Novel endogenous peptide agonists of cannabinoid receptors

Hemopressin (Hp), a 9-residue alpha-hemoglobin-derived peptide, was previously reported to function as a CB(1) cannabinoid receptor antagonist (1). In this study, we report that mass spectrometry (MS) data from peptidomics analyses of mouse brain extracts identified N-terminally extended forms of Hp containing either three (RVD-Hp alpha) or two (VD-Hp alpha) additional amino acids, as well as a beta-hemoglobinderived peptide with sequence similarity to that of hemopressin (VD-Hp beta). Characterization of the alpha-hemoglobin-derived peptides using binding and functional assays shows that in contrast to Hp, which functions as a CB(1) cannabinoid receptor antagonist, both RVD-Hp alpha and VD-Hp alpha function as agonists. Studies examining the increase in the phosphorylation of ERK1/2 levels or release of intracellular Ca(2+) indicate that these peptides activate a signal transduction pathway distinct from that activated by the endo-cannabinoid, 2-arachidonoylglycerol, or the classic CB(1) agonist, Hu-210. This finding suggests an additional mode of regulation of endogenous cannabinoid receptor activity. Taken together, these results suggest that the CB(1) receptor is involved in the integration of signals from both lipid-and peptide-derived signaling molecules.-Gomes, I., Grushko, J. S., Golebiewska, U., Hoogendoorn, S., Gupta, A., Heimann, A. S., Ferro, E. S., Scarlata, S., Fricker, L. D., Devi, L. A. Novel endogenous peptide agonists of cannabinoid receptors. FASEB J. 23, 3020-3029 (2009). www.fasebj.org

Continuous GRASP with a local active-set method for bound-constrained global optimization

Global optimization seeks a minimum or maximum of a multimodal function over a discrete or continuous domain. In this paper, we propose a hybrid heuristic-based on the CGRASP and GENCAN methods-for finding approximate solutions for continuous global optimization problems subject to box constraints. Experimental results illustrate the relative effectiveness of CGRASP-GENCAN on a set of benchmark multimodal test functions.

Bayesian density estimation using Skew Student-t-Normal mixtures

We present a Bayesian approach for modeling heterogeneous data and estimate multimodal densities using mixtures of Skew Student-t-Normal distributions [Gomez, H.W., Venegas, O., Bolfarine, H., 2007. Skew-symmetric distributions generated by the distribution function of the normal distribution. Environmetrics 18, 395-407]. A stochastic representation that is useful for implementing a MCMC-type algorithm and results about existence of posterior moments are obtained. Marginal likelihood approximations are obtained, in order to compare mixture models with different number of component densities. Data sets concerning the Gross Domestic Product per capita (Human Development Report) and body mass index (National Health and Nutrition Examination Survey), previously studied in the related literature, are analyzed. (c) 2008 Elsevier B.V. All rights reserved.

Multimilligram enantioresolution of sulfoxide proton pump inhibitors by liquid chromatography on polysaccharide-based chiral stationary phase

The enantiomers of sulfoxide proton pump inhibitors - omeprazole, lansoprazole, rabeprazole and Ro 18-5364 - were enantiomerically separated by liquid chromatography at multimilligram scale on a poly saccharide-based chiral stationary phase using normal and polar organic conditions as mobile phase. The values of the recovery and production rate were significant for each enantiomer; better results were achieved using a solid-phase injection system. However, this system was applied just for the enantionteric separation of omeprazole to demonstrate the applicability of this injection mode at milligram scale. The chiroptical characterization of the compounds was performed using a polarimeter and a circular dichroism detector. The higher enantiomeric purity obtained for the isolated enantiomers suggests that the methods here described should be considered as a simple and rapid way to obtain enantiomeric pure standards for analytical purpose. (C) 2007 Elsevier B.V. All rights reserved.

