bluuebunny/crossref_metadata_2025 huggingface dataset:
When the Subject is More Than Just the Subject: Two Case Studies of Family Involvement in Human Subjects Research
Authors: Sauder Sara , Stein Rachel , Feinberg Emily , Bauchner Howard , Banks Mary , Silverstein Michael
Published: June 2011

Institutional review boards (IRBs) protect human research subjects by reviewing research to ensure compliance with federal regulations and institutional policies. One of the most important functions of IRBs is to ensure that investigators anticipate, plan for, and minimize risks to subjects. Under certain circumstances, however, participation in research may pose risks to nonsubject family members or other members of a subject's social network. In the context of a research protocol designed to test an intervention to prevent depression among a population of culturally diverse, urban mothers, we present two case studies of unanticipated problems, which demonstrate how nonsubject family members can either impact, or be impacted by, an individual's participation in research. The case studies illustrate the incongruence between federal regulations addressing IRB approval of research—which focus specifically on risks to subjects—and regulations on reporting incidents that occur during the conduct of the research, which extend to risks involving “others” as well. The cases also illustrate how risks to “others” can be accentuated in certain cultures where codependent family structures may increase the role that family members play in an individual's decision to participate in research. The question is raised as to whether this incongruence can inadvertently result in investigators and IRBs under-appreciating the risks that participation in research can pose to nonsubjects.
Ethical Behaviors of Latin American Psychotherapy Researchers
Authors: Roussos Andrés J. , Braun Malena , De Duarte Adela Leibovich
Published: June 2011

The ethical practices of psychotherapy researchers in Latin America were surveyed online. Of the 114 psychotherapy researchers to whom the survey was sent, 76 responded (67% response rate). Seventy-seven percent of the respondents had not received formal training in research ethics, yet 84% indicated that formal training is useful for the prevention of scientific misbehavior. Researchers admitted to various ethically questionable practices, the most common of which were related to authorship. None reported having fabricated or falsified data. The need for adequate training and evaluation of research projects is addressed.
Measuring How People View Biomedical Research: Reliability and Validity Analysis of the Research Attitudes Questionnaire
Authors: Rubright Jonathan D. , Cary Mark S. , Karlawish Jason H. , Kim Scott Y. H.
Published: June 2011

With increasing numbers of studies on research ethics and a need to improve the recruitment of research subjects, the ability to measure attitudes toward biomedical research has become important. The Research Attitudes Questionnaire is a significant predictor of the public's attitudes toward and willingness to participate in research, yet limited data are available on its psychometric properties. This study establishes the scale's internal consistency and dimensionality using a large Internet-based sample from the United States. One item was removed due to a poor item-total correlation, and three additional items were removed which formed a reverse-wording measurement artifact factor. With improved internal consistency and dimensionality, the seven-item version has the advantages of shorter administration time and improved psychometric properties.
Computer Science Security Research and Human Subjects: Emerging Considerations for Research Ethics Boards
Authors: Buchanan Elizabeth , Aycock John , Dexter Scott , Dittrich David , Hvizdak Erin
Published: June 2011

This paper explores the growing concerns with computer science research, and in particular, computer security research and its relationship with the committees that review human subjects research. It offers cases that review boards are likely to confront, and provides a context for appropriate consideration of such research, as issues of bots, clouds, and worms enter the discourse of human subjects review.
Musical Tension and the Interaction of Dynamic Auditory Parameters
Authors: Granot Roni Y. , Eitan Zohar
Published: June 2011

Though the Perception of Musical Tension has recently received considerable attention, the effect of interactions among auditory parameters on perceived tension has hardly been examined systematically. In this study, 132 participants (60 with music training) listened to short melodic sequences that combined manipulations of pitch direction, pitch register, loudness change, and tempo change, and rated in each sequence the overall tension level, as well as the direction of tension change (increasing or decreasing). For overall tension ratings, repeated measures ANOVAs showed main effects of loudness change, pitch direction, and pitch register (lower more tense), but not of tempo change. Importantly, several highly significant interactions among musical parameters (e.g., tempo and loudness, contour and loudness, tempo, contour, and register) were revealed. Tension change ratings were significantly affected by changes in loudness and tempo; register and contour elicited no main effect on tension change ratings, but interacted significantly. Results indicated that the mutual effect of auditory parameters on perceived tension is often strongly interactive, rather than additive. Increased loudness and low pitch register emerged as powerful determinants of perceived tension, often modulating the effects of pitch contour and tempo. We discuss results in light of an ecological model, in which perceived musical tension is affected by auditory cues for impending threat.
Experiential and Cognitive Changes Following Seven Minutes Exposure to Music and Speech
Authors: Ilie Gabriela , Thompson William Forde
Published: June 2011

