Imposter syndrome in academic libraries: Indigenous women edition

This is a written proceeding of the LACUNY 2022 panel presentation “Imposter Syndrome in Academic Libraries: Indigenous Women Edition”. The authors discuss personal instances and feelings of the imposter phenomenon (also known as imposter syndrome) as it may relate to their Indigenous identities. Additionally, the authors describe how imposter syndrome may affect their ability to be successful in their careers, and the internal pressure they feel to present a more Indigenous identity (whatever that may entail) for scholarship and positions. The authors also share their experiences with external pressures to exhibit a more “stereotypical Indigenous” appearance for the sake of their role as Indigenous library staff members, peers, or when applying for academic opportunities and how this relates when interacting with other Indigenous people through their work. They speak on the recent developments in academia in terms of hiring Indigenous peoples and avoiding pretendians (people who falsely claim to have Indigenous ancestry). The goal of the authors is to encourage discourse in the vein of Truth and Reconciliation and spreading awareness about imposter syndrome

Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-Cell effector activity during skin infection with HSV-1

Efficient infection control requires potent T-cell responses at sites of pathogen replication. However, the regulation of T-cell effector function in situ remains poorly understood. Here, we show key differences in the regulation of effector activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN-γ-producing CD4+ T cells disseminated widely throughout the skin and draining lymph nodes (LN), clearly exceeding the epithelial distribution of infectious virus. By contrast, IFN-γ-producing CD8+ T cells were only found within the infected epidermal layer of the skin and associated hair follicles. Mechanistically, while various subsets of lymphoid- and skin-derived dendritic cells (DC) elicited IFN-γ production by CD4+ T cells, CD8+ T cells responded exclusively to infected epidermal cells directly presenting viral antigen. Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger IFN-γ production by CD8+ T-cells. Thus, we describe a previously unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector activity that is subset-specific, microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (APC).The work was funded by grant (APP628423 and APP1059514) and fellowship support from the National Health and Medical Research Council Australia (NHMRC)and the Australian Research Council (ARC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus

Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. Methods: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. Results: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. Discussion: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs

Validation of CyTOF Against Flow Cytometry for Immunological Studies and Monitoring of Human Cancer Clinical Trials

Flow cytometry is a widely applied approach for exploratory immune profiling and biomarker discovery in cancer and other diseases. However, flow cytometry is limited by the number of parameters that can be simultaneously analyzed, severely restricting its utility. Recently, the advent of mass cytometry (CyTOF) has enabled high dimensional and unbiased examination of the immune system, allowing simultaneous interrogation of a large number of parameters. This is important for deep interrogation of immune responses and particularly when sample sizes are limited (such as in tumors). Our goal was to compare the accuracy and reproducibility of CyTOF against flow cytometry as a reliable analytic tool for human PBMC and tumor tissues for cancer clinical trials. We developed a 40+ parameter CyTOF panel and demonstrate that compared to flow cytometry, CyTOF yields analogous quantification of cell lineages in conjunction with markers of cell differentiation, function, activation, and exhaustion for use with fresh and viably frozen PBMC or tumor tissues. Further, we provide a protocol that enables reliable quantification by CyTOF down to low numbers of input human cells, an approach that is particularly important when cell numbers are limiting. Thus, we validate CyTOF as an accurate approach to perform high dimensional analysis in human tumor tissue and to utilize low cell numbers for subsequent immunologic studies and cancer clinical trials

New World Civitas, Contested Jurisdictions and Intercultural Conversation in the Construction of the Spanish Monarchy

Jurisdictional frontiers were created, contested, and negotiated among a wide range of actors, including native Americans and Europeans, with reference to the cities founded in Castilla del Oro (roughly present-day Panama). This research deals, first, with the reshaping of the concept of a city in the New World, based on its inhabitants' sense of civitas. It analyses, secondly, the creation and redefinition of jurisdiction during political conflicts and, third, the construction and maintenance of jurisdiction through local relations with indigenous populations described as "conversation". The analysis of the creation and preservation of local jurisdictions allows for an interpretation of the complexities involved in the configuration of political power and political space from below in the territories claimed by the Spanish Monarchy.Art Empir

Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

The Acquisition of Vocalic Sequences by English-Speaking L2 Learners of Spanish

While previous studies have investigated the acquisition of Spanish vowels by English speakers, none has examined how sequences of vowels are acquired.  Spanish incorporates a contrast between two vowels syllabified as a diphthong or as a hiatus, which is not found in English.    This study seeks to determine the developmental path of acquisition of the diphthong/hiatus contrast by English speakers with respect to the acoustic manifestation of the contrast (in terms of two acoustic correlates of the contrast: duration and %-transition) as well as in terms of the effects of phonological transfer (in the form of an English syllabification constraint) and phonetic transfer (in the form of the acoustic realization of English glides).    Through an experiment testing beginning and intermediate learners, it was found that the duration of vowels in sequence is somewhat exaggerated by learners and that while phonological transfer was not evident, a positive effect of phonetic transfer occurred, resulting in an almost native-like pronunciation of certain Spanish syllables that are illicit in English.   The conclusions of this study contribute to the gap in the literature regarding acquisition of vocalic sequences and illustrate the need for a consistent clarification between phonological and phonetic transfer

