bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a case‐based e‐learning environment in a lecture‐oriented anaesthesiology class: Do learning styles matter in complex problem solving over time?*
Authors: Choi Ikseon , Lee Sang Joon , Kang Jeongwan
Published: August 2008

This study explores how students' learning styles influence their learning while solving complex problems when a case‐based e‐learning environment is implemented in a conventional lecture‐oriented classroom. Seventy students from an anaesthesiology class at a dental school participated in this study over a 3‐week period. Five learning‐outcome tests and two course‐satisfaction surveys were implemented during the case‐based instruction using a blended approach (online and face‐to‐face). The results of one‐way ANOVAs with repeated measures revealed that the four learning styles (active–reflective, sensing–intuitive, visual–verbal, sequential–global) did not influence students' learning experience and learning outcomes during the implementation of case‐based e‐learning. However, the pattern of the students' performance graph and further analysis with a liberal approach implied that the active–reflective learning style may influence learning outcomes slightly at an earlier time during the case‐based learning implementation; however, as time passed, this learning style no longer influenced their learning at all. Thus, learning styles may not be considered important or may be considered only during the early stages of instructional implementation in order to facilitate the students' transition to the new case‐based learning environment. It is more efficient to encourage students to adapt to different learning environments than to design adaptive systems in order to embrace diverse learning styles.
Promoting ethical reflection in the teaching of business ethics
Authors: Harris Howard
Published: August 2008

A case study provides the basis for consideration of the purpose of business ethics teaching, the importance of reflection and the evaluation of ethics teaching. The way in which personal reflection and an increased capacity for ethical action can be encouraged and openly identified as aims of the course is discussed. The paper considers changes in the design and delivery of the international management ethics and values course taught at the University of South Australia as part of the undergraduate management degree in Australia, Singapore and Hong Kong. As a result of student and teaching staff responses, and course evaluations, the course design, teaching and assessment has moved steadily toward an aim which explicitly refers to behaviour, without losing the significant conceptual base. Ways in which opportunities can be provided to enhance the development of a reflective capability are considered, including narrative, role models, ethical reflection, journal‐keeping and practice. The changes required a change in assessment practice. The difficulties of assessing intention and commitment to ethical action, whether in an individual course or across the curriculum, are discussed.
Lasting False Beliefs and Their Behavioral Consequences
Authors: Geraerts Elke , Bernstein Daniel M. , Merckelbach Harald , Linders Christel , Raymaekers Linsey , Loftus Elizabeth F.
Published: August 2008

False beliefs and memories can affect people's attitudes, at least in the short term. But can they produce real changes in behavior? This study explored whether falsely suggesting to subjects that they had experienced a food-related event in their childhood would lead to a change in their behavior shortly after the suggestion and up to 4 months later. We falsely suggested to 180 subjects that, as children, they had gotten ill after eating egg salad. Results showed that, after this manipulation, a significant minority of subjects came to believe they had experienced this childhood event even though they had initially denied having experienced it. This newfound autobiographical belief was accompanied by the intent to avoid egg salad, and also by significantly reduced consumption of egg-salad sandwiches, both immediately and 4 months after the false suggestion. The false suggestion of a childhood event can lead to persistent false beliefs that have lasting behavioral consequences.
How to Accurately Detect Autobiographical Events
Authors: Sartori Giuseppe , Agosta Sara , Zogmaister Cristina , Ferrara Santo Davide , Castiello Umberto
Published: August 2008

We describe a new method, based on indirect measures of implicit autobiographical memory, that allows evaluation of which of two contrasting autobiographical events (e.g., crimes) is true for a given individual. Participants were requested to classify sentences describing possible autobiographical events by pressing one of two response keys. Responses were faster when sentences related to truly autobiographical events shared the same response key with other sentences reporting true events and slower when sentences related to truly autobiographical events shared the same response key with sentences reporting false events. This method has possible application in forensic settings and as a lie-detection technique.
When Hurt Will Not Heal
Authors: Chen Zhansheng , Williams Kipling D. , Fitness Julie , Newton Nicola C.
Published: August 2008

Recent discoveries suggest that socialpain is as real and intense as physical pain, and that the social-pain system may have piggybacked on the brain structure that had evolved earlier for physical pain. The present study examined an important distinction between social and physical pain: Individuals can relive and reexperience social pain more easily and more intensely than physical pain. Studies 1 and 2 showed that people reported higher levels of pain after reliving a past socially painful event than after reliving a past physically painful event. Studies 3 and 4 found, in addition, that people performed worse on cognitively demanding tasks after they relived social rather than physical pain. Implications for research on social pain and theories about social pain are discussed.
Search in External and Internal Spaces
Authors: Hills Thomas T. , Todd Peter M. , Goldstone Robert L.
Published: August 2008

