bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Oral HPV Infection among a High Prevalence Population of HIV-Positive and At-Risk HIV-Negative Adults
Authors: Beachler Daniel C. , Weber Kathleen M. , Margolick Joseph B. , Strickler Howard D. , Cranston Ross D. , Burk Robert D. , Wiley Dorothy J. , Minkoff Howard , Reddy Susheel , Stammer Emily E. , Gillison Maura L. , D'Souza Gypsyamber
Published: January 2012

Introduction: Human papillomavirus (HPV) is an important risk factor for oropharyngeal cancer. Individuals with human immunodeficiency virus (HIV) have higher oral HPV prevalence but the risk factors for oral HPV infection are not well understood for either HIV-positive or HIV-negative individuals.

Methods: This study was nested within the Multicenter AIDS Cohort Study (MACS; men) and Women Interagency HIV Study (WIHS; women) cohorts. Exfoliated oral epithelial cells were collected from 379 HIV-positive and 266 at-risk HIV-negative individuals using a rinse and gargle with Scope mouthwash. Samples were tested for 36 types of HPV DNA using PGMY09/11 consensus primers and reverse line blot hybridization. Risk factors for oral HPV infection were explored using logistic regression with generalized estimating equations in this cross-sectional analysis.

Results: Prevalent oral HPV infection was common (34%), including HPV16 infection in 5.7% of participants. HIV-positive individuals had increased odds of prevalent oral HPV infection compared with HIV-negative individuals [adjusted OR = 2.1; 95% confidence interval (CI), 1.6–2.8]. Risk factors for prevalent oral HPV differed in HIV-positive and HIV-negative participants. Among HIV-negative individuals, higher number of recent oral sex or rimming partners were strong risk factors for prevalent oral HPV infection (each Ptrend < 0.01). In contrast, among HIV-positive individuals, lower CD4 T-cell count (Ptrend < 0.001) and higher number of lifetime sexual partners (Ptrend = 0.03) were strong risk factors.

Conclusions: Oral HPV prevalence was elevated in HIV-positive individuals after controlling for differences in cigarette smoking and sexual behavior, supporting the possibility that HIV may affect the natural history of oral HPV.

Impact: Immunosuppression may contribute to increased persistence or progression of oral HPV infection. Cancer Epidemiol Biomarkers Prev; 21(1); 122–33. ©2011 AACR.
Results of a Phase 1 Study of AME-133v (LY2469298), an Fc-Engineered Humanized Monoclonal Anti-CD20 Antibody, in FcγRIIIa-Genotyped Patients with Previously Treated Follicular Lymphoma
Authors: Forero-Torres Andres , de Vos Sven , Pohlman Brad L. , Pashkevich Maksim , Cronier Damien M. , Dang Nam H. , Carpenter Susan P. , Allan Barrett W. , Nelson James G. , Slapak Christopher A. , Smith Mitchell R. , Link Brian K. , Wooldridge James E. , Ganjoo Kristen N.
Published: January 2012

Purpose: AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).

Patients and Methods: AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m2 weekly × 4 doses.

Results: AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.

Conclusions: AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable FcγRIIIa F-carrier genotype. Clin Cancer Res; 18(5); 1395–403. ©2012 AACR.
Inhibition of Collagen Receptor Discoidin Domain Receptor-1 (DDR1) Reduces Cell Survival, Homing, and Colonization in Lung Cancer Bone Metastasis
Authors: Valencia Karmele , Ormazábal Cristina , Zandueta Carolina , Luis-Ravelo Diego , Antón Iker , Pajares María J. , Agorreta Jackeline , Montuenga Luis M. , Martínez-Canarias Susana , Leitinger Birgit , Lecanda Fernando
Published: January 2012

Purpose: We investigated the role of the collagen-binding receptor discoidin domain receptor-1 (DDR1) in the initiation and development of bone metastasis.

Experimental Design: We conducted immunohistochemical analyses in a cohort of 83 lung cancer specimens and examined phosphorylation status in a panel of human lung cancer cell lines. Adhesion, chemotaxis, invasiveness, metalloproteolytic, osteoclastogenic, and apoptotic assays were conducted in DDR1-silenced cells. In vivo, metastatic osseous homing and colonization were assessed in a murine model of metastasis.

Results: DDR1 was expressed in a panel of human lung cancer cell lines, and high DDR1 levels in human lung tumors were associated with poor survival. Knockdown (shDDR1) cells displayed unaltered growth kinetics in vitro and in vivo. In contrast, shDDR1 cells showed reduced invasiveness in collagen matrices and increased apoptosis in basal conditions and induced apoptosis in vitro. More importantly, conditioned media of DDR1-knockdown cells decreased osteoclastogenic activity in vitro. Consequently, in a model of tumor metastasis to bone, lack of DDR1 showed decreased metastatic activity associated with reduced tumor burden and osteolytic lesions. These effects were consistent with a substantial reduction in the number of cells reaching the bone compartment. Moreover, intratibial injection of shDDR1 cells significantly decreased bone tumor burden, suggesting impaired colonization ability that was highly dependent on the bone microenvironment.

