Benzodiazepines and Cognitive Functioning in Older Adults. With Emphasis on Long-Term Use and Withdrawal

Benzodiazepines (BZD) and benzodiazepine related drugs (RD) are the most commonly used psychotropics among the aged. The use of other psychotropics taken concomitantly with BZD/ RD or their cognitive effects with BZD/RD have not been studied frequently. The aim of this academic thesis was to describe and analyse relationships between the use of BZD/RD alone or concomitantly with antipsychotics, antidepressants, opioids, antiepileptics, opioids and anticholinergics in the aged and their health. Especially, the relationships between long-term use of BZD/RD and cognitive decline were studied. Additionally, the effect of melatonin on BZD/RD withdrawal and the cognitive effects of BZD/RD withdrawal were studied. This study used multiple data sets: the first study (I) was based on clinical data containing aged patients (≥65 years; N=164) admitted to Pori City Hospital due to acute disease. The second data set (Studies II and III) was based on population-based data from the Lieto Study, a clinico-epidemiological longitudinal study carried out among the aged (≥65 years) in the municipality of Lieto. Follow-up data was formed by combining the cohort data collected in 1990-1991 (N=1283) and in 1998-1999 (N=1596) from those who participated in both cohorts (N=617). The third data set (Studies IV and V) was based on the Satauni Study’s data. This study was performed in the City of Pori in 2009-2010. In the RCT part of the Satauni Study, ninety-two long-term users of BZD/RD were withdrawn from their drugs using melatonin against placebo. The change of their cognitive abilities was measured during and after BZD/ RD withdrawal. BZD/RD use was related to worse cognitive and functional abilities, and their use may predict worse cognitive outcomes compared with BZD/RD non-users. Hypnotic use of BZD/RD could be withdrawn with psychosocial support in motivated participants, but melatonin did not improve the withdrawal results compared to those with placebo. Cognitive abilities in psychomotor tests did not show, or showed only modest, improvements for up to six months after BZD/RD withdrawal. This suggests that the cognitive effects of BZD/RD may be longlasting or permanent.

Adaptive value of ryegrass biotypes with low-level resistance and susceptible to the herbicide fluazifop and competitive ability with the wheat culture

Ryegrass is the main weed in wheat crop, causing yield loss due to competition by environmental resources. The objectives of this study were to estimate the fitness cost of ryegrass biotypes with low-level resistance and susceptible to fluazifop and to investigate the relative competitive ability of these biotypes between themselves and against the crop. Thus, fitness cost and competitive ability experiments were conducted under greenhouse conditions. For the fitness cost experiments, the low-level resistant ryegrass biotypes and those susceptible to fluazifop were used. For competitive ability, the treatments were arranged in a replacement series, with five proportions of the wheat cultivar FUNDACEP Horizonte and the low-level resistant and susceptible ryegrass biotypes 100:0, 75:25, 50:50, 25:75 and 0:100. Competitive analysis was carried out through diagrams applied to the replacement experiments and use of relative competitiveness indices. Variables evaluated were plant height, in the fitness cost experiment, and leaf area and shoot dry biomass in both experiments. The ryegrass biotypes show overall similar fitness cost and competitive ability. The wheat cultivar FUNDACEP Horizonte is superior in competitive ability to the ryegrass biotype with low-level resistance and equivalent to the susceptible biotype.

Tropical inselbergs: habitat types, adaptive strategies and diversity patterns

Inselbergs are isolated rock outcrops that rise abruptly above the surrounding plains. Granitic and gneissic inselbergs are geologically and geomorphologically old and occur throughout a broad spectrum of climatic zones. They form microclimatically and edaphically dry growth sites that support a highly specialized vegetation. Based on physiognomic criteria a number of habitat types can be distinguished that are widespread on inselbergs (e.g. ephemeral flush vegetation, monocotyledonous mats, rock pools). Three hot spots of global inselberg plant diversity can be identified which are both rich in species and endemics: a) southeastern Brazil, b) Madagascar and c) southwestern Australia.