There is compelling molecular and behavioral evidence that goal-directed cognition is an evolutionary descendant of spatial-foraging behavior. Across animal species, similar dopaminergic processes modulate between exploratory and exploitative foraging behaviors and control attention. Consequently, we hypothesized that spatialforaging activity could prime attentional cognitive activity. We examined how searching in physical space influences subsequent search in abstract cognitive space by presenting participants with a spatial-foraging task followed by a repeated Scrabble task involving search for words that could be made from letter sets. Participants who searched through clumpier distributions in space behaved as if words were more densely clumped in the Scrabble task. This was not a function of arousal, but was consistent with predictions of optimal-foraging theory. Furthermore, individual differences in exploratory search were conserved across the two types of tasks. Along with the biological evidence, our results support the idea that there are generalized cognitive search processes.
Assessment of sexual dysfunction in patients with Parkinson’s disease: a case–control study
Authors: Celikel E. , Ozel‐Kizil E. T. , Akbostanci M. C. , Cevik A.
Published: August 2008

Background:  Sexual dysfunction (SD) in patients with Parkinson’s disease (PD) has not been very well studied, as most of the research has methodological restrictions like having no control group, using invalid assessment tools, unidimensional investigation of sexual functions and inclusion of males/females only. This study aimed to examine different sexual functions in patients with PD and compare with matched non‐parkinsonian controls by using a valid instrument. Predicting factors of SD in PD were also investigated.

Methods:  The sample consisted of 45 patients with PD and 45 age‐ and sex‐matched healthy controls. Sexual functions were evaluated by Arizona Sexual Experiences Scale (ASEX).

Results:  Female patients had reduced sexual drive and they were less satisfied with orgasm, while male patients had easier orgasms than did the controls. Regression analysis identified increased age and female sex predictive of reduced sexual drive and sexual arousal. Ability to reach orgasm and satisfaction with orgasm were associated with female sex, while erection/lubrication was associated with marital status. The severity and duration of PD, as well as the severity of anxiety and depression were not associated with SD.

Conclusion:  Using ASEX in the detection of SD in PD might be important in directing patients to further evaluation and treatment.
Angiotensin‐converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in Taiwan
Authors: Chen C.‐M. , Chen Y.‐C. , Wu Y.‐R. , Hu F.‐J. , Lyu R.‐K. , Chang H.‐S. , Ro L.‐S. , Hsu W.‐C. , Chen S.‐T. , Lee‐Chen G.‐J.
Published: August 2008

Background and purpose:  This study examines whether angiotensin‐converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case–control study.

Methods:  Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A‐240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors.

Results:  Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T‐D (OR = 2.7, 95% CI, 1.1–6.5, P = 0.02) was associated with female SDICH.

Conclusions:  This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan.
Effects of zonisamide on isolated head tremor
Authors: Song I.‐U. , Kim J.‐S. , Lee S.‐B. , Ryu S.‐Y. , An J.‐Y. , Kim H.‐T. , Kim Y.‐I. , Lee K.‐S.
Published: August 2008

Background and purpose:  The medical treatment available for patients with essential tremor (ET) is often inadequate. Furthermore, the efficacy of the medical treatments currently available for patients with ET of cranial nerve areas is less satisfactory than that of the medical treatments available for patients with ET involving the upper extremities. This pilot study was performed to evaluate whether zonisamide (ZNS) is effective in the treatment of patients with isolated head tremor.

Methods:  All subjects with isolated head tremor were randomly treated with either ZNS or propranolol. After a washout period, the subjects were switched to the alternative drug.

Results:  ZNS was found to be more effective in the treatment of patients with isolated head tremor than propranolol. No severe adverse effects were reported with either ZNS or propranolol.

Conclusion:  ZNS may be more useful than propranolol for the treatment of ET patients with head tremor.
Composition and evolution of fluids during skarn development in the Monte Capanne thermal aureole, Elba Island, central Italy
Authors: ROSSETTI F. , TECCE F.
Published: August 2008

We describe the chemistry of the fluids circulating during skarn formation by focusing on fluids trapped in calcsilicate minerals of the inner thermal aureole of the Late Miocene Monte Capanne intrusion of western Elba Island (central Italy). Primary, CH4‐dominant, C‐O‐H‐S‐salt fluid inclusions formed during prograde growth of the main skarn‐forming mineral phases: grossular/andradite and vesuvianite. The variable phase ratios attest to heterogeneous entrapment of fluid, with co‐entrapment of an immiscible hydrocarbon–brine mixture. Chemical elements driving skarn metasomatism such as Na, K, Ca, S and Cl, Fe and Mn were dominantly partitioned into the circulating fluid phase. The high salinity (apparent salinity between 58 and 70 wt% NaCl eq.) and the C‐component of the fluids are interpreted as evidence for a composite origin of the skarn‐forming fluids that involves both fluids derived from the crystallizing intrusion and contributions from metamorphic devolatilization. Oxidation of a Fe‐rich brine in an environment dominated by fluctuation in pressure from lithostatic to hydrostatic conditions (maintained by active crack‐sealing) contributed to skarn development. Fluid infiltration conformed to a geothermal gradient of about 100°C km−1, embracing the transition from high‐temperature contact metamorphism and fluid‐assisted skarn formation (at ca 600°C) to a barren hydrothermal stage (at ca 200°C).
Mobilization of ore fluids during Alpine metamorphism: evidence from hydrothermal veins in the Variscan basement of Western Carpathians, Slovakia
Authors: HURAI V. , LEXA O. , SCHULMANN K. , MONTIGNY R. , PROCHASKA W. , FRANK W. , KONEČNÝ P. , KRÁĽ J. , THOMAS R. , CHOVAN M.
Published: August 2008