Conclusions: Disruption of DDR1 hampers tumor cell survival, leading to impaired early tumor–bone engagement during skeletal homing. Furthermore, inhibition of DDR1 crucially alters bone colonization. We suggest that DDR1 represents a novel therapeutic target involved in bone metastasis. Clin Cancer Res; 18(4); 969–80. ©2012 AACR.
Effects of Anti-VEGF on Pharmacokinetics, Biodistribution, and Tumor Penetration of Trastuzumab in a Preclinical Breast Cancer Model
Authors: Pastuskovas Cinthia V. , Mundo Eduardo E. , Williams Simon P. , Nayak Tapan K. , Ho Jason , Ulufatu Sheila , Clark Suzanna , Ross Sarajane , Cheng Eric , Parsons-Reponte Kathryn , Cain Gary , Van Hoy Marjie , Majidy Nicholas , Bheddah Sheila , dela Cruz Chuh Josefa , Kozak Katherine R. , Lewin-Koh Nicholas , Nauka Peter , Bumbaca Daniela , Sliwkowski Mark , Tibbitts Jay , Theil Frank-Peter , Fielder Paul J. , Khawli Leslie A. , Boswell C. Andrew
Published: January 2012

Both human epidermal growth factor receptor 2 (HER-2/neu) and VEGF overexpression correlate with aggressive phenotypes and decreased survival among breast cancer patients. Concordantly, the combination of trastuzumab (anti-HER2) with bevacizumab (anti-VEGF) has shown promising results in preclinical xenograft studies and in clinical trials. However, despite the known antiangiogenic mechanism of anti-VEGF antibodies, relatively little is known about their effects on the pharmacokinetics and tissue distribution of other antibodies. This study aimed to measure the disposition properties, with a particular emphasis on tumor uptake, of trastuzumab in the presence or absence of anti-VEGF. Radiolabeled trastuzumab was administered alone or in combination with an anti-VEGF antibody to mice bearing HER2-expressing KPL-4 breast cancer xenografts. Biodistribution, autoradiography, and single-photon emission computed tomography–X-ray computed tomography imaging all showed that anti-VEGF administration reduced accumulation of trastuzumab in tumors despite comparable blood exposures and similar distributions in most other tissues. A similar trend was also observed for an isotype-matched IgG with no affinity for HER2, showing reduced vascular permeability to macromolecules. Reduced tumor blood flow (P < 0.05) was observed following anti-VEGF treatment, with no significant differences in the other physiologic parameters measured despite immunohistochemical evidence of reduced vascular density. In conclusion, anti-VEGF preadministration decreased tumor uptake of trastuzumab, and this phenomenon was mechanistically attributed to reduced vascular permeability and blood perfusion. These findings may ultimately help inform dosing strategies to achieve improved clinical outcomes. Mol Cancer Ther; 11(3); 752–62. ©2012 AACR.
MYC Is Activated by USP2a-Mediated Modulation of MicroRNAs in Prostate Cancer
Authors: Benassi Barbara , Flavin Richard , Marchionni Luigi , Zanata Silvio , Pan Yunfeng , Chowdhury Dipanjan , Marani Marina , Strano Sabrina , Muti Paola , Blandino Giovanni , Loda Massimo
Published: January 2012

Ubiquitin-specific protease 2a (USP2a) is overexpressed in almost half of human prostate cancers and c-Myc is amplified in one third of these tumor types. Transgenic MYC expression drives invasive adenocarcinomas in the murine prostate. We show that overexpression of USP2a downregulates a set of microRNAs that collectively increase MYC levels by MDM2 deubiquitination and subsequent p53 inactivation. By establishing MYC as a target of miR-34b/c, we demonstrate that this cluster functions as a tumor suppressor in prostate cancer cells. We identify a distinct mRNA signature that is enriched for MYC-regulated transcripts and transcription factor binding sites in USP2a overexpressing prostate cancer cells. We demonstrate that these genes are associated with an invasive phenotype in human prostate cancer and that the proliferative and invasive properties of USP2a overexpressing cells are MYC-dependent. These results highlight an unrecognized mechanism of MYC regulation in prostate cancer and suggest alternative therapeutic strategies in targeting MYC.

Significance: The deubiquitinating enzyme USP2a has previously been shown to be oncogenic, overexpressed in almost half of human prostate adenocarcinomas, and prolongs the half-life of targets such as fatty acid synthase, MDM2, and cyclin D1. Here, we highlight a new mechanism by which USP2a enhances MYC levels through the modulation of specific subsets of microRNAs in prostate cancer, suggesting alternative therapeutic strategies for targeting MYC. Cancer Discovery; 2(3); 236–47. ©2012 AACR.

