Cross Adaptation - Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia

To prepare for extremes of heat, cold or low partial pressures of O2, humans can undertake a period of acclimation or acclimatization to induce environment specific adaptations e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. Whilst these strategies are effective, they are not always feasible, due to logistical impracticalities. Cross adaptation is a term used to describe the phenomenon whereby alternative environmental interventions e.g. HA, or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate intensity exercise at altitude via adaptations allied to improved oxygen delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on oxygen delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross tolerance. The effects of CA on markers of cross tolerance is an area requiring further investigation. Because much of the evidence relating to cross adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross adaptation between heat and altitude, and between cold and altitude, is warranted, as is exploration of benefits across different populations and physical activity profiles

Using An Inquiry-based Teaching Approach to Improve Science Outcomes for Students with Disabilities: Snapshot and Longitudinal Data

Poor science achievement has been an educational issue for a number of years. Students with disabilities have traditionally fared worse. Research suggests that students with disabilities may respond better to instruction using an inquiry-based approach vs. traditional textbook instruction when measuring science achievement on standardized measures. The researchers report achievement data on the Iowa Test of Basic Skills from a target school district for students Individualized Education Program’s (IEP) and non-IEP students, as well as students with IEP’s at the state level. Using an argument-based inquiry approach to science instruction called the Science Writing Heuristic (SWH); the researchers report data supporting its impact on student achievement in science. Data suggest that the SWH may contribute to science achievement for students with IEP’s

User testing digital, multimedia information to inform children, adolescents and their parents about healthcare trials

Digital, multimedia information resources (MMIs) containing text, video, animation and pictures are a promising alternative to written participant information materials designed to inform children, adolescents and parents about healthcare trials, but little research has tested whether they are fit for purpose. This study employed a consecutive groups design and user testing questionnaire to assess whether participants were able to find and understand key information in multimedia resources. Two rounds of testing were completed. In each round, seven children aged 7–11 tested the MMI with a parent; six adolescents aged 12–17 and seven parents tested the MMI independently. After round 1, the resources were revised based on participant scores, behaviour and feedback. Round 1 identified problems with 2/10 information items (length of trial and use of insulin pump); only 3/20 participants could locate all information items without difficulty. After revisions, 14/20 participants scored a clear round. Information comprehension was high: 96% understood in round 1 and 99% in round 2. Participant feedback on the multimedia resources was positive, although presentation preferences varied. User testing was employed successfully with children, adolescents and parents to identify issues with, and improve, multimedia resources developed to inform potential healthcare trial participants

Initial Conditions for Models of Dynamical Systems

The long-time behaviour of many dynamical systems may be effectively predicted by a low-dimensional model that describes the evolution of a reduced set of variables. We consider the question of how to equip such a low-dimensional model with appropriate initial conditions, so that it faithfully reproduces the long-term behaviour of the original high-dimensional dynamical system. Our method involves putting the dynamical system into normal form, which not only generates the low-dimensional model, but also provides the correct initial conditions for the model. We illustrate the method with several examples. Keywords: normal form, isochrons, initialisation, centre manifoldComment: 24 pages in standard LaTeX, 66K, no figure

Pigmentsynthese bei Exophiala dermatitidis : Einfluss auf Phagozytose und Oxidative Burst