Hydrothermal polymetallic veins of the Gemeric unit of the Western Carpathians are oriented coherently with the foliation of their low‐grade Variscan basement host. Early siderite precipitated from homogeneous NaCl‐KCl‐CaCl2‐H2O brines with minor CO2, while immiscible gas–brine mixtures are indicative of the superimposed barite, quartz–tourmaline and quartz–sulphide stages. The high‐salinity aqueous fluid (18–35 wt%) found in all mineralization stages corresponds to formation water modified by interaction with crystalline basement rocks at temperatures between 140 and 300°C. High brominity (around 1000 ppm in average) resulted from evaporation and anhydrite precipitation in a Permo‐Triassic marine basin, and from secondary enrichment by dissolution of organic matter in the marine sediments at diagenetic temperatures. Sulphate depletion reflects thermogenic reduction during infiltration of the formation waters into the Variscan crystalline basement. Crystallization temperatures of the siderite fill (140–300°C) and oxygen isotope ratios of the parental fluids (4–10‰) increase towards the centre of the Gemeric cleavage fan, probably as a consequence of decreasing water/rock ratios in rock‐buffered hydrothermal systems operating during the initial stages of vein evolution. In contrast, buoyant gas–water mixtures, variable salinities and strongly fluctuating P–T parameters in the successive mineralization stages reflect transition from a closed to an open hydrothermal system and mixing of fluids from various sources. Depths of burial were 6–14 km (1.7–4.4 kbar, in a predominantly lithostatic fluid regime) during the siderite and barite sub‐stages of the north‐Gemeric veins, and up to 16 km (1.6–4.5 kbar, in a hydrostatic to lithostatic fluid regime) in the quartz–tourmaline stage of the south‐Gemeric veins. The fluid pressure decreased down to approximately 0.6 kbar during crystallization of sulphides. U‐Pb‐Th, 40Ar/39Ar and K/Ar geochronology applied to hydrothermal muscovite–phengite and monazite, as well as cleavage phyllosilicates in the adjacent basement rocks and deformed Permian conglomerates corroborated the opening of hydrothermal veins during Lower Cretaceous thrusting and their rejuvenation during Late Cretaceous sinistral transpressive shearing and extension.
Reduced activation in right lateral prefrontal cortex and anterior cingulate gyrus in medication‐naïve adolescents with attention deficit hyperactivity disorder during time discrimination
Authors: Smith Anna B. , Taylor Eric , Brammer Michael , Halari Rozmin , Rubia Katya
Published: August 2008

Background: Patients with attention deficit hyperactivity disorder (ADHD) under‐perform when discriminating between durations differing by several hundred milliseconds. This function involves right prefrontal and anterior cingulate (AC) brain regions, which are structurally and functionally compromised in this patient group during executive tasks. We investigated the neuro‐anatomical substrates mediating fine temporal discrimination in adolescents with ADHD compared with controls, using functional magnetic resonance imaging (fMRI).

Methods: Twenty‐one male medication‐naïve adolescents aged 10–15 years with aDSM‐IVdiagnosis of ADHD (combined subtype) and without comorbid Axis I disorders (except conduct disorder) were compared to a group of 17 age‐ and IQ‐matched healthy adolescents. Using fMRI on a 1.5T scanner, we compared brain activation and performance between adolescents with ADHD and controls during a time discrimination task contrasted with a temporal order task.

Results: Despite comparable performance, patients with ADHD showed decreased activation in right dorsolateral and inferior prefrontal cortex and AC during time discrimination compared with controls.

Conclusions: Right hemispheric fronto‐cingulate abnormalities in ADHD, previously observed during inhibitory and executive functions, are also associated with temporal perception. Furthermore, recruitment of medication‐naïve patients precludes the possibility that deficits are attributable to stimulant exposure.
Consumer receptiveness to universal design features
Authors: Nunn Teresa L. , Sweaney Anne L. , Cude Brenda J. , Hathcote Jan M.
Published: August 2008

As homeowners age and struggle to adapt to the built environment, the addition of universal design features could allow added mobility and independence within their homes. Universal design means building residences in such a way that they are usable to the greatest extent possible, by all ages and abilities. The research used a descriptive analysis of survey data from 444 randomly selected US households to determine which characteristics of universal design were currently used in homes. In addition, the research examined the desire for future universal design elements. The findings indicate that the particular design features desired in the future varied depending on age. These findings are especially relevant as the desire to age in place continues to grow among our ever‐increasing elderly population.
THE ‘FRYING PANS’ OF THE EARLY BRONZE AGE AEGEAN: AN EXPERIMENTAL APPROACH TO THEIR POSSIBLE USE AS LIQUID MIRRORS*
Authors: PAPATHANASSOGLOU D. A. , GEORGOULI CH. A.
Published: August 2008

