bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR423-5p As a Circulating Biomarker for Heart Failure
Authors: Tijsen Anke J. , Creemers Esther E. , Moerland Perry D. , de Windt Leon J. , van der Wal Allard C. , Kok Wouter E. , Pinto Yigal M.
Published: February 2010

Rationale
:

Aberrant expression profiles of circulating microRNAs (miRNAs) have been described in various diseases and provide high sensitivity and specificity. We explored circulating miRNAs as potential biomarkers in patients with heart failure (HF).

Objective
:

The goal of this study was to determine whether miRNAs allow to distinguish clinical HF not only from healthy controls but also from non-HF forms of dyspnea.

Methods and Results
:

A miRNA array was performed on plasma of 12 healthy controls and 12 HF patients. From this array, we selected 16 miRNAs for a second clinical study in 39 healthy controls and in 50 cases with reports of dyspnea, of whom 30 were diagnosed with HF and 20 were diagnosed with dyspnea attributable to non–HF-related causes. This revealed that miR423-5p was specifically enriched in blood of HF cases and receiver-operator-characteristics (ROC) curve analysis showed miR423-5p to be a diagnostic predictor of HF, with an area under the curve of 0.91 (
P
<0.001). Five other miRNAs were elevated in HF cases but also slightly increased in non-HF dyspnea cases.

Conclusion
:

We identify 6 miRNAs that are elevated in patients with HF, among which miR423-5p is most strongly related to the clinical diagnosis of HF. These 6 circulating miRNAs provide attractive candidates as putative biomarkers for HF.
Carotid Artery Stenting in Octogenarians
Authors: Chaturvedi Seemant , Matsumura Jon S. , Gray William , Xu Chuanbo , Verta Patrick
Published: February 2010

Background and Purpose—

Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events (CAPTURE 2) is an ongoing prospective, nonrandomized, multicenter clinical trial enrolling patients undergoing carotid artery stenting. The aim of this analysis is to identify risk predictors for periprocedural stroke in patients ≥80 years old.

Methods—

Symptomatic patients with ≥50% stenosis and asymptomatic patients with ≥80% stenosis were enrolled. Patients’ neurological status was assessed by an independent neurologist before as well as 24 hours and 30 days postprocedure. All strokes and suspected strokes were adjudicated by an independent committee. Logistic regression analysis was conducted to identify baseline demographic, lesion, procedural, or comorbidity parameters associated with outcomes in patients ≥80 years of age.

Results—

As of January 10, 2009, 5297 patients underwent carotid artery stenting in 186 US CAPTURE 2 clinical centers and 1166 were ≥80 years old. Octogenarians were similar to nonoctogenarians in terms of gender and symptomatic status but had fewer of certain risk factors (prior myocardial infarction or carotid endarterectomy, diabetes, smoking history) and more cardiac arrhythmia and renal insufficiency. For the overall cohort, death/stroke rate was 3.3%; stroke rate was 2.7% (0.8% major, 1.9% minor). Death/stroke rates were significantly higher for octogenarians than nonoctogenarians (4.5% versus 3.0%) as were stroke rates (3.8% versus 2.4%). Symptomatic status, embolic protection device dwell time, and lesion length were risk predictors for periprocedural stroke in octogenarians.

Conclusions—

Patients ≥80 years old have higher periprocedural event rates than nonoctogenarians. Age, symptomatic status, and lesion length should be considered when identifying appropriate candidates for the procedure.
Systematic Review and Pooled Analysis of Published and Unpublished Validations of the ABCD and ABCD2 Transient Ischemic Attack Risk Scores
Authors: Giles Matthew F. , Rothwell Peter M.
Published: February 2010

Background and Purpose—

The ABCD system was derived to predict early risk of stroke after transient ischemic attack. Independent validations have reported conflicting results. We therefore systematically reviewed published and unpublished data to determine predictive value and generalizability to different clinical settings and users.

Methods—

Validations of the ABCD and ABCD2 scores were identified by searching electronic databases, reference lists, relevant journals, and conference abstracts. Unpublished tabulated data were obtained where available. Predictive value, expressed as pooled areas under the receiver operator characteristic curves (AUC), was calculated using random-effects meta-analysis, and analyses for heterogeneity were performed by categorization according to study setting and method.

Results—

Twenty cohorts were identified reporting the performance of the ABCD system in 9808 subjects with 456 strokes at 7 days. Among the 16 studies of both the ABCD and ABCD2 scores, pooled AUC for the prediction of stroke at 7 days were 0.72 (0.66 to 0.78) and 0.72 (0.63 to 0.82), respectively (
P
diff=0.97). The pooled AUC for the ABCD and ABCD2 scores in all cohorts reporting relevant data were 0.72 (0.67 to 0.77) and 0.72 (0.63 to 0.80), respectively (both
P
<0.001). Predictive value varied significantly between studies (
P
<0.001), but 75% of the variance was accounted for by study method and setting, with the highest pooled AUC for face-to-face clinical evaluation and the lowest for retrospective extraction of data from emergency department records.