Indolderivate wurden von der Arbeitsgruppe um Prof. Mayser 1998 erstmals bei der Hefe Malassezia furfur beschrieben, bei der sie vermutlich in einem klinischen Zusammenhang mit der Hautkrankheit Pityriasis versicolor stehen. Im Jahr 2006 konnten Nies et al. solche Indolderivate erstmals bei Exophiala dermatitidis nachweisen. Ziel der vorliegenden Arbeit war die vergleichende Untersuchung der Pigmentspektren verschiedener Stämme von Exophiala dermatitidis und ihre Überprüfung auf eine mögliche Rolle in der Pathogenese von Exophiala-dermatitidis-Infektionen. Hierfür wurden der Wildtyp und seine Mutanten Mel-1, Mel-3 und Mel-4 zur Pigmentsynthese auf 1b-Minimalagar angezüchtet. Nach vierwöchiger Wachstumsphase wurde das dabei entstandene Pigment als Rohextrakt gewonnen, durch chromatographische Methoden vorgereinigt, sowie einzelne farbige Bestandteile weiter aufgereinigt. Die Stukturaufklärung isolierter Reinsubstanzen erfolgte an der TU München. Grundlage zur Untersuchung des Oxidative Burst stellte der von Schnitzler et al. (1999) etablierte Vollblutansatz mit Dihydrorhodamine 123 als Indikator für die Sauerstoffradikalsynthese von neutrophilen Granulozyten dar. Die anschließende Messung erfolgte am Durchflußzytometer. Im Rahmen der Untersuchung der Pigmentspektren konnte beim Wildtyp von Exophiala dermatitidis erstmals die Synthese von Pityriacitrin, Pityriarubin C, Exophialin und Desoxyexophialin nachgewiesen werden. Für die Mutante Mel-1 konnte erstmals das bislang nur durch vergleichende DC nachgewiesene Pityriacitrin in der HPLC, sowie durch Analyse der TU München bestätigt werden. Desweiteren konnte Exophialin aus zwei violetten Banden mit einem Rf-Wert von 0,38 und 0,56 isoliert werden. Unter den Syntheseprodukten der Mutante Mel-3 wurde erstmals Exophialin, Pityriarubin C und Pityriacitrin nachgewiesen. Beim Vergleich des Wildtyps von Exophiala dermatitidis mit seiner Melaninmangel-Mutante Mel-3 hinsichtlich ihrer Auswirkung auf den Oxidative Burst in Vollblutproben konnte eine deutliche Hemmung des Oxidative Burst durch den Wildtyp gegenüber Mel-3 aufgezeigt werden. Dies läßt den Rückschluß auf eine deutliche Schutzwirkung des vom Wildtyp synthetisierten Melanins vor der ROS-Synthese zu. Auch die untersuchten Pigment-Rohextrakte von Wildtyp, Mel-1, Mel-3 und Mel-4 hatten alle eine hemmende Wirkung auf die ROS-Synthese, wobei der Rohextrakt von Mel-3 den stärksten Einfluß hatte. Bei den Sephadex-Fraktionen der Mutante Mel-3 ergaben unterschiedliche Einflüsse auf die ROS-Synthese. Die Fraktionen zwei und sechs zeigten in allen Zeitstufen zwischen 0 und 60 Minuten die stärkste Unterdrückung, wohingegen bei den Fraktionen drei und acht zu keinem Zeitpunkt Auswirkungen auf die ROS-Synthese beobachtet wurden. Nach weiterer Unterteilung der hemmenden Fraktion sechs der Mutante Mel-3 mittels präparativer Dünnschichtchromatographie in acht Banden konnte eine deutliche Hemmung des Oxidative Burst durch die Banden 5-8 verzeichnet werden. In diesem Bereich kam neben zahlreichen Fluorochromen und Pityriarubin C eine prominente Bande von grauer Farbe vor. Diese Substanz hemmte die ROS-Synthese deutlich, wohingegen Pityriarubin C keinen Einfluß darauf hatte. Auch die acht Banden der Fraktion zwei der Mutante Mel-3 unterschieden sich in ihrer Auswirkung auf den Oxidative Burst. Hier wirkten sich nur die Fraktionen 1,4,5 hemmend auf die ROS-Synthese aus. Die weiterhin untersuchten Reinsubstanzen Exophialin und Malassezin hatten selbst in hohen Konzentrationen keinen signifikanten Einfluß auf die ROS-Synthese. Insgesamt konnte gezeigt werden, daß Exophiala dermatitidis Wildtyp und seine Mutanten unter den eingesetzten Anzuchtbedingungen ein sehr unterschiedliches Spektrum an pigmentierten Indolderivaten bilden, das sich stets reproduzieren ließ. Es wurde eine Hemmung der ROS-Synthese durch diese Pigmente in Form von Rohextrakten einzelner Stämme, in Form weiter aufgereinigten Säulenchromatographie-Fraktionen, sowie in Form von Einzelbanden beobachtet. Die läßt Rückschlüsse auf deren wichtige Rolle in der Pathogenese von Exophiala dermatitidis-Infektionen bei Mensch und