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The purpose of the study reported on in this paper was to gain insight into how instructional designers conceptualise learning objects (LOs) and their attributes. It aimed to identify the range and types of conceptualisations of LO attributes held by a group of designers. Data were collected during two phases of semi-structured phone interviews with 10 instructional designers working in Canadian colleges and universities. Open, axial and selective coding were used to analyse data. Designers identified the following attributes of LOs: digital, interactive, pedagogically purposeful, pedagogically worthwhile, pedagogically assessable, usable, reusable, peer reviewable and granular. Designers conceptualised LOs and their attributes with more of a focus on pedagogical best practices rather than a focus on technical definitions of LOs.

It has been well documented that pre-menopausal females have a lower incidence of cardiovascular disease than their male counterparts. However, post-menopausal women reach the rates of disease in men suggesting a protective role of estrogen. Numerous animal studies have also demonstrated that estrogen is cardioprotective. Historically, estrogen has been thought to signal through two nuclear receptors, ERa and ERb; however, a third, membrane bound receptor, GPR30, has been identified and shown to bind estrogen with high affinity. GPR30 is a G protein coupled receptor localized to the plasma membrane and endoplasmic reticulum. To date, there is little information on GPR30 in the heart and no study has looked at the effect of GPR30 activation during myocardial ischemia and reperfusion. Therefore, the goal of this study was to determine whether activation of GPR30 results in a cardioprotective phenotype in rats. A highly specific GPR30 agonist, G-1, was administered to Sprague Dawley (200–300g) rat hearts 10 minutes prior to 20 minutes of ischemia followed by 120 minutes of reperfusion using a Langendorff model. Recovery of post-ischemic function was significantly better in G-1 treated hearts compared to controls (39.4±5.5 vs 23.6±2.5% of pre-ischemic rate pressure product, p

The goal of the study was to explore post-secondary students’ purposes for blogging with particular attention to the social and instructional purposes. The sample of blogs came from an all-women’s college in the United Arab Emirates. Content analysis was conducted on eight blogs using previously tested instruments to identify social presence and knowledge construction. Authors of the blogs participated in a focus group discussion about the purposes for blogging. Findings revealed that the primary use of blogging was for social purposes. Self-disclosure was the most notable purpose for blogging, in addition to sharing emotional responses to learning. The lack of teaching presence may have influenced students’ use of blogging for social rather than instructional purposes.

Objectives: Supplementary prescribing (SP) by pharmacists and nurses in the UK represents a unique approach to improving patients’ access to medicines and better utilizing health care professionals’ skills. Study aims were to explore the views of stakeholders involved in SP policy, training and practice, focusing upon issues such as SP benefits, facilitators, challenges, safety and costs, thereby informing future practice and policy. Method: Qualitative, semi-structured interviews were conducted with 43 purposively sampled UK stakeholders, including pharmacist and nurse supplementary prescribers, doctors, patient groups representatives, academics and policy developers. Analysis of transcribed interviews was undertaken using a process of constant comparison and framework analysis, with coding of emergent themes. Results: Stakeholders generally viewed SP positively and perceived benefits in terms of improved access to medicines and fewer delays, along with a range of facilitators and barriers to the implementation of this form of non-medical prescribing. Stakeholders’ views on the economic impact of SP varied, but safety concerns were not considered significant. Future challenges and implications for policy included SP being potentially superseded by independent nurse and pharmacist prescribing, and the need to improve awareness of SP. Several potential tensions emerged including nurses’ versus pharmacists’ existing skills and training needs, supplementary versus independent prescribing, SP theory versus practice and prescribers versus non-prescribing peers. Conclusion: SP appeared to be broadly welcomed by stakeholders and was perceived to offer patient benefits. Several years after its introduction in the UK, stakeholders still perceived several implementation barriers and challenges and these, together with various tensions identified, might affect the success of supplementary and other forms of non-medical prescribing.

This paper describes how activity theory (AT) and its principle of contradictions may be relied on to guide research in educational technology. The paper begins with a theoretical overview of AT and of its principle of contradictions. It follows with a synthesis of studies that have used AT as a lens to study information and communication technologies (ICTs) in educational contexts. We analyse educational technology studies that have focused on contradictions in terms of their underlying assumptions, research questions, approaches to analysis, findings, and implications. The lens of AT and contradictions provides a versatile tool to inquire into various aspects of educational technology use, taking into account individual and institutional perspectives as well as evolution over time. AT and its principle of contradictions provide insights into how transformation may occur with use of ICTs in educational contexts.

See related article, pages 307–314 Preconditioning (PreC) and postconditioning (PostC) have been shown to initiate a number of signaling cascades that reduce cell death. However, the mechanisms by which these signals reduce cell death have been elusive.1 PreC has been shown to phosphorylate and thereby inhibit glycogen synthase kinase (GSK)-3β, and perfusion with GSK inhibitors has been shown to reduce cell death induced by ischemia/reperfusion, when added before ischemia2 or when added at the start of reperfusion.3–5 These studies are consistent with data in other tissues showing that inhibition of GSK-3β reduces apoptosis. Information regarding the mechanism by which inhibition of GSK protects has been provided by Juhaszova et al,6 who report that inhibition of GSK-3β delays the opening of the mitochondrial permeability transition pore (MPT) (see the Figure). The MPT is a large-conductance pore in the inner mitochondrial membrane which is opened under conditions associated with ischemia/reperfusion, such as high matrix reactive oxygen species and high matrix calcium. Pharmacological inhibitors of the MPT have been shown to reduce ischemia/reperfusion injury, suggesting that activation of MPT might have a role in ischemia/reperfusion-mediated cell death. However the molecular components of the MPT have not been identified.7 Figure. Nishino et al8 raise 2 questions: (1) whether inhibition of GSK is required for protection in mice; and (2) whether inhibition of GSK is protective in mouse hearts. PreC and PostC activate a number of redundant signaling pathways that lead to inhibition of MPT. The relative importance of different pathways may vary depending on the model and species. Previous studies6 have suggested that inhibition of GSK is a major signaling pathway that results in inhibition of MPT; this is illustrated with the large arrow. However, other pathways exist and it is not surprising that under different …

