Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

MCP-1 induces migration of adult neural stem cells

As a model for brain inflammation we previously studied transcriptional profiles of tumor necrosis factor-alpha (TNF)treated U373 astroglioma cells. In previous work we were able to demonstrate that the chemokine monocyte chemoattractant protein-1 (MCP-1, SCYA2, CCL2, MCAF) expression in U373 cells was inducible by TNF-alpha treatment. Demonstrably MCP-1 mRNA and protein expression in U373 cells was sustainable over time and at the highest level of all genes analyzed (Schwamborn et al., BMC Genomics 4, 46, 2003). In the hematopoietic system MCP-1 is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. In search of further functions in brain inflammation we tested the hypothesis that MCP-1 acts as a chemokine on neural stem cells. Here we report that MCP-1 activates the migration capacity of rat-derived neural stem cells. The migration of stem cells in a Boyden chamber analysis was elevated after stimulation with MCP-1. Time-lapse video microscopy visualized the migration of single stem cells from neurospheres in MCP-1-treated cultures, whereas untreated cultures depicted no migration at all, but showed signs of sprouting. Expression of the MCP-1 receptor CCR2 in neurosphere cultures was verified by RT-PCR and immunofluorescence microscopy. Supernatants from TNF-treated U373 cells also induced migration of neural stem cells.

Neural stem cells adopt tumorigenic properties by constitutively activated NF-kappaB and subsequent VEGF up-regulation

One of the challenges in stem cell research is to avoid transformation during cultivation. We studied high passage subventricular zone derived neural stem cells (NSCs) cultures of adult rats in the absence of growth factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). We termed this culture exogenous growth factor independent neural stem cells (GiNSCs). GiNSCs expressed stemness markers, displayed a high constitutive NF-kappaB activity and an increased, aberrant, polyploid DNA content. GiNSCs showed a tumorigenic phenotype and formed colonies in a soft agar assay. Microarray analysis showed the up-regulation of the NF-kappaB target gene vascular endothelial growth factor (VEGF). In contrast, proneuronal genes were down-regulated. Under neuronal differentiation conditions GiNSCs adopted a glioma-like phenotype, with nuclear p53, preserving high amounts of Nestin positive cells and prolonged proliferation. Neutralization of VEGF strongly inhibited proliferation and induced differentiation. In a gain of function approach, the transfection of NSCs with constitutively active upstream kinase IKK-2 led to constitutively activated NF-kappaB, proliferation in absence of growth factors and augmented VEGF secretion. In a rescue experiment a reduction of NF-kappaB activity by overexpression of IkappaB-AA1 was able to shift the morphology toward an elongated cell form, increased cell death, and decreased proliferation. Thus GiNSCs may provide a potent tool in cancer research, as their exogenous cytokine independent proliferation and their constitutively high NF-kappaB expression presumes cancerous properties observed in gliomas. In addition, this study might add a novel mechanism for detecting oncogenic transformation in therapeutic stem cell cultures.

En retorisk analys av Fahrenheit 9/11 ur ett dokumentärhistoriskt perspektiv

The history of rhetorics in documentary film is a long one. The French brothers Louise and Auguste Lumiére were among the first persons who produced a documentary and their work has had a big impression in the history of documentary during the 1900 century. John Grierson has been called “the father” of documentary film. He produced films in the English speaking part of the world and he is the founder of the concept “documentary film”. Propaganda filming has a big part in the history of documentary film. Most frequently it appeard in Germany before and during the secound WW II, but propaganda films has been produced in Great Britain and USA as well as in other parts of the world. Rhetorics are of current interest today. It effects the news, papers, magazines, books and movies. The purpose with this essay is to investigate the rhetorics in Michael Moores controversial documentary of September 11th, Fahrenheit 9/11. The main question is: what rhetorical tools does Michael Moore use in order to communicate his politcal message in Fahrenheit 9/11? The rhetorical analysis includes exordium, narratio, propsitio, argumentatio and conclusio as well as ethos, logos and pathos. In order to conduct the analysis I have used Kurt Johannesson’s book Retorik eller konsten att övertyga, Maria Karlberg and Brigitte Mral’s book Heder och påverkan. Att analysera modern retorik. And at last a chapter by Brigitte Mral named Retorikanalys in the book Metoder i kommunikationeverenskap, by Mats Ekström and Larsåke Larsson. For the background about the history of documentary film I have used Barsam M. Richard, Nonfiction Film A Critical History and Bjørn Sørenssen’s book Å fange virkeligheten –Dokumentarfilmens århundre.The analysis shows that Moore uses different rhetorical tools in order to point out that George W Bush is the wrong man for the role as the president of United States of America. Some of the most effective tools that Moores uses are his own voice, pictures who awakes emotions, recordings and sharp arguments. His way of using ethos, logos and pathos is very clear. The disposal can also be distinct discern, however there are some exceptions towards the classical rhetoric. One example is that Moore doesn´t describe the arrangement of the movie in exordium.

