bluuebunny/crossref_metadata_2025 huggingface dataset:
Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction
Authors: DeMarco Vincent G. , Johnson Megan S. , Ma Lixin , Pulakat Lakshmi , Mugerfeld Irina , Hayden Melvin R. , Garro Mona , Knight William , Britton Steven L. , Koch Lauren G. , Sowers James R.
Published: February 2012

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy.
Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction
Authors: Vaseghi Marmar , Lux Robert L. , Mahajan Aman , Shivkumar Kalyanam
Published: February 2012

The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients ( n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones ( P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI ( P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts ( P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.
Aging attenuates the coronary blood flow response to cold air breathing and isometric handgrip in healthy humans
Authors: Muller Matthew D. , Gao Zhaohui , Mast Jessica L. , Blaha Cheryl A. , Drew Rachel C. , Leuenberger Urs A. , Sinoway Lawrence I.
Published: February 2012

The purpose of this echocardiography study was to measure peak coronary blood flow velocity (CBVpeak) and left ventricular function (via tissue Doppler imaging) during separate and combined bouts of cold air inhalation (−14 ± 3°C) and isometric handgrip (30% maximum voluntary contraction). Thirteen young adults and thirteen older adults volunteered to participate in this study and underwent echocardiographic examination in the left lateral position. Cold air inhalation was 5 min in duration, and isometric handgrip (grip protocol) was 2 min in duration; a combined stimulus (cold + grip protocol) and a cold pressor test (hand in 1°C water) were also performed. Heart rate, blood pressure, O2 saturation, and inspired air temperature were monitored on a beat-by-beat basis. The rate-pressure product (RPP) was used as an index of myocardial O2 demand, and CBVpeak was used as an index of myocardial O2 supply. The RPP response to the grip protocol was significantly blunted in older subjects (Δ1,964 ± 396 beats·min−1·mmHg) compared with young subjects (Δ3,898 ± 452 beats·min−1·mmHg), and the change in CBVpeak was also blunted (Δ6.3 ± 1.2 vs. 11.2 ± 2.0 cm/s). Paired t-tests showed that older subjects had a greater change in the RPP during the cold + grip protocol [Δ2,697 ± 391 beats·min−1·mmHg compared with the grip protocol alone (Δ2,115 ± 375 beats·min−1·mmHg)]. An accentuated RPP response to the cold + grip protocol (compared with the grip protocol alone) without a concomitant increase in CBVpeak may suggest a dissociation between the O2 supply and demand in the coronary circulation. In conclusion, older adults have blunted coronary blood flow responses to isometric exercise.
Inactivation of the potent Pseudomonas aeruginosa cytotoxin pyocyanin by airway peroxidases and nitrite
Authors: Reszka Krzysztof J. , Xiong Ye , Sallans Larry , Pasula Rajamouli , Olakanmi Oyebode , Hassett Daniel J. , Britigan Bradley E.
Published: February 2012

Pyocyanin (1-hydroxy- N-methylphenazine, PCN) is a cytotoxic pigment and virulence factor secreted by the human bacterial pathogen, Pseudomonas aeruginosa . Here, we report that exposure of PCN to airway peroxidases, hydrogen peroxide (H2O2), and NaNO2generates unique mononitrated PCN metabolites (N-PCN) as revealed by HPLC/mass spectrometry analyses. N-PCN, in contrast to PCN, was devoid of antibiotic activity and failed to kill Escherichia coli and Staphylococcus aureus . Furthermore, in contrast to PCN, intratracheal instillation of N-PCN into murine lungs failed to induce a significant inflammatory response. Surprisingly, at a pH of ∼7, N-PCN was more reactive than PCN with respect to NADH oxidation but resulted in a similar magnitude of superoxide production as detected by electron paramagnetic resonance and spin trapping experiments. When incubated with Escherichia coli or lung A549 cells, PCN and N-PCN both led to superoxide formation, but lesser amounts were detected with N-PCN. Our results demonstrate that PCN that has been nitrated by peroxidase/H2O2/NO2−systems possesses less cytotoxic/proinflammatory activity than native PCN. Yield of N-PCN was decreased by the presence of the competing physiological peroxidase substrates (thiocyonate) SCN−(myeloperoxidase, MPO, and lactoperoxidase, LPO) and Cl−(MPO), which with Cl−yielded chlorinated PCNs. These reaction products also showed decreased proinflammatory ability when instilled into the lungs of mice. These observations add important insights into the complexity of the pathogenesis of lung injury associated with Pseudomonas aeruginosa infections and provide additional rationale for exploring the efficacy of NO2−in the therapy of chronic Pseudomonas aeruginosa airway infection in cystic fibrosis.
CXCR4 regulates migration of lung alveolar epithelial cells through activation of Rac1 and matrix metalloproteinase-2
Authors: Ghosh Manik C. , Makena Patrudu S. , Gorantla Vijay , Sinclair Scott E. , Waters Christopher M.
Published: February 2012

