A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.

Seventy-five percent of breast cancers are estrogen receptor α positive (ER(+)). Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER(+) tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER(+) tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER(+) PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.

Vertical cultural transmission effects on demic front propagation: Theory and application to the Neolithic transition in Europe

It is shown that Lotka-Volterra interaction terms are not appropriate to describe vertical cultural transmission. Appropriate interaction terms are derived and used to compute the effect of vertical cultural transmission on demic front propagation. They are also applied to a specific example, the Neolithic transition in Europe. In this example, it is found that the effect of vertical cultural transmission can be important (about 30%). On the other hand, simple models based on differential equations can lead to large errors (above 50%). Further physical, biophysical, and cross-disciplinary applications are outlined

Análisis de los apoyos que reciben los jóvenes con discapacidad intelectual en su transición a la vida adulta en España: una investigación a partir de experiencias de profesionales y personas con discapacidad = Analysis of support received by young people with intellectual disabilities in their transition to adulthood in Spain: an investigation based on the experiences of professionals and people with disabilities

The objective of this study is to gather information regarding the adaptation of the range of socio educational projects and services aimed at the transition to an adult life of young persons with intellectual disabilities in Spain. The research of the study has been done in three stages. During each stage, a specific tool has been used. One to one in-depth interviews have been undertaken with 45 professionals and 20 individuals with intellectual disabilities. The Delphi method has been applied to two panels consisting of 20 experts each. Firstly, results focus on the approach to different issues related to the devices. Secondly, the training opportunities that these individuals receive to ease the transition period is addressed. And finally, the study refers to the participation of the individuals themselves and their families in the process. The developed analysis allows us to propose strategies to improve the transition to adult life

The use of Rich and Suter diagrams to explain the electron configurations of transition elements

Rich and Suter diagrams are a very useful tool to explain the electron configurations of all transition elements, and in particular, the s¹ and s0 configurations of the elements Cr, Cu, Nb, Mo, Ru, Rh, Pd, Ag, and Pt. The application of these diagrams to the inner transition elements also explains the electron configurations of lanthanoids and actinoids, except for Ce, Pa, U, Np, and Cm, whose electron configurations are indeed very special because they are a mixture of several configurations.

Proactive and Preventive Student Welfare Activities in Finnish Preschool and Elementary School: Handling of Transition to Formal Schooling and a National Anti-Bullying Program as Examples

Prerequisites and effects of proactive and preventive psycho-social student welfare activities in Finnish preschool and elementary school were of interest in the present thesis. So far, Finnish student welfare work has mainly focused on interventions and individuals, and the voluminous possibilities to enhance well-being of all students as a part of everyday school work have not been fully exploited. Consequently, in this thesis three goals were set: (1) To present concrete examples of proactive and preventive psycho-social student welfare activities in Finnish basic education; (2) To investigate measurable positive effects of proactive and preventive activities; and (3) To investigate implementation of proactive and preventive activities in ecological contexts. Two prominent phenomena in preschool and elementary school years—transition to formal schooling and school bullying—were chosen as examples of critical situations that are appropriate targets for proactive and preventive psycho-social student welfare activities. Until lately, the procedures concerning both school transitions and school bullying have been rather problem-focused and reactive in nature. Theoretically, we lean on the bioecological model of development by Bronfenbrenner and Morris with concentric micro-, meso-, exo- and macrosystems. Data were drawn from two large-scale research projects, the longitudinal First Steps Study: Interactive Learning in the Child–Parent– Teacher Triangle, and the Evaluation Study of the National Antibullying Program KiVa. In Study I, we found that the academic skills of children from preschool–elementary school pairs that implemented several supportive activities during the preschool year developed more quickly from preschool to Grade 1 compared with the skills of children from pairs that used fewer practices. In Study II, we focused on possible effects of proactive and preventive actions on teachers and found that participation in the KiVa antibullying program influenced teachers‘ self-evaluated competence to tackle bullying. In Studies III and IV, we investigated factors that affect implementation rate of these proactive and preventive actions. In Study III, we found that principal‘s commitment and support for antibullying work has a clear-cut positive effect on implementation adherence of student lessons of the KiVa antibullying program. The more teachers experience support for and commitment to anti-bullying work from their principal, the more they report having covered KiVa student lessons and topics. In Study IV, we wanted to find out why some schools implement several useful and inexpensive transition practices, whereas other schools use only a few of them. We were interested in broadening the scope and looking at local-level (exosystem) qualities, and, in fact, the local-level activities and guidelines, along with teacherreported importance of the transition practices, were the only factors significantly associated with the implementation rate of transition practices between elementary schools and partner preschools. Teacher- and school-level factors available in this study turned out to be mostly not significant. To summarize, the results confirm that school-based promotion and prevention activities may have beneficial effects not only on students but also on teachers. Second, various top-down processes, such as engagement at the level of elementary school principals or local administration may enhance implementation of these beneficial activities. The main message is that when aiming to support the lives of children the primary focus should be on adults. In future, promotion of psychosocial well-being and the intrinsic value of inter- and intrapersonal skills need to be strengthened in the Finnish educational systems. Future research efforts in student welfare and school psychology, as well as focused training for psychologists in educational contexts, should be encouraged in the departments of psychology and education in Finnish universities. Moreover, a specific research centre for school health and well-being should be established.

