bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Electroacupuncture on Benign Prostate Hyperplasia Patients with Lower Urinary Tract Symptoms: A Single‐Blinded, Randomized Controlled Trial
Authors: Yu Jung-Sheng , Shen Kun-Hung , Chen Wen-Chi , Her Jiann-Shyan , Hsieh Ching-Liang
Published: April 2011

We tested the effect of electroacupuncture (EA) on lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH) patients. A total of 42 BPH patients with LUTS were randomly assigned to either the EA group (EG), received 2 Hz EA for 20 min twice/week for a total of twelve treatments, or a sham EA group (CG), received sham EA. The increase of voiding volume, average flow rate, and maximal flow rate in the EG were 32.2 ± 104.4 mL, 1.2 ± 1.6 mL/sec, and 2.3 ± 3.7 mL/sec, respectively, from baseline value (before EA) using the measurement of an uroflowmetry. These increases were greater than −37.9 ± 120.4, −0.22 ± 2.7, and −0.3 ± 4.3, respectively, in the CG (P = .038.026, and .030, resp.). The changes of prostate special antigen and international prostatic symptom score were not significantly different between two groups (P = .573.175, resp.), suggesting the clinical improvement of 2 Hz EA was quite limited to the LUTS of patients with BPH.
Mechanisms of Neuroprotection by Protein Disulphide Isomerase in Amyotrophic Lateral Sclerosis
Authors: Walker Adam K. , Atkin Julie D.
Published: April 2011

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterised by the progressive loss of motor neurons, leading to paralysis and death within several years of onset. Although protein misfolding is a key feature of ALS, the upstream triggers of disease remain elusive. Recently, endoplasmic reticulum (ER) stress was identified as an early and central feature in ALS disease models as well as in human patient tissues, indicating that ER stress could be an important process in disease pathogenesis. One important chaperone induced by ER stress is protein disulphide isomerase (PDI), which is both upregulated and posttranslationally inhibited by S-nitrosylation in ALS. In this paper, we present evidence from studies of genetics, model organisms, and patient tissues which indicate an active role for PDI and ER stress in ALS disease processes.
Year 7 Pupils' Views of the Future
Authors: Roberts Ken , Atherton Graeme , Remedios Richard
Published: April 2011

This paper reports
findings from a study among 610 Year 7
(typically age 12) pupils at 27 nonselective
secondary schools in three English
regions: Cornwall and Devon, London, and
Greater Manchester. Data was gathered in
workshops, each with 15–25 pupils, who
completed questionnaires and performed
individual tasks, all related to their
vocational and educational aims, their ideas on
what counted as success, and the main influences
on their forward thinking, then discussed their
answers and results. The discussions were
tape recorded. Most pupils expressed robust
occupational aims, and most said that they
wanted to go to university. Family class did not
predict levels of educational or occupational
aims, but was related to the importance attached
to “the job that I want to do” in
the pupils' forward thinking. SAT scores did
predict levels of occupational aspiration, ideas
on what counted as success, and by whom and what
the pupils were most influenced. These findings
are interpreted to challenge the view, on which
a raft of current policies are based, that
social class disparities in educational and
labour market outcomes are due to the
intergenerational transmission of low
aspirations in lower-class families and
neighbourhoods. The paper concludes with an
alternative model of status transmission
processes in which attainments during secondary
education are posited as the key intervening
variable.
Stability and Robust Stability of 2D Discrete Stochastic Systems
Authors: Cui Jia-Rui , Hu Guang-Da , Zhu Qiao
Published: April 2011

New stability and robust stability results are given based on weaker conservative assumptions. First, new boundary
condition is designed. It is less conservative and has broader application range than that has been given. Then,
we derive the results which have the same form, but under a weaker conservative assumption. Meanwhile, the process of the proofs has been simplified. Finally, an example is given to illustrate our results. Our results can be extended to the fields of stabilization, filtering and state estimation, and so forth.
Extended Stokes′ First Problem of an Oldroyd‐B Fluid for Relatively Moving Half‐Planes
Authors: Liu Chi-Min
Published: April 2011

An Oldroyd‐B fluid suddenly disturbed by relatively moving half‐planes is theoretically studied in this paper. This new problem, extended from the traditional Stokes′ problem, recently attracts a great deal of attention due to its potential applications in engineering. Using integral transformations and dividing the original system into two subsystems, the exact solution is derived and shown in a series form. In addition to the general understanding of velocity developments, the effects of the relaxation time and the retardation time on the velocity profiles are examined in a series of figures. It is found that above two rheological parameters influence the induced flow in an opposite way. Other interesting characteristics are also elucidated from present results.
The Nonlinear Instability Modes of Dished Shallow Shells under Circular Line Loads
Authors: Chang-Jiang Liu , Zhou-Lian Zheng , Cong-Bing Huang , Xiao-Ting He , Jun-Yi Sun , Shan-Lin Chen
Published: April 2011