Conclusion—

Independent validations of the ABCD system showed good predictive value, with the exception of studies based on retrospective extraction of nonsystematically collected data from emergency department records.
Oxidative Stress After Thrombolysis-Induced Reperfusion in Human Stroke
Authors: Domínguez Carmen , Delgado Pilar , Vilches Angel , Martín-Gallán Pilar , Ribó Marc , Santamarina Estevo , Molina Carlos , Corbeto Natalia , Rodríguez-Sureda Victor , Rosell Anna , Alvarez-Sabín Jose , Montaner Joan
Published: February 2010

Background and Purpose—

Animal models of transient ischemia suggest that oxygen-derived free radicals produced on reperfusion of ischemic brain could constitute the main cause of reperfusion injury. We aimed to determine the presence and role of lipid peroxidation and protein oxidation-related molecules after tissue plasminogen activator-induced recanalization in human stroke.

Methods—

A total of 160 patients with strokes involving the middle cerebral artery and treated with tissue plasminogen activator and 60 healthy controls were included. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale scores were obtained at baseline (pretreatment), 1 hour and 2 hours after tissue plasminogen activator bolus, and 12 hours and 24 hours after stroke onset. The main lipid peroxidation end-product malondialdehyde, advanced oxidation protein products, and plasma concentrations of myeloperoxidase were assessed.

Results—

At baseline, all oxidative stress biomarkers were higher than in control subjects (
P
<0.01 for all comparisons). Malondialdehyde remained high compared with controls during the study period, whereas myeloperoxidase concentrations were significantly raised at baseline, 1 hour after tissue plasminogen activator administration, and 12 hours after stroke onset. Malondialdehyde concentrations correlated with stroke severity and were associated with outcome and with hemorrhagic complications. Regarding recanalization, among those patients with middle cerebral artery recanalization by the end of tissue plasminogen activator infusion (44%) or anytime thereafter, no peaking of any of the studied molecules could be identified.

Conclusions—

Our study showed that systemic oxidative damage to lipids and proteins had already occurred at baseline in stroke. In contrast to animal studies, a relationship between free radical-mediated oxidative damage to lipids or proteins and reperfusion injury after arterial recanalization could not be established.
Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke
Authors: Haley E. Clarke , Thompson John L.P. , Grotta James C. , Lyden Patrick D. , Hemmen Thomas G. , Brown Devin L. , Fanale Christopher , Libman Richard , Kwiatkowski Thomas G. , Llinas Rafael H. , Levine Steven R. , Johnston Karen C. , Buchsbaum; Richard , Levy Gilberto , Levin Bruce
Published: February 2010

Background and Purpose—

Intravenous alteplase (rtPA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to (1) choose a best dose of tenecteplase to carry forward; and (2) to provide evidence for either promise or futility of further testing of tenecteplase versus rtPA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rtPA.

Methods—

The trial began as a small, multicenter, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rtPA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24-hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rtPA could be compared by 3-month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III.

Results—

The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4-mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3-month outcomes between the remaining tenecteplase groups and rtPA. Symptomatic intracranial hemorrhage rates were highest in the discarded 0.4-mg/kg tenecteplase group and lowest (0 of 31) in the 0.1-mg/kg tenecteplase group. Neither promise nor futility could be established.

Conclusion—

This prematurely terminated trial has demonstrated the potential efficiency of a novel design in selecting a propitious dose for future study of a new thrombolytic agent for acute stroke. Given the truncation of the trial, no convincing conclusions can be made about the promise of future study of tenecteplase in acute stroke.
Renin Angiotensin System Gene Polymorphisms and Cerebral Blood Flow Regulation
Authors: Hajjar Ihab , Sorond Farzaneh , Hsu Yi-Hsiang , Galica Andrew , Cupples L. Adrienne , Lipsitz Lewis A.
Published: February 2010

Background and Purpose—

Our objective was to investigate the associations between polymorphisms in representative genes of the renin angiotensin system with measures of cerebral blood flow regulation in older adults.

Methods—

Participants in this analysis were white subjects (n=335) in the MOBILIZE Boston study (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston), an observational study of community-dwelling elders who underwent transcranial Doppler while sitting and standing and during hypercapnea and hypocapnea. Autoregulation phenotype was the change in cerebrovascular resistance from sit to stand. Vasoreactivity phenotype was the slope of the change in cerebrovascular conductance versus change in end-tidal CO
2
. A total of 33 tagged single nucleotide polymorphisms were selected in the angiotensinogen gene, the angiotensin converting enzyme gene, and the angiotensin receptor gene. Regression analyses adjusted for age, gender, body mass index, mean arterial blood pressure, stroke, and use of antihypertensives were conducted for each single nucleotide polymorphism and outcome. Bonferroni corrections were used to adjust
P
values for multiple testing.

Results—

In the angiotensinogen gene, only the rs699 single nucleotide polymorphism was associated with vasoreactivity after Bonferroni correction (
P
=0.00028). Homozygous carriers of the CC genotype of this single nucleotide polymorphism had lower vasoreactivity compared with the CT or TT genotypes. There were no significant associations with autoregulation measures. None of the single nucleotide polymorphisms in the other genes were associated with our phenotypes.