Treatment of type 2 diabetes mellitus (T2DM) patients with pioglitazone results in a more favorable lipid profile, and perhaps more favorable cardiac outcomes, than treatment with rosiglitazone. Pioglitazone treatment increases VLDL-triacylglycerol clearance, but the role of de novo lipogenesis (DNL) has not been explored, and no direct comparison has been made between the thiazolidinediones (TZDs). Twelve subjects with T2DM and hypertriacylglyceridemia were randomized to either rosiglitazone or pioglitazone treatment. Stable isotope infusion studies were performed at baseline and after 20 weeks of treatment. Both treatments reduced glucose and HbA(1c) concentrations equally. Pioglitazone treatment resulted in a 40% reduction in hepatic DNL (P < 0.01) and in a 25% reduction in hepatic glucose production (P < 0.05), while rosiglitazone did not significantly change either parameter, although comparisons of changes between treatments were not significantly different. These pilot results indicate that pioglitazone reduces hepatic DNL while rosiglitazone does not. Larger follow-up studies are required to confirm differential effects of these agents definitively. The reduction in DNL may underlie altered assembly or atherogenicity of lipoprotein particles and may reflect PPARalpha or other non-PPARgamma actions on the liver by pioglitazone. These differences might help explain previously reported differences in lipid profiles and cardiovascular disease outcomes for rosiglitazone and pioglitazone.

This article reflects upon the introduction of nonmedical prescribing in the United Kingdom and describes the historical developments within the National Health Service over the last 2 decades, together with an assessment of the impact of this prescribing for various stakeholders, drawing upon relevant research. We argue that a number of issues are associated with the introduction and development of nonmedical prescribing, including benefits to patients, the promise of increased autonomy for professions such as nursing and pharmacy, explicit and implicit government objectives, and threats to medical dominance and autonomy. Refereed/Peer-reviewed

Cytosolic phospholipase A(2) alpha (cPLA(2)alpha, type IVA phospholipase) acts at the membrane surface to release free arachidonic acid, which is metabolized into inflammatory mediators, including leukotrienes and prostaglandins. Thus, specific cPLA(2)alpha inhibitors are predicted to have antiinflammatory properties. However, a key criterion in the identification and development of such inhibitors is to distinguish between compounds that bind stoichiometrically to cPLA(2)alpha and nonspecific membrane perturbants. In the current study, we developed a method employing isothermal titration calorimetry (ITC) to characterize the binding of several distinct classes of cPLA(2)alpha inhibitors. Thermodynamic parameters and the binding constants were obtained following titration of the inhibitor to the protein at 30 degrees C and pH 7.4. The compounds tested bound cPLA(2)alpha with a 1:1 stoichiometry, and the dissociation constant K(d) of the inhibitors calculated from the ITC experiments correlated well with the IC(50) values obtained from enzymatic assays. Interestingly, binding was observed only in the presence of a micellar surface, even for soluble compounds. The site of binding of these inhibitors within cPLA(2)alpha was analyzed by testing for binding in the presence of methyl arachidonyl fluorophosphonate (MAFP), an irreversible active site inhibitor of cPLA(2)alpha. Lack of binding of inhibitors in the presence of MAFP suggested that the compounds tested bound specifically at or near the active site of the protein. Furthermore, the effect of various detergents on the binding of certain inhibitors to cPLA(2)alpha was also tested. The results are discussed with reference to thermodynamic parameters such as changes in enthalpy (DeltaH), entropy (DeltaS), and free energy (DeltaG). The data obtained from these studies provide not only structure-activity relationships for compounds but also important information regarding mechanism of binding. This is the first example of ITC used for studying inhibitors of enzymes with interfacial kinetics.

Objectives To assess the quality of mixed methods studies in health services research (HSR). Methods We identified 118 mixed methods studies funded by the Department of Health in England between 1994 and 2004, and obtained proposals and/or final reports for 75. We applied a set of quality questions to both the proposal and report of each study, addressing the success of the study, the mixed methods design, the individual qualitative and quantitative components, the integration between methods and the inferences drawn from completed studies. Results Most studies were completed successfully. Researchers mainly ignored the mixed methods design and described only the separate components of a study. There was a lack of justification for, and transparency of, the mixed methods design in both proposals and reports, and this had implications for making judgements about the quality of individual components in the context of the design used. There was also a lack of transparency of the individual methods in terms of clear exposition of data collection and analysis, and this was more a problem for the qualitative than the quantitative component: 42% (19/45) versus 18% (8/45) of proposals (p 5 0.011). Judgements about integration could rarely be made due to the absence of an attempt at integration of data and findings from different components within a study. Conclusions The HSR community could improve mixed methods studies by giving more consideration to describing and justifying the design, being transparent about the qualitative component, and attempting to integrate data and findings from the individual components.