In Two Experiments, We Assessed the Experiential and cognitive consequences of seven minutes exposure to music (Experiment 1) and speech (Experiment 2). In Experiment 1, participants listened to music for seven minutes and reported their emotional experiences based on ratings of valence (pleasant-unpleasant) and two types of arousal: energy (energetic-boring) and tension (tense-calm). They were then assessed on two cognitive skills: speed of processing and creativity. Music varied in pitch height (high or low pitched), rate (fast or slow), and intensity (loud or soft). Experiment 2 replicated Experiment 1 using male and female speech. Experiential and cognitive consequences of stimulus manipulations were overlapping in the two experiments, suggesting that music and speech draw on a common emotional code. There were also divergent effects, however, implicating domain-specific influences on emotion induction. We discuss the results in view of a psychological framework for understanding auditory signals of emotion.
Music Notation, But Not Action on a Keyboard, Influences Pianists' Judgments of Ambiguous Melodies
Authors: Repp Bruno H. , Goehrke Robert M.
Published: June 2011

Pitch Increases from Left to Right on Piano keyboards. When pianists press keys on a keyboard to hear two successive octave-ambiguous tones spanning a tritone (half-octave interval), they tend to report hearing the tritone go in the direction consistent with their key presses (Repp & Knoblich, 2009). This finding has been interpreted as an effect of action on perceptual judgment. Using a modified design, the present study separated the effect of the action itself from that of the visual stimuli that prompt the action. Twelve expert pianists reported their perception of octave-ambiguous three-note melodies ending with tritones in two conditions: In the active condition, they saw a notated melody and played it on a keyboard to hear it, while in the passive condition they viewed the notation while the melody was played to them. Participants tended to report hearing the tritone as it appeared in the notation, but action had no additional effect. We discuss whether the "action direction effect" described by Repp and Knoblich may have been caused by the visual action prompts, not by the action itself.
Absolute Tempo in Multiple Performances of Aboriginal Songs: Analyzing Recordings of Djanba 12 and Djanba 14
Authors: Bailes Freya , Barwick Linda
Published: June 2011

songs that are not notated but transmitted through live performance are of particular interest for the psychological study of the stability of tempo across multiple performances. While experimental research points to highly accurate memory for the tempi of well-known recorded music, this study asks whether there is any evidence of absolute tempo in a performance tradition that does not draw on such reference recordings. Fifty-four field recordings of performances of one Aboriginal dance-song, Djanba 14, were analyzed. Results showed that over a span of 34 years, performance tempi deviated positively or negatively, on average, by 2%. Such small tempo variation is similar to JND thresholds to discriminate the tempi of isochronous sequences. Thirty-five field recordings of another song from the same repertory, Djanba 12, deviated in tempi by an average of 3%. We discuss the musical, psychological, physical, and cultural factors likely to shape such temporal stability.
Musician Advantages in Music Perception: An Issue of Motivation, Not Just Ability
Authors: McAuley J. Devin , Henry Molly J. , Tuft Samantha
Published: June 2011

two experiments examined effects of regulatory fit and music training on performance on one subtest of the Montreal Battery of Evaluation of Amusia (MBEA). Participants made same-different judgments about melody pairs, while either gaining points for correct answers (gains condition) or losing points for incorrect answers (losses condition). In Experiment 1, participants were told that the test was diagnostic of their music ability and then were asked to self-identify as a musician or a nonmusician. In Experiment 2, participants were given either a promotion-focus prime (a performance-based opportunity to gain entry into a raffle) or a prevention-focus prime (a raffle ticket was awarded at the start of the experiment and participants prevented its loss by maintaining a certain level of performance). Consistent with a regulatory fit hypothesis, nonmusicians and promotion-primed participants performed better in the gains condition than the losses condition, while musicians and prevention-primed participants performed better in the losses condition than the gains condition. Experiment 2 additionally revealed that regulatory fit effects were stronger for musicians than nonmusicians. This study demonstrates that regulatory fit impacts performance on the MBEA and highlights the importance of motivational orientation with respect to musician performance advantages in music perception.
Science as Social Identity Marker
Authors: Zeller Benjamin E.
Published: June 2011

This article considers the place of science in the thought of three Unificationist groups in the United States from 1959 to 1971, those operated by Young Oon Kim, David S. C. Kim and Sang Ik Choi, all associated with Sun Myung Moon's Unification Church. The manner in which these groups treated science reveals and illuminates a number of distinct characteristics of each one: demographic draw, sub-cultural identity, historical context and perspective on modernity. The way these three Unificationist groups and their teachers talked about science reveals how their shared Unificationist worldview condensed those multiple characteristics and forces in different manners. Science functioned for each group as a powerful symbol of modernity, allowing each one to define itself, its relation to the wider world and its over­arching goals.
Genetic Drift Widens the Expected Cline but Narrows the Expected Cline Width
Authors: Polechová Jitka , Barton Nick
Published: June 2011