Sockerlösningens smärtlindrande effekt -avseende nyfödda En systematisk litteraturstudie

Syftet med denna litteraturstudie var att beskriva vilken aktuell vetenskap som lett till rekommendationen av att administrera sockerlösning till nyfödda barn i smärtlindrande syfte, i samband med hälstick/venpunktion. Litteraturstudien var av kvantitativ, deskriptiv art. Data analyserades med hjälp av Forsberg och Wengströms granskningsmall för randomiserade kontrollerade studier. De studier som granskades i denna uppsats visade genomgående att sockerlösningen har betydelse för smärtlindringen hos det nyfödda barnet som genomgått någon form av procedursmärta. Vad gäller styrkan på sockerlösningarna kunde konstateras att högre styrka gav bättre effekt. Utöver sockerlösningen vidtogs i studierna även andra omvårdnadsmässiga strategier för att reducera stress och smärta. Det är viktigt ur ett sjuksköterskeperspektiv att tänka på att till exempel hålla barnet varmt och bara klä av den extremitet som ska stickas i. Det anses att ett tryggt, lugnt och mätt barn visar mindre smärtreaktioner än ett hungrigt och irriterat. Författarna till denna litteraturstudie anser att man inte bara ska förlita sig på som i det här fallet sockerlösningen i smärtlindringssyfte utan se helheten då planering och eftertanke också är viktiga bitar vid provtagningar av spädbarn. Sockerlösningen skall ses som ett bra komplement i smärtlindringssyfte.

Acupuncture with manual and electrical stimulation for labour pain : a longitudinal randomised controlled trial

Background: Acupuncture is commonly used to reduce pain during labour despite contradictory results. The aim of this study is to evaluate the effectiveness of acupuncture with manual stimulation and acupuncture with combined manual and electrical stimulation (electro-acupuncture) compared with standard care in reducing labour pain. Our hypothesis was that both acupuncture stimulation techniques were more effective than standard care, and that electro-acupuncture was most effective.  Methods: A longitudinal randomised controlled trial. The recruitment of participants took place at the admission to the labour ward between November 2008 and October 2011 at two Swedish hospitals. 303 nulliparous women with normal pregnancies were randomised to: 40 minutes of manual acupuncture (MA), electro-acupuncture (EA), or standard care without acupuncture (SC). Primary outcome: labour pain, assessed by Visual Analogue Scale (VAS). Secondary outcomes: relaxation, use of obstetric pain relief during labour and post-partum assessments of labour pain. The sample size calculation was based on the primary outcome and a difference of 15 mm on VAS was regarded as clinically relevant, this gave 101 in each group, including a total of 303 women.  Results: Mean estimated pain scores on VAS (SC: 69.0, MA: 66.4 and EA: 68.5), adjusted for: treatment, age, education, and time from baseline, with no interactions did not differ between the groups (SC vs MA: mean difference 2.6, 95% confidence interval [CI] -1.7-6.9 and SC vs EA: mean difference 0.6 [95% CI] -3.6-4.8). Fewer number of women in the EA group used epidural analgesia (46%) than women in the MA group (61%) and SC group (70%) (EA vs SC: odds ratio [OR] 0.35; [95% CI] 0.19-0.67).  Conclusions: Acupuncture does not reduce women's experience of labour pain, neither with manual stimulation nor with combined manual and electrical stimulation. However, fewer women in the EA group used epidural analgesia thus indicating that the effect of acupuncture with electrical stimulation may be underestimated. These findings were obtained in a context with free access to other forms of pain relief.

Acupuncture with manual and electrical stimulation for labour pain : a two month follow up of recollection of pain and birth experience.

BACKGROUND: In a previous randomised controlled trial we showed that acupuncture with a combination of manual- and electrical stimulation (EA) did not affect the level of pain, as compared with acupuncture with manual stimulation (MA) and standard care (SC), but reduced the need for other forms of pain relief, including epidural analgesia. To dismiss an under-treatment of pain in the trial, we did a long-term follow up on the recollection of labour pain and the birth experience comparing acupuncture with manual stimulation, acupuncture with combined electrical and manual stimulation with standard care. Our hypothesis was that despite the lower frequency of use of other pain relief, women who had received EA would make similar retrospective assessments of labour pain and the birth experience 2 months after birth as women who received standard care (SC) or acupuncture with manual stimulation (MA). METHODS: Secondary analyses of data collected for a randomised controlled trial conducted at two delivery wards in Sweden. A total of 303 nulliparous women with normal pregnancies were randomised to: 40 min of MA or EA, or SC without acupuncture. Questionnaires were administered the day after partus and 2 months later. RESULTS: Two months postpartum, the mean recalled pain on the visual analogue scale (SC: 70.1, MA: 69.3 and EA: 68.7) did not differ between the groups (SC vs MA: adjusted mean difference 0.8, 95 % confidence interval [CI] -6.3 to 7.9 and SC vs EA: mean difference 1.3 CI 95 % -5.5 to 8.1). Positive birth experience (SC: 54.3 %, MA: 64.6 % and EA: 61.0 %) did not differ between the groups (SC vs MA: adjusted Odds Ratio [OR] 1.8, CI 95 % 0.9 to 3.7 and SC vs EA: OR 1.4 CI 95 % 0.7 to 2.6). CONCLUSIONS: Despite the lower use of other pain relief, women who received acupuncture with the combination of manual and electrical stimulation during labour made the same retrospective assessments of labour pain and birth experience 2 months postpartum as those who received acupuncture with manual stimulation or standard care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01197950.