Conclusion—

This analysis suggests that the angiotensinogen gene may be involved in vasoreactivity independent of blood pressure. Larger studies are needed to confirm the role of this gene in cerebrovascular health and aging.
Extreme Summer Convection in South America
Authors: Romatschke Ulrike , Houze Robert A.
Published: February 2010

Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) and National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis data are used to indicate mechanisms responsible for extreme summer convection over South America. The three-dimensional reflectivity field is analyzed to define three types of extreme echo, deep convective cores, wide convective cores, and broad stratiform regions. The location and timing of these echoes are sensitive to midlatitude synoptic disturbances crossing the Andes. At the leading edges of these disturbances the nocturnal South American low-level jet (SALLJ) transports moisture along the eastern edge of the Andes from the tropical to the subtropical part of the continent. Where the SALLJ rises over lower but steep mountains on the east side of the southern central Andes, deep and wide convective cores are triggered in the evening. When the SALLJ withdraws to the north as the disturbance passes, nocturnal triggering occurs in the northeastern foothills of the central Andes. Extreme convection over the Amazon basin takes the form of broad stratiform regions that evolve from systems with wide convective cores moving into the center of the region from both the southwest and northeast. The systems from the northeast form at the northeast coast and are likely squall lines. Along the coast of the Brazilian Highlands, diurnal/topographic forcing leads to daytime maxima of deep convective cores followed a few hours later by wide convective cores. Wide convective cores and broad stratiform regions form in the South Atlantic convergence zone (SACZ) with a diurnal cycle related to continental heating.
Impacts of Polarimetric Radar Observations on Hydrologic Simulation
Authors: Gourley Jonathan J. , Giangrande Scott E. , Hong Yang , Flamig Zachary L. , Schuur Terry , Vrugt Jasper A.
Published: February 2010

Rainfall estimated from the polarimetric prototype of the Weather Surveillance Radar-1988 Doppler [WSR-88D (KOUN)] was evaluated using a dense Micronet rain gauge network for nine events on the Ft. Cobb research watershed in Oklahoma. The operation of KOUN and its upgrade to dual polarization was completed by the National Severe Storms Laboratory. Storm events included an extreme rainfall case from Tropical Storm Erin that had a 100-yr return interval. Comparisons with collocated Micronet rain gauge measurements indicated all six rainfall algorithms that used polarimetric observations had lower root-mean-squared errors and higher Pearson correlation coefficients than the conventional algorithm that used reflectivity factor alone when considering all events combined. The reflectivity based relation R(Z) was the least biased with an event-combined normalized bias of −9%. The bias for R(Z), however, was found to vary significantly from case to case and as a function of rainfall intensity. This variability was attributed to different drop size distributions (DSDs) and the presence of hail. The synthetic polarimetric algorithm R(syn) had a large normalized bias of −31%, but this bias was found to be stationary.

To evaluate whether polarimetric radar observations improve discharge simulation, recent advances in Markov Chain Monte Carlo simulation using the Hydrology Laboratory Research Distributed Hydrologic Model (HL-RDHM) were used. This Bayesian approach infers the posterior probability density function of model parameters and output predictions, which allows us to quantify HL-RDHM uncertainty. Hydrologic simulations were compared to observed streamflow and also to simulations forced by rain gauge inputs. The hydrologic evaluation indicated that all polarimetric rainfall estimators outperformed the conventional R(Z) algorithm, but only after their long-term biases were identified and corrected.
Microbiology of Acute Otitis Media, Puget Sound Region, 2005-2009
Authors: Grubb Mark S. , Spaugh David C.
Published: February 2010

This review of electronic patient records was conducted to identify trends in acute otitis media (AOM) microbiology in the Puget Sound region. Culture results from tympanocentesis procedures performed between July 1, 2005 and June 30, 2009 were compiled into 4 respiratory disease seasons: 2005-2006, 2006-2007, 2007-2008, 2008-2009. Heptavalent pneumococcal conjugate vaccination coverage within the cohort was 85%; average patient age was 13 months (SD = 6.6). The proportion of AOM isolates positive for Streptococcus pneumoniae for the four periods covered was 48%, 41%, 35%, and 54%, respectively (P = 0.185, 3rd to 4th season). For Haemophilus influenzae, the proportions were 42%, 41%, 59%, and 38%, respectively (P = 0.182, 3rd to 4th season). Penicillin resistance among S pneumoniae isolates increased from 13% to 61% across the study period (P = 0.016). S pneumoniae may be regaining prevalence as an otopathogen in PCV7-vaccinated populations, and levels of penicillin resistance are increasing.
A Note on Reinforcement of Polymer Matrix Composites Using Carbon Residues Derived From Woody Biomass
Authors: Pries Malte , Militz Holger , Goodell Barry , Xinfeng Xie  , Yuhui Qian  , Peterson Michael , Lopez-Anido Roberto
Published: February 2010