Adaptive Markov chain Monte Carlo and Bayesian filtering for state space models

This thesis is concerned with the state and parameter estimation in state space models. The estimation of states and parameters is an important task when mathematical modeling is applied to many different application areas such as the global positioning systems, target tracking, navigation, brain imaging, spread of infectious diseases, biological processes, telecommunications, audio signal processing, stochastic optimal control, machine learning, and physical systems. In Bayesian settings, the estimation of states or parameters amounts to computation of the posterior probability density function. Except for a very restricted number of models, it is impossible to compute this density function in a closed form. Hence, we need approximation methods. A state estimation problem involves estimating the states (latent variables) that are not directly observed in the output of the system. In this thesis, we use the Kalman filter, extended Kalman filter, Gauss–Hermite filters, and particle filters to estimate the states based on available measurements. Among these filters, particle filters are numerical methods for approximating the filtering distributions of non-linear non-Gaussian state space models via Monte Carlo. The performance of a particle filter heavily depends on the chosen importance distribution. For instance, inappropriate choice of the importance distribution can lead to the failure of convergence of the particle filter algorithm. In this thesis, we analyze the theoretical Lᵖ particle filter convergence with general importance distributions, where p ≥2 is an integer. A parameter estimation problem is considered with inferring the model parameters from measurements. For high-dimensional complex models, estimation of parameters can be done by Markov chain Monte Carlo (MCMC) methods. In its operation, the MCMC method requires the unnormalized posterior distribution of the parameters and a proposal distribution. In this thesis, we show how the posterior density function of the parameters of a state space model can be computed by filtering based methods, where the states are integrated out. This type of computation is then applied to estimate parameters of stochastic differential equations. Furthermore, we compute the partial derivatives of the log-posterior density function and use the hybrid Monte Carlo and scaled conjugate gradient methods to infer the parameters of stochastic differential equations. The computational efficiency of MCMC methods is highly depend on the chosen proposal distribution. A commonly used proposal distribution is Gaussian. In this kind of proposal, the covariance matrix must be well tuned. To tune it, adaptive MCMC methods can be used. In this thesis, we propose a new way of updating the covariance matrix using the variational Bayesian adaptive Kalman filter algorithm.

Adaptive Dynamics of Resource Specialization

Ecological specialization in resource utilization has various facades ranging from nutritional resources via host use of parasites or phytophagous insects to local adaptation in different habitats. Therefore, the evolution of specialization affects the evolution of most other traits, which makes it one of the core issues in the theory of evolution. Hence, the evolution of specialization has gained enormous amounts of research interest, starting already from Darwin’s Origin of species in 1859. Vast majority of the theoretical studies has, however, focused on the mathematically most simple case with well-mixed populations and equilibrium dynamics. This thesis explores the possibilities to extend the evolutionary analysis of resource usage to spatially heterogeneous metapopulation models and to models with non-equilibrium dynamics. These extensions are enabled by the recent advances in the field of adaptive dynamics, which allows for a mechanistic derivation of the invasion-fitness function based on the ecological dynamics. In the evolutionary analyses, special focus is set to the case with two substitutable renewable resources. In this case, the most striking questions are, whether a generalist species is able to coexist with the two specialist species, and can such trimorphic coexistence be attained through natural selection starting from a monomorphic population. This is shown possible both due to spatial heterogeneity and due to non-equilibrium dynamics. In addition, it is shown that chaotic dynamics may sometimes inflict evolutionary suicide or cyclic evolutionary dynamics. Moreover, the relations between various ecological parameters and evolutionary dynamics are investigated. Especially, the relation between specialization and dispersal propensity turns out to be counter-intuitively non-monotonous. This observation served as inspiration to the analysis of joint evolution of dispersal and specialization, which may provide the most natural explanation to the observed coexistence of specialist and generalist species.

Role of the cardiac nerve in the adaptive changes of heart rate in response to an aversive stimulus in Megalobulimus mogianensis