Read the Commentary on this article by Nelson et al., p. 206

This article is highlighted in the In This Issue feature, p. 193
Serotonin Transporter Gene Promoter Polymorphism and Alexithymia
Authors: Kano Michiko , Mizuno Tomoko , Kawano Yuko , Aoki Masashi , Kanazawa Motoyori , Fukudo Shin
Published: January 2012

Background: Recent neurobiological studies have reported that alexithymia may result from altered brain function related to emotional processing. Serotonin (5-hydroxytryptamine, 5-HT) has been shown to regulate central nervous system development associated with psychological processing. We investigated the possibility that polymorphism of the 5-HT transporter-linked promoter region (5-HTTLPR) is associated with alexithymia. Methods: This study included 304 healthy Japanese volunteers (148 males, 156 females). The subjects were categorized according to genotype (L/L, L/S, S/S) and results of the 20-item Toronto Alexithymia Scale (TAS-20), State-Trait Anxiety Inventory (STAI) and Self-Rating Depression Scale (SDS). Results: Subjects with the L/L genotype showed significantly higher TAS-20 scores, as well as significantly higher scores on the difficulty identifying feeling (DIF) subscale, than those with the L/S or S/S genotype (p < 0.05). There was a gender difference in the association between 5-HTTLPR genotype and DIF score. Female subjects with the L/L genotype showed significantly higher DIF scores than those with the L/S or S/S genotype (p ≤ 0.001). Neither STAI nor SDS was significantly associated with the 5-HTTLPR genotype. Conclusion: These results suggest a link between low synaptic 5-HT and alexithymia.
Specific and Nonspecific Host Adaptation during Arboviral Experimental Evolution
Authors: Novella Isabel S. , Presloid John B. , Smith Sarah D. , Wilke Claus O.
Published: January 2012

During the past decade or so, there has been a substantial body of work to dissect arboviral evolution and to develop models of adaptation during host switching. Regardless of what species serve as host or vectors, and of the geographic distribution and the mechanisms of replication, arboviruses tend to have slow evolutionary rates in nature. The hypothesis that this is the result of replication in the disparate environments provided by host and vector did not receive solid experimental support in any of the many viral species tested. Instead, it seems that from the virus’s point of view, either the two environments are sufficiently similar or one of the environments so dominates viral evolution that there is tolerance for suboptimal adaptation to the other environment. Replication in alternating environments has an unexpected cost in that there is decreased genetic variance that translates into a compromised adaptability for bypassed environments. Arboviruses under strong and continuous positive selection may have unusual patterns of genomic changes, with few or no mutations accumulated in the consensus sequence or with dN/dS values typically consistent with random drift in DNA-based organisms.
Gastric Cancer Development after Helicobacter pylori Eradication Therapy: A New Form of Gastric Neoplasia
Authors: Matsuo Taiji , Ito Masanori , Tatsugami Masana , Boda Tomoyuki , Takata Shunsuke , Tanaka Shinji , Chayama Kazuaki
Published: January 2012

Background and Aim: Along with the widespread use of eradication for Helicobacter pylori (H. pylori), the incidence of gastric cancer after eradication has also been increasing. There is a need for clarification of the clinical and biological characteristics of these neoplasms. Patients and Methods: We studied 27 cases of gastric cancer that developed after eradication (group AE). Out of the 27, we selected 26 with early-stage gastric cancer and compared them with 78 age-matched gastric cancer patients with H. pylori infection (group Pos) and 20 patients without H. pylori (group Neg). The patient with autoimmune gastritis was not included. Clinicopathological features, mucus patterns and Wnt5a expressions were compared among these groups. Results: Among group AE patients, there were more males than females, and the tumor histology was mainly intestinal type, a significant difference from group Neg. In contrast, macroscopically, the tumors were predominantly of the flat-depressed type, a feature similar to that of group Neg but significantly different from that of group Pos. MUC2 and Wnt5a expression was significantly lower in group AE than in group Pos. Conclusion: Gastric cancer development after eradication may have a carcinogenic pathway similar to that in cancer with H. pylori infection, though macroscopic/biological features may be modified by eradication therapy.
Socioeconomic Status, Cardiovascular Risk Factors, and Subclinical Atherosclerosis in Young Adults
Authors: Kestilä Paula , Magnussen Costan G. , Viikari Jorma S.A. , Kähönen Mika , Hutri-Kähönen Nina , Taittonen Leena , Jula Antti , Loo Britt-Marie , Pietikäinen Matti , Jokinen Eero , Lehtimäki Terho , Kivimäki Mika , Juonala Markus , Raitakari Olli T.
Published: January 2012

Objective—

The goal of this study was to investigate the extent to which socioeconomic status (SES) in young adults is associated with cardiovascular risk factor levels and carotid intima-media thickness (IMT) and their changes over a 6-year follow-up period.

Methods and Results—

The study population included 1813 subjects participating in the 21- and 27-year follow-ups of the Cardiovascular Risk in Young Finns Study (baseline age 24–39 years in 2001). At baseline, SES (indexed with education) was inversely associated with body mass index (
P
=0.0002), waist circumference (
P
<0.0001), glucose (
P
=0.01), and insulin (
P
=0.0009) concentrations; inversely associated with alcohol consumption (
P
=0.02) and cigarette smoking (
P
<0.0001); and directly associated with high-density lipoprotein cholesterol levels (
P
=0.05) and physical activity (
P
=0.006). Higher SES was associated with a smaller 6-year increase in body mass index (
P
=0.001). Education level and IMT were not associated (
P
=0.58) at baseline, but an inverse association was observed at follow-up among men (
P
=0.004). This became nonsignificant after adjustment with conventional risk factors (
P
=0.11). In all subjects, higher education was associated with a smaller increase in IMT during the follow-up (
P
=0.002), and this association remained after adjustments for conventional risk factors (
P
=0.04).

