells was synergistic in affecting platelet–endothelial interactions. Time until arterial occlusion, measured after photochemical injury, was significantly shorter in CRPtg and prolonged in CRPtgTp
−/−
compared with controls (n=10–15, 35±3.4, 136±13.8, and 67±8.9 minutes, respectively;
P
<0.05).

Conclusion—

TP pathway is of major importance in CRP-induced thrombosis. The expression of TP is increased in CRPtg endothelial cells, and its blockade significantly suppresses the prothrombotic effect of CRP.
Aneurysms Increase the Risk of Rebleeding After Stereotactic Radiosurgery for Hemorrhagic Arteriovenous Malformations
Authors: Kano Hideyuki , Kondziolka Douglas , Flickinger John C. , Yang Huai-che , Park Kyung-Jae , Flannery Thomas J. , Liu Xiaomin , Niranjan Ajay , Lunsford L. Dade
Published: August 2012

Background and Purpose—

The purpose of this study was to define the risk of rebleeding after stereotactic radiosurgery (SRS) for hemorrhagic arteriovenous malformations with or without associated intracranial aneurysms.

Methods—

Between 1987 and 2006, we performed Gamma Knife SRS on 996 patients with brain arteriovenous malformations; 407 patients had sustained an arteriovenous malformation hemorrhage. Sixty-four patients (16%) underwent prior embolization and 84 (21%) underwent prior surgical resection. The median target volume was 2.3 mL (range, 0.1–20.7 mL). The median margin dose was 20 Gy (range, 13.5–27 Gy).

Results—

The overall rate of total obliteration defined by angiography or MRI was 56%, 77%, 80%, and 82% at 3, 4, 5, and 10 years, respectively. Before obliteration, 33 patients (8%) sustained an additional hemorrhage after SRS. The overall annual hemorrhage rate until obliteration after SRS was 1.3%. The presence of a patent aneurysm was significantly associated with an increased rehemorrhage risk after SRS (annual hemorrhage rate, 6.4%) compared with patients with a clipped or embolized aneurysm (annual hemorrhage rate, 0.8%;
P
=0.033).

Conclusions—

When an aneurysm is identified in patients with arteriovenous malformations selected for SRS, additional endovascular or surgical strategies should be considered to reduce the risk of bleeding during the latency interval.
Memantine Improves Safety of Thrombolysis for Stroke
Authors: Montagne Axel , Hébert Marie , Jullienne Amandine , Lesept Flavie , Le Béhot Audrey , Louessard Morgane , Gauberti Maxime , Orset Cyrille , Ali Carine , Agin Véronique , Maubert Eric , Vivien Denis
Published: August 2012

Background and Purpose—

Despite side effects including N-methyl-
d
-aspartate-mediated neurotoxicity, recombinant tissue-type plasminogen activator (rtPA) remains the only approved acute treatment for ischemic stroke. Memantine, used for treatment of Alzheimer disease, is an antagonist for N-methyl-
d
-aspartate receptors. We investigated whether memantine could be used as a neuroprotective adjunct therapy for rtPA-induced thrombolysis after stroke.

Methods—

In vitro N-methyl-
d
-aspartate exposure, oxygen and glucose deprivation, and N-methyl-
d
-aspartate-mediated calcium videomicroscopy experiments were performed on murine cortical neurons in the presence of rtPA and memantine. The therapeutic safety of rtPA and memantine coadministration was evaluated in mouse models of thrombotic stroke and intracerebral hemorrhage. Ischemic and hemorrhagic volumes were assessed by MRI and neurological evaluation was performed by the string test and automated gait analysis.

Results—

Our in vitro observations showed that memantine was able to prevent the proneurotoxic effects of rtPA in cultured cortical neurons. Although memantine did not alter the fibrinolytic activity of rtPA, our in vivo observations revealed that it blunted the noxious effects of delayed thrombolysis on lesion volumes and neurological deficits after ischemic stroke. In addition, memantine rescued rtPA-induced decrease in survival rate after intracerebral hemorrhage.