Acupuncture for labour pain

Background: Acupuncture involves puncturing the skin with thin sterile needles at defined acupuncture points. Previous studies are inconclusive regarding the effect of acupuncture on labour pain, but some studies have found a reduction in the use of pharmacological pain relief when acupuncture is administered. The appropriate dose of acupuncture treatment required to elicit a potential effect on labour pain has not been fully explored. The dose is determined by many different factors, including the number of needles used and the intensity of the stimulation. In Sweden, manual stimulation of the needles is common practice when acupuncture is used for labour pain, but electrical stimulation of the needles, which gives a higher dose, could possibly be more effective. The overall aim of this thesis was to evaluate the effectiveness of acupuncture with manual stimulation (MA) of the needles as well as acupuncture with a combination of manual and electrical stimulation (EA) in reducing labour pain, compared with standard care without any form of acupuncture (SC). Methods: The study was designed as a three-armed randomised controlled trial in which 303 nulliparous women with normal pregnancies were randomised to MA, EA, or SC. The primary outcome was labour pain, assessed using the Visual Analogue Scale (VAS). Secondary outcomes were relaxation during labour, use of obstetric pain relief, and associations between maternal characteristics and labour pain and use of epidural analgesia respectively. Also, labour and infant outcomes, recollection of labour pain, and maternal experiences, such as birth experience and experience of the midwife, were investigated two months after the birth. The sample size calculation was based on the potential to discover a difference of 15 mm on the VAS. Data were collected during labour before the interventions, the day after birth, and two months later. Besides using the VAS, information was collected by means of study specific protocol, questionnaires and medical records. Results: The mean VAS scores were 66.4 in the MA group, 68.5 in the EA group, and 69.0 in the SC group (mean differences: MA vs. SC 2.6 95% CI -1.7 to 6.9, and EA vs. SC 0.6 95% CI -3.6 to 4.8). Other methods of pain relief were used less frequently in the EA group, including epidural analgesia, MA 61.4%, EA 46%, and SC 69.9%. (EA vs. SC OR 0.4 95% CI 0.2 to 0.7). No statistically significant differences were found in the recollection of labour pain between the three groups two months after birth (mean VAS score: MA 69.3, EA 68.7 and SC 70.1). A few maternal characteristics were associated with labour pain (age, dysmenorrhea, and cervix dilatation), but none of the investigated characteristics predicted the outcome of the acupuncture treatment in MA or EA. Women in the EA group experienced acupuncture as being effective for labour pain to a higher extent than women who received MA, MA 44.4%, EA 67.1% (EA vs. MA OR 2.4 95% CI 1.2 to 4.8). Women in the EA group also spent less time in labour (mean 500 min) than those who received MA (mean 619 min) and SC (mean 615 min) (EA vs. MA HR 1.4 95% CI 1.0 to1.9, EA vs. SC HR 1.4, 95% CI 1.1 to 2.0), and had less blood loss than women receiving SC, (EA vs. SC OR 0.1 95% CI 0.3 to 0.7). The women’s assessment of the midwife as being supportive during labour (MA 77.2%, EA 83.5%, SC 80%), overall satisfaction with midwife care (MA 100%, EA 97.5%, SC 98.7%), and having an overall positive childbirth experience (MA 64.6%, EA 61.0%, SC 54.3%) did not differ statistically. No serious side effects of the acupuncture treatment were reported. Conclusion: Acupuncture, regardless of type of stimulation, did not differ from standard care without acupuncture in terms of reducing women’s experience of pain during labour, or their memory of pain and childbirth overall two months after the birth. However, other forms of obstetric pain relief were less frequent in women receiving a combination of manual and electrical stimulation, suggesting that this method could facilitate coping with labour pain.