The mechanical properties of phenolic resin reinforced with three different carbon materials were investigated experimentally. The carbon materials: (1) commercially produced carbon nanotubes (CNTs), (2) flash-heated lignocellulose containing CNTs and carbon-black, and (3) cyclically oxidized lignocellulose (Goodell, B. et al. (2008). Journal of Nanoscience and Nanotechnology, 8: 2472-2474) were added to phenolic resin in different weight percentages to fabricate composites. Carbon nanotubes were found to be an effective reinforcing filler increasing tensile strength by 45.34% and Young’s modulus by 19.08% with a 2% loading. The flash-heated material increased Young’s modulus by 11.04% with a 2% loading but did not affect tensile strength. The cyclically heated material did not contain CNTs, their inclusion in the composites reduced Young’s modulus and, for the 1% loading, reduced tensile strength as well.
Transverse Failure Behavior of Fiber-epoxy Systems
Authors: Cid Alfaro M.V. , Suiker A.S.J. , De Borst R.
Published: February 2010

The transverse failure response of unidirectional fiber-epoxy systems is studied by means of finite element simulations. An interface damage model is used for modeling fiber debonding and epoxy cracking. The convergence of the numerical results upon mesh refinement is analyzed. It is found that the failure response depends on the relative strength and relative toughness of the fiber-epoxy interface and the epoxy matrix. The tensile failure response of epoxy systems containing multiple fibers is also analyzed. In addition, the simulations demonstrate the influence on the failure response by the relative strength of the fiber-epoxy interface and the epoxy matrix, and by the fiber volume fraction and fiber distribution. The simulated fracture patterns are shown to be in good agreement with experimental observations reported in the literature.
Characterization and Spark Plasma Sintering of Mechanically Milled Aluminum-Carbon Nanotube (CNT) Composite Powders
Authors: Morsi K. , Esawi A.M.K. , Borah P. , Lanka S. , Sayed A.
Published: February 2010

Carbon nanotube (CNT) reinforced metallic composites have been recently gaining a significant amount of scientific interest. The promise of transmitting part of the remarkable and outstanding properties of CNTs to metals has spurred efforts to design and manufacture metallic composites reinforced with CNTs. Out of the metallic matrices investigated, Al has received significant attention. The stability of these powders at high temperatures is important to investigate, since they would ultimately be consolidated at elevated temperatures into useful products, and service temperature limits will be important. In this article, we discuss the detailed characterization of SPEX milled Al-CNT powders (well-dispersed CNTs in an Al matrix at 2.5 and 5.0 wt% loading), their heat treatment and consolidation using spark plasma sintering.
Proactively Addressing the Shortage of Blacks in Psychology: Highlighting the School Psychology Subfield
Authors: Chandler Daphne R.
Published: February 2010

To circumvent the disproportionately low number of persons of African descent in psychology, this study offers strategies for recruiting and retaining Black students and professionals. Data for this study were collected from 44 Black students and 3 Black faculty. Participants responded to questions that inquired about their perspectives regarding (a) effective recruitment and retention strategies, (b) being the vast minority in school/work settings, and (c) counselor race-ethnicity. Data were analyzed using the grounded theory constant comparative analysis approach. This study contributes to all psychology fields in at least two ways: first in its presentation of innovative strategies that have the potential to enhance racial-ethnic diversity in psychology and second in its presentation of insights that may improve the mental and behavioral health services provided to diverse people. While the need for greater diversity is highlighted for the school psychology subfield, it is noted that psychology in general is in need. Additionally, though the study pays greater attention to student concerns, all the findings also factor into postgraduate life. Recommendations for future research are offered.
Drug-Induced QTc-Interval Prolongation in the Intensive Care Unit: Incidence and Predictors
Authors: Ng Tien M. H. , Olsen Keith M. , McCartan Megan A. , Puumala Susan E. , Speidel Katie M. , Miller Melissa A. , Sears Tom D.
Published: February 2010

There is a paucity of information regarding QTc prolongation in critically ill patients. A prospective observational study was conducted to assess the incidence and predictors of QTc prolongation associated with medications in intensive care unit (ICU) patients. Consecutive adult patients prescribed prespecified QTc-prolonging medications were assessed for development of the combined incidence of QTc >500 ms at anytime and QTc increase >60 ms above baseline. Over 3 months, 200 consecutive patients (63 ± 18 years; 52% female; 73% Caucasian; baseline QTc 447.3 ± 51.5 ms) were evaluated. The primary end point occurred in 48% of the patients (QTc >500 ms 40%, QTc increase >60 ms 29%). The majority of patients experienced a QTc >470 or 450 ms (60.5%). Mean increase in QTc at 48 hours was 20 ± 35 ms. Upon multivariate analysis, length of stay [odds ratio 1.30, 95% confidence interval (1.15, 1.47)] and baseline QTc [1.01 (1.01, 1.02)] were associated with an increased risk for the primary end point, while beta-blockers [0.41 (0.20, 0.81)] were associated with a risk reduction. In conclusion, increased risk of proarrhythmia, as assessed by QTc prolongation, occurs in the majority of ICU patients when prescribed medications with electrophysiologic properties. Increased vigilance is warranted. The possible protective effect of beta-blockers requires confirmation.
Continuing Education: Alternative Approaches to Optimizing Antimicrobial Pharmacodynamics in Critically Ill Patients
Authors: Winterboer Tammy M. , Lecci Kassandra A. , Olsen Keith M.
Published: February 2010