The Effect of Perceptual Salience on Phonetic Accommodation in Cross-dialectal Conversation in Spanish

Phonetic accommodation is the process whereby speakers in an interaction modify their speech in response to their interlocutor. The social-psychological theory of Communication Accommodation Theory (Giles 1973) predicts that speakers will converge towards (become more similar to) their interlocutors in order to decrease social distance, whereas they will diverge from (become less similar to) their interlocutors to accentuate distinctiveness or show disdain. Previous studies have found that phonetic accommodation is affected by many social, situational and linguistic factors (Abrego-Collier et al. 2011; Black 2012; Babel 2009, 2010, 2012; Babel et al. 2012; Kim, Horton & Bradlow 2011; Nielsen 2011; Pardo et al. 2012). With respect to accommodation across dialects, a handful of studies have suggested that the perceptual salience of the various differences between two dialects might affect the pattern; however, these studies make conflicting predictions. Trudgill (1986) predicts that speakers will converge more towards the more salient dialectal differences, while Kim et al. (2011) and Babel (2009, 2010) suggest the opposite: that speakers will converge on the less salient differences. This thesis investigates how the perceptual salience of 6 differences between Buenos Aires Spanish and Madrid Spanish affect the pattern of phonetic accommodation in conversation. The results are considered both in terms of the magnitude of the changes that the participants make as well as the direction of the change (convergence or divergence). The results show that perceptual salience has a significant effect on the magnitude of the change, with all participants making greater changes as perceptual salience increases. On the other hand, perceptual salience was found not to have a consistent effect for all speakers on the likelihood of converging or diverging on the dialectal differences. I argue that the lack of consistent effect of salience on the direction of the change stems from individual differences in motivation to take on the opposing dialect norms and issues of personal identity, whereas the very consistent effect of salience on the magnitude of the change suggests that there is something more basic or systematic about how salience interacts with the extent to which speakers accommodate.Ph

Regulation of CD4+ and CD8+ T cell effector function during HSV-1 skin infection

© 2014 Dr. Bethany Lee MacleodT cell priming by professional antigen presenting cells (APCs) has traditionally been thought to be restricted to lymphoid organs. However, recent studies have indicated that T cells may require further interactions with APCs at peripheral sites of infection for optimal accumulation and execution of effector functions. Cytokine production is an important antiviral effector function, for both CD4+ and CD8+ T cell subsets. However, few studies have assessed the kinetics of cytokine production during infection, without resorting to in vitro restimulation of T cells. Furthermore, in order to better understand the progression of T cell-mediated antiviral immune responses, it is of interest to delineate how cytokine production by each T cell subset is regulated in vivo. During cutaneous HSV-1 infection, effector CD4+ and CD8+ T cells that infiltrated virus-containing skin continued to expand locally, while concurrently producing the cytokine IFN-g. Interestingly, the presence or absence of antigen had no bearing on T cell proliferation. However, local antigen presentation was strictly required to stimulate IFN-g production. Furthermore, each T cell subset produced IFN-g in different anatomic sites in the skin and associated lymphoid tissue; CD4+ T cells produced IFN-g throughout the epidermis, dermis and draining lymph nodes, while CD8+ T cell IFN-g production was strictly confined to the epidermis and hair follicles. The distribution of cytokine production by each T cell subset was a consequence of their distinct responses to various APCs. Professional APCs, including many subsets of cutaneous dendritic cells, were the major stimulators of cytokine production by CD4+ T cells. Furthermore, CD4+ T cell cytokine production did not depend on the infection status of the professional APC. In contrast, CD8+ T cells only responded to HSV-1-infected APCs from the skin epithelium, including keratinocytes, dendritic epidermal T cells and other infiltrating immune cells. Thus in contrast to CD8+ T cell priming during HSV-1 infection, which is though to rely on cross-presentation, CD8+ T cell effector responses are skewed toward those cells directly presenting antigen. We speculate that this compartmentalisation of effector function may be indicative of non-overlapping roles for each T cell subset in local virus control. Furthermore, we describe a mechanism that may be of evolutionary advantage to target ‘killer’ CD8+ T cell to destroy virus-infected cells while concurrently limiting collateral damage