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Clyde and Stephanie Brenek see little cause for alarm when their youngest daughter Em becomes oddly obsessed with an antique wooden box she purchased at a yard sale. But as Em's behavior becomes increasingly erratic, the couple fears the presence of a malevolent force in their midst, only to discover that the box was built to contain a Dibbuk, a dislocated spirit that inhabits and ultimately devours its human host.

Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4 , exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice. Barrett’s oesophagus is associated with an increased risk of oseophageal cancer, but its cell of origin is unclear. Here the authors show, using single-cell RNA sequencing of biopsies from six patients and two unaffected subjects, that cells in Barrett’s oesophagus show a transcriptional profile that is similar to that of cells in oesophageal submucosal glands.

In recent years, gastro-oesophageal cancers have increased in incidence in the western world with no known cause. Barrett's oesophagus (BO) is a premalignant lesion induced by chronic biliary reflux. The cell of origin of BO has been greatly contested yet elusive. Non-dysplastic BO is a poorly understood but highly heterogeneous metaplastic tissue with deranged differentiation and a high incidence of early P53 mutations. Intestinal metaplasia (IM) is an internationally accepted defining criterion for BO diagnosis. In this thesis, I have examined the role of early P53 mutation in the development of gastro-oesophageal cancers by using a combined P53 mutant transgenic mouse in combination with a biliary reflux model. Although gastric cancers did not consistently occur, I found evidence that P53 mutations may potentiate inflammation in non-dysplastic BO. Further investigation of BO cellular complexity using sc-RNA-seq also found that BO shared transcriptional similarity with a subset of oesophageal cells, but not with gastric or duodenal cells, and identified a number of potential biomarkers. Lastly, I have developed organoid models for BO, and demonstrated their ability to differentiate into cell populations see in the scRNA-seq data. In conclusion, my findings reveal a striking similarity between normal OSG cells and BO cells with the high expression of LEFTY1 and TFF3. I identify potential early markers for goblet cell differentiation, SPINK4 and ITLN1 and OLFM4 expression as a marker of BO progenitor cells, which may have clinical implications.

This book offers a broader, more positive picture of African American fathers. Featuring case studies of African-descended fathers, this edited volume brings to life the achievements and challenges of being a black father in America. Leading scholars and practitioners provide unique insight into this understudied population. Short-sighted social policies which do not encourage father involvement are critically examined and the value of father engagement is promoted. The problems associated with the absence of a father are also explored. The second edition features an increased emphasis on: the historical issues confronting African descended fathers the impact of health issues on Black fathers and their children the need for therapeutic interventions to aid in the healing of fathers and their children the impact of an Afrikan-centered fathering approach and the need for research which considers systemic problems confronting African American fathers community focused models that provide new ideas for (re)connecting absent fathers learning tools including reflective questions and a conclusion in each chapter and more theory and research throughout the book. Part I provides a historical overview of African descended fathers including their strengths and shortcomings over the years. Next, contributors share their personal stories including one from a communal father working with underserved youth and two others that highlight the impact of absent fathers. Then, the research on father-daughter relationships is examined including the impact of father absence on daughters and on gender identity. This section concludes with a discussion of serving adolescents in the foster care system. Part II focuses on the importance of a two-parent home, communal fathering, and equalitarian households. Cultural implications and barriers to relationships are also explored. This section concludes with a discussion of the struggles Black men face with role definitions. The book concludes with a discussion of the impact of adoption and health issues on Black fathers and their children, and the need for more effective therapeutic interventions that include a perspective centered in the traditions and cultures of Afrika in learning to become a father. The final chapter offers an intervention model to aid in fatherhood. An ideal supplementary text for courses on fathers and fathering, introduction to the family, parenting, African American families/men, men and masculinity, Black studies, race and ethnic relations, and family issues taught in a variety of departments, the book also appeals to social service providers, policy makers, and clergy who work with community institutions.

Research on recovery from addictive substances is necessary to provide a more complete picture of the addictive process. The proposed research was developed to further expand the knowledge base regarding the process of recovery with respect to two potential components of that process: spirituality and identity. First, spirituality has been considered a key component of recovery by adherents of the 12 Step model of recovery but has not been empirically validated within that context. As a concept, spirituality has not been well understood by researchers and many professionals, has often been defined solely as religiosity, and has frequently been regarded with disdain and/or suspicion. In this study, spirituality was operationally defined and tested as a predictor of recovery. Second, early experience with substance use has been found to interfere with (e.g., delay, block) adequate resolution of relevant issues of psychosocial development, especially the identity crisis. Inadequate psychosocial development may also interfere with a person's ability to understand and commit to spirituality. Poor resolution of the identity crisis, then, may directly influence recovery and indirectly influence the association between spirituality and recovery. Therefore, assessment of the fifth stage of psychosocial development (identity versus role confusion) was also addressed in this research. The primary focus of this study was to examine the empirical association of recovery with (a) spirituality and identify and (b) to determine whether recovery acts as an intervening variable between identity and spirituality. Results suggest that spirituality and identity are positively correlated and that both are positively correlated with recovery. Individuals with longer sobriety utilize the most mature identity style (i.e., Information) and individuals with shorter sobriety utilize the less mature styles (i.e., Normative and Diffuse). Additionally, interactions were found between recovery behavior and identity styles for quality of recovery and spirituality. Individuals with an Information style who engaged in more recovery behaviors had higher quality of recovery and spirituality scores than individuals with the Normative or Diffuse categories and who had fewer recovery behaviors. Greater understanding of the influence of the spirituality and identity constructs, especially over time, are called for.

Barretts esophagus is a precursor of esophageal adenocarcinoma. In this common condition, squamous epithelium in the esophagus is replaced by columnar epithelium in response to acid reflux. Barretts esophagus is highly heterogeneous and its relationships to normal tissues are unclear. We investigated the cellular complexity of Barretts esophagus and the upper gastrointestinal tract using RNA-sequencing of 2895 single cells from multiple biopsies from four patients with Barretts esophagus and two patients without esophageal pathology. We found that uncharacterised cell populations in Barretts esophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with a subset of esophageal cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barretts esophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice.

The thousands of German immigrants settling in antebellum Cincinnati were a diverse people who created a rich associational life to perpetuate a variety of religious and regional distinctions. The thirty Protestant and Catholic congregations that they supported from 1814--the founding date of the first German Protestant church -- until 1870 reflected the Germans' diversity and their commitment to carrying on traditions brought from the homeland. Drawing from traditional ideas of community life from German home town culture, Cincinnati Germans formed their community life around these congregations. Among the Germans who had contact with a church, three religious subcultures emerged by the end of the period. German Protestants adhering to congregations that had been founded upon local popular initiative without assistance from an outside church or synod comprised 38% of the German church-goers. German Protestants belonging to German-speaking congregations affiliated with and founded by American Protestant denominations composed only about 4% of the church-going Germans. The German Catholics comprised the largest group with 58%. Eight of the ten Protestant churches that local Germans started for themselves were independent congregations carrying on the union tradition of state-established German Protestantism. The union concept combined elements of the Lutheran and Reformed traditions. These congregations, each one representing a set of regional customs or dialect, subscribed to the rationlism that long been predominant in German Protestantism. Belief and piety were generally anti-orthodox and humanist. While not making exacting religious demands on individuals, these churches were supported as social organizations providing a set of useful church services and as a basis for community life with like-minded people. Only two Protestant churches founded on a popular basis before 1870 were theologically conservative. These congregations joined Lutheran and Evangelical synods. A small group of Cincinnati Germans joined German-speaking congregations started by Baptist, Methodist, Reformed, and Presbyterian demoninations. The general unwillingness of most Germans to abandon traditions associated with the religious life and behavior known in the homeland is reflected in the fact that only a small minority joined these American Protestant churches. Unlike the other Protestant and the Catholic German congregations, the American Protestant congregations made no commitment to the preservation of German language and culture. German Roman Catholics established twelve churches and numerous associations on their own initiative and governed them with minimal reference to hierarchical authority. They built a comprehensive community life centered on the neighborhood parish with its church, school, mutual aid societies, and social and religious organizations for all ages. In so doing, they attempted to integrate their religion with all aspects of life. The durability of the German churches when compared to secular community organizations, the nature of community life that they fostered, and the fact that conflicts within local German society were often waged along sectarian lines point to the conclusion that the Germans' primary loyalty lay with their churches. Only through identification with and participation in the life of a particular religious subculture could Germans belong to a community. The total German society in Cincinnati had no common values and interests to command the loyalties of so many diverse individuals.

This research sought to make a quantitative assessment of the effect of the Federal urban renewal program on the social and demographic characteristics of neighborhoods within the context of theories of residential location and city growth. Consistent with its disciplinary orientation in human

White reviews Faith and Action: A History of the Archdiocese of Cincinnati, 1821-1996 by Roger Fortin.

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed 1 , 2 . Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy ( NCT02231775 , n  = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P  = 0.001; RFS, 64% versus 32% at 2 years, P  = 0.021). The findings were validated in several additional cohorts 2 – 4 of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy ( n  = 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy ( P  = 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control ( P  = 0.0006 and P  = 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice ( P  = 0.018 and P  = 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients ( P  = 0.021 and P  < 0.0001). Together, these results have important implications for therapy. Treatment with neoadjuvant BRAF/MEK-targeted therapy results in higher rates of major pathological response in female compared with male patients with melanoma, and pharmacological inhibition of androgen receptor signalling improved the responses of male and female mice to BRAF/MEK-targeted therapy.