Critical illness results in a constellation of physiologic changes that subsequently impact antibiotic pharmacokinetic and pharmacodynamic parameters. These changes can result in poorly treated infections that in turn lead to longer intensive care unit (ICU) and hospital stays, prolonged use of mechanical ventilation, and higher mortality rates. Research has expanded our understanding of antibiotic pharmacodynamics among ICU patients, and some investigators and clinicians have questioned traditional antibiotic dosing schemes among this population. Alternative dosing strategies to optimize antibiotic pharmacodynamics of aminoglycosides, beta-lactams, fluoroquinolones, and vancomycin have been explored. Appropriate duration of exposure to beta-lactam antibiotics has been recognized as an important parameter associated with successful treatment outcomes. To maximize this exposure, continuous infusions over a 24-hour period have resulted in higher clinical response rates and improved surrogate markers of infection. Equally as promising is the alternative of extending the infusion time to increase exposure while maintaining the same daily beta-lactam dose and frequency. Data from clinical trials have suggested that the area under the concentration–time curve to minimum inhibitory concentration ratio for aminoglycosides, fluoroquinolones, and vancomycin is a better correlate for successful treatment outcomes. Optimizing antibiotic pharmacodynamics by changing dosage methods should be considered in ICU patients to improve treatment response and success.
Invasive Candidiasis and the Utility of Antifungal Susceptibility Testing in the ICU
Authors: Coyle Elizabeth A.
Published: February 2010

Invasive fungal infections are a major cause of health care–associated morbidity and mortality in the ICU. In particular, Candida spp. are among one of the leading causes of bloodstream infections and sepsis. Advances in antifungal therapy in the last decade have led to many more options in the treatment of fungal infections, yet increasing resistance and clinical failures are common, especially in the management of invasive candidiasis in the ICU. Prompt diagnosis of these infections and appropriate antifungal treatment are imperative for improving survival. Although reliable antifungal susceptibility testing is available to aid in the therapy of fungal infections, testing is not always recommended. This review addresses the epidemiology of Candida infections in the ICU, antifungal resistance, therapy, and the usefulness of antifungal susceptibility testing in the ICU setting.
Antimicrobial Stewardship in the Intensive Care Unit: A Focus on Potential Pitfalls
Authors: Njoku Jessica C. , Hermsen Elizabeth D.
Published: February 2010

Patients in the intensive care unit (ICU) have many risk factors for resistant pathogens such as prolonged length of stay, frequent and broad-spectrum antimicrobial therapy, presence of foreign materials, and proximity with other patients. However, of the risk factors associated with acquisition of resistant pathogens, inappropriate use of antimicrobial agents has been the most implicated. Thus, many health care institutions have adopted antimicrobial stewardship programs (ASPs) as a mechanism to ensure more appropriate antimicrobial use. ASPs can have a significant impact in the ICU, leading to improved antimicrobial use and resistance patterns and decreased infection rates and costs, due to the inherent nature of infections encountered and high and often inappropriate antibiotic utilization in this setting. However, certain challenges exist for ASPs in the ICU including issues with infrastructure and personnel, information technology, the core ASP strategy, patient-specific factors, conversion of intravenous to oral therapy, and dose optimization. The combination of comprehensive infection control (IC) and effective antimicrobial stewardship can prevent the emergence of resistance among microorganisms and may decrease the negative consequences associated with antimicrobial misuse.
Assessment and Management of Fatigue in Neuromuscular Disease
Authors: Lou Jau-Shin , Weiss Michael D. , Carter Gregory T.
Published: February 2010

Fatigue is a common and potentially debilitating symptom of neuromuscular disease (NMD). Studies show that patients with NMD subjectively report increased levels of fatigue. Laboratory testing has demonstrated that patients with NMD show objective physiological signs of increased fatigue, with both central and peripheral components. To date, no treatment has been proven to be truly effective through evidence-based medicine. Thus, the clinician must use a multimodality approach to treating fatigue in patients with NMD. Management interventions are generally based on a sequential approach including treatment of comorbid factors, with the goal of maximizing physical and psychological functioning. This might include low-intensity exercise training, cognitive therapy, treatment of associated depression, correction of risk factors such as obesity, poor nutrition, and inactivity (deconditioning). Optimizing cardiopulmonary function is also critical and measures such as noninvasive, positive pressure ventilation may reduce fatigue in patients with NMD. Novel medications such as modafinil, a nonamphetamine stimulant, may be a helpful pharmacological treatment. Nutraceutical agents, such as creatine monohydrate, coenzyme Q10 (CoQ10), and α-lipoic acid, may also improve neuromuscular function and reduce fatigue.
A Social Network Analysis of Positive and Negative Gossip in Organizational Life
Authors: Grosser Travis J. , Lopez-Kidwell Virginie , Labianca Giuseppe
Published: February 2010