Restoration of the epithelial barrier following acute lung injury is critical for recovery of lung homeostasis. After injury, alveolar type II epithelial (ATII) cells spread and migrate to cover the denuded surface and, eventually, proliferate and differentiate into type I cells. The chemokine CXCL12, also known as stromal cell-derived factor 1α, has well-recognized roles in organogenesis, hematopoiesis, and immune responses through its binding to the chemokine receptor CXCR4. While CXCL12/CXCR4 signaling is known to be important in immune cell migration, the role of this chemokine-receptor interaction has not been studied in alveolar epithelial repair mechanisms. In this study, we demonstrated that secretion of CXCL12 was increased in the bronchoalveolar lavage of rats ventilated with an injurious tidal volume (25 ml/kg). We also found that CXCL12 secretion was increased by primary rat ATII cells and a mouse alveolar epithelial (MLE12) cell line following scratch wounding and that both types of cells express CXCR4. CXCL12 significantly increased ATII cell migration in a scratch-wound assay. When we treated cells with a specific antagonist for CXCR4, AMD-3100, cell migration was significantly inhibited. Knockdown of CXCR4 by short hairpin RNA (shRNA) caused decreased cell migration compared with cells expressing a nonspecific shRNA. Treatment with AMD-3100 decreased matrix metalloproteinase-14 expression, increased tissue inhibitor of metalloproteinase-3 expression, decreased matrix metalloproteinase-2 activity, and prevented CXCL12-induced Rac1 activation. Similar results were obtained with shRNA knockdown of CXCR4. These findings may help identify a therapeutic target for augmenting epithelial repair following acute lung injury.
Cadmium-mediated toxicity of lung epithelia is enhanced through NF-κB-mediated transcriptional activation of the human zinc transporter ZIP8
Authors: Napolitano Jessica R. , Liu Ming-Jie , Bao Shengying , Crawford Melissa , Nana-Sinkam Patrick , Cormet-Boyaka Estelle , Knoell Daren L.
Published: February 2012

Cadmium (Cd), a toxic heavy metal and carcinogen that is abundantly present in cigarette smoke, is a cause of smoking-induced lung disease. SLC39A8 (ZIP8), a zinc transporter, is a major portal for Cd uptake into cells. We have recently identified that ZIP8 expression is under the transcriptional control of the NF-κB pathway. On the basis of this, we hypothesized that cigarette-smoke induced inflammation would increase ZIP8 expression in lung epithelia, thereby enhancing Cd uptake and cell toxicity. Herein we report that ZIP8 is a central mediator of Cd-mediated toxicity. TNF-α treatment of primary human lung epithelia and A549 cells induced ZIP8 expression, resulting in significantly higher cell death attributable to both apoptosis and necrosis following Cd exposure. Inhibition of the NF-κB pathway and ZIP8 expression significantly reduced cell toxicity. Zinc (Zn), a known cytoprotectant, prevented Cd-mediated cell toxicity via ZIP8 uptake. Consistent with cell culture findings, a significant increase in ZIP8 mRNA and protein expression was observed in the lung of chronic smokers compared with nonsmokers. From these studies, we conclude that ZIP8 expression is induced in lung epithelia in an NF-κB-dependent manner, thereby resulting in increased cell death in the presence of Cd. From this we contend that ZIP8 plays a critical role at the interface between micronutrient (Zn) metabolism and toxic metal exposure (Cd) in the lung microenvironment following cigarette smoke exposure. Furthermore, dietary Zn intake, or a lack thereof, may be a contributing factor in smoking-induced lung disease.
Common Variation atBARD1Results in the Expression of an Oncogenic Isoform That Influences Neuroblastoma Susceptibility and Oncogenicity
Authors: Bosse Kristopher R. , Diskin Sharon J. , Cole Kristina A. , Wood Andrew C. , Schnepp Robert W. , Norris Geoffrey , Nguyen Le B. , Jagannathan Jayanti , Laquaglia Michael , Winter Cynthia , Diamond Maura , Hou Cuiping , Attiyeh Edward F. , Mosse Yael P. , Pineros Vanessa , Dizin Eva , Zhang Yongqiang , Asgharzadeh Shahab , Seeger Robert C. , Capasso Mario , Pawel Bruce R. , Devoto Marcella , Hakonarson Hakon , Rappaport Eric F. , Irminger-Finger Irmgard , Maris John M.
Published: February 2012