Dental fear in adolescents' transition to early adulthood

The aims of the study were to assess the validity of a clinical dental fear question (Short Dental Fear Question, SDFQ) and an instrument measuring interaction between adolescents and dental staff (Patient Dental Staff Interaction Questionnaire, PDSIQ). Also, adolescents’ subjective perception of interaction with dental staff, the association with adolescents’ dental fear and sense of coherence as well as a multi-professional small-group intervention model for decreasing high dental fear were assessed. The study sample comprised Finnish adolescents in transition to early adulthood, aged 18–26 years (n = 777, n = 773, n = 5), except for a sample of 15-year-old adolescents (n = 27). Dental fear, sense of coherence (SOC) and the adolescents’ perceived interaction with dental staff were assessed with questionnaires. The principles of fear treatment such as gradual exposure, relaxation, encouragement and cornerstones of the reteaming method based on a solution-focused framework to maintain motivation and peer support were used to decrease fear in the intervention study. The SDFQ was found to be a valid dental fear instrument and the PDSIQ a valid interaction instrument with five factors of interaction retrieved: ‘kind atmosphere and mutual communication’, ‘roughness’, ‘insecurity’, ‘trust and safety’, and ‘shame and guilt’. Highly fearful young adults more often perceived their interaction with dental staff as negative, more often felt insecure and had a weaker sense of coherence compared to their peers with no to moderate dental fear. The results of the intervention study showed that young adults’ high dental fear decreased and their commitment to dental treatment increased. The SDFQ is clinically feasible and informative instrument in measuring dental fear. Knowledge of the level of fear enables dental staff to better consider an adolescent’s fear. Dental staff should be aware that a supportive interaction style, creating trust and safety, is especially beneficial for highly dentally fearful young adults. A weak SOC may affect young adults’ high dental fear in that they would not have enough tools to manage their fear. A multi-professional small therapeutic group seems to increase fearful young adults’ resources for confronting dental treatment.

Asthma: where is it going?

Asthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Although our understanding of its pathophysiological mechanisms continues to evolve, the relative contributions of airway hyperresponsiveness and inflammation are still debated. The first mechanism identified as important for asthma was bronchial hyperresponsiveness. In a second step, asthma was recognized also as an inflammatory disease, with chronic inflammation inducing structural changes or remodeling. However, persistence of airway dysfunction despite inflammatory control is observed in chronic severe asthma of both adults and children. More recently, a potential role for epithelial-mesenchymal communication or transition is emerging, with epithelial injury often resulting in a self-sustaining phenotype of wound repair modulation by activation/reactivation of the epithelial-mesenchymal trophic unit, suggesting that chronic asthma can be more than an inflammatory disease. It is noteworthy that the gene-environmental interactions critical for the development of a full asthma phenotype involve processes similar to those occurring in branching morphogenesis. In addition, a central role for airway smooth muscle in the pathogenesis of the disease has been explored, highlighting its secretory function as well as different intrinsic properties compared to normal subjects. These new concepts can potentially shed light on the mechanisms underlying some asthma phenotypes and improve our understanding of the disease in terms of the therapeutic strategies to be applied. How we understand asthma and its mechanisms along time will be the focus of this overview.

The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding

The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33% of the newborns presented weak sucking, 23% slow rhythm, 30% absence of at least one adaptive oral reflex, and 14% with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100%. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.

Helicobacter pylori adhesion to gastric epithelial cells is mediated by glycan receptors

Helicobacter pylori adhesion to gastric epithelial cells constitutes a key step in the establishment of a successful infection of the gastric mucosa. The high representation of outer membrane proteins in the bacterial genome suggests the relevance of those proteins in the establishment of profitable interactions with the host gastric cells. Gastric epithelial cells are protected by a mucous layer gel, mainly consisting of the MUC5AC and MUC6 mucins. In addition to this protective role, mucins harbor glycan-rich domains that constitute preferential binding sites of many pathogens. In this article we review the main players in the process of H. pylori adhesion to gastric epithelial cells, which contribute decisively to the high prevalence and chronicity of H. pylori infection. The BabA adhesin recognizes both H-type 1 and Lewis b blood-group antigens expressed on normal gastric mucosa of secretor individuals, contributing to the initial steps of infection. Upon colonization, persistent infection induces an inflammatory response with concomitant expression of sialylated antigens. The SabA adhesin mediates H. pylori binding to inflamed gastric mucosa by recognizing sialyl-Lewis a and sialyl-Lewis x antigens. The expression of the BabA and SabA adhesins is tightly regulated, permitting the bacteria to rapidly adapt to the changes of glycosylation of the host gastric mucosa that occur during infection, as well as to escape from the inflammatory response. The growing knowledge of the interactions between the bacterial adhesins and the host receptors will contribute to the design of alternative strategies for eradication of the infection.