This paper investigated the nonlinear stability problem of dished shallow shells under circular line loads. We derived the dimensionless governing differential equations of dished shallow shell under circular line loads according to the nonlinear theory of plates and shells and solved the governing differential equations by combing the free‐parameter perturbation method (FPPM) with spline function method (SFM) to analyze the nonlinear instability modes of dished shallow shell under circular line loads. By analyzing the nonlinear instability modes and combining with concrete computational examples, we obtained the variation rules of the maximum deflection area of initial instability with different geometric parameters and loading action positions and discussed the relationship between the initial instability area and the maximum deflection area of initial instability. The results obtained from this paper provide some theoretical basis for engineering design and instability prediction and control of shallow‐shell structures.
Safety and Tolerability of Antiretrovirals during Pregnancy
Authors: Weinberg Adriana , Forster-Harwood Jeri , Davies Jill , McFarland Elizabeth J. , Pappas Jennifer , Kinzie Kay , Barr Emily , Paul Suzanne , Salbenblatt Carol , Soda Elizabeth , Vazquez Anna , Levin Myron J.
Published: April 2011

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.
Structure and Dynamics of Glycosphingolipids in Lipid Bilayers: Insights from Molecular Dynamics Simulations
Authors: Patel Ronak Y. , Balaji Petety V.
Published: April 2011

Glycolipids are important constituents of biological membranes, and understanding their structure and dynamics in lipid bilayers provides insights into their physiological and pathological roles. Experimental techniques have provided details into their behavior at model and biological membranes; however, computer simulations are needed to gain atomic level insights. This paper summarizes the insights obtained from MD simulations into the conformational and orientational dynamics of glycosphingolipids and their exposure, hydration, and hydrogen-bonding interactions in membrane environment. The organization of glycosphingolipids in raft-like membranes and their modulation of lipid membrane structure are also reviewed.
The Molecular Pathogenesis of Osteosarcoma: A Review
Authors: Broadhead Matthew L. , Clark Jonathan C. M. , Myers Damian E. , Dass Crispin R. , Choong Peter F. M.
Published: April 2011

Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.
Lung Cancer Diagnosis from Proteomic Analysis of Preinvasive Lesions
Authors: Rahman S.M. Jamshedur , Gonzalez Adriana L. , Li Ming , Seeley Erin H. , Zimmerman Lisa J. , Zhang Xueqiong J. , Manier M. Lisa , Olson Sandra J. , Shah Ronak N. , Miller Alison N. , Putnam Joe B. , Miller York E. , Franklin Wilbur A. , Blot William J. , Carbone David P. , Shyr Yu , Caprioli Richard M. , Massion Pierre P.
Published: April 2011

Early detection may help improve survival from lung cancer. In this study, our goal was to derive and validate a signature from the proteomic analysis of bronchial lesions that could predict the diagnosis of lung cancer. Using previously published studies of bronchial tissues, we selected a signature of nine matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) mass-to-charge ratio features to build a prediction model diagnostic of lung cancer. The model was based on MALDI MS signal intensity (MALDI score) from bronchial tissue specimens from our 2005 published cohort of 51 patients. The performance of the prediction model in identifying lung cancer was tested in an independent cohort of bronchial specimens from 60 patients. The probability of having lung cancer based on the proteomic analysis of the bronchial specimens was characterized by an area under the receiver operating characteristic curve of 0.77 (95% CI 0.66–0.88) in this validation cohort. Eight of the nine features were identified and validated by Western blotting and immunohistochemistry. These results show that proteomic analysis of endobronchial lesions may facilitate the diagnosis of lung cancer and the monitoring of high-risk individuals for lung cancer in surveillance and chemoprevention trials. Cancer Res; 71(8); 3009–17. ©2011 AACR.
Transcriptional Control of Cellular Metabolism by mTOR Signaling
Authors: Yecies Jessica L. , Manning Brendan D.
Published: April 2011

