Interim analysis of clinical trials: Simulation studies of fractional Brownian motion

Interim clinical trial monitoring procedures were motivated by ethical and economic considerations. Classical Brownian motion (Bm) techniques for statistical monitoring of clinical trials were widely used. Conditional power argument and α-spending function based boundary crossing probabilities are popular statistical hypothesis testing procedures under the assumption of Brownian motion. However, it is not rare that the assumptions of Brownian motion are only partially met for trial data. Therefore, I used a more generalized form of stochastic process, called fractional Brownian motion (fBm), to model the test statistics. Fractional Brownian motion does not hold Markov property and future observations depend not only on the present observations but also on the past ones. In this dissertation, we simulated a wide range of fBm data, e.g., H = 0.5 (that is, classical Bm) vs. 0.5< H <1, with treatment effects vs. without treatment effects. Then the performance of conditional power and boundary-crossing based interim analyses were compared by assuming that the data follow Bm or fBm. Our simulation study suggested that the conditional power or boundaries under fBm assumptions are generally higher than those under Bm assumptions when H > 0.5 and also matches better with the empirical results. ^

The effects of antipsychotic medications on eye movements in schizophrenia

Schizophrenia is the most prevalent mental disorder in the world, affecting approximately one percent of the population. Antipsychotic medications have successfully treated schizophrenic psychotic symptoms for years, however their positive effects on cognitive dysfunction, a core feature of schizophrenia, are inconclusive. Recent studies have shown that improved cognitive functioning is most often associated with the best long-term prognosis. Thus, clarifying the cognitive effects of commonly prescribed antipsychotic medications is pivotal to improving quality of life and long-term care of schizophrenic patients.^ Previous studies on cognitive dysfunction in schizophrenia utilized complex neuropsychological tasks requiring many intact areas of the brain for proper completion. These complexities make interpretation of acquired data difficult. Recently, eye movements have been identified as a more effective surrogate for investigating cognitive functioning. Eye movements are easily measured, require known discrete areas of the brain for processing, and are ubiquitous. They influence what we attend to and process in the brain; thus they are a pivotal aspect of cognitive functioning. This study sought to examine the effects of antipsychotic medications on eye movements in forty-two schizophrenic patients. These patients were divided equally into the three tested medication groups: haloperidol, olanzapine, and aripiprazole. To the extent possible, these groups were further separated into task-impaired and task-nonimpaired subgroups, and again analyzed. Clinical and neuropsychological scales were administered to assess clinical and eye movement changes.^ The results of this study found the olanzapine-treated group exhibited superior cognitive effects to the aripiprazole-treated group, who was superior to the haloperidol-treated group. Furthermore, upon subdivision into cognitively impaired and nonimpaired subgroups, both olanzapine-treated subgroups continued to show improvement, while only the aripiprazole-treated impaired subgroup showed cognitive benefit. The haloperidol-treated nonimpaired subgroup actually demonstrated worsening effects. Interestingly, despite the cognitive decline of some subgroups, the clinical assessment results indicated virtually all subgroups exhibited significant clinical improvement. Hence, careful selection of an antipsychotic medication is crucial, as this study shows some treatments may help whereas others may hinder cognitive functioning in schizophrenia. ^ The results of this study are extremely important given the relationship between cognitive improvement and long-term prognosis in schizophrenia. Finally, and perhaps most importantly, these results indicate that clinical improvement is not necessarily indicative of cognitive improvement. ^

The relationship between supermarket nutrient movements and the mortality rates from fat-associated and non-fat-associated cardiovascular disease: Development of an ecologic method for determining community food patterns

Supermarket nutrient movement, a community food consumption measure, aggregated 1,023 high-fat foods, representing 100% of visible fats and approximately 44% of hidden fats in the food supply (FAO, 1980). Fatty acid and cholesterol content of foods shipped from the warehouse to 47 supermarkets located in the Houston area were calculated over a 6 month period. These stores were located in census tracts with over 50% of a given ethnicity: Hispanic, black non-Hispanic, or white non-Hispanic. Categorizing the supermarket census tracts by predominant ethnicity, significant differences were found by ANOVA in the proportion of specific fatty acids and cholesterol content of the foods examined. Using ecological regression, ethnicity, income, and median age predicted supermarket lipid movements while residential stability did not. No associations were found between lipid movements and cardiovascular disease mortality, making further validation necessary for epidemiological application of this method. However, it has been shown to be a non-reactive and cost-effective method appropriate for tracking target foods in populations of groups, and for assessing the impact of mass media nutrition education, legislation, and fortification on community food and nutrient purchase patterns. ^

Tab. 1: Number and percentage of glacier movements in the Austrian Alps between 1960 and 1975

The statistical record of the length of Austrian glaciers is continued with an improved classification scheme. The tendency of increasing glacier advance is maintained since 1965. 54 glaciers, or 58 % of the 93 observed, were advancing in 1975. A relation that is noticed between the behavior of the terminus and mean air temperature of the ablation period is discussed in qualitative terms.

