bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuregulin/ErbB Signaling Regulates Cardiac Subtype Specification in Differentiating Human Embryonic Stem Cells
Authors: Zhu Wei-Zhong , Xie Yiheng , Moyes Kara White , Gold Joseph D. , Askari Bardia , Laflamme Michael A.
Published: July 2010

Rationale:

Human embryonic stem cell–derived cardiomyocytes (hESC-CMs) exhibit either a “working” chamber or a nodal-like phenotype. To generate optimal hESC-CM preparations for eventual clinical application in cell-based therapies, we will need to control their differentiation into these specialized cardiac subtypes.

Objective:

To demonstrate intact neuregulin (NRG)-1β/ErbB signaling in hESC-CMs and test the hypothesis that this signaling pathway regulates cardiac subtype abundance in hESC-CM cultures.

Methods and Results:

All experiments used hESC-CM cultures generated using our recently reported directed differentiation protocol. To support subsequent action potential phenotyping approaches and provide a higher-throughput method of determining cardiac subtype, we first developed and validated a novel genetic label that identifies nodal-type hESC-CMs. Next, control hESC-CM preparations were compared to those differentiated in the presence of exogenous NRG-1β, an anti–NRG-1β neutralizing antibody, or the ErbB antagonist AG1478. We used 3 independent approaches to determine the ratio of cardiac subtypes in the resultant populations: direct action potential phenotyping under current-clamp, activation of the aforementioned genetic label, and subtype-specific marker expression by RT-PCR. Using all 3 end points, we found that inhibition of NRG-1β/ErbB signaling greatly enhanced the proportion of cells showing the nodal phenotype.

Conclusions:

NRG-1β/ErbB signaling regulates the ratio of nodal- to working-type cells in differentiating hESC-CM cultures and presumably functions similarly during early human heart development. We speculate that, by manipulating NRG-1β/ErbB signaling, it will be possible to generate preparations of enriched working-type myocytes for infarct repair, or, conversely, nodal cells for potential use in a biological pacemaker.
Unexpected Role of the Copper Transporter ATP7A in PDGF-Induced Vascular Smooth Muscle Cell Migration
Authors: Ashino Takashi , Sudhahar Varadarajan , Urao Norifumi , Oshikawa Jin , Chen Gin-Fu , Wang Huan , Huo Yuqing , Finney Lydia , Vogt Stefan , McKinney Ronald D. , Maryon Edward B. , Kaplan Jack H. , Ushio-Fukai Masuko , Fukai Tohru
Published: July 2010

Rationale:

Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from
trans
-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation.

Objective:

To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration.

Methods and Results:

Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model.

Conclusions:

These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.
Early Depressed Mood After Stroke Predicts Long-Term Disability
Authors: Willey Joshua Z. , Disla Norbelina , Moon Yeseon Park , Paik Myunghee C. , Sacco Ralph L. , Boden-Albala Bernadette , Elkind Mitchell S.V. , Wright Clinton B.
Published: July 2010

Background and Purpose—

Depression is highly prevalent after stroke and may influence recovery. We aimed to determine whether depressed mood acutely after stroke predicts subsequent disability and mortality.

Methods—

As part of the Northern Manhattan Stroke Study, a population-based incident stroke case follow-up study performed in a multiethnic urban population, participants were asked about depressed mood within 7 to 10 days after stroke. Participants were followed every 6 months the first 2 years and yearly thereafter for 5 years for death and disability measured by the Barthel Index. We fitted polytomous logistic regression models using a canonical link to examine the association between depressed mood after stroke and disability comparing moderate (Barthel Index 60 to 95) and severe (Barthel Index <60) disability with no disability (Barthel Index ≥95). Cox proportional hazards models were created to examine the association between depressed mood and mortality.

Results—

A question about depressed mood within 7 to 10 days after stroke was asked in 340 of 655 patients with ischemic stroke enrolled, and 139 reported that they felt depressed. In multivariate analyses controlling for sociodemographic factors, stroke severity, and medical conditions, depressed mood was associated with a greater odds of severe disability compared with no disability at 1 (OR 2.91, 95% CI 1.07 to 7.91) and 2 years (OR 3.72, 95% CI 1.29 to 10.71) after stroke. Depressed mood was not associated with all-cause mortality or vascular death.

Conclusion—

Depressed mood after stroke is associated with disability but not mortality after stroke. Early screening and intervention for mood disorders after stroke may improve outcomes and requires further research.
A Simple Positron Emission Tomography-Based Calibration for Perfusion-Weighted Magnetic Resonance Maps to Optimize Penumbral Flow Detection in Acute Stroke
Authors: Zaro-Weber Olivier , Moeller-Hartmann Walter , Heiss Wolf-Dieter , Sobesky Jan
Published: July 2010

Background and Purpose—

Perfusion-weighted (PW) MRI is increasingly used to identify the tissue at risk. The adequate PW-MRI map and threshold remain controversial due to a considerable individual variation of values. By comparative positron emission tomography, we evaluated a simple MR-based and positron emission tomography-validated calibration of PW maps.