The mechanisms underlying genetic susceptibility at loci discovered by genome-wide association study (GWAS) approaches in human cancer remain largely undefined. In this study, we characterized the high-risk neuroblastoma association at the BRCA1-related locus, BARD1, showing that disease-associated variations correlate with increased expression of the oncogenically activated isoform, BARD1β. In neuroblastoma cells, silencing of BARD1β showed genotype-specific cytotoxic effects, including decreased substrate-adherence, anchorage-independence, and foci growth. In established murine fibroblasts, overexpression of BARD1β was sufficient for neoplastic transformation. BARD1β stabilized the Aurora family of kinases in neuroblastoma cells, suggesting both a mechanism for the observed effect and a potential therapeutic strategy. Together, our findings identify BARD1β as an oncogenic driver of high-risk neuroblastoma tumorigenesis, and more generally, they illustrate how robust GWAS signals offer genomic landmarks to identify molecular mechanisms involved in both tumor initiation and malignant progression. The interaction of BARD1β with the Aurora family of kinases lends strong support to the ongoing work to develop Aurora kinase inhibitors for clinically aggressive neuroblastoma. Cancer Res; 72(8); 2068–78. ©2012 AACR.
FGFR2 Isoforms Support Epithelial–Stromal Interactions in Thyroid Cancer Progression
Authors: Guo Miao , Liu Wei , Serra Stefano , Asa Sylvia L. , Ezzat Shereen
Published: February 2012

Alternate splicing yields two distinct isoforms of the fibroblast growth factor (FGF) receptor FGFR2-IIIb and FGFR2-IIIc varying their extracellular structure in human thyroid cancer, in which FGFR expression is commonly dysregulated. In this study, we characterized the function of these variants in modulating thyroid cancer behavior. Enforced expression of either FGFR2-IIIb or FGFR2-IIIc in thyroid epithelial cancer cells reduced expression of fibronectin, MAGE-A3 and MMP9, while increasing p21 and enhancing Rb dephosphorylation. Consistent with these tumor-suppressive properties, FGFR2-IIIb and FGFR2-IIIc each diminished invasive behavior in vitro and reduced tumor growth and metastasis in vivo. Notably, these effects contrasted with those produced by expression of these FGFR isoforms in fibroblasts, in which they both stimulated cell growth. Moreover, in xenograft tumors generated by coimplantation of epithelial and fibroblast cells expressing that same isoform, there was no significant effect on tumor progression. Conversely, FGFR2-IIIb expression in epithelial cells yielded higher FGF4/FGF7 expression that, in the presence of FGFR2-IIIc–expressing fibroblasts, enhanced tumor progression. Together, our findings highlight the importance of cellular context in assigning growth properties to growth factor receptor isoforms. More specifically, they show how alternative splicing of FGFR2 yields heteroisoforms critical to the growth-promoting actions of FGFs that exert distinct epithelial–stromal effects in thyroid cancer. Cancer Res; 72(8); 2017–27. ©2012 AACR.
Mesothelin-Targeted Agents in Clinical Trials and in Preclinical Development
Authors: Kelly Ronan J. , Sharon Elad , Pastan Ira , Hassan Raffit
Published: February 2012

Mesothelin is a tumor differentiation antigen that is highly expressed in several malignant diseases in humans, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. The limited expression of mesothelin on normal human tissues and its high expression in many common cancers make it an attractive candidate for cancer therapy. Several agents, including an immunotoxin, monoclonal antibody, antibody drug conjugate, and tumor vaccine, are in various stages of development to treat patients with mesothelin-expressing tumors. This review highlights ongoing clinical trials, as well as other approaches to exploit mesothelin for cancer therapy, that are in preclinical development. Mol Cancer Ther; 11(3); 517–25. ©2012 AACR.
Novel Therapies for Metastatic Renal Cell Carcinoma: Efforts to Expand beyond the VEGF/mTOR Signaling Paradigm
Authors: Pal Sumanta Kumar , Williams Stephen , Josephson David Y. , Carmichael Courtney , Vogelzang Nicholas J. , Quinn David I.
Published: February 2012

With six agents approved for metastatic renal cell carcinoma (mRCC) within the past 5 years, there has undoubtedly been progress in treating this disease. However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). The current review will focus on investigational agents that diverge from this paradigm. Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues. Mol Cancer Ther; 11(3); 526–37. ©2012 AACR.
The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center: A Unique Resource for Defining the “Molecular Histology” of the Breast
Authors: Sherman Mark E. , Figueroa Jonine D. , Henry Jill E. , Clare Susan E. , Rufenbarger Connie , Storniolo Anna Maria
Published: February 2012

