40 research outputs found

    A compilation, classification, and comparison of lists of spontaneous speaking vocabulary of children in kindergarten, Grade I, Grade II, and Grade III

    Full text link
    Thesis (Ed.M.)--Boston UniversityLanguage development has been studied for many years. The beginning vocabularies are easy to count ana record. As tne child grows and moves about, his speaking vocabulary increases very rapidly. Some estimates suggest that a minimum speaking vocabulary at six years would include three thousand words. New words have come into children's speaking vocabularies as a result of modern technology since World War II. Lists of spontaneous vocabulary furnish material for teachers and text book writers. The purpose of this study is to analyze two lists recorded in 1954 and 1955. An attempt has been made to classify the new list. The lists were compared with three existing lists, Rinsland, International Kindergarten Union and Gates

    Internet & human rights in foreign policy: comparing narratives in the US and EU internet governance agenda

    Get PDF
    The intricate relationship between Internet, on the one hand, and Human Rights, on the other, is increasingly becoming relevant in foreign policy. Discussions are animated by different actors, providing contributions from multiple perspectives, yet the debate on Internet and Human Rights is still fragmented and has not evolved into a unified agenda. This paper explores this on-going debate over competing perspectives, and frames the current discussion on Internet and Human Rights in foreign policy by providing an overview of the key governmental conferences addressing the Internet and Human rights over the first 3 years (2010-2012) since the beginning of the debate. It then proceeds to analyze key narratives, stakeholders and agendas within these conferences, as well as questions of power and legitimacy. Finally, it argues that the conferences draw from a common discourse and language, but are also representing divergent agendas between stakeholders and states

    Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

    Get PDF
    CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

    Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

    Get PDF
    Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

    Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

    Get PDF
    The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

    Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

    Get PDF

    Care partner–assisted intervention to improve oral health for older adults with cognitive impairment: A feasibility study

    No full text
    Background and objectivesOlder adults with cognitive impairment often experience poor oral health outcomes due to inadequate oral hygiene practices. This pilot study aimed to evaluate the feasibility of a care partner-assisted intervention to improve the oral hygiene of community-dwelling older adults with cognitive impairment.Material and methodsThe 6-month intervention included 25 older adults with mild dementia or mild cognitive impairment, who were randomly assigned to Treatment Group 1 or Treatment Group 2. Treatment Group 1 (n = 7) received an educational booklet. Treatment Group 2 (n = 18) received a booklet, a tailored care plan for the participants with cognitive impairment and the care partner received four coaching sessions to learn to facilitate good oral hygiene. Both groups received electric toothbrushes. The study consisted of a 3-month active intervention and 3-month maintenance phase. The outcomes of gingival index, plaque index and overall oral health status based on the Oral Health Assessment Tool were measured at baseline, 3 months (end of active intervention) and 6 months of the study.ResultsThis study had very low dropout rate. Participants' oral hygiene improved in this study. In comparison to Treatment Group 1, participants in Treatment Group 2 had a greater reduction in plaque level and gingival inflammation, and greater improvement in overall oral health status.ConclusionThis study demonstrates the feasibility of this intervention designed to improve the oral health of persons with cognitive impairment and it lays the foundation for using this protocol in a future large randomised clinical trial

    Rewarding effects of opiates are absent in mice lacking the receptor for substance P

    No full text
    Modulation of substance P activity offers a radical new approach to the management of depression, anxiety and stress(1-3). The substance P receptor is highly expressed in areas of the brain that are implicated in these behaviours, but also in other areas such as the nucleus accumbens which mediate the motivational properties of both natural rewards such as food and of drugs of abuse such as opiates(4-7). Here we show a loss of the rewarding properties of morphine in mice with a genetic disruption of the substance P receptor. The loss was specific to morphine, as both groups of mice responded when cocaine or food were used as rewards. The physical response to opiate withdrawal was also reduced in substance P receptor knockout mice. We conclude that substance P has an important and specific role in mediating the motivational aspects of opiates and may represent a new pharmacological route for the control of drug abuse
    corecore