Introduction : L'hémophilie B (HB) est une maladie hémorragique héréditaire due à un défaut en facteur IX (FIX) de la coagulation. Le traitement substitutif est efficace mais pose deux problèmes : la fréquence des injections intraveineuses de concentrés de FIX et leurs coûts. La production d'un FIX recombinant à activité améliorée et à demi-vie prolongée est un enjeu important du traitement. Matériel et méthodes : Afin d'améliorer l'activité du FIX, l'étude s'est portée sur un résidu impliqué dans l'interaction du FIX activé avec son cofacteur, le facteur VIII activé (FVIIIa). Quatre FIX mutés au niveau de l'acide aminé E410 ont été développés. Afin de prolonger la demi-vie, un ADN complémentaire de FIX chimérique a été généré de façon à produire la protéine correspondante par la lignée cellulaire humaine Huh-7. Résultats : L'activité coagulante in vitro des FIX-E410 était 3 à 5 fois plus élevée que celle du FIX wild-type (FIX-WT). De plus, le FIX-E410H induisait une génération de thrombine 5,2 fois plus élevée comparée à celle du FIX-WT. Chez la souris HB, l'activité coagulante et la capacité de génération de thrombine du FIX-E410H in vivo étaient significativement plus élevées que celles du FIX-WT. La protéine chimérique a présenté une activité molaire spécifique 10 fois augmentée in vitro et une demi-vie jusqu'à 2,8 fois plus allongée, par rapport à celles du FIX-WT. Conclusion : Nous avons développé et caractérisé quatre molécules de FIX ayant une activité améliorée in vitro et in vivo, ainsi qu'un FIX modifié à activité augmentée et à demi-vie prolongée in vivo. Ces nouvelles molécules pourraient ouvrir de nouvelles perspectives thérapeutiques de traitement de l'HB / Introduction: Hemophilia B (HB) is an inherited X-linked recessive bleeding disorder, due to a defect in human factor IX (FIX). Replacement therapy, in severe HB is very effective but is limited by FIX concentrates injections frequency and cost issues. Production of a recombinant FIX with enhanced clotting activity and prolonged half-life is one of the current challenges for HB treatment. Materials and Methods: To improve activity, we focused on an important residue known to be involved in the interaction of activated FIX with its cofactor, activated factor VIII (FVIIIa), and four mutated FIX-E410 were developed. To prolong stability, a new chimeric FIX cDNA was constructed too. Recombinant FIX molecules were produced by the human hepatoma cell line Huh-7. Results: The in-vitro clotting activity of FIX-E410 was 3 to 5-fold higher than wild-type FIX (FIX-WT) and this improvement was confirmed using thrombin generation assay. FIX-E410H induced 5.2-fold higher thrombin generation than FIX-WT. In HB mice, we observed significantly higher in-vivo clotting activity and thrombin generating capacity with FIX-E410H compared to FIX-WT, mainly explained by 2.5-fold enhanced affinity of the mutant for FVIIIa. Chimeric FIX showed a 10-fold increase in the in-vitro molar specific activity and a significantly increased half-life in mice (up to 2.8-fold), compared to FIX-WT. Conclusion: We have engineered and characterized four improved FIX proteins with enhanced in- vitro and in-vivo activity, and a new chimeric FIX with in-vivo increased activity and prolonged half- life. These results suggest that these new molecules could optimize protein replacement therapy forHB treatment

The scope of this thesis is the Miller engine cycle analysis and its practical application on a turbocharged spark ignited engine. Based on the sensitivity analysis of the limits affecting the ideal Miller cycle thermal efficiency a thermodynamic model of the engine with a prolonged expansion was set up in the GT-POWER software. The results of the analyses were used to evaluate the feasibility of the reference engine conversion for an operation with Miller cycle.