There is growing interest in the use of interactive telephone technology to support chronic disease management. We used the implementation of an automated telephone self-management support program for diabetes patients as an opportunity to monitor patient safety.We identified adverse and potential adverse events among a diverse group of diabetes patients who participated in an automated telephone health-IT self-management program via weekly interactions augmented by targeted nurse follow-up. We defined an adverse event (AE) as an injury that results from either medical management or patient self-management, and a potential adverse event (PotAE) as an unsafe state likely to lead to an event if it persists without intervention. We distinguished between incident, or new, and prevalent, or ongoing, events. We conducted a medical record review and present summary results for event characteristics including detection trigger, preventability, potential for amelioration, and primary care provider awareness.Among the 111 patients, we identified 111 AEs and 153 PotAEs. Eleven percent of completed calls detected an event. Events were most frequently detected through health IT-facilitated triggers (158, 59%), followed by nurse elicitation (80, 30%), and patient callback requests (28, 11%). We detected more prevalent (68%) than incident (32%) events. The majority of events (93%) were categorized as preventable or ameliorable. Primary care providers were aware of only 13% of incident and 60% of prevalent events.Surveillance via a telephone-based, health IT-facilitated self-management support program can detect AEs and PotAEs. Events detected were frequently unknown to primary providers, and the majority were preventable or ameliorable, suggesting that this between-visit surveillance, with appropriate system-level intervention, can improve patient safety for chronic disease patients.

During ischemia, ATP and phosphocreatine (PCr) decline, whereas intracellular hydrogen ion, intracellular sodium (Na+), calcium (Ca2+), and magnesium (Mg2+) concentrations all rise. If the ischemia is relatively short and there is little irreversible injury (cell death), PCr, pH, Na+, Mg2+, and Ca2+all recovery quickly on reperfusion. ATP recovery can take up to 24 h because of loss of adenine base from the cell and the need for de novo synthesis. There are correlative data showing that a sustained rise in Ca2+during ischemia and/or lack of recovery during reperfusion is associated with irreversible cell injury. Interventions that reduce the rise in Ca2+during ischemia and reperfusion have been shown to reduce cell death. Therefore, a better understanding of the mechanisms responsible for the rise in Ca2+during ischemia and early reperfusion could have important therapeutic implications. This review will discuss mechanisms involved in alterations in ions and high energy phosphate metabolites in perfused or intact heart during ischemia and reperfusion.

Pharmacist prescribing is a relatively new initiative in the extension of prescribing responsibilities to non-medical healthcare professionals. Pharmacist supplementary prescribing was introduced in 2003 and allowed prescribing in accordance with a clinical management plan agreed with a medical practitioner and patient to improve patient access to medicines and better utilize the skills of healthcare professionals. The objective of this research was to examine the volume, cost and trends in pharmacist prescribing in community and primary care using Prescription Analysis and Cost (PACT) data and to suggest possible reasons for the trends.Using PACT data at national, chapter and subchapter level for 2004-2006 the volume, costs and trends for pharmacist prescribing were obtained. Supplemental data and statistical analysis from other sources, relating to prescribing of individual drugs, were also utilized.The total number of items prescribed by pharmacists in community and primary care increased from 2706 in 2004 to 31 052 in 2006. In 2006, pharmacist prescribing represented only 0.004% of all prescribing in the community and primary care setting. Cardiovascular medicines were the most frequently prescribed therapeutic class followed by central nervous system, respiratory, endocrine and gastrointestinal medicines.Pharmacist prescribing is increasing but represents an extremely small proportion of primary care prescribing. PACT data between 2004 and 2006 reflects pharmacist supplementary prescribing alone and has been in the anticipated therapeutic areas of drugs which treat chronic conditions such as hypertension.

A critical component to instituting compassionate, patient-centered diabetes care is the training of health care providers. Our institution developed the Family Centered Experience (FCE), a comprehensive 2-year preclinical program based on longitudinal conversations with patients about living with chronic illness. The goal of the FCE is to explore the experience of illness from the patient's perspective and ultimately to incorporate this perspective in clinical practice. In this qualitative study, we wished to investigate the impact of "diabetes stories"--the stories of FCE volunteers with diabetes--on medical students' understanding of diabetes and its management. Individual interviews were conducted with medical students who had worked with a volunteer with diabetes to answer the questions: "in what ways was learning through these 'diabetes stories' different from that acquired through lectures and textbooks," and "how did these stories impact the students' understanding of diabetes and its care?" Thematic analysis of the transcribed interviews was performed using Grounded Theory. Several major themes emerged: There was more to diabetes than the "scientific" knowledge acquired through lectures; the stories challenged students' assumptions about having or working with people with diabetes and allowed students to see the world through the perspective of someone with diabetes, and the stories motivated students' development as physicians and influenced their general perspectives of doctoring and medicine. First-person narratives of living with diabetes allow for learning in affective, experiential, and cognitive dimensions, stimulate self reflection and perspective-taking, and enhance growth through the challenging of previous assumptions, beliefs, and perspectives. This type of learning is transformative and may result in a shift in students' perspectives towards more open, inclusive attitudes towards patient-centered diabetes care.

Fluorine-19 nuclear magnetic resonance (NMR) studies of cells and perfused organs loaded with fluorinated ion chelators represent a new approach to determining cytosolic free calcium levels in situ. The molecular basis for this approach and the relative advantages and disadvantages of the NMR technique are discussed in this paper. Results obtained on perfused normoxic and ischemic rat hearts are presented, indicating that ischemia is associated with an elevation in the level of cytosolic free calcium before the onset of irreversible cell injury. The results are therefore consistent with this elevation playing a causative role in the mediation of myocardial cell injury resulting from ischemia.