Random genetic drift shifts clines in space, alters their width, and distorts their shape. Such random fluctuations complicate inferences from cline width and position. Notably, the effect of genetic drift on the expected shape of the cline is opposite to the naive (but quite common) misinterpretation of classic results on the expected cline. While random drift on average broadens the overall cline in expected allele frequency, it narrows the width of any particular cline. The opposing effects arise because locally, drift drives alleles to fixation—but fluctuations in position widen the expected cline. The effect of genetic drift can be predicted from standardized variance in allele frequencies, averaged across the habitat: 〈F〉. A cline maintained by spatially varying selection (step change) is expected to be narrower by a factor of 1−〈F〉 relative to the cline in the absence of drift. The expected cline is broader by the inverse of this factor. In a tension zone maintained by underdominance, the expected cline width is narrower by about 1 – 〈F〉 relative to the width in the absence of drift. Individual clines can differ substantially from the expectation, and we give quantitative predictions for the variance in cline position and width. The predictions apply to clines in almost one-dimensional circumstances such as hybrid zones in rivers, deep valleys, or along a coast line and give a guide to what patterns to expect in two dimensions.
Ectopic Gene Expression and Organogenesis in Arabidopsis Mutants Missing BRU1 Required for Genome Maintenance
Authors: Ohno Yusuke , Narangajavana Jarunya , Yamamoto Akiko , Hattori Tsukaho , Kagaya Yasuaki , Paszkowski Jerzy , Gruissem Wilhelm , Hennig Lars , Takeda Shin
Published: June 2011

Chromatin reconstitution after DNA replication and repair is essential for the inheritance of epigenetic information, but mechanisms underlying such a process are still poorly understood. Previously, we proposed that Arabidopsis BRU1 functions to ensure the chromatin reconstitution. Loss-of-function mutants of BRU1 are hypersensitive to genotoxic stresses and cause release of transcriptional gene silencing of heterochromatic genes. In this study, we show that BRU1 also plays roles in gene regulation in euchromatic regions. bru1 mutations caused sporadic ectopic expression of genes, including those that encode master regulators of developmental programs such as stem cell maintenance and embryogenesis. bru1 mutants exhibited adventitious organogenesis, probably due to the misexpression of such developmental regulators. The key regulatory genes misregulated in bru1 alleles were often targets of PcG SET-domain proteins, although the overlap between the bru1-misregulated and PcG SET-domain-regulated genes was limited at a genome-wide level. Surprisingly, a considerable fraction of the genes activated in bru1 were located in several subchromosomal regions ranging from 174 to 944 kb in size. Our results suggest that BRU1 has a function related to the stability of subchromosomal gene regulation in the euchromatic regions, in addition to the maintenance of chromatin states coupled with heritable epigenetic marks.
A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq
Authors: Wang Xu , Soloway Paul D , Clark Andrew G
Published: June 2011

Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of 23 known imprinted genes in the placenta and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a well-replicated design using an orthogonal allelic-expression technology, we verified 5 novel imprinted genes that were not previously known to be imprinted in mouse (Pde10, Phf17, Phactr2, Zfp64, and Htra3). Our data suggest that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally expressed imprinted genes, with the addition of our validated set of placenta-imprinted genes, this maternal bias has disappeared.
Pathways of Resistance to Thymineless Death in Escherichia coli and the Function of UvrD
Authors: Fonville Natalie C , Vaksman Zalman , DeNapoli Jessica , Hastings P J , Rosenberg Susan M
Published: June 2011

Thymineless death (TLD) is the rapid loss of viability in bacterial, yeast, and human cells starved of thymine. TLD is the mode of action of common anticancer drugs and some antibiotics. TLD in Escherichia coli is accompanied by blocked replication and chromosomal DNA loss and recent work identified activities of recombination protein RecA and the SOS DNA-damage response as causes of TLD. Here, we examine the basis of hypersensitivity to thymine deprivation (hyper-TLD) in mutants that lack the UvrD helicase, which opposes RecA action and participates in some DNA repair mechanisms, RecBCD exonuclease, which degrades double-stranded linear DNA and works with RecA in double-strand-break repair and SOS induction, and RuvABC Holliday-junction resolvase. We report that hyper-TLD in ∆uvrD cells is partly RecA dependent and cannot be attributed to accumulation of intermediates in mismatch repair or nucleotide-excision repair. These data imply that both its known role in opposing RecA and an additional as-yet-unknown function of UvrD promote TLD resistance. The hyper-TLD of ∆ruvABC cells requires RecA but not RecQ or RecJ. The hyper-TLD of recB cells requires neither RecA nor RecQ, implying that neither recombination nor SOS induction causes hyper-TLD in recB cells, and RecQ is not the sole source of double-strand ends (DSEs) during TLD, as previously proposed; models are suggested. These results define pathways by which cells resist TLD and suggest strategies for combating TLD resistance during chemotherapies.
Novel Rank-Based Approaches for Discovery and Replication in Genome-Wide Association Studies
Authors: Kuo Chia-Ling , Zaykin Dmitri V
Published: June 2011