Prolonged-release (PR) fampridine is the only approved medication to improve walking in multiple sclerosis (MS), having been shown to produce a clinically meaningful improvement in walking ability in the subset of MS patients with Expanded Disability Status Scale 4–7. Recent responder subgroup analyses in the phase III ENHANCE study show a large effect size in terms of an increase of 20.58 points on the patient-reported 12-item MS Walking Scale in the 43% of patients classified as responders to PR-fampridine, corresponding to a standardized response mean of 1.68. Use of PR-fampridine in clinical practice varies across Europe, depending partly on whether it is reimbursed. A group of European MS experts met in June 2017 to discuss their experience with using PR-fampridine, including their views on the patient population for treatment, assessment of treatment response, re-testing and retreatment, and stopping criteria. This article summarizes the experts’ opinions on how PRfampridine can be used in real-world clinical practice to optimize the benefits to people with MS with impaired walking ability.

Bakgrund: LARO i Sverige är omgärdat av strikta regler. Läkemedlen som används, däribland buprenorfin, intas dagligen övervakat av sjuksköterska de tre första månaderna och vidare till dess att patienten bedöms kunna ta läkemedlet på egen hand. Sedan 2018 finns buprenorfin som depotinjektion veckovis eller månadsvis, vilket innebär en ny omvårdnadssituation. Syfte: Att utforska sjuksköterskans perspektiv på införandet av buprenorfin som depotinjektion i LARO. Metod: Tolv semistrukturerade intervjuer av sjuksköterskor med erfarenhet av depotinjektioner buprenorfin i LARO. Resultat: Införandet av depotinjektioner innebar ett fokusskifte i behandling och omvårdnad med bland annat minskad kontroll och ökad tillit mellan sjuksköterska och patient. Behandlingen med depotinjektioner ansågs kunna öppna för ökad egenmakt för patienterna. LARO-enheternas organisatoriska förutsättningar påverkade hur de tagit sig an den nya behandlingsformen. Kunskap och samsyn efterfrågades. Slutsats: Depotinjektioner buprenorfin kan öppna upp för nya sätt att främja egenmakt i LARO. Det finns ett behov av forskning på området. / Background: Opioid substitution treatment in Sweden is strictly regulated. Medications like Buprenorphine are taken daily supervised by a nurse during the initial three months and thereafter until the patient is assessed to be trusted with self-administration. Prolonged-release injectable Buprenorphine has beenavailable since 2018 for weekly or monthly use. This has implications for nursing care and practices. Purpose: To explore the nurse’s perspective on introducing prolonged-release injectable buprenorphine in opioid substitution treatment. Method: Twelve semi-structured interviews were conducted with nurses experienced in treatment with prolonged-release injectable buprenorphine. Results: The introduction of injection treatment entailed a shift in focus regarding restrains, trust and patient empowerment. The care units’ approaches to the new treatment differed and was influenced by organisational conditions. Nurses requested more knowledge and consensus about the new treatment. Conclusion:Prolonged-release injectable formulations may enable new approaches to patientempowerment in opioid substitution treatment. Research in this field is required.

Worker fatigue has been the focus of research for many years. However, there is limited research available on the evaluation and measurement of fatigue for prolonged mentally demanding activities. The objectives of the study are (1 )to evaluate fatigue for prolonged, mentally demanding work-tasks by considering task-dependent, task-independent and personal factors, (2) to identify effective subjective and objective fatigue measures, (3) to establish a relationship between time and factors that affect fatigue (4) to develop models to predict fatigue. A total of 16 participants, eight participants with western cultural backgrounds and eight participants with eastern cultural backgrounds, currently employed in mentally demanding work-tasks (e.g., programmers, computer simulation experts, etc.) completed the study protocols. Each participant was evaluated during normal working hours in their workplace for a 4-hour test session, with a 15-minute break provided after two hours. Fatigue was evaluated using subjective questionnaires (Borg Perceived Level of Fatigue Scale and the Swedish Occupational Fatigue Index (SOFI)); and objective measures (change in resting heart rate and salivary cortisol excretion). Workload was also assessed using the NASA-TLX. Fatigue and workload scales were collected every 30 minutes, cortisol at the start and finish of each 2-hour work block, and heart rate throughout the test session. Fatigue significantly increased over time (p-value <0.0001). All measures, except cortisol hormone, returned to near baseline level following the 15-minute break (p-value <0.0001). Ethnicity was found to have limited effects on fatigue development. Poor to moderate (Rho = 0.35 to 0.75) significant correlations were observed between the subjective and objective measures. Time and fatigue load (a factor that impacts fatigue development) significantly interact to explain fatigue represented by a hyperbolic relationship. Predictive models explained a maximum of 87% of the variation in the fatigue measures. As expected, fatigue develops over time, especially when considering other factors that can impact fatigue (e.g. hours slept, hours of work), providing further evidence of the complex nature of fatigue. As the 15-minute break was found to reduce all measures of fatigue, the development of appropriate rest breaks may mitigate some of the negative consequences of fatigue.

