(Table 2, page 50) Toolik lake sediment chemistry (0-1 cm interval)

The sediments within Toolik Lake in arctic Alaska are characterized by extremely low rates of organic matter sedimentation and unusually high concentrations of iron and manganese. Pore water and solid phase measurements of iron, manganese, trace metals, carbon, nitrogen, phosphorus, and sulfur are consistent with the hypothesis that the reduction of organic matter by iron and manganese is the most important biogeochemical reaction within the sediment. Very low rates of dissolved oxygen consumption by the sediments result in an oxidizing environment at the sediment-water interface. This results in high retention of upwardly-diffusing iron and manganese and the formation of metal-enriched sediment. Phosphate in sediment pore waters is strongly adsorbed by the metal-enriched phases. Consequently, fluxes of phosphorus from the sediments to overlying waters are very small and contribute to the oligotrophic nature of the Toolik Lake aquatic system. Toolik Lake contains an unusual type of lacustrine sediment, and in many ways the sediments are similar to those found in oligotrophic oceanic environments.

A Group-Enhanced Sprint Interval Training Program for Amateur Athletes

Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 ± 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s “all-out” efforts with 4 min active recovery, repeated 4–6 times per session), and were assigned to “true group”, aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants— regardless of condition — significant main effects for time were identified for maximal oxygen uptake (2.5–2.8 mL·kg−1·min−1, p < 0.001, η2 = 0.03), time-trial performance (14–32 s, p < 0.001, η2 = 0.37), and anaerobic power (1.1–1.7 k·h−1, p < 0.001, η2 = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, η2 = 0.13), task self-efficacy (p = 0.018, η2 = 0.15), and scheduling self-efficacy (p = 0.003, η2 = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self-efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements

Individual Variation in VO2peak Response Following Sprint Interval Training: The Role of Peripheral Adaptation

There is a large degree of heterogeneity in response to regular physical activity at the individual level, with some exhibiting no or very small improvements in VO2peak following highly controlled exercise training. The purpose of this thesis was to examine individual variation in VO2peak response to sprint interval training (SIT) in relation to individual responses to multiple measures of peripheral physiological adaptation. Specifically, VO2peak, capillary density, fibre-specific SDH content, and type I fibre % were measured in 23 young, healthy, recreationally active males before and after 4 weeks SIT (Tabata protocol 4 x per week). The key findings of this experiment included that, when separated into tertiles of VO2peak response, the high (HI) and low (LO) groups differed significantly in VO2peak change after training. Secondly, there was no difference between HI and LO groups for response in any of capillary density, fibre-specific SDH content, or fibre type %, with no correlation found between individual VO2peak response and changes in any measured peripheral variable. Together, these results confirm that individuals respond heterogeneously to SIT and suggest that this heterogeneity does not result from differences in individual changes in capillary density, fibre-specific SDH content or type I fibre %. It is speculated that some other combination of peripheral physiological adaptation must explain variability in VO2peak response to 4 weeks of SIT.

Effect of accelerated rehabilitation on function after ankle sprain:randomised controlled trial

OBJECTIVE: To compare an accelerated intervention incorporating early therapeutic exercise after acute ankle sprains with a standard protection, rest, ice, compression, and elevation intervention.

DESIGN: Randomised controlled trial with blinded outcome assessor.

SETTING: Accident and emergency department and university based sports injury clinic.

PARTICIPANTS: 101 patients with an acute grade 1 or 2 ankle sprain.

INTERVENTIONS: Participants were randomised to an accelerated intervention with early therapeutic exercise (exercise group) or a standard protection, rest, ice, compression, and elevation intervention (standard group).

MAIN OUTCOME MEASURES: The primary outcome was subjective ankle function (lower extremity functional scale). Secondary outcomes were pain at rest and on activity, swelling, and physical activity at baseline and at one, two, three, and four weeks after injury. Ankle function and rate of reinjury were assessed at 16 weeks.

RESULTS: An overall treatment effect was in favour of the exercise group (P=0.0077); this was significant at both week 1 (baseline adjusted difference in treatment 5.28, 98.75% confidence interval 0.31 to 10.26; P=0.008) and week 2 (4.92, 0.27 to 9.57; P=0.0083). Activity level was significantly higher in the exercise group as measured by time spent walking (1.2 hours, 95% confidence interval 0.9 to 1.4 v 1.6, 1.3 to 1.9), step count (5621 steps, 95% confidence interval 4399 to 6843 v 7886, 6357 to 9416), and time spent in light intensity activity (53 minutes, 95% confidence interval 44 to 60 v 76, 58 to 95). The groups did not differ at any other time point for pain at rest, pain on activity, or swelling. The reinjury rate was 4% (two in each group).

