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Internationally, educators are calling for teachers to help students learn to respect and value social and cultural difference. Literature teachers can also contribute to such a revolution in consciousness through literature study. It is crucial to education in a multicultural society that students are taught ways of reading and talking about literature which create respect for multiple perspectives. One means of doing this is through a "dialogic pedagogy," a conversational teaching approach in which the teacher and students engage in purposeful collaboration, guiding and inviting each other in talk and activity. Since readers construct different meanings from identical texts, text discussion can be particularly suited to provoke an interplay of differences. However, research indicates that such reflection about different perspectives rarely occurs in American schools, including literature classes, in which many teachers still rely on closed questioning. After observing teachers who successfully created conditions that produced motivated discussions about texts, four principles emerged: (1) inducing a new stance towards texts; (2) provoking collaborative reflection about alternatives; (3) scaffolding dialogic heuristics; and (4) encouraging student-initiated and sustained dialogic inquiry. If multicultural education is limited to new book lists or curricular add-ons, it may fail to become an integral part of student and citizen consciousness. (A list of 59 references is attached.) (HB)

Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.

Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.

In Aotearoa New Zealand, healthy women giving birth for the first time may plan to give birth in range of settings - from home to a tertiary hospital where surgical and anaesthetic services are available. Each birth location has its own culture, and the extent to which this culture influences the birth experience lies at the heart of this research. Just twenty-three percent of first-time mothers experience a normal birth with no obstetric interventions, and the chosen place of birth is implicated in this statistical outcome. Tertiary maternity settings report the highest rates of birth interventions, even for healthy women who can anticipate straightforward labour experiences. Among the most frequently used birth interventions are labour augmentation procedures - artificial rupture of membranes and administration of synthetic oxytocin infusions. My critical realist ethnography aims to explore the cultural landscape within one tertiary birthing suite and in doing so to identify the generative mechanisms that influence the likelihood of labour augmentation for well first-time mothers. I begin with a retrospective chart review to uncover the magnitude of the use of augmentation procedures for a sample of healthy women presenting in labour to the birthing suite over one calendar year. Interviews with women who experienced long labours yield insights about their decision-making with respect to augmentation. Focus groups and interviews with midwives and obstetric doctors contribute an understanding of factors associated with their use of augmentation, and a period of non-participant observation in the birthing suite illuminates the nuanced ways the unit culture contributes to the permissive use of augmentation procedures in this birthing environment. Findings reveal that sixty percent of women experienced labour augmentation procedures and for one third of them, the augmentation was not indicated according to the clinical guideline in use at the time. Pressure to be “movi

Aims: Approximately 6–9% pregnancies are affected by fetal growth restriction (FGR). Placental alterations related to utero‐placental insufficiency in FGR may induce placental vascular remodelling to the detriment of the fetus. The objective of this article was to study histopathological features of placentae in a cohort of preterm growth‐restricted infants in comparison to a cohort of preterm appropriately grown infants. Methods: In a cohort of 40 preterm infants of 28–32 weeks' gestation, placental histopathology was evaluated by a histopathologist, who was blinded to the identity of the grouping. Twenty infants had FGR, while 20 were appropriate for gestational age (AGA). Predefined histopathological characteristics were assessed based on the Amsterdam Placental Workshop Group Consensus Statement. Results: The gestational age and birthweight of the FGR and AGA cohorts were 29.8 ± 1.3 versus 30 ± 0.9 weeks, P = 0.78 and 923 ± 168 versus 1403 ± 237 g, <0.001, respectively. Maternal vascular malperfusion, accelerated villous maturation and fetal vascular malperfusion were features that were significantly more common in FGR placentae. Conclusion: Based on the results of the present study, specific placental histopathological changes may be present in FGR placentae, which may reflect the effects of utero‐placental insufficiency