“Molecular histology” of the breast may be conceptualized as encompassing the normative ranges of histologic structure and marker expression in normal breast tissues in relation to a woman's age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University (Indianapolis, IN) is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin-fixed, paraffin-embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank's website. Cancer Prev Res; 5(4); 528–35. ©2012 AACR.
Starting the Same . . . Finishing the Same? Race, Occupational Origins, and Mobility Into Managerial Positions
Authors: Wilson George
Published: February 2012

Data from the 1994-2001 waves of the Panel Study of Income Dynamics are used to examine the theory of “disparate occupational effects,” which maintains that among men there are race-specific incidence and determinants of intragenerational mobility from the same occupational origins into managerial positions. Findings support theory: Across both occupational origins considered, lower white collar and blue collar, the two minority groups considered, African Americans and Latinos—relative to Whites—are handicapped along both issues. Specifically, both minority groups suffer from a lower incidence of mobility into managerial slots and attain them in a more narrow and restrictive manner then Whites. Furthermore, the racial gap between Whites and minorities support a qualification to this general finding: Racial differences in the incidence and determinants are greater from those originating at blue collar than lower white collar slots. Implications of the findings for identifying racial inequality in the dynamics of mobility into management positions and advancing theoretical development in racial stratification are discussed.
Pentoxifylline Lowers Plasminogen Activator Inhibitor 1 Levels in Obese Individuals: A Pilot Study
Authors: Muldowney James A. S. , Chen Qingxia , Blakemore Dana L. , Vaughan Douglas E.
Published: February 2012

Plasminogen activator inhibitor 1 (PAI-1), the primary inhibitor of fibrinolysis and C-reactive protein (CRP), is a predictor of myocardial infarction. Both are upregulated by tumor necrosis factor-alpha (TNF-α) within the obese population. This pilot study tested the hypothesis that TNF-α blockade with pentoxifylline lowers PAI-1 and high-sensitivity CRP (hsCRP) in obese individuals. Twenty participants were treated with pentoxifylline for 8 weeks. A proportional odds model was used to compare the change in PAI-1 and CRP in the pentoxifylline and placebo groups. Plasminogen activator inhibitor 1, but not hsCRP levels, decreased over the 8-week period of the study ( P = .025 and P = NS). There was significant dropout of participants due to drug tolerability. These findings suggest that these markers of cardiovascular risk are differentially regulated in obesity and that PAI-1 levels can be reduced by pentoxifylline in this population.
Rural and Nonrural Differences in Providing Care for Children With Complex Chronic Conditions
Authors: Murphy Kelly L. , Kobayashi Daisuke , Golden Shannon L. , Nageswaran Savithri
Published: February 2012

To better understand the challenges faced by primary care providers in rural locations in providing care for children with complex chronic conditions (CCC), the authors conducted a cross-sectional survey of primary care providers (N = 132), including physicians, nurse practitioners, and physician assistants, in community settings in 6 counties in northwest North Carolina. Pediatric practices were significantly less likely to be located in rural areas. Practices in rural areas were more likely to be small, with fewer staff members (odds ratio [OR] = 7) and providers (OR = 15) compared with practices in nonrural areas. Additionally, nonrural practices were 3 times as likely as rural practices to have a larger clientele of children with CCC. A majority of primary care providers (77%) reported difficulty caring for children with CCC. Strategies for supporting primary care providers are needed to enable them to provide care for the growing number of children with CCC.
The Nature and Effects of Transformational School Leadership
Authors: Leithwood Kenneth , Sun Jingping
Published: February 2012

Background: Using meta-analytic review techniques, this study synthesized the results of 79 unpublished studies about the nature of transformational school leadership (TSL) and its impact on the school organization, teachers, and students. This corpus of research associates TSL with 11 specific leadership practices. These practices, as a whole, have moderate positive effects on a wide range of consequential school conditions. They also have moderately strong and positive effects on individual teachers’ internal states, followed by their influence on teacher behaviors and collective teachers’ internal states. TSL has small but significant positive effects on student achievement. Research Design: This synthesis of unpublished research results is accomplished by a systematic series of meta-correlations and is compared with the results of earlier systematic reviews of published TSL research. Findings: Among the conclusions arising from the study is that several of the most widely advocated models of effective educational leadership actually include many of the same practices. Conclusions: More attention by researchers, practitioners, and researchers needs to be devoted to the impact of specific leadership practices and less to leadership models.
Building a Network Administrative Organization’s Social Base
Authors: Hoflund A. Bryce
Published: February 2012