Conclusions—

Memantine could be used as an adjunct therapy to improve the safety of thrombolysis.
Relationships of Fire and Precipitation Regimes in Temperate Forests of the Eastern United States
Authors: Lafon Charles W. , Quiring Steven M.
Published: August 2012

Fire affects virtually all terrestrial ecosystems but occurs more commonly in some than in others. This paper investigates how climate, specifically the moisture regime, influences the flammability of different landscapes in the eastern United States. A previous study of spatial differences in fire regimes across the central Appalachian Mountains suggested that intra-annual precipitation variability influences fire occurrence more strongly than does total annual precipitation. The results presented here support that conclusion. The relationship of fire occurrence to moisture regime is also considered for the entire eastern United States. To do so, mean annual wildfire density and mean annual area burned were calculated for 34 national forests and parks representing the major vegetation and climatic conditions throughout the eastern forests. The relationship between fire activity and two climate variables was analyzed: mean annual moisture balance [precipitation P − potential evapotranspiration (PET)] and daily precipitation variability (coefficient of variability for daily precipitation). Fire activity is related to both climate variables but displays a stronger relationship with precipitation variability. The southeastern United States is particularly noteworthy for its high wildfire activity, which is associated with a warm, humid climate and a variable precipitation regime, which promote heavy fuel production and rapid drying of fuels.
Simulating Hydrological Drought Properties at Different Spatial Units in the United States Based on Wavelet–Bayesian Regression Approach
Authors: Mishra Ashok K. , Singh Vijay P.
Published: August 2012

Because of their stochastic nature, droughts vary in space and time, and therefore quantifying droughts at different time units is important for water resources planning. The authors investigated the relationship between meteorological variables and hydrological drought properties using the Palmer hydrological drought index (PHDI). Twenty different spatial units were chosen from the unit of a climatic division to a regional unit across the United States. The relationship between meteorological variables and PHDI was investigated using a wavelet–Bayesian regression model, which enhances the modeling strength of a simple Bayesian regression model. Further, the wavelet–Bayesian regression model was tested for the predictability of global climate models (GCMs) to simulate PHDI, which will also help understand their role for downscaling purposes.
A Pseudoproxy Evaluation of Bayesian Hierarchical Modeling and Canonical Correlation Analysis for Climate Field Reconstructions over Europe*
Authors: Werner Johannes P. , Luterbacher Juerg , Smerdon Jason E.
Published: August 2012

A pseudoproxy comparison is presented for two statistical methods used to derive annual climate field reconstructions (CFRs) for Europe. The employed methods use the canonical correlation analysis (CCA) procedure presented by Smerdon et al. and the Bayesian hierarchical model (BHM) method adopted from Tingley and Huybers. Pseudoproxy experiments (PPEs) are constructed from modeled temperature data sampled from the 1250-yr paleo-run of the NCAR Community Climate System Model (CCSM) version 1.4 model by Ammann et al. Pseudoproxies approximate the distribution of the multiproxy network used by Mann et al. over the European region of interest. Gaussian white noise is added to the temperature data to mimic the combined signal and noise properties of real-world proxies. Results indicate that, while both methods perform well in areas with good proxy coverage, the BHM method outperforms the CCA method across the entire field and additionally returns objective error estimates.
Atmospheric Circulation Response to an Instantaneous Doubling of Carbon Dioxide. Part II: Atmospheric Transient Adjustment and Its Dynamics
Authors: Wu Yutian , Seager Richard , Shaw Tiffany A. , Ting Mingfang , Naik Naomi
Published: August 2012

