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Background: Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases. Methods: We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases. Results: At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed in EOPD. Lifetime use of amantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD. Conclusions: Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD. Maladie de Parkinson à début précoce et à début tardif : étude anatomo-clinique. Contexte: Plusieurs études ont comparé la maladie de Parkinson à début précoce (MPDP) et la maladie de Parkinson à début tardif (MPDT), mais la plupart de ces études ne reposent pas sur des cas dont le diagnostic a été confirmé en anatomopathologie. Méthode : Nous avons comparé les profiles cliniques et pharmacologiques, le délai pour atteindre le stade 3 irréversible à l’échelle de Hoehn and Yahr (H&Y) et les complications motrices du traitement par la lévodopa chez des cas de MPDP et de MPDT confirmés à l’autopsie. Résultats : Au moment de la première consultation, les cas de MPDP étaient plus jeunes, mais leur maladie durait depuis plus longtemps et ils sont morts plus jeunes (p<0,0001). L’utilisation de médicaments antiparkinsoniens, incluant la lévodopa, était significativement plus tardive chez les cas de MPDP. L’utilisation de l’amantadine au cours de la vie (p<0,05) et d’agonistes de la dopamine (p<0,01) étaient plus élevée chez les patients atteints de MPDP. Bien que la prise de lévodopa était similaire dans les deux groupes, la lévodopa avait été utilisée pendant plus longtemps par les patients atteints de MPDP (p<0,0001). L’incidence cumulative de dyskinésies était plus élevée chez les cas de MPDP (p<0,01), ainsi que les signes de l’épuisement de l’effet thérapeutique en fin de dose (p<0,01) et les fluctuations de la motricité, phénomène « on-off », (p<0,01). Cependant, le temps écoulé avant le début des dyskinésies était similaire dans les deux groupes. Le seuil de l’épuisement de l’effet thérapeutique était beaucoup plus long chez les patients atteints de la MPDP (p<0,01). Le profile du stade de H&Y à la première consultation était similaire dans les deux groupes. Le temps écoulé depuis le début de la maladie jusqu’au stade 3 irréversible de H&Y était significativement plus long chez les patients atteints de MPDP. Conclusions : Nos observations indiquent que la progression de la MP est plus lente chez les patients atteints de la MPDP ce qui suggère que l’intervalle préclinique est plus long chez ce groupe de patients. Ces observations peuvent être utilisées pour sélectionner les patients à inclure dans les essais thérapeutiques et les études sur la pathogenèse de la MP.

The genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP). In stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes. Individuals were included if they had clinical data available on sex, age at motor symptom onset, disease duration (from motor symptom onset to death or to the date of censoring, Dec 1, 2019, if individuals were alive), and PSP phenotype (with reference to the 2017 Movement Disorder Society criteria). Genotype data were used to do a survival GWAS using a Cox proportional hazards model. In stage two, data from additional individuals from the Mayo Clinic brain bank, which were obtained after the 2011 PSP GWAS, were used for a pooled analysis. We assessed the expression quantitative trait loci (eQTL) profile of variants that passed genome-wide significance in our GWAS using the Functional Mapping and Annotation of GWAS platform, and did colocalisation analyses using the eQTLGen and PsychENCODE datasets. Data were collected and analysed between Aug 1, 2016, and Feb 1, 2020. Data were available for 1001 individuals of white European ancestry with PSP in stage one. We found a genome-wide significant association with survival at chromosome 12 (lead single nucleotide polymorphism rs2242367, p=7·5 × 10−10, hazard ratio 1·42 [95% CI 1·22–1·67]). rs2242367 was associated with survival in the individuals added in stage two (n=238; p=0·049, 1·22 [1·00–1·48]) and in the pooled analysis of both stages (n=1239; p=1·3 × 10−10, 1·37 [1·25–1·51]). An eQTL database screen revealed that rs2242367 is associated with increased expression of LRRK2 and two long intergenic non-coding RNAs (lncRNAs), LINC02555 and AC079630.4, in whole blood. Although we did not detect a colocalisation signal for LRRK2, analysis of the PSP survival signal and eQTLs for LINC02555 in the eQTLGen blood dataset revealed a posterior probability of hypothesis 4 of 0·77, suggesting colocalisation due to a single shared causal variant. Genetic variation at the LRRK2 locus was associated with survival in PSP. The mechanism of this association might be through a lncRNA-regulated effect on LRRK2 expression because LINC02555 has previously been shown to regulate LRRK2 expression. LRRK2 has been associated with sporadic and familial forms of Parkinson's disease, and our finding suggests a genetic overlap with PSP. Further functional studies will be important to assess the potential of LRRK2 modulation as a disease-modifying therapy for PSP and related tauopathies. PSP Association, CBD Solutions, Medical Research Council (UK).

