217 research outputs found

    Case Comments

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    Histopathologic findings in malignant peripheral nerve sheath tumor predict response to radiotherapy and overall survival

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    BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive and poorly understood malignant neoplasm. Even in the setting of multimodal therapy, the clinical course of MPNST is frequently marked by metastatic conversion and poor overall prognosis, with optimal treatment paradigms for this rare tumor unknown. METHODS: We reviewed the medical records and histopathology of 54 consecutive patients who were treated at University of California San Francisco between 1990 and 2018. RESULTS: Our cohort consisted of 24 male and 30 female patients (median age 38 years). Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) sarcoma grading criteria segregated patients into groups with differences in overall survival (OS) ( CONCLUSIONS: Our results lend support to the FNCLCC sarcoma grading criteria as a prognostic scheme for MPNST, although few cases of grade 1 were included. Further, we identify increased Ki-67 labeling as a strong predictor of poor OS from MPNST. Finally, we identify a subset of MPNSTs with a predictive immunohistochemical profile that has improved local control with adjuvant radiotherapy. These data provide insights into the grading and therapy for patients with MPNST, although further studies are needed for independent validation

    Spatiotemporal Patterns in Nest Box Occupancy by Tree Swallows Across North America

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    Data from the North American Breeding Bird Survey (BBS) suggest that populations of aerial insectivorous birds are declining, particularly in northeastern regions of the continent, and particularly since the mid-1980s. Species that use nest boxes, such as Tree Swallows (Tachycineta bicolor), may provide researchers with large data sets that better reveal finer-scale geographical patterns in population trends. We analyzed trends in occupancy rates for ca. 40,000 Tree Swallow nest-box-years from 16 sites across North America. The earliest site has been studied intensively since 1969 and the latest site since 2004. Nest box occupancy rates declined significantly at five of six (83%) sites east of -78° W longitude, whereas occupancy rates increased significantly at four of ten sites (40%) west of -78° W longitude. Decreasing box occupancy trends from the northeast were broadly consistent with aspects of a previous analysis of BBS data for Tree Swallows, but our finding of instances of increases in other parts of the continent are novel. Several questions remain, particularly with respect to causes of these broad-scale geographic changes in population densities of Tree Swallows. The broad geographic patterns are consistent with a hypothesis of widespread changes in climate on wintering, migratory, or breeding areas that in turn may differentially affect populations of aerial insects, but other explanations are possible. It is also unclear whether these changes in occupancy rates reflect an increase or decrease in overall populations of Tree Swallows. Regardless, important conservation steps will be to unravel causes of changing populations of aerial insectivores in North America

    Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas

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    Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications

    Perceptions of the neighbourhood environment and self rated health: a multilevel analysis of the Caerphilly Health and Social Needs Study

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    Background In this study we examined whether (1) the neighbourhood aspects of access to amenities, neighbourhood quality, neighbourhood disorder, and neighbourhood social cohesion are associated with people's self rated health, (2) these health effects reflect differences in socio-demographic composition and/or neighbourhood deprivation, and (3) the associations with the different aspects of the neighbourhood environment vary between men and women. Methods Data from the cross-sectional Caerphilly Health and Social Needs Survey were analysed using multilevel modelling, with individuals nested within enumeration districts. In this study we used the responses of people under 75 years of age (n = 10,892). The response rate of this subgroup was 62.3%. All individual responses were geo-referenced to the 325 census enumeration districts of Caerphilly county borough. Results The neighbourhood attributes of poor access to amenities, poor neighbourhood quality, neighbourhood disorder, lack of social cohesion, and neighbourhood deprivation were associated with the reporting of poor health. These effects were attenuated when controlling for individual and collective socio-economic status. Lack of social cohesion significantly increased the odds of women reporting poor health, but did not increase the odds of men reporting poor health. In contrast, unemployment significantly affected men's health, but not women's health. Conclusion This study shows that different aspects of the neighbourhood environment are associated with people's self rated health, which may partly reflect the health impacts of neighbourhood socio-economic status. The findings further suggest that the social environment is more important for women's health, but that individual socio-economic status is more important for men's health
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