In recent years, genome-wide association studies (GWAS) have uncovered a large number of susceptibility variants. Nevertheless, GWAS findings provide only tentative evidence of association, and replication studies are required to establish their validity. Due to this uncertainty, researchers often focus on top-ranking SNPs, instead of considering strict significance thresholds to guide replication efforts. The number of SNPs for replication is often determined ad hoc. We show how the rank-based approach can be used for sample size allocation in GWAS as well as for deciding on a number of SNPs for replication. The basis of this approach is the “ranking probability”: chances that at least j true associations will rank among top u SNPs, when SNPs are sorted by P-value. By employing simple but accurate approximations for ranking probabilities, we accommodate linkage disequilibrium (LD) and evaluate consequences of ignoring LD. Further, we relate ranking probabilities to the proportion of false discoveries among top u SNPs. A study-specific proportion can be estimated from P-values, and its expected value can be predicted for study design applications.
CLAVATA Signaling Pathway Receptors of Arabidopsis Regulate Cell Proliferation in Fruit Organ Formation as well as in Meristems
Authors: Durbak Amanda R , Tax Frans E
Published: June 2011

The CLAVATA1 (CLV1), CLV2, and CORYNE (CRN) receptors in Arabidopsis thaliana maintain cell proliferation in shoot apical meristems by restricting expression of the transcription factor WUSCHEL (WUS). Previously characterized receptor mutants generate extra fruit and floral organs that are proposed to arise from enlarged floral meristems (FMs). We identified new alleles in clv1, clv2, and crn and found that most mutants produce only extra fruit organs and generate FMs of similar dimensions as wild type. Characterization of gynoecium development in receptor mutants revealed increased cell proliferation and ectopic fruit organ initiation after FM termination. These regions of increased cell division also display expanded expression of the cell proliferation-promoting transcription factor SHOOTMERISTEMLESS (STM), similar to the expansion of WUS expression in the shoot apical meristems of strong clv1 mutants. We also examined genetic interactions between the ERECTA (ER) and BARELY ANY MERISTEM 1 (BAM1) receptor-like kinases and CLV pathway receptors. Our results suggest a model in which CLV1/BAM1 and CLV2/CRN complexes act in separate, parallel pathways in shoot meristems, while the CLV1, CLV2, and CRN receptors function together in a linear pathway during fruit development. These results demonstrate the importance of regulating cell proliferation in plants that undergo organogenesis throughout their life cycle.
ELAV-Mediated 3′-End Processing of ewg Transcripts Is Evolutionarily Conserved Despite Sequence Degeneration of the ELAV-Binding Site
Authors: Haussmann Irmgard U , Li Min , Soller Matthias
Published: June 2011

Regulation of alternative mRNA processing by ELAV (embryonic lethal abnormal visual system)/Hu proteins is mediated by binding to AU-rich elements of low complexity. Since such sequences diverge very rapidly during evolution, it has not been clear if ELAV regulation is maintained over extended phylogenetic distances. The transcription factor Erect wing (Ewg) is a major target of ELAV in Drosophila melanogaster and coordinates metabolic gene expression with regulation of synaptic plasticity. Here, we demonstrate evolutionary conservation of ELAV regulation of ewg despite massive degeneration of its binding site and of associated elements in the regulated intronic 3′-end processing site in distantly related Drosophila virilis. In this species, the RNA-binding part of ELAV protein is identical to D. melanogaster. ELAV expression as well as expression and regulation of ewg are also conserved. Using in vitro binding assays and in vivo transgene analysis, we demonstrate, however, that the ELAV-binding site of D. virilis is fully functional in regulating alternative splicing of ewg intron 6 in D. melanogaster. Known features of the ELAV-binding site, such as the requirement of multiple poly(U) motifs spread over an extended binding site of ∼150 nt and a higher affinity to the 3′ part of the binding site, are conserved. We further show that the 135-bp ELAV-binding site from D. melanogaster is sufficient for ELAV recruitment in vivo. Hence, our data suggest that ELAV/Hu protein-regulated alternative RNA processing is more conserved than anticipated from the alignment of degenerate low-complexity sequences.
Optical coherence tomography in otolaryngology
Authors: Óvári Attila , Pau Hans-Wilhelm , Just Tino
Published: June 2011

Optical coherence tomography is an imaging technique based on coherence interferometry. It is used in many medical fields due to its non-invasive imaging capabilities with micrometer resolution. The aim of the authors was to review the applicability of the optical coherence tomography in otolaryngology. Literature data and their own studies show that optical coherence tomography is a reliable method for identifying and targeted biopsy of inflammated, pre-malignant or cancer tissue in human laryngeal and pharyngeal mucosa. Another emerging field for optical coherence tomography is diagnosis of middle ear diseases, especially stapes ankylosis and cholesteatoma. Orv. Hetil., 2011, 152, 1125–1132.[Formula: see text]
Effects of Paroxetine on the Pharmacokinetics and Pharmacodynamics of Immediate‐Release and Extended‐Release Metoprolol
Authors: Parker Robert B. , Soberman Judith E.
Published: June 2011

Study Objective. To compare the effects of paroxetine on the pharmacokinetics and pharmacodynamics of the immediate‐release (IR) and extended‐release (ER) formulations of metoprolol.