Methods—

PW-MRI and quantitative positron emission tomography (15O-water) of patients with acute stroke were used to calculate averaged as well as individual thresholds of penumbral flow (positron emission tomography cerebral blood flow (<20 mL/100 g/min) for maps of time to peak, mean transit time, cerebral blood flow, and cerebral blood volume. A linear regression analysis studied the variability of the individual thresholds using 3 different PW reference regions (hemispheric, white matter, gray matter). The best model was used for volumetric analysis to compare averaged and scaled individual thresholds and to calculate look-up tables for PW maps.

Results—

In 26 patients, the averaged thresholds were (median/interquartile range): cerebral blood flow 21.7 mL/100 g/min (19.9 to 32); cerebral blood volume 1.5 mL/100 g (0.9 to 1.8); mean transit time seconds 5.2 (3.9 to 6.9); and relative time to peak 4.2 seconds (2.8 to 5.8). The large individual variability was best explained by the mean value of the hemispheric reference derived from a region of interest on a level with the basal ganglia of the unaffected hemisphere (
R
2
: cerebral blood flow 0.76, cerebral blood volume 0.55, mean transit time 0.83, time to peak 0.95). Hemispheric reference-corrected thresholds clearly improved the detection of penumbral flow. Look-up tables were calculated to identify the individual thresholds according to the hemispheric reference value.

Conclusion—

The individual variation of PW values, even if calculated by deconvolution, remains a major obstacle in quantitative PW imaging and can be significantly improved by a simple MR-based calibration. Easily applicable look-up tables identify the individual best threshold for each PW map to optimize mismatch detection.
Erythropoietin in Combination of Tissue Plasminogen Activator Exacerbates Brain Hemorrhage When Treatment Is Initiated 6 Hours After Stroke
Authors: Jia Longfei , Chopp Michael , Zhang Li , Lu Mei , Zhang Zhenggang
Published: July 2010

Background and Purpose—

Erythropoietin (EPO), a hematopoietic cytokine, exerts neuroprotective effects in experimental stroke. In the present study, we investigated the effect of recombinant human EPO (rhEPO) in combination with tissue plasminogen activator (tPA) on embolic stroke.

Methods—

Rats subjected to embolic middle cerebral artery occlusion (MCAO) were treated with rhEPO (5000 U/kg) in combination with tPA (10 mg/kg) at 2 or 6 hours after MCAO. Control groups consisted of ischemic rats treated with rhEPO (5000 U/kg) alone, tPA (10 mg/kg) alone, or saline at 2 or 6 hours after MCAO.

Results—

The combination therapy of rhEPO and tPA initiated 6 hours after MCAO did not reduce the ischemic lesion volume and significantly (
P
<0.05) increased the incidence of brain hemorrhage measured by frequency of gross hemorrhage and a quantitative spectrophotometric hemoglobin assay compared with rats treated with rhEPO alone and tPA alone. However, when the combination therapy was initiated 2 hours after MCAO, the treatment significantly (
P
<0.05) reduced the lesion volume and did not substantially increase the incidence of hemorrhagic transformation compared with saline-treated rats. Immunostaining analysis revealed that the combination therapy of rhEPO and tPA at 6 hours significantly (
P
<0.05) increased matrix metalloproteinase-9, NF-κB, and interleukin-1 receptor-associated kinase-1 immunoreactive cerebral vessels compared with rats treated with rhEPO alone and saline.

Conclusions—

EPO exacerbates tPA-induced brain hemorrhage without reduction of ischemic brain damage when administered 6 hours after stroke in a rat model of embolic MCAO and that matrix metalloproteinase-9, NF-κB, and interleukin-1 receptor-associated kinase-1 upregulated by the delayed combination therapy may contribute to augmentation of brain hemorrhage.
Cerebral Small Vessel Disease and Kidney Function Predict Long-Term Survival in Patients With Acute Stroke
Authors: Oksala Niku K.J. , Salonen Tapani , Strandberg Timo , Oksala Anni , Pohjasvaara Tarja , Kaste Markku , Karhunen Pekka J. , Erkinjuntti Timo
Published: July 2010

Background and Purpose—

Cerebral small vessel disease reflected by white matter lesions (WMLs) in MRI and kidney function reflected by estimated glomerular filtration rate (eGFR) is closely associated in patients without stroke. We studied whether eGFR and WMLs predict long-term survival in patients with acute stroke.

Methods—

After exclusion of patients with low eGFR (N=5 [1.3%]; <30 mL/min/1.73 m
2
), consecutive patients with acute stroke (N=378) subjected to MRI and serum creatinine determination were included in the study and prospectively followed-up up to 12 years.

Results—

Of the patients, 71.2% had died during the follow-up, 152 (40.2%) had moderate (eGFR <60 mL/min/1.73 m
2
), and 226 (59.8%) had normal or mildly impaired eGFR (≥60 mL/min/1.73 m
2
). Of the patients, 108 (28.6%) had mild, 68 (18.0%) had moderate, and 202 (53.4%) had severe WMLs. In logistic regression analysis adjusted with age and sex, eGFR <60 mL/min/1.73 m
2
was associated with severe WMLs (relative risk 2.77, 95% CI 1.10 to 6.98,
P
=0.030). In Cox regression survival analysis adjusted with significant covariates, eGFR <60 mL/min/1.73 m
2
(1.30, 95% CI 1.00 to 1.68,
P
=0.047) and severe WMLs (hazard ratio 1.32, 95% CI 1.02 to 1.71,
P
=0.033) were associated with poor survival, whereas they were not independent from each other. In further analyses, presence of either eGFR ≥60 mL/min/1.73 m
2
or only mild to moderate WMLs, or both, was associated with improved survival compared with all other combinations.

