bluuebunny/crossref_metadata_2025_split huggingface dataset:
A distinct epigenetic signature at targets of a leukemia protein
Authors: Rossetti Stefano , Hoogeveen André T , Liang Ping , Stanciu Cornel , van der Spek Peter , Sacchi Nicoletta 
Published: February 2007

AbstractBackgroundHuman myelogenous leukemia characterized by either the non random t(8; 21)(q22; q22) or t(16; 21)(q24; q22) chromosome translocations differ for both their biological and clinical features. Some of these features could be consequent to differential epigenetic transcriptional deregulation at AML1 targets imposed by AML1-MTG8 and AML1-MTG16, the fusion proteins deriving from the two translocations. Preliminary findings showing that these fusion proteins lead to transcriptional downregulation of AML1 targets, marked by repressive chromatin changes, would support this hypothesis. Here we show that combining conventional global gene expression arrays with the power of bioinformatic genomic survey of AML1-consensus sequences is an effective strategy to identify AML1 targets whose transcription is epigenetically downregulated by the leukemia-associated AML1-MTG16 protein.ResultsWe interrogated mouse gene expression microarrays with probes generated either from 32D cells infected with a retroviral vector carrying AML1-MTG16 and unable of granulocyte differentiation and proliferation in response to the granulocyte colony stimulating factor (G-CSF), or from 32D cells infected with the cognate empty vector. From the analysis of differential gene expression alone (using as criteria a p value < 0.01 and an absolute fold change > 3), we were unable to conclude which of the 37 genes downregulated by AML1-MTG16 were, or not, direct AML1 targets. However, when we applied a bioinformatic approach to search for AML1-consensus sequences in the 10 Kb around the gene transcription start sites, we closed on 17 potential direct AML1 targets. By focusing on the most significantly downregulated genes, we found that both the AML1-consensus and the transcription start site chromatin regions were significantly marked by aberrant repressive histone tail changes. Further, the promoter of one of these genes, containing a CpG island, was aberrantly methylated.ConclusionThis study shows that a leukemia-associated fusion protein can impose a distinct epigenetic repressive signature at specific sites in the genome. These findings strengthen the conclusion that leukemia-specific oncoproteins can induce non-random epigenetic changes.
Closing the access gap for health innovations: an open licensing proposal for universities
Authors: Chaifetz Samantha , Chokshi Dave A , Rajkumar Rahul , Scales David , Benkler Yochai 
Published: February 2007

Abstract

Background
This article centers around a proposal outlining how research universities could leverage their intellectual property to help close the access gap for health innovations in poor countries. A recent deal between Emory University, Gilead Sciences, and Royalty Pharma is used as an example to illustrate how 'equitable access licensing' could be put into practice.

Discussion
While the crisis of access to medicines in poor countries has multiple determinants, intellectual property protection leading to high prices is well-established as one critical element of the access gap. Given the current international political climate, systemic, government-driven reform of intellectual property protection seems unlikely in the near term. Therefore, we propose that public sector institutions, universities chief among them, adopt a modest intervention – an Equitable Access License (EAL) – that works within existing trade-law and drug-development paradigms in order to proactively circumvent both national and international obstacles to generic medicine production. Our proposal has three key features: (1) it is prospective in scope, (2) it facilitates unfettered generic competition in poor countries, and (3) it centers around universities and their role in the biomedical research enterprise. Two characteristics make universities ideal agents of the type of open licensing proposal described. First, universities, because they are upstream in the development pipeline, are likely to hold rights to the key components of a wide variety of end products. Second, universities acting collectively have a strong negotiating position with respect to other players in the biomedical research arena. Finally, counterarguments are anticipated and addressed and conclusions are drawn based on how application of the Equitable Access License would have changed the effects of the licensing deal between Emory and Gilead.
Stability of early-phase primary psychotic disorders with
concurrent substance use and substance-induced psychosis
Authors: Caton Carol L. M. , Hasin Deborah S. , Shrout Patrick E. , Drake Robert E. , Domínguez Boanerges , First Michael B. , Samet Sharon , Schanzer Bella 
Published: February 2007