DNA replication during S-phase represents a biochemical metric of cell division. We present here a protocol for measuring very low rates of cell proliferation, on the basis of the incorporation of deuterium ((2)H) from heavy water ((2)H(2)O) into the deoxyribose moiety of purine deoxyribonucleotides in DNA of dividing cells, by use of gas chromatography/pyrolysis/isotope ratio-mass spectrometry (GC/P/IRMS). Very low levels of label incorporation (>or=0.002% atom percent excess (2)H) can be quantified by GC/P/IRMS. This protocol thereby permits shorter periods or lower amounts of (2)H(2)O administration than would be required using standard GC/MS techniques for measuring cell proliferation kinetics (see accompanying protocol in this issue). A disadvantage of this approach compared to GC/MS is the requirement for larger numbers of cells (> approximately 10(7)). This protocol enables definitive in vivo studies of the fraction or absolute number of newly divided cells and their subsequent survival kinetics in animals and humans, even when turnover rates are very low. Indolent hematologic malignancies, such as chronic lymphocytic leukemia, and other relatively quiescent cells represent promising areas of application.

Although estrogen has effects on the heart, little is known regarding which genes in the heart are directly responsive to estrogen. We have shown previously that lipoprotein lipase (LPL) expression was increased in female hearts compared with male hearts. To test whether LPL gene expression in heart is regulated by estrogen, we perfused mouse hearts from ovariectomized females with 100 nM 17beta-estradiol or vehicle for 2 h, after which hearts were frozen, and RNA was isolated. The SYBR green real-time PCR method was used to detect LPL gene expression. We found that addition of 17beta-estradiol to hearts from ovariectomized females resulted in a significant increase in LPL mRNA. This estrogen effect on LPL gene expression in mouse heart can be blocked by the estrogen receptor (ER) antagonist ICI 182,780 or by progesterone. We also identified a potential estrogen receptor element (ERE) enhancer sequence located in the first intron of the mouse LPL gene. The potential ERE sequence was linked to a TATA-luciferase (LUC) reporter plasmid in HeLa cells. Both ERalpha and ERbeta stimulated strong activity on the heterologous promoter reporter in Hela cells upon estrogen addition. Both ERalpha and ERbeta activities on the LPL ERE reporter were abrogated by the ER antagonist ICI 182,780. Progesterone also dose dependently inhibited the estrogen-mediated increase in LPL ERE reporter activity. These results show that heart LPL is an estrogen-responsive gene exhibiting an intronic regulatory sequence.

The publisher of IRRODL, The Canadian Institute of Distance Education Research (CIDER), is pleased to provide links to a series of online seminars that took place over Spring 2007, using Elluminate. These interactive CIDER Sessions disseminate research emanating from North America's and Canada's vibrant DE research community, and we feel these archived recordings are highly relevant to many in the international distance education research community. To access these sessions, you must first download FREE software from Elluminate (see http://www.elluminate.com/support/ )

Biomechanical overload induces cardiac hypertrophy and heart failure, and reactive oxygen species (ROS) play a role in both processes. Thioredoxin-Interacting Protein (Txnip) is encoded by a mechanically-regulated gene that controls cell growth and apoptosis in part through interaction with the endogenous dithiol antioxidant thioredoxin. Here we show that Txnip is a critical regulator of the cardiac response to pressure overload. We generated inducible cardiomyocyte-specific and systemic Txnip-null mice (Txnip-KO) using Flp/frt and Cre/loxP technologies. Compared with littermate controls, Txnip-KO hearts had attenuated cardiac hypertrophy and preserved left ventricular (LV) contractile reserve through 4 weeks of pressure overload; however, the beneficial effects were not sustained and Txnip deletion ultimately led to maladaptive LV remodeling at 8 weeks of pressure overload. Interestingly, these effects of Txnip deletion on cardiac performance were not accompanied by global changes in thioredoxin activity or ROS; instead, Txnip-KO hearts had a robust increase in myocardial glucose uptake. Thus, deletion of Txnip plays an unanticipated role in myocardial energy homeostasis rather than redox regulation. These results support the emerging concept that the function of Txnip is not as a simple thioredoxin inhibitor but as a metabolic control protein.

According to the International Headache Society, idiopathic stabbing headache (ISH), an indomethacin-responsive headache syndrome, is a paroxysmal disorder of short duration manifested as head pain occurring as a single stab or a series of stabs involving the area supplied in the distribution of the first division of the trigeminal nerve. Stabs last for approximately a few seconds, occurring and recurring from once to multiple times per day in an irregular frequency, with no underlying attributable disorder. Previously indomethacin was the principle treatment option for ISH, despite therapeutic failure in up to 35% of cases, until reports showed gabapentin, melatonin and selective cyclo-oxygenase-2 (COX-2) inhibitors were also possibly effective. In this report we present the full case report of an 88 year old lady with a history of untreated ISH where etoricoxib, a selective COX-2 inhibitor, was used to effectively treat her ISH.

Amiodarone is commonly used to treat supraventricular and ventricular arrhythmias in various inpatient and outpatient settings. Over- and under-use of amiodarone is common, and data regarding patterns of use are sparse and largely anecdotal. Because of adverse drug reactions, proper use is essential to deriving optimal benefits from the drug with the least risk. This guide updates an earlier version published in 2000, reviews indications for use of amiodarone and recommends strategies to minimize adverse effects. The recommendations included herein are based on the best available data and the collective experience of the member of the writing committee.

