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.

Effects of allometry, productivity and lifestyle on rates and limits of body size evolution

Body size affects nearly all aspects of organismal biology, so it is important to understand the constraints and dynamics of body size evolution. Despite empirical work on the macroevolution and macroecology of minimum and maximum size, there is little general quantitative theory on rates and limits of body size evolution. We present a general theory that integrates individual productivity, the lifestyle component of the slow–fast life-history continuum, and the allometric scaling of generation time to predict a clade's evolutionary rate and asymptotic maximum body size, and the shape of macroevolutionary trajectories during diversifying phases of size evolution. We evaluate this theory using data on the evolution of clade maximum body sizes in mammals during the Cenozoic. As predicted, clade evolutionary rates and asymptotic maximum sizes are larger in more productive clades (e.g. baleen whales), which represent the fast end of the slow–fast lifestyle continuum, and smaller in less productive clades (e.g. primates). The allometric scaling exponent for generation time fundamentally alters the shape of evolutionary trajectories, so allometric effects should be accounted for in models of phenotypic evolution and interpretations of macroevolutionary body size patterns. This work highlights the intimate interplay between the macroecological and macroevolutionary dynamics underlying the generation and maintenance of morphological diversity.

Towards a framework for managing IT-enabled change, sourcing and governance

In the resource-based view, organisations are represented by the sum of their physical, human and organisational assets, resources and capabilities. Operational capabilities maintain the status quo and allow an organisation to execute their existing business. Dynamic capabilities, otherwise, allow an organisation to change this status quo including a change of the operational ones. Competitive advantage, in this context, is an effect of continuously developing and reconfiguring these firm-specific assets through dynamic capabilities. Deciding where and how to source the core operational capabilities is a key success factor. Furthermore, developing its dynamic capabilities allows an organisation to effectively manage change its operational capabilities. Many organisations are asserted to have a high dependency on - as well as a high benefit from - the use of information technology (IT), making it a crucial and overarching resource. Furthermore, the IT function is assigned the role as a change enabler and so IT sourcing affects the capability of managing business change. IT sourcing means that organisations need to decide how to source their IT capabilities. Outsourcing of parts of the IT function will also outsource some of the IT capabilities and therefore some of the business capabilities. As a result, IT sourcing has an impact on the organisation's capabilities and consequently on the business success. And finally, a turbulent and fast moving business environment challenges organisations to effectively and efficiently managing business change. Our research builds on the existing theory of dynamic and operational capabilities by considering the interdependencies between the dynamic capabilities of business change and IT sourcing. Further it examines the decision-making oversight of these areas as implemented through IT governance. We introduce a new conceptual framework derived from the existing theory and extended through an illustrative case study conducted in a German bank. Under a philosophical paradigm of constructivism, we collected data from eight semi-structured interviews and used additional sources of evidence in form of annual accounts, strategy papers and IT benchmark reports. We applied an Interpretative Phenomenological Analysis (IPA), which emerged the superordinate themes for our tentative capabilities framework. An understanding of these interdependencies enables scholars and professionals to improve business success through effectively managing business change and evaluating the impact of IT sourcing decisions on the organisation's operational and dynamic capabilities.

Coordinated ground-based, low altitude satellite and Cluster observations on global and local scales during a transient post-noon sector excursion of the magnetospheric cusp

On 14 January 2001, the four Cluster spacecraft passed through the northern magnetospheric mantle in close conjunction to the EISCAT Svalbard Radar (ESR) and approached the post-noon dayside magnetopause over Greenland between 13:00 and 14:00 UT During that interval, a sudden reorganisation of the high-latitude dayside convection pattern accurred after 13:20 UT most likely caused by a direction change of the Solar wind magnetic field. The result was an eastward and poleward directed flow-channel, as monitored by the SuperDARN radar network and also by arrays of ground-based magnetometers in Canada, Greenland and Scandinavia. After an initial eastward and later poleward expansion of the flow-channel between 13:20 and 13:40 UT, the four Cluster spacecraft, and the field line footprints covered by the eastward looking scan cycle of the Sondre Stromfjord incoherent scatter radar were engulfed by cusp-like precipitation with transient magnetic and electric field signatures. In addition, the EISCAT Svalbard Radar detected strong transient effects of the convection reorganisation, a poleward moving precipitation, and a fast ion flow-channel in association with the auroral structures that suddenly formed to the west and north of the radar. From a detailed analysis of the coordinated Cluster and ground-based data, it was found that this extraordinary transient convection pattern, indeed, had moved the cusp precipitation from its former pre-noon position into the late post-noon sector, allowing for the first and quite unexpected encounter of the cusp by the Cluster spacecraft. Our findings illustrate the large amplitude of cusp dynamics even in response to moderate solar wind forcing. The global ground-based data proves to be an invaluable tool to monitor the dynamics and width of the affected magnetospheric regions.