CONCLUSION: An accelerated exercise protocol during the first week after ankle sprain improved ankle function; the group receiving this intervention was more active during that week than the group receiving standard care.

TRIAL REGISTRATION: Current Controlled Trials ISRCTN13903946.

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.

PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.

RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.

CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.

Développement de matériaux à base de protéines extraites du byssus de la moule bleue Mytilus edulis

Le byssus est un amas de fibres que les moules produisent afin de s’ancrer aux surfaces immergées sous l’eau. Ces fibres sont pourvues de propriétés mécaniques impressionnantes combinant rigidité, élasticité et ténacité élevées. De plus, elles possèdent un comportement d’auto-guérison de leurs propriétés mécaniques en fonction du temps lorsque la contrainte initialement appliquée est retirée. Les propriétés mécaniques de ces fibres sont le résultat de l’agencement hiérarchique de protéines de type copolymère blocs riches en collagène et de la présence de métaux formant des liens sacrificiels réversibles avec certains acides aminés comme les DOPA et les histidines. Bien que cette fibre soit très intéressante pour la production de matériaux grâce à son contenu élevé en collagène potentiellement biocompatible, cette ressource naturelle est traitée comme un déchet par les mytiliculteurs. L’objectif de cette thèse était de valoriser cette fibre en extrayant les protéines pour générer une nouvelle classe de matériaux biomimétiques. Un hydrolysat de protéines de byssus (BPH) riche en acides aminés chargés, i.e. ~30 % mol, et permettant de former des films a pu être généré. Lorsque solubilisé à pH 10.5, le BPH forme un hydrogel contenant des structures en triple hélice de collagène et des feuillets β anti-parallèles intra- et inter-moléculaires. Suite à l’évaporation de l’eau, le film de BPH résultant est insoluble en milieu aqueux à cause des structures secondaires très stables agissant comme points de réticulation effectifs. Les propriétés mécaniques des films de BPH sont modulables en fonction du pH. Au point isoélectrique (pI = 4.5), les interactions électrostatiques entre les charges opposées agissent comme points de réticulation et augmentent la rigidité des films et leur contrainte à la rupture sans affecter la déformation à la rupture. À pH plus élevé ou plus bas que le pI, les performances mécaniques des films sont plus faibles à cause de la répulsion entre les groupements fonctionnels de même charge qui interagissent plutôt avec les molécules d’eau et causent le gonflement de la matrice protéique des films. Le BPH contenant un nombre élevé d’acides aminés chargés et réactifs, nous avons pu réticuler les films de manière covalente à l’aide d’EDC ou de glutaraldéhyde. Les propriétés mécaniques des films sont modulables en fonction de la concentration d’EDC utilisée lors de la réticulation ou en employant du glutaraldéhyde comme agent réticulant. Les films sont à la fois plus rigides et plus forts avec un degré de réticulation élevé, mais perdent leur extensibilité à mesure que les segments libres de s’étirer lors d’une traction deviennent entravés par les points de réticulation. La réticulation augmente également la résistance à la dégradation enzymatique par la collagénase, les films les plus fortement réticulés lui étant pratiquement insensibles. La spectroscopie infrarouge montre enfin que la réticulation entraîne une transition de feuillets β anti-parallèles inter-moléculaires vers des structures de type hélices de collagène/PPII hydratées. Des liens sacrificiels ont été formés dans les films de BPH par traitement au pI et/ou avec différents métaux, i.e. Na+, Ca2+, Fe3+, afin de moduler les propriétés mécaniques statiques et d’évaluer le rôle de ces traitements sur le comportement d’auto-guérison lors de tests mécaniques cycliques avec différents temps de repos. Plus la valence des ions métalliques ajoutés augmente, plus les propriétés mécaniques statiques affichent un module, une contrainte à la rupture et une ténacité élevés sans toutefois affecter la déformation à la rupture, confirmant la formation de liens sacrificiels. Les tests mécaniques cycliques montrent que les traitements au pI ou avec Ca2+ créent des liens sacrificiels ioniques réversibles qui mènent à un processus d’auto-guérison des performances mécaniques dépendant du pH. L’ajout de Fe3+ à différentes concentrations module les performances mécaniques sur un plus large intervalle et la nature plus covalente de son interaction avec les acides aminés permet d’atteindre des valeurs nettement plus élevées que les autres traitements étudiés. Le Fe3+ permet aussi la formation de liens sacrificiels réversibles menant à l’auto-guérison des propriétés mécaniques. Les spectroscopies Raman et infrarouge confirment que le fer crée des liaisons avec plusieurs acides aminés, dont les histidines et les DOPA. Les résultats dans leur ensemble démontrent que les films de BPH sont des hydrogels biomimétiques du byssus qui peuvent être traités ou réticulés de différentes façons afin de moduler leurs performances mécaniques. Ils pourraient ainsi servir de matrices pour des applications potentielles dans le domaine pharmaceutique ou en ingénierie tissulaire.