The so‐called ‘frying pans’ are peculiar vessels, most of them made of terracotta, flat and shallow, usually decorated on the outside part and dated to the Early Bronze Age. They were unearthed mostly in the Cyclades, in Crete and on the Helladic mainland. There are also a few artefacts made of stone and of bronze, from the Cyclades and Asia Minor, respectively. The intended purpose of these objects is disputed. Several interpretations exist for their function, the earliest one being that of liquid mirror vessels. We investigated the mirror hypothesis experimentally, by testing trays with attributes similar to those of the original ‘frying pans’, filled with a series of liquids familiar to the people of the time and the place where those vessels were made. The criterion employed was the contrast of mirror images. We conclude that, provided that some minimal prerequisites are met, the ‘frying pans’ are quite appropriate as liquid mirror vessels.
Self‐Reported Dietary Intake of Omega‐3 Fatty Acids and Association with Bone and Lower Extremity Function
Authors: Rousseau James H. , Kleppinger Alison , Kenny Anne M.
Published: August 2008

OBJECTIVES: To assess the relationship between self‐reported omega‐3 fatty acid (O3FA) intake and bone mineral density (BMD) and lower extremity function in older adults.

DESIGN: Cross‐sectional analysis of baseline information from three separate ongoing studies of older adults, pooled for this analysis.

SETTING: Academic health center.

PARTICIPANTS: Two hundred forty‐seven men (n=118) and women (n=129) residing in the community or an assisted living facility.

MEASUREMENTS: Self‐reported dietary intake (O3FA, omega‐6 fatty acids (O6FA), protein, and total calorie); BMD of the hip or heel; and lower extremity function including leg strength, chair rise time, walking speed, Timed Up and Go, and frailty.

RESULTS: The mean reported intake of O3FA was 1.27 g/day. Correlation coefficients (r) between O3FA and T‐scores from total femur (n=167) were 0.210 and 0.147 for combined femur and heel T scores. Similar correlations were found for leg strength (r=0.205) and chair rise time (r=−0.178), but the significance was lost when corrected for protein intake. Subjects with lower reported O3FA intake (<1.27 g/day) had lower BMD than those with higher reported O3FA intake. In a multiple regression analysis with femoral neck BMD as the dependent variable and reported intake of O3FA, O6FA, protein, and vitamin D as independent variables, reported O3FA intake was the only significant variable, accounting for 6% of the variance in BMD.

CONCLUSION: Older adults had low reported intakes of O3FA. There was an association between greater reported O3FA intake and higher BMD. There was no independent association between reported O3FA intake and lower extremity function. Results from this preliminary report are promising and suggest further investigation.
Photodynamic treatment with mono‐phenyl‐tri‐(N‐methyl‐4‐pyridyl)‐porphyrin for pathogen inactivation in cord blood stem cell products
Authors: Trannoy Laurence L. , Van Hensbergen Yvette , Lagerberg Johan W.M. , Brand Anneke
Published: August 2008

BACKGROUND: Hematopoietic stem cell transplants and culture of hematopoietic progenitor cells require pathogen‐free conditions. The application of a method of pathogen inactivation in red blood cells using photodynamic treatment (PDT) was investigated for the decontamination of cord blood stem cell (CBSC) products.

STUDY DESIGN AND METHODS: CBSC products, spiked with Gram‐positive and Gram‐negative bacteria, were treated with PDT using mono‐phenyl‐tri‐(N‐methyl‐4‐pyridyl)‐porphyrin (Tri‐P(4)) and red light. After PDT, in vitro and in vivo evaluation of the CBSC functions were performed.

RESULTS: PDT of CBSC products resulted in the inactivation of the bacteria, with Staphylococcus aureus being the most resistant. Complete decontamination was achieved when CBSC products were contaminated with low titers of bacteria. PDT had no effect on white blood cell viability, the ex vivo expansion potential of the progenitor cells, and their capacity to differentiate to various hematopoietic cell lineages. However, PDT reduced the engraftment of human CBSCs in NOD/SCID mice, particularly affecting the B‐cell lineage engraftment.

CONCLUSION: Pathogen inactivation of CBSC with Tri‐P(4)‐mediated PDT is feasible at contamination level up to 10 to 20 colony‐forming units per mL and can be considered when ex vivo expansion culture is anticipated. However, this treatment is not recommended for transplantation purposes at this time. Further investigations may elucidate why engraftment is diminished.
Novel GYP(A‐B‐A) hybrid gene in a DANE+ person who made an antibody to a high‐prevalence MNS antigen
Authors: Velliquette Randall W. , Palacajornsuk Poonsub , Hue‐Roye Kim , Lindgren Sally , Ilstrup Sarah , Green Carole , Lomas‐Francis Christine , Reid Marion E.
Published: August 2008

BACKGROUND: The glycophorin (GP) molecule associated with the GP.Dane phenotype is a GP(A‐B‐A) hybrid that contains some amino acids encoded by the Pseudoexon 3 of GYPB and Asn45 of GPA and carries the low‐prevalence MNS antigens DANE and Mur. Serum from a woman of English ancestry contained an immunoglobulin M alloantibody to a high‐prevalence MNS antigen, and the purpose of this study was to identify the molecular basis of her phenotype.

STUDY DESIGN AND METHODS: Hemagglutination, Western blotting, and DNA analyses were performed by standard methods.