The authors use social network analysis to understand how employees’ propensity to engage in positive and negative gossip is driven by their underlying relationship ties.They find that expressive friendship ties between employees are positively related to engaging in both positive and negative gossip, whereas instrumental workflow ties, which are less trusting than friendship ties, are related solely with positive gossip. The authors also find that structural embeddedness in the friendship network further increases the chance that the pair will engage in negative gossip. Finally, an employee’s total gossiping activity (both positive and negative) is negatively related to supervisors’ evaluations of the employee’s performance, whereas total gossip activity is positively related to peers’ evaluations of the employee’s informal influence.
Adult Day Health Care for Participants With Alzheimer’s Disease
Authors: Silverstein Nina M. , Wong Cathy M. , Brueck Kristen E.
Published: February 2010

The purpose of this study was to explore existing practices and services provided by adult day health care (ADHC) in Massachusetts and to document how providers are addressing the specific needs of participants with Alzheimer’s disease and related disorders. Specific focus related to the early, late, and end stages of the disease process, and to early-onset dementia. Both quantitative and qualitative methods were used. A total of 93 (60%) providers responded to an electronic survey in 2008. In-person interviews were conducted with eight sites purposively chosen for their delivery of Alzheimer’s specific services. Results demonstrate that ADHC providers are adapting to the cognitive and physical abilities of their participants; however, there is need for enhancing stage-specific services, especially for participants at later stages and for early-onset dementia. This analysis provides preliminary insights into understanding the criteria that define ‘‘dementia-capable’’ programs and services.
Integrated Behavior Therapy in the Treatment of Complicated Tourette’s Disorder and Its Comorbidities
Authors: Bryson W. Jeff , Edwards Christopher L. , Sommer David B. , Scott Burton L.
Published: February 2010

Gilles de la Tourette’s syndrome (GTS) is a neuropsychiatric disorder that often presents with a complex array of motor and phonic tics that persist over the majority of a person’s life. GTS often presents with comorbidities such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and mood disorders. Psychosocial sequelae are also common among this population.We present the case of a 49-year-old female with severe, lifelong GTS complicated by OCD, inattention, impulsivity, disinhibition, mood disturbances, generalized anxiety, and pain secondary to motor tics. Habit reversal therapy (HRT) was used with full body relaxation conditioned as a competitive response to target her tics, anxiety, and pain simultaneously. The patient demonstrated significant reduction of symptoms and improvement in psychosocial status within four sessions. She was able to maintain this status at a 3 month follow-up session. Aspects of case conceptualization and therapeutic technique are discussed.
An Examination of the Covariates of Female Homicide Victimization and Offending
Authors: Pizarro Jesenia M. , DeJong Christina , McGarrell Edmund F.
Published: February 2010

This study examines and compares the covariates of female homicide offending and victimization in Indianapolis, Indiana, and Newark, New Jersey. Four research questions are examined: (a) What individual and structural factors differentiate female and male victimization? (b) Are there individual and structural factors that differentiate female and male offending? (c) Do the covariates of female involvement in lethal acts differ by location as compared to male offending and victimization? and (d) Do the covariates of female offending and victimization differ? Similar to previous research, the findings suggest that female homicide offending and victimization have similar covariates, although some distinct patterns emerged pertaining to the social structural covariates of offending and victimization. Specifically, homicides involving female actors were more likely to occur in Indianapolis than in Newark. The implications of these findings for policy and research are discussed.
A Continuation of the Paradigm Wars? Prevalence Rates of Methodological Approaches Across the Social/Behavioral Sciences
Authors: Alise Mark A. , Teddlie Charles
Published: February 2010

A new line of research has emerged that examines the prevalence rates of mixed methods within disciplines in the social/behavioral sciences. Research presented in this article is unique in that it examines prevalence rates across multiple disciplines using an established cross-disciplinary classification scheme. Results indicate that there are significant differences in the methods employed (quantitative, mixed, qualitative) in pure (psychology, sociology) as opposed to applied (education, nursing) disciplines. The prevalence rate for mixed methods research is higher in applied (16%) compared with pure disciplines (6%). Quantitative methods and the underlying postpositivistic paradigm are prevalent in articles from ‘‘elite’’ journals from pure disciplines, especially psychology. Methodological issues are discussed, including the importance of the sampling procedures employed in prevalence rates studies.
Online Master’s Degrees in Music Education: The Growing Pains of a Tool to Reach a Larger Community
Authors: Groulx Timothy J. , Hernly Patrick
Published: February 2010