Running economy and blood lactate accumulation in elite football players with high and low maximal aerobic power

The purpose was to determine running economy and lactate threshold among a selection of male elite football players with high and low aerobic power. Forty male elite football players from the highest Swedish division (“Allsvenskan”) participated in the study. In a test of running economy (RE) and blood lactate accumulation the participants ran four minutes each at 10, 12, 14, and 16 km•h-1 at horizontal level with one minute rest in between each four minutes interval. After the last sub-maximal speed level the participants got two minutes of rest before test of maximal oxygen uptake (VO2max). Players that had a maximal oxygen uptake lower than the average for the total population of 57.0 mL O2•kg-1•minute-1 were assigned to the low aerobic power group (LAP) (n=17). The players that had a VO2max equal to or higher than 57.0 mL O2•kg-1•minute-1 were selected for the high aerobic power group (HAP) (n=23). The VO2max was significantly different between the HAP and LAP group. The average RE, measured as oxygen uptake at 12, 14 and 16km•h-1 was significantly lower but the blood lactate concentration was significantly higher at 14 and 16 km•h-1 for theLAP group compared with the HAP group.

ICTM: an interval tessellation-based model for reliable topographic segmentation

This work introduces a tessellation-based model for the declivity analysis of geographic regions. The analysis of the relief declivity, which is embedded in the rules of the model, categorizes each tessellation cell, with respect to the whole considered region, according to the (positive, negative, null) sign of the declivity of the cell. Such information is represented in the states assumed by the cells of the model. The overall configuration of such cells allows the division of the region into subregions of cells belonging to a same category, that is, presenting the same declivity sign. In order to control the errors coming from the discretization of the region into tessellation cells, or resulting from numerical computations, interval techniques are used. The implementation of the model is naturally parallel since the analysis is performed on the basis of local rules. An immediate application is in geophysics, where an adequate subdivision of geographic areas into segments presenting similar topographic characteristics is often convenient.

Cardiorespiratory fitness and aerobic performance adaptations to a 4-week sprint interval training in young healthy untrained females

Purpose The aim of this study was to test the effects of sprint interval training (SIT) on cardiorespiratory fitness and aerobic performance measures in young females. Methods Eight healthy, untrained females (age 21 ± 1 years; height 165 ± 5 cm; body mass 63 ± 6 kg) completed cycling peak oxygen uptake ( V˙O2V˙O2 peak), 10-km cycling time trial (TT) and critical power (CP) tests pre- and post-SIT. SIT protocol included 4 × 30-s “all-out” cycling efforts against 7 % body mass interspersed with 4 min of active recovery performed twice per week for 4 weeks (eight sessions in total). Results There was no significant difference in V˙O2V˙O2 peak following SIT compared to the control period (control period: 31.7 ± 3.0 ml kg−1 min−1; post-SIT: 30.9 ± 4.5 ml kg−1 min−1; p > 0.05), but SIT significantly improved time to exhaustion (TTE) (control period: 710 ± 101 s; post-SIT: 798 ± 127 s; p = 0.00), 10-km cycling TT (control period: 1055 ± 129 s; post-SIT: 997 ± 110 s; p = 0.004) and CP (control period: 1.8 ± 0.3 W kg−1; post-SIT: 2.3 ± 0.6 W kg−1; p = 0.01). Conclusions These results demonstrate that young untrained females are responsive to SIT as measured by TTE, 10-km cycling TT and CP tests. However, eight sessions of SIT over 4 weeks are not enough to provide sufficient training stimulus to increase V˙O2V˙O2 peak.

REST is a hypoxia-responsive transcriptional repressor

Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia.