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

Shawna V Hudson,1 Denalee M O’Malley,2 Suzanne M Miller3 1Department of Family Medicine and Community Health, Rutgers Robert Wood Johnson Medical School, Somerset, 2Rutgers School of Social Work, New Brunswick, NJ, 3Cancer Prevention and Control Program, Fox Chase Cancer Center/Temple University Health System, Philadelphia, PA, USA Background: Prostate cancer is the most commonly diagnosed cancer in men in the US, and the second most prevalent cancer in men worldwide. High incidence and survival rates for prostate cancer have resulted in a large and growing population of long-term prostate cancer survivors. Long-term follow-up guidelines have only recently been developed to inform approaches to this phase of care for the prostate cancer population. Methods: A PubMed search of English literature through August 2014 was performed. Articles were retrieved and reviewed to confirm their relevance. Patient-reported measures that were used in studies of long-term prostate cancer survivors (ie, at least 2 years posttreatment) were reviewed and included in the review. Results: A total of 343 abstracts were initially identified from the database search. After abstract review, 105 full-text articles were reviewed of which seven met inclusion criteria. An additional 22 articles were identified from the references of the included articles, and 29 were retained. From the 29 articles, 68 patient-reported outcome measures were identified. The majority (75%) were multi-item scales that had been previously validated in existing literature. We identified four main areas of assessment: 1) physical health; 2) quality of life – general, physical, and psychosocial; 3) health promotion – physical activity, diet, and tobacco cessation; and 4) care quality outcomes. Conclusion: There are a number of well-validated measures that assess patient-reported outcomes that document key aspects of long-term follow-up with respect to patient symptoms and quality of life.

The original document contains color images.

This technical note (TN), part of an ongoing Software Engineering Institute (SEI) series on Agile in the Department of Defense (DoD), addresses key issues that occur when Agile software teams engage with systems engineering functions in the development and acquisition of software-reliant systems. Published acquisition guidance still largely focuses on a system perspective, and fundamental differences exist between systems engineering and software engineering approaches. Those differences are compounded when Agile becomes a part of the mix, rather than adhering to more traditional ?waterfall?-based development lifecycles. For this TN, the SEI gathered more data from users of Agile methods in the DoD and delved deeper into the existing body of knowledge about Agile and systems engineering before addressing them. Topics considered here include various interaction models for integrating systems engineering functions with Agile engineering teams, automation, insight and oversight, training, the role of Agile advocates/sponsors and coaches, the use of pilot programs, stakeholder involvement, requirements evolution, verification and validation activities, and the means by which Agile teams align their increments with program milestones. This TN offers insight into how systems engineers and Agile software engineers can better collaborate when taking advantage of Agile as they deliver incremental mission capability.

Adoption of methodologies that generally come under the umbrella of Agile in the software development community includes consideration of how those adopting agile methods interface with elements of the acquisition community who provide the requirements and other constraints that govern how the software part of a system will be developed. Several Agile methods have expectations about how requirements are handled that are different from the typical approach used in government acquisition settings. This qualitative research study from the Software Engineering Institute explores issues that practitioners in the field who are actively adopting Agile methods have identified in our interviews about their experience in defining and managing requirements.

This technical note is one in a series of publications from the Software Engineering Institute intended to aid United States Department of Defense acquisition professionals in the use of Agile software development methods. As the prevalence of suppliers using Agile methods grows, these professionals supporting the acquisition and maintenance of software-reliant systems are witnessing large portions of the industry moving away from so-called traditional waterfall life cycle processes. The existing infrastructure supporting the work of acquisition professionals has been shaped by the experience of the industry -- which up until recently has tended to follow a waterfall process. The industry is finding that the methods geared toward legacy life cycle processes need to be realigned with new ways of doing business. This technical note aids acquisition professionals who are affected by that realignment.

Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1 mutation in a child with a PinB. This was accompanied by loss of heterozygosity (LOH) of the wild-type allele within the tumour. We set out to establish the prevalence of DICER1 mutations in an opportunistically ascertained series of PinBs. Twenty-one PinB cases were studied: Eighteen cases had not undergone previous testing for DICER1 mutations; three patients were known carriers of germ-line DICER1 mutations. The eighteen PinBs were sequenced by Sanger and/or Fluidigm-based next-generation sequencing to identify DICER1 mutations in blood gDNA and/or tumour gDNA. Testing for somatic DICER1 mutations was also conducted on one case with a known germ-line DICER1 mutation. From the eighteen PinBs, we identified four deleterious DICER1 mutations, three of which were germ line in origin, and one for which a germ line versus somatic origin could not be determined; in all four, the second allele was also inactivated leading to complete loss of DICER1 protein. No somatic DICER1 RNase IIIb mutations were identified. One PinB arising in a germ-line DICER1 mutation carrier was found to have LOH. This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility gene for PinB and demonstrates PinB to be a manifestation of a germ-line DICER1 mutation. The means by which the second allele is inactivated may differ from other DICER1-related tumours.

