Effects of oral calcium sensitizers on experimental heart failure

Suun kautta annosteltava kalsiumherkistäjä parantaa sydämen vajaatoimintaan liittyvää pumppausvajetta kokeellisissa sydämen vajaatoimintamalleissa Huolimatta viime vuosikymmenien lääketieteellisestä kehityksestä krooninen sydämen vajaatoiminta on silti edelleen vakava, elämänlaatua voimakkaasti rajoittava sairaus. Kalsiumherkistäjät ovat uusi, sydämen pumppausvoimaa lisäävä lääkeryhmä. Levosimendaani, kotimaista alkuperää oleva kalsiumherkistäjä, on kliinisessä käytössä akuutin vajaatoiminnan hoitoon suonensisäisesti ja lyhytaikaisesti annosteltavana valmisteena. Levosimendaanilla on aktiivinen metaboliitti, OR-1896, jonka oletetaan olevan vuorokauden mittaisen levosimendaani-infuusion jälkeen havaittujen useita päiviä kestävien hyödyllisisten vaikutuksisten takana. Levosimendaanin kroonisen, suun kautta tapahtuvan annostelun vaikutuksista tieto on vähäisempää, mutta sillä näyttää olevan positiivisia vaikutuksia potilaiden raportoimana. FM Marjut Louhelainen on selvittänyt väitöskirjassaan suun kautta annosteltavan levosimendaanin ja sen pitkäkestoisen aktiivisen metaboliitin vaikutuksia kroonisen vajaatoiminnan hoidossa käyttämällä sekä hypertensiivisen sydäntaudin että 2 tyypin diabeteksen komplisoimaan sydäninfarktin kokeellisia malleja. Tutkimuksessa selvitettiin lisäksi vajaatoimintaan johtavia molekyylitason tapahtumia sydänlihaksessa. Tutkimuksessa osoitettiin, että krooninen suun kautta annosteltu hoito sekä kalsiumherkistäjä levosimendaanilla että sen aktiivisella metaboliitilla estää hypertensiiviseen sydämen vajaatoiminnan aikaasaamaa sydämen uudelleenmuovaantumista ja siihen liittyvää kuolleisuutta. Nämä vaikutukset välittyivät vähentyneen sydänlihassoluhypertrofian, solukuolleisuuden ja neurohumaraalisen aktivaation kautta. Levosimendaanin ja OR-1896:n osoitettiin myös parantavan sydämen pumppausfunktiota tyyppi 2 diabeteksen komplisoimassa sydäninfarktissa. Ei-diabeettiseen tilanteeseen verrattuna diabetekseen liittyvä infarktin jälkeinen vajaatoiminnan kehitys oli yhteydessä lisääntyneeseen tulehdukseen, fibroosiin, solukuolemaan, neurohumoraaliseen aktivaatioon ja ennenaikaiseen kudoksen vanhenemiseen. Sekä levosimendaani, että OR-1869 vähensivät tulehduksen, fibroosin ja solukuoleman merkkejä ja vaimensi neurohumoraalista aktivaatiota. OR-1896 myös vähensi solujen vanhenemiseen liittyvien merkkiaineiden ilmentymistä. Väitöskirjassa todettiin, että suun kautta annosteltuna sekä levosimendaani, että sen aktiivinen metaboliitti OR-1896, omaavat terapeuttista potentiaalia sekä hypertensiivisen sydäntaudin hoitoon että sydäninfarktin jälkeisen vajaatoiminnan estoon. FM Marjut Louhelaisen farmakologian alaan kuuluva väitöskirja Effects of oral calcium sensitizers on experimental heart failure tarkastetaan Helsingin yliopiston Lääketieteellisessä tiedekunnassa perjantaina 29.01.2010 klo 12 (Biomedicum Helsinki, luentosali 2, Haartmaninkatu 8, Helsinki). Vastaväittäjänä toimii professori Raimo Tuominen, Helsingin yliopiston Farmasian tiedekunnasta ja kustoksena professori Eero Mervaala Helsingin yliopiston Lääketieteellisestä tiedekunnasta.

Effectiveness factor for zeroth-order catalytic reactions with volume change and nonuniform catalyst activity profiles

Analytical solutions are presented for the effectiveness factor of a zeroth-order reaction with volume change and nonuniform catalyst activity profile in slab, cylinder and spherical pellets. The possibility of shape normalization is considered for a variety of activity profiles and pellet shapes. When the catalyst activity at the external surface of the pellet is non-zero, shape normalization is obtained, which makes the asymptotic behavior of the effectiveness factor identical for small and large values of Thiele modulus, however, the normalization can lead to significant errors, particularly for the case of activity profiles decreasing towards the outer surface of the catalyst.