Networks are an increasingly common aspect of administrative life. One organization in health care, the National Quality Forum (NQF), is attempting to address issues of health care quality in a new way by bringing together organizations from the public and private sectors to discuss and debate measures of quality and, ultimately, to effect change. Little, however, is known about a network leader’s tasks during the creation of an organization like the NQF. The purpose of this article is to discuss and elaborate on one critical task, building a social base, that the NQF’s president and CEO engaged in during the NQF’s formative stages.
Endoscopic Nasoseptal Flap Repair of Skull Base Defects
Authors: Eloy Jean Anderson , Choudhry Osamah J. , Friedel Mark E. , Kuperan Arjuna B. , Liu James K.
Published: February 2012

Objective

We compared the incidence of postoperative cerebrospinal fluid (CSF) leaks in patients undergoing endoscopic skull base repair with a pedicled nasoseptal flap (PNSF) with or without the addition of a dural sealant.

Study Design and Setting

Retrospective analysis at a tertiary care medical center.

Methods

A retrospective analysis was performed at our tertiary care medical center on patients who underwent endoscopic repair of high‐flow CSF leaks using a PNSF between December 2008 and August 2011. Repair materials, incidence of postoperative CSF leaks, and demographic data were collected.

Results

Thirty‐two high‐flow CSF leaks were repaired with a PNSF alone without dural sealant (group A), and 42 were repaired with a PNSF with the addition of a dural sealant (group B). In group A, there were no postoperative CSF leaks (0%), whereas in group B, there was 1 delayed postoperative CSF leak, resulting in a 2.4% leak rate. The incidence of postoperative CSF leakage was not significantly different between the 2 groups (P =. 38). The overall postoperative CSF leak rate was 1.4%.

Conclusions

The use of dural sealants when performing endoscopic PNSF repair of high‐flow CSF leaks is not supported by our data. In addition, this practice may significantly increase surgical cost. We encountered no postoperative CSF leaks in patients with high‐flow CSF leaks treated with PNSF alone without dural sealants. Meticulous surgical technique and proper positioning of the PNSF seem to obviate the need for dural sealants during endoscopic skull base reconstruction of high‐flow CSF leaks.
Long‐Term Performance of Cochlear Implants in Postlingually Deafened Adults
Authors: Lenarz Minoo , Sönmez Hasibe , Joseph Gert , Büchner Andreas , Lenarz Thomas
Published: February 2012

Objective

To evaluate the stability of long‐term hearing performance after cochlear implantation (CI) in postlingually deafened adults and to explore the boundaries and limitations of the present test batteries for adult CI patients.

Study Design

Case series with chart review.

Setting

Tertiary referral center.

Subjects and Methods

A cohort of 1005 postlingually deafened adult cochlear implantees, who received their implants after age 18 years, was unilaterally implanted and had no inner ear malformations or cochlear ossification. Hearing performance with cochlear implant was evaluated with the help of 5 standard German speech tests.

Results

The average performance improved significantly during the first 6 months in all tests (learning phase) and afterward entered a plateau phase in which no statistically significant improvements or deteriorations were observed for more than 20 years of follow‐up. For each test, the average performance of the cohort, the ceiling effect, and the average results for high and low performers are presented.

Conclusions

In this study, postlingually deafened adults required about 6 months to learn how to process the artificial signals delivered by the cochlear implant. After this learning phase, the hearing performance entered a stable plateau phase for more than 20 years. This stability reveals the long‐term reliability of the technology and the biological stability of the electrode‐nerve interface over years. In this study, the authors also evaluated the “ceiling effect” with 5 standard German speech tests, used for evaluation of postlingually deafened adult CI patients.
The New Baha Implant
Authors: D’Eredità Riccardo , Caroncini Matteo , Saetti Roberto
Published: February 2012

Objectives

To assess stability of a new‐design titanium implant (Cochlear Baha BAI300) in bone‐anchored hearing aid (Baha) recipients over time.

Study Design and Setting

Prospective case series with planned data collection at a tertiary care institution. Twelve patients who underwent Baha surgery over 12 months were analyzed.

Subjects

All patients (3 children, age range 6‐10 years, mean 7.7 years, median 7.3 years; 9 adults, age range 34‐73 years, mean 52.8 years, median 48 years) underwent the 1‐stage procedure following the standard Brånemark technique. In all procedures, the single‐skin incision was applied.