A large proportion of patients with central motoneuron lesions is at risk of spastic paresis and formation of contractures. One of the therapeutic techniques used in patients with spastic paresis is prolonged stretching. The theoretical part summarizes the knowledge regarding spastic paresis, its clinical evaluation, the development of contractures and therapeutic interventions, especially botulinum toxin (BTX) and stretching. The aim of this study was to compare the effectiveness of prolonged stretching on spastic muscle contracture before and after BTX application. In our retrospective comparative study there were included 30 patients divided into two groups. The first group consisted of 15 patients performing prolonged stretching of the m. rectus femoris (m. RF) for three months according to Guided Self-rehabilitation Contract of Professor J. M. Gracies. The second group (15 patients) performing the same procedure, but at the same time BTX was injected into the m. RF. We monitored the change in passive knee joint range of motion into flexion and the change in 10MWT time. Statistical evaluation showed that the difference in knee joint range of motion after three months of performing prolonged stretching was statistically insignificant (p=0.194). The difference in knee joint range of motion after...

Swimming performance strongly influences fitness in aquatic organisms and is closely tied to external body morphology. Although this connection has been closely examined at the individual and species level, few studies have focused on this relationship as it pertains to functional group assemblages. Using functional groups based on similarities in habitat use and morphology, I tested the hypothesis that swimming performance can be reliably predicted by functional group composition. I measured swimming performance as burst speed using a simulated predator attack and as prolonged speed using a step-endurance test in a laboratory flume. I measured morphology using geometric morphometric techniques. A difference in swimming behavior in four of the seven species was observed in the step-endurance test. Benthic species exhibited bracing behavior as an alternative to body-caudal fin (BCF) propulsion in the prolonged speed trials. Swimming performance exhibited a weak relationship with functional groups based on habitat or morphology. Rather a species-based model was the best predictor of swimming performance. Although species exhibited variation in swimming performance, body size was the strongest predictor of absolute swimming performance across all models. Relative swimming performance (measured in body lengths/sec) was negatively related to body size. The results of this study suggest that functional groups are not always reliable predictors of performance and they necessitate empirical testing to validate their effectiveness. This study also provides critical swimming performance data for previously unstudied Great Basin fishes which could be valuable for predicting fish passage through culverts, weirs and fish ladders.