Ausencia, prohibición y carencia : Estudio de los personajes y el deseo frustrado en tres obras de García Lorca

In this thesis, the main male characters in three of the plays written by Federico García Lorca are analysed with the aim of seeingthe role they play in the frustration of desire. After two chapters dedicated to a review of published critical studies on Lorca and tocertain theoretical considerations, Chapter Three examines desire drawing on Ubersfeld's actancial model and observes that thesemale characters can be divided into two groups: those who are desired and those who are undesired.In Chapter Four this classification is linked to an analysis of absence, prohibition and lack. Absence is here defined not asrelated to their non-appearance on stage but rather to their non-presence in the lives of the desiring female protagonists. It isobserved that a number of male characters are absent in the plays mainly due to death or a journey. As far as prohibition isconcerned, in two of the works, there is a moral code associated with concepts such as "honour" and "decency", which blocks thefemale characters' access to the males they desire. Chapter Four also shows how several characters can be considered as lacking inthe sense that they do not possess the ideal male qualities contained in the plays. This chapter reaches the conclusion that desiredmale characters are either absent or forbidden in the world of the desiring female, whereas undesired male characters are lacking inthe sense that they fail to live up to the ideal highlighted in the plays.Chapter Five analyses the female characters' perception of the male figures, making use of René Girard's notion of"transfiguration", which alludes to a process of idealisation of the object of desire. Our analysis reveals a connection betweendesire, denied access to the object of desire and transfiguration in the main subjects of desire. The phenomenon of "transfiguration"has several functions in the play: firstly, the creation of hyperbolical male characters; secondly, that of transmitting the intensity ofthe desire experienced and, finally, the highlighting of the lack of certain qualities in several male characters.We thus observe that, in these three plays written by García Lorca, Girard's pessimistic view of desire is confirmed, since desireneeds a series of obstacles, such as absence or prohibition, to survive. However, this is not the only explanation for the frustrationof desire: other factors, like the actions of certain male characters or destiny, also play a decisive role.

Health problems in elderly patients during the first post-stroke year

BACKGROUND: A wide range of health problems has been reported in elderly post-stroke patients. AIM: The aim of this study was to analyse the prevalence and timing of health problems identified by patient interviews and scrutiny of primary health care and municipality elderly health care records during the first post-stroke year. METHODS: A total of 390 consecutive patients, ≥65 years, discharged alive from hospital after a stroke event, were followed for 1 year post-admission. Information on the health care situation during the first post-stroke year was obtained from primary health care and municipal elderly health care records and through interviews with the stroke survivors, at 1 week after discharge, and 3 and 12 months after hospital admission. RESULTS: More than 90% had some health problem at some time during the year, while based on patient record data only 4-8% had problems during a given week. The prevalence of interview-based health problems was generally higher than record-based prevalence, and the ranking order was moderately different. The most frequently interview-reported problems were associated with perception, activity, and tiredness, while the most common record-based findings indicated pain, bladder and bowel function, and breathing and circulation problems. There was co-occurrence between some problems, such as those relating to cognition, activity, and tiredness. CONCLUSIONS: Almost all patients had a health problem during the year, but few occurred in a given week. Cognitive and communication problems were more common in interview data than record data. Co-occurrence may be used to identify subtle health problems.