BackgroundThe stability of the diagnostic distinction between a substance-induced
psychosis and a primary psychotic disorder co-occurring with substance
use is not established.AimsTo describe DSM – IV diagnostic changes over 1 year and determine the
predictive validity of baseline indicators of the substance-induced
psychosis v. primary psychosis distinction.MethodWe conducted a 1-year follow-up study of 319 psychiatric emergency
department admissions with diagnoses of early-phase psychosis and
substance use comorbidity.ResultsOf those with a baseline DSM—IV diagnosis of substance-induced psychosis,
25% had a diagnosis of primary psychosis at follow-up. These patients had
poorer premorbid functioning, less insight into psychosis and greater
family mental illness than patients with a stable diagnosis of
substance-induced psychosis. Reclassifying change cases to primary
psychoses on follow-up, key baseline predictors of the
primary/substance-induced distinction at 1 year also included greater
family history of mental illness in the primary psychosis group.ConclusionsFurther study of substance-induced psychoses should employ
neuroscientific and behavioural approaches. Study findings can guide more
accurate diagnoses at first treatment.
Psychological treatments for chronic post-traumatic stress disorder
Authors: Bisson Jonathan I. , Ehlers Anke , Matthews Rosa , Pilling Stephen , Richards David , Turner Stuart 
Published: February 2007

BackgroundThe relative efficacy of different psychological treatments for chronic post-traumatic stress disorder (PTSD) is unclear.AimsTo determine the efficacy of specific psychological treatments for chronic PTSD.MethodIn a systematic review of randomised controlled trials, eligible studies were assessed against methodological qualitycriteria and data were extracted and analysed.ResultsThirty-eight randomised controlled trials were included in the meta-analysis. Trauma-focused cognitive-behavioural therapy (TFCBT), eye movement desensitisation and reprocessing (EMDR), stress management and group cognitive-behavioural therapy improved PTSD symptoms more than waiting-list or usual care. There was inconclusive evidence regarding other therapies. There was no evidence of a difference in efficacy between TFCBT and EMDR butthere was some evidence that TFCBT and EMDR were superior to stress management and other therapies, and that stress management was superior to other therapies.ConclusionsThe first-line psychological treatment for PTSD should be trauma-focused (TFCBTor EMDR).
Best practice when service users do not consent to sharing
information with carers
Authors: Slade Mike , Pinfold Vanessa , Rapaport Joan , Bellringer Sophie , Banerjee Sube , Kuipers Elizabeth , Huxley Peter 
Published: February 2007

BackgroundService users with psychosis may not consent to sharing information with
carers. However, carers require access to relevant information to support
them in their role.AimsTo inform clinical practice when service users withhold consent to share
information with their carer.MethodStudy data were derived from a synthesis of policy review
(n=91), national survey (n=595) and
individual interviews (n=24).ResultsKey principles to guide information-sharing practices were identified.
Service users highlighted confidentiality being guaranteed by consent
processes. Carers suggested a ‘culture shift’ was required, with
professionals trained to work with carers. Professionals emphasised
mental capacity, professional judgement and the context of care. A best
practice framework is proposed.ConclusionsAn important distinction is between general information, which can always
be shared without consent, and personal information, which is new to the
carer and where consent needs to be considered. Clinical judgement is
central to balancing conflicting ethical imperatives in this area.
Neural correlates of the misattribution of speech in
schizophrenia
Authors: Allen Paul , Amaro Edson , Fu Cynthia H. Y. , Williams Steven C. R. , Brammer Michael J. , Johns Louise C. , McGuire Philip K. 
Published: February 2007