Design. Prospective, randomized, open‐label, 3‐way crossover study.

Setting. General clinical research center.

Subjects. Fifteen healthy volunteers with at least one active cytochrome P450 (CYP) CYP2D6 allele (CYP2D6*1 or CYP2D6*2).

Intervention. In each of three phases conducted in random sequence, subjects received one of three metoprolol formulations administered on day 1: a single dose of metoprolol ER 100 mg, a single dose of metoprolol ER 200 mg, or two 100‐mg doses of metoprolol IR administered 12 hours apart. Oral paroxetine 20 mg/day was then given alone on days 2–7 and coadministered with the same metoprolol formulation on day 8. Subjects received each of the other two formulations during the next two phases, with a 14‐day washout period between each phase.

Measurements and Main Results. After receiving metoprolol on days 1 (before paroxetine) and 8 (after paroxetine), S‐ and R‐metoprolol pharmacokinetic parameters and exercise heart rate and blood pressure responses were measured. The mean area under the plasma concentration‐time curve values of both S‐ and R‐metoprolol for each formulation were increased approximately 3‐ and 4‐fold, respectively, by paroxetine. Paroxetine significantly increased the S‐ and R‐metoprolol maximum concentration (Cmax) of each formulation and increased the elimination half‐life of both isomers approximately 2‐fold. When metoprolol IR was given with paroxetine, the S‐metoprolol Cmax was significantly greater than that of either the 100‐mg or 200‐mg ER products. The maximum effect of metoprolol IR on heart rate was significantly greater than that of metoprolol ER 200 mg, independent of whether the agents were administered alone or with paroxetine. Both the heart rate and systolic blood pressure area under the effect‐time curve values were significantly decreased by paroxetine.

Conclusion. Paroxetine significantly inhibits the metabolism of both metoprolol IR and ER, resulting in an increase in the magnitude and duration of β‐blockade. The potential risk of adverse effects from excessive β‐blockade may be greater with metoprolol IR than with metoprolol ER because of the significantly higher peak S‐metoprolol plasma concentrations achieved with the IR formulation. Thus, if paroxetine treatment is indicated in patients receiving metoprolol, use of the ER formulation may reduce the risk of adverse effects.
Otoacoustic Emission Screen Results in Critically Ill Neonates Who Received Gentamicin in the First Week of Life
Authors: Cooper Aaron C. , Commers Amy R. , Finkelstein Marsha , Lipnik Polina G. , Tollefson Lisa M. , Wilcox Roger A. , Hoff David S.
Published: June 2011

Study Objective. To characterize the extent that serum gentamicin concentrations are associated with hearing loss indicated by otoacoustic emission (OAE) screen failure in critically ill neonates receiving gentamicin in accordance with a high‐dose, extended‐interval dosing protocol.

Design. Retrospective medical record review.

Setting. Two neonatal intensive care units in a pediatric tertiary care system.

Patients. Sequential sample of 528 critically ill neonates who were admitted between February 2003 and January 2008 and who received a gentamicin pharmacokinetic consultation during the first week of life and an OAE hearing screen before hospital discharge. Neonates were stratified into two groups: very low birth weight (VLBW [≤ 1500 g]) and non‐VLBW (> 1500 g).

Measurements and Main Results. Gentamicin was dosed intravenously to achieve a target calculated gentamicin peak serum concentration (Cmax) of 7–10 μg/ml and a target trough serum concentration (Cmin) of less than 2 μg/ml. The dosage administered was 4 mg/kg/dose every 48 hours if the neonate's birth weight was less than 1250 g or if the neonate was receiving indomethacin. Otherwise, the dosing interval was every 24 hours. Initial OAE screen results were obtained from the medical records, and follow‐up results were collected for neonates who failed the initial OAE screen. The overall rate of OAE screen failure was 13.1% (69/528 patients). The rate of OAE screen failure was 34.1% (29/85 patients) in the VLBW neonates, which was significantly higher than the failure rate in non‐VLBW neonates (9.0% [40/443 patients], p=0.001). Multivariate analysis of non‐VLBW neonates determined that each 1–μg/ml increase in gentamicin Cmax was associated with an increased risk of OAE screen failure (odds ratio [OR] 1.4, 95% confidence interval (CI) 1.1–1.7, p=0.003). Further, the non‐VLBW neonate subpopulation had an increased rate of OAE screen failure if the gentamicin Cmax exceeded 10 μg/ml (OR 2.2, 95% CI 1.1–4.2, p=0.022) compared with neonates whose Cmax was 10 μg/ml or lower. No association between serum gentamicin concentration and OAE screen failure could be determined among the VLBW neonates.