Methods

The stability of the implant was measured with implant stability quotient (ISQ) measurement tests. All patients were tested at surgery and every week after for 1 year. Wound‐healing time, degree of soft tissue reactions around the abutment, and need for revision surgery were examined. Two‐tailed Student t test and χ2 for all comparisons were calculated; P <. 05 values were considered significant.

Results

The new implant showed a steep increase of ISQ values over the first 2 weeks and reached stable ISQ values 3 weeks after surgery. Complete skin healing time was obtained in 8 days on average (range, 7‐12 days; median 7.6 days). Neither implant extrusion nor skin revision surgery was observed in our patients during the first year of follow‐up.

Conclusions

This new implant revealed stability and fast integration. The data from the present study suggest the new implant may be suitable for early loading protocols.
Dreaming the ordinary
Authors: Staeheli Lynn A. , Ehrkamp Patricia , Leitner Helga , Nagel Caroline R.
Published: February 2012

This paper introduces the concept of ‘ordinary’ to analyze citizenship’s complexities. Ordinary is often taken to mean standard or routine, but it also invokes order and authority. Conceptualizing citizenship as ordinary trains our attention on the ways in which the spatiality of laws and social norms are entwined with daily life. The idea of ordinariness fuses legal structures, normative orders and the experiences of individuals, social groups and communities, making citizenship both a general category and a contingent resource for political life. We explore this argument using immigrants as an example, but the conceptualization of citizenship extends more broadly.
WIC Infant Food Package Issuance Data Are a Valid Measure of Infant Feeding Practices
Authors: Whaley Shannon E. , Koleilat Maria , Jiang Lu
Published: February 2012

Background: Multiple datasets collect breastfeeding data in the United States (US), but a coordinated monitoring and surveillance system does not currently exist. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) reaches over 50% of all infants in the US and provides a potential wealth of administrative data about the breastfeeding practices of low-income women.

Objective: The objective of this research was to assess whether WIC administrative data are a valid source of information about breastfeeding practices.

Methods: A phone survey of 2015 postpartum WIC mothers in Southern California was conducted to assess the feeding practices of mothers with infants 2-12 months old. Survey data were linked with WIC administrative records from the same month in order to assess the percent agreement between feeding behavior as reported by survey methods and as documented in WIC administrative records.

Results: The unweighted κ test statistic was used to test the agreement between survey responses and WIC administrative data. Substantial to almost perfect agreement was found between the two measures.

Conclusions: WIC administrative data are a valid source of information about breastfeeding. With appropriate funding support, WIC administrative data should be considered for use in nationwide breastfeeding surveillance and monitoring systems.
The Cost of Collaboration
Authors: Minson Julia A. , Mueller Jennifer S.
Published: February 2012

Prior investigators have asserted that certain group characteristics cause group members to disregard outside information and that this behavior leads to diminished performance. We demonstrate that the very process of making a judgment collaboratively rather than individually also contributes to such myopic underweighting of external viewpoints. Dyad members exposed to numerical judgments made by peers gave significantly less weight to those judgments than did individuals working alone. This difference in willingness to use peer input was mediated by the greater confidence that the dyad members reported in the accuracy of their own estimates. Furthermore, dyads were no better at judging the relative accuracy of their own estimates and the advisor’s estimates than individuals were. Our analyses demonstrate that, relative to individuals, dyads suffered an accuracy cost. Specifically, if dyad members had given as much weight to peer input as individuals working alone did, then their revised estimates would have been significantly more accurate.
Library subject guides: A case study of evidence-informed library development
Authors: Wakeham Maurice , Roberts Angharad , Shelley Jane , Wells Paul
Published: February 2012

This paper describes the process whereby a university library investigated the value of its subject guides to its users. A literature review and surveys of library staff, library users and other libraries were carried out. Existing library subject guides and those of other higher education libraries were evaluated. The project team reported regularly to the wider library team throughout the year long investigation and made recommendations. The project served to develop the professional skills of the project team, to expand the knowledge of the wider library team and encouraged new ways of thinking about guide provision to users.
Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort
Authors: Willis R , Seif AM , McGwin G , Martinez-Martinez LA , González EB , Dang N , Papalardo E , Liu J , Vilá LM , Reveille JD , Alarcón GS , Pierangeli SS
Published: February 2012