Conclusions—

Cerebral small vessel disease is closely associated with kidney function in patients with acute stroke. Cerebral small vessel disease and kidney function are closely associated predictors of poor poststroke survival.
Niacin Treatment of Stroke Increases Synaptic Plasticity and Axon Growth in Rats
Authors: Cui Xu , Chopp Michael , Zacharek Alex , Roberts Cynthia , Buller Benjamin , Ion Madalina , Chen Jieli
Published: July 2010

Background and Purpose—

Niacin is the most effective medication in current clinical use for increasing high-density lipoprotein cholesterol. We tested the hypothesis that niacin treatment of stroke promotes synaptic plasticity and axon growth in the ischemic brain.

Methods—

Male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion and treated with or without Niaspan (a prolonged-release formulation of niacin, 40 mg/kg) daily for 14 days starting 24 hours after middle cerebral artery occlusion. The expression of synaptophysin, Nogo receptor, Bielschowsky silver, brain-derived neurotrophic factor, and its receptor tropomyosin-related kinase B were measured by immunohistostaining and Western blot, respectively, in the ischemic brain. Complementing in vivo studies, primary cultured neurons were used to test the effect of niacin and high-density lipoprotein on neurite outgrowth and brain-derived neurotrophic factor/tropomyosin-related kinase B expression.

Results—

Niaspan treatment of stroke significantly increased synaptophysin, Bielschowsky silver, brain-derived neurotrophic factor/tropomyosin-related kinase B expression, and decreased Nogo receptor expression in the ischemic brain compared with middle cerebral artery occlusion control animals (
P
<0.05, n=8/group). Niacin and high-density lipoprotein treatment significantly increased neurite outgrowth and brain-derived neurotrophic factor/tropomyosin-related kinase B expression in primary cultured neurons. Tropomyosin-related kinase B inhibitor attenuated niacin-induced neurite outgrowth (
P
<0.05, n=6/group).

Conclusions—

Niacin treatment of stroke promotes synaptic plasticity and axon growth, which is mediated, at least partially, by the brain-derived neurotrophic factor/tropomyosin-related kinase B pathways.
Pythagorean Number Symbolism, Alchemy, and the Disciplina Noua of John Dee's Monas Hieroglyphica
Authors: Clucas Stephen
Published: July 2010

Tant dans sa Monas Hieroglyphica (1564) que dans sa Mathematical Praeface (1570), John Dee défend une vue des mathématiques qui se veut compatible avec l'idée d'un 'Pythagoricall, and Platonicall perfect scholer'. Cet article montre que ce furent les doctrines arithmologiques contenues dans les épîtres de Trithème—lues par Dee dans une copie du De vsu et mysteriis notarum (1550), qu'il acheta à Anvers en 1562/3—qui exercèrent sur les doctrines pythagoriciennes de la Monas de Dee un impact en profondeur. Alors que des commentateurs antérieurs ont mis l'accent sur l'orientation alchimique de l'oeuvre de Dee, une lecture serrée des lettres de Trithème (et les annotations portées par Dee sur celles-ci) montre qu'il croyait que le connaissance des mystères arithmologiques de Trithème s'étendait bien au-delà de l'alchimie, et devait constituer une 'discipline nouvelle' appelée à devenir une science occulte universelle.
Oratorium—Auditorium—Laboratorium: Early Modern Improvisations on Cabala, Music, and Alchemy
Authors: Forshaw Peter
Published: July 2010

La gravure du Lab-Oratorium, dans l'Amphithéâtre de la Sagesse Eternelle (1595/1609), du paracelsien Heinrich Khunrath de Leipzig (1560–1605)—'docteur des deux médecines et fidèle amoureux de la théosophie'—est une image bien connue des historiens de l'ésotérisme du début des Temps Modernes, mais peu de choses ont été dites sur la signification des instruments musicaux qui sont au premier plan de l'image. Cet article examine les diverses références qui, dans les écrits de Khunrath, concernent la musique et le thème y relatif de l'harmonie dans le contexte des activités kabbalistiques et alchimiques de Khunrath en son Oratoire et son Laboratoire. Il examine l'influence d'idées pythagoriciennes sur les pratiques théurgiques de Khunrath, identifie la source christiano-kabbalistique de l'hymne polyglotte qu'il relie à l'une des images théosophiques sur la table de son Oratoire, et propose une réflexion sur l'usage de la musique dans cette dimension kabbalistique de son œuvre. Etant donné que Khunrath est connu surtout comme praticien de l'alchimie, la seconde section de l'article traite de quelques exemples de chant et de musique, à commencer par un manuscrit qui a survécu dans le travail de Khunrath, et se termine par un bref examen de la plus célèbre combinaison d'alchimie et de musique; à savoir, l' Atlanta Fugiens (1617), de son admirateur le Comte Michael Maier (1568–1622).
Nous and Two Kinds of Epistêmê in Aristotle’s Posterior Analytics
Authors: Perelmuter Zeev
Published: July 2010