Sequence variants in three loci influence monocyte counts and erythrocyte volume

Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Testing the efficacy of low volume herbicide applications on Chromolaena odorata

Siam Weed (Chromoleana odorata) is the target of an eradication program in north Queensland; however some infestations occur on ground inaccessible to high volume, ground based herbicide spray equipment. Four foliar herbicides were applied to dense infestations of mature Siam Weed in March 2009, near Townsville, north Queensland. Low volume, high concentration solutions containing 40 g L-1 a.i. glyphosate, 1.2 g L-1 a.i metsulfuron-methyl, 10 g L-1 a.i. fluroxypyr + 0.7 g L-1 a.i. aminopyralid and 15 g L-1 a.i. triclopyr + 5 g L-1 a.i. picloram + 0.4 g L-1 a.i. aminopyralid were applied using a 5 L backpack and hand gun (or splatter gun). Relatively small amounts (approximately 24-28 mL) of the high concentration solutions were applied to each bush and assessments of the replicated treated and untreated control plots were conducted 76, 207 and 356 days after treatment. These assessments demonstrated that the fluroxypyr and triclopyr based herbicides controlled 96 to 100% of plants. The metsulfuron-methyl and glyphosate based herbicides controlled 40 and 57% of plants respectively 12 months after treatment, when 3% of untreated control plants were dead. The trial demonstrated that this application method and either of two herbicides provides an additional tool for controlling Siam weed in remote areas, which are inaccessible to traditional higher volume foliar herbicide applications. Lower volume herbicide solutions reduce the volume of water and thus the effort needed to effectively treat less accessible infestations.

R-parameter: A local truncation error based adaptive framework for finite volume compressible flow solvers

A residual-based strategy to estimate the local truncation error in a finite volume framework for steady compressible flows is proposed. This estimator, referred to as the -parameter, is derived from the imbalance arising from the use of an exact operator on the numerical solution for conservation laws. The behaviour of the residual estimator for linear and non-linear hyperbolic problems is systematically analysed. The relationship of the residual to the global error is also studied. The -parameter is used to derive a target length scale and consequently devise a suitable criterion for refinement/derefinement. This strategy, devoid of any user-defined parameters, is validated using two standard test cases involving smooth flows. A hybrid adaptive strategy based on both the error indicators and the -parameter, for flows involving shocks is also developed. Numerical studies on several compressible flow cases show that the adaptive algorithm performs excellently well in both two and three dimensions.

Wind drift of snowfall between the radar volume and ground

This study evaluates how the advection of precipitation, or wind drift, between the radar volume and ground affects radar measurements of precipitation. Normally precipitation is assumed to fall vertically to the ground from the contributing volume, and thus the radar measurement represents the geographical location immediately below. In this study radar measurements are corrected using hydrometeor trajectories calculated from measured and forecasted winds, and the effect of trajectory-correction on the radar measurements is evaluated. Wind drift statistics for Finland are compiled using sounding data from two weather stations spanning two years. For each sounding, the hydrometeor phase at ground level is estimated and drift distance calculated using different originating level heights. This way the drift statistics are constructed as a function of range from radar and elevation angle. On average, wind drift of 1 km was exceeded at approximately 60 km distance, while drift of 10 km was exceeded at 100 km distance. Trajectories were calculated using model winds in order to produce a trajectory-corrected ground field from radar PPI images. It was found that at the upwind side from the radar the effective measuring area was reduced as some trajectories exited the radar volume scan. In the downwind side areas near the edge of the radar measuring area experience improved precipitation detection. The effect of trajectory-correction is most prominent in instant measurements and diminishes when accumulating over longer time periods. Furthermore, measurements of intensive and small scale precipitation patterns benefit most from wind drift correction. The contribution of wind drift on the uncertainty of estimated Ze (S) - relationship was studied by simulating the effect of different error sources to the uncertainty in the relationship coefficients a and b. The overall uncertainty was assumed to consist of systematic errors of both the radar and the gauge, as well as errors by turbulence at the gauge orifice and by wind drift of precipitation. The focus of the analysis is error associated with wind drift, which was determined by describing the spatial structure of the reflectivity field using spatial autocovariance (or variogram). This spatial structure was then used with calculated drift distances to estimate the variance in radar measurement produced by precipitation drift, relative to the other error sources. It was found that error by wind drift was of similar magnitude with error by turbulence at gauge orifice at all ranges from radar, with systematic errors of the instruments being a minor issue. The correction method presented in the study could be used in radar nowcasting products to improve the estimation of visibility and local precipitation intensities. The method however only considers pure snow, and for operational purposes some improvements are desirable, such as melting layer detection, VPR correction and taking solid state hydrometeor type into account, which would improve the estimation of vertical velocities of the hydrometeors.

Refining low-volume, high-concentration herbicide applications to control Chromolaena odorata (L.) King & Robinson (Siam weed) in remote areas