Tumor cells are characterized by adaptations in cellular metabolism that afford growth and proliferative advantages over normal cells and, thus, contribute to cancer pathophysiology. There is an increasing appreciation of the fact that oncogenic signaling controls the metabolic reprogramming of cancer cells; however, the mechanisms and critical players are only beginning to be elucidated. Recent studies have revealed that mTOR complex 1 (mTORC1), a master regulator of cell growth and proliferation downstream of oncogenic signaling pathways, controls specific aspects of cellular metabolism through the induction of metabolic gene expression. mTORC1 activation is sufficient to promote flux through glycolysis and the oxidative branch of the pentose phosphate pathway, as well as to stimulate de novo lipogenesis, all processes that are important in tumor biology. As mTORC1 signaling is aberrantly elevated in the majority of genetic tumor syndromes and sporadic cancers, this pathway is poised to be a major driver of the metabolic conversion of tumor cells. Cancer Res; 71(8); 2815–20. ©2011 AACR.
Cytoplasmic CUL9/PARC Ubiquitin Ligase Is a Tumor Suppressor and Promotes p53-Dependent Apoptosis
Authors: Pei Xin-Hai , Bai Feng , Li Zhijun , Smith Matthew D. , Whitewolf Gabrielle , Jin Ran , Xiong Yue
Published: April 2011

A wide range of cell stresses, including DNA damage, signal to p53 through posttranslational modification of p53. The cytoplasmic functions of p53 are emerging as an important constituent of role of p53 in tumor suppression. Here, we report that deletion of the Cul9 (formerly Parc) gene, which encodes an E3 ubiquitin ligase that binds to p53 and localizes in the cytoplasm, resulted in spontaneous tumor development, accelerated Eμ-Myc–induced lymphomagenesis, and rendered mice susceptible to carcinogenesis. Cul9-p53 double-mutant mice exhibited indistinguishable tumor phenotypes as p53 single-mutant mice, indicating that the function of Cul9 in tumor suppression is largely mediated by p53. Deletion of Cul9 had no significant effect on cell-cycle progression, but attenuated DNA damage–induced apoptosis. Ectopic expression of wild-type CUL9, but not a point mutant CUL9 deficient in p53 binding, promotes apoptosis. These results show CUL9 as a potential p53-activating E3 ligase in the cytoplasm. Cancer Res; 71(8); 2969–77. ©2011 AACR.
Identification of an Unintended Consequence of Nrf2-Directed Cytoprotection against a Key Tobacco Carcinogen plus a Counteracting Chemopreventive Intervention
Authors: Paonessa Joseph D. , Ding Yi , Randall Kristen L. , Munday Rex , Argoti Dayana , Vouros Paul , Zhang Yuesheng
Published: April 2011

NF-E2–related factor 2 (Nrf2) is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. Although Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP–DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. Although glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, although higher liver UGT activity may protect the liver against ABP, it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further show that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues but does not seem to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. Cancer Res; 71(11); 3904–11. ©2011 AACR.
Social and Economic Factors Influencing a Fetal Surgery Program for Complicated Monochorionic Twin Pregnancies in a Developing Country
Authors: Hernandez-Andrade E. , Benavides-Serralde J.A. , Guzmán Huerta M.E. , Moreno-Alvarez O. , Mancilla-Ramírez J.
Published: April 2011

Objective: To analyze social and economic factors affecting the implementation of a fetal surgery program in a developing country. Materials and Methods: During an 18-month period, 30 women with complicated monochorionic diamniotic twin pregnancies were evaluated. 27 women had twin-to-twin transfusion syndrome (TTTS), 2 women had a selective intrauterine growth restriction, and 1 a discordant twin pregnancy with 1 fetus with a severe open neural tube defect. The TTTS cases were treated with fetoscopic laser ablation of the interplacental vascular communications and the remaining 3 cases with bipolar cord occlusion of the affected twin. The patients were evaluated using family income levels (very low, low, median, and high income). Demographic characteristics, gestational age at referral, the prevalence of infections, tocolysis care with hospital readmission, prolonged hospital stay until delivery, and gestational age at delivery were evaluated. Results: The overall survival rate of fetuses treated with laser ablation was 60% (32/54). Survival of at least 1 twin was achieved in 21/27 pregnancies (77%), and survival of both twins in 12/27 pregnancies (44%). The 3 pregnancies treated with cord occlusion had survival of the normal twin. Patients with low and very low family income showed a significantly higher prevalence of vaginal infections, increased periods of tocolysis requiring hospitalization, prolonged hospital stay until the end of pregnancy, and lower gestational age at delivery. Conclusion: When a fetal surgery program is implemented in a developing country, social and economic factors will influence the overall healthcare costs and treatment outcomes.
Schizotypal Personality in Healthy Adults Is Related to Blunted Cortisol Responses to the Combined Dexamethasone/ Corticotropin-Releasing Hormone Test
Authors: Hori Hiroaki , Teraishi Toshiya , Ozeki Yuji , Hattori Kotaro , Sasayama Daimei , Matsuo Junko , Kawamoto Yumiko , Kinoshita Yukiko , Higuchi Teruhiko , Kunugi Hiroshi
Published: April 2011