Conclusion—

This study shows that high education in young adults is associated with favorable cardiovascular risk factor profile and 6-year change of risk factors. Most importantly, the progression of carotid atherosclerosis was slower among individuals with higher educational level.
Regulatory T-Cell Response to Apolipoprotein B100–Derived Peptides Reduces the Development and Progression of Atherosclerosis in Mice
Authors: Herbin Olivier , Ait-Oufella Hafid , Yu Wang , Fredrikson Gunilla Nordin , Aubier Benjamin , Perez Nicolas , Barateau Véronique , Nilsson Jan , Tedgui Alain , Mallat Ziad
Published: January 2012

Objective—

The immunoinflammatory response plays a critical role in the development and progression of atherosclerosis. Recent studies suggested an important role for regulatory T (Treg) cells in the inhibition of disease-related vascular inflammation. We hypothesized that induction of a specific Treg cell response to atherosclerosis-relevant antigens would be an attractive strategy to limit the development and progression of atherosclerosis through the promotion of immune tolerance.

Methods and Results—

Young or old
Apoe
−/−
mice were subcutaneously infused for 2 weeks with either a control ovalbumin (OVA) peptide or with apolipoprotein B100 (ApoB100)–derived peptides without adjuvant. Atherosclerosis development, progression and immunologic status were assessed at 8 weeks after the end of the infusion. Treatment with ApoB100 peptides led to significant reduction of lesion development in young
Apoe
−/−
mice (
P
=0.001 versus OVA group) and abrogated atherosclerosis progression in old
Apoe
−/−
mice with already established lesions (0% progression in ApoB100 versus 17% in OVA group,
P
<0.005). Limitation of plaque progression was associated with reduced vascular inflammation and increased collagen content, indicative of plaque stabilization. Infusion of ApoB100 peptides did not alter antibody production but promoted a specific Treg cell response, which was associated with a reduction of both T helper type 1–related and T helper type 2–related cytokines. Interestingly, depletion of CD4
+
CD25
+
Treg cells abrogated ApoB100 peptides-dependent immune modulation and atheroprotection.

Conclusion—

Subcutaneous infusion of adjuvant-free ApoB100-derived peptides to
Apoe
−/−
mice reduces atherosclerosis through the induction of a specific Treg cell response.
Tissue Factor Pathway Inhibitor Blocks Angiogenesis via Its Carboxyl Terminus
Authors: Holroyd Eric W. , Delacroix Sinny , Larsen Katarina , Harbuzariu Adriana , Psaltis Peter J. , Wang Ling , Pan Shuchong , White Thomas A. , Witt Tyra A. , Kleppe Laurel S. , Mueske Cheryl S. , Mukhopadhyay Debabrata , Simari Robert D.
Published: January 2012

Objective—

Tissue factor pathway inhibitor (TFPI) is the primary regulator of the tissue factor (TF) coagulation pathway. As such, TFPI may regulate the proangiogenic effects of TF. TFPI may also affect angiogenesis independently of TF, through sequences within its polybasic carboxyl terminus (TFPI C terminus [TFPIct]). We aimed to determine the effects of TFPI on angiogenesis and the role of TFPIct.

Methods and Results—

Transgenic overexpression of TFPI attenuated angiogenesis in the murine hindlimb ischemia model and an aortic sprout assay. In vitro, TFPI inhibited endothelial cell migration. Peptides within the human TFPIct inhibited endothelial cell cord formation and migration in response to vascular endothelial growth factor (VEGF) 165 but not VEGF121. Furthermore, exposure to human TFPIct inhibited the phosphorylation of VEGF receptor 2 at residue Lys951, a residue known to be critical for endothelial cell migration. Finally, systemic delivery of a murine TFPIct peptide inhibited angiogenesis in the hindlimb model.

Conclusion—

These data demonstrate an inhibitory role for TFPI in angiogenesis that is, in part, mediated through peptides within its carboxyl terminus. In addition to its known role as a TF antagonist, TFPI, via its carboxyl terminus, may regulate angiogenesis by directly blocking VEGF receptor 2 activation and attenuating the migratory capacity of endothelial cells.
Regulation of the Inflammatory Response in Cardiac Repair
Authors: Frangogiannis Nikolaos G.
Published: January 2012

Myocardial necrosis triggers an inflammatory reaction that clears the wound from dead cells and matrix debris, while activating reparative pathways necessary for scar formation. A growing body of evidence suggests that accentuation, prolongation, or expansion of the postinfarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction. This review manuscript discusses the cellular effectors and endogenous molecular signals implicated in suppression and containment of the inflammatory response in the infarcted heart. Clearance of apoptotic neutrophils, recruitment of inhibitory monocyte subsets and regulatory T cells, macrophage differentiation and pericyte/endothelial interactions may play an active role in restraining postinfarction inflammation. Multiple molecular signals may be involved in suppressing the inflammatory cascade. Negative regulation of toll-like receptor signaling, downmodulation of cytokine responses, and termination of chemokine signals may be mediated through the concerted action of multiple suppressive pathways that prevent extension of injury and protect from adverse remodeling. Expression of soluble endogenous antagonists, decoy receptors, and posttranslational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin-10, members of the transforming growth factor-β family, and proresolving lipid mediators (such as lipoxins, resolvins, and protectins) may suppress proinflammatory signaling. In human patients with myocardial infarction, defective suppression, and impaired resolution of inflammation may be important mechanisms in the pathogenesis of remodeling and in progression to heart failure. Understanding of inhibitory and proresolving signals in the infarcted heart and identification of patients with uncontrolled postinfarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.
The Fire Within: Cardiac Inflammatory Signaling in Health and Disease
Authors: Coggins Matthew , Rosenzweig Anthony
Published: January 2012