The dynamical mechanisms underlying the transient circulation adjustment in the extratropical atmosphere after the instantaneous doubling of carbon dioxide are investigated using the National Center for Atmospheric Research Community Atmosphere Model version 3 coupled to a Slab Ocean Model. It is shown that the transient process during the first few months of integration is important in setting up the extratropical circulation response in equilibrium such as the poleward shift of the tropospheric jet streams. Three phases are found during the transient thermal/dynamical adjustment in the Northern Hemisphere: 1) a radiatively driven easterly anomaly in the subpolar stratosphere, 2) an acceleration of the westerly anomaly in the subpolar stratosphere as a result of anomalous planetary-scale eddy momentum flux convergence, and 3) a “downward migration” of the westerly anomaly from the lower stratosphere to the troposphere, followed by the tropospheric jet shift. Several proposed mechanisms for inducing the poleward shift of the tropospheric jet streams are examined. No significant increase in eddy phase speed is found. The rise in tropopause height appears to lead the tropospheric jet shift but no close relation is observed. The length scale of transient eddies does increase but does not lead the tropospheric jet shift. Finally, the tropospheric jet shift can be captured by changes in the index of refraction and the resulting anomalous eddy propagation in the troposphere.
Inconsistencies between Long-Term Trends in Storminess Derived from the 20CR Reanalysis and Observations
Authors: Krueger Oliver , Schenk Frederik , Feser Frauke , Weisse Ralf
Published: August 2012

Global atmospheric reanalyses have become a common tool for both validation of climate models and diagnostic studies, such as assessing climate variability and long-term trends. Presently, the Twentieth Century Reanalysis (20CR), which assimilates only surface pressure reports, sea ice, and sea surface temperature distributions, represents the longest global reanalysis dataset available covering the period from 1871 to the present. Currently the 20CR dataset is extensively used for the assessment of climate variability and trends. Here, the authors compare the variability and long-term trends in northeast Atlantic storminess derived from 20CR and from observations. A well-established storm index derived from pressure observations over a relatively densely monitored marine area is used. It is found that both variability and long-term trends derived from 20CR and from observations are inconsistent. In particular, both time series show opposing trends during the first half of the twentieth century: both storm indices share a similar behavior only for the more recent periods. While the variability and long-term trend derived from the observations are supported by a number of independent data and analyses, the behavior shown by 20CR is quite different, indicating substantial inhomogeneities in the reanalysis, most likely caused by the increasing number of observations assimilated into 20CR over time. The latter makes 20CR likely unsuitable for the identification of trends in storminess in the earlier part of the record, at least over the northeast Atlantic. The results imply and reconfirm previous findings that care is needed in general when global reanalyses are used to assess long-term changes.
Repeatability of the Seasonal Variations of Ozone near the Mesopause from Observations of the 11.072-GHz Line
Authors: Rogers A. E. E. , Erickson P. , Fish V. L. , Kittredge J. , Danford S. , Marr J. M. , Arndt M. B. , Sarabia J. , Costa D. , May S. K.
Published: August 2012

Ground-based observations of the 11.072-GHz line of ozone were made from January 2008 through the middle of September 2011 to estimate the maximum in the nighttime ozone in the upper mesosphere at an altitude of about 95 km for a region centered at 38°N, 290°E. The measurements show seasonal variation with a high degree of repeatability with peaks in ozone concentration about a month following each equinox. A significant increase in ozone concentration above the yearly trend occurred in 2010 from mid-November until the end of December, which the authors attribute to delay in the start of the meridional circulation for the austral summer of 2010.
Testing Competing Precipitation Forecasts Accurately and Efficiently: The Spatial Prediction Comparison Test
Authors: Gilleland Eric
Published: August 2012