Life situations and the care burden for stroke pa­tients and their informal caregivers in a prospective cohort study

Background. The purpose of this study was to analyse whether the parallel life situation between stroke patients and their informal caregivers (dyads) shown in cross-sectional studies prevails also in a longitudinal perspective. Methods. A total of 377 Swedish stroke patients, aged ‡65 years, and their 268 informal caregivers were followed from hospital admission and one year on. Analyses were based on patient interviews, functional ability (MMSE) score, Nottingham Health Profile (NHP) score, Hospital Anxiety and Depression (HAD) score, self-rated health score, and the Gothenburg Quality of Life (GQL) activity score. Similar information was obtained by postal questionnaires from informal caregivers, also including information on the nature and amount of assistance provided and on Caregiver Burden (CB) score. Results. Before index admission informal caregivers provided care on average 5 h per week and after discharge 11 h per week (P < 0.0001). Support volume was associated with patient sex (more for men), low patient’s functional ability, low received municipal social service support, closeness of patient–caregiver relation, and short distance to patient’s home. Significant positive associations within the dyads were found for HAD anxiety score (P < 0.0001), total NHP score (P < 0.0001), and GQL activity score (P < 0.0001) after adjustment for patient’s age, sex, functional ability, and patient–caregiver relationship. CB score increased with amount of informal caregiver support, patient’s age, and with low functional ability and low amount of municipal social service support. All these associations were constant across time. Conclusions. There was an association within the dyads regarding anxiety score, NHP score, and activity score. CB score was generally high.

Från traditionellt akademiskt bibliotek till modern lärmiljö : Högskolan Dalarnas bibliotek – förväntningar och resultat

I denna rapport beskrivs idéerna bakom Högskolan Dalarnas prisbelönta bibliotek i Falun. Planerings- och byggprocessen beskrivs och det färdiga resultatet utvärderas, samt de erfarenheter som har gjorts delas.

From a traditional academic library to a modern learning environment : Dalarna University Library - expectations and results

This report describes the ideas and vision behind Dalarna University's award-winning library in Falun. A description of the planning and construction processes and an evaluation of the final outcome are presented together with experiences and observations drawn from the project.

Accelerating linear causal model discovery using hoeffding bounds

Efficiently inducing precise causal models accurately reflecting given data sets is the ultimate goal of causal discovery. The algorithms proposed by Dai et al. has demonstrated the ability of the Minimum Message Length (MML) principle in discovering Linear Causal Models from training data. In order to further explore ways to improve efficiency, this paper incorporates the Hoeffding Bounds into the learning process. At each step of causal discovery, if a small number of data items is enough to distinguish the better model from the rest, the computation cost will be reduced by ignoring the other data items. Experiments with data set from related benchmark models indicate that the new algorithm achieves speedup over previous work in terms of learning efficiency while preserving the discovery accuracy.

Wastewater irrigation: the state of play

As demand for fresh water intensifies, wastewater is frequently being seen as a valuable resource. Furthermore, wise reuse of wastewater alleviates concerns attendant with its discharge to the environment. Globally, around 20 million ha of land are irrigated with wastewater, and this is likely to increase markedly during the next few decades as water stress intensifies. In 1995, around 2.3 billion people lived in water-stressed river basins and this could increase to 3.5 billion by 2025. We review the current status of wastewater irrigation by providing an overview of the extent of the practice throughout the world and through synthesizing the current understanding of factors influencing sustainable wastewater irrigation. A theme that emerges is that wastewater irrigation is not only more common in water-stressed regions such as the Near East, but the rationale for the practice also tends to differ between the developing and developed worlds. In developing nations, the prime drivers are livelihood dependence and food security, whereas environmental agendas appear to hold greater sway in the developed world. The following were identified as areas requiring greater understanding for the long-term sustainability of wastewater irrigation: (i) accumulation of bioavailable forms of heavy metals in soils, (ii) environmental fate of organics in wastewater-irrigated soils, (iii) influence of reuse schemes on catchment hydrology, including transport of salt loads, (iv) risk models for helminth infections (pertinent to developing nations), (v) microbiological contamination risks for aquifers and surface waters, (vi) transfer efficiencies of chemical contaminants from soil to plants, (vii) health effects of chronic exposure to chemical contaminants, and (viii) strategies for engaging the public.

The three R`s of resilience: redundancy, requisite variety and resources

This paper offers a way of operationalizing resilience according to the sub-systems that comprise a business (technical, social and economic), the kinds of perturbations that might impact a business (local, national and global) and the criteria that determine resilient capacity (redundancy, requisite variety and resources). When a business system has incorporated redundancy, developed requisite variety and adequately monitors its resources, we might then conclude that such a business is a resilient business. The model offered here is theoretical, and is yet to undergo empirical scrutiny. Empirical modeling will enable us to ascertain the strength of a business's internal characteristics against different levels/kinds of external perturbation. Sensitivity analysis of this kind will lead to more in-depth understanding of the dynamics that generate resilient businesses in a complex world.