Languaging in virtual learning sites : studies of online encounters in the language-focused classroom

This thesis focuses upon a series of empirical studies which examine communication and learning in online glocal communities within higher education in Sweden. A recurring theme in the theoretical framework deals with issues of languaging in virtual multimodal environments as well as the making of identity and negotiation of meaning in these settings; analyzing the activity, what people do, in contraposition to the study of how people talk about their activity. The studies arise from netnographic work during two online Italian for Beginners courses offered by a Swedish university. Microanalyses of the interactions occurring through multimodal video-conferencing software are amplified by the study of the courses’ organisation of space and time and have allowed for the identification of communicative strategies and interactional patterns in virtual learning sites when participants communicate in a language variety with which they have a limited experience. The findings from the four studies included in the thesis indicate that students who are part of institutional virtual higher educational settings make use of several resources in order to perform their identity positions inside the group as a way to enrich and nurture the process of communication and learning in this online glocal community. The sociocultural dialogical analyses also shed light on the ways in which participants gathering in discursive technological spaces benefit from the opportunity to go to class without commuting to the physical building of the institution providing the course. This identity position is, thus, both experienced by participants in interaction, and also afforded by the ‘spaceless’ nature of the online environment.

Multimodalt skrivande i praktiken : Sex lärares beskrivningar om och hur det multimodala skrivandet på Åland sker samt deras upplevelser av och attityder till multimodalt skrivande

Huvudsyftet med denna empiriska studie har varit att undersöka om och hur några lärare på Åland praktiskt arbetar med multimodalt skrivande i årskurs 4-6, samt deras upplevelser av och inställning till det multimodala skrivandet i skolan. Det multimodala skrivandet har i denna studie definierats som att skriftlig, visuell och auditiv teckenvärld kombineras på ett eller annat sätt. Skrivuppgifter där text kombinerats med bild och ljud är exempel på detta. Genom halvstrukturerade intervjuer visar studien att det multimodala skrivandet förekommer relativt ofta, främst det som innefattar text och bild. Dessutom förekommer både analoga och digitala multimodala skrivuppgifter i undervisningen. Det visar sig att möjligheterna är många med lärare som generellt är positiva till det multimodala skrivandet i skolan. Det är snarare lärarna själva som begränsar den multimodala skrivundervisningen på grund av egen osäkerhet. Den digitala tekniken kan stundtals också ställa till med bekymmer. Vidare visar studien att lärare behöver utveckla och förstå att den multimodala skrivprocessen är en integrerad process där helheten är det centrala. Lärare behöver även utveckla den multimodala skrivkompetensen eftersom den granskande aspekten av texters budskap är lika viktig som att låta olika teckenvärldar samspela. Trots en obekanthet med begreppet så inkluderar lärare multimodalt skrivande i sin undervisning.

Rapport från projektet Multimodala uppgifter och bedömning i matematik : Video och kollaborativa samtal som metod vid lärares bedömning av elevers matematiska kunskaper

This research will discuss some experiences from a four year school research study. It was conducted in cooperation with teachers from four municipalities in Dalarna. The aim of the research was to examine teachers´ professional development when they participated in collaborative discussions based on video recordings and video edited material from specific lessons in their own practice. The study had two foci one was to investigate methods and tools that teachers can use to develop their ability to assess their students while working on multimodal tasks. The other was to examine how video can be used by teachers wanting to obtain knowledge about assessing students. The study is based on several theories about when teachers collaborate to create new knowledge. The first is the design theoretical approach – where visual ethnography and a semiotic approach contribute to problematize the use and mixture of different modes. A basic assumption of the framework here is that meanings are made and communicated in mathematics through a wide range of semiotic modes. By using video as an essential tool in the research the framework theories concerning visual ethnography, video documentation and individuals as reflective practitioners were also needed. The findings can be divided into the following themes: the use of tasks for assessment, collaborative discussion, equipment, ethical dilemmas. Collaborative discussions were evaluated as a meaningful way of sharing knowledge. The use of video recordings in association with these discussions raised important ethical issues. Working with the assessment framework was of great interest to the teachers but it took a lot of time from their ordinary work. In this way the project highlighted more general aspects of school development. The research also concerns teachers´ use of collaborative discussions in assessment work, multimodal tasks in mathematics and video as a research tool in general.