Which model is best? Many challenges exist when testing competing forecast models, especially for those with high spatial resolution. Spatial correlation, double penalties, and small-scale errors are just a few such challenges. Many new methods have been developed in recent decades to tackle these issues. The spatial prediction comparison test (SPCT), which was developed for general spatial fields and applied to wind speed, is applied here to precipitation fields; which pose many unique challenges in that they are not normally distributed, are marked by numerous zero-valued grid points, and verification results are particularly sensitive to small-scale errors and double penalties. The SPCT yields a statistical test that solves one important issue for verifying forecasts spatially by accounting for spatial correlation. Important for precipitation forecasts is that the test requires no distributional assumptions, is easy to perform, and can be applied efficiently to either gridded or nongridded spatial fields. The test compares loss functions between two competing forecasts, where any such function can be used, but most still suffer from the limitations of traditional gridpoint-by-gridpoint assessment techniques. Therefore, two new loss functions to the SPCT are introduced here that address these concerns. The first is based on distance maps and the second on image warping. Results are consistent with other spatial assessment methods, but provide a relatively straightforward mechanism for comparing forecasts with a statistically powerful test. The SPCT combined with these loss functions provides a new mechanism for appropriately testing which of two competing precipitation models is best, and whether the result is statistically significant or not.
Association of Adiponectin Gene Polymorphism (+T45G) With Acute Coronary Syndrome and Circulating Adiponectin Levels
Authors: Rizk Nasser M. , El-Menyar Ayman , Marei Isra , Sameer Maha , Musad Tasneem , Younis Dima , Farag Fathi , Basem Nora , Al-Ali Khalid , Suwaidi Jassim Al
Published: August 2012

We investigated the association of adiponectin gene polymorphisms (+T45G and +G276T) and adiponectin levels with acute coronary syndrome (ACS) among Arabs in Qatar. A case–control study was performed in 142 Arab patients with ACS and 122 controls. Genotypes were determined using TaqMan real-time polymerase chain reaction assay. The TT, TG, and GG genotype frequencies of the T45G variant were significantly different among cases and controls ( P = .023) but not significant for G276T genotypic frequencies. It was found that only the +45G allele was significantly associated with 3-fold increased risk of ACS (odds ratio = 2.77; 1.03-6.96; P = .043) among patients, using the genetic recessive model. Carriers of GG alleles had significantly lower adiponectin levels compared to TT/TG carriers of T45G in patients with ACS. The present study suggests that only T45G single-nucleotide polymorphism in the adiponectin gene is associated with higher odds for ACS events and has an effect on serum adiponectin levels among Arab populations.
Investigating the Long-Term Impacts of Climate Change Communications on Individuals’ Attitudes and Behavior
Authors: Howell Rachel A.
Published: August 2012

To assess the effectiveness of climate change communications, it is important to examine their long-term impacts on individuals’ attitudes and behavior. This article offers an example study and a discussion of the challenges of conducting long-term investigations of behavioral change related to climate change communications (a vital and underresearched area). The research reported is a longitudinal panel study of the impacts on UK viewers of the climate change movie The Age of Stupid. The heightened levels of concern, motivation to act, and sense of agency about action that were initially generated by the movie did not measurably persist over the long term. The results also show that behavioral intentions do not necessarily translate into action. Data analysis raised issues concerning the reliability of participants’ causal attributions of their behavior. This and other methodological challenges are discussed, and some ways of avoiding or lessening problems are suggested.
A Test of the Biographical Availability Argument for Gender Differences in Environmental Behaviors
Authors: Xiao Chenyang , McCright Aaron M.
Published: August 2012

Compared with men, women often express stronger proenvironmental attitudes and values and more frequently engage in private environmental behaviors (e.g., recycling), but not in public environmental behaviors (e.g., joining a protest about an environmental issue). This study uses the 2010 General Social Survey data to test whether this pattern is driven by the differing biographical availability of men and women. Do women’s time constraining commitments, such as having a paid job, living in multi-adult households, or parenting, relate to fewer public environmental behaviors but not fewer private behaviors? Results show that living with other adults while parenting increases the odds that a woman rather than a man performs no public behavior, but having a paid job does not. Living with other adults and not having a paid job also increase women’s participation in private behaviors. This study offers partial support for the biographical availability thesis, while also discovering a link between biographical availability and private environmental behaviors.
Maximal Acceptable Torques of Six Highly Repetitive Hand-Wrist Motions for Male Industrial Workers
Authors: Ciriello Vincent M. , Maikala Rammohan V. , O’Brien Niall V.
Published: August 2012