Background/Aims: Schizotypy is viewed as a dimensional trait ranging from healthy people to schizophrenic spectrum patients. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and accumulated evidence suggests that schizophrenia is associated with altered HPA axis function; however, HPA axis function in relation to schizotypal personality has not been well documented. Methods: We examined the relationship between schizotypal traits as assessed with the Schizotypal Personality Questionnaire (SPQ) and cortisol responses to the combined dexamethasone/corticotropin- releasing hormone test in 141 healthy volunteers. Subjects were divided into three groups based on their cortisol responses to the dexamethasone/corticotropin-releasing hormone test: incomplete suppressors, moderate suppressors, and enhanced suppressors. SPQ scores were compared between these three groups using the analysis of covariance, controlling for age and sex. Results: The analysis of covariance showed significant main effects of the suppressor status on the ideas of reference and suspiciousness/paranoid ideation subscales and cognitive-perceptual factor. Post-hoc analyses with Bonferroni correction revealed that the enhanced suppressors scored significantly higher than the moderate suppressors on these SPQ indices. Conclusion: These results indicate that nonclinical schizotypal traits in healthy adults are associated with blunted cortisol reactivity, potentially suggesting a shared neuroendocrinological mechanism across schizophrenia spectrum pathology.
Congenital Abdominal Aortic Aneurysm with Porencephaly: A Case Report
Authors: Tsunematsu Ryosuke , Shinozaki Tomoko , Fukushima Kotaro , Yumoto Yasuo , Hidaka Nobuhiro , Morokuma Seiichi , Fujita Yasuyuki , Hojo Satoshi , Wake Norio
Published: April 2011

An abdominal aortic aneurysm is a rare disease in the paediatric population and is mainly caused by intrauterine infection, connective tissue diseases, such as Ehlers-Danlos syndrome and Marfan’s syndrome, and iatrogenic trauma due to umbilical artery catheterization. Although several cases have been reported in the English literature, they were rarely diagnosed prenatally. Vascular obstruction in utero is also believed to be the major cause of porencephaly. Recently, gene mutations have been reported as the cause of both the above-mentioned diseases. We present a prenatally diagnosed case of congenital abdominal aortic aneurysm with porencephaly.
Prenatal Diagnosis of a Fetus with Terminal Deletion of Chromosome 1 (q43) in First-Trimester Screening: Is There a Characteristic Antenatal 1q Deletion Phenotype? A Case Report and Review of the Literature
Authors: Wagner N. , Guengoer E. , Mau-Holzmann U.A. , Maden Z. , Hoopmann M. , Abele H. , Kagan K.O.
Published: April 2011

The terminal deletion of chromosome 1q is a disease of rare incidence. It might be hereditary or caused by spontaneous changes within the chromosome. Phenotypic characteristics including typical facial appearance, microcephaly, psychomotor retardation and variable other anomalies are suggested to be based on the loss of macrochromosomal materials within the long arm of chromosome 1. The number of symptoms is related to the loss of genetic material. To date, only very few cases of terminal 1q deletion syndrome have been diagnosed in utero, mainly after 20 weeks of gestation. Here, we present a case of del(1q)syndrome in a first-trimester fetus. Besides other structural anomalies of the fetus, prenatal ultrasound at 13 weeks’ gestation demonstrated severe microgenia and suspicion of cardiac defect. Chorionic villous sampling was performed, and cytogenetic analysis showed a de novo terminal chromosome 1 long arm deletion. We discuss the structural features of antenatally diagnosed fetuses with terminal deletion of chromosome 1 and try to give an answer to the question whether there is a characteristic antenatal 1q deletion phenotype.
Neurobiological and Psychopathological Variables Related to Emotional Instability: A Study of Their Capability to Discriminate Patients with Bulimia Nervosa from Healthy Controls
Authors: Vaz-Leal Francisco J. , Rodríguez-Santos Laura , García-Herráiz M. Angustias , Ramos-Fuentes M. Isabel
Published: April 2011