BackgroundThe neurocognitive basis of auditory verbal hallucinations is
unclear.AimsTo investigate whether people with a history of such hallucinations would
misattribute their own speech as external and show differential
activation in brain areas implicated in hallucinations compared with
people without such hallucinations.MethodParticipants underwent functional magnetic resonance imaging (fMRI) while
listening to pre-recorded words. The source (self/non-self) and acoustic
quality (undistorted/distorted) were varied across trials. Participants
indicated whether the speech they heard was their own or that of another
person. Twenty people with schizophrenia (auditory verbal hallucinations
n=10, no hallucinations n=10) and
healthy controls (n=11) were tested.ResultsThe hallucinator group made more external misattributions and showed
altered activation in the superior temporal gyrus and anterior cingulate
compared with both other groups.ConclusionsThe misidentification of self-generated speech in patients with auditory
verbal hallucinations is associated with functional abnormalities in the
anterior cingulate and left temporal cortex. This may be related to
impairment in the explicit evaluation of ambiguous auditory verbal
stimuli.
Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline
Authors: Bania Theodore C. , Chu Jason , Perez Eric , Su Mark , Hahn In‐Hei 
Published: February 2007

BackgroundIntravenous fat emulsion (IFE) decreases cardiotoxicity from several lipid‐soluble drugs, including verapamil.ObjectivesTo verify if the addition of IFE to the standard treatment of severe verapamil toxicity would improve hemodynamics and survival.MethodsFourteen dogs were instrumented to measure systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate, cardiac output, central venous pressures, left ventricular pressure changes over time, mixed venous oxygen saturation, pH, and base excess. Verapamil toxicity, defined as a 50% decrease in MAP, was induced with verapamil at 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil infusion rate. Following verapamil toxicity, the verapamil infusion rate was changed to 2 mg/kg/hr and continued for 90 minutes. All dogs were resuscitated with atropine (0.04 mg/kg intravenously) and calcium chloride (15 mg/kg intravenously every 5 minutes for three doses) and then randomized to receive either IFE (7 mg/kg of 20%) intravenously or equivalent volumes of 0.9% normal saline over 30 minutes. Measurements were recorded for 120 minutes by investigators blinded to the treatment. Data were analyzed using analysis of variance, survival analysis, and log‐rank test.ResultsBefore the 30‐minute IFE or normal saline infusion, there were no differences in hemodynamic parameters. After IFE or normal saline infusion, the IFE‐treated group had higher MAP at 30 minutes (95% confidence interval [CI] = 5.6 to 44.7 mm Hg), 45 minutes (95% CI = 10.8 to 50.0 mm Hg), and 60 minutes (95% CI = 10.2 to 53.1 mm Hg). Kaplan–Meier 120‐minute survival rate was 14% (95% CI = 0.5% to 53%) for the saline group as compared with 100% (95% CI = 59% to 100%) for the IFE group (p = 0.01).ConclusionsStandard resuscitation and IFE increase MAP and survival in an animal model of severe verapamil toxicity compared with standard resuscitation alone.
Embedding Medical Student Computer Tutorials into a Busy Emergency Department
Authors: Pusic Martin V. , Pachev George S. , MacDonald Wendy A. 
Published: February 2007

ObjectivesTo explore medical students' use of computer tutorials embedded in a busy clinical setting; to demonstrate that such tutorials can increase knowledge gain over and above that attributable to the clinical rotation itself.MethodsSix tutorials were installed on a computer placed in a central area in an emergency department. Each tutorial was made up of between 33 and 85 screens of information that include text, graphics, animations, and questions. They were designed to be brief (10 minutes), focused, interactive, and immediately relevant. The authors evaluated the intervention using quantitative research methods, including usage tracking, surveys of faculty and students, and a randomized pretest‐posttest study.ResultsOver 46 weeks, 95 medical students used the tutorials 544 times, for an overall average of 1.7 times a day. The median time spent on completed tutorials was 11 minutes (average [SD], 14 [±12] minutes). Seventy‐four students completed the randomized study. They completed 65% of the assigned tutorials, resulting in improved examination scores compared with the control (effect size, 0.39; 95% confidence interval = 0.15 to 0.62). Students were positively disposed to the tutorials, ranking them as “valuable.” Fifty‐four percent preferred the tutorials to small group teaching sessions with a preceptor. The faculty was also positive about the tutorials, although they did not appear to integrate the tutorials directly into their teaching.ConclusionsMedical students on rotation in a busy clinical setting can and will use appropriately presented computer tutorials. The tutorials are effective in raising examination scores.
Variation in estradiol level affects cortical bone growth in response to mechanical loading in sheep
Authors: Devlin Maureen J. , Lieberman Daniel E. 
Published: February 2007