RESULTS: Tests of the proband's RBCs with monoclonal antibodies indicated a change of amino acids between positions 27 and 55 of GPA. Her RBCs expressed M, s, Mur, and DANE antigens and were Mg‐negative. The antigen recognized by her antibody was sensitive to treatment with papain, ficin, and trypsin and resistant to α‐chymotrypsin and dithiothreitol. Sequencing of DNA from the proband revealed a sequence of nucleotides identical to the GYP(A‐B‐A) encoding GP.Dane but without the adenyl nucleotide substitution, which has been predicted to change Ile46 of GPA to Asn45. Testing of her immediate family revealed the presence of an Mk gene.

CONCLUSION: The proband had a novel GYP(A‐B‐A) encoding a DANE+ GP that is in cis to GYPBs and in trans to Mk. The high‐prevalence antigen lacking from this GP.Dane phenotype and recognized by the proband's serum is called ENDA (ISBT Number MNS44). Our results indicate that the change of Ile46 of GPA to Asn45 of GP.Dane is not required for expression of the DANE antigen.
Exact Confidence Bounds Following Adaptive Group Sequential Tests
Authors: Brannath Werner , Mehta Cyrus R. , Posch Martin
Published: August 2008

Summary We provide a method for obtaining confidence intervals, point estimates, and p‐values for the primary effect size parameter at the end of a two‐arm group sequential clinical trial in which adaptive changes have been implemented along the way. The method is based on applying the adaptive hypothesis testing procedure of Müller and Schäfer (2001, Biometrics57, 886–891) to a sequence of dual tests derived from the stage‐wise adjusted confidence interval of Tsiatis, Rosner, and Mehta (1984, Biometrics40, 797–803). In the nonadaptive setting this confidence interval is known to provide exact coverage. In the adaptive setting exact coverage is guaranteed provided the adaptation takes place at the penultimate stage. In general, however, all that can be claimed theoretically is that the coverage is guaranteed to be conservative. Nevertheless, extensive simulation experiments, supported by an empirical characterization of the conditional error function, demonstrate convincingly that for all practical purposes the coverage is exact and the point estimate is median unbiased. No procedure has previously been available for producing confidence intervals and point estimates with these desirable properties in an adaptive group sequential setting. The methodology is illustrated by an application to a clinical trial of deep brain stimulation for Parkinson's disease.
Diagnosis of Random‐Effect Model Misspecification in Generalized Linear Mixed Models for Binary Response
Authors: Huang Xianzheng
Published: August 2008

Summary Generalized linear mixed models (GLMMs) are widely used in the analysis of clustered data. However, the validity of likelihood‐based inference in such analyses can be greatly affected by the assumed model for the random effects. We propose a diagnostic method for random‐effect model misspecification in GLMMs for clustered binary response. We provide a theoretical justification of the proposed method and investigate its finite sample performance via simulation. The proposed method is applied to data from a longitudinal respiratory infection study.
On Assessing Surrogacy in a Single Trial Setting Using a Semicompeting Risks Paradigm
Authors: Ghosh Debashis
Published: August 2008

SummaryThere has been a recent emphasis on the identification of biomarkers and other biologic measures that may be potentially used as surrogate endpoints in clinical trials. We focus on the setting of data from a single clinical trial. In this article, we consider a framework in which the surrogate must occur before the true endpoint. This suggests viewing the surrogate and true endpoints as semicompeting risks data; this approach is new to the literature on surrogate endpoints and leads to an asymmetrical treatment of the surrogate and true endpoints. However, such a data structure also conceptually complicates many of the previously considered measures of surrogacy in the literature. We propose novel estimation and inferential procedures for the relative effect and adjusted association quantities proposed byBuyse and Molenberghs(1998,Biometrics54, 1014–1029). The proposed methodology is illustrated with application to simulated data, as well as to data from a leukemia study.
Subdissociative‐dose Ketamine versus Fentanyl for Analgesia during Propofol Procedural Sedation: A Randomized Clinical Trial
Authors: Messenger David W. , Murray Heather E. , Dungey Paul E. , Van Vlymen Janet , Sivilotti Marco L.A.
Published: August 2008

Objectives:  The authors sought to compare the safety and efficacy of subdissociative‐dose ketamine versus fentanyl as adjunct analgesics for emergency department (ED) procedural sedation and analgesia (PSA) with propofol.

Methods:  This double‐blind, randomized trial enrolled American Society of Anesthesiology (ASA) Class I or II ED patients, aged 14–65 years, requiring PSA for orthopedic reduction or abscess drainage. Subjects received 0.3 mg/kg ketamine or 1.5 μg/kg fentanyl intravenously (IV), followed by IV propofol titrated to deep sedation. Supplemental oxygen was not routinely administered. The primary outcomes were the frequency and severity of cardiorespiratory events and interventions, rated using a composite intrasedation event rating scale. Secondary outcomes included the frequency of specific scale component events, propofol doses required to achieve and maintain sedation, times to sedation and recovery, and physician and patient satisfaction.

Results:  Sixty‐three patients were enrolled. Of patients who received fentanyl, 26/31 (83.9%) had an intrasedation event versus 15/32 (46.9%) of those who received ketamine. Events prospectively rated as moderate or severe were seen in 16/31 (51.6%) of fentanyl subjects versus 7/32 (21.9%) of ketamine subjects. Patients receiving fentanyl had 5.1 (95% confidence interval [CI] = 1.9 to 13.6; p < 0.001) times the odds of having a more serious intrasedation event rating than patients receiving ketamine. There were no significant differences in secondary outcomes, apart from higher propofol doses in the ketamine arm.