At the beginning of Posterior Analytics 2.19 Aristotle reminds us that we cannot claim demonstrative knowledge (epistêmê apodeiktikê) unless we know immediate premisses, the archai of demonstrations. By the end of the chapter he explains why the cognitive state whereby we get to know archai must be Nous. In between, however, Aristotle describes the process of the acquisition of concepts, not immediate premisses. How should we understand this? There is a general agreement that it is Nous by means of which we acquire both premisses and concepts. I argue that this cannot be the case. Since concepts are simples while premisses are composites (predications of concepts), the two cannot be objects of the same cognitive state. I further argue that, whereas Nous is responsible for our grasp of concepts, the state Aristotle elsewhere calls non-demonstrable knowledge is the one whereby we get to know the premisses of demonstrations.
The Form and Meaning of Hebrew ’ašrê
Authors: Rubin Aaron D.
Published: July 2010

The poetic Hebrew word ’ašrê is difficult to parse, and is without a good Semitic etymology. By suggesting that the word is in fact a remnant of the elative pattern, we can explain its shape and syntactic function, and provide a solid Semitic etymology.
Short Note
Authors: Angel Andrew
Published: July 2010

4Q541 uses to refer to the chaos sea. This provides a parallel for reading the same phrase in Dan 7:2 as the mythological sea rather than the Mediterranean.
Ideology and Organization in the Qing Empire
Authors: Guy R. Kent
Published: July 2010

This article considers an essay on provincial government written by the Yongzheng Emperor of China shortly after his ascension to the throne in 1723. The essay treats provincial governors’ role in personnel, financial and military matters and the problems of China’s southwest. It reflects the emperor’s dissatisfaction with policies in each of these areas, which were all to be the focus of reforming efforts during his reign. But perhaps more important, it expresses the Emperor’s new concern with the value of administrative efficacy. The essay argues that this was a fundamental innovation in the political theology of the Chinese state. Although practical ideas for reform often came from governors themselves, who were closer to the problems than the Emperor and more familiar with the details of solution, imperial leadership created a climate in which reform ideas would be welcomed and implemented.
News and Views
Authors: Hout F.A.G. , Frederiks B.J.M. , Nienhuis E.D. , Legemaate J. , Robben P.B.M.
Published: July 2010

The Dutch Healthcare Inspectorate’s (Inspectie voor de Gezondheidszorg) supervisory activities are based on proportional use of the instruments. The primary instruments it uses are advice and encouragement. If these do not achieve the desired result, it can implement corrective action by, for example, enhancing its supervision or through agreements limiting the ability to practise a profession. Recourse to disciplinary or administrative measures can be sought, if necessary. There is a tendency to use statutory instruments, which means greater equality before the law and greater legal certainty. It is important in this respect for the Inspectorate to make its considerations more uniform, transparent and predictable.
Printing and Social Control in Russia 1: Passports
Authors: Franklin Simon
Published: July 2010

Studies of the history of print in Russia tend to focus on the printing of books, and to a lesser extent pictures. However, the implications of the spread of information technologies extend beyond their cultural uses. In particular, the adoption of printing (like the spread of writing before it, and the spread of electronic and digital technologies in recent decades) has potential implications for administration and social control. This study – the first in a series on related themes – considers the introduction and uses of print in one category of document, the passport, in the 18th and early 19th centuries. The main sources are legislative. The printing of passports was not just an administrative practice but a legislative issue and a recurrent problem. The use of print for specified types of passport was first decreed in 1726, as an anti-forgery measure, but successive revisions and modifications of the legislation show that precisely the feature which made print attractive as a device to combat fraud - centralised State control of the means of production - also created logistical difficulties which could obstruct the effective operations of the passport system itself. The final section of the survey is comparative, setting Russia's practices and preoccupations in the printing of passports in a wider European and American context, in order to identify what may have been distinctive to Russia.
The Post Recession Growth Prospects of South East European Economies
Authors: Kukavčić Jasena , Bićanić Ivo , Spajić Vjerana
Published: July 2010

This paper starts with a discussion of how the world recession as an external shock influenced the already vulnerable South East European (SEE) economies. All countries except Albania and Kosovo experienced a recession as well as a termination of the foreign debt based heating-up that generated high growth rates after 2000. The paper provides an overview of states' policy responses, with individual countries surveyed in the appendix. We argue that, with the exception of Albania, all SEE economies started with a fiscal expansion, which coincided with elections in which the existing governments were not re-elected. This was followed by public finance crises, fiscal consolidation and more active monetary policy which averted a financial crisis, with only three of these economies turning to the IMF for help. Nevertheless, the cumulative effect was an extended trough. The paper then discusses the recession's impact on growth in terms of three growth projections derived from historical experience and two ad hoc benchmarks. We examine the consequences of returning to a lower post recession growth trajectory and calculate the time required to return to secular growth and achieve chosen benchmarks. The conclusion for both is that convergence time varies from less than a decade to no convergence before 2040, with the exception of Albania.
Inequality and Democratization: A Contractarian Approach
Authors: Ansell Ben , Samuels David
Published: July 2010

