(1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.

Massively parallel sequencing has revealed many de novo mutations in the etiology of developmental and epileptic encephalopathies (EEs), highlighting their genetic heterogeneity. Additional candidate genes have been prioritized in silico by their co-expression in the brain. Here, we evaluate rare coding variability in 20 candidates nominated with the use of a reference gene set of 51 established EE-associated genes. Variants within the 20 candidate genes were extracted from exome-sequencing data of 42 subjects with EE and no previous genetic diagnosis. We identified 7 rare non-synonymous variants in 7 of 20 genes and performed Sanger sequence validation in affected probands and parental samples. De novo variants were found only in SLC1A2 (aka EAAT2 or GLT1) (c.244G>A [p.Gly82Arg]) and YWHAG (aka 14-3-3g) (c.394C>T [p.Arg132Cys]), highlighting the potential cause of EE in 5% (2/42) of subjects. Seven additional subjects with de novo variants in SLC1A2 (n ¼ 1) and YWHAG (n ¼ 6) were subsequently identified through online tools. We identified a highly significant enrichment of de novo variants in YWHAG, establishing their role in early-onset epilepsy, and we provide additional support for the prior assignment of SLC1A2. Hence, in silico modeling of brain co-expression is an efficient method for nominating EE-associated genes to further elucidate the disorder's etiology and genotype-phenotype correlations.

The Canada Excellence Research Chairs (CERC), Leading Edge Endowment Fund (LEEF), Don Rix BC Leadership Chair in Genetic Medicine, National Institute on Aging, National Institute of Neurological Disorders and Stroke, the Michael J Fox Foundation, Mayo Foundation, the Roger de Spoelberch Foundation, and GlaxoSmithKline.

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). Research to date has demonstrated that men have prostate-specific and general health needs across the entire illness trajectory, and a growing body of empirical evidence indicates that psychosocial support and health and illness information are integral to the well-being of men who have prostate cancer. Increasingly, community-based support services such as prostate cancer support groups (PCSGs) have emerged as resources for men and their families to deal with the challenges of living with prostate cancer.PCSGs are relatively recent phenomena in several countries and are more common in North America than the rest of the world (Coreil & Behal, 1999;Visser, Riemens, Van der Jagt, Vingerhoets, & Voerman, 2001). Canadian-based PCSGs began in the early 1990s in urban centers, and two British Columbian (BC; Vancouver and Victoria) groups were among the first to operate. Since that time, the number of PCSGs has grown to 31 in BC and 118 P rostate cancer is the most common malignancy among men in Western society (Schiff & Mulhall, 2005) and results in diverse psychosocial and health issues for survivors and their families. There is evidence about the associated challenges and effects of prostate cancer and its treatments on quality of life (Kirschner-Hermanns & Jakse, 2002;Palmer, Fogarty, Somerfield, & Powel, 2003) Many prostate cancer support groups (PCSGs) have formed in North America during the past decade, yet their operation or factors influencing sustainability are poorly understood. This article reports micro (intragroup), meso (intergroup), and macro (group/structure) analyses drawn from the fieldwork and participant observations conducted for an ethnographic study of PCSGs based in British Columbia, Canada. The findings indicate that effective group leadership is integral to group sustainability and the recruitment and retention of attendees. At the meso level, intergroup connections and communication were often informal; however, the primary purpose of all the PCSGs was to provide information and support to men and their families. Many PCSGs were uncertain how formal associations with cancer fund-raising societies would influence group effectiveness. Macro issues such as prostate cancer activism resided with individual group "champions" through activities coordinated by provincial and national PCSG organizations. However, activism did not guarantee group sustainability. The study findings reveal why some groups flourish while others appear untenable, and form the basis for discussion about how PCSG sustainability might be best achieved.