The development of anti-tumor necrosis factor (TNF) therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

This paper reports on an exploratory case study designed to gain insight into instructors' experiences with web based synchronous communication using two way audio and direct messaging. We conducted semi-structured interviews with eight instructors who used Elluminate Live in their web based, asynchronous courses in Education, Nursing, and Social Work at a Canadian university during the Winter 2004-05. We grouped the findings into two categories. The first category relates to use of text based communication or direct messaging (DM). We subdivided this category as follows: trouble shooting versus teaching; and public versus private conversations. The second category relates to use of voice based communication or audio conferencing (two way audio) subdivided into four sub-categories as follows: talkers versus listeners; patience versus prompting; whole group versus breakout groups; and two way versus one way communication. Use of text based messaging and two way audio raised issues of the need to divide one's attention and to promote student-student interaction. Implications for research and practice are presented.

Previous studies have revealed a novel interaction between deoxyhemoglobin and nitrite to generate nitric oxide (NO) in blood. It has been proposed that nitrite acts as an endocrine reservoir of NO and contributes to hypoxic vasodilation and signaling. Here, we characterize the nitrite reductase activity of deoxymyoglobin, which reduces nitrite approximately 36 times faster than deoxyhemoglobin because of its lower heme redox potential. We hypothesize that physiologically this reaction releases NO in proximity to mitochondria and regulates respiration through cytochrome c oxidase. Spectrophotometric and chemiluminescent measurements show that the deoxymyoglobin-nitrite reaction produces NO in a second order reaction that is dependent on deoxymyoglobin, nitrite and proton concentration, with a bimolecular rate constant of 12.4 mol/L −1 s −1 (pH 7.4, 37°C). Because the IC 50 for NO-dependent inhibition of mitochondrial respiration is approximately 100 nmol/L at physiological oxygen tensions (5 to 10 μmol/L); we tested whether the myoglobin-dependent reduction of nitrite could inhibit respiration. Indeed, the addition of deoxymyoglobin and nitrite to isolated rat heart and liver mitochondria resulted in the inhibition of respiration, while myoglobin or nitrite alone had no effect. The addition of nitrite to rat heart homogenate containing both myoglobin and mitochondria resulted in NO generation and inhibition of respiration; these effects were blocked by myoglobin oxidation with ferricyanide but not by the xanthine oxidoreductase inhibitor allopurinol. These data expand on the paradigm that heme-globins conserve and generate NO via nitrite reduction along physiological oxygen gradients, and further demonstrate that NO generation from nitrite reduction can escape heme autocapture to regulate NO-dependent signaling.

he purpose of the study reported on in this paper was to explore how teachers and students manifest social presence in the web-based synchronous secondary classroom (WBSSC). Data were collected using structured and unstructured observations of twelve online recordings of web-based synchronous classes in the province of Newfoundland and Labrador, Canada. Structured observations were guided by an instrument developed by Rourke, Anderson, Garrison and Archer (2001) for identifying and measuring social presence in an online context. Findings revealed that teachers and students relied on different tools when providing affective, interactive and cohesive responses related to social presence. Manifestations of social presence by the teachers occurred through use of two-way audio whereas students relied on text-based Direct Messaging. Expressions of social presence by the students and teachers occurred most often in a context of digressions that drew attention away from the delivery of content. In addition, students demonstrated social presence using discourse conventions transferred from informal social contexts of instant messaging such as ICQ and MSN. Résumé : L’objet de la présente étude consistait à examiner de quelle façon les enseignants et les étudiants font preuve de présence sociale dans les salles de classe synchrones en ligne du secondaire. Des données ont été recueillies au moyen d’observations structurées et non structurées provenant de douze enregistrements en ligne de classes synchrones accessibles par Internet dans la province de Terre-Neuve et Labrador, Canada. Les observations structurées ont été dirigées au moyen d’un instrument développé par Rourke, Anderson, Garrison, et Archer (2001) afin d’identifier et de mesurer la présence sociale en ligne. Les résultats démontrent que les enseignants et les élèves utilisent des outils différents pour offrir des réponses affectives, interactives et homogènes liées à leur présence sociale. Les manifestations de présence sociale par les enseignants se sont produites au moyen de l’utilisation d’un système de transmission audio bilatéral où les étudiants comptaient sur la messagerie texte directe. Les expressions de présence sociale des étudiants et des enseignants se produisent la plupart du temps dans un contexte de digressions qui fait en sorte qu’on s’éloigne du contenu. De plus, les étudiants ont fait preuve de présence sociale au moyen de conventions sur le discours provenant de contextes sociaux informels de messagerie instantanée comme ICQ et MSN.

This article examines how a sample of first-time mothers in the UK constitute childhood in general, and their own children in particular, in and through their talk about the mundane practices of childcare. The data analysed are drawn from a longitudinal qualitative interview study that followed a sample of mothers from late pregnancy until their babies were 2 years old. The analysis explores links between mothers' representations of childhood and the actualities of their childrearing practices. The extent to which both the representations of childhood and the practices of individual mothers are consistent or contradictory, and change or remain constant over time, is also examined.