Framed against educational policies that conceptualize teacher understanding as best advanced by quantitative measures and standardization, this study explores the lived experiences of three reflective teachers to inquire how practicing teachers understand their students’ learning. This phenomenological study asks: How do three secondary school English teachers use reflection to understand their students’ learning? This guiding question is supported by three subsidiary questions: 1) How do these teachers describe their students’ learning? 2) How do these teachers describe their understanding of students’ learning? 3) How do teachers perceive reflection has shaped their understanding of students’ learning? This study is theoretically situated in Gadamer’s theory of hermeneutic as it examines the ways in which the teachers interpret their students’ learning. Data collection followed Seidman’s (2013) phenomenological interview protocol as well as Nakkula and Ravitch’s (1998) memoing process. Data analysis began with an application of The Listening Guide method (Gilligan, Spenser, Weinberg, & Bertsch, 2003) and then proceeded to thematic analysis (Bernarnd & Ryan, 2010). The data analysis process surfaced seven themes related to teachers’ understanding of student learning as well as a rich context for understanding those themes. These themes support the theoretical framework described in Gadamer’s hermeneutics. They also reveal the complexity of student learning and the complexity of analysis and interpretation involved in understanding this phenomenon.

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.

Although the idea of environmentally conscious building is as old as architecture itself, people tend to associate the concept with a lifestyle radically different from the mainstream. Green building is, however, a growing trend and does not have to mean living in a cave or building with hay bales. Even large-scale developers of residential homes are leaning toward more environmentally sound habitats with Energy Star-qualified homes that are at least 30% more energy efficient than homes built to the 1993 national Model Energy Code. The idea is that anyone can contribute to conserving natural resources and promoting healthier living spaces because even a series of small efforts will add up to significant improvement.

Ferguson-Dietz comments on meeting the family of a boy who sustained massive head injuries as a result of a car-bike accident. The boy's family agreed to donate his organs when he was clinically brain-dead.

\"But don't say, 'I don't want it around here.' ... NIMBYism will no longer prevail,\" he added, using the acronym for \"not in my backyard.\" \"We're not going away - residents won't lay down,\" said local activist John Laforet, adding opponents are already fired up \"because of the way we've been treated by the government. I expect residents will only get noisier.\" \"If it's such a great idea, why not do an environmental assessment and prove there are no health risks?\" said an angry Laforet. \"Why do we need to be bludgeoned by legislation if the facts are on their (the government's) side?\"

The purpose of this study was to define empirically, rough latent partition analysis, the basic research needs for community education. A classification system or a rankinc community education research needs was seen as pre-Liminary to the development of a national cooperative research strategy. VIENA systematic attempt was made to categorize and analyze statements on needed research is specified by regional community educators. Defined problem categorizations were examined for their effects by Latent partition analysis after a free sort was completed by the directors of the Regional Centers for the Development of Community Education.The analysis of results was performed in two successive chases. Phase One delineated the population aspects and the format of the sorting operations utilized. Phase wo specifically described and interpreted the application of ne Latent partition analysis to the previously identified parameters.The substance and structure of the sorters' categorizations were specified in terms of two computational outputs: a latent category membership matrix which identified the statement item composition on the latent categories and reflected the common perceptions of the sorters; and 2) a confusion matrix omega which specified the extent to which pairs of statements were related to eachThis study suggested a taxonomy of seven research caseories composed of constellations and clusters of related Latent categories.