Human sepsis-associated Escherichia coli (SEPEC) is able to adhere to and invade kidney epithelial cells in culture

The adhesins of extraintestinal pathogenic Escherichia coli are essential for mediating direct interactions between the microbes and the host cell surfaces that they infect. Using fluorescence microscopy and gentamycin protection assays, we observed that 49 sepsis-associated E. coli (SEPEC) strains isolated from human adults adhered to and invaded Vero cells in the presence of D-mannose (100%). In addition, bacteria concentrations of approximately 2 x 10(7) CFU/mL were recovered from Vero cells following an invasion assay. Furthermore, PCR analysis of adhesin genes showed that 98.0% of these SEPEC strains tested positive for fimH, 69.4% for flu, 53.1% for csgA, 38.8% for mat, and 32.7% for iha. Analysis of the invasin genes showed that 16.3% of the SEPEC strains were positive for tia, 12.3% for gimB, and 10.2% for ibeA. Therefore, these data suggest that SEPEC adhesion to cell surfaces occurs through non-fimH mechanisms. Scanning electron microscopy showed the formation of microcolonies on the Vero cell surface. SEPEC invasiveness was also confirmed by the presence of intracellular bacteria, and ultrastructural analysis using electron transmission microscopy revealed bacteria inside the Vero cells. Taken together, these results demonstrate that these SEPEC strains had the ability to adhere to and invade Vero cells. Moreover, these data support the theory that renal cells may be the predominant pathway through which SEPEC enters human blood vessels.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

An examination of learning resulting from a transition from a directed to a self-directed work environment

~ This study focuses on the process of self-directed learning that individuals go through as they adapt to new work situations. This is a study of how one critical incident, specifically the transition from a traditional office structure to a home office structure, affected employees and what their learning process was as they adapted to the new environment. This study has 3 educational foundations: adult learning, self-directed learning, and the social context from which the learning will occur. Six women and 2 men were interviewed approximately 1 year following the transition. Analysis of the data revealed 5 themes of: impacts of the self-directed environment on participants' personal lives, their roles, skill set, productivity, and the physical environment; support offered by the organization, family, and office administration; personal development, specific learning needs, and personal skills; boundaries as they relate to family and work; and skill set and orientation requirements of new home office employees. The findings revealed the learning processes of the 8 participants. The learning processes of these participants were discussed within a theoretical framework of the learners, their immediate surroundings, and the larger social environment. The results indicated that the transition from a directed work environment to a self directed work environment is a complex, interrelated process. An element found throughout the theoretical framework is that of control. A second critical element is the need for participants to have a clearly defined work role and an opportunity to engage in discussion with peers and the community. Further findings reinforced the importance of climate and found that the physical environment is a key factor in a successful selfdirected work environment. The findings of this study revealed that no one factor makes an individual function successfully in a self-directed work environment, but that it is a complex interplay among the leamer, their immediate surroundings, and the social environment that will have the greatest impact on success. Recommendations are made which can be used to guide organizational leaders in facilitating employees' transition from a directed to a self-directed work environment. Additionally, recommendations are made for further research in the area of self-directed work environments.

A study of the role learning and socialization during the transition from teacher to elementary school administrator

This thesis examined the role transition from an elementary teacher to an elementary principal. In particular, the training and socialization process of becoming an elementary principal was explored through the study of the hierarchical and political structure of a southern Ontario school board, and how this influenced the learning experiences of new elementary principals. A qualitative methodology, with a grounded theory design, was employed to investigate this process through interviews with 10 participants to examine their experiences and role learning occurs during their development. Specifically, participants perspective shifts, developmental experiences, understanding of group culture, and expansion of a board profile were highlighted in the data. One of the compelling results of the study was the degree to which principals of aspiring administrators influence the socialization of their subordinates. The beliefs and practices of the school principal determine the socialization orientation that teachers and vice-principals will experience during role learning. The results of this study also imply that role orientation needs to be understood as a continuum between custodial and innovative role assumption. Varying degrees of custodianship or innovation depended on the context of the administrative placement and the personal attributes of administrative candidates. Principals who are willing to share responsibilities, who are good communicators, and who wish to develop a collaborative relationship with their viceprincipals are the individuals the participants in this study described as making the best mentors.