Tenecteplase and alteplase in acute ischaemic stroke thrombolysis: clinical and imaging study

Introduction: Intravenous thrombolysis in acute ischaemic stroke with alteplase improves clinical outcomes, but it has limited efficacy and is associated with increased risk of intracranial haemorrhage. An improved tissue plasminogen activator, tenecteplase, was evidenced to be at least equally effective with lower risk of haemorrhage in acute myocardial infarction thrombolysis. To date, two completed phase II randomised controlled studies comparing tenecteplase and alteplase in acute ischaemic strokes showed variable results. Methods: A literature review of thrombolytic agents used in myocardial infarction and acute ischaemic stroke was performed, followed by a retrospective investigation of the bolus-to- infusion delay of alteplase administration. The main focus of this thesis is the report of our single centre phase II randomised controlled trial that compared tenecteplase (0.25mg/kg, maximum 25mg) and alteplase (0.9mg/kg, maximum 90mg, 10% as the initial bolus, following by one hour infusion with the rest of the dose) in acute ischaemic stroke thrombolysis using advanced imaging as biomarkers. Imaging comprised baseline computed tomography (CT), CT perfusion (CTP) and CT angiography (CTA), and CT+CTA at 24-48 hours. The primary end-point was penumbral salvage (CTP-defined penumbra volume minus follow-up CT infarct volume). A sub-study of coagulation and fibrinolysis analysis of the two agents was performed by comparing a group of coagulation variables measured pre-treatment, 3-12 hours, and 24±3 hours post thrombolysis. An individual patient data (IPD) meta-analysis was carried out using all three completed tenecteplase/alteplase comparison studies in stroke thrombolysis. We compared clinical outcomes including modified Rankin scale at 3 months, early neurological improvement at 24 hours, intracerebral haemorrhage rate and mortality at 3 months between all three tenecteplase doses (0.1mg/kg, 0.25 mg/kg, and 0.4mg/kg) examined and standard alteplase. Imaging outcomes including penumbra salvage, recanalisation rates were also compared using the data from the two studies that had advance imaging carried out. Results: Delay between the initial bolus and the subsequent infusion in administration of alteplase is common. This may reduce the likelihood of achieving a good functional outcome. Among the 104 patients recruited in ATTEST trial, 71 contributed to the imaging primary outcome. No significant differences were observed for penumbral salvage [68 (SD 28) % tenecteplase vs 68 (SD 23) % alteplase], mean difference 1% (95% confidence interval -10%, 12%, p=0·81) or for any secondary end-point. The SICH incidence (1/52, 2% vs 2/51, 4%, by SITS-MOST definition, p=0·55; by ECASS-2 definition, 3/52, 6% tenecteplase vs 4/51, 8% alteplase, p=0.59) did not differed significantly. There was a trend towards lower ICH risk in the tenecteplase group (8/52 tenecteplase, 15% vs 14/51 alteplase, 29%, p=0·091). Compared to baseline, alteplase caused significant hypofibrinogenaemia (p=0.002), prolonged Prothrombin Time (PT) (p=0.011), hypoplasminogenaemia (p=0.001) and lower Factor V (p=0.002) at 3-12 hours after administration with persistent hypofibrinogenaemia at 24h (p=0.011), while only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (p<0.001) and fibrinogen (p=0.002) compared with alteplase. In a pooled analysis, tenecteplase 0.25mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p=0.093), excellent functional outcome (mRS 0-1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p= 0.28), with reduced odds of ICH (OR [95%CI] 0.6 [0.2, 1.8], P=0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4mg/kg, which showed increased odds of SICH compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]). In the two studies where advanced imaging was performed, the imaging outcomes did not differ in the IPD analysis. Conclusion: Tenecteplase 0.25 mg/kg has the potential to be a better alternative to alteplase. It can be given as a single bolus, does not cause disruption to systemic coagulation, and is possibly safer and more effective in clot lysis. Further phase III study to compare tenecteplase and alteplase in acute ischaemic stroke is warranted.

API de servicios web REST extensible dinámicamente basada en una arquitectura Plug-in para el procesado de imágenes recibidas desde dispositivos móviles

Se ha diseñado una aplicación móvil que permite examinar el riesgo de melanoma mediante el análisis de una foto. La memoria documenta la realización de una aplicación de servidor que forma parte de una solución de eHealth con un cliente ya desarrollado por un proyecto previo de fin de carrera en forma de una aplicación Android. La aplicación de servidor desarrollada expone una API de servicios web REST y presenta una arquitectura extensible dinámicamente mediante la implementación de un patrón plug-in.