Objective: We sought to determine the effect of hydroxychloroquine therapy on the levels proinflammatory/prothrombotic markers and disease activity scores in patients with systemic lupus erythematosus (SLE) in a multiethnic, multi-center cohort (LUMINA). Methods: Plasma/serum samples from SLE patients ( n = 35) were evaluated at baseline and after hydroxychloroquine treatment. Disease activity was assessed using SLAM-R scores. Interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, inducible protein (IP)-10, monocyte chemotactic protein-1, tumor necrosis factor (TNF)-α and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Anticardiolipin antibodies were evaluated using ELISA assays. Thirty-two frequency-matched plasma/serum samples from healthy donors were used as controls. Results: Levels of IL-6, IP-10, sCD40L, IFN-α and TNF-α were significantly elevated in SLE patients versus controls. There was a positive but moderate correlation between SLAM-R scores at baseline and levels of IFN-α ( p = 0.0546). Hydroxychloroquine therapy resulted in a significant decrease in SLAM-R scores ( p = 0.0157), and the decrease in SLAM-R after hydroxychloroquine therapy strongly correlated with decreases in IFN-α ( p = 0.0087). Conclusions: Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE.
Symptoms of Depression Depend on Rigid Parenting Attitudes, Gender, and Race in an At-Risk Sample of Early Adolescents
Authors: Weed Keri , Morales Dawn A. , Harjes Rachel
Published: February 2012

Trajectories of depressive symptoms were compared between European American and African American boys and girls from ages 8 to 14 in a longitudinal sample of 130 children born to adolescent mothers. Mixed-effects regression modeling was used to analyze individual and group differences in level of depressive symptoms and their changes over time. Time-varying predictors included rigid parenting attitudes, maternal depression, and maternal educational attainment. African American boys reported more symptoms of depression at age 8 than African American girls or European American boys or girls. Symptoms of depression increased over time only for European American girls. Rigid parenting attitudes, but not maternal depression or maternal educational attainment, were associated with children’s depressive symptoms. Results substantiate the importance of differentiating groups by gender and race in conceptual models of depression.
The Incremental Utility of Behavioral Rating Scales and a Structured Diagnostic Interview in the Assessment of Attention-Deficit/Hyperactivity Disorder
Authors: Vaughn Aaron J. , Hoza Betsy
Published: February 2012

The current study examined the incremental utility of rating scales, a structured diagnostic interview, and multiple informants in a comprehensive assessment of attention-deficit/hyperactivity disorder (ADHD). The sample included 185 children with ADHD ( Mage = 9.22, SD = 0.95) and 82 children without ADHD ( Mage = 9.24, SD = 0.88). Logistic regressions were used to examine the incremental contribution of each method within an assessment of ADHD. Results indicated that information collected from a structured diagnostic interview was unable to significantly improve a prediction model including parent and teacher ratings (Block χ2 = 0.91, ρ = .64). Teacher ratings on symptom-based scales resulted in significant model improvement beyond parent ratings alone (Block χ2 = 48.47, ρ < .001). Exploratory analyses indicated that using behavioral rating scales correctly classified all participants by diagnosis. Clinical implications are highlighted, and future research directions are discussed.
Treatment Response to an Intensive Summer Treatment Program for Adolescents With ADHD
Authors: Sibley Margaret H. , Smith Bradley H. , Evans Steven W. , Pelham William E. , Gnagy Elizabeth M.
Published: February 2012

Objective:

There are presently almost no empirically validated treatments for adolescents with ADHD. However, in childhood, behavioral treatments for ADHD typically include behavioral parent training, classroom interventions, and intensive child-directed interventions.

Method:

The present investigation examines treatment gains following an 8-week intensive summer day treatment program for adolescents with ADHD (STP-A). Baseline measures of functioning and parent improvement ratings were obtained for 34 STP-A participants.

Results:

Parent ratings indicated that adolescents who attended the STP-A improved across all target domains. Across domains, 63.0% to 90.9% of adolescents improved during the STP-A. There was no evidence of iatrogenic effects during the STP-A. Correlates of treatment response included adolescent effort, oppositional-defiant behavior, and cognitive/scholastic functioning.

Conclusion:

Findings are discussed with regard to effective treatment delivery for adolescents with ADHD.
Muslims and the Left: An English case study
Authors: Glynn Sarah
Published: February 2012

In fighting alongside those whom society has oppressed, Socialists have often found themselves shoulder to shoulder with Muslims, but British Left groups have recruited relatively few Muslim members. Then, with the formation of the Respect Coalition, Leftists and Muslims appeared to have tied the knot. This article examines the nature and limitations of this coalition through an exploration of wider ideological relationships between Islam and the Left. It argues that the coalition was based on a fundamental misconception that it would be possible to combine two different ways of understanding the world, with the result that Respect was ideologically stillborn. It could never have built up a genuine political base, leaving it to rely on opportunism.
Working in the Classroom
Authors: Lundblom Erin E. G. , Woods Juliann J.
Published: February 2012