Inflammatory mediators are operative in the pathogenesis of the most common forms of heart disease. Although in most cases the induction of these pathways is maladaptive and deleterious, there are notable exceptions when inflammatory pathways participate in healing or limiting the extent of injury. The appreciation of the role of these mechanisms in myocardial homeostasis and pathophysiology has led to increased efforts to elucidate the specific signaling pathways most relevant to the heart. Our goal in this introductory overview is to provide context for the five detailed reviews that follow by introducing the major relevant stimuli, the receptors, and pathways that mediate inflammatory signaling in the heart. We try to impart a sense of the scope and complexity of these pathways, as well as their interactions with signaling pathways regulating cell survival and metabolism. These complexities underscore the potential challenges of therapeutically targeting inflammatory mechanisms in heart disease and may help explain the mostly disappointing results of this approach to date.
Autoantibodies in Heart Failure and Cardiac Dysfunction
Authors: Kaya Ziya , Leib Christoph , Katus Hugo A.
Published: January 2012

Human heart failure is a disease with multifactorial causes, considerable morbidity, and high mortality. Several circulating autoantibodies, some of them being heart-specific, play a crucial role in the progression and induction of heart failure. However the precise mechanisms on how these autoantibodies perpetuate or even induce an organ specific autoimmune response are not yet fully understood. Also it is being a matter of current research to elucidate a potential pathophysiological role of the innate immune system in generating auto-reactive antibodies. In this review we will summarize the current available literature on circulating autoantibodies which are related to human heart failure. We will present clinical and animal studies that demonstrate the occurrence and pathophysiological relevance of several autoantibodies in heart failure, as well as point out biological mechanisms on molecular and cellular level. Finally the beneficial therapeutic effects of numerous clinical studies that target the humoral arm of the immune system by using either intravenous immunoglobulins and/or immunoadsorption will be critically discussed.
Hyponatremia, Hypernatremia, and Mortality in Patients With Chronic Kidney Disease With and Without Congestive Heart Failure
Authors: Kovesdy Csaba P. , Lott Evan H. , Lu Jun Ling , Malakauskas Sandra M. , Ma Jennie Z. , Molnar Miklos Z. , Kalantar-Zadeh Kamyar
Published: January 2012

Background—

Hyponatremia is common in patients with conditions such as congestive heart failure and is associated with increased mortality in hospitalized patients. Congestive heart failure is common in patients with chronic kidney disease, but the association of serum sodium concentration with mortality in such patients is not well characterized.

Methods and Results—

We examined the association of serum sodium concentration with all-cause mortality in a nationally representative cohort of 655 493 US veterans with non–dialysis-dependent chronic kidney disease (95 961 [15%] of them with congestive heart failure). Associations were examined in time-dependent Cox models with adjustment for potential confounders. During a median follow-up of 5.5 years, a total of 193 956 patients died (mortality rate, 62.5/1000 patient-years; 95% confidence interval, 62.2–62.8). The association of serum sodium level with mortality was U-shaped, with the lowest mortality seen in patients with sodium level of 140 mEq/L and with both lower and higher levels showing significant associations with increased mortality. Patients with serum sodium levels of <130, 130 to 135.9, 145.1 to 150, and ≥150 mEq/L compared with 136 to 145 mEq/L had multivariable-adjusted mortality hazard ratios (95% confidence interval) of 1.93 (1.83–2.03), 1.28 (1.26–1.30), 1.33 (1.28–1.38), and 1.56 (1.33–1.83) (
P
<0.001 for all). The associations remained consistent in subgroups of patients with and without congestive heart failure.

Conclusions—

Both lower and higher serum sodium levels are independently associated with higher mortality in patients with non–dialysis-dependent chronic kidney disease, irrespective of the presence or absence of congestive heart failure.
Baroreflex Sensitivity to Predict Malignant Middle Cerebral Artery Infarction
Authors: Sykora Marek , Steiner Thorsten , Rocco Andrea , Turcani Peter , Hacke Werner , Diedler Jennifer
Published: January 2012

Background and Purpose—

Hemicraniectomy has been shown to be an effective treatment of life-threatening edema (LTE) in malignant middle cerebral artery infarction when performed early. Identifying patients who will develop LTE is therefore imperative. We hypothesize that autonomic shift toward sympathetic dominance may relate to LTE formation. We aimed to investigate the predictive potential of baroreflex sensitivity (BRS) as a marker of autonomic balance for calculating the course of large middle cerebral artery infarction.

Methods—

Patients with middle cerebral artery infarction >2/3 of the territory and BRS measurement at admission were analyzed. BRS was estimated using the cross-correlational method. Demographic, clinical, and radiological data including stroke severity, infarct size, and basal ganglia involvement were recorded. Malignant course with LTE was defined as clinical deterioration and midline shift ≥5 mm in the first 48 hours.

