Understanding Shame: The Clinical Implications of Trauma Work with Female Adolescents

Childhood trauma and the accompanying negative neurobiological effects can lead to a variety of detrimental physical and mental health outcomes. This presentation, based on data from the CDC\u27s Adverse Childhood Experiences (ACE) Study and related childhood trauma studies, examines the psychological and behavioral vulnerabilities of at-risk teenage girls and highlights evidence-based treatment interventions and shame-reducing activities for working with this susceptible, yet resilient, adolescent population

Structure-activity relationships in Werner clathrates

Includes bibliographical references.The synthesis and characterization of a series of inorganic coordination compounds which, upon crystallization, have the ability to include solvent or guest molecules spatially within the lattice are reported. The compounds have the following general formula: [NiX2B4] - where X is isothiocyanate or bromine and B is 4-ethylpyridine, 4-vinylpiridine or 3,5-dimethylpyridine; [NiX2B2]n - where X is isothiocyanate, B is 2-aminopyridine and n indicates it is a polymer; [NiX2AB2]2 - where X is isothiocyanate, B is 3-aminopyridine (two of these four ligands in the dimer are bridging) and A is water. The various guest molecules have been carefully chosen, according to their point symmetry, which is a key factor in yielding structures of a particular type. The structures of seventeen compounds have been elucidated by single crystal x-ray analysis. The difficulty has been found to lie in refining disordered guest molecules. Other techniques employed in the initial characterization of these compounds are Microanalysis, Mass Spectrometry and UV/Visible Spectrophotometry. An intramolecular potential energy study on the [Ni(NCS)2(3,5-diMepy)4] complex reveals that the orthohydrogens on the 3,5-dimethylpyridine ligands control the conformation of the molecule. Packing densities and volume comparisons of the [Ni(NCS)2(4-Etpy)4] and [Ni(NCS)2(4-Vipy)4] complexes and their clathrates have been carried out. The exact sizes and shapes of the cavities in which the guest molecules are located in the x-ray crystal structures have been evaluated by both intermolecular potential energy and molecular volume calculations. Thermodynamic and spectroscopic properties of the [Ni(NCS)2(4-Etpy)4] and [Ni(NCS)2(4-Vipy)4] clathrates have been studied in both solution and the solid state. The techniques used are x-ray powder diffractometry, IR spectroscopy and Thermogravimetry (including Differential Thermal Analysis)

High-order asymptotic methods provide accurate, analytic solutions to intractable potential problems

The classical problem of determining the density and capacity of arrays of potential sources is studied. This corresponds to a wide variety of physical problems such as electrostatic capacitance, stress in elastostatics and the evaporation of fluid droplets. An asymptotic solution is derived that is shown to give excellent accuracy for arbitrary arrays of sources with non-circular footprints, including polygonal footprints. The solution is extensively validated against both experimental and numerical results. We illustrate the power of the solution by showcasing a variety of newly accessible classical problems that may be solved in a rapid, accurate manner

Near edge tractions for a rounded quarter-plane pressed into an elastically similar half-plane

Asymptotic forms are a useful way of representing the state of stress at a contact edge, allowing us to characterise the region in which cracks nucleate. The asymptotes must match the behaviour implied by the local geometry. In this paper, we study the behaviour of a flat contact with a circular arced edge (i.e. a flat and rounded contact); a geometry that has extensive applications. We show explicitly how the very convenient closed-form solution for this problem, derived from half-plane theory, may be collocated into the more realistic three-quarter plane far field solution, obtained from Williams’ solution. This provides a closed-form representation of the edge, correctly geared to the far-field solution, for the first time

Activating senescence in p16-positive Basal-like breast cancer.

PhDBreast cancer is the most common cancer in the UK and Basal-like breast cancer (a highly aggressive subtype) accounts for approximately 8-22% of all cases depending on ethnicity. Unlike most human malignancies and indeed other PAM50 breast cancer subtypes, the vast majority of Basal-like tumours are positive for wild type p16. This p16 signature is associated with a particularly poor prognosis and p16-positive Basal-like breast cancer remains the most clinically challenging subtype and is the focus of this project. Pro-senescence therapies are gaining momentum as attractive strategies for the treatment of those breast cancers with current unmet clinical need. To identify targets for pro-senescence therapy in p16-positive Basal-like breast cancer, a genome‐wide siRNA screen and two subsequent validation screens using two p16-positive cancer cell lines were performed. Screening revealed 20 siRNAs that induced senescence within both cancer cell lines. Strikingly, 11 of these 20 siRNAs targeted ribosomal proteins, implicating disrupted ribosomal biosynthesis in senescence activation in p16-positive Basal-like breast cancer. Importantly, subsequent experiments in normal human mammary epithelial cells established that specific ribosomal protein knockdown is well tolerated by normal cells. Analysis of the METABRIC data set showed a high degree of ribosomal dysregulation in Basal-like tumours and revealed that all 11 ribosomal hits identified were frequently overexpressed in p16-positive Basal-like breast cancers. Kaplan Meier analysis confirmed that elevated expression of six of the 11 ribosomal proteins correlates with a reduced overall survival in these women, further supporting a role for these proteins as drivers of disease. These six ribosomal hits, associated with the poorest patient survival, were prioritised for further validation. Senescence induction was found to be highly stable, and associated with dramatic changes to nucleolar morphology, reminiscent of the nucleolar signature observed upon premature senescence induction in normal human mammary epithelial cells. In addition, siRNA rescue experiments indicated that senescence initiation is dependent on p16 and p21 expression and is accompanied by p16 nuclear translocation and p21 degradation. Further, ribosomal protein silencing in MDA-MB-231 cells (p16-null Basal-like breast cancer cell line) resulted in a ‘death-like’ phenotype, partially dependent on p21 expression suggesting that, within a cancer context, ribosomal protein silencing may induce a differential response depending on the status of p16. In conclusion, it is proposed that these six ribosomal candidates may form the basis of a novel pro-senescence therapy for p16-positive Basal-like breast cancer. They may also represent novel prognostic biomarkers for this disease subset and may help to improve disease stratification and future directed personalised therapies.Medical Research Council PhD Studentship (Grant number: RGJZZY4)