SUMMARY
Although mechanical loading can stimulate cortical bone growth, little is known about how individual physiology affects this response. This study demonstrates that in vivo variation in estradiol (E2)level alters osteoblast sensitivity to exercise-induced strains, affecting cortical bone responses to mechanical loading. Subadult sheep were divided into treatment groups that varied in terms of circulating E2 levels and loading (exercised and sedentary). After 45 days, periosteal cortical bone growth rates and cross-sectional properties were measured at the midshafts of hindlimb bones and compared with strain data. The results indicate significant interactions between E2 and strain. Cortical bone growth in exercised animals with elevated E2 levels was 27% greater in the femur, 6% greater in the tibia, and 14% greater in the metatarsal than in exercised animals with lower E2 levels, or sedentary animals regardless of E2 dose (P&lt;0.05). There was also a trend toward greater resistance to deformation in the tibia, but not the metatarsal,in the exercised, high-E2 group compared to the other treatment groups. These results demonstrate that E2 plays a role in mediating skeletal responses to strain, such that physiological variation in E2 levels among individuals may lead to differential growth responses to similar mechanical loading regimes. Efforts to model the relationship between environmental strain and bone morphology should include the effects of physiological variation in hormone levels.
V-type H+-ATPase and Na+,K+-ATPase in the gills of 13 euryhaline crabs during salinity acclimation
Authors: Tsai Jyuan-Ru , Lin Hui-Chen 
Published: February 2007

SUMMARYBecause of their diverse habitats, crabs are excellent experimental species to study owing to the morphological changes and physiological adaptation that occur during their terrestrial invasion. Their hemolymphic osmoregulation in brackish water is crucial for a successful terrestrial invasion. Crabs can actively uptake or excrete ions upon salinity change, and the gills play a major role among the osmoregulatory organs. Several enzymes are involved in the osmoregulatory process, including Na+,K+-ATPase and V-type H+-ATPase (V-H+-ATPase). Na+,K+-ATPase is the driving force in establishing an ion gradient across the epithelial cell membrane in marine crabs. It has been reported that the osmoregulatory mechanisms in freshwater crabs are different from those in marine ones, suggesting that the driving force may come from V-H+-ATPase by generating the H+ ion gradient to facilitate the ion flow. Thirteen crab species from two families were used in this study. These crabs lived in five different habitats, including marine,intertidal, bimodal, freshwater and terrestrial habitats. The distribution of V-H+-ATPase in the 13 euryhaline crabs was revealed by histochemistry. V-H+-ATPase was localized in the apical region in crabs that could survive in the freshwater environment. We found that the freshwater and terrestrial crabs with stable Na+,K+-ATPase activity during salinity changes tended to have an apical V-H+-ATPase, whereas the intertidal ones with varying Na+,K+-ATPase activity showed a cytoplasmic V-H+-ATPase distribution. Finally, in Uca formosensis, a crab that had stable Na+,K+-ATPase activity, a significant difference in V-H+-ATPase activity between salinities was found. In conclusion, the hypothesis that V-H+-ATPase plays a crucial role in the freshwater adaptation of crabs is supported by our systemic investigation on 13 euryhaline crabs.
Non-invasive measurement of instantaneous forces during aquatic locomotion: a case study of the bluegill sunfish pectoral fin
Authors: Peng Jifeng , Dabiri John O. , Madden Peter G. , Lauder George V. 
Published: February 2007