Nowadays, prolonged sitting among office workers is a widespread problem, which is highly related to several health problems. Many proposals have been reported and evaluated to address this issue. However, motivating and engaging workers to change health behavior to a healthier working life is still a challenge. In this project, a specific application has been deployed for real-time monitoring and alerting office workers for prolonged sitting. The proposed system consists of three distinct parts: The first one is an android smartwatch, which was used to collect sensor data e.g., accelerometer and gyro data, with a custom android wear app. The second one is an android application, which was developed to act as a gateway for receiving the smartwatch’s data and sending them to IBM Bluemix cloud with MQTT protocol. The final part is a Node-Red cloud application, which was deployed for storing, analyzing and processing of the sensor data for activity detection i.e., sitting or walking/standing. The main purpose of the last one was to return relevant feedback to the user, while combining elements from gaming contexts (gamification methods), for motivating and engaging office workers to a healthier behavior. The system was firstly tested for defining appropriate accelerometer thresholds to five participants (control group), and then evaluated with five different participants (treatment group), in order to analyze its reliability for prolonged sitting detection. The results showed a good precession for the detection. No confusing between sitting and walking/standing was noticed. Communication, storage and analysis of the data was successfully done, while the push notifications to the participants, for alerting or rewarding them, were always accurate and delivered on time. Every useful information was presented to the user to a web-based dashboard accessed through a smartphone, tablet or a PC.     The proposed system can easily be implemented at a real-life scenario with office workers. Certainly, there is a lot space for improvement, considering mostly the type of data registered at the system, the method for sitting detection, and the user interface for presenting relevant information. / Numera är förlängt sittande bland kontorsarbetare ett utbrett problem som är väldigt relaterat till flera hälsoproblem. Många förslag har rapporterats och utvärderas för att ta itu med denna fråga. Tydligen är det fortfarande en utmaning att motivera och engagera arbetstagare för att förändra deras hälsobeteende till hälsosammare arbetsliv. I detta projekt har en särskild applikation använts för realtidsövervakning och varnar kontorsarbetare för förlängt sittande. Det föreslagna systemet består av tre olika delar: Den första är en android smartwatch, som användes för att samla sensordata t.ex. accelerometer och gyrodata, med en anpassad android wear app. Den andra är en en androidapplikation som fungerade som en gateway för att ta emot smartwatchens data och skickar datan till IBM Bluemix-Cloud med MQTT-protokollet. Den sista delen är en Node-RED Cloud-Applikation som användes för lagring, analysering och behandling av sensordata för aktivitetsdetektering. Detta innebär sittande eller gå/stående med det huvudsakliga ändamålet att returnera relevant återkoppling till användaren, samtidigt som man kombinerar element från spelkontekster (gamification metoder), för att motivera och engagera arbetarna till ett hälsosammare beteende. Systemet testades först för att definiera lämpliga accelerometertrösklar till fem deltagare (kontroll grupp) och utvärderades sedan med fem olika deltagare (behandingsgrupp) för att analysera dess tillförlitlighet för långvarig sittdetektering. Resultaten visade en bra precession för detektionen. Ingen förvirring mellan att sitta och gå / stående märktes. Kommunikation, lagring och analys av data gjordes framgångsrikt, medan push-meddelandena till deltagarna, för att varna eller belöna dem, var alltid korrekta och levererade i tid. All användbar information presenterades för användaren på en webbaserad dashboard som nås via en smartphone surfplatta eller en dator. Det föreslagna systemet kan enkelt implementeras i ett verkligt scenario med kontorsarbetare. Visst finns det mycket utrymme för förbättring om man tänker på majoriteten av data som registrerats i systemet, metoden för sittande detektion och användargränssnittet för presentering av relevant information.

The current study takes an initial step toward deriving a method for empirically based, theory-driven treatment matching in a military population suffering from PTSD. Along with the more overt symptoms of PTSD (e.g., persistent hyperarousal), secondary cognitive symptoms have also been shown to be significantly associated with avoidance and intrusive symptoms, as well as contribute to functional impairment. Based on the factor analytic and treatment literature for PTSD, it appears that there are two central mechanisms associated with beneficial therapeutic change that underlies both CPT and PE treatments (i.e., habituation, changes in cognitions). Additionally, different traumatic events and peritraumatic responses may be associated with unique symptom profiles and may necessitate targeted treatment. The present study proposes a novel approach to treatment matching based on the factor structure of PTSD and underlying mechanisms of treatment response. More broadly, this paper provides evidence for a broader understanding of peritraumatic responses and the potential implications of these responses for symptom profiles and illness trajectories.

Frågan om ”normal” respektive ”patologisk” sorg har under en lång tid varit ett omdiskuterat ämne inom psykologin och psykiatrin. En grupp forskare har tagit fram kriterier på ett syndrom som fått benämningen ihållande sorg (”prolonged grief”). Studier har visat på att ihållande sorg är ett distinkt syndrom separat från depression, posttraumatisk stressyndrom och generaliserat ångestsyndrom. Ihållande sorg föreslås ingå som en diagnos i de kommande versionerna av de diagnostiska manualerna DSM och ICD. Syftet med denna studie var att översätta självskattningsinstrumentet Prolonged Grief Disorder (PG-13) till svenska, och undersöka dess reliabilitet och validitet genom bland annat en explorativ och konfirmatorisk faktoranalys. Studien genomfördes på ett annonsrekryterat heterogent sample (n=162 varav 90 % var kvinnor) vad gäller typ av dödsfall och relation till den avlidne. Respondenterna besvarade en webb- eller pappersenkät som bestod av 75 items. PG-13 bedöms ha en hög reliabilitet, god begrepps- och samtidig validitet samt en måttlig diskriminativ validitet.