Over the past several years there has been a steady increase in the incidence of immunologically compromised patients. This has been the result of both chemical agents, such as those used in cancer chemotherapy, and biological agents such as HIV, the cause of Acquired lmmunodefeciency Syndrome (AIDS). The increase in immune-suppressed patients has lead to an increase in life-threatening mycoses requiring treatment with antifungal agents. Pharmaceutical companies have increased research for the development of new antifungal agents which are more effective and less toxic than those that are currently used. Several researchers have reported on antifungal agents that demonstrate both positive and negative effects on the immune system. Because antifungal therapy relies on host immune defenses in eliminating diseases, more emphasis is being placed on how antifungal agents interact with the immune system. The purpose of this study was to evaluate the effects of Ketoconazole, ltraconazole and Fluconazole on T- and B-cell proliferation and natural killer cell activity using normal, cyclosporine-compromised and cyclophosphamide-compromised immune models in mice. T and B cells obtained from the spleens Balb/c mice were mitogen stimulated and grown in the presence of 0, 1, 2, 4, 8 and 16 µg/ml of these 3 antifungal agents. Cell proliferation was determined by the uptake of 3[H]-thymidine and was measured as counts per minute. Natural killer cell activity was measured by the release of 51-sodium chromate (51Cr) into the supernatant by 51Cr-labeled Yac cells. Ketoconazole caused a significant reduction in cell proliferation in all immune models in both T and B cells. Itraconazole also significantly inhibited cell proliferation in all models in both T and B cells as well as natural killer (NK) cell activity in the immune-normal model. Viability studies on mitogen-stimulated lymphocytes suggest that inhibitory effects of Katoconazole and Itraconazole on lymphocyte proliferation are due to toxic effects. Fluconazole appears to have few if any inhibitory effects on either cell proliferation or natural killer cell activity.

Because of the increasing number of serious risk factors which predispose a normally immune competent host to infection, the incidence of systemic fungal infections is steadily increasing. This epidemiological rise has especially become apparent since the onset of the AIDS epidemic. Amphotericin B is the drug of choice for these life-threatening mycotic infections. Complications due to drug toxicity, however, severely limit amphotericin B's clinical usefulness. The major complication associated with the administration of amphotericin B is renal toxicity. Research has indicated, however, that besides its antifungal activities, amphotericin B may act as an immune stimulant of both humoral and cellular responses. A new formulation, liposomal amphotericin B, has been developed which has proven to be significantly less toxic to the kidneys. Research has suggested that liposomal amphotericin B may also act as an immune stimulant. Recent reports have also suggested that its stimulatory capabilities may possibly exceed those of the non-liposomal preparations. The purpose of this study was to quantify the specific effects of amphotericin B and liposomal amphotericin B on the in vitro indices: cellular viability, B- and T-lymphocyte proliferation and macrophage activation as indicators of immune system functions. Spleen cells from immune normal, and immune compromised BALB/c female mice were harvested following euthanasia and incubated in the presence of the two drugs. Drug doses were chosen to correlate with those surrounding clinically relevant plasma concentrations. Cyclosporine and cyclophosphamide were used as immune suppressants to simulate organ transplant patients and patients receiving cancer chemotherapy, respectively. Results indicated that amphotericin B consistently reduces the ability of B-cells and T-cells to proliferate and the ability of macrophages to produce interleukin-1. Though direct cytotoxicity may play a part in these assays, it is probably minor because viability studies show no more than a ten percent reduction due to amphotericin B compared with its liposomal analogue. Liposomal amphotericin B was shown to be non-toxic in each of the immune parameters. It appeared that liposomes may be an important means of delivering more drug to a host infected with a fungal organism without further compromising the patient's already suppressed immune system.

