53 research outputs found

    Remnants

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    Remnants are pieces that were once part of a greater entity, an entity that has since been removed. A remnant needn‚Äôt be viewed as ‚Äúgood‚ÄĚ or ‚Äúbad,‚ÄĚ but just ‚Äúas is‚ÄĚ ‚Äď the state of what remains, of what you physically see right in front of you. The idea of remnants and what they represent began to take shape for me over the course of this photographic project. Feelings I had not previously acknowledged found their space to come forward, embodying themselves in my photographs. As a reticent person, familiar with keeping feelings hidden, I discovered that my photos could serve as a doorway to access concealed experiences and feelings. Looking closely at the images, I began to see how they presented to me my own deep resonance with all that is left behind. Through these images I learned that I too am a remnant, a trace of something larger that is no longer in evidence. I was found in the early morning in Wuhan, China, having been placed in the side of an old stone wall where a stone was missing. The police found me. There was no information other than what was visible: a girl toddler with bilateral clubfeet and a ball of yarn. I was given a name, date of birth, and estimated to be about 2-years-old. At the time, I was one of many abandoned daughters, a noticeable result of China‚Äôs one child policy. I was lucky to be adopted by a loving family and to receive surgery to correct my feet. Because I was raised in such a positive environment, there was no need to dwell on my early start in life. I knew my story, but never gave it special attention, until my images began to embody the dynamics that were essential to my start in life. Through these photos, I have unearthed aspects of myself that I could claim and work with. Through them, I have taken the time to honor the remnants I know about my early life, discovering parallels with many things in the world. Following my eye led me to various ‚Äúleftovers‚ÄĚ in different towns around me. My desire intensified to photograph these remnants, pretty or not. I approached these scenes knowing each one has a special story belonging to it. While some of this story is not accessible, bits and pieces of it are. Each remnant is evidence of and a clue about the greater thing of which it was a part. States of production and consumption can turn into excess, depending on the world around us and our definitions. These ‚Äúexcesses‚ÄĚ-- buildings, possessions, or children‚ÄĒcan become inconvenient, difficult, or impossible to care for. Spending days photographing in the little towns around me, I found things and places that someone was no longer taking responsibility for, and, as a result, often left behind to fall into disrepair. Plentiful moments and times of decline are all part of life. Through this project I was able to let periods of decline speak for themselves, showing how light shines and interacts with their remnants, reminding you, the viewer, of things that can be found on the land, down a lane, and beside a wall. When we witness a remnant, we retrieve the past for a moment. We see the strength and the vulnerability of the trace, allowing its past to be heard, and its future possibilities to be hinted at

    Paths Forward to Salary Parity for New York: National Models for Equity in Early Childhood Education Compensation

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    Pay parity for early childhood educators is critical to reducing turnover, improving job quality, and achieving an equitable child care system. This publication explores compensation reform nationwide and offers ideas for local and state financing options to better support the early childhood workforce and New York families.https://educate.bankstreet.edu/bsec/1013/thumbnail.jp

    Cultivating Powerful Mentorship in Educator Credential Programs

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    This publication explores Bank Street’s approach to mentorship and lessons learned through implementation and features an interview with three Graduate School faculty members: Valentine Burr, Chair of the Department of Teaching and Learning; Jessica Wontropski, D13 Residency Program Administrator and Director of General and Special Education Programs; and Cristian Solorza, Director of the TESOL and Bilingual/Dual Language Programs.https://educate.bankstreet.edu/bsec/1010/thumbnail.jp

    A Snapshot of ECE Apprenticeship Programs

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    This publication offers a closer look at the key features of existing apprenticeship programs across the United States‚ÄĒsuch as the diversity and range of approaches to credentials, partnership models, funding, and how programs deliver quality mentoring and/or coaching support‚ÄĒto reimagine how program quality can be strengthened to deepen learning for participants.https://educate.bankstreet.edu/bsec/1012/thumbnail.jp

    Inclusion of Adolescents in STI/HIV Biomedical Prevention Trials: Autonomy, Decision Making, and Parental Involvement

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    In order to develop new methods for prevention and treatment of sexually transmitted infection (STI) and human immunodeficiency virus (HIV), clinical trials must be conducted in relevant populations. In the U.S., half of all STI incident infections are among 15-24 year olds (Satterwhite et al., 2013), making healthy adolescents a highly relevant population. The inclusion of adolescents in STD/HIV prevention research is critical for developing appropriate strategies to promote adolescent sexual health. Results from adult studies may not generalize to adolescents, given their biological and psychosocial developmental status (Hwang et al., 2009). In order to understand the extent to which these differences are applicable to safety, efficacy, and acceptability, the products must be tested in minors. Enrolling adolescents who have not reached the legal age of majority in sexual health research, though, poses legal and ethical challenges. Investigators have been described as facing moral conflict between their responsibility to protect the scientific rigor of the study and the well-being of the participants (Merritt, 2005). Institutional Review Boards (IRBs) must balance the interests of minors, their parents, and the institution (Knopf et al., 2016). Data suggest that adolescents are under-represented in biomedical trials of HIV and STD prevention (Tolley et al., 2014; Hoffman et al., 2016). We propose that the inclusion of these adolescents in sexual health research is not only ethically permissible but is ethically required

    Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

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    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

    The evolution of lung cancer and impact of subclonal selection in TRACERx

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    Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1‚ÄČyear after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

    The evolution of non-small cell lung cancer metastases in TRACERx

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    Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8‚ÄČmm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

    Genomic‚Äďtranscriptomic evolution in lung cancer and metastasis

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    Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic‚Äďtranscriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary‚Äďmetastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

    Antibodies against endogenous retroviruses promote lung cancer immunotherapy

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    B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response
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