Tier zu. Die aus diesen Resultaten hervorgehenden neuen Fragestellungen sind weiteren Untersuchungen vorbehalten.In 1998, the working group of Prof. Mayser first described some particular indole derivatives in the yeast Malassezia furfur, which might be clinically related to the skin disease pityriasis versicolor. In 2006, Nies et al. were the first ones able to show the production of these indole derivatives in Exophiala dermatitidis. The aim of this study was to compare the pigment spectrum of different species of Exophiala dermatitidis and to clarify whether they are part of the pathogenese of infections with Exophiala dermatitidis. The wildtype and its mutants Mel-1, Mel-3 and Mel-4 were cultivated on minimal agar as a base for pigment production. The pigment was extracted after a period of growth of 4 weeks and chromatographically purified to obtain pure substances. Structural analyses of the isolated substances were performed at Munich Technological University. Following the studies of Schnitzler et al. (1999), unlabeled yeast cells were incubated in heparinized whole blood and dihydrorhodamine 123 was added as an indicator for the ROS-synthesis in the granulocytes. Flow cytometric analysis was performed in a FACScan flow cytometer. By investigating the pigment spectrum of Exophiala dermatitidis, the synthesis of Pityriacitrin, Pityriarubin C, Exophialin and Desoxyexophialin in the wildtype could be shown. In former studies, the pigments of the mutant Mel-1 were already investigated by comparative DC and the indole pyruvate Pityriacitrin was found to be produced by this yeast. In the present study, this achievement could be approved by HPLC and the analysis of Munich Technological University. Exophialin, an almost ankwown indole derivate which was isolated from Mel-3 for the first time by Nies et al. (2006) was found in two violet DC-bands of Mel-1 (Rf=0,38; Rf=0,56). The indole derivates Exophialin, Pityriarubin C and Pityriacitrin were detected in the mutant Mel-3 in this present study. The degree of the oxidative burst evoked by Exophiala dermatitidis wildtype was found to be lower when it was compared with its mutant Mel-3. The wildtype is probably protected from the oxidative burst by its synthesised Melanin. When the raw extracts of the wildtype, Mel-1, Mel-3 and Mel-4 were added in the experimental series of oxidative burst, evoked oxidative burst levels were also found to be lower compared with the contol without any indole derivates. The raw extract of Mel-3 inhibited the oxidative burst most. The sephadex-fractions of the mutant Mel-3 had different influences on the synthesis of ROS. Fractions two and six suppressed the oxidative burst in all time levels between 0 and 60 minutes strongly, while fractions three and eight had no influence on the synthesis of ROS at any time. Fraction six was subdivided by preparative thin layer chromatography into eight bands and the bands 5-8 were able to inhibit evoked oxidative burst levels. Beside the already known Pityriarubin C and other fluorochromes these three bands 5-8 include an unknown greycoloured pigment. This grey pigment was able to inhibit the synthesis of ROS strongly, while Pityriarubin C had no influence on the evoked oxidative burst. The eight bands of fraction two of the mutant Mel-3 differed in the way tey influenzed the oxidative burst. Only fractions 1,4,5 led to a decreased oxidative burst level. Although added in high concentrations, the pure substances Exophialin and Malassezin did not have any influence on the synthesis of ROS. I summary can be said that the wildtype of Exophiala dermatitidis an its mutants are able to produce a very bright and different spectrum of pigmented indole derivates when cultivated on minimal agar. This pigment spectrum is reproducable at any time. An inhibition of the ROS synthesis was shown by these indole derivates when they were added as raw extracts, fractions of thin layer chromatographie and as single bunches. The indole derivates seem to play an important role in the pathogenesis of infections in human beings and animals caused by Exophiala dermatitidis