A latent class analysis of parental alcohol and drug use: findings from the Avon Longitudinal Study of Parents and Children

Previous measures of parental substance use have often paid limited attention to the co-occurrence of alcohol and drugs, or to the between-parent dynamics in the use of substances. These shortcomings may have important implications for our understandings of the relationship between parental substance use and child wellbeing. Using data from the Avon Longitudinal Study of Parents and Children, a UK community-based cohort study from 1990 onwards (n=9,451), we identified groups of parental substance use using latent class analysis. The 4-class solution offered the best fit, balancing statistical criteria and theoretical judgement. The results show distinct classes across the range of parental substance use, including very low users, low users, moderate users and heavy users. These classes suggest that substance use patterns among mothers are somewhat mirrored by those of their partners, while heavy use of alcohol by mothers and their partners is related to increased mothers drug use. We suggest that studies that investigate the effects of parental substance use on child wellbeing should pay greater attention to the dynamics of substance use by parental figures

Contrast perception as a visual heuristic in the formulation of referential expressions

We hypothesize that contrast perception works as a visual heuristic, such that when speakers perceive a significant degree of contrast in a visual context, they tend to produce the corresponding adjective to describe a referent. The contrast perception heuristic supports efficient audience design, allowing speakers to produce referential expressions with minimum expenditure of cognitive resources, while facilitating the listener's visual search for the referent. We tested the perceptual contrast hypothesis in three language-production experiments. Experiment 1 revealed that speakers overspecify color adjectives in polychrome displays, whereas in monochrome displays they overspecified other properties that were contrastive. Further support for the contrast perception hypothesis comes from a re-analysis of previous work, which confirmed that color contrast elicits color overspecification when detected in a given display, but not when detected across monochrome trials. Experiment 2 revealed that even atypical colors (which are often overspecified) are only mentioned if there is color contrast. In Experiment 3, participants named a target color faster in monochrome than in polychrome displays, suggesting that the effect of color contrast is not analogous to ease of production. We conclude that the tendency to overspecify color in polychrome displays is not a bottom-up effect driven by the visual salience of color as a property, but possibly a learned communicative strategy. We discuss the implications of our account for pragmatic theories of referential communication and models of audience design, challenging the view that overspecification is a form of egocentric behavior

Effect of Aspergillus fumigatus and Candida albicans on pro-inflammatory response in cystic fibrosis epithelium

AbstractBackgroundThe identification of filamentous fungi and/or yeasts in the airway secretions of individuals with cystic fibrosis (CF) is becoming increasingly prevalent; yet the importance of these organisms in relation to underlying inflammation is poorly defined.MethodsCystic fibrosis bronchial epithelial cells (CFBE) and human bronchial epithelial cells (HBE) were co-incubated with Candida albicans whole cells or Aspergillus fumigatus conidia for 24h prior to the measurement of pro-inflammatory cytokines IL-6 and IL-8 by ELISA.ResultsTreatment of HBE or CFBE with C. albicans whole cells did not alter cytokine secretion. However treatment of CFBE with A. fumigatus conidia resulted in a 1.45-fold increase in IL-6 and a 1.65-fold increase in IL-8 secretion in comparison to basal levels; in contrast there was far less secretion from HBE cells.ConclusionOur data indicate that A. fumigatus infection modulates a pro-inflammatory response in CF epithelial cells while C. albicans does not

High-order asymptotic methods provide accurate, analytic solutions to intractable potential problems

The classical problem of determining the density and capacity of arrays of potential sources is studied. This corresponds to a wide variety of physical problems such as electrostatic capacitance, stress in elastostatics and the evaporation of fluid droplets. An asymptotic solution is derived that is shown to give excellent accuracy for arbitrary arrays of sources with non-circular footprints, including polygonal footprints. The solution is extensively validated against both experimental and numerical results. We illustrate the power of the solution by showcasing a variety of newly accessible classical problems that may be solved in a rapid, accurate manner

Correction: A novel asymptotically consistent approximation for integral evaporation from a spherical cap droplet

Correction to: Journal of Engineering Mathematics https://doi.org/10.1007/s10665-024-10355-