Long-term variations in the magnetic fields of the Sun and the heliosphere: their origin, effects, and implications

Recent studies of the variation of geomagnetic activity over the past 140 years have quantified the "coronal source" magnetic flux F-s that leaves the solar atmosphere and enters the heliosphere and have shown that it has risen, on average, by an estimated 34% since 1963 and by 140% since 1900. This variation of open solar flux has been reproduced by Solanki et al. [2000] using a model which demonstrates how the open flux accumulates and decays, depending on the rate of flux emergence in active regions and on the length of the solar cycle. We here use a new technique to evaluate solar cycle length and find that it does vary in association with the rate of change of F-s in the way predicted. The long-term variation of the rate of flux emergence is found to be very similar in form to that in F-s, which may offer a potential explanation of why F-s appears to be a useful proxy for extrapolating solar total irradiance back in time. We also find that most of the variation of cosmic ray fluxes incident on Earth is explained by the strength of the heliospheric field (quantified by F-s) and use observations of the abundance of the isotope Be-10 (produced by cosmic rays and deposited in ice sheets) to study the decrease in F-s during the Maunder minimum. The interior motions at the base of the convection zone, where the solar dynamo is probably located, have recently been revealed using the helioseismology technique and found to exhibit a 1.3-year oscillation. This periodicity is here reported in observations of the interplanetary magnetic field and geomagnetic activity but is only present after 1940, When present, it shows a strong 22-year variation, peaking near the maximum of even-numbered sunspot cycles and showing minima at the peaks of odd-numbered cycles. We discuss the implications of these long-term solar and heliospheric variations for Earth's environment.

Effects of a mid-latitude solar eclipse on the thermosphere and ionosphere: a modelling study

A modelling study is presented which investigates in-situ generated changes of the thermosphere and ionosphere during a solar eclipse. Neutral temperatures are expected to drop by up to 40 degrees K at 240 km height in the totality footprint, with neutral winds of up to 26 m/s responding to the change of pressure. Both temperatures and winds are found to respond with a time lag of 30 min after the passing of the Moon's shadow. A gravity wave is generated in the neutral atmosphere and propagates into the opposite hemisphere at around 300 m/s. The combined effects of thermal cooling and downwelling lead to an overall increase in [O], while [N(2)] initially rises and then for several hours after the eclipse is below the "steady state" level. An enhancement of [NmF2] is found and explained by the atmosphere's contraction during, and the reduced [O]/[N(2)] ratio after the eclipse.

Implications of the altitude of transient 630-nm dayside auroral emissions

The altitude from which transient 630-nm (“red line”) light is emitted in transient dayside auroral breakup events is discussed. Theoretically, the emissions should normally originate from approximately 250 to 550 km. Because the luminosity in dayside breakup events moves in a way that is consistent with newly opened field lines, they have been interpreted as the ionospheric signatures of transient reconnection at the dayside magnetopause. For this model the importance of these events for convection can be assessed from the rate of change of their area. The area derived from analysis of images from an all-sky camera and meridian scans from a photometer, however, depends on the square of the assumed emission altitude. From field line mapping, it is shown for both a westward and an eastward moving event, that the main 557.7-nm emission comes from the edge of the 630 nm transient, where a flux transfer event model would place the upward field-aligned current (on the poleward and equatorward edge, respectively). The observing geometry for the two cases presented is such that this is true, irrespective of the 630-nm emission altitude. From comparisons with the European incoherent scatter radar data for the westward (interplanetary magnetic field By > 0) event on January 12, 1988, the 630-nm emission appears to emanate from an altitude of 250 km, and to be accompanied by some 557.7-nm “green-line” emission. However, for a large, eastward moving event observed on January 9, 1989, there is evidence that the emission altitude is considerably greater and, in this case, the only 557.7-nm emission is that on the equatorward edge of the event, consistent with a higher altitude 630-nm excitation source. Assuming an emission altitude of 250 km for this event yields a reconnection voltage of >50 kV during the reconnection burst but a contribution to the convection voltage of >15 kV. However, from the motion of the event we infer that the luminosity peaks at an altitude in the range of 400 and 500 km, and for the top of this range the reconnection and average convection voltages would be increased to >200 kV and >60 kV, respectively. (These are all minimum estimates because the event extends in longitude beyond the field-of-view of the camera). Hence the higher-emission altitude has a highly significant implication, namely that the reconnection bursts which cause the dayside breakup events could explain most of the voltage placed across the magnetosphere and polar cap by the solar wind flow. Analysis of the plasma density and temperatures during the event on January 9, 1989, predicts the required thermal excitation of significant 630-nm intensities at altitudes of 400-500 km.