Tab. 1: Number and percentage of glacier movements in the Austrian Alps between 1890 and 1969

Since 1890 the variations of the fronts of numerous glaciers in the Eastern Alps have been measured for the Österreichischer Alpenverein. The present paper presents the results of these measurements and the percentage of advancing, retreating, and stationary glaciers as calculated for each year from the total number of glaciers measured. The measurements reveal two distinct periods of advance, i. e. one period from 1890 to 1900 with up to 47% of glaciers advancing, and one period from 1909 to 1928 with up to 75% of glaciers advancing. The period from 1928 to 1964 is marked by a strong retreat of glaciers. A comparison with the results of measurements of glaciers in the Western Alps of Switzerland shows good agreement. The behaviour of glaciers corresponds well to the climatic conditions prevailing during the summer months of the 80 years observed.

Social movements and the crisis of neoliberalism in Malaysia and Thailand

Of the Southeast Asian countries most badly affected by the 1997 financial crisis, Malaysia and Thailand remain the most unsettled by its political fallout. Their present political situations are not akin to 'politics as usual'. Instead, they capture the unpredicted outcomes of post-crisis struggles to reorganize structures of economic and political power. Comparing the situations in Malaysia and Thailand, this paper focuses on their differing state and civil society engagements with neoliberalism. It is suggested that the post-crisis contestations, sometimes tied to pre-crisis conflicts in political economy, left something of a stalemate: neither neoliberalism nor the social movements satisfactorily fulfilled their agendas in either country.

Optimal fits of diffusion constants from single-time data points of Brownian trajectories

Experimental methods based on single particle tracking (SPT) are being increasingly employed in the physical and biological sciences, where nanoscale objects are visualized with high temporal and spatial resolution. SPT can probe interactions between a particle and its environment but the price to be paid is the absence of ensemble averaging and a consequent lack of statistics. Here we address the benchmark question of how to accurately extract the diffusion constant of one single Brownian trajectory. We analyze a class of estimators based on weighted functionals of the square displacement. For a certain choice of the weight function these functionals provide the true ensemble averaged diffusion coefficient, with a precision that increases with the trajectory resolution.

On ergodic least-squares estimators of the generalized diffusion coefficient for fractional Brownian motion

We analyse a class of estimators of the generalized diffusion coefficient for fractional Brownian motion Bt of known Hurst index H, based on weighted functionals of the single time square displacement. We show that for a certain choice of the weight function these functionals possess an ergodic property and thus provide the true, ensemble-averaged, generalized diffusion coefficient to any necessary precision from a single trajectory data, but at expense of a progressively higher experimental resolution. Convergence is fastest around H ? 0.30, a value in the subdiffusive regime.

Quantitative assessment based on kinematic measures of functional impairments during upper extremity movements: a review

Quantitative measures of human movement quality are important for discriminating healthy and pathological conditions and for expressing the outcomes and clinically important changes in subjects' functional state. However the most frequently used instruments for the upper extremity functional assessment are clinical scales, that previously have been standardized and validated, but have a high subjective component depending on the observer who scores the test. But they are not enough to assess motor strategies used during movements, and their use in combination with other more objective measures is necessary. The objective of the present review is to provide an overview on objective metrics found in literature with the aim of quantifying the upper extremity performance during functional tasks, regardless of the equipment or system used for registering kinematic data.

Effects of different swimming race constraints on turning movements

The aim of this study was to investigate the effects of different swimming race constraints on the evolution of turn parameters. One hundred and fifty-eight national and regional level 200-m (meters) male swimming performances were video-analyzed using the individualized-distance model in the Open Comunidad de Madrid tournament. Turn (p < .001, ES = 0.36) and underwater distances (p < .001, ES = 0.38) as well as turn velocity (p < .001, ES = 0.69) significantly dropped throughout the race, although stroke velocity and underwater velocity were maintained in the last lap of the race (p > .05). Higher expertise swimmers obtained faster average velocities and longer distances in all the turn phases (p < .001, ES = 0.59), except the approach distance. In addition, national level swimmers showed the ability to maintain most of the turn parameters throughout the race, which assisted them in improving average velocity at the end of races. Therefore, the variations in the turning movements of a swimming race were expertise-related and focused on optimizing average velocity. Turning skills should be included in the swimming race action plan.