Understanding the diverse needs of subtitle users in a rapidly evolving media landscape

Audiences are increasingly using services, such as video on demand and the Web, to watch television programs. Broadcasters need to make subtitles available across all these new platforms. These platforms also create new design opportunities for subtitles along with the ability to customize them to an individual’s needs. To explore these new opportunities for subtitles, we have begun the process of reviewing the guidance for subtitles on television and evaluating the original user research. We have found that existing guidelines have been shaped by a mixture of technical constraints, industry practice, and user research, constrained by existing technical standards. This paper provides an overview of the subtitle research at BBC R&D over the past two years. Our research is revealing significant diversity in the needs and preferences of frequent subtitle users, and points to the need for personalization in the way subtitles are displayed. We are developing a new approach to the authoring and display of subtitles that can respond to the user requirements by adjusting the subtitle layout on the client device

Learning by building: A visual modelling language for psychology students

Cognitive modelling involves building computational models of psychological theories in order to learn more about them, and is a major research area allied to psychology and artificial intelligence. The main problem is that few psychology students have previous programming experience. The course lecturer can avoid the problem by presenting the area only in general terms. This leaves the process of building and testing models, which is central to the methodology, an unknown. Alternatively, students can be introduced to one of the existing cognitive modelling languages, though this can easily be overwhelming, hindering rather than helping their understanding. Our solution was to design and build a programming language for the intended population. The result is Hank, a visual cognitive modelling language for the psychologist. Our informal analyses have investigated the effectiveness of Hank in its intended context of use, both as a paper and pencil exercise for individuals, and as a computer based project to be carried out in groups. The findings largely support the Hank design decisions, and illuminate many of the challenges inherent in designing a programming language for an educational purpose

Vitamin D Status of Anabaptist Children in Southwestern Ontario, Canada

The objective was to determine vitamin D status of Old Order Anabaptist children in rural Southwestern, Ontario, Canada, given concerns of community healthcare professionals. Fifty-two children (2.5 months - 6.5 years) (56% female) were recruited. Finger prick blood spot (BSp) samples were analyzed for 25-hydroxy (OH) vitamins D2 & D3 (BSp25(OH)D). Three-day food records were evaluated using Dietary Reference Intakes and Canada’s Food Guide (CFG) (Bush, et al. 2007). Compared to national Canadian data: mean BSp25(OH)D concentrations (78±31 nmol/L) were similar; a slightly smaller proportion (0% vs 2%) were at risk of deficiency (\u3c30 nmol/L) or had inadequate status (4% vs 7%) (\u3c40 nmol/L); and 10% vs 1% had BSp25(OH)D higher than 125 nmol/L. BSp25(OH)D was significantly associated (r2=0.358; p=0.001) with total vitamin D intake. From food alone, vitamin D intake was 68±39 IU/day, lower than the Recommended Dietary Allowance (RDA) of 600 IU/day, and intakes were all below the Estimated Average Requirement (EAR) of 400 IU. Even including supplemental vitamin D, 87% were below the EAR (total intake=213±194 IU/day). No children had vitamin D intakes greater than the Upper Limit. Servings of milk and alternates were 1.6±0.8/day (CFG=2/day). Unfortified farm milk was consumed by 88% of children and 89% received a vitamin D supplement. Results were comparable to recent Canadian data suggesting that most children have adequate vitamin D status. Nevertheless, these findings support the need to encourage appropriate vitamin D intake (from food and supplements) to achieve the RDA for Old Order Anabaptist children in these communities. [Abstract by authors.

Cerebral salt wasting following traumatic brain injury

Hyponatraemia is the most commonly encountered electrolyte disturbance in neurological high dependency and intensive care units. Cerebral salt wasting (CSW) is the most elusive and challenging of the causes of hyponatraemia, and it is vital to distinguish it from the more familiar syndrome of inappropriate antidiuretic hormone (SIADH). Managing CSW requires correction of the intravascular volume depletion and hyponatraemia, as well as mitigation of on-going substantial sodium losses. Herein we describe a challenging case of CSW requiring large doses of hypertonic saline and the subsequent substantial benefit with the addition of fludrocortisone