Outcomes of a radiation sparing approach in medulloblastoma by subgroup in young children: an institutional review.

OBJECTIVE To describe disease outcomes including overall survival and relapse patterns by subgroup in young pediatric patients treated for medulloblastoma with a radiation-sparing approach. METHODS Retrospective analysis of clinical outcomes includes treatment, relapse, and salvage therapy and late effects in children treated for medulloblastoma with a radiation-sparing approach at British Columbia Children's Hospital (BCCH) between 2000 and 2020. RESULTS There were 30 patients (median age 2.8 years, 60% male) treated for medulloblastoma with a radiation-sparing approach at BCCH. Subgroups included Sonic Hedgehog (SHH) (n = 14), group 3 (n = 7), group 4 (n = 6), and indeterminate status (n = 3). Three- and 5-year event-free survival (EFS) were 49.0% (30.2-65.4%) and 42.0% (24.2-58.9%) and overall survival (OS) 66.0% (95% CI 46.0-80.1%) and 62.5% (95% CI 42.5 and 77.2%), respectively, with a median follow-up of 9.5 years. Relapse occurred in 12/25 patients following a complete response, of whom six (group 4: n = 4; group 3: n = 1; unknown: n = 1) were successfully salvaged with craniospinal axis (CSA) RT and remain alive at a median follow-up of 7 years. Disease/treatment-related morbidity included endocrinopathies (n = 8), hearing loss n = 16), and neurocognitive abnormalities (n = 9). CONCLUSIONS This radiation sparing treatment approach for young patients with medulloblastoma resulted in a durable cure in most patients with SHH subgroup medulloblastoma. In those patients with groups 3 and 4 medulloblastoma, relapse rates were high; however, most group 4 patients were salvaged with RT

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Visions for nature and nature’s contributions to people for the 21st century : Report from an IPBES visioning workshop held on 4-8 September 2017 in Auckland, New Zealand

Existing scenarios of biodiversity and ecosystem services (BES) have important limitations and gaps that constrain their usefulness for the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES). Specifically, they fail to incorporate policy objectives related to nature conservation and social-ecological feedbacks, they do not address the linkages between biodiversity and ecosystem services, and they are typically relevant at only a particular spatial scale. In addition, nature and its benefits are treated as the consequence of human decisions, but are not at the centre of the analysis. To address these issues, the IPBES Scenarios and Models Expert Group initiated the development of a set of Multiscale Scenarios for Nature Futures based on positive visions for human relationships with nature.The first step of this process was a visioning workshop with stakeholders and experts on 4-8 September 2017 in Auckland, New Zealand. A total of 73 participants from inter-governmental organisations, national government organisations, non-governmental organisations, academia and the private sector, from 31 countries, and with a range of sectoral expertise on biodiversity topics, from urban development to agriculture to fisheries, worked together in a visioning exercise. This report documents the results from this visioning workshop to inform further stakeholder consultation and the development of the associated multiscale scenarios by modelers and experts. This creative visioning exercise was carried out in four steps based on a suite of participatory methods that were used to develop visions of alternative futures. First the participants identified important themes to develop the visions. Next, thematic groups identified the main trends for BES in each theme and a set of “Seeds” of emerging initiatives leading to positive futures for our relationship with nature. Implications of what would happen across a range of sectors were identified for each seed. Then a pathway analysis of how the current regime in each theme may be transformed into the future desirable regime was carriedout. Narratives were then built for the visions emerging from each group. Finally, commonalities of visions across the groups were identified, and the regional relevance of each vision for different parts of the world was assessed

Visions for nature and nature’s contributions to people for the 21st century : Report from an IPBES visioning workshop held on 4-8 September 2017 in Auckland, New Zealand

Existing scenarios of biodiversity and ecosystem services (BES) have important limitations and gaps that constrain their usefulness for the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES). Specifically, they fail to incorporate policy objectives related to nature conservation and social-ecological feedbacks, they do not address the linkages between biodiversity and ecosystem services, and they are typically relevant at only a particular spatial scale. In addition, nature and its benefits are treated as the consequence of human decisions, but are not at the centre of the analysis. To address these issues, the IPBES Scenarios and Models Expert Group initiated the development of a set of Multiscale Scenarios for Nature Futures based on positive visions for human relationships with nature.The first step of this process was a visioning workshop with stakeholders and experts on 4-8 September 2017 in Auckland, New Zealand. A total of 73 participants from inter-governmental organisations, national government organisations, non-governmental organisations, academia and the private sector, from 31 countries, and with a range of sectoral expertise on biodiversity topics, from urban development to agriculture to fisheries, worked together in a visioning exercise. This report documents the results from this visioning workshop to inform further stakeholder consultation and the development of the associated multiscale scenarios by modelers and experts. This creative visioning exercise was carried out in four steps based on a suite of participatory methods that were used to develop visions of alternative futures. First the participants identified important themes to develop the visions. Next, thematic groups identified the main trends for BES in each theme and a set of “Seeds” of emerging initiatives leading to positive futures for our relationship with nature. Implications of what would happen across a range of sectors were identified for each seed. Then a pathway analysis of how the current regime in each theme may be transformed into the future desirable regime was carriedout. Narratives were then built for the visions emerging from each group. Finally, commonalities of visions across the groups were identified, and the regional relevance of each vision for different parts of the world was assessed

Rapid control of male typical behaviors by brain-derived estrogens

Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field