Conclusion. Neonates weighing more than 1500 g at birth and whose gentamicin Cmax exceeded 10 μg/ml were at an increased risk for OAE screen failure. Monitoring and maintaining gentamicin Cmax at or below 10 μg/ml may minimize hearing impairment; however, further studies are necessary.
Safety of Daptomycin in Patients Receiving Hemodialysis
Authors: Mueller Bruce A. , Crompton Jason A. , Donovan Brian J. , Yankalev Sara , Lamp Kenneth C.
Published: June 2011

Study Objective. To determine the safety of daptomycin administered using a variety of doses and dosing frequencies in patients receiving intermittent hemodialysis who had probable or confirmed gram‐positive infections.

Design. Analysis of data from the Cubicin Outcomes Registry and Experience (CORE), a multicenter, retrospective, observational registry.

Setting. Fifty‐four study sites, mostly (46%) large teaching hospitals.

Patients. Three hundred ninety‐three adults in the CORE registry who received intermittent hemodialysis between 2005 and 2008.

Measurements and Main Results. The CORE registry is noninterventional and collects standard‐of‐care data on daptomycin treatment from health care institutions. Of the 393 patients, 370 (94%) could be categorized by daptomycin dosing frequency: every 48 hours (251 patients [64%]), 3 times/week (87 [22%]), and every 24 hours (32 [8%]); the remaining 23 (6%) had unreported dosing frequencies or received a single dose of daptomycin. Three hundred eighty‐four patients (98%) received part of their daptomycin therapy as an inpatient and 129 patients (33%) received part of their daptomycin therapy in an intensive care setting. The primary infection type was bacteremia (224 patients [57%]), and the most common pathogen was Staphylococcus aureus (155 patients [39%]). Thirty‐eight adverse events possibly related to daptomycin occurred in 28 patients (7%); increased blood creatine kinase level (7 patients [1.8%]) was the most common adverse event. Adverse‐event rates were similar across all dosing regimens.

Conclusion. In these patients undergoing hemodialysis, daptomycin was a well‐tolerated treatment for gram‐positive infections across several doses and dosing frequencies. Further study in prospective trials is warranted.
Understanding Risk Evaluation and Mitigation Strategies in Organ Transplantation
Authors: Gabardi Steven
Published: June 2011

The United States Food and Drug Administration (FDA) Amendments Act of 2007 mandated that Risk Evaluation and Mitigation Strategies (REMS) be required of manufacturers. These REMS are strategies implemented to manage known or potential risks associated with drugs and to ensure ongoing pharmacovigilance throughout the life of a pharmaceutical product, including once the product becomes available as generic. The elements of an individual REMS program consist of three levels: medication guide or patient package insert, communication plan, and elements to assure safe use (ETASU). A medication guide or patient package insert is used to help prevent serious adverse events, aid in patient decision making, and enhance drug adherence. Communication plans are used to educate health care providers and to encourage their compliance with REMS. The ETASU is a restrictive process that is implemented when it is deemed necessary to ensure that patients have safe access to products with known serious risks that would otherwise be unavailable. To review the components of REMS and specifically assess their impact on health care providers practicing within the organ transplantation arena, a literature search of the MEDLINE database (January 2007‐December 2010) was performed, and published materials from the FDA and its Web site were also reviewed. In transplantation, REMS programs exist for both everolimus (medication guide and communication plan) and sirolimus (medication guide). The FDA has stated that all mycophenolic acid derivatives will be subject to a proposed REMS that has not yet been approved; however, both branded mycophenolic acid agents already have approved medication guides. The REMS are a permanent fixture in the development and marketing of pharmaceutical agents, and their further implementation in solid organ transplantation is inevitable. Transplantation providers should take a proactive role in patient education and implementation of REMS within the therapeutic area. It is imperative for health care providers to realize that the ultimate goals of REMS are to reduce the potential for serious risks and to make outcomes from the treatment of disease more predictable.
TOP2A Amplification in the Absence of That of HER-2/neu: Toward Individualization of Chemotherapeutic Practice in Breast Cancer
Authors: Glynn Ronan W. , Mahon Sarah , Curran Catherine , Callagy Grace , Miller Nicola , Kerin Michael J.
Published: June 2011

Primary objective.

To investigate the relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase IIα (TOP2A) in breast cancer, while elucidating their association with clinicopathological variables.