Passive hallux adduction has been shown to decrease blood flow in the lateral plantar artery (LPA) in a non-weight-bearing condition. Further research in weight-bearing and shod conditions is necessary to explore relationships between altered blood flow and injury or tissue healing. However, measuring blood flow in a shod foot would require an alternate measurement location to accommodate footwear, such as the more proximal posterior tibial artery (PTA). PURPOSE: To determine changes in blood flow in the PTA and LPA subsequent to passive hallux adduction and to compare the observed changes between the two arteries. Second, to determine if measurement at the PTA is a viable surrogate for measurement at the LPA. METHODS: Forty-one subjects (21 males, 20 females) participated in this study (age 23.5 ± 4.5 years, body mass 72.6 ± 13.7 kg, and height 173.1 ± 10.2 cm). PTA and LPA vessel diameter and velocity were measured via doppler ultrasound (L8-18i transducer GE Logiq S8). LPA was imaged distal to the abductor hallucis and the PTA posterior to the medial malleolus. Each artery was measured for 120 s: 60 s at rest followed by 60 s of passive hallux adduction. PTA and LPA metrics were log transformed and compared using a two-way repeated measures ANOVA, then the log transformed data was assessed with paired t-tests and Bland-Altman plots (alpha = 0.05). RESULTS: There was an expected decrease in blood flow within each artery after passive hallux adduction (p < 0.001). The volume of blood flow differed between the arteries (p < .0001), but the change between baseline to first 5 cardiac cycles after hallux adduction was similar in each artery (p = 0.419). Bland-Altman analysis showed large spread limits of agreement, indicating the PTA underestimated or overestimated measurements at the LPA. CONCLUSIONS: These data suggest that PTA blood flow behaves in a similar manner as LPA blood flow in consequence to passive hallux adduction. There is no significant difference in the absolute change of blood flow during hallux adduction between the LPA and PTA. However, Bland-Altman analysis suggests that the PTA is not a direct surrogate for the LPA due to the large variance in flow between the arteries. Despite this, the PTA can still be a beneficial location of measurement for plantar blood flow. Some reasons are that the PTA has a larger diameter making it an easier artery to image and allows for further research implications due to its ease of access in more applicable circumstances, such as in a shod condition.

There is considerable evidence suggesting an innate linkage between the human perceptual and motor systems, which evolve together and assist one another in the production and coordination of movement. A major contributor to this relationship is optic flow, providing movement variables such as navigation, obstacle avoidance, and depth perception. The absence of optic flow leads to the decoupling of perception and action, which has been shown to contribute to decrements in human movement (i.e., negatively impacted locomotion and posture, and slower adaptation to gait perturbations). Despite the importance of maintaining this linkage, optic flow manipulations are often found to be underrepresented in locomotion literature when specifically related to rehabilitation training (i.e., treadmills). This may be a contributor to the lengthy and exhaustive treatment plans. The literature has shown instances where reintroducing optic flow into training protocols has shown larger gait improvements in shorter times than typical ambulation protocols, however, the strength of the perception-action linkage in adulthood is still not well understood and its impact not yet fully explored. Therefore, the current research program aims to fill this gap by evaluating how the reintroduction of optic flow into atypical gait training protocols in both healthy and gait-compromised individuals may provide evidence that could be used to enhance rehabilitative outcomes. This series of conceptually related experiments explores outcome enhancements through neuromuscular level changes (Study One), the recalibration process of perception-action given newly acquired physical constraints (Study Two), and on larger scale gait cycle performances in a rehabilitation setting (Study Three). It is hypothesized that perception- action coupling will lead to increases in neuromuscular elicitation in the absence of voluntary movement (Study One), assist the recalibration process to improve measures of spatial awareness and atypical gait parameters (Study Two), and finally, improve rehabilitative outcomes in a spinal cord injury (SCI) ambulation protocol, both objectively (i.e., gait parameters, dynamic balance, SCI measures) and subjectively (i.e., questionnaires) (Study Three). / Thesis / Master of Science (MSc)