Results—

Eighteen (62.8%) patients developed LTE. Patients with LTE had lower BRS (2.3 versus 4.4 mm Hg/ms,
P
=0.007), larger infarcts (214 versus 144 mL,
P
=0.03), more frequent involvement of the basal ganglia (14 versus 4,
P
=0.03), and more often underwent thrombolysis combined with endovascular intervention (6 versus 0,
P
=0.04). In a multivariate model, BRS (OR, 0.36; CI, 0.14–0.93;
P
=0.03) and basal ganglia involvement (OR, 11.53; CI, 1.15–115.9;
P
=0.04) were independent predictors for LTE. This model correctly classified 86.2% of the malignant cases.

Conclusions—

Decreased BRS, mirroring sympathetic activation, and basal ganglia involvement were associated with development of malignant course with LTE in large middle cerebral artery infarction. The predictive relevance of our findings needs to be confirmed in further studies.
Variable Presentations of Postpartum Angiopathy
Authors: Fugate Jennifer E. , Ameriso Sebastián F. , Ortiz Gustavo , Schottlaender Lucia V. , Wijdicks Eelco F.M. , Flemming Kelly D. , Rabinstein Alejandro A.
Published: January 2012

Background and Purpose—

Postpartum angiopathy (PPA), a rare cause of stroke in the puerperium, is heralded by severe headaches within 1–2 weeks after delivery. Angiography demonstrates segmental vasoconstriction that often resolves spontaneously. PPA is generally regarded as benign. We aimed to define clinical presentations, radiological findings, and outcomes of patients with PPA.

Methods—

We retrospectively reviewed patients from 3 centers with acute neurological symptoms and angiography showing vasoconstriction in the postpartum period. Patients without neuroimaging and with diagnoses of cerebral venous sinus thrombosis and aneurysmal hemorrhage were excluded. Patient characteristics, clinical symptoms, neuroimaging findings, and clinical condition at hospital discharge were collected.

Results—

Eighteen patients (mean age, 31 years; range, 15–41) were identified. Median gestation was 38 weeks. Twelve (67%) had a history of prior uneventful pregnancy. Neurological symptoms began on median day 5 postpartum and included headache (n=16, 89%), focal deficit (n=9, 50%), visual disturbance (n=8, 44%), encephalopathy (n=6, 33%), and seizure (n=5, 28%), often in combination. Brain imaging was abnormal in most (n=13, 72%). The most common abnormalities were intracranial hemorrhage (n=7, 39%), vasogenic edema (n=6, 35%), and infarction (n=6, 35%). Clinical outcomes were markedly variable with full recovery seen in 9 (50%), death after a fulminant course in 4 (22%), and residual deficits in 5 (28%).

Conclusions—

In contrast to prior reports, this group of patients with PPA had a higher proportion of nonbenign outcomes. Most patients who undergo neuroimaging have parenchymal abnormalities, which are most often stroke (hemorrhagic or ischemic) or reversible vasogenic edema.
The Flight of Pudicitia: Juvenal’s Vision of the Past and the Programmatic Function of the Prologue in the Sixth Satire
Authors: Watson Patricia
Published: January 2012

Abstract

In the prologue toSatire6, Juvenal depicts the primitive woman of the Golden Age as an idealmatrona, only to undercut humorously the paradigmatic value of this picture. The poet’s intentions in so doing have been variously explained; this article views the parodic tone of the passage in terms of its programmatic function. A detailed discussion is offered of Juvenal’s depiction of the cavewife and it is demonstrated how this foreshadows the speaker’s unfavourable treatment of all women, even paradigms such as Cornelia. In short, the prologue establishes the speaker ofSatire6 as a misogynist whose views are so extreme that they cannot be taken seriously.
All’s Well that Ends Well: Storytelling, Predictive Signs, and the Voice of the Author in Chariton’s Callirhoe
Authors: Doulamis Konstantin
Published: January 2012

Abstract

This article takes a new approach to the study of narrative technique in Chariton’sCallirhoe. Following Chariton’s self-identification at the start of the novel, considerable emphasis is placed upon the narrator, who makes his presence felt throughout the narrative and whose role is further underscored by self-reflexive comments about storytelling made by various characters. This, combined with the fact that the novelist appears to have delegated all responsibility for the shaping of the plot to personified deities, allows the author to remain ‘concealed’ for most of the narrative, thus giving him a voice independent from that of the narrator. With assistance from divine agents, author and narrator operate a suspense-generating system of forewarnings, false predictive signs, and intervention, which enhances the anticipation of the expected happy ending. In the last Book, with the finale drawing near, the narrator hints at the authorial presence behind the novel, but it is only in the last sentence and after the story has reached its dénouement that theauctor’s voice can be heard loud and clear in an undisputed authorial statement.
The Amazonian toad Rhaebo guttatus is able to voluntarily squirt poison from the paratoid macroglands
Authors: Felipe Toledo Luís , Trefaut Rodrigues Miguel , Jared Carlos , Kruth Verdade Vanessa , Maria Antoniazzi Marta
Published: January 2012

Amphibian defence mechanisms commonly rely on cutaneous toxins produced in either isolated or clustered glands, such as toad parotoid macroglands. In contrast to the passive mechanism of poison liberation in other amphibians, we discovered that the Amazonian toad Rhaebo guttatus is unique because it can voluntarily squirt jets of poison from its parotoids.
To What Ends EU Foreign Policy? Contending Approaches to the Union’s Diplomatic Objectives and Representation
Authors: Thomas Daniel C. , Tonra Ben
Published: January 2012