Objective:

The purpose of the study was to quantify maximum acceptable torques (MATs) in 16 healthy male industrial workers while performing six motions: screw driving clockwise with a 40 mm handle and a 39 mm yoke handle, flexion and extension with a pinch grip, ulnar deviation with a power grip (similar to knife cutting), and a handgrip task (similar to a pliers task).

Background:

Psychophysical studies on repetitive motions of the wrist and hand were previously reported on women; however, it is not clear how men will psychophysically respond to similar motions.

Method:

A psychophysical methodology was used in which the participant adjusted the resistance on the handle. Repetition rates for these tasks were 15 and 25 per minute. Participants performed the tasks for 7 hours per day, 5 days per week, and for 12 days. Symptoms were recorded by the subjects at the end of each hour.

Results:

The mean MATs ranged from 1.15 Nm to 1.88 Nm for screw driving, 2.26 Nm to 3.71 Nm for pinch flexion and extension, 3.88 Nm to 4.07 Nm for ulnar deviation, and 11.47 Nm to 13.98 Nm for the handgrip task. The higher the repetition rate, the lower the MAT. Depending on the type of task and repetition rate, these values represented 15% to 35% (median of 23%) of their maximum isometric torque.

Application:

Based on aforementioned findings, a table of MATs and derived acceptable forces for six tasks at different percentage capabilities of the male industrial populations is formulated.
Changes in Pronoun Use in American Books and the Rise of Individualism, 1960-2008
Authors: Twenge Jean M. , Campbell W. Keith , Gentile Brittany
Published: August 2012

Change over time in culture can appear among individuals and in cultural products such as song lyrics, television, and books. This analysis examines changes in pronoun use in the Google Books ngram database of 766,513 American books published 1960-2008. We hypothesize that pronoun use will reflect increasing individualism and decreasing collectivism in American culture. Consistent with this hypothesis, the use of first person plural pronouns (e.g., we, us) decreased 10% first person singular pronouns (I, me) increased 42%, and second person pronouns (you, your) quadrupled. These results complement previous research finding increases in individualistic traits among Americans.
Effects of Red Light-emitting Diode Irradiation on Dental Pulp Cells
Authors: Holder M.J. , Milward M.R. , Palin W.M. , Hadis M.A. , Cooper P.R.
Published: August 2012

Light irradiation activates a range of cellular processes in a variety of cell types, including stem cells, and can promote tissue repair. This study investigated the effects of light-emitting diode (LED) exposure on dental pulp cells (DPCs). Dose response analysis at 20-second intervals up to 120 seconds demonstrated that a LED array emitting 653-nm red light stimulated significantly increased cell growth at 3 and 7 days post-irradiation with 40 (149 mJ/cm2) and 60 (224 mJ/cm2) seconds of radiant exposure. Double-dosing cells at days 1 and 4 of a 7-day culture period with 60-second (224 mJ/cm2) LED exposure significantly increased cell growth compared with a single dosing regime. BrdU analysis demonstrated significantly increased proliferation rates associated with significantly increased ATP, nitric oxide (NO), and mitochondrial metabolic activity. LED-stimulated NO levels were not reduced by inhibition of NO-synthase activity. Light exposure also rescued the inhibition of mitochondrial dysfunction and increased levels of in vitro mineralization compared with control. Media exchange experiments indicated that autocrine signaling was not likely responsible for red-light-induced DPC activity. In conclusion, data analysis indicated that 653-nm LED irradiation promoted DPC responses relevant to tissue repair, and this is likely mediated by increased mitochondrial activity.