Prognostic factors associated with disease progression in parkinson's disease

This thesis examined the factors correlated with rapid and benign progression of disease in a group of 1452 Parkinson’s disease (PD) patients. The data were collected in a movement disorders clinic at the Royal University Hospital, University of Saskatchewan run by Dr. Alex Rajput and Dr. Ali Rajput. This data is a clinical dataset of PD patients collected from 1970 through to February, 2005. This was a retrospective cases-only study, with anticipated analytical follow-up if any correlations were detected between progression type of PD and the many independent variables available in the dataset. Rapid progression was defined as those subjects who reached Hoehn and Yahr stage 3 within three years or H&Y stage 4 or 5 within five years. Subjects who remained in Hoehn and Yahr stage 1 or 2, ten years after onset of disease, were defined as having benign progression. The study analyzed demographic and clinical findings at first visit to this clinic associated with rapid and benign progression of PD. Analysis revealed that, at first clinic visit, benign progression was positively associated with disease duration (OR=1.41; 95% CI 1.27, 1.57), male sex (OR=3.23; 95% CI 1.70, 6.16), and current smoking habit (OR=2.33; 95% CI 0.67, 8.11). Benign progression was negatively associated with older age of onset (OR=0.36; 95% CI 0.25, 0.50), past history of smoking (OR=0.46; 95% CI 0.24, 0.89), current or past use of levodopa (OR=0.45; 95% CI 0.21, 0.98), and mild to severe rigidity (OR=0.43; 95% CI 0.23, 0.80). Analysis also revealed that, at first clinic visit, rapid progression was positively associated with older age of onset (OR=2.45; 95% CI 1.80, 3.33) and mild to severe rigidity (OR=1.73; 95% CI 1.02, 2.94). Rapid progression was negatively associated with disease duration (OR=0.52; 95% CI 0.44, 0.62), male sex (OR=0.58; CI 0.35, 0.95), and mild to severe resting tremor (OR=0.47; CI 0.28, 0.77). The results of this study indicate that age of onset, disease duration, male sex, and rigidity are good potential predictors of disease progression in PD because they have opposite associations with rapid and benign progression. History of levodopa use was negatively associated with benign progression and as such may be good indicator of non-benign progression. Although previous studies found no predictive value for smoking history, the current study reported a unique association between smoking history and benign progression. Past smoking history was negatively associated with benign progression. While there was a positive association with current smoking history, the result was not statistically significant. Resting tremor was negatively associated with rapid progression and as such may be a good indicator of non-rapid progression. Disease characteristics collected at first clinic visit are useful in predicting the course of progression of PD. With more rapid progression of PD closer and more frequent follow-up of patients may be necessary

Rethinking our composing, recomposing our thinking : composition studies and cognitive psychology consider writing

This thesis strives for an interdisciplinary conversation between composition studies and cognitive psychology. Under particular consideration is the role of automatic thinking in reading and writing and how certain pedagogies of writing might move students away from automatic thinking and towards deliberate, intentional thinking. Of particular interest is the pedagogy of Ann E. Berthoff, who is placed in a lineage of interdisciplinary thinkers including Lev Vygotsky, I.A. Richards, and Paulo Freire. Concepts advocated by Berthoff's composition theories and by her contemporaries, including David Bartholomae, Anthony Petrosky, and Mariolina Salvatori, closely correlate with cognitive psychology principles regarding how to overcome automatic thinking and reestablish executive control, responsible for intentional thought, within the brain. Berthoff's concepts include the use of the dialectic, collaborative learning, and time. These concepts are considered theoretically, scientifically, and practically within the context of the first-year writing classroom. Surrounding the theoretical discussion is the question of what the role of the first-year writing classroom can play in preparing students for a rapidly changing, increasingly unpredictable world and how interdisciplinary work can enhance understanding within and potential for the field composition studies

Pbx loss in cranial neural crest, unlike in epithelium, results in cleft palate only and a broader midface.