In the myocardium, the Na+/H+exchanger isoform-1 (NHE1) activity is detrimental during ischemia-reperfusion (I/R) injury, causing increased intracellular Na+(Nai+) accumulation that results in subsequent Ca2+overload. We tested the hypothesis that increased expression of NHE1 would accentuate myocardial I/R injury. Transgenic mice were created that increased the Na+/H+exchanger activity specifically in the myocardium. Intact hearts from transgenic mice at 10–15 wk of age showed no change in heart performance, resting intracellular pH (pHi) or phosphocreatine/ATP levels. Transgenic and wild-type (WT) hearts were subjected to 20 min of ischemia followed by 40 min of reperfusion. Surprisingly, the percent recovery of rate-pressure product (%RPP) after I/R improved in NHE1-overexpressing hearts (64 ± 5% vs. 41 ± 5% in WT; P < 0.05). In addition, NMR spectroscopy revealed that NHE1 overexpressor hearts contained higher ATP during early reperfusion (levels P < 0.05), and there was no difference in Na+accumulation during I/R between transgenic and WT hearts. HOE642 (cariporide), an NHE1 inhibitor, equivalently protected both WT and NHE1-overexpressing hearts. When hearts were perfused with bicarbonate-free HEPES buffer to eliminate the contribution of HCO3−transporters to pHiregulation, there was no difference in contractile recovery after reperfusion between controls and transgenics, but NHE1-overexpressing hearts showed a greater decrease in ATP during ischemia. These results indicate that the basal activity of NHE1 is not rate limiting in causing damage during I/R, therefore, increasing the level of NHE1 does not enhance injury and can have some small protective effects.

Nitric oxide has been shown to be an important signaling messenger in ischemic preconditioning (IPC). Accordingly, we investigated whether protein S-nitrosylation occurs in IPC hearts, and if so to...

Using the recently adopted nomenclature of cell death (Levin et al. 1999), necrosis refers to cell death and disintegration, regardless of the pathway; the modifiers apoptotic and oncotic are used to refer to the mechanism of death. Traditionally cell death following ischemia has been thought to be primarily oncotic necrosis. As detailed in numerous reviews, during ischemia when the ATP falls to very low levels, the ion pumps cannot function resulting in a rise in Ca2+ which further consumes ATP (Farber and Gerson 1984; Jennings et al. 1990; Jennings and Reimer 1981; Jennings and Steenbergen 1985). The rise in Ca2+ during ischemia and reperfusion leads to mitochondrial Ca2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen provides a terminal electron acceptor (oxygen) allowing electron transport to occur; however damage to electron transport chain can lead to increased mitochondrial generation of reactive oxygen species (ROS).

1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification. Alternatives to metformin were not associated with a reduced risk of hypoglycemia, emergency department visits, or cardiovascular events.

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using2H2O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 μg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.

This study was designed to investigate whether treatment with an estrogen receptor-beta (ER-beta)-selective agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN) can provide cardioprotection in female mice lacking endogenous estrogen. To study the effect of ER-beta stimulation in ischemia-reperfusion injury, we treated ovariectomized (ovx) female mice with 0.1 mg/kg/day of 17beta-estradiol, 0.8 mg/kg/day of DPN, or vehicle for 2 weeks. Isolated hearts were Langendorff perfused for 25 min prior to a 1-min treatment with isoproterenol, followed by 20 min of normothermic global ischemia and 40 min of reperfusion. Left ventricular developed pressure (LVDP) and heart rate were measured. Recovery of function at the end of 40 min of reperfusion was expressed as a percentage of pre-ischemic rate pressure product (RPP=LVDP x heart rate). Hearts from ovx female mice had a significantly lower recovery of LVDP than the hearts from intact female mice (12.4+/-1.6% vs. 19.6+/-1.6%, p0.05, respectively). Furthermore, hearts from ovx female mice treated with DPN exhibited significantly better functional recovery than hearts from either vehicle-treated ovx female mice (20.1+/-2.2% vs. 12.4+/-1.6%, p0.05, respectively) or wild type male mice (20.1+/-2.2% vs. 6.4+/-0.6%, p0.05, respectively). DPN did not increase uterine weight in ovx females compared to vehicle treatment. Gene profiling showed that treatment with DPN resulted in upregulation of a number of protective genes such as heat shock protein 70, the antiapoptotic protein, growth arrest and DNA damage 45 beta, and cyclooxygenase 2.

In this paper we examine the application of informed consent to ethnographic research in health care settings. We do not quarrel with either the principle of informed consent or its translation into the requirement that research should only be carried out with consenting participants. However, we do challenge the identification of informed consent with the particular set of bureaucratic practices of ethical review which currently operate in Canada, the US and elsewhere. We argue that these anticipatory regulatory regimes threaten the significant contribution of ethnographic research to the creation of more efficient, more effective, more equitable and more humane health care systems. Informed consent in ethnographic research is neither achievable nor demonstrable in the terms set by anticipatory regulatory regimes that take clinical research or biomedical experimentation as their paradigm cases. This is because of differences in the practices of ethnographic and biomedical research which we discuss. These include the extended periods of time ethnographers spend in the research setting, the emergent nature of ethnographic research focus and design , the nature and positioning of risk in ethnographic research, the power relationships between researchers and participants, and the public and semi-public nature of the settings normally studied . Anticipatory regulatory regimes are inimical to ethnographic research and risk undermining the contribution of systematic inquiry to understanding whether institutions do what they claim to do, fairly and civilly and with an appropriate mobilisation of resources. We do not suggest that we should simply ignore ethics or leave matters to the individual consciences of researchers. Rather, we need to develop and strengthen professional models of regulation which emphasise education, training and mutual accountability. We conclude the paper with a number of suggestions about how such professional models might be implemented.

Over the past decade there has been considerable progress in elucidating the signaling pathways involved in cardioprotection. Considerable recent data suggest that many of these signaling pathways converge on the mitochondria, where such pathways alter the activity of key mitochondrial proteins, leading to reduced apoptosis and necrosis. Inhibition of the mitochondrial permeability transition pore is emerging as a central mechanism in cardioprotection. This review focuses on mechanisms by which cardioprotection alters mitochondrial proteins and channels that regulate cell death and survival.