The circadian rhythms are not solely regulated by photoperiod but are also influenced by feed regimen. Therefore, maternal nutrient restriction during gestation could potentially impact the fetal circadian rhythm. Melatonin, a circadian rhythm modulator hormone, has shown to act as an antioxidant reducing reactive oxygen species during stress exposure; and two potential mechanisms have been proposed for melatonin causing vasoconstriction and vasodilation regulating blood flow. In livestock species, nutrient restriction during gestation reduces uterine blood flow, limiting nutrients availability to the fetus for growth and development. Therefore, this project aimed to use beef heifers to evaluate the maternal nutrient restriction and/ or melatonin supplementation in (1) temporal transcript abundance of clock genes, angiogenic factors and nutrient sensing genes in bovine placenta, (2) temporal alterations of uteroplacental blood flow, vaginal temperatures, and placentome vascularization, and (3) fetal morphometrics. Early maternal nutrient restriction did not alter placental explants gene expression. Furthermore, the maternal portion of the placentome exhibited limit temporal variation, while the fetal tissue exhibited a clear temporal rhythm in the mRNA relative abundance of the genes measured. Additionally, melatonin supplementation during late gestation, showed to increased uterine blood flow, reduced vaginal temperatures, and rescued fetal weights during compromised pregnancies in a season dependent manner. In conclusion, the bovine placenta exhibited an autonomous circadian rhythm, while the fetal and maternal circadian rhythms appeared to be independent systems. Future research should examine the effects of melatonin supplementation in fetal organ development.

In dieser Masterthese werden Zwischenergebnisse einer dreijährigen Studie vorgestellt, die eine resektive mit einer regenerativen Methode zur Behandlung von Periimplantitis vergleicht. Derzeit liegen Daten über einen sechsmonatigen Beobachtungszeitraum für vier Patienten in der (resektiven) Kontrollgruppe und fünf in der (regenerativen) Testgruppe vor. Patienten beider Gruppen mit einer extensiven Parodontitisvorgeschichte präsentieren sich in der Regel mit größeren Sondierungstiefen. Größere Sondiertiefen zu Beginn der Behandlung zeigen eine Tendenz zu schlechteren Ergebnissen im Verlauf der Beobachtungsphase, wobei der kausale Zusammenhang dazu in einer ähnlichen Pathogenese der Parodontitis und des schlechten Periimplantitisbehandlungserfolges liegen kann, die durch dieselben Risikofaktoren beeinflusst wird (Mundhygiene, genetische Faktoren, Mundflora etc.). Die Wundabdeckung nach der Augmentation scheint eine noch bedeutendere Rolle für die Prognose zu spielen als die Parodontitisvorgeschichte. Wund- und Nahtdehiszenzen sind die häufigsten Komplikationen in der Testgruppe. Bei einem Patienten der Testgruppe entwickelte sich aufgrund einer Wunddehiszenz eine fulminante Infektion und Entzündung, die letztlich zum Verlust des Implantates führte. Sondiertiefen und PES der Testgruppe zeigen drei und sechs Monate nach der Behandlung eine deutliche Verbesserung, wobei der Unterschied in den durchschnittlichen Sondiertiefen zwischen Behandlungsbeginn und drei oder sechs Monate danach z. T. statistisch signifikant war. In der Kontrollgruppe veränderten sich dagegen die Sondiertiefen und der PES nach der Behandlung nicht. Insgesamt sind die Ergebnisse vielversprechend mit deutlichen Verbesserungen des BOP und der Sondiertiefe, jedoch ist der Erfolg der Augmentation von der Operationstechnik abhängig. Für die Beurteilung eines Langzeiterfolges ist es derzeit noch zu früh. / This master thesis presents intermediate results of a three-year study that compares a resective with a regenerative method for the treatment of peri-implantitis. Currently, data are available over a six-month observation period for four patients in the (resective) control group and five in the (regenerative) test group. Patients in both groups with an extensive history of peri-ondotitis present usually with larger probing depths. Larger probing depths at the beginning of treatment show a tendency to result in worse outcomes during the monitoring phase. The causal relationship of this could be a similar pathogenesis of both peri-odontitis and a unfavorable outcome of the peri-implantitis treatment, which is influenced by the same risk factors (oral hygiene, genetic factors, oral flora, etc.). The wound covering after augmentation seems to play an even greater role for the prognosis compared to a history of peri-ondotitis. Wound and suture dehiscence are the most common complication in the test group. In one patient of the test group, a fulminant infection and inflammation developed as a result of wound dehiscence that ultimately led to the loss of the implant. Probing depths and PES in the test group at three and six months after treatment showed a significant improvement compared to the baseline before the treatment. This difference in the average probing depths between baseline and three or six months thereafter was in part statistically significant. In the control group, however, the probing depths and the PES did not change after treatment. Overall, the results are promising with significant improvements in the BOP and the probing depth, but the success of the augmentation depends on the surgical technique. At this point it is still to early to assess long-term success.