Orofacial clefting represents the most common craniofacial birth defect. Cleft lip with or without cleft palate (CL/P) is genetically distinct from cleft palate only (CPO). Numerous transcription factors (TFs) regulate normal development of the midface, comprising the premaxilla, maxilla and palatine bones, through control of basic cellular behaviors. Within the Pbx family of genes encoding Three Amino-acid Loop Extension (TALE) homeodomain-containing TFs, we previously established that in the mouse, Pbx1 plays a preeminent role in midfacial morphogenesis, and Pbx2 and Pbx3 execute collaborative functions in domains of coexpression. We also reported that Pbx1 loss from cephalic epithelial domains, on a Pbx2- or Pbx3-deficient background, results in CL/P via disruption of a regulatory network that controls apoptosis at the seam of frontonasal and maxillary process fusion. Conversely, Pbx1 loss in cranial neural crest cell (CNCC)-derived mesenchyme on a Pbx2-deficient background results in CPO, a phenotype not yet characterized. In this study, we provide in-depth analysis of PBX1 and PBX2 protein localization from early stages of midfacial morphogenesis throughout development of the secondary palate. We further establish CNCC-specific roles of PBX TFs and describe the developmental abnormalities resulting from their loss in the murine embryonic secondary palate. Additionally, we compare and contrast the phenotypes arising from PBX1 loss in CNCC with those caused by its loss in the epithelium and show that CNCC-specific Pbx1 deletion affects only later secondary palate morphogenesis. Moreover, CNCC mutants exhibit perturbed rostro-caudal organization and broadening of the midfacial complex. Proliferation defects are pronounced in CNCC mutants at gestational day (E)12.5, suggesting altered proliferation of mutant palatal progenitor cells, consistent with roles of PBX factors in maintaining progenitor cell state. Although the craniofacial skeletal abnormalities in CNCC mutants do not result from overt patterning defects, osteogenesis is delayed, underscoring a critical role of PBX factors in CNCC morphogenesis and differentiation. Overall, the characterization of tissue-specific Pbx loss-of-function mouse models with orofacial clefting establishes these strains as unique tools to further dissect the complexities of this congenital craniofacial malformation. This study closely links PBX TALE homeodomain proteins to the variation in maxillary shape and size that occurs in pathological settings and during evolution of midfacial morphology

Probabilistic Clustering of Time-Evolving Distance Data

We present a novel probabilistic clustering model for objects that are represented via pairwise distances and observed at different time points. The proposed method utilizes the information given by adjacent time points to find the underlying cluster structure and obtain a smooth cluster evolution. This approach allows the number of objects and clusters to differ at every time point, and no identification on the identities of the objects is needed. Further, the model does not require the number of clusters being specified in advance -- they are instead determined automatically using a Dirichlet process prior. We validate our model on synthetic data showing that the proposed method is more accurate than state-of-the-art clustering methods. Finally, we use our dynamic clustering model to analyze and illustrate the evolution of brain cancer patients over time

Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer

The risk factors and potential practice implications of radiation-induced pleural effusion (RIPE) are undefined. This study examined lung cancer patients treated with thoracic radiation therapy (TRT) having follow-up computed tomography (CT) or 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Increased volumes of pleural effusion after TRT without evidence of tumor progression was considered RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5-55 Gy (V5-V55) and mean lung dose (MLD) were analyzed by receiver operating characteristic analysis. Clinical and treatment-related risk factors were detected by univariate and multivariate analyses. 175 out of 806 patients receiving TRT with post-treatment imaging were included. 51 patients (24.9%) developed RIPE; 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and dyspnea (35.3%). Female (OR = 0.380, 95% CI: 0.156–0.926, p = 0.033) and Caucasian race (OR = 3.519, 95% CI: 1.327–9.336, p = 0.011) were significantly associated with lower risk of RIPE. Stage and concurrent chemotherapy had borderline significance (OR = 1.665, p = 0.069 and OR = 2.580, p = 0.080, respectively) for RIPE. Patients with RIPE had significantly higher whole lung V5-V40, V50 and MLD. V5 remained as a significant predictive factor for RIPE and symptomatic RIPE (p = 0.007 and 0.022) after adjusting for race, gender and histology. To include, the incidence of RIPE is notable. Whole lung V5 appeared to be the most significant independent risk factor for symptomatic RIPE