This paper presents the accounts of eight instructors’ metaphorical travels in landscapes without bearings. The instructors were part of a pilot project at a Canadian university involving the integration of a synchronous communication and collaboration environment into asynchronous distance education courses. To establish their bearings, the instructors need to be aware of their goals and combine them with strategies and techniques that effectively manage the affordances and constraints of the environment. That process may require a degree of risk–taking combined with a willingness to help students lead themselves. It requires developing a proficiency in the simultaneous use of multiple tools and recognizing the differences and similarities between Web–based synchronous environments and face–to–face or asynchronous environments. Above all, it requires an interest in and focus on pedagogy.

Mechanisms underlying gender differences in cardiovascular disease are poorly understood. We found previously that, under hypercontractile conditions, female hearts exhibit significantly less ischemia/reperfusion injury than males. Here we show that male wild-type (WT) mouse hearts pretreated with 10 nmol/L isoproterenol before ischemia exhibited increased injury versus female hearts, but this relative protection in females was absent in eNOS −/− and nNOS −/− hearts. In isoproterenol-treated female versus male hearts, there was also more endothelial NO synthase (eNOS) associated with cardiomyocyte caveolin-3, and more neuronal NOS (nNOS) translocation to caveolin-3 during ischemia/reperfusion. S -nitrosothiol (SNO) formation was increased in isoproterenol-treated ischemic/reperfused hearts in all mouse genotypes, but only in WT mice was SNO content significantly higher in females than males. Using the biotin switch method, we identified the L-type Ca 2+ channel α1 subunit as the predominant S -nitrosylated protein in membrane fractions, and following isoproterenol and ischemia/reperfusion male/female differences in SNO were seen only in WT hearts, but not in constitutive NOS −/− genotypes. The isoproterenol-induced increase in L-type Ca 2+ current ( I Ca ) was smaller in females versus in males, but NOS blockade increased I Ca in females. This gender difference in I Ca in isoproterenol-treated myocytes (and abolition on NOS inhibition) was mirrored exactly in Ca 2+ transients and SR Ca 2+ contents. In conclusion, these data suggest that eNOS and nNOS both play roles in the gender differences observed in ischemia/reperfusion injury under adrenergic stimulation, and also demonstrate increased S -nitrosylation of the L-type Ca 2+ channels in female cardiomyocytes.

Measuring and fulfilling user requirements during medical device development will result in successful products that improve patient safety, improve device effectiveness and reduce product recalls and modifications. Medical device users are an extremely heterogeneous group and for any one device the users may include patients and their carers as well as various healthcare professionals. There are a number of factors that make capturing user requirements for medical device development challenging including the ethical and research governance involved with studying users as well as the inevitable time and financial constraints. Most ergonomics research methods have been developed in response to such practical constraints and a number of these have potential for medical device development. Some are suitable for specific points in the device cycle such as contextual inquiry and ethnography. Others, such as usability tests and focus groups, may be used throughout development. When designing user research there are a number of factors that may affect the quality of data collected, including the sample of users studied, the use of proxies instead of real end-users and the context in which the research is performed. As different methods are effective in identifying different types of data, ideally more than one method should be used at each point in development. However, financial and time factors may often constrain this.

This paper reports on a study which contrasts results obtained using semantic and syntactic units of analysis in a context of content analysis of an online asynchronous discussion. The paper presents a review of literature on both types of units. The data set consisted of 80 messages posted by ten participants in an online learning module. Data were coded twice by two coders working independently. In the first instance, each coder divided all messages into semantic units and then coded those units. The second coding was conducted on the basis of a syntactic unit of a paragraph. Analysis at the level of the whole group showed little difference in results between the two types of coding. At the level of individual participants, those differences were greater. Results are discussed within a framework of reliability, capability of the unit to discriminate between behaviors, feasibility of different units, and their identifiability. Implications for research are discussed.

Background— Mitochondria and sarcomeres have a well-defined architectural relation that partially depends on the integrity of the cytoskeletal network. An R120G missense mutation in the small heat shock protein α-B-crystallin (CryAB) causes desmin-related cardiomyopathy. Desmin-related cardiomyopathy is characterized by the formation of intracellular aggregates containing CryAB and desmin that are amyloid positive, and disease can be recapitulated in transgenic mice by cardiac-specific expression of the mutant protein. Methods and Results— To understand the resultant pathology, we explored the acute effects of R120G expression both in vitro and in vivo. In vitro, transfection of adult cardiomyocytes with R120G-expressing adenovirus resulted in altered contractile mechanics. In vivo, as the cytoskeletal network is disturbed but before deficits in organ function can be detected, alterations in mitochondrial organization and architecture occur, leading to a reduction in the maximal rate of oxygen consumption with substrates that utilize complex I activity, alterations in the permeability transition pore, and compromised inner membrane potential. Apoptotic pathways are subsequently activated, which eventually results in cardiomyocyte death, dilation, and heart failure. Conclusions— Cardiac chaperone dysfunction acutely leads to altered cardiomyocyte mechanics, perturbations in mitochondrial-sarcomere architecture, and deficits in mitochondrial function, which can result in activation of apoptosis and heart failure.

During ischemia and reperfusion, with an increase in intracellular Na + and a depolarized membrane potential, Ca 2+ may enter the myocyte in exchange for intracellular Na + via reverse-mode Na + -Ca 2+ exchange (NCX). To test the role of Ca 2+ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode Ca 2+ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using 31 P-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular Na + using 23 Na-NMR. Consistent with Ca 2+ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced Na + overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX-KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca 2+ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury.