Methods.

Real-time quantitative polymerase chain reaction (RQ-PCR) was performed on a 96-patient study group to assess gene amplification, and levels were determined using the comparative cycle threshold approach and Taqman assays. An immunohistochemistry (IHC) microarray (n = 76) was then employed to check for correlation between gene amplification and protein expression levels.

Results.

Amplification levels of TOP2A did not differ significantly according to HER-2/neu status by either RQ-PCR or IHC microarray. Of the HER-2/neu− patients, 29.1% demonstrated levels of TOP2A above the third quartile, whereas 22.9% of the HER-2/neu+ patients had values in the first quartile (log TOP2A <0.62), thereby indicating low-level amplification. Of the 60 patients characterized as HER-2/neu− using IHC and fluorescence in situ hybridization (FISH), 22.9% were classified as TOP2A+ on the IHC microarray. Of the 14 patients deemed HER-2/neu+ using IHC and FISH, meanwhile, the majority (n = 10) were classified as TOP2A+.

Conclusions.

Our results indicate that amplification of TOP2A in breast cancer is not confined to those who are concomitantly HER-2/neu+, and suggest that a significant proportion of HER-2/neu− patients exhibit high levels of TOP2A.
Tobacco Prevention Education in Schools for the Deaf: The Faculty Perspective
Authors: Berman Barbara A. , Guthmann Debra S. , Liu Weiqing , Streja Leanne
Published: June 2011

We report results of a survey of tobacco education practices and perspectives among faculty at four Schools for the Deaf participating in the trial of a tailored tobacco prevention curriculum. Few faculty (20.4%) included tobacco use among the three most important health problems facing their students, although 88.8% considered tobacco education to be worthwhile. Despite perceived unmet needs among their students, classroom or school-wide attention to tobacco prevention was limited. Only 13.9% reported delivering tobacco programming in the prior year, most often reporting lack of deaf-friendly curriculum and materials (60.9%), time (47.8%), and training (43.5%) as barriers to program delivery. Perceptions, attitudes, and institutional issues, including lack of tailored curriculum, were seen as contributing to the limited focus on this important health problem.
Preferred Drug Resistance Strategies of Urban American Indian Youth of the Southwest
Authors: Kulis Stephen , Brown Eddie F.
Published: June 2011

This study explored the drug resistance strategies that urban American Indian adolescents consider the best and worst ways to respond to offers of alcohol, cigarettes, and marijuana. Focus group data were collected from 11 female and 9 male American Indian adolescents attending urban middle schools in the southwest. The youth were presented with hypothetical substance offer scenarios and alternative ways of responding, based on real-life narratives of similar youth. They were asked to choose a preferred strategy, one that would work every time, and a rejected strategy, one they would never use. Using eco-developmental theory, patterns in the preferred and rejected strategies were analyzed to identify culturally specific and socially competent ways of resisting substance offers. The youth preferred strategies that included passive, non-verbal strategies like pretending to use the substance, as well as assertive strategies like destroying the substance. The strategies they rejected were mostly socially non-competent ones like accepting the substance or responding angrily. Patterns of preferred and rejected strategies varied depending on whether the offer came from a family member or non-relative. These patterns have suggestive implications for designing more effective prevention programs for the growing yet underserved urban American Indian youth population.
Self-Regulated Learning and Externally Generated Feedback with Hypermedia
Authors: Moos Daniel C.
Published: June 2011

Think-aloud and self-report data from 65 undergraduates were used to examine the effect of feedback on self-regulation during learning with hypermedia. Participants, randomly assigned to one of three conditions (Control, Questions, Questions+Feedback), used hypermedia for 30 minutes to learn about the circulatory system. Results indicated that participants in the Questions+Feedback condition initially reported significantly lower levels of self-efficacy. However, they also reported increased levels as they progressed through the learning task. Additionally, participants in the Questions and Questions+Feedback conditions engaged in monitoring processes and activated prior knowledge more frequently, on average, than those in the Control condition. Lastly, participants in the Questions condition used significantly more strategies and outperformed those participants in the Questions+Feedback condition.
Gender Differences in the use of Laptops in Higher Education: A Formative Analysis
Authors: Kay Robin H. , Lauricella Sharon
Published: June 2011