Scholars continue to grapple with the question of the relationship between economic development and democratization; prominent recent research has focused on the effects of economic inequality. Boix suggests that democratization is likelier when inequality is low, whereas Acemoglu and Robinson argue that democratization is likelier when inequality is at middling levels. Both assume that democratization is a function of autocratic elites’ fear of the extent to which a future median voter would redistribute under different levels of inequality. Drawing on contractarian political theory, the authors suggest that democratization is instead a function of demands by rising economic groups for protection from the state. This alternative approach suggests that land and income inequality affect democratization differently: Autocracies with equal land distribution are indeed more likely to democratize, but contrary to the conventional wisdom, income inequality is more likely to promote democratization.
Oral and Systemic Health Correlates of HIV-1 Shedding in Saliva
Authors: Navazesh M. , Mulligan R. , Kono N. , Kumar S.K.S. , Nowicki M. , Alves M. , Mack W.J.
Published: July 2010

The relationship among oral and systemic health and HIV shedding in saliva is not well-understood. We hypothesized that oral and systemic health are associated with HIV shedding in saliva of HIV-infected women. Saliva from 127 participants enrolled in the Women’s Interagency HIV Study (WIHS) was collected at repeated visits over a 5½-year study period (October 1998 through March 2004) and was evaluated for HIV-1 RNA. Demographic, lifestyle, and systemic and oral health characteristics were evaluated as possible correlates of salivary HIV-1 shedding. Multivariate models showed significantly increased risk of HIV-1 shedding in saliva as blood levels of CD4 cell counts decreased (p < 0.0001) and HIV RNA increased (p < 0.0001). Diabetes (p = 0.002) and a high proportion of gingival bleeding sites (p = 0.01) were associated with increased likelihood, while anti-retroviral therapy (p = 0.0003) and higher levels of stimulated saliva flow rates (p = 0.02) were associated with a lower likelihood of HIV-1 RNA shedding in saliva.
A Randomized Trial on Root Caries Prevention in Elders
Authors: Tan H.P. , Lo E.C.M. , Dyson J.E. , Luo Y. , Corbet E.F.
Published: July 2010

Root caries is common in institutionalized elders, and effective prevention methods are needed. This clinical trial compared the effectiveness of four methods in preventing new root caries. From 21 residential homes, 306 generally healthy elders having at least 5 teeth with exposed sound root surfaces were randomly allocated into one of four groups: (1) individualized oral hygiene instruction (OHI); (2) OHI and applications of 1% chlorhexidine varnish every 3 months; (3) OHI and applications of 5% sodium fluoride varnish every 3 months; and (4) OHI and annual applications of 38% silver diamine fluoride (SDF) solution. Two-thirds (203/306) of the elders were followed for 3 years. Mean numbers of new root caries surfaces in the four groups were 2.5, 1.1, 0.9, and 0.7, respectively (ANOVA, p < 0.001). SDF solution, sodium fluoride varnish, and chlorhexidine varnish were more effective in preventing new root caries than giving OHI alone.
An Exploration of African American Students’ Attitudes Toward Online Learning
Authors: Okwumabua Theresa M. , Walker Kristin M. , Hu Xiangen , Watson Andrea
Published: July 2010

The current work presents exploratory research findings concerning African American students’ attitudes toward online learning. The Online Tutoring Attitudes Scale (OTAS; Graff, 2003) was administered to 124 African American students in a positive youth development program. Findings suggest that African American students’ attitudes toward computers are inconsistent with their attitudes toward online learning. African American students reported positive attitudes toward computers; however, their attitudes reflected anxiety, lack of confidence, and little use for online learning experiences. Implications of this research are relevant to educational interventions, academic achievement, and technological advancement with respect to underrepresented populations.
A Brief Survey of First‐in‐Human Studies
Authors: Wexler David , Bertelsen Kirk M.
Published: July 2010

First‐in‐human (FIH) studies are a critical step in the drug development process and typically aim to characterize a compound's pharmacokinetics, potential effective concentration or dose, and safety or tolerability margins. Although effort continues to enhance the predictive quality of the selection of FIH doses from preclinical data, and little consensus is available on the design and conduct of FIH studies, detailed surveys describing general approaches taken in FIH studies are useful in the optimization of early‐phase clinical drug development. Although allometric scaling techniques continue to provide poor predictive estimates for human pharmacokinetic parameters, FIH starting doses are selected with substantial safety factors applied to human equivalent dose, often in excess of regulatory guidelines. Based on these examples, it appears that relatively conservative 2‐fold dose escalations are the most common escalation approach within FIH single ascending dose studies. The combination of conservative dose escalations with low starting doses can result in large FIH trials, consuming both time and resources. Approaches that could enhance the predictive nature of a compound's disposition and adaptive nature of FIH studies could provide a tremendous benefit for drug development.
Effect of Arrangement of Stick Figures on Estimates of Proportion in Risk Graphics
Authors: Ancker Jessica S. , Weber Elke U. , Kukafka Rita
Published: July 2010