Online graduate degree programs are a growing phenomenon as technology continues to develop and becomes more widely available and the needs of an increasingly educated society require better access to higher learning. In this study, the authors identified and studied the nine online (80% of the program or more) graduate music education programs accredited by the National Association of Schools of Music in the United States. They examined curriculum requirements, program requirements, and factors pertaining to application and enrollment. A fundamental belief in this study is that these online degrees are neither inferior nor superior to traditional coursework but rather represent an additional tool a university may employ to reach and educate its ever-expanding community. As suggested in the literature, these online programs offer significant benefits of convenience, although drawbacks include feelings of weaker interpersonal interactions and limited curricular options.
Multicultural Music Represented in Current Elementary Music Textbooks: A Comparative Study of Two Published Music Series
Authors: Mason Emily
Published: February 2010

Research investigating music textbook series is limited and has primarily focused on series no longer in publication, on two grade levels, and/or on limited cultures. The purpose of this study is to examine what countries are and have been represented in current music textbook series. Additional questions in the study pertain to frequency and distribution of songs across grade levels. Two different elementary music textbook publishers were used for kindergarten through fifth grade: Music Connection (1995) and Making Music (2002, 2005) by Silver Burdett Ginn and Share the Music (1995, 2003) and Spotlight on Music (2006) by Macmillan McGraw-Hill. The total number of songs appearing in the Macmillan McGraw-Hill series was 3,665, with 100 countries represented across the curriculum. The Silver Burdett Ginn textbook series contained a total of 4,000 songs from 107 countries. Further results and discussions are included.
Effects of Practice Schedule on Wind Instrument Performance: A Preliminary Application of a Motor Learning Principle
Authors: Stambaugh Laura A. , Demorest Steven M.
Published: February 2010

The effects of three practice schedules on beginning instrumental achievement were explored. A total of 19 seventh-grade clarinet and saxophone students completed one 18-minute practice session using either a blocked schedule causing a low level of cognitive (contextual) interference, a hybrid schedule causing a moderate level of interference, or a serial schedule causing a high level of interference. No main effects were found at immediate acquisition testing or 24-hr delayed retention testing for technical accuracy, attitude toward practice, or musicality. A significant practice Condition × Trial interaction was found for musicality. The discussion examines the discrepancy between technical and musical achievement. Recommendations are given for future research applying motor learning principles to instrumental music contexts.
Separation of graft-versus-host disease from graft-versus-leukemia responses by targeting CC-chemokine receptor 7 on donor T cells
Authors: Coghill James M. , Carlson Michael J. , Panoskaltsis-Mortari Angela , West Michelle L. , Burgents Joseph E. , Blazar Bruce R. , Serody Jonathan S.
Published: February 2010

CC-chemokine receptor 7 (CCR7) is expressed on the surface of naive T cells, and plays a critical role in their movement into secondary lymphoid tissue. Here, we show that murine T cells lacking CCR7 (CCR7−/−) generate attenuated graft-versus-host disease (GVHD) responses compared with wild-type (WT) cells, with the difference varying inversely with the degree of major histocompatibility complex (MHC) disparity between the donor and recipient. CCR7−/− T cells exhibited an impaired ability to traffic to recipient lymph nodes, with an increased capacity to home to the spleen. CCR7−/− T cells, however, demonstrated a reduced ability to undergo in vivo expansion in the spleen due to impaired interactions with splenic antigen-presenting cells. On a cellular level, CCR7−/− T cells were functionally competent, demonstrating a normal in vitro proliferative capacity and a preserved ability to produce inflammatory cytokines. Importantly, CCR7−/− T cells were capable of generating robust graft-versus-leukemia (GVL) responses in vivo, as well as complete donor T-cell reconstitution. CCR7−/− regulatory T cells were able to protect against lethal GVHD when administered before WT conventional T cells. Our data suggest that CCR7 inhibition in the early posttransplantation period may represent a feasible new therapeutic approach for acute GVHD attenuation without compromising GVL responses.
STAT3 controls the neutrophil migratory response to CXCR2 ligands by direct activation of G-CSF–induced CXCR2 expression and via modulation of CXCR2 signal transduction
Authors: Nguyen-Jackson Hoainam , Panopoulos Athanasia D. , Zhang Huiyuan , Li Haiyan S. , Watowich Stephanie S.
Published: February 2010