Data Recovery Investigations: Murvaul Creek Site (41PN175), Panola County, Texas

This report summarizes the archeological findings of the 2011 data recovery investigations at the Murvaul Creek site, 41PN175, in far northeastern Texas in Panola County. The site is located along Farm-to-Market Road (FM) 10 approximately 1 mile north of Gary, Texas (Figure 1). Geo-Marine, Inc. (GMI), performed this work under contract to the Texas Department of Transportation, Environmental Affairs Division (TxDOT ENV) under the Texas Antiquities Permit Number 5879 (Work Authorization [WA] 579 06 SA005; WA 590 08 SA005; CSJ:1222-01-014; Geo-Marine project numbers 22005.00.06 and 22005.00.09). The fieldwork for this project was conducted in advance of the planned widening of FM 10 that was to replace three bridges and a culvert over Murvaul Creek with a larger structure and shift the road approximately 26 meters (m; 85 feet [ft]) to the east. Since the planned improvements of FM 10 would result in the loss of information at the Murvaul Creek site—a site that was recommended eligible for inclusion in the National Register of Historic Places (NRHP) and for designation as a State Antiquities Landmark (SAL; formerly State Archeological Landmark)—the current data recovery investigations were initiated. The data recovery investigations were conducted between February 7, 2011, and April 3, 2011. During this period, the fieldwork was conducted in several stages: site clearing, geophysical survey, 50-x-50-centimeter (cm) excavations, block excavations, and mechanical site scraping. With the exception of the site clearing stage, the results of each of the fieldwork stages are reviewed individually in this report. The investigations resulted in the documentation of numerous features that appeared to have been the remains of a small Middle-to-Late Caddo settlement or farmstead situated on the edge of an interfluve south of the Murvaul Creek floodplain. Additionally, materials pertaining to the Archaic period were documented across the site. Although the site has been intensively studied within the TxDOT right-of-way (ROW), both the current investigations and previous work were limited to the ROW (cf. Cliff and Perttula 2002). Hence, the site is very likely larger than has been adequately documented

GABA A Receptor α1 Subunit Deletion Prevents Developmental Changes of Inhibitory Synaptic Currents in Cerebellar Neurons

Developmental changes in miniature IPSC (mIPSC) kinetics have been demonstrated previously in cerebellar neurons in rodents. We report that these kinetic changes in mice are determined primarily by developmental changes in GAB

Life on Jackson Creek, Smith County, Texas: Archeological Investigations of a 14th Century Caddo Domicile at the Leaning Rock Site (41SM325)

The 14th century Caddo Leaning Rock site was initially discovered in the Fall of 2004. It was located during reconnaissance to search out a location for the survey portion of the Texas Archeologica! Society\u27s Academy IO I held in Tyler in February 2005. This was not a formal survey with transect lines. nor one using regularly spaced shovel tests. but was rather more of a windshield \u27 type survey, consisting of driving across pasture lands looking at gopher mounds and checking fore, evidence of archeological deposits on likely looking landforms. !n this area. landform and soil type seem to be the major determining factors in locating Caddo sites. The sandy soils in the scattered gopher mounds appeared almost white. especially in droughty conditions that prevailed at the time. causing an area with darker mounds of soil to catch my attention. Pocket gophers (G. breviceps) can play havoc with buried archeological deposits but can also be useful in bringing buried soils along with archeological materials to the surface from their underground tunnel system. While this dark area could have been the result of past historic land clearing and burning activities. a closer inspection revealed burned bone. mussel she!L and Caddo sherds mixed in the dark brown soils in the scattered gopher mounds. The next step was to record the site with the State of Texas, obtaining the trinomial 41SM325. It is common practice to also gin: sites informal names and after recording several hundred sites, selecting a name becomes a challenge. One large sandstone slab, pan of the R-horizon that is exposed around the margins of Leaning Rock. was unearthed during prior landclearing activities and pushed up against a lonely pine tree on the northern margins of the site: consequently the nom de plume Leaning Rock

Archeological Investigations at the Santa Maria Creek Site (41CW104) Caldwell County, Texas

The excavations by Atkins at the Santa Maria Creek site (41CW104) described in the following report have succeeded in bringing together a myriad of information regarding aboriginal occupations in eastern Central Texas at the dawn of the Historic period. The analysis of the materials recovered from National Register of Historic Places testing and data recovery has demonstrated that even a site buried in sandy, bioturbated sediments can still significantly add to the archeological record. This becomes even more important for areas such as Caldwell County, Texas, which have witnessed few such investigations. The report utilized a wide array of analytical techniques to unravel the site, including extensive ethnohistorical research, artifact analysis, special studies, and experimental archeology