Over the past 18 years, a number of large scale reviews of the literature have documented that gender differences in computer attitudes, ability, and use tend to favor males. Since the use of laptops in higher education classrooms is increasing, it is important to examine whether this use is disproportionally advantageous to males and disadvantageous to females. The purpose of this study was to explore gender differences in the use of laptops in higher education classrooms. Two key areas were examined: on-task behaviors (note-taking, academic activities, instant messaging) and off-task behaviors (e-mail, instant messaging, games, movies, distractions). With respect to on-task behaviors, females reported significantly more note-taking and participation in academic laptop-based activities. No gender differences were observed with respect to instant messaging for academic purposes. Regarding off-task behaviors, females were more distracted by their peers' use of laptops than males, whereas males reported that they played significantly more games during class. Recommendations for future research include expanding the breadth of off- and on-task behaviors assessed, exploring the role of teaching strategies, and focusing on learning performance.
Depression, unlike Normal Sadness, is Associated with a “Flatter” Self-Perception and a “Flatter” Phenomenal World
Authors: Kunzendorf Robert G. , Flynn Hayley , Shedlack Jessica , Georges Murielle , Deno Sophia , Rosa Nichole , Burns Jennifer
Published: June 2011

Three variables—manifest anxiety, psychological resilience, and phenomenal flatness—were tested for their ability to qualitatively differentiate depression from normal sadness. Toward this end, 221 college students completed the Center for Epidemiological Studies' Depression Scale, our newly developed Multidimensional Sadness Inventory, the Short Form of the Manifest Anxiety Scale, the Connor-Davidson Resilience Scale, the Scale of Social Desirability, our newly developed Test for Flat versus Deep Object-Perception, our newly developed Survey of Flat versus Deep Person-Perception, and our newly developed Survey of Flat versus Deep Self-Perception. On each trial in the Test for Flat versus Deep Object-Perception, the students observed two ambiguous figures—a circle/sphere with a radius of 1 unit and a square/cube with sides 1.675 units long—and they selected the bigger object—either the “phenomenally flat” circle with an area 12% larger than the area of the square, or the “spatially deep” cube with a volume 12% larger than the volume of the sphere. On the Survey of Flat versus Deep Person-Perception, the students indicated how they perceive other students on 43 rating scales anchored by one adjective synonymous with flat and by another adjective synonymous with deep, and on the Survey of Flat versus Deep Self-Perception, they rated how they perceive themselves on the same 43 scales. Our results indicate that lower resilience and higher anxiety are associated not only with greater depression, but also with greater sadness controlling for depression. Greater phenomenal flatness on the other hand, as gauged by our measures of flat versus deep object-perception, person-perception, and self-perception, is associated with greater depression but not with greater sadness controlling for depression.
Perinatal Loss and Parental Grief: The Challenge of Ambiguity and Disenfranchised Grief
Authors: Lang Ariella , Fleiszer Andrea R. , Duhamel Fabie , Sword Wendy , Gilbert Kathleen R. , Corsini-Munt Serena
Published: June 2011

Following perinatal loss, a type of ambiguous loss, bereaved couples struggle with and experience distress due to various forms of ambiguity. Moreover, the juxtaposition of their grief with society's minimization often disenfranchises them from traditional grieving processes. The purpose of this study was to explore sources of ambiguity and disenfranchised grief related to perinatal loss. Audio-taped interviews with 13 bereaved couples at 2, 6, and 13 months following the death of their fetus or infant were analyzed. Several categories of ambiguity and disenfranchised grief emerged, pertaining to: (a) the viability of the pregnancy; (b) the physical process of pregnancy loss; (c) making arrangements for the remains; and (d) sharing the news. This study uncovers the many sources of ambiguity and disenfranchised grief that bereaved couples face in interactions with family, friends, society, and healthcare professionals. These insights may inform healthcare professionals in their attempts to ease distress related to perinatal loss.
Long-term Outcome of Renal Transplantation Patients with Henoch-Schönlein Purpura
Authors: Samuel Joyce P. , Bell Cynthia S. , Molony Donald A. , Braun Michael C.
Published: June 2011

Background and objectives

Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP.

Design, setting, participants, & measurements

This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival.

Results

Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively).

Conclusions

These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.
Low Lead Exposure During Foetal and Early Postnatal Life Impairs Passive Avoidance Learning in Adulthood in Rats
Authors: Barkur Rajashekar , Rao Muddanna , Bairy Laxminarayana
Published: June 2011

Low Lead Exposure During Foetal and Early Postnatal Life Impairs Passive Avoidance Learning in Adulthood in Rats

This follow-up study investigated the effects of low-level lead exposure during prenatal and early postnatal period on learning and memory in rats immediately after exposure has ceased at weaning and later in their adulthood. Male Wistar-derived rats were exposed to lead (as 0.2 % lead acetate solution) through their mothers during pregnancy and lactation until they were weaned. Mothers of control rats were given tap water during pregnancy and lactation. All pups were weaned on tap water at 21 days of age and were followed up until 120 days old. Low-level lead exposure did not affect their body weight at any time during the experiment. Blood lead in the exposed rats was significantly higher on postnatal day 22 and dropped to control values by day 120. Passive avoidance test showed impaired memory retention in the exposed rats on postnatal days 25 and 120. This suggests that exposure to low-lead levels during foetal and early postnatal development of brain tissue can cause memory impairment that lasts into adulthood.