Conclusions:  Subdissociative‐dose ketamine is safer than fentanyl for ED PSA with propofol and appears to have similar efficacy.
Global food demand, productivity growth, and the scarcity of land and water resources: a spatially explicit mathematical programming approach
Authors: Lotze‐Campen Hermann , Müller Christoph , Bondeau Alberte , Rost Stefanie , Popp Alexander , Lucht Wolfgang
Published: August 2008

In the coming decades, an increasing competition for global land and water resources can be expected, due to rising demand for food and bio‐energy production, biodiversity conservation, and changing production conditions due to climate change. The potential of technological change in agriculture to adapt to these trends is subject to considerable uncertainty. In order to simulate these combined effects in a spatially explicit way, we present a model of agricultural production and its impact on the environment (MAgPIE). MAgPIE is a mathematical programming model covering the most important agricultural crop and livestock production types in 10 economic regions worldwide at a spatial resolution of three by three degrees, i.e., approximately 300 by 300 km at the equator. It takes regional economic conditions as well as spatially explicit data on potential crop yields and land and water constraints into account and derives specific land‐use patterns for each grid cell. Shadow prices for binding constraints can be used to valuate resources for which in many places no markets exist, especially irrigation water. In this article, we describe the model structure and validation. We apply the model to possible future scenarios up to 2055 and derive required rates of technological change (i.e., yield increase) in agricultural production in order to meet future food demand.
Stemming heart failure with cardiac‐ or reprogrammed‐stem cells
Authors: Tateishi Kento , Takehara Naofumi , Matsubara Hiroaki , Oh Hidemasa
Published: August 2008

Despite extensive efforts to control myocyte growth by genetic targeting of the cell cycle machinery and small molecules for cardiac repair, adult myocytes themselves appeared to divide a limited number of times in response to a variety of cardiac muscle stresses. Rare tissue‐resident stem cells are thought to exist in many adult organs that are capable of self‐renewal and differentiation and possess a range of actions that are potentially therapeutic. Recent studies suggest that a population of cardiac stem cells (CSCs) is maintained after cardiac development in the adult heart in mammals including human beings; however, homeostatic cardiomyocyte replacement might be stem cell‐dependent, and functional myocardial regeneration after cardiac muscle damage is not yet considered as sufficient to fully maintain or reconstitute the cardiovascular system and function. Although it is clear that adult CSCs have limitations in their capabilities to proliferate extensively and differentiate in response to injury in vivo for replenishing mature car‐diomyocytes and potentially function as resident stem cells. Transplantation of CSCs expanded ex vivo seems to require an integrated strategy of cell growth‐enhancing factor(s) and tissue engineering technologies to support the donor cell survival and subsequent proliferation and differentiation in the host microenvironment. There has been substantial interest regarding the evidence that mammalian fibroblasts can be genetically reprogrammed to induced pluripotent stem (iPS) cells, which closely resemble embryonic stem (ES) cell properties capable of differentiating into functional cardiomyocytes, and these cells may provide an alternative cell source for generating patient‐specific CSCs for therapeutic applications.
Are antidepressants safe in the treatment of bipolar depression? A critical evaluation of their potential risk to induce switch into mania or cycle acceleration
Authors: Licht R. W. , Gijsman H. , Nolen W. A. , Angst J.
Published: August 2008

Objective:  To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself.

Method:  A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford–Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose–response relation, temporal relation with exposure to agent preceding effect and biological plausibility.

Results:  There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone.

Conclusion:  When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied.
Antidepressant use and suicide prevention: a prescription database study in the region Friuli Venezia Giulia, Italy
Authors: Castelpietra G. , Morsanutto A. , Pascolo‐Fabrici E. , Isacsson G.
Published: August 2008

Objective:  To investigate the possible impact of the increased use of antidepressants on suicide rates in the Italian region of Friuli Venezia Giulia (FVG).

Method:  Individual‐based data on antidepressants in FVG from 1997 to 2006 were obtained from the regional prescription database, and linked to data on suicide for the same period obtained from the regional health information system. Age and sex were considered.

Results:  The number of users of antidepressants increased almost fivefold during the study period. Selective serotonin reuptake inhibitors accounted for 71% of the individual users in 2006. The number of defined daily doses (DDD) per patient increased almost sevenfold. In parallel, the suicide rate decreased by one‐third in men as well as in women, and in subjects under and over the age of 60 years.

Conclusion:  Suicide rates in FVG have declined in agreement with the hypothesis that the use of antidepressants may prevent suicide.
Economic evaluation of posaconazole vs. standard azole prophylaxis in high risk neutropenic patients in the Netherlands
Authors: Stam Wiro B. , O’Sullivan Amy K. , Rijnders Bart , Lugtenburg Elly , Span Lambert F. R. , Janssen Jeroen J. W. M. , Jansen Jeroen P.
Published: August 2008

Background:  Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients experience prolonged neutropenia after treatment with intensive chemotherapy, leading to a high risk of invasive fungal infections (IFI). The present study evaluates the cost effectiveness of posaconazole vs. standard azoles for the prevention of IFIs in neutropenic patients in the Netherlands.