Background. Health risks are sometimes illustrated with stick figures, with a certain proportion colored to indicate they are affected by the disease. Perception of these graphics may be affected by whether the affected stick figures are scattered randomly throughout the group or arranged in a block. Objective. To assess the effects of stick-figure arrangement on first impressions of estimates of proportion, under a 10-s deadline. Design. Questionnaire. Participants and Setting. Respondents recruited online (n = 100) or in waiting rooms at an urban hospital (n = 65). Intervention. Participants were asked to estimate the proportion represented in 6 unlabeled graphics, half randomly arranged and half sequentially arranged. Measurements. Estimated proportions. Results. Although average estimates were fairly good, the variability of estimates was high. Overestimates of random graphics were larger than overestimates of sequential ones, except when the proportion was near 50%; variability was also higher with random graphics. Although the average inaccuracy was modest, it was large enough that more than one quarter of respondents confused 2 graphics depicting proportions that differed by 11 percentage points. Low numeracy and educational level were associated with inaccuracy. Limitations. Participants estimated proportions but did not report perceived risk. Conclusions. Randomly arranged arrays of stick figures should be used with care because viewers’ ability to estimate the proportion in these graphics is so poor that moderate differences between risks may not be visible. In addition, random arrangements may create an initial impression that proportions, especially large ones, are larger than they are.
Communication of Uncertainty Regarding Individualized Cancer Risk Estimates
Authors: Han Paul K. J. , Klein William M. P. , Lehman Tom , Killam Bill , Massett Holly , Freedman Andrew N.
Published: July 2010

Objective. To examine the effects of communicating uncertainty regarding individualized colorectal cancer risk estimates and to identify factors that influence these effects. Methods. Two Web-based experiments were conducted, in which adults aged 40 years and older were provided with hypothetical individualized colorectal cancer risk estimates differing in the extent and representation of expressed uncertainty. The uncertainty consisted of imprecision (otherwise known as “ambiguity”) of the risk estimates and was communicated using different representations of confidence intervals. Experiment 1 ( n = 240) tested the effects of ambiguity (confidence interval v. point estimate) and representational format (textual v. visual) on cancer risk perceptions and worry. Potential effect modifiers, including personality type (optimism), numeracy, and the information’s perceived credibility, were examined, along with the influence of communicating uncertainty on responses to comparative risk information. Experiment 2 ( n = 135) tested enhanced representations of ambiguity that incorporated supplemental textual and visual depictions. Results. Communicating uncertainty led to heightened cancer-related worry in participants, exemplifying the phenomenon of “ambiguity aversion.” This effect was moderated by representational format and dispositional optimism; textual (v. visual) format and low (v. high) optimism were associated with greater ambiguity aversion. However, when enhanced representations were used to communicate uncertainty, textual and visual formats showed similar effects. Both the communication of uncertainty and use of the visual format diminished the influence of comparative risk information on risk perceptions. Conclusions. The communication of uncertainty regarding cancer risk estimates has complex effects, which include heightening cancer-related worry—consistent with ambiguity aversion—and diminishing the influence of comparative risk information on risk perceptions. These responses are influenced by representational format and personality type, and the influence of format appears to be modifiable and content dependent.
Health Effects in Significant Others
Authors: Bobinac Ana , van Exel N. Job A. , Rutten Frans F. H. , Brouwer Werner B. F.
Published: July 2010

Background. Changes in the health of patients may affect the health of so-called “significant others” in 2 distinct ways. First, an individual may provide informal care to the patient and be burdened by the process of care giving. We label this indirect effect of a patient’s health on the health of the care giver the “care-giving effect.” Second, a person may suffer from health losses because someone in his or her social environment is ill, regardless of his or her care-giving status. The health of the patient then directly affects the health of this significant other, which we label the “family effect.” Methods. We investigate the occurrence of the family and care-giving effect in a convenience sample of Dutch care givers ( n = 751). The family effect was approximated by the health status of the patient (measured on EuroQol-VAS), and the care-giving effect by the number of the care-giving tasks was provided. It was assumed that care givers’ health is positively associated with patients’ health, that is, the family effect, and negatively associated with care-giving burden, that is, the care-giving effect. Relationships are studied using multivariate regressions. Results. Our results support the existence of both types of health effects. The analysis shows that the 2 effects are separable and independently associated with the health of care givers. Not accounting for the family effect conflates the care-giving effect. Conclusions. If the goal of health care policy is to optimize health, all important effects should be captured. The scope of economic evaluations should also include health effects in significant others. This study suggests that significant others include both care givers and broader groups of affected individuals, such as family members.
CAD Model-based Tracking and 3D Visual-based Control for MEMS Microassembly
Authors: Tamadazte B. , Marchand E. , Dembélé S. , Le Fort-Piat N.
Published: July 2010

This paper investigates sequential robotic microassembly for the construction of 3D micro-electro-mechanical systems (MEMSs) structures using a 3D visual servoing approach. The previous solutions proposed in the literature for these kinds of problems are based on 2D visual control because of the lack of precise and robust 3D measures from the work scene. In this paper, the relevance of the real-time 3D visual tracking method and the 3D vision-based control law proposed is demonstrated. The 3D poses of the MEMSs are supplied in real-time by a computer-aided design model-based tracking algorithm. This algorithm is sufficiently accurate and robust to enable a precise regulation toward zero of the 3D error using the proposed pose-based visual servoing approach. Experiments on a microrobotic setup have been carried out to achieve assemblies of two or more 400 μm × 400 μm × 100 μm silicon micro-objects by their respective 97 μm × 97 μm × 100 μm notches with an assembly clearance from 1 μm to 5 μm. The different microassembly processes are performed with a mean error of 0.3 μm in position and 0.35× 10−2 rad in orientation.
Guidance for the management of headache in sport on behalf of The Royal College of General Practitioners and The British Association for the Study of Headache
Authors: Kernick David P , Goadsby Peter J
Published: July 2010