SUMMARYSwimming and flying animals generate unsteady locomotive forces by delivering net momentum into the fluid wake. Hence, swimming and flying forces can be quantified by measuring the momentum of animal wakes. A recently developed model provides an approach to empirically deduce swimming and flying forces based on the measurement of velocity and vortex added-mass in the animal wake. The model is contingent on the identification of the vortex boundary in the wake. This paper demonstrates the application of that method to a case study quantifying the instantaneous locomotive forces generated by the pectoral fins of the bluegill sunfish (Lepomis macrochirusRafinesque), measured using digital particle image velocimetry (DPIV). The finite-time Lyapunov exponent (FTLE) field calculated from the DPIV data was used to determine the wake vortex boundary, according to recently developed fluid dynamics theory. Momentum of the vortex wake and its added-mass were determined and the corresponding instantaneous locomotive forces were quantified at discrete time points during the fin stroke. The instantaneous forces estimated in this study agree in magnitude with the time-averaged forces quantified for the pectoral fin of the same species swimming in similar conditions and are consistent with the observed global motion of the animals. A key result of this study is its suggestion that the dynamical effect of the vortex wake on locomotion is to replace the real animal fin with an `effective appendage', whose geometry is dictated by the FTLE field and whose interaction with the surrounding fluid is wholly dictated by inviscid concepts from potential flow theory. Benefits and limitations of this new framework for non-invasive instantaneous force measurement are discussed, and its application to comparative biomechanics and engineering studies is suggested.
Orienting and avoidance turning are precisely computed by the predatory sea-slugPleurobranchaea californicaMcFarland
Authors: Yafremava Liudmila S. , Anthony Christopher W. , Lane Laura , Campbell Jessica K. , Gillette Rhanor 
Published: February 2007

SUMMARYComputing the direction and amplitude of orienting and avoidance turns is fundamental to prey pursuit and risk avoidance in motile foragers. We examined computation of turns in the predatory sea-slug Pleurobranchaea californica, observing orienting and aversive turn responses to chemotactile stimuli applied to the chemosensory oral veil. We made seven observations: (1) the relation of turn angle/stimulus site on the oral veil was linear; (2) turn amplitudes increased with stimulus strength; (3) turn responses markedly overshot the target stimulus; (4) responses to two simultaneous stimuli at different loci were averaged to an intermediate angle;(5) stimuli could induce sequential turns in which the angles of the first and third turns were similar, a form of working memory; (6) turn direction was affected by appetitive state, so that animals with higher feeding thresholds tended to avoid appetitive stimuli; and (7) avoidance turns induced by mildly noxious stimuli were computed similarly to orienting, while differing in direction. These observations appear to outline a framework of behavior that could be employed for efficient tracking of odor trails, and which is regulated by decision mechanisms that integrate sensation, internal state and experience.
Are beliefs elicited biased by question order? A theory of planned behaviour belief elicitation study about walking in the UK general population
Authors: Darker Catherine D. , French David P. , Longdon Stuart , Morris Katie , Eves Frank F. 
Published: February 2007

Objectives. To elicit salient beliefs about walking for an average of 30 minutes per day, with the aims of investigating whether the order of Theory of Planned Behaviour (TPB) belief elicitation questions affects the number and types of beliefs elicited and whether affective and instrumental questions elicit different beliefs.Design. A 3 × 2×2 × 2 mixed factorial design was employed, with order of behavioural, normative and control questions, and affective and instrumental questions as between‐subjects variables, and affective/instrumental and positive/negative questions as within‐subjects variables.Method. Quota sampling with regards to age and gender (N = 180) was employed to obtain a sample that was broadly representative of the adult general population.Results. The order in which behavioural, normative and control beliefs were asked had little impact on the number or type of beliefs elicited. The affective/instrumental attitude distinction was supported. Few differences were apparent between older and younger respondents and between men and women.Conclusion. TPB belief elicitation studies are not biased by order effects. Interventions to promote walking should consider targeting affective beliefs, e.g. stress relief, in addition to beliefs about health, which is the traditional focus of health campaigns. Given the similarities in beliefs across demographic groups, ‘one size fits all’ interventions to promote walking are appropriate.