This technical note (TN) is part of the Software Engineering Institute s series on Agile in the Department of Defense (DoD). It primarily addresses what at first seems a small issue on the road to Agile adoption the confusion of terms. However, this is a much larger issue, as ineffective communications among and between stakeholders is often cited as a significant stumbling block on any project.3 Confusion over simple terms is a needless hurdle. Many terms and concepts used by Agile practitioners seem to confound those working in the DoD s Traditional World of waterfall-based environment, and vice versa. The goal of this paper is to assemble terms and concepts from both environments to show both the similarities (of which there are many) and differences (of which there are also many). A comprehensive cross dictionary was beyond the scope of this work; the authors strove to select from those terms most commonly encountered when considering Agile adoption. Therefore, the authors selected terms based on suggestions from both inside and outside the SEI, but deliberately limited themselves to 25 terms from each environment.

This technical note (TN), the second in an SEI series on Agile in the DoD, addresses some of the key issues that either must be understood to ease the adoption of Agile or are seen as potential barriers to adoption of Agile in the DoD acquisition context. These topics were introduced in the first TN of the series, CMU/SEI-2010-TN-002. For this TN, the SEI gathered more data from users of Agile methods in the DoD and delved deeper into the existing body of knowledge about Agile before addressing them. Topics considered here include: why DoD is interested in Agile methods; what it means to be Agile in the DoD; managing and contracting for Agile programs; technical milestone reviews in a DoD Agile acquisition context; estimating in a DoD Agile acquisition context; and moving toward adopting Agile practices. The authors hope that this report continues to stimulate discussion about and appropriate adoption of Agile in the DoD and federal agencies.

Presented at the 22nd Systems and Software Technology Conference (SSTC), 26-29 April 2010, Salt Lake City, UT. Sponsored in part by the USAF. U.S. Government or Federal Rights License

The primary aim of this two-arm prospective randomized controlled trial (N=232) was to evaluate the efficacy of a theory-based printed brochure intervention, directed to the partners of African American men, in promoting informed decision making about PSA screening for prostate cancer. Intervention participants received the intervention brochure and a control brochure; control participants received only the latter. Both brochures included information concerning prostate cancer, the heightened risk of African American for the disease, and prostate cancer screening. The intervention brochure also contained content designed to motivate and facilitate the partner's efforts in promoting informed decision making by the proband about PSA screening. The primary outcome variable was the proband's engagement in informed decision making about PSA screening, as reported by the partner. Secondary outcome variables included the extent of the partner's efforts to promote informed decision making about PSA screening, and the nature and utility of partner/proband communication about prostate cancer risk and screening. Secondary study aims included investigating the moderating role of attentional style (high vs low monitoring) with respect to the intervention's impact on the primary outcome variable, as well as the mediating role of cognitive-affective factors, partner-proband communication, and process variables.

The Carnegie Mellon Software Engineering Institute (SEI) facilitated an Army workshop, Beyond Technology Readiness Levels for Software, on August 10-11, 2010. The workshop, part of the ongoing Army Strategic Software Improvement Program (ASSIP), was an attempt to develop an Army perspective on the "right" software information to gather and analyze at significant program decision points (especially Milestones A, B, and C) to determine readiness to proceed to the next acquisition phase. This report synthesizes the workshop presentations, discussions, and outcomes., This work was created in the performance of Federal Government Contract Number FA8721-05-C-0003 with Carnegie Mellon University for the operation of the Software Engineering Institute, a federally funded research and development center. The Government of the United States has a royalty-free government-purpose license to use, duplicate, or disclose the work, in whole or in part and in any manner, and to have or permit others to do so, for government purposes pursuant to the copyright license under the clause at 252.227-7013.. The original document contains color images.

Early menarche is a risk factor for breast cancer. We investigated the variation in age at menarche by socioeconomic status (SES) and race. A cohort study was conducted on 1,091 black and 986 white girls from the three sites in the United States as part of the NHLBI Growth and Health Study (NGHS), who were aged 9–10 years at baseline and followed through adolescence over a 10-year period with annual exams. Using logistic regression models, we evaluated the nature and strength of associations between two socioeconomic indicators (household income and parental education) and early menarche (<12 years old) unadjusted and adjusted for anthropometry and maternal age at menarche. Proportionately, more black girls were menarcheal before 12 years of age compared to their white counterparts (46%, n = 468 vs. 26%, n = 240, respectively, p < 0.0001). Parental education was not a significant predictor of early menarche. The graded association between household income and age at menarche was strong and significant among black girls but less clear among white girls. Compared with those in the lowest quartile of household income, white girls in the highest quartile were at a significantly lower risk of early menarche [adjusted odds ratio (OR) = 0.37, 95% confidence intervals (CIs) 0.18–0.80]. The inverse was true for black girls: those in the highest quartile of household income were at an increased risk of early menarche (adjusted OR = 2.15, 95% CI 1.27–3.63) The SES factor selected (household income versus parental education) affected the findings regarding racial differences in the timing of menarche. It will be important for future studies to elucidate the link between household income and age at menarche in developed countries.

