The American Upper Ordovician Standard. VI, The Covington Sequence at Maysville, Kentucky

Author Institution: Department of Geology, The Ohio State University, Columbus 1

FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma

Oncogenic transcription factors drive many human cancers, yet identifying and therapeutically targeting the resulting deregulated pathways has proven difficult. Squamous cell carcinoma (SCC) is a common and lethal human cancer, and relatively little progress has been made in improving outcomes for SCC due to a poor understanding of its underlying molecular pathogenesis. While SCCs typically lack somatic oncogene-activating mutations, they exhibit frequent overexpression of the p53-related transcription factor p63. We developed an in vivo murine tumor model to investigate the function and key transcriptional programs of p63 in SCC. Here, we show that established SCCs are exquisitely dependent on p63, as acute genetic ablation of p63 in advanced, invasive SCC induced rapid and dramatic apoptosis and tumor regression. In vivo genome-wide gene expression analysis identified a tumor-survival program involving p63-regulated FGFR2 signaling that was activated by ligand emanating from abundant tumor-associated stroma. Correspondingly, we demonstrate the therapeutic efficacy of extinguishing this signaling axis in endogenous SCCs using the clinical FGFR2 inhibitor AZD4547. Collectively, these results reveal an unanticipated role for p63-driven paracrine FGFR2 signaling as an addicting pathway in human cancer and suggest a new approach for the treatment of SCC

Crónica de Derecho Internacional Público. Año 2006

El presente artículo expone los desarrollos habidos durante el año 2006 en diversos sectores e instituciones del Derecho Internacional Público: Organización de las Naciones Unidas, mantenimiento de la paz y la seguridad internacionales, Tribunales internacionales, donde se exponen los casos resueltos por la Corte Internacional de Justicia y el Consejo General de la Organización Mundial del Comercio, así como la celebración del décimo aniversario del Tribunal Internacional para el Derecho del Mar, Derechos Humanos, donde se destaca la creación del Consejo de Derechos Humanos como órgano que sucede a la Comisión de Derechos Humanos, y Acuerdos internacionales de interés para España en 2006, concluidos, aplicados provisionalmente o entrados en vigor durante el año.This articles presents the developments occurred during 2006 in several fields and institutions of Public International Law: United Nations Organisation, the maintenance of international peace and security, international courts, where the cases ruled by the International Court of Justice and the General Council of the World Trade Organisation are presented, as well as the celebrations ot the tenth anniversary of the International Tribunal for the Law of the Sea, Human Rights, matter about which the creation of the Human Rights Council, as the body that succeeds the Human Rights Commission, is emphasized, and international agreements that have had interest for Spain in 2006, signed, provisionally enforced or come into force during that year

Asthma beliefs among mothers and children from different ethnic origins living in Amsterdam, the Netherlands

<p>Abstract</p> <p>Background</p> <p>Doctors and patients hold varying beliefs concerning illness and treatment. Patients' and families' explanatory models (EMs) vary according to personality and sociocultural factors. In a multi-ethnic society, it is becoming increasingly significant that doctors understand the different beliefs of their patients in order to improve patient/doctor communication as well as patient adherence to treatment.</p> <p>Methods</p> <p>Twelve focus groups were formed, consisting of 40 children diagnosed with asthma, as well as 28 mothers of these children. These groups included mothers and children of different ethnicities who were living in Amsterdam, the Netherlands. In order to understand the beliefs that both mothers and children hold regarding asthma and its treatment, the explanatory models were analysed and compared.</p> <p>Results</p> <p>Study findings show that mothers and children, regardless of ethnicity and age, have their own EMs. Overall, there is a great deal of uncertainty related to the causes, consequences, problems, and symptoms of asthma and its treatment. It also seems that many concerns and feelings of discomfort are the result of lack of knowledge. For instance, the fact that asthma is not seen as a chronic disease requiring daily intake of an inhaled corticosteroid, but rather as an acute phenomenon triggered by various factors, may be very relevant for clinical practice. This particular belief might suggest an explanation for non-adherent behaviour.</p> <p>Conclusion</p> <p>A thorough understanding of the mothers' and children's beliefs regarding the illness and its treatment is an important aspect in the management of asthma. Gaining an understanding of these beliefs will provide a foundation for a solid clinician-patient/family partnership in asthma care. Although ethnic differences were observed, the similarities between the mothers' and children's beliefs in this multi-ethnic population were striking. In particular, a common belief is that asthma is considered an acute rather than a chronic condition. In addition, there is a lack of knowledge about the course and the self-management of asthma. Health care providers should be aware of these commonly held beliefs, and this information could be shared in educational programs.</p

Challenges Associated with Multi-institutional Multi-site Clinical Trial Collaborations: Lessons from a Diabetes Self-Management Interventions Study in Primary Care

Purpose: Project management for multi-institutional, multi-site clinical trials poses significant challenges. We describe the response to challenges encountered in a 5-year National Institutes of Health multi-institutional 7-site randomized controlled trial of type 2 diabetes (T2DM) self-management interventions study. Methods: The collaborating institutions consisted of a large 220,000-member integrated healthcare system and a university academic health science center partner. The clinical team comprised the principal investigator and research coordinators covering 6 of the 7 clinical sites, while the academic team comprised the co-principal investigator, coinvestigators, and other research and clinical coordination staff. Subjects recruited for the study had a glycosylated hemoglobin ≥ 7.5 within the last 6 months and received primary care at the participating clinics. Patients who met the inclusion criteria were consented at private orientation meetings, randomized into one of 4 study arms, and followed every 6 months over a 24-month period for data collection. Results: The encountered challenges concerned: 1) communication across the multiple clinic sites; 2) multiinstitutional coordinator training; 3) multiple record-keeping methods; 4) clinical access for academic personnel; 5) unanticipated clinical coordinator turnover; 6) subject recruitment and retention; and 7) multiple Institutional Review Boards (IRBs). Solutions included conducting full team weekly or bimonthly research meetings, coordinator crosstraining, adding study-specific templates with downloadable fields, developing a protocol for working with single point of contact in each clinic, securing commitment from the centralized clinical system to dedicate coordinator(s) to the project for the duration of the study period, setting explicit monthly recruitment goals for each clinic, and establishing a lead IRB up-front. Conclusion: Our challenges reflect the complexity of clinical trial collaborations across clinical and academic partners. Of critical importance to the success of clinical/academic collaborations is the commitment by all institutions for advance determination of communication strategies, IRB processes, records access and storage systems, and online training needs. Trial Registration Number/Site: NCT01221090, https://clinicaltrials.govThe open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund