Clinical significance of BRAF mutations in metastatic melanoma

Forty to eighty percent of melanoma tumors have activating mutations in BRAF although the clinical importance of these mutations is not clear. We previously reported an analysis of BRAF mutations in metastatic melanoma samples from 68 patients. In this study, we correlated patient baseline characteristics, prognostic factors, and/or clinical outcomes with the presence of BRAF mutations. No significant differences were observed in age, gender, location of primary melanoma, stage at the diagnosis, and depth of primary tumor between patients with and without BRAF mutations. Melanomas harboring BRAF mutations were more likely to metastasize to liver (P = 0.02) and to metastasize to multiple organs (P = 0.048). Neither time to progression to stage IV nor overall survival were associated with BRAF mutations. In conclusion, we observed no significant differences in clinical characteristics or outcomes between melanomas with or without BRAF mutations. Although there was an increased frequency of liver metastasis and tendency to metastasize to multiple organs in tumors with BRAF mutations, there was no detectable effect on survival. Future prospective studies should include analysis of whether BRAF mutations in melanoma tumors correlate with an increased tendency to metastasize to liver or to multiple organs

Reprint of The production of urban vacant land: Relational placemaking in Boston, MA neighborhoods

The persistence of vacant land in urban areas exhibits geographic unevenness. While central cities have experienced waves of reinvestment over the past decades, vacant lands often persist in adjacent low-income neighborhoods. Thus a networked local-scale perspective is integral for understanding metropolitan areas. Local scale analyses require an understanding of informal decision-makers and institutions and the ways that they connect more broadly with other actors. Drawing on focus groups with civil society organizations (CSOs) and a neighborhood design/build case study, this paper characterizes on the ground perceptions of and responses to vacant lots in urban neighborhoods in order to provide insight into their analysis and management. The fieldwork extends insights from studies of community gardens to suggest that access to and potential ownership of vacant parcels, in addition to the political economic forces driving land-use change, are critical factors that drive vacant land governance at the neighborhood-scale. Public-civic partnerships in weak market areas have the potential to strengthen this access and ownership in a way that improves vacant lot management. © 2013 Elsevier Ltd

The production of urban vacant land: Relational placemaking in Boston, MA neighborhoods

The persistence of vacant land in urban areas exhibits geographic unevenness. While central cities have experienced waves of reinvestment over the past decades, vacant lands often persist in adjacent low-income neighborhoods. Thus a networked local-scale perspective is integral for understanding metropolitan areas. Local scale analyses require an understanding of informal decision-makers and institutions and the ways that they connect more broadly with other actors. Drawing on focus groups with civil society organizations (CSOs) and a neighborhood design/build case study, this paper characterizes on the ground perceptions of and responses to vacant lots in urban neighborhoods in order to provide insight into their analysis and management. The fieldwork extends insights from studies of community gardens to suggest that access to and potential ownership of vacant parcels, in addition to the political economic forces driving land-use change, are critical factors that drive vacant land governance at the neighborhood-scale. Public-civic partnerships in weak market areas have the potential to strengthen this access and ownership in a way that improves vacant lot management. © 2013 Elsevier Ltd

Social well-being and environmental governance in urban neighbourhoods in Boston, MA

Well-being is an holistic concept that examines individuals in their social, economic, and environmental contexts. In geographical settings where social deprivation is common, civil society organisations (CSOs) represent important actors in environmental governance, which refers to the suite of actions and discourses shaping environmental conditions or resources. These CSOs operate in neoliberal governance frameworks in which they act as formal partners of city governments in providing public services. In this study, we seek to shed light on the role of social interventions and environmental governance in promoting well-being. We examine the social, political, and economic dimensions of environmental governance and social well-being in urban neighbourhoods. We employ a relational place perspective to widen the analytical focus from the immediate boundaries of urban neighbourhoods towards larger social, political, and economic influences. This study describes exploratory focus groups with urban neighbourhood-based CSOs working to improve urban neighbourhoods in Boston, MA in order to identify key social processes that may affect environmental outcomes in urban neighbourhoods. Focus groups examined relationships between neighbourhood well-being and environmental perception, especially of urban land and water resources. We identify four critical factors shaping senses of well-being among neighbourhood residents active in CSOs: stewardship; political and economic control; safety; and familiarity and social control

Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer’s disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid β (Aβ)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. Recognition of Aβ-like peptides and candidalysin promotes fungal clearance from the brain, and disruption of candidalysin recognition through CD11b markedly prolongs C. albicans cerebral mycosis. Thus, C. albicans is cleared from the brain through innate immune mechanisms involving Saps, Aβ, candidalysin, and CD11b

Baseline risk markers and visit-to-visit variability in relation to kidney outcomes - A post-hoc analysis of the PERL study.

BACKGROUND: Baseline risk variables and visit-to-visit variability (VV) of systolic blood pressure (SBP), HbA METHODS: Post-hoc analysis of a double-blind randomized placebo-controlled clinical trial investigating allopurinol\u27s effect on iohexol-derived glomerular filtration rate (iGFR) in type 1 diabetes with elevated UA. Primary outcome was iGFR change over three years. Linear regression with backwards selection of baseline clinical variables was performed to identify an optimized model forecasting iGFR change. Furthermore, VVs of SBP, HbA RESULTS: 404 participants were included in the primary analyses. In the optimized baseline variable model, higher HbA CONCLUSIONS: We identified several risk markers for faster iGFR decline in a high-risk population with type 1 diabetes. While further research is needed, our results indicate possible new and clinically feasible measures to risk stratify for DKD in type 1 diabetes