Headache is prevalent within the community and can have an impact on sport in both the amateur and elite player, either coincidentally or as a direct result of participation. Against a background of a limited evidence base, this paper suggests how headache can be classified within this context and offers guidance for treating both the amateur and elite athlete. The impact of headache in sport may be unrecognised and undertreated, and further research is needed in this area.
Migraine diagnosis and management in general emergency departments in France
Authors: Valade D , Lucas C , Calvel L , Plaisance P , Derouet N , Meric G , Lanteri-Minet M , Giroud M
Published: July 2010

Background

We conducted a prospective study of patients admitted to 22 general emergency departments in France over 1 week.

Patients and methods

Of 15,835 adult patients, 483 (3.1%) had headache and 98 (0.6%) had migraine.

Results

Compared with the migraine population in France, our migraine patients were similar in terms of proportion of female patients (75%) and mean age (37.6 ± 13.8 years) but presented earlier in their disease course. Patients sought emergency treatment because of a severe attack (49%) or because of ineffective treatment (20%). Non-opioid analgesics excluding non-steroidal anti-inflammatory drugs (NSAIDs), and NSAIDs, were most commonly prescribed as acute treatment, yet it took more than 48 h for symptom resolution in 36% of 92 follow-up patients.

Conclusions

Results suggest there is room for improvement in choice of agents prescribed. We propose additional education and training of clinicians to improve adherence to clinical practice guidelines.
Cluster headache associated with a sixth nerve palsy: A case report
Authors: Grosberg Brian M , Vollbracht Sarah , Robbins Matthew S , Lipton Richard B
Published: July 2010

Background: Cluster headache is a rare primary headache disorder characterized by recurrent, stereotyped short-lasting attacks of severe, unilateral head pain accompanied by autonomic symptoms.

Methods/results: Ophthalmic features such as conjunctival injection, lacrimation, ptosis and miosis occur in the vast majority of patients with cluster headache, whereas co-existent ocular movement disorders are rare.

Conclusions: To the best of our knowledge, only two documented cases of cluster headache with external ocular movement disorders have been reported. We describe herein an additional case with this unusual finding and discuss the putative pathophysiology of cluster headache associated with ophthalmoparesis.
Structural Properties of the Primary Medial Knee Ligaments
Authors: Wijdicks Coen A. , Ewart David T. , Nuckley David J. , Johansen Steinar , Engebretsen Lars , LaPrade Robert F.
Published: July 2010

Background: The structural properties of the individual components of the superficial medial collateral ligament (MCL), deep MCL, and posterior oblique ligament (POL) have not been studied in isolation. To define the necessary strength requirements for an anatomical medial knee reconstruction, knowledge of these structural properties is necessary.

Hypothesis: The components of the superficial MCL, POL, and deep MCL have significantly different structural properties.

Study Design: Controlled laboratory study.

Methods: This study used 20 fresh-frozen nonpaired cadaveric knee specimens with a mean age of 54 years (range, 27 to 68 years). These knees provided 8 samples for each tested medial knee structure, which was individually isolated and loaded to failure at 20 mm per minute. Specifically tested were the superficial MCL with intact femoral and detached proximal tibial attachments, the superficial MCL with intact femoral and detached distal tibial attachments, the central arm of the POL, and the isolated deep MCL. Load was recorded as a function of displacement. Stiffness of the ligament at failure was calculated from these measurements.

Results: The mean load at failure for the superficial MCL with the intact femoral and distal tibial attachments was 557 N. Mean load at failure was 88 N for the intact femoral and proximal tibial divisions of the superficial MCL, 256 N for the POL, and 101 N for the deep MCL. Stiffness of the ligaments just before failure was 63, 17, 38, and 27 N/mm, in the same order as above.

Conclusion: The proximal and distal tibial divisions of the superficial MCL, POL, and deep MCL produced loads of clinical importance.

Clinical Relevance: Knowledge of the structural properties of these attachment sites will assist in reconstruction graft choices, fixation method choices, and overall operative treatment of medial knee injury.
Kinematic Impact of Anteromedial and Posterolateral Bundle Graft Fixation Angles on Double-Bundle Anterior Cruciate Ligament Reconstructions
Authors: Anderson Colin J. , Westerhaus Benjamin D. , Pietrini Sean D. , Ziegler Connor G. , Wijdicks Coen A. , Johansen Steinar , Engebretsen Lars , LaPrade Robert F.
Published: July 2010

Background: Currently in double-bundle anterior cruciate ligament (ACL) reconstructions, the range of knee flexion angles that surgeons use for anteromedial (AM) and posterolateral (PL) bundle graft fixation spans from 0° to 90° for both bundle grafts. Despite the recent popularity of this procedure, no consensus exists on an optimal set of AM and PL graft fixation angles.

Hypothesis: Graft fixation angles that simulate the native tensioning relationship of the AM and PL bundles will produce kinematic results similar to the intact knee, while graft fixation angles that do not simulate this relationship will under- or overconstrain the knee.

Study design: Controlled laboratory study.

Methods: Twelve cadaveric knees were biomechanically tested in the intact state, ACL-sectioned state, and a randomized order of 7 double-bundle ACL reconstructed states at multiple graft fixation angle combinations. For each test state, data were collected for 88 N anterior tibial loads, 10 N·m valgus torques, 5 N·m internal rotation torques, and 2 simulated pivot shift loads consisting of a 5 N·m internal rotation torque coupled with either a 10 N·m valgus torque or an 88 N anterior tibial load at 0°, 20°, 30°, 60°, and 90° of knee flexion.

Results: The AM and PL graft fixation angle combinations of 0°/0° (AM graft fixation angle/PL graft fixation angle), 60°/0°, 45°/15°, and 75°/15° restored normal laxity to the reconstructed knee in all of the biomechanical tests. The 30°/30°, 60°/60°, and 90°/90° graft fixation angle combinations significantly restricted knee laxity compared with the intact state in various biomechanical tests.

Conclusion: We found that as long as the PL bundle graft was fixed between 0° and 15°, the AM graft could be fixed up to 75° without restricting knee laxity. However, fixation of the PL graft at 30° of knee flexion and above significantly overconstrained the knee.

Clinical Relevance: This study provides a range of angles that can be used in double-bundle ACL reconstructions to restore normal knee stability without causing overconstraint.
In-field experimental verification of cultivation of microalgae Chlorella sp. using the flue gas from a cogeneration unit as a source of carbon dioxide
Authors: Kaštánek František , Šabata Stanislav , Šolcová Olga , Maléterová Ywette , Kaštánek Petr , Brányiková Irena , Kuthan Karel , Zachleder Vilém
Published: July 2010

A complex treatment of agricultural waste including the following major steps: anaerobic fermentation of suitable waste, cogeneration of the obtained biogas and growth of microalgae consuming the CO2 from biogas and flue gas was verified under field conditions in a pilot-scale photobioreactor. The growth kinetics of microalgae Chlorella sp. consuming mixture of air and carbon dioxide (2% (v/v) of CO2), or flue gas (8—10% (v/v) of CO2) was investigated. The results obtained in the pilot photobioreactor were compared with results previously measured in laboratory photobioreactors. The field tests were performed in a pilot-scale outdoor solar-bubbled photobioreactor located at a biogas station. The pilot-scale photobioreactor was in the shape of a flat and narrow vertical prism with a volume of 300 L. The microalgae growth rates were correlated with empirical formulas. Laboratory analyses of the produced microalgae confirmed that it meets the strict EU criteria for relevant contaminants level in foodstuffs. Utilization of flue gases from cogeneration therefore was not found to be detrimental to the quality of microalgal biomass, and may be used in these types of bioreactors.
Synthesis, characterization and sintering behaviour of indialite ceramic from fly ash
Authors: Yao Zhitong , Tan Shengheng , Xia Meisheng , Ye Ying , Li Jinhui
Published: July 2010

Indialite ceramic was prepared using fly ash and magnesium carbonate powder as precursors. The effects of sintering aids LiOH · H2O and TiO2 on its crystallization and morphology evolution were studied as well. X-ray diffraction results indicated that the formation of indialite was achieved by solid-state sintering reactions at 1200°C for 4 h. With increasing amounts of LiOH · H2O, the viscosity decreased and β-spodumene, spinel phases started to develop at the expense of indialite. Scanning electron microscopy observations revealed that the surface of the sintered samples became smoother with higher porosity losses and grain size reduction. As the TiO2 contents increased from 4 to 10%, dauphine-twinned quartz and rutile were formed by simultaneously consuming indialite. In this process, the viscosity showed no significant changes.
In vivo anti-inflammatory effect and toxicological screening of Maytenus heterophylla and Maytenus senegalensis extracts
Authors: da Silva G. , Taniça M. , Rocha J. , Serrano R. , Gomes ET , Sepodes B. , Silva O.
Published: July 2010

Maytenus heterophylla (Eckl & Zeyh.) Robson and Maytenus senegalensis (Lam). Exell are two African medicinal plants used to treat painful and inflammatory diseases. We evaluated the in vivo (per os) anti-inflammatory activity of M. heterophylla leaf, stem and root extracts and of M. senegalensis leaf and stem extracts. Additionally, we assessed their in vivo acute and sub-acute toxicities. Anti-inflammatory activities of ethanol extracts were determined in Wistar albino rats, by the carrageenan-induced paw oedema method. Acute and sub-acute toxicity screening of the extracts was evaluated in adult male CD-6 mice. Leaf extracts of M. heterophylla and M. senegalensis exhibited significant anti-inflammatory activity (120 mg/kg, per os), reducing oedema by 51% and 35%, respectively. While M. heterophylla extracts at 1200 mg/kg have shown to be non-toxic, M. senegalensis extracts indicated some toxicity. Our results show a significant anti-inflammatory effect of both M. heterophylla and M. senegalensis leaf extracts in a local model of acute inflammation and suggest the absence of acute and sub-acute toxicity signs of the M. heterophylla leaf extract (but not of M. senegalensis). Ongoing studies will surely shed some light into the mechanism of action of this active extract and establish its chemical fingerprint.