Methods:  A decision‐tree model was developed using data from a randomized trial that compared posaconazole and standard azole (fluconazole or itraconazole) prophylaxis in neutropenic patients receiving remission–induction chemotherapy for AML/MDS (Cornely et al., N Engl J Med 2007;356:348–359). Following initiation of prophylaxis, clinical events are modeled with chance nodes reflecting probabilities of IFIs, IFI‐related death, and death from other causes. Patients surviving the prophylaxis are assumed to have a life expectancy according to the underlying condition. This allows translation of the trial outcomes to a lifetime horizon. Data on life expectancy, quality of life, medical resource consumption and costs were obtained from the literature. Model outcomes include cost per life year (LY) gained and cost per quality adjusted life year (QALY) gained.

Results:  The total cost (treatment of breakthrough IFI + prophylaxis) for posaconazole amounted to €4412 (95% uncertainty interval €3403–€5666), which is −€183 (−€1985 to €1564) less than costs with standard azoles. Posaconazole prophylaxis resulted in 0.08 (0.02–0.15) QALYs gained in comparison with prophylaxis with standard azoles. Results from a probabilistic sensitivity analysis indicate that there is a 90% probability that the cost per QALY gained with posaconazole is below €20 000. Additional scenario analyzes with different assumptions confirmed these findings.

Conclusion:  Given the underlying data and assumptions, the economic evaluation demonstrated that posaconazole prophylaxis is expected to be cost‐effective compared with fluconazole/itraconazole in neutropenic AML/MDS patients after intensive chemotherapy.
Iron homeostasis: new players, newer insights
Authors: Edison Eunice S. , Bajel Ashish , Chandy Mammen
Published: August 2008

Although iron is a relatively abundant element in the universe, it is estimated that more than 2 billion people worldwide suffer from iron deficiency anemia. Iron deficiency results in impaired production of iron‐containing proteins, the most prominent of which is hemoglobin. Cellular iron deficiency inhibits cell growth and subsequently leads to cell death. Hemochromatosis, an inherited disorder results in disproportionate absorption of iron and the extra iron builds up in tissues resulting in organ damage. As both iron deficiency and iron overload have adverse effects, cellular and systemic iron homeostasis is critically important. Recent advances in the field of iron metabolism have led to newer understanding of the pathways involved in iron homeostasis and the diseases which arise from alteration in the regulators. Although insight into this complex regulation of the proteins involved in iron homeostasis has been obtained mainly through animal studies, it is most likely that this knowledge can be directly extrapolated to humans.
Eradication of the invasive Pseudorasbora parva results in increased growth and production of native fishes
Authors: Britton J. R. , Davies G. D. , Brazier M.
Published: August 2008

Abstract –  The topmouth gudgeon, Pseudorasbora parva, has been described as Europe’s most invasive fish. To control their UK invasion, some lentic populations at risk of causing fluvial dispersal have been eradicated. The first of these operations was from a lake in north‐west UK in March 2005 using rotenone application; prior to eradication, their mean density was estimated as 6.1 m−2 whereas since eradication, no P. parva have been recorded. Prior to rotenone application, the majority of native fishes were removed, held off‐site and reintroduced following degradation of rotenone to safe levels. In the three growth seasons since their reintroduction and P. parva eradication, the abundance, somatic growth rate and production of roach Rutilus rutilus and common bream Abramis brama have increased significantly; production is now driven by a lower number of comparatively larger, faster growing individuals. These data suggest that the eradication of this P. parva population has been highly beneficial for the growth, recruitment and production of these native species.
On Voxel Based Iso‐Tumor‐Control Probability and Iso‐Complication Maps for Selective Boosting and Selective Avoidance Intensity‐Modulated Radiotherapy
Authors: Kim Y. , Tomé W. A.
Published: August 2008

Voxel‐based iso‐tumor‐control probability (TCP) maps and iso‐Complication maps are proposed as a plan‐review tool especially for functional image‐guided intensity‐modulated radiotherapy (IMRT) strategies such as selective boosting (dose painting) and conformal avoidance IMRT. The maps employ voxel‐based phenomenological biological dose–response models for target volumes and normal organs. Two IMRT strategies for prostate cancer, namely conventional uniform IMRT delivering an equivalent uniform dose (EUD) = 84 Gy to the entire planning target volume (PTV) and selective boosting delivering an EUD = 82 Gy to the entire PTV, are investigated, to illustrate the advantages of this approach over iso‐dose maps. Conventional uniform IMRT did yield a more uniform isodose map to the entire PTV while selective boosting did result in a non‐uniform isodose map. However, when employing voxel‐based iso‐TCP maps selective boosting exhibited a more uniform TCP map compared to what could be achieved using conventional uniform IMRT, which showed TCP cold spots in high‐risk tumor subvolumes despite delivering a higher EUD to the entire PTV. Voxel‐based iso‐Complication maps are presented for rectum and bladder, and their utilization for selective avoidance IMRT strategies are discussed. We believe as the need for functional image‐guided treatment planning grows, voxel‐based iso‐TCP and iso‐Complication maps will become an important tool to assess the integrity of such treatment plans.
Abnormal vessel morphology in boys born after intracytoplasmic sperm injection
Authors: Wikstrand Margareta Hök , Niklasson Aimon , Strömland Kerstin , Hellström Ann
Published: August 2008

Aim: Children born after intracytoplasmic sperm injection (ICSI) are at risk of preterm birth, low birth weight and perinatal morbidity which may predispose for diseases of the central nervous and vascular systems. Our aim was to investigate the ocular fundus morphology in children born after ICSI.