The publisher of IRRODL, The Canadian Institute of Distance Education Research (CIDER), is pleased to link here to a series of eight online seminars that took place over Spring 2005, using Elluminate live e-learning and collaborative solutions. These interactive CIDER Sessions disseminate research emanating from Canada's vibrant DE research community, and we feel these archived recordings are highly relevant to many in the international distance education research community. To access these sessions, you must first download FREE software. Visit http://www.elluminate.com/support/ to download this software.

This paper reports on a case study which identifies and illustrates sources of difference in agreement in relation to reliability in a context of quantitative content analysis of a transcript of an online asynchronous discussion (OAD). Transcripts of 10 students in a month-long online asynchronous discussion were coded by two coders using an instrument with two categories, five processes, and 19 indicators of Problem Formulation and Resolution (PFR). Sources of difference were identified in relation to: coders; tasks; and students. Reliability values were calculated at the levels of categories, processes, and indicators. At the most detailed level of coding on the basis of the indicator, findings revealed that the overall level of reliability between coders was .591 when measured with Cohen’s kappa. The difference between tasks at the same level ranged from .349 to .664, and the difference between participants ranged from .390 to .907. Implications for training and research are discussed. Keywords: content analysis; online discussions; reliability; Cohen's kappa; sources of difference; coding

This paper presents an example of an approach that involves both the student and the instructor in the evaluation of an online discussion in a context of teaching and learning. According to this approach, the student conducts a self analysis of his or her contributions to the discussion, using criteria supplied in advance of the discussion. One student's four part self analysis of his contribution to an online discussion is presented to illustrate the approach. The self analysis focused on the number and length of postings, claims and grounds, and on knowledge construction, and was designed to engage students in higher levels of thinking. The approach to self analysis is discussed in terms of its modification for use in other contexts and implications for practice are presented.

Cardiovascular disease is the major cause of morbidity and mortality in western countries such as the US. Myocardial infarction leads to loss of myocytes and with extremely limited ability to replenish cardiomyocytes, the heart exhibits depressed contractility. This ultimately results in hypertrophy of the remaining viable myocytes, which is the primary predictor for heart failure. Thus, drug therapies which can reduce myocyte cell death and reduce postischaemic dysfunction would be expected to greatly reduce cardiac hypertrophy and subsequent heart failure and death. Inhibition of glycogen synthase kinase (GSK)-3beta has been proposed as a strategy to improve postischaemic cardiomyocyte survival, as inhibition of GSK-3beta has been shown to reduce myocardial cell death following ischaemia and reperfusion. Therapies for inhibiting GSK are feasible as there are a number of newly developed specific inhibitors of GSK available, although most of these drugs have not been tested in long-term animal studies.

An imbalance between triacylglycerol synthesis and breakdown is necessary for the development of obesity. The direct precursor for triacylglycerol biosynthesis is alpha-glycerol phosphate, which can have glycolytic and glyceroneogenic origins. We present a technique for determining the relative glyceroneogenic contribution to triacylglyceride glycerol by labeling the glycerol moiety with 2H2O. The number of hydrogen atoms (n) incorporated from H2O into C-H bonds reflects the metabolic source of alpha-glycerol phosphate and can be calculated by combinatorial analysis of the distribution of mass isotopomers in triacylglyceride glycerol. Three physiological settings with potential effects on glyceroneogenesis and glycolysis were studied in rodents. Adipose tissue acylglyceride glycerol in mice fed a low carbohydrate diet had significantly higher values of n than in mice fed a high carbohydrate diet, suggesting an increased contribution from glyceroneogenesis of from 17 to 50% on the low carbohydrate diet. Similarly, mice administered rosiglitazone had a significant relative increase in glyceroneogenesis (from 17 to 53%), indicated by an increase in adipose acylglyceride glycerol n. Fructose infusion in overnight fasted rats rapidly lowered plasma triacylglyceride glycerol n, reflecting a decreased contribution from glyceroneogenesis (from 66 to 34%) presumably because of increased glycolytic input. In conclusion, we demonstrate that the number of C-H atoms derived from cellular H2O in triacylglyceride glycerol is an informative indicator of alpha-glycerol phosphate origin and, ultimately, triacylglycerol metabolism. Under certain physiological conditions, glyceroneogenesis can be up-regulated in adipose (e.g. low carbohydrate diet) or down-regulated in liver (e.g. fructose infusion). Additionally, stimulation of glyceroneogenesis by rosiglitazone in adipose tissue may be an important factor in the antilipolytic actions of thiazolidinediones.

BACKGROUND: Commercial sea fishing is known to be a hazardous occupation, but little quantitative research has been conducted in the UK. OBJECTIVE: To describe the demography of commercial fishermen accessing NHS accident and emergency (A&E) services and profile the reasons for attendance. METHODS: Eight NHS A&E departments in North East Scotland participated in the audit. A structured data collection form was completed by the attending nurse or doctor during a 6 month period (March-August). All commercial sea fishermen attending during this time were included whether or not the reason for attendance was work-related. RESULTS: There were 164 cases of which 133 (81%) presented with injuries and 19 (12%) with illnesses (12 unknown). Twenty-seven (16%) cases had required emergency evacuation from commercial vessels. The most frequent category of injury was 'hand', 'wrist' or 'finger' followed by 'head', 'face' and 'throat'. CONCLUSION: Commercial sea fishing is a dangerous occupation with many injuries requiring NHS A&E treatment. The relatively high level of injuries compared to illness indicates that there are still safety issues to be addressed and current risk assessment requirements need to be reviewed.

Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water (2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.