The effect of an aversive stimulus represented by contact with a hot plate on the heart rate of Megalobulimus mogianensis was evaluated with electrocardiogram recording in intact snails (N = 8). All stimulated animals showed an increase in heart rate, with mean values ranging from 35.6 ± 1.2 (basal heart rate) to 43.8 ± 0.9 bpm (post-stimulation heart rate). The cardioacceleration was followed by gradual recovery of the basal heart rate, with mean recovery times varying from 4.3 ± 0.3 to 5.8 ± 0.6 min. Repetition of the stimulus did not affect the magnitude of variation nor did it influence the basal heart rate recovery time. To investigate the role of the cardiac nerve in mediating the heart rate alterations induced by the aversive stimulus, denervated (N = 8) and sham-operated (N = 8) animals were also tested. Although the aversive stimulus caused the heart rate to increase significantly in both experimental groups, the mean increase in heart rate in denervated animals (4.4 ± 0.4 bpm) was 57% of the value obtained in sham-operated animals (7.7 ± 1.3 bpm), indicating that the cardiac nerve is responsible for 43% of the cardioacceleration induced by the aversive stimulus. The cardioacceleration observed in denervated snails may be due to an increase in venous return promoted by the intense muscular activity associated with the withdrawal response. Humoral factors may also be involved. A probable delaying inhibitory effect of the cardiac nerve on the recuperation of the basal heart rate is suggested.

Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load). One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im). Acute immobilization stress (2 h) was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g): sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.

Power and Performance Management Strategies on NoC-Based Multicore Platforms, Using DVFS, Adaptive Algorithm and Task Parallelism

This work presents synopsis of efficient strategies used in power managements for achieving the most economical power and energy consumption in multicore systems, FPGA and NoC Platforms. In this work, a practical approach was taken, in an effort to validate the significance of the proposed Adaptive Power Management Algorithm (APMA), proposed for system developed, for this thesis project. This system comprise arithmetic and logic unit, up and down counters, adder, state machine and multiplexer. The essence of carrying this project firstly, is to develop a system that will be used for this power management project. Secondly, to perform area and power synopsis of the system on these various scalable technology platforms, UMC 90nm nanotechnology 1.2v, UMC 90nm nanotechnology 1.32v and UMC 0.18 μmNanotechnology 1.80v, in order to examine the difference in area and power consumption of the system on the platforms. Thirdly, to explore various strategies that can be used to reducing system’s power consumption and to propose an adaptive power management algorithm that can be used to reduce the power consumption of the system. The strategies introduced in this work comprise Dynamic Voltage Frequency Scaling (DVFS) and task parallelism. After the system development, it was run on FPGA board, basically NoC Platforms and on these various technology platforms UMC 90nm nanotechnology1.2v, UMC 90nm nanotechnology 1.32v and UMC180 nm nanotechnology 1.80v, the system synthesis was successfully accomplished, the simulated result analysis shows that the system meets all functional requirements, the power consumption and the area utilization were recorded and analyzed in chapter 7 of this work. This work extensively reviewed various strategies for managing power consumption which were quantitative research works by many researchers and companies, it's a mixture of study analysis and experimented lab works, it condensed and presents the whole basic concepts of power management strategy from quality technical papers.

Real-time adaptive control of ultra-fast laser scribing process with spectrometer online monitoring

There exist several researches and applications about laser welding monitoring and parameter control but not a single one have been created for controlling of laser scribing processes. Laser scribing is considered to be very fast and accurate process and thus it would be necessary to develop accurate turning and monitoring system for such a process. This research focuses on finding out whether it would be possible to develop real-time adaptive control for ultra-fast laser scribing processes utilizing spectrometer online monitoring. The thesis accurately presents how control code for laser parameter tuning is developed using National Instrument's LabVIEW and how spectrometer is being utilized in online monitoring. Results are based on behavior of the control code and accuracy of the spectrometer monitoring when scribing different steel materials. Finally control code success is being evaluated and possible development ideas for future are presented.

A case study of a high functioning autistic female in a games setting

This study detennined whether or not a high functioning autistic girl can develop game structure strategies that may allow her to become an active participant in a game or sport environment. This qualitative case study involved the in-depth observation and description of one high functioning autistic student whose experience in a game setting would be studied. The type of case study carried out was a combination of descriptive and evaluative. This experience was investigated through structured, individual programming. Through on-site observation, journal entries, and hands on instruction, I was able to describe what progress the autistic student made in tenns of skill development. The results of the study demonstrated that a high-functioning autistic female has the potential to develop the necessary motor skills to participate in the chosen sport of basketball. The observation results and field notes contributed to a movement profile which described her habits of body. Teaching strategies and frameworks utilized during the study were described and listed. Insights and commentary are further provided. A thorough examination of autism and games programming is provided in the literature review.