Σκοπός αυτής της διπλωματικής είναι η έρευνα και ανάπτυξη ενός συστήματος ανάκτησης μολυσμένων συστημάτων. Αρχικά, γίνεται μια ανασκόπηση των σφαλμάτων των οποίων έγκειται στην χρήση ενός υπολογιστή και τα διάφορα σενάρια τα οποία αναπτύσσονται στην περίπτωση που υπάρχει κάποιο πρόβλημα. Στη συνέχεια, αναπτύσσονται μέθοδοι και διάφορες εφαρμογές στα πλαίσια ενός υπολογιστή διακομιστή, ο οποίος αναλαμβάνει την ιδιότητα της ανάκτησης όλων των υπολογιστών που έχουν μολυνθεί είτε υποστεί βλάβη στο υποδίκτυο του. Η βασική εφαρμογή στην οποία υλοποιείται το συγκεκριμένο σύστημα είναι η ιδιότητα που έχουν όλοι οι καινούργιοι υπολογιστές, να μπορούν να ξεκινήσουν το λειτουργικό τους σύστημα μέσω δικτύου. Η διαχείριση του συστήματος γίνεται μέσω ενός απλού φυλλομετρητή από την πλευρά του «χαλασμένου» υπολογιστή. Αφού δοθούν οι απαραίτητες ρυθμίσεις για την ανάκτηση του συστήματος, γίνεται επανεκκίνηση και ξεκινάει το σύστημα υπό το νέο λειτουργικό το οποίο παρέχεται από τον διακομιστή. Πλατφόρμα υλοποίησης του διακομιστή είναι το λειτουργικό σύστημα Windows 2008 Server R2 x64 και η ιστοσελίδα που παρέχει την λειτουργία για ανάκτηση δεδομένων έχει υλοποιηθεί στην γλώσσα PHP(Preprocessor Hypertext Language) και MySQL . Η υλοποίηση του διακομιστή γίνεται μέσω των υπηρεσιών της Microsoft και – συγκεκριμένα - για να υλοποιηθεί το κομμάτι της εκκίνησης από το δίκτυο χρησιμοποιούνται τα Windows Deployment Services μαζί με το πρωτόκολλο TFTP (Trivial File Transfer Protocol) για τη μεταφορά των δεδομένων των εικόνων λειτουργικών συστημάτων. H ιστοσελίδα που χρησιμοποιείται στον διακομιστή ρυθμίστηκε να τρέχει από τον διακομιστή Apache. Στο τελευταίο κεφάλαιο παρουσιάζονται συμπεράσματα και παρατηρήσεις από την όλη εφαρμογή του συστήματος, καθώς και προτείνονται λύσεις για την περεταίρω επέκταση του συστήματος σε ένα πιο ευρύ φάσμα, ξεφεύγοντας από το υποδίκτυο στο οποίο έγινε η παρακάτω υλοποίηση. / The purpose of this thesis is to research and develop a system for recovering compromised systems. Initially, there is a review of the errors and different scenarios which occur during the use of a computer. Then, there are developed different methods and applications in a computer server, which assumes that the status of a computer in the subnet is either infected or damaged. The basic application that implemented this system is the property all new computers have: the fact that they can start their operating system through a network. The management system is via a simple browser-side of the "compromised" computer. After providing the necessary parameters for recovering the computer, the system restarts and boots the system in the new OS that is supplied by the server. The platform implementation of the server operating system is Windows 2008 Server R2 x64 and the website that provides the service for data recovery has been implemented in ​​PHP (Preprocessor Hypertext Language) and MySQL. The implementation of the server is done via Microsoft Services and to implement the part of the boot from the network, Windows Deployment Services are used along with the Protocol TFTP (Trivial File Transfer Protocol) for the data transfer of the images of the operating systems. The site is running on an Apache server. The final chapter presents conclusions and observations from the system application view and there are proposed solutions to further extend the scheme to a wider range, escaping from the subnet.