Chromolaena odorata (L.) King and Robinson (Siam weed) is a highly invasive plant and a high priority for control in north Queensland. It can be effectively treated using high-volume, groundbased herbicide spray equipment, but operational information shows that this control method becomes increasingly difficult in areas where vehicle access is prevented by rougher terrain. Low-volume, high-concentration herbicide applications have proven capable of causing high mortality in these remote situations. Two trials were undertaken between May 2010 and May 2012 to refine effective rates of aminopyralid/fluroxypyr, fluroxypyr and metsulfuron-methyl, only using low-volume, high-concentration applications on Siam weed. Fluroxypyr on its own was as effective as aminopyralid/fluroxypyr as both herbicides caused 95-100% mortality at overlapping rates containing 5 to 18.85 g a.i. L-1 of fluroxypyr. Metsulfuron-methyl caused 100% mortality when applied at 3 and 6 g a.i. L-1. Effective control was achieved with approximately 16 to 22 mL of the solutions per plant, so a 5 L mixture in a backpack could treat 170 to 310 adult plants. There are several options for treating Siam weed on the ground and the choice of methods reflects the area, plant density and accessibility of the infestation. Control information from Siam weed field crews shows that low volume, high concentration herbicide applications applied using a splatter gun are a more efficient method for controlling larger, denser remote infestations than physical removal. By identifying effective herbicides that are applied through low-volume equipment, these trials provide an additional and more efficient tool for controlling Siam weed in remote areas.

Queensland Agricultural Journal Volume 13 Parts 1-6 July to December 1903

General Index Vol 13 Parts 1-6, pages 1-81

Editorial of "International Journal of Critical Indigenous Studies Volume 1, Number 1, 2008"

We perceive the epistemological boundaries of Critical Indigenous Studies as marked by analyses of contemporary colonising power in its multiple forms in different contexts. This first issue brings together a diverse group of international Indigenous scholars who are politically and intellectually engaged in theorising from their respective standpoints as well as spatial and geographic locations. As such these essays enable dialogue across and within different colonial power contexts addressing epistemological ethical and methodological concerns within the broad field of Indigenous studies. In each essay a connecting theme is the need for intercultural and comparative work and to import Indigenous agency in the writing of history...

Editorial of "International Journal of Critical Indigenous Studies Volume 2, Number 1, 2009"

Over the past two decades neo liberalism has shaped global economic activity. The international reach of the current economic crisis propelled by the subprime mortgage meltdown in the United States has affected Indigenous communities in different ways to those whose investments were depleted by the Wall Street activities of an unregulated corporate and banking sector. Throughout this roller coaster economic ride the low socio-economic position of Indigenous peoples continued in Canada, the United States of America, New Zealand, Hawaii and Australia. The logic, or illogic of capital, failed to extend the boom of the economic upturn to Indigenous peoples, but is poised to extend the repercussions of the current downturn deep into Indigenous lives. The consistency of the Indigenous socio-economic position across these countries, even where treaties exist, indicates that the phenomenon is based on a shared Indigenous reality. In this special edition, the commonality in the way in which Indigenous people are engaged in and positioned by market forces and regulation by their respective nation states is proposed as one of the foundation plates of that Indigenous positioning...

Editorial of "International Journal of Critical Indigenous Studies Volume 2, Number 2, 2009"

This edition of the International Critical Indigenous Studies Journal, our second for 2009 takes alternative understandings as its theme. All four articles in this edition attend to citizenship and Indigenous sovereignty though in different ways...

Editorial of "International Journal of Critical Indigenous Studies Volume 3, Number 1, 2010"

The articles in this edition of the International Journal of Critical Indigenous Studies engage collectively with how different epistemologies and cultural values inform power relations in different locations, situations and contemporary contexts. As a group, these articles demonstrate, over varying facets, how meaning, communicative intent and interpretive effect are constitutive of power relations between Indigenous people and non Indigenous people. Jackie Grey discusses the labour of belonging as played out in a dispute over Indigenous fishing rights in a small New England town of Aquinnah, located on Noepe Island the traditional lands of the Wampanoag in the United States of America. She reveals the ways in which the jurisdiction of non Indigenous belonging operates discursively and materially to preclude Indigenous rights and self determination. Grey's analysis highlights the incommensurability of Indigenous and non Indigenous belonging that are played out in power relations born of colonisation.

Editorial of "International Journal of Critical Indigenous Studies Volume 3, Number 2, 2010"

In this of the International Journal of Critical Indigenous Studies, the articles reveal how competing economies of knowledge, capital and values are operationalised through colonising power within inter-subjective relations. Writing in the Australian context, Greg Blyton demonstrates how tobacco was used by colonists as a means of control and exchange in their relations with Indigenous people. He focuses on the Hunter region of New South Wales, Australia, in the early to mid-nineteenth century to reveal how colonists exchanged tobacco for food, safe passage and Indigenous services. Blyton suggests that these colonial practices enabled tobacco addiction to spread throughout the region, passing from one generation of Indigenous people to another. He asks us to consider the link between the colonial generation of Indigenous tobacco consumption and addiction, and Indigenous mortality rates today whereby twenty percent of deaths are attributed to smoking.

Editorial of "International Journal of Critical Indigenous Studies Volume 4, Number 1, 2011"

This special edition of the International Journal of Critical Indigenous Studies highlights the work of emerging scholars in the field of Indigenous Studies. The five featured authors were all finalists for the prize awarded by the Native American and Indigenous Studies Association (NAISA) to the best post-graduate student paper at the NAISA meeting held in 2010 in Tucson, Arizona. While the breadth of scholarship encompassed by the term ‘Indigenous Studies’ and the global representation of Indigenous peoples at NAISA mean that the topics and approaches vary widely, a common thematic of fraught post-colonial relations can be discerned within all five articles.