Summary

The strengthened Office of the High Representative for Foreign Affairs and Security Policy and the new European External Action Service (EEAS) presuppose a set of interests and/or values that the European Union (EU) wishes to pursue on the world stage. But what are those interests and/or values and how does the EU reach agreement on them? Rather than simply ‘cutting and pasting’ from EU treaties and strategy papers, this article identifies seven distinct theoretical models of how the EU and its member states arrive collectively at a definition of their diplomatic objectives. The seven models include intergovernmentalist models of veto threats and log-rolling, normative institutionalist models of cooperative bargaining and entrapment, and constructivist and sociological institutionalist models of elite socialization, Europeanization and collective identity formation. The article identifies the logics of each model and notes their implications for the role of the EU’s new foreign policy institutions.
Connecting Subseasonal Movements of the Winter Mean Ridge in Western North America to Inversion Climatology in Cache Valley, Utah
Authors: Wang Shih-Yu , Gillies Robert R. , Martin Randy , Davies Robert E. , Booth Marty R.
Published: January 2012

A 10-yr record of PM2.5 (particulate matter of aerodynamic diameter ≤ 2.5 μm), collected in Cache Valley near downtown Logan, Utah, reveals a strong peak in the PM2.5 concentration climatology that is tightly localized in mid-January. The cause of this subseasonal variation in the PM2.5 climatology is investigated through dynamical downscaling and large-scale diagnostics. Climatological analysis of the U.S. winter mean ridge reveals a mid-January subseasonal shift in the zonal direction, likely in response to variations in the Rossby wave source over the central North Pacific Ocean. This displacement of the winter mean ridge, in turn, has an impact on regional-scale atmospheric conditions—specifically, subsidence with local leeside enhancements and midlevel warming over Cache Valley. The analyses of this study indicate that the subseasonal peak of long-term mean PM2.5 concentrations in Cache Valley is linked to the large-scale circulations’ subseasonal evolution, which involves remote forcing in the circumpolar circulations as well as possible tropical–midlatitude interactions. This subseasonal evolution of the winter mean circulation also affects precipitation along the West Coast.
Estimating the Urban Heat Island in Residential Areas in the Netherlands Using Observations by Weather Amateurs
Authors: Wolters Dirk , Brandsma Theo
Published: January 2012

A better quantification of the urban heat islands (UHIs) in the Netherlands is urgently needed given the heat stress–related problems in the recent past combined with the expected temperature rise for the coming decades. Professional temperature observations in Dutch urban areas are scarce, however. Therefore, this research explores the use of observations from weather stations that were installed and maintained by weather amateurs. From a set of over 200 stations, suitable and representative data have been selected from 20 stations, using a set of objective selection criteria that are based on metadata. One year of data (January–December 2010) was considered. From these data, estimates have been obtained of the magnitude of the UHI in Dutch low-rise residential areas. A positive relation (linear model with r2 ≈ 0.7) was derived between the summer-averaged UHI and the (neighborhood scale) population density around the observational sites. It was found that the UHI in summer is strongest in nighttime conditions and that it increases with decreasing wind speed, decreasing cloud cover, and increasing sea level air pressure. The summer-averaged UHI was ~0.9°C. During nighttime in a relatively warm 1-month subperiod of the summer, the average UHI was ~1.4°C. During spring and autumn, the UHI was lower than in summer; during winter, no significant UHI was observed. The agreement in results among the different stations and the accordance of the magnitude and variation of the observed UHI with those described in the literature show that automatic observations from weather amateurs can be of sufficient quality for atmospheric research, provided that detailed metadata are available.
A Modeling Study on the Development of a Bowing Structure and Associated Rear Inflow within a Squall Line over South China
Authors: Meng Zhiyong , Zhang Fuqing , Markowski Paul , Wu Duochang , Zhao Kun
Published: January 2012

Through convection-permitting simulations, this study examines a large bowing structure within a squall line that occurred during the rainy season in South China. The bowing structure is closely associated with a local enhancement of (and balance between) the cold pool and the line-normal environmental low-level vertical shear. Rear inflow plays an essential role in the formation and evolution of this large bowing structure. It is found that the low-level rear inflow is largely a natural consequence of the baroclinically generated horizontal vorticity near the surface, while the midtropospheric rear inflow is forced by several pairs of bookend vortices. Vorticity budget and vortex-line analyses show that the bookend vortices form mainly through the tilting of horizontal vorticity. Consolidation of these pairs of bookend vortices forms a broad zone of contiguous rear inflow. The environmental flow and horizontal pressure gradient force associated with the midlevel pressure deficit induced by the rearward-tilting buoyant updrafts, on the other hand, are not primarily responsible for the formation of the rear inflow.
Tropical Cyclone Climatology in a 10-km Global Atmospheric GCM: Toward Weather-Resolving Climate Modeling
Authors: Manganello Julia V. , Hodges Kevin I. , Kinter James L. , Cash Benjamin A. , Marx Lawrence , Jung Thomas , Achuthavarier Deepthi , Adams Jennifer M. , Altshuler Eric L. , Huang Bohua , Jin Emilia K. , Stan Cristiana , Towers Peter , Wedi Nils
Published: January 2012

Northern Hemisphere tropical cyclone (TC) activity is investigated in multiyear global climate simulations with the ECMWF Integrated Forecast System (IFS) at 10-km resolution forced by the observed records of sea surface temperature and sea ice. The results are compared to analogous simulations with the 16-, 39-, and 125-km versions of the model as well as observations.