In dieser Masterthese werden Zwischenergebnisse einer dreijährigen Studie vorgestellt, die eine resektive mit einer regenerativen Methode zur Behandlung von Periimplantitis vergleicht. Derzeit liegen Daten über einen sechsmonatigen Beobachtungszeitraum für vier Patienten in der (resektiven) Kontrollgruppe und fünf in der (regenerativen) Testgruppe vor. Patienten beider Gruppen mit einer extensiven Parodontitisvorgeschichte präsentieren sich in der Regel mit größeren Sondierungstiefen. Größere Sondiertiefen zu Beginn der Behandlung zeigen eine Tendenz zu schlechteren Ergebnissen im Verlauf der Beobachtungsphase, wobei der kausale Zusammenhang dazu in einer ähnlichen Pathogenese der Parodontitis und des schlechten Periimplantitisbehandlungserfolges liegen kann, die durch dieselben Risikofaktoren beeinflusst wird (Mundhygiene, genetische Faktoren, Mundflora etc.). Die Wundabdeckung nach der Augmentation scheint eine noch bedeutendere Rolle für die Prognose zu spielen als die Parodontitisvorgeschichte. Wund- und Nahtdehiszenzen sind die häufigsten Komplikationen in der Testgruppe. Bei einem Patienten der Testgruppe entwickelte sich aufgrund einer Wunddehiszenz eine fulminante Infektion und Entzündung, die letztlich zum Verlust des Implantates führte. Sondiertiefen und PES der Testgruppe zeigen drei und sechs Monate nach der Behandlung eine deutliche Verbesserung, wobei der Unterschied in den durchschnittlichen Sondiertiefen zwischen Behandlungsbeginn und drei oder sechs Monate danach z. T. statistisch signifikant war. In der Kontrollgruppe veränderten sich dagegen die Sondiertiefen und der PES nach der Behandlung nicht. Insgesamt sind die Ergebnisse vielversprechend mit deutlichen Verbesserungen des BOP und der Sondiertiefe, jedoch ist der Erfolg der Augmentation von der Operationstechnik abhängig. Für die Beurteilung eines Langzeiterfolges ist es derzeit noch zu früh. / This master thesis presents intermediate results of a three-year study that compares a resective with a regenerative method for the treatment of peri-implantitis. Currently, data are available over a six-month observation period for four patients in the (resective) control group and five in the (regenerative) test group. Patients in both groups with an extensive history of peri-ondotitis present usually with larger probing depths. Larger probing depths at the beginning of treatment show a tendency to result in worse outcomes during the monitoring phase. The causal relationship of this could be a similar pathogenesis of both peri-odontitis and a unfavorable outcome of the peri-implantitis treatment, which is influenced by the same risk factors (oral hygiene, genetic factors, oral flora, etc.). The wound covering after augmentation seems to play an even greater role for the prognosis compared to a history of peri-ondotitis. Wound and suture dehiscence are the most common complication in the test group. In one patient of the test group, a fulminant infection and inflammation developed as a result of wound dehiscence that ultimately led to the loss of the implant. Probing depths and PES in the test group at three and six months after treatment showed a significant improvement compared to the baseline before the treatment. This difference in the average probing depths between baseline and three or six months thereafter was in part statistically significant. In the control group, however, the probing depths and the PES did not change after treatment. Overall, the results are promising with significant improvements in the BOP and the probing depth, but the success of the augmentation depends on the surgical technique. At this point it is still to early to assess long-term success.