Objective: To analyze the capability of a set of neurobiological and psychopathological variables to discriminate bulimia nervosa (BN) patients from healthy controls. Method: Seventy-five female patients with purging BN and 30 healthy controls were compared for psychopathology (impulsivity, borderline personality traits, depressive symptoms and self-defeating personality traits) and neurobiological parameters reflecting hypothalamic-pituitary-adrenal axis activity (morning serum cortisol before and after dexamethasone) and monoamine activity (24-hour urinary excretion of norepinephrine, serotonin, dopamine, and their main metabolites: 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid). Furthermore, the relationships between the 2 sets of variables were compared in the 2 samples. Results: BN patients displayed higher impulsivity, more severe depressive features, and more borderline and self-defeating personality traits than controls. The 4 psychopathological variables were strongly interrelated in patients, whereas only depressive features correlated with self-defeating personality traits in controls. Patients had lower 24-hour excretion of serotonin and dopamine than controls, as well as lower ability to suppress cortisol. The relations between the biochemical and the psychopathological variables were only significant in the BN patients, but not in the control group. When discriminant analysis methods were applied, patients and controls differed for psychopathology (impulsive behaviors and borderline personality traits) and biological parameters (baseline cortisol and dopamine excretion), but when the variables were analyzed together, the differences in neurobiological parameters appeared as mediated by the psychopathological status. Discussion: Our results suggest that hypothalamic-pituitary-adrenal axis activity, dopamine activity and other biological parameters are worthy of further study as potential dimensional markers of BN, although they seem to depend on the psychopathological status of the patients, in such a way that the psychopathological items associated with emotional instability (impulsivity and borderline personality traits) seem to be more reliable as clinical markers at the time being.
Association of Blood Monocyte and Platelet Markers with Carotid Artery Characteristics: The Atherosclerosis Risk in Communities Carotid MRI Study
Authors: Matijevic N. , Wu K.K. , Howard A.G. , Wasserman B. , Wang W.Y.-W. , Folsom A.R. , Sharrett A.R.
Published: April 2011

Background: Atherosclerosis is characterized by infiltration of inflammatory cells from circulating blood. Blood cell activation could play an important role in plaque formation. Methods: We analyzed the relationship between blood cellular markers and quantitative measures of carotid wall components in 1,546 participants from the ARIC (Atherosclerosis Risk in Communities) Carotid MRI Study. Carotid imaging was performed using a gadolinium contrast-enhanced MRI and cellular phenotyping by flow cytometry. Results: Monocyte Toll-like receptor (TLR)-2 is associated with larger plaques, while CD14, myeloperoxidase, and TLR-4 associate with smaller. Platelet CD40L is associated with smaller plaques and thinner caps, while P-selectin is associated with smaller core size. Conclusions: Blood cell activation is significantly associated with atherosclerotic changes of the carotid wall.
Temperature Management in Stroke – an Unsolved, but Important Topic
Authors: Kallmünzer Bernd , Kollmar Rainer
Published: April 2011

Clinical data clearly show that elevated body temperature contributes to an unfavorable outcome after ischemic and hemorrhagic stroke. Two promising therapeutic strategies arise from this observation: (1) treatment of fever aiming to sustain normothermia and (2) induced hypothermia, targeting core body temperatures below 36.5°C. A limited number of studies investigated antipyretic strategies after acute stroke and their results were rather disappointing in terms of clinical efficacy. For that reason, it remains unproven, whether sufficient fever treatment improves functional outcome. On the other hand, strong experimental evidence supports neuroprotective effects of induced hypothermia after stroke. Yet, clinical data on this topic remain preliminary and rely on a limited number of patients, mostly enrolled in nonrandomized trials. Therefore, induced hypothermia may be considered safe and feasible after ischemic stroke, but little can be said regarding efficacy. This review summarizes the data, both on fever treatment and induced hypothermia following stroke, starting with a synopsis of the most important experimental investigations, leading to the latest clinical trials. Given the promising data and the lack of successful acute neuroprotective therapies available thus far, suggestions are given for future investigation on both topics.
Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats
Authors: Chen Zhih-Cherng , Shieh Ja-Ping , Chung Hsien-Hui , Hung Ching-Hsia , Lin Hung Jung , Cheng Juei-Tang
Published: April 2011

Background/Aims: The role of opioid receptors in the regulation of vascular function remains unclear. In the current study, we evaluated the ability of loperamide, a peripheral opioid receptor agonist, to regulate blood pressure in spontaneously hypertensive rats (SHRs) and examined the mechanism(s) by which loperamide exerts its effects. Methods: In male SHRs, mean arterial pressure (MAP) was measured and hemodynamic analysis was recorded. Additionally, the isometric tension of aortic rings isolated from SHRs was determined. Results: Loperamide dose-dependently decreased MAP in SHRs but not in the normal group of Wistar-Kyoto rats. This reduction of MAP in conscious SHRs was abolished by the selective opioid µ-receptor antagonist cyprodime, but not by naloxonazine, the µ1-opioid receptor antagonist. However, cardiac output was not altered by loperamide in anesthetized SHRs. Moreover, loperamide-induced relaxation in isolated aortic rings precontracted with phenylephrine or vasopressin. This relaxation was abolished by cyprodime, but not by naloxonazine. Loperamide-induced relaxation was also attenuated by glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. Additionally, vasodilatation by loperamide was reduced by an inhibitor of protein kinase A (PKA) and enhanced by an inhibitor of phosphodiesterases. Conclusion: We suggest that loperamide can lower MAP in SHRs via µ2-opioid receptor-dependent cAMP-PKA pathway that induces vascular relaxation by opening KATP channels.
Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury
Authors: Hechler Béatrice , Gachet Christian
Published: April 2011

Arterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets.
Benefit of Intensive Statin Therapy in Women
Authors: Truong Quynh A. , Murphy Sabina A. , McCabe Carolyn H. , Armani Annemarie , Cannon Christopher P.
Published: April 2011

Background—

Despite the known benefit of intensive statin therapy for reducing future cardiovascular events, its effectiveness in women has been questioned by some.

Methods and Results—

In the Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, 911 (21.9%) women and 3251 (78.1%) men were randomized to intensive statin (atorvastatin 80 mg) versus standard therapy (pravastatin 40 mg) therapy for a median duration of 2.1 years. The primary end point was death, myocardial infarction, unstable angina; revascularization (occurring after 30 days); or stroke. Safety end points included elevations in liver function tests, creatine kinase, and myalgias/myositis. Women had a reduction in low-density lipoprotein (LDL) of 42.8% from baseline at 30 days (to a median of 60 mg/dL) in the intensive therapy arm, with 88.8% reaching the LDL goal of <100 mg/dL and 65.0% of <70 mg/dL, compared with a 16.8% reduction in LDL (to a median of 88 mg/dL) in the standard therapy arm. Women receiving intensive statin therapy had a significant 25% relative reduction over standard dose (hazard ratio, 0.75; 95% CI, 0.57 to 0.99;
P
=0.04) for the primary composite end point compared with a 14% reduction for men (hazard ratio, 0.86; 95% CI, 0.75 to 0.99;
P
=0.04;
P
-interaction, 0.38). No differences were observed between sexes for safety (all
P
-interaction ≥0.11).

Conclusions—

This trial provides evidence that both women and men derived benefit from intensive statin therapy after acute coronary syndrome, and thus, sex should not be a factor in determining who should be treated with intensive statin therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00382460.
The Globalization of Carbon Trading: Transnational Business Coalitions in Climate Politics
Authors: Meckling Jonas
Published: April 2011

Over the past decade, carbon trading has emerged as the policy instrument of choice in the industrialized world to address global climate change. In this article I argue that a transnational business coalition, representing mostly energy firms and energy-intensive manufacturers, actively promoted the global rise of carbon trading. In this process, business was able to draw on the support of government allies and business-oriented environmental groups, particularly in the UK and the US. Alongside its allies, the coalition had pivotal influence in the internationalization of carbon trading through the Kyoto Protocol, in the U-turn of the EU from skeptic to frontrunner on carbon trading and in the re-import of carbon trading to the US. While business was not able to prevent mandatory emission controls, it was able to critically affect the regulatory style of climate policy in favor of low-cost, market-based options.
Aristotle on Various Types of Alteration in De Anima II 5
Authors: Bowin John
Published: April 2011

In De Anima II 5, 417a21-b16, Aristotle makes a number of distinctions between types of transitions, affections, and alterations. The objective of this paper is to sort out the relationships between these distinctions by means of determining which of the distinguished types of change can be coextensive and which cannot, and which can overlap and which cannot. From the results of this analysis, an interpretation of 417a21-b16 is then constructed that differs from previous interpretations in certain important respects, chief among which is its characterization of transitions from first potentiality to first actuality, e.g., learning, not as ‘ordinary’, but rather as acquisitions of natural dispositions or faculties.
Shame, Guilt and Morality
Authors: Teroni Fabrice , Bruun Otto
Published: April 2011

The connection between shame, guilt and morality is the topic of many recent debates. A broad tendency consists in attributing a higher moral status and a greater moral relevance to guilt, a claim motivated by arguments that tap into various areas of morality and moral psychology. The Pro-social Argument has it that guilt is, contrary to shame, morally good since it promotes pro-social behaviour. Three other arguments claim that only guilt has the requisite connection to central moral concepts: the Responsibility Argument appeals to the ties between guilt and responsibility, the Autonomy Argument to the heteronomy of shame and the Social Argument to shame's link with reputation. In this paper, we scrutinize these arguments and argue that they cannot support the conclusion that they try to establish. We conclude that a narrow focus on particular criteria and a misconception of shame and guilt have obscured the important roles shame plays in our moral lives.
A Century of America on Chinese Screens
Authors: Xiao Zhiwei
Published: April 2011