Idioms occur frequently in classroom language. Students with literacy or language weaknesses are often challenged by idioms; therefore, the failure to comprehend idioms can impact academic performance. Four 7th-grade female students (mean age: 12 years, 6 months) participated in a multiple baseline single subject study during their general education intensive reading class. Three sets of idioms were taught to examine the effects of classwide peer tutoring (CWPT) intervention on idiom comprehension. Following implementation of CWPT, comprehension of most idiomatic phrases increased and remained largely stable as indicated through visual analysis. Teaching idioms with CWPT was flexible, effective, and time-efficient in a general education classroom setting. Speech language pathologists collaborating with educators should provide evidence-based interventions as guided by educational standards and curriculum. Response to intervention provides a framework to implement a classroom intervention for all students to facilitate idiom understanding.
Scaffolded-Language Intervention
Authors: Bellon-Harn Monica L. , Credeur-Pampolina Maggie E. , LeBoeuf Lexie
Published: February 2012

This study investigated the effects of a scaffolded-language intervention using cloze procedures, semantically contingent expansions, contrastive word pairs, and direct models on speech abilities in two preschoolers with speech and language impairment speaking African American English. Effects of the lexical and phonological characteristics (i.e., word frequency, neighborhood density, and phonotactic probability) of contrastive word pairs and direct models on speech production accuracy were examined. Speech outcomes support the application of a scaffolded-language intervention with children with speech and language impairment. Results lend support to the assertion that fundamental intervention principles are applicable regardless of native dialect. Effects of word frequency, neighborhood density, and phonotactic probability clarified their role within the scaffolded-language intervention.
Applying Modern Robotics Technologies to Demand Prediction and Production Management in the Quick-Service Restaurant Sector
Authors: Noone Breffni M. , Coulter R. Craig
Published: February 2012

Given the twin objectives of ensuring consistent quality and controlling costs, quick-service restaurants have been in the forefront of automating their operations whenever possible. This article explores a novel approach to achieving these two objectives by using modern robotics technologies to improve operations. Instead of applying robotics technology for direct labor replacement, robotics can augment workers’ cognitive capacity. This alternative application of robotics technologies encompasses two key components: (1) robotic sensing for demand prediction and (2) robotic planning for production management. Using the example of Zaxby’s Franchising Inc., this article explains the improvements possible with modern robotics technologies and the challenges of implementing it. Unusual for quick-service, Zaxby’s uses a fresh, cook-to-order concept, which resulted in backlogs during busy times. Zaxby’s robotics application substantially reduced both service times and food waste. The system tracks customer arrivals, starts the cooking process as customers arrive, and then gives employees specific directions to expedite cooking and service, so that wait times have been reduced. Developing the algorithms needed for robotic systems gives corporate operators the opportunity to analyze their operating systems, resolve inconsistencies, and provide for clear performance assessment.
Natural killer cell degranulation capacity predicts early onset of the immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients with tuberculosis
Authors: Pean Polidy , Nerrienet Eric , Madec Yoann , Borand Laurence , Laureillard Didier , Fernandez Marcelo , Marcy Olivier , Sarin Chan , Phon Kerya , Taylor Sylvia , Pancino Gianfranco , Barré-Sinoussi Françoise , Scott-Algara Daniel
Published: February 2012

Immune reconstitution inflammatory syndrome (IRIS) is a common and potentially serious complication occurring in HIV-infected patients being treated for tuberculosis (TB) using combined antiretroviral treatment. A role of adaptive immunity has been suggested in the onset of IRIS, whereas the role of natural killer (NK) cells has not yet been explored. The present study sought to examine the involvement of NK cells in the onset of IRIS in HIV-infected patients with TB and to identify predictive markers of IRIS. A total of 128 HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretroviral Drugs (CAMELIA) trial were enrolled in Cambodia. Thirty-seven of the 128 patients developed IRIS. At inclusion, patients had low CD4 cell counts (27 cells/mm3) and high plasma viral load (5.76 and 5.50 log/mL in IRIS and non-IRIS patients, respectively). At baseline, NK-cell degranulation capacity was significantly higher in IRIS patients than in non-IRIS patients (9.6% vs 6.38%, P < .005). At IRIS onset, degranulation capacity did not differ between patients, whereas activating receptor expression was lower in IRIS patients. Patients with degranulation levels > 10.84% had a higher risk of IRIS (P = .002 by log-rank test). Degranulation level at baseline was the most important IRIS predictor (hazard ratio = 4.41; 95% confidence interval, 1.60-12.16). We conclude that NK-degranulation levels identify higher IRIS risk in HIV-infected patients with TB.