Decreasing the interference of visual-based P300 BCI using facial expression changes

Interferences from the spatially adjacent non-target stimuli evoke ERPs during non-target sub-trials and lead to false positives. This phenomenon is commonly seen in visual attention based BCIs and affects the performance of BCI system. Although, users or subjects tried to focus on the target stimulus, they still could not help being affected by conspicuous changes of the stimuli (flashes or presenting images) which were adjacent to the target stimulus. In view of this case, the aim of this study is to reduce the adjacent interference using new stimulus presentation pattern based on facial expression changes. Positive facial expressions can be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast will be big enough to evoke strong ERPs. In this paper, two different conditions (Pattern_1, Pattern_2) were used to compare across objective measures such as classification accuracy and information transfer rate as well as subjective measures. Pattern_1 was a “flash-only” pattern and Pattern_2 was a facial expression change of a dummy face. In the facial expression change patterns, the background is a positive facial expression and the stimulus is a negative facial expression. The results showed that the interferences from adjacent stimuli could be reduced significantly (P<;0.05) by using the facial expression change patterns. The online performance of the BCI system using the facial expression change patterns was significantly better than that using the “flash-only” patterns in terms of classification accuracy (p<;0.01), bit rate (p<;0.01), and practical bit rate (p<;0.01). Subjects reported that the annoyance and fatigue could be significantly decreased (p<;0.05) using the new stimulus presentation pattern presented in this paper.

Transcriptomic analysis of Enterohaemorrhagic Escherichia coli O157:H7 in response to plant extracts

Enterohaemorrhagic Escherichia coli (EHEC) are a group of food and contact-borne pathogens responsible for haemorrhagic colitis. The bacteria can be transmitted by contaminated meat, but importantly, also by plants. The bacteria can use plants as an alternative host, where they associate with both the leaves and the roots. Colonisation in the rhizosphere of plants is thought to be the main habitat for colonisation. Four different plant species, commonly associated with EHEC outbreaks, were infected with EHEC O157:H7 isolates Sakai and TUV 93-0 over ten days to assess the colonisation potential of the bacteria in both the phyllosphere and rhizosphere of plants. The rhizosphere was found to sustain a higher population level of bacteria over time in comparison to the phyllosphere, yet both strains were unable to utilize root exudates for growth. Global gene expression changes of EHEC O157:H7 strain Sakai were measured in response to plant extracts such as leaf lysates, root exudates and leaf cell wall polysaccharides from spinach cultivar Amazon and lettuce cultivar Salinas. Microarrays analysis showed a significant change in expression of 17 % of genes on exposure to leaf lysates of spinach. A more specific response was seen to spinach leaf cell wall polysaccharides with only a 1.5 % change. In contrast, when exposed to lettuce leaf cell wall polysaccharides a higher change of 4.8 % was seen. Genes that were differentially expressed belonged to multiple functional groups, including metabolism, indicating the utilization of plant-specific polysaccharides. Several areas of further investigation have been determined from this project, including the importance of culturing bacterial strains at a relevant temperature, the proposed lack of the type III secretion system in plant colonization by EHEC O157:H7 and the utilization of plant components for growth and persistence in the plant environment.