No serious study has been published on how Chinese filmmakers have portrayed the United States and the American people over the last century. The number of such films is not large. That fact stands in sharp contrast not only to the number of "China pictures" produced in the United States, which is not surprising, but also in contrast to the major role played by Chinese print media. This essay surveys the history of Chinese cinematic images of America from the early twentieth century to the new millennium and notes the shifts from mostly positive portrayal in the pre-1949 Chinese films, to universal condemnation during the Mao years and to a more nuanced, complex, and multi-colored presentation of the last few decades.
Polarimetric Radar Analysis of Raindrop Size Variability in Maritime and Continental Clouds
Authors: Wilson James W. , Knight Charles A. , Tessendorf Sarah A. , Weeks Courtney
Published: April 2011

During the Queensland Cloud Seeding Research Program, the “CP2” polarimetric radar parameter differential radar reflectivity Zdr was used to examine the raindrop size evolution in both maritime and continental clouds. The focus of this paper is to examine the natural variability of the drop size distribution. The primary finding is that there are two basic raindrop size evolutions, one associated with continental air masses characterized by relatively high aerosol concentrations and long air trajectories over land and the other associated with maritime air masses with lower aerosol concentrations. The size evolution difference is during the growth stage of the radar echoes. The differential radar reflectivity in the growing continental clouds is dominated by large raindrops, whereas in the maritime clouds differential reflectivity is dominated by small raindrops and drizzle. The drop size evolution in many of the maritime air masses was very similar to those observed in the maritime air of the Caribbean Sea observed with the NCAR S-band polarimetric radar (S-Pol) during the Rain in Cumulus over the Ocean (RICO) experiment. Because the tops of the Queensland continental clouds ascended almost 2 times as fast as the maritime ones in their growth stage, both dynamical and aerosol factors may be important for the systematic difference in drop size evolution. Recommendations are advanced for future field programs to understand better the causes for the observed variability in drop size evolution. Also, considering the natural variability in drop size evolution, comments are provided on conducting and evaluating cloud seeding experiments.
Path-Average Rainfall Estimation from Optical Extinction Measurements Using a Large-Aperture Scintillometer
Authors: Uijlenhoet R. , Cohard J.-M. , Gosset M.
Published: April 2011

The potential of a near-infrared large-aperture boundary layer scintillometer as path-average rain gauge is investigated. The instrument was installed over a 2.4-km path in Benin as part of the African Monsoon Multidisciplinary Analysis (AMMA) Enhanced Observation Period during 2006 and 2007. Measurements of the one-minute-average received signal intensity were collected for 6 rainfall events during the dry season and 16 events during the rainy season. Using estimates of the signal base level just before the onset of the rainfall events, the optical extinction coefficient is estimated from the path-integrated attenuation for each minute. The corresponding path-average rain rates are computed using a power-law relation between the optical extinction coefficient and rain rate obtained from measurements of raindrop size distributions with an optical spectropluviometer and a scaling-law formalism for describing raindrop size distribution variations. Comparisons of five-minute rainfall estimates with measurements from two nearby rain gauges show that the temporal dynamics are generally captured well by the scintillometer. However, the instrument has a tendency to underestimate rain rates and event total rain amounts with respect to the gauges. It is shown that this underestimation can be explained partly by systematic differences between the actual and the employed mean power-law relation between rain rate and specific attenuation, partly by unresolved spatial and temporal rainfall variations along the scintillometer path. Occasionally, the signal may even be lost completely. It is demonstrated that if these effects are properly accounted for by employing appropriate relations between rain rate and specific attenuation and by adapting the pathlength to the local rainfall climatology, scintillometer-based rainfall estimates can be within 20% of those estimated using rain gauges. These results demonstrate the potential of large-aperture scintillometers to estimate path-average rain rates at hydrologically relevant scales.
Global Oral Health Inequalities in Incidence and Outcomes for Oral Cancer
Authors: Johnson N.W. , Warnakulasuriya S. , Gupta P.C. , Dimba E. , Chindia M. , Otoh E.C. , Sankaranarayanan R. , Califano J. , Kowalski L.
Published: April 2011

The mouth and oropharynx are among the ten most common sites affected by cancer worldwide, but global incidence varies widely. Five-year survival rates exceed 50% in only the best treatment centers. Causes are predominantly lifestyle-related: Tobacco, areca nut, alcohol, poor diet, viral infections, and pollution are all important etiological factors. Oral cancer is a disease of the poor and dispossessed, and reducing social inequalities requires national policies co-ordinated with wider health and social initiatives – the common risk factor approach: control of the environment; safe water; adequate food; public and professional education about early signs and symptoms; early diagnosis and intervention; evidence-based treatments appropriate to available resources; and thoughtful rehabilitation and palliative care. Reductions in inequalities, both within and between countries, are more likely to accrue from the application of existing knowledge in a whole-of-society approach. Basic research aimed at determining individual predisposition and acquired genetic determinants of carcinogenesis and tumor progression, thus allowing for targeted therapies, should be pursued opportunistically.
Global Oral Health Inequalities
Authors: Mossey P.A. , Shaw W.C. , Munger R.G. , Murray J.C. , Murthy J. , Little J.
Published: April 2011