No description available.

Despite much discussion in the literature of uncertainties in relation to the innovation process, there is little knowledge of how they emerge in this process. This thesis accordingly aims to understand how uncertainty emerges in the innovation process and how firms address that uncertainty to create novelty from the process. Uncertainty is embedded in the innovation process (Jalonen, 2012), which implies that it is not only a factor affecting the innovation process but also an outcome of the process itself. To fulfil the purpose of this study, it is important to understand how the innovation process unfolds over time. It is well established that innovation is a process of recombining resources (Schumpeter, 1934) through the performing and linking of certain activities in sequence (Richardson, 1972; Dubois, 1994; Bankvall, 2011) by various actors (i.e., firms and organizations) in a network context (Håkansson and Olsen, 2012; Lampela, 2012; Love and Roper, 2001; Pittaway et al., 2004; Powell et al., 1996). To fulfil the purpose of this study, the following research question has been asked: How and why do actors undertake and link resource recombination activities in a network context, thereby managing uncertainties in the innovation process? The thesis investigates the innovation process in two companies. One of the companies had completed its innovation journey and the other had almost done so. The discussion gives a detailed account of: the activities these companies performed alone and jointly with their partners in a network context; the resources they exchanged with each other and recombined to bring new solutions to the market; the uncertainties created in the process of recombining the resources; and the activities they undertook in response to address these uncertainties. The innovation process in the case companies is analysed in light of a conceptual model developed here based on Dubois’ (1994) “end product related activity structure model”, Håkansson’s (1987) “ARA model/network model”, and Goldratt’s (1997) “critical chain concept”. This study identifies the conditions under which uncertainties emerged in the innovation process in the studied companies. One of the significant conditions was resource unavailability, which was caused by actors’ reluctance to share resources, prohibition by government policy, and the resources’ own conflicting conditions and internal resistance (Håkansson and Snehota, 1995; Håkansson and Waluszewski, 2002; Waluszewski, 2004). Resource unavailability caused inertial and repetitive activities and delayed the process of producing an outcome, having such an impact on the activities under the condition of path dependency (Arthur, 1994; David, 2000). Another observed condition was the actors’ lack of knowledge of resource combination (Jalonen, 2011). A type of uncertainty that seriously affects the outcome of the innovation process is the activity void, a situation in which no activity is taking place. Activity voids are created from resource unavailability either by an actor’s reluctance to share resources or by the outcome of combining conflicting resource properties. The outcome of the innovation process is therefore affected by the key actor’s attempt to reduce the activity void by making compromises at the three levels, interplay among which construct the process, i.e., actors, resources, and activities. To manage uncertainties, managers make many compromises when they perform and link various activities. Although the underlying motivation for making compromises is rational, it is boundedly rational (Simon, 1957) because by making compromises, managers forego expectations of having all the properties or of being able to plan, undertake, and link activities as intended. This study also reveals that sometimes actors prefer not to make compromises despite knowing that this might cost a great deal. Accordingly, the findings suggest that compromises made within a working relationship allow actors to produce novelty without deviating from the desired path by ensuring access to resources and partners’ abilities. On the contrary, compromises not made in the relationship can threaten actors’ ability to produce the desired novelty, as the exchange of partners’ resources and abilities is hindered in a poor relationship. Compromises made in resource configuration and activities threaten actors’ ability to produce the desired novelty by limiting their choices, while compromises not made in resource configuration and activities allow actors to produce the desired novelty without deviation.