Institutional Map and Atlas Collecting in Eighteenth-Century America

Many colonists brought books, atlases, and maps to America; some assembled personal libraries that would ultimately benefit public institutions. The establishment of academic and subscription libraries initiated institutional collecting. Printed catalogues and other records document the cartographic collections formed in early America. This essay surveys those collection

Phonological and visual processing deficits can dissociate in developmental dyslexia: Evidence from two case studies

International audienceThe present study describes two French teenagers with developmental reading and writing impairments whose performance was compared to that of chronological age and reading age matched non-dyslexic participants. Laurent conforms to the pattern of phonological dyslexia: he exhibits a poor performance in pseudo-word reading and spelling, produces phonologically inaccurate misspellings but reads most exception words accurately. Nicolas, in contrast, is poor in reading and spelling of exception words but is quite good at pseudo-word spelling, suggesting that he suffers from surface dyslexia and dysgraphia. The two participants were submitted to an extensive battery of metaphonological tasks and to two visual attentional tasks. Laurent demonstrated poor phonemic awareness skills but good visual processing abilities, while Nicolas showed the reverse pattern with severe difficulties in the visual attentional tasks but good phonemic awareness. The present results suggest that a visual attentional disorder might be found to be associated with the pattern of developmental surface dyslexia. The present findings further show that phonological and visual processing deficits can dissociate in developmental dyslexia

Predicting Symptoms of Depression and Anxiety Using Smartphone and Wearable Data

Background: Depression and anxiety are leading causes of disability worldwide but often remain undetected and untreated. Smartphone and wearable devices may offer a unique source of data to detect moment by moment changes in risk factors associated with mental disorders that overcome many of the limitations of traditional screening methods. Objective: The current study aimed to explore the extent to which data from smartphone and wearable devices could predict symptoms of depression and anxiety. Methods: A total of N = 60 adults (ages 24-68) who owned an Apple iPhone and Oura Ring were recruited online over a 2-week period. At the beginning of the study, participants installed the Delphi data acquisition app on their smartphone. The app continuously monitored participants' location (using GPS) and smartphone usage behavior (total usage time and frequency of use). The Oura Ring provided measures related to activity (step count and metabolic equivalent for task), sleep (total sleep time, sleep onset latency, wake after sleep onset and time in bed) and heart rate variability (HRV). In addition, participants were prompted to report their daily mood (valence and arousal). Participants completed self-reported assessments of depression, anxiety and stress (DASS-21) at baseline, midpoint and the end of the study. Results: Multilevel models demonstrated a significant negative association between the variability of locations visited and symptoms of depression (beta = -0.21, p = 0.037) and significant positive associations between total sleep time and depression (beta = 0.24, p = 0.023), time in bed and depression (beta = 0.26, p = 0.020), wake after sleep onset and anxiety (beta = 0.23, p = 0.035) and HRV and anxiety (beta = 0.26, p = 0.035). A combined model of smartphone and wearable features and self-reported mood provided the strongest prediction of depression. Conclusion: The current findings demonstrate that wearable devices may provide valuable sources of data in predicting symptoms of depression and anxiety, most notably data related to common measures of sleep.Peer reviewe

Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer

Tumor–stroma interactions contribute to tumorigenesis. Tumor cells can educate the stroma at primary and distant sites to facilitate the recruitment of heterogeneous populations of immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs). MDSCs suppress T cell responses and promote tumor proliferation. One outstanding question is how the local and distant stroma modulate MDSCs during tumor progression. Down-regulation of β-catenin is critical for MDSC accumulation and immune suppressive functions in mice and humans. Here, we demonstrate that stroma-derived Dickkopf-1 (Dkk1) targets β-catenin in MDSCs, thus exerting immune suppressive effects during tumor progression. Mice bearing extraskeletal tumors show significantly elevated levels of Dkk1 in bone microenvironment relative to tumor site. Strikingly, Dkk1 neutralization decreases tumor growth and MDSC numbers by rescuing β-catenin in these cells and restores T cell recruitment at the tumor site. Recombinant Dkk1 suppresses β-catenin target genes in MDSCs from mice and humans and anti-Dkk1 loses its antitumor effects in mice lacking β-catenin in myeloid cells or after depletion of MDSCs, demonstrating that Dkk1 directly targets MDSCs. Furthermore, we find a correlation between CD15(+) myeloid cells and Dkk1 in pancreatic cancer patients. We establish a novel immunomodulatory role for Dkk1 in regulating tumor-induced immune suppression via targeting β-catenin in MDSCs

AdvManuNet: a networking project on metrology for advanced manufacturing

The networking project AdvManuNet has been started recently to accelerate the process of establishing an European Metrology Network (EMN) on Advanced Manufacturing. EMNs are intended by EURAMET, the association of metrology institutes in Europe, to provide a sustainable structure for ongoing stakeholder interaction in different thematic areas. Advanced manufacturing has been identified by the European Commission (EC) as one of six Key Enabling Technologies (KETs) with applications in multiple industries. Various EURAMET projects have partly addressed metrology needs for advanced manufacturing. However, a high-level coordination of the metrology community is currently absent and limits the impact of metrology developments on advanced manufacturing. AdvManuNet will address these limits by establishing a single hub for stakeholder consultation, a knowledge base on research results, and a strategic agenda for research and training to push forward advanced manufacturing and related KETs and strengthen Europe’s position in advanced manufacturing via the EMN