The birth prevalence of orofacial clefts, one of the most common congenital anomalies, is approximately one in 700 live births, but varies with geography, ethnicity, and socio-economic status. There is a variation in infant mortality and access to care both between and within countries, so some clefts remain unrepaired into adulthood. Quality of care also varies, and even among repaired clefts there is residual deformity and morbidity that significantly affects some children. The two major issues in attempts to address these inequalities are (a) etiology/possibilities for prevention and (b) management and quality of care. For prevention, collaborative research efforts are required in developing countries, in line with the WHO approach to implement the recommendations of the 2008 Millennium Development Goals ( www.un.org/millenniumgoals ). This includes the “common risk factor” approach, which analyzes biological and social determinants of health alongside other chronic health problems such as diabetes and obesity, as outlined in the Marmot Health inequalities review (2008) ( www.ucl.ac.uk/gheg/marmotreview ). Simultaneously, orofacial cleft research should involve clinical researchers to identify inequalities in access to treatment and identify the best interventions for minimizing mortality and residual deformity. The future research agenda also requires engagement with implementation science to get research findings into practice.
The Diffusion of Market-Based Instruments
Authors: Dolšak Nives , Sampson Karen
Published: April 2011

This article examines adoption of a market instrument for reducing air pollution across the U.S. states. Because market instruments are viewed as reducing compliance costs, we hypothesize that market instruments should be more likely adopted in states whose electricity prices are higher than the average price in other states, especially their economic peers. Using a hazard model for a panel of 35 states from 1991 to 2003, we find that the adoption and the timing of market instruments are positively associated with the relative price of electricity even after controlling for a slate of variables, including the political context, the severity of air pollution, and neighborhood effects.
Attacks on Indian students: the commerce of denial in Australia
Authors: Dunn Kevin , Pelleri Danielle , Maeder-Han Karin
Published: April 2011

The issue of racist violence appeared in the Australian media and politics in mid-2009 following a spate of attacks on international students in Melbourne and Sydney. The racist aspect of these attacks was downplayed, authorities describing them as ‘opportunistic’ and a ‘regrettable fact of urban life’. The denial of racism is a familiar hallmark of contemporary racism; for some scholars, it is a defining criterion of what has been called the ‘new racism’. But the denial of racism around the attacks on Indian international students also had an economic imperative. Negative media coverage within India posed a substantial threat to the AUS$18.6 billion international education export market, with potential students and sponsors becoming concerned about their security should they elect to study in Australia. Data from the Challenging Racism project provide compelling evidence on the racist context of the attacks. The Indian media and politicians maintained an outraged position on the attacks, affecting student interest in Australia. And as the substantial economic costs became clearer, Australian governments came to more openly acknowledge a racist element to the attacks, also hinting at structural issues regarding community relations and attitudes which required policy attention.
Accelerated removals: the human cost of EU deportation policies
Authors: Fekete Liz
Published: April 2011

As European countries implement policies of ‘accelerated removal’, the legal rights of migrants and ‘failed’ asylum seekers are being eroded and force is being used more often in their deportations. Certain groups, including the Roma, unaccompanied children, the elderly and ill as well as asylum seekers from many African countries, are being targeted for removal as readmission agreements are negotiated, and many deportations now take place to Afghanistan and Iraq — regarded as safe countries.
Failure modes for FRP wrapped cylindrical concrete columns
Authors: Dandapat Ramkrishna , Deb Arghya , Bhattacharyya S.K.
Published: April 2011

The effect of damage at the cohesive concrete—laminate interface on failure of FRP-reinforced concrete columns is considered. Analytical expressions, obtained for the shear stress at the interfacial bond, show that higher fabric thickness and strength result in higher interfacial shear. Hence, as fabric thickness and strength are increased, there is increased likelihood of distress in the bond due to high shear stresses. In case of damage at the interface, the nature of the interfacial bond may change and thus affect the failure load. Damage in the bond is modeled to allow transition from cohesive bond to unbonded contact, using stress-based damage initiation and energy-based damage evolution. Bond failure, resulting in damage to the surface concrete, is found to facilitate failure by fabric rupture through three distinct mechanisms.