Neutrophil mobilization, the release of neutrophils from the bone marrow reserve into circulating blood, is important to increase peripheral neutrophil amounts during bacterial infections. Granulocyte colony-stimulating factor (G-CSF) and chemokines, such as macrophage-inflammatory protein-2 (MIP-2; CXCL2), can induce neutrophil mobilization, but the mechanism(s) they use remain unclear. Signal transducers and activator of transcription 3 (STAT3) is the principal intracellular signaling molecule activated upon G-CSF ligation of its receptor. Using a murine model with conditional STAT3 deletion in bone marrow, we demonstrated previously that STAT3 regulates acute G-CSF–responsive neutrophil mobilization and MIP-2–dependent neutrophil chemotaxis. In this study, we show STAT3 is also necessary for MIP-2–elicited neutrophil mobilization. STAT3 appears to function by controlling extracellular signal-regulated kinase (ERK) activation, which is important for MIP-2–mediated chemotaxis. In addition, we demonstrate that G-CSF stimulates the expression of the MIP-2 receptor via STAT3-dependent transcriptional activation of Il8rb. G-CSF treatment also induces STAT3-dependent changes in bone marrow chemokine expression levels which may further affect neutrophil retention and release. Taken together, our study demonstrates that STAT3 regulates multiple aspects of chemokine and chemokine receptor expression and function within the bone marrow, indicating a central role in the neutrophil mobilization response.
A zinc-finger transcriptional activator designed to interact with the γ-globin gene promoters enhances fetal hemoglobin production in primary human adult erythroblasts
Authors: Wilber Andrew , Tschulena Ulrich , Hargrove Phillip W. , Kim Yoon-Sang , Persons Derek A. , Barbas Carlos F. , Nienhuis Arthur W.
Published: February 2010

Fetal hemoglobin (HbF) is a potent genetic modifier of the severity of β-thalassemia and sickle cell anemia. We used an in vitro culture model of human erythropoiesis in which late-stage erythroblasts are derived directly from human CD34+ hematopoietic cells to evaluate HbF production. This system recapitulates expression of globin genes according to the developmental stage of the originating cell source. When cytokine-mobilized peripheral blood CD34+ cells from adults were cultured, background levels of HbF were 2% or less. Cultured cells were readily transduced with lentiviral vectors when exposed to vector particles between 48 and 72 hours. Among the genetic elements that may enhance fetal hemoglobin production is an artificial zinc-finger transcription factor, GG1-VP64, designed to interact with the proximal γ-globin gene promoters. Our data show that lentiviral-mediated, enforced expression of GG1-VP64 under the control of relatively weak erythroid-specific promoters induced significant amounts of HbF (up to 20%) in erythroblasts derived from adult CD34+ cells without altering their capacity for erythroid maturation and only modestly reducing the total numbers of cells that accumulate in culture after transduction. These observations demonstrate the potential for sequence-specific enhancement of HbF in patients with β-thalassemia or sickle cell anemia.
Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells
Authors: Ren Xi , Gomez Gustavo A. , Zhang Bo , Lin Shuo
Published: February 2010

Recent lineage studies suggest that hematopoietic stem cells (HSCs) may be derived from endothelial cells. However, the genetic hierarchy governing the emergence of HSCs remains elusive. We report here that zebrafish ets1-related protein (etsrp), which is essential for vascular endothelial development, also plays a critical role in the initiation of definitive hematopoiesis by controlling the expression of 2 stem cell leukemia (scl) isoforms (scl-α and scl-β) in angioblasts. In etsrp morphants, which are deficient in endothelial and HSC development, scl-α alone partially rescues angioblast specification, arterial-venous differentiation, and the expression of HSC markers, runx1 and c-myb, whereas scl-β requires angioblast rescue by fli1a to restore runx1 expression. Interestingly, when vascular endothelial growth factor (Vegf) signaling is inhibited, HSC marker expression can still be restored by scl-α in etsrp morphants, whereas the rescue of arterial ephrinb2a expression is blocked. Furthermore, both scl isoforms partially rescue runx1 but not ephrinb2a expression in embryos deficient in Vegf signaling. Our data suggest that downstream of etsrp, scl-α and fli1a specify the angioblasts, whereas scl-β further initiates HSC specification from this angioblast population, and that Vegf signaling acts upstream of scl-β during definitive hematopoiesis.
Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell–lymphotoxin-dependent pathway
Authors: Kumar Varsha , Scandella Elke , Danuser Renzo , Onder Lucas , Nitschké Maximilian , Fukui Yoshinori , Halin Cornelia , Ludewig Burkhard , Stein Jens V.
Published: February 2010

Adaptive immune responses are characterized by substantial restructuring of secondary lymphoid organs. The molecular and cellular factors responsible for virus-induced lymphoid remodeling are not well known to date. Here we applied optical projection tomography, a mesoscopic imaging technique, for a global analysis of the entire 3-dimensional structure of mouse peripheral lymph nodes (PLNs), focusing on B-cell areas and high endothelial venule (HEV) networks. Structural homeostasis of PLNs was characterized by a strict correlation between total PLN volume, B-cell volume, B-cell follicle number, and HEV length. After infection with lymphocytic choriomeningitis virus, we observed a substantial, lymphotoxin (LT) β-receptor–dependent reorganization of the PLN microarchitecture, in which an initial B-cell influx was followed by 3-fold increases in PLN volume and HEV network length on day 8 after infection. Adoptive transfer experiments revealed that virus-induced PLN and HEV network remodeling required LTα1β2-expressing B cells, whereas the inhibition of vascular endothelial growth factor-A signaling pathways had no significant effect on PLN expansion. In summary, lymphocytic choriomeningitis virus-induced PLN growth depends on a vascular endothelial growth factor-A–independent, LT- and B cell–dependent morphogenic pathway, as revealed by an in-depth mesoscopic analysis of the global PLN structure.