Method: Children born after ICSI (n = 82) had ocular fundus photographs taken at the age of 5 years and results were compared with those of a control group (n = 203). The ocular fundus morphology with the central retinal vessels was evaluated by digital image analysis.

Results: Children born after ICSI (n = 57) had abnormal retinal vascularization as evidenced by a lower number of vascular branching points compared with the control group (n = 181) (p = 0.0002). A gender difference was found whereby the ICSI boys (n = 35) had significantly fewer retinal branching points (median 24, range 19–29.5) compared with the control boys (median 27.5, range 20–37) (p < 0.0001).

Conclusion: Our findings showed that ICSI boys have abnormal vessel morphology as demonstrated by a reduced number of central retinal branching points. The difference still remained after elimination of factors earlier shown to be associated with a low number of vascular branching points, i.e. low birth weight and preterm, suggesting other mechanisms responsible for the low number of vascular branching points.
Long‐term non‐invasive positive airway pressure ventilation in infants
Authors: Markström Agneta , Sundell Kerstin , Stenberg Nader , Katz‐Salamon Miriam
Published: August 2008

Aim: To evaluate the clinical application of long‐term non‐invasive ventilation (NIV) in infants with life‐threatening ventilatory failure with regard to: diagnosis, age at initiation, indication for and duration of treatment, clinical outcome and mortality and adverse effects.

Patients and methods: The medical records of 18 infants treated in a home setting during a 7‐year period were reviewed. The criteria for ventilatory support were: (a) transcutaneous partial pressures of carbon dioxide (TcPCO2) >6.5 kPa and oxygen (TcPO2) < 8.5 kPa and (b) decreased cough ability and/or recurrent chest infections.

Results: The median age at initiation was 4 months (range 1–12). NIV was initiated because of hypoventilation in 12 infants and because of reduced cough ability and/or recurrent infections in six infants. Tracheotomy was eventually needed in two infants. The median duration of treatment was 24 months (range 1–84). NIV produced significant improvements, with median TcPCO2 falling from 9.9 to 6.1 kPa, and median TcPO2 rising from 9.8 to 11.1 kPa.

Conclusion: NIV can be successfully and safely used in infants with prolonged life‐threatening ventilatory failure, potentially avoiding intubation and tracheotomy.
Diagnostic pitfalls in children with sleep disorders: two cases with hypersomnia
Authors: Yilmaz Kutluhan , Uyar Meral , Adaletli Hilal , Kilincaslan Ayse
Published: August 2008

Sleep disorders are common in children, yet several clinical pitfalls give rise to the unrecognition or improper management of those children. Here, we present diagnostic difficulties in two adolescents with narcolepsy and Kleine–Levin syndrome. The first patient was a 12‐year‐old girl who had been given Na‐valproate for nearly a year because hypersomnia was initially perceived as unconsciousness periods of epileptic spells, and later attributed to the antiepileptic drug. The other patient was a 14‐year‐old boy who had been managed as a specific psychiatric disorder for several months despite the characteristic symptoms of Kleine–Levin syndrome (hypersomnia, hyperphagia, hypersexuality, behavioural and cognitive dysfunction). Both cases emphasize that sleep disorders could be manifested with various clinics and that there are several diagnostic challenges in children.

Conclusion: Sleep medicine needs to be given larger role in both training curriculum and post‐graduate education for paediatricians.
Submembraneous microtubule cytoskeleton: interaction of TRPP2 with the cell cytoskeleton
Authors: Chen Xing‐Zhen , Li Qiang , Wu Yuliang , Liang Genqing , Lara Carlos J. , Cantiello Horacio F.
Published: August 2008

TRPP2, also called polycystin‐2, the gene product of PKD2, is a membrane protein defective in 10–15% of cases of autosomal dominant polycystic kidney disease. Mutations in PKD2 are also associated with extrarenal disorders, such as hepatic cystogenesis and cardiovascular abnormalities. TRPP2 is a Ca‐permeable nonselective cation channel present in the endoplasmic reticulum and plasma membrane, as well as in cilia of renal epithelial and embryonic nodal cells, in which it likely forms part of a flow sensor. Recent studies have identified a number of TRPP2‐interacting proteins, of which many are cytoskeletal components. Work from our and other laboratories indicates that cytoskeletal partner proteins seem to play important, albeit highly complex, roles in the regulation of TRPP2 expression, localization and channel function. This minireview covers current knowledge about cytoskeletal interactions with TRPP2, and suggests that mutations in proteins of the TRPP2‐cytoskeleton complex may be implicated in the pathogenesis of autosomal dominant polycystic kidney disease.