Inferring the age and sex of ancient potters from fingerprint ridge densities: A data-driven, Bayesian mixture modelling approach

The density of epidermal ridges in a fingerprint varies predictably by age and sex. Archaeologists are therefore interested in using recovered fingerprints to learn about the ancient people who produced them. Recent studies focus on estimating the age and sex of individuals by measuring their fingerprints with one of two similar metrics: mean ridge breadth (MRB) or ridge density (RD). Yet these attempts face several critical problems: expected values for adult females and adolescent males are inherently indistinguishable, and inter-assemblage variation caused by biological and technological differences cannot be easily estimated. Each of these factors greatly decreases the accuracy of predictions based on individual prints, and together they condemn this strategy to relative uselessness. However, information in fingerprints from across an assemblage can be pooled to generate a more accurate depiction of potter demographics. We present a new approach to epidermal ridge density analysis using Bayesian mixture models with the following key benefits: Age and sex are estimated more accurately than existing methods by incorporating a data-driven understanding of how demographics and ridge density covary. Uncertainty in demographic estimates is automatically quantified and included in output. The Bayesian framework can be easily adapted to fit the unique needs of different researchers. </p

Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis.

BACKGROUND: Numerous trials combining radiation therapy (RT) and immunotherapy in head and neck squamous cell carcinoma (HNSCC) are failing. Using preclinical immune cold models of HNSCC resistant to RT-immune checkpoint inhibitors, we investigate therapeutic approaches of overcoming such resistance by examining the differential microenvironmental response to RT. METHODS: We subjected two HPV-negative orthotopic mouse models of HNSCC to combination RT, regulatory T cells (Treg) depletion, and/or CD137 agonism. Tumor growth was measured and intratumorous and lymph node immune populations were compared among treatment groups. Human gene sets, genetically engineered mouse models DEREG and BATF3-/-, flow and time-of-flight cytometry, RNA-Seq, Treg adoptive transfer studies, and in vitro experiments were used to further evaluate the role of dendritic cells (DCs) and Tregs in these treatments. RESULTS: In MOC2 orthotopic tumors, we find no therapeutic benefit to targeting classically defined immunosuppressive myeloids, which increase with RT. In these radioresistant tumors, supplementing combination RT and Treg depletion with anti-CD137 agonism stimulates CD103+ DC activation in tumor-draining lymph nodes as characterized by increases in CD80+ and CCR7+ DCs, resulting in a CD8 T cell-dependent response. Simultaneously, Tregs are reprogrammed to an effector phenotype demonstrated by increases in interferonγ+, tumor necrosis factorα+, PI3K+, pAKT+ and Eomes+ populations as well as decreases in CTLA4+ and NRP-1+ populations. Tumor eradication is observed when RT is increased to an 8 Gy x 5 hypofractionated regimen and combined with anti-CD25+ anti-CD137 treatment. In a human gene set from oral squamous cell carcinoma tumors, high Treg number is associated with earlier recurrence. CONCLUSIONS: Regulating Treg functionality and DC activation status within the lymph node is critical for generating a T cell effector response in these highly radioresistant tumors. These findings underscore the plasticity of Tregs and represent a new therapeutic opportunity for reprogramming the tumor microenvironment in HNSCCs resistant to conventional radioimmunotherapy approaches

An essential role for the IL-2 receptor in Treg cell function

Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage–specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+ T cells but was important for limiting the activation of CD8+ T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of Treg cells separable from signaling via the T cell antigen receptor

Saying it with feeling: Analysing speakable emotions

In this article we examine accounts of emotional experiences in one organization. Drawing upon data from interviews across a range of employees, we analyse aspects of emotion, identity and power. Adopting a constructionist perspective we use a method of discourse analysis to analyse how participants constructed emotions according to tacitly understood rules regarding appropriate emotional displays. These rules were made visible through an examination of the participants' positioning strategies as they described emotional experiences. Our findings suggest that, rather than an institutionally held level of appropriate articulations of emotionality, there was a role-related, socially located rule system linked to separate categories of teachers, managers and administrative employees. The contribution of the article is threefold. First, we use in-depth case data from 44 semi-structured interviews to analyse how teachers and managers/administrators in a UK-based further education (FE) college constructed emotions according to certain rules (informal norms) regarding appropriate kinds of emotional displays. Teachers acknowledged and upgraded labelled emotions, while managers and administrators denied and downgraded accounts of emotional experiences. Second, we discuss the implications of talk about emotion for the (re)production of teachers' and managers/administrators' work identities. Third, we consider how people's talk about emotions was bound-up in relations of power