The fractured lives of German Bohemian children, born 1933-40 in the area known as Sudetenland: a memory study, Nablonz-Neugablonz

At the Paris Peace Conferences of 1918-1919, new states aspiring to be nation-states were created for 60 million people, but at the same time 25 million people found themselves as ethnic minorities. This change of the old order in Europe had a considerable impact on one such group, more than 3 million Bohemian German-speakers, later referred to as Sudeten Germans. After the demise of the Habsburg Empire In 1918, they became part of the new state of Czechoslovakia. In 1938, the Munich Agreement – prelude to the Second World War – integrated them into Hitler’s Reich; in 1945-1946 they were expelled from the reconstituted state of Czechoslovakia. At the centre of this War Child case study are German children from the Northern Bohemian town and district, formerly known as Gablonz an der Neisse, famous for exquisite glass art, now Jablonec nad Nisou in the Czech Republic. After their expulsion they found new homes in the post-war Federal Republic of Germany. In addition, testimonies have been drawn upon of some Czech eyewitnesses from the same area, who provided their perspective from the other side, as it were. It turned out to be an insightful case study of the fate of these communities, previously studied mainly within the context of the national struggle between Germans and Czechs. The inter-disciplinary research methodology adopted here combines history and sociological research to demonstrate the effect of larger political and social developments on human lives, not shying away from addressing sensitive political and historical issues, as far as these are relevant within the context of the study. The expellees started new lives in what became Neugablonz in post-war Bavaria where they successfully re-established the industries they had had to leave behind in 1945-1946. Part 1 of the study sheds light on the complex Czech-German relationship of this important Central European region, addressing issues of democracy, ethnicity, race, nationalism, geopolitics, economics, human geography and ethnography. It also charts the developments leading to the expulsion of the Sudeten Germans from Czechoslovakia after 1945. What is important in this War Child study is how the expellees remember their history while living as children in Sudetenland and later. The testimony data gained indicate that certain stereotypes often repeated within the context of Sudeten issues such as the confrontational nature of inter-ethnic relations are not reflected in the testimonies of the respondents from Gablonz. In Part 2 the War Child Study explores the memories of the former Sudeten war children using sociological research methods. It focuses on how they remember life in their Bohemian homeland and coped with the life-long effects of displacement after their expulsion. The study maps how they turned adversity into success by showing a remarkable degree of resilience and ingenuity in the face of testing circumstances due to the abrupt break in their lives. The thesis examines the reasons for the relatively positive outcome to respondents’ lives and what transferable lessons can be deduced from the results of this study.

Differentiation in populations of the apple scab fungus Venturia inaequalis on cultivars in a mixed orchard remains over time

The ascomycete Venturia inaequalis causes annual epidemics of apple scab worldwide. Scab development is reduced in mixed cultivar orchards compared with monocultures. To use mixtures in commercial production, we need to understand how the population of scab changes in a mixed orchard and how likely a super race, with virulence factors overcoming multiple resistance factors in the mixed orchard, is to emerge and become dominant. We used short sequence repeat (SSR) markers to investigate the temporal change of scab populations in two mixed cultivar orchards in the UK to infer the likelihood of emergence of a scab super race. There were no significant differences between the populations at the two sampling times (six or seven years apart) in either of the two mixed orchards. In one of the orchards apple scab populations on different cultivars were significantly different and the differences did not diminish over time. These results suggest that it is not inevitable that a super race of V. inaequalis will become dominant during the lifetime of a commercial apple orchard.

Prebiotic potential of a maize-based soluble fibre and impact of dose on the human gut microbiota

Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12g and 18g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention.

Design and analysis of a haptic device design for large and fast movements

Haptic devices tend to be kept small as it is easier to achieve a large change of stiffness with a low associated apparent mass. If large movements are required there is a usually a reduction in the quality of the haptic sensations which can be displayed. The typical measure of haptic device performance is impedance-width (z-width) but this does not account for actuator saturation, usable workspace or the ability to do rapid movements. This paper presents the analysis and evaluation of a haptic device design, utilizing a variant of redundant kinematics, sometimes referred to as a macro-micro configuration, intended to allow large and fast movements without loss of impedance-width. A brief mathematical analysis of the design constraints is given and a prototype system is described where the effects of different elements of the control scheme can be examined to better understand the potential benefits and trade-offs in the design. Finally, the performance of the system is evaluated using a Fitts’ Law test and found to compare favourably with similar evaluations of smaller workspace devices.