Spatial-temporal variability of in situ cyanobacteria vertical structure in Western Lake Erie: Implications for remote sensing observations

Remote sensing has provided expanded temporal and spatial range to the study of harmful algal blooms (cyanoHABs) in western Lake Erie, allowing for a greater understanding of bloom dynamics than is possible through in situ sampling. However, satellites are limited in their ability to specifically target cyanobacteria and can only observe the water within the first optical depth. This limits the ability of remote sensing to make conclusions about full water column cyanoHAB biomass if cyanobacteria are vertically stratified. FluoroProbe data were collected at nine stations across western Lake Erie in 2015 and 2016 and analyzed to characterize spatio-temporal variability in cyanobacteria vertical structure. Cyanobacteria were generally homogenously distributed during the growing season except under certain conditions. As water depth increased and high surface layer concentrations were observed, cyanobacteria were found to be more vertically stratified and the assumption of homogeneity was less supported. Cyanobacteria vertical distribution was related to wind speed and wave height, with increased stratification at low wind speeds (bathymetry and environmental conditions could lead to improved biomass estimates. Additionally, cyanobacteria contributions to total chlorophyll-a were shown to change throughout the season and across depth, suggesting the need for remote sensing algorithms to specifically identify cyanobacteria

Seasonal total methane depletion in limestone caves

Methane concentration in caves is commonly much lower than the external atmosphere, yet the cave CH4 depletion causal mechanism is contested and dynamic links to external diurnal and seasonal temperature cycles unknown. Here, we report a continuous 3-year record of cave methane and other trace gases in Jenolan Caves, Australia which shows a seasonal cycle of extreme CH4 depletion, from ambient ∼1,775 ppb to near zero during summer and to ∼800 ppb in winter. Methanotrophic bacteria, some newly-discovered, rapidly consume methane on cave surfaces and in external karst soils with lifetimes in the cave of a few hours. Extreme bacterial selection due to the absence of alternate carbon sources for growth in the cave environment has resulted in an extremely high proportion 2-12% of methanotrophs in the total bacteria present. Unexpected seasonal bias in our cave CH4 depletion record is explained by a three-step process involving methanotrophy in aerobic karst soil above the cave, summer transport of soil-gas into the cave through epikarst, followed by further cave CH4 depletion. Disentangling cause and effect of cave gas variations by tracing sources and sinks has identified seasonal speleothem growth bias, with implied palaeo-climate record bias

A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging

The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously quantify in situ expression of 36 proteins covering identity, function, and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and enriched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology

A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging

The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously quantify in situ expression of 36 proteins covering identity, function, and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and enriched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology

Histological and Somatic Mutational Profiles of Mismatch Repair Deficient Endometrial Tumours of Different Aetiologies

SIMPLE SUMMARY: Endometrial cancers can arise due to an error in DNA mending known as mismatch repair. This can happen because of an error in the cancer itself (somatic) or due to an inherited error (Lynch syndrome). Treatment trials have considered endometrial cancers caused by either of these errors as identical. As it is easier to recruit people with Lynch syndrome, they may be overrepresented in this group despite being less numerous in clinical practice. This would not be an issue if somatic and Lynch syndrome-related endometrial cancers were similar at a molecular level. The data presented herein, however, indicates that these two routes to mismatch repair, although sharing many similarities, lead to endometrial cancers with distinct molecular and pathological features. This may explain the range of outcomes observed in clinical trials of endometrial cancers with mismatch repair errors. ABSTRACT: Background: Mismatch repair deficient (MMRd) tumours may arise from somatic events acquired during carcinogenesis or in the context of Lynch syndrome (LS), an inherited cancer predisposition condition caused by germline MMR pathogenic variants. Our aim was to explore whether sporadic and hereditary MMRd endometrial cancers (EC) display distinctive tumour biology. Methods: Clinically annotated LS-EC were collected. Histological slide review was performed centrally by two specialist gynaecological pathologists. Mutational analysis was by a bespoke 75- gene next-generation sequencing panel. Comparisons were made with sporadic MMRd EC. Multiple correspondence analysis was used to explore similarities and differences between the cohorts. Results: After exclusions, 135 LS-EC underwent independent histological review, and 64 underwent mutational analysis. Comparisons were made with 59 sporadic MMRd EC. Most tumours were of endometrioid histological subtype (92% LS-EC and 100% sporadic MMRd EC, respectively, p = NS). Sporadic MMRd tumours had significantly fewer tumour infiltrating lymphocytes (p ≤ 0.0001) and showed more squamous/mucinous differentiation than LS-EC (p = 0.04/p = 0.05). PTEN mutations were found in 88% sporadic MMRd and 61% LS-EC, respectively (p < 0.001). Sporadic MMRd tumours had significantly more mutations in PDGFRA, ALK, IDH1, CARD11, CIC, MED12, CCND1, PTPN11, RB1 and KRAS, while LS-EC showed more mutations affecting SMAD4 and ARAF. LS-EC showed a propensity for TGF-β signalling disruption. Cluster analysis found that wild type PTEN associates predominantly with LS-EC, whilst co-occurring mutations in PTEN, PIK3CA and KRAS predict sporadic MMRd EC. Conclusions: Whilst MMRd EC of hereditary and sporadic aetiology may be difficult to distinguish by histology alone, differences in infiltrating immune cell counts and mutational profile may predict heterogenous responses to novel targeted therapies and warrant further study