Completing the picture: the effects of video game practice on verbal and performance I.Q. scores in high functioning children

The strength and nature of the video game practice effect on tests of visual and perceptual skills were examined using high functioning Grades Four and Five students who had been tested with the WISC-R .for the purpose of gifted identification and placement. The control group, who did not own and .play video games on a sustained basis, and the experimental group, who did own a video game system and had some mastery of video games, including the -Nintendo game, "Tetris", were each composed of 18 juniorg:r;-ade students and were chosen from pre-existing conditions. The experimental group corresponded to the control group in terms of age, sex, and community. Data on the Verbal and Performance I.Q. Scores were· collected for both groups and the author was interested in the difference between the Verbal and Performance Scores within each group, anticipating a P > V outcome for the experimental group. The results showed a significant P > V difference in the experimental, video game playing group, as expected, but no significant difference between the Performance $cores of the control and experimental groups. The results, thus, indicated lower Verbal I.Q. Scores in the experimental group relat'ive to 'the control group.' The study conclu~ed that information about a sUbject's video game experience and "learhing style pref~rence is important for a clear interpretation of the Verbal and Performance I.Q. Scores of the WISC-R. Although the time spent on video game play may, 'indeed, increase P~rformance Scores relative to Verbal Scores for an individual, the possibilities exist that the time borrowed and spent away from language based activities may retard verbal growth and/or that the cognitive style associated with some Performance I.Q.subtests may have a negative effect on the approach to the tasks on the Verbal I.Q. Scale. The study also discussed the possibility that exposure to ,the video game experience, in pre-puberty, can provide spatial instruction which will result in improved spatial skills. strong spatial skills have been linked to improved performance and preference in mathematics, science, and engineering and it was suggested that appropriate video game play might be a way to involve girls more in the fields of mathematics and science.

Carbohydrate refeeding rapidly reverses the adaptive upregulation of human skeletal muscle pyruvate dehydrogenase kinase following a high fat diet

The time course for the reversal of the adaptive increase in pyruvate dehydrogenase kinase (PDK) activity following a 6d high fat diet (HP: 4.2 ± 0.2 % carbohydrate; 75.6 ± 0.4 % fat; 19.5 ± 0.8 % protein) was investigated in human skeletal muscle (vastus lateralis). HF feeding increased PDK activity by 44% (from 0.081 ± 0.025 min"' to 0.247 ± 0.025 mm\p < 0.05). Following carbohydrate re-feeding, (88% carbohydrate; 5% fat; 7% protein), PDK activity had returned to baseline (0.111 ± 0.014 min"') within 3h of re-feeding. The active fraction of pyruvate dehydrognease (PDHa) was depressed following 6d of the HF diet (from 0.89 ± 0.21 mmol/min/kg WW to 0.32 ± 0.05 mmol/min/kg ww,p <0.05) and increased to pre-HF levels by 45 min of post re-feeding (0.74 ±0.19 mmol/min/kg ww) and remained elevated for 3h. Western blotting analysis of the PDK isoforms, PDK4 and PDK2, revealed a 31% increase in PDK4 protein content following the HF diet, with no change in PDK2 protein. This adaptive increase in PDK4 protein content was reversed with carbohydrate re-feeding. It was concluded that the adaptive up-regulation in PDK activity and PDK4 protein content was fiilly reversed by 3h following carbohydrate re-feeding.

The practical application of a meta-analysis of deinstitutionalization : adaptive behaviour outcomes and the piloting of a transitional questionnaire for adults with intellectual disabilities

This investigation examined the effects of de institutionalization on the adaptive behaviour and adjustment of adults with intellectual disabilities (ID). In study 1, a meta-analysis was conducted with 23 studies on deinstitutionalization adaptive behaviour outcomes. Deinstitutionalization was associated with modest improvements in adaptive behaviour however outcomes varied across adaptive behaviour domains and other substantive variables. Clinical and service implications of these results were explicated. Noting the trends from the meta-analysis, study 2 used this information in refining and piloting an Agency Transition Survey used to evaluate community transitions for persons with ID. Information derived from the survey was found to be valuable and adequate for the effective evaluation of transitional success. Potential applications of the survey and meta-analysis results were illustrated.