In the North Atlantic, mean TC frequency in the 10-km model is comparable to the observed frequency, whereas it is too low in the other versions. While spatial distributions of the genesis and track densities improve systematically with increasing resolution, the 10-km model displays qualitatively more realistic simulation of the track density in the western subtropical North Atlantic. In the North Pacific, the TC count tends to be too high in the west and too low in the east for all resolutions. These model errors appear to be associated with the errors in the large-scale environmental conditions that are fairly similar in this region for all model versions.

The largest benefits of the 10-km simulation are the dramatically more accurate representation of the TC intensity distribution and the structure of the most intense storms. The model can generate a supertyphoon with a maximum surface wind speed of 68.4 m s−1. The life cycle of an intense TC comprises intensity fluctuations that occur in apparent connection with the variations of the eyewall/rainband structure. These findings suggest that a hydrostatic model with cumulus parameterization and of high enough resolution could be efficiently used to simulate the TC intensity response (and the associated structural changes) to future climate change.
Emerging Approaches to Counseling Intervention
Authors: Neacsiu Andrada D. , Ward-Ciesielski Erin F. , Linehan Marsha M.
Published: January 2012

Dialectical Behavior Therapy (DBT) is a comprehensive, multimodal cognitive behavioral treatment originally developed for individuals who met criteria for borderline personality disorder (BPD) who displayed suicidal tendencies. DBT is based on behavioral theory but also includes principles of acceptance, mindfulness, and validation. Since its development, DBT has been adapted to various populations and has been successfully used in a wide array of settings. This article presents the approaches used in DBT with a particular emphasis on (a) the philosophy and assumptions on which the treatment is based, (b) the major theoretical constructs and the DBT conceptualization of the client, (c) the intervention and specific techniques used, (d) research supporting the theory and treatment, and (e) the integration of diversity, culture, and social justice.
Impact of Outliers Arising From Unintended and Unknowingly Included Subpopulations on the Decisions About the Number of Factors in Exploratory Factor Analysis
Authors: Liu Yan , Zumbo Bruno D.
Published: January 2012

There is a lack of research on the effects of outliers on the decisions about the number of factors to retain in an exploratory factor analysis, especially for outliers arising from unintended and unknowingly included subpopulations. The purpose of the present research was to investigate how outliers from an unintended and unknowingly included subpopulation affected the decisions about the number of factors to retain using four commonly used methods separately. The results showed that all the decision methods could provide biased results and the number of factors could be inflated, deflated, or remain the same depending on the decision methods used and outlier conditions. The findings also revealed that symmetric outliers did not affect the three principal component analysis–based methods but affected chi-square (ML) sequential tests. Finally, sample size did not play a role in the effect of outliers.
Exploring the acceptance of religious assistance among patients of a psychiatric hospital
Authors: Lucchetti Giancarlo , Braguetta Camilla C , Vallada Candido , Vallada Homero
Published: January 2012

Background:

Spiritual issues are rarely addressed by psychiatric institutions in daily routine practice.

Aims:

To report the prevalence of, and factors associated with, inpatients’ acceptance of religious assistance in a psychiatric hospital.

Methods:

All patients evaluated by the religious assistance service in a psychiatric hospital were included. Patients admitted were asked about their need for religious assistance and were assessed on several religious aspects. Additional information was collected from patients’ hospital charts. A comparison between those who accepted the religious assistance and those who did not was performed.

Results:

Most of the 213 patients evaluated requested religious assistance (85.0%), including those that reported having no religion (79.1%). Patients with a diagnosis of schizophrenia ( p = .010) and lower intrinsic religiousness ( p = .002) tended to request less religious assistance. More than 80% of patients requested assistance based on religious traditions other than their own.

Conclusion:

Most psychiatric inpatients were willing to participate in religious assistance sessions, even those without formal religious affiliations. Patients with lower intrinsic religiosity and schizophrenia tended to request less assistance. We believe the findings of this study can serve to foster discussion on whether psychiatric hospitals should provide a structured religious care service.
The Geography of Intrametropolitan KIBS Innovation: Distinguishing Agglomeration Economies from Innovation Dynamics
Authors: Shearmur Richard
Published: January 2012

Much has been written about innovation, territory, knowledge spill-overs and agglomeration economies, but neighbourhood-level processes of innovation have rarely been studied in a systematic fashion. This article explores whether knowledge-intensive business services (KIBS) are systematically more innovative when they are located in employment clusters. In doing so, it distinguishes between the simple co-location of innovative firms with other activities, and possible dynamic effects (identified by controlling for firm-level innovation factors): most identified geographical patterns are resilient to controls, but the geography of innovation is not straightforward. In Montreal, whilst certain types of innovation occur in employment clusters, others display no spatial patterns. Furthermore, the most intensive KIBS innovators tend to locate away from high-employment and from high-KIBS zones. KIBS innovation does not behave as expected if innovation dynamics were localised in a fashion similar to agglomeration economies: it is therefore important to distinguish between the two.