Prostate cancer is the second leading cause of cancer death in men. Like other cancers, prostate cancer exists in both sporadic and hereditary forms. A family history of prostate cancer and African-American ethnicity are two key factors that have been found to place men at increased risk for developing the disease. However, at-risk men exhibit low levels of prostate cancer risk-related knowledge, despite their increased risk as a group. Prostate cancer risk assessment provides an opportunity to weigh available information and make decisions about screening options; it also provides a window of opportunity to offer concrete instruction in specific prevention behaviors. While there is controversy over the benefits and liabilities associated with prostate cancer screening, there is agreement that at-risk men need to understand the issues related to prostate cancer risk management. Family members can help facilitate health-related behavior and may serve as an important, but underutilized, gateway into the health care system. Thus, guided by the Cognitive-Social Health Information Processing (C-SHIP) model, the current study will evaluate the impact of a communication message intervention tailored to the partners of at-risk men enrolling in prostate cancer risk assessment to facilitate screening adherence.

A woman's first birth experience can be a powerfully transformative event in her life, or can be so traumatic it affects her sense of 'self' for years. It can influence her maternity future, her physical and emotional health, and her ability to mother her baby. It matters greatly how her first birth unfolds. Women in Aotearoa/New Zealand enjoy a range of options for provision of maternity care, including, for most, their choice of birth setting. Midwives who practice in a range of settings perceive that birth outcomes for first-time mothers appear to be 'better' at home. An exploration of this perception seems warranted in light of the mainstream view that hospital is the optimal birth setting. The research question was: "Do midwives offer the same intrapartum care at home and in hospital, and if differences exist, how might they be made manifest in the labour and birth events of first-time mothers?" This mixed-methods study compared labour and birth events for two groups of first-time mothers who were cared for by the same midwives in a continuity of care context. One group of mothers planned to give birth at home and the other group planned to give birth in a hospital where anaesthetic and surgical services were available. Labour and birth event data were collected by a survey which was generated following a focus group discussion with a small group of midwives. This discussion centred around whether these midwives believed their practice differed in each setting, and what influenced care provision in each place. Content analysis of the focus group data saw the emergence of four themes relating to differences in practice: midwives' use of space, their use of time, the 'being' and 'doing' of midwifery and aspects relating to safety. Survey data were analysed using SPSS. Despite being cared for by the same midwives, women in the hospital-birth group were more likely to use pharmacological methods of pain management, experienced more interventions (ARM, vaginal exami

The Behavioral Center of Excellence (BCE) in Breast Cancer was established to provide a comprehensive, multidisciplinary approach for studying the process of, and methods for facilitating, successful adaptation in the context of breast cancer risk, treatment, and recovery. The four ongoing studies are derived from and integrated by a unifying theoretical framework, and ere supported by four care facilities ( i . e . , Administrative, Communication, Genetic Testing and Bioinformatics Core). The four projects are: 1) development of an intervention to promote utilization of breast cancer risk assessment programs and adherence to screening recommendations and underserved African-American women; 21 use of a "teachable moments and tailored communication materials to g r a t e utilization of risk assessment and adherence to screening amen0 daughters of diagnosed breast cancer patients 3) the g r m t i o n of psychological and physical adaptation among breast cancer patients at the completion of active treatments., during the re-entry phase); 4) promotion of psychological adaptation among metastatic breast cancer patients. The overarching goal is to develop theoretically guided, tailored, and transportable breast cancer communications to enhance screening adherence, decision-making, and quality of life across the spectrum of disease ( i . e . , from risk through treatment to survivorship)., The original document contains color images.

Approximately 20-30% of women develop lymphedema (LE) following breast cancer treatment. Effective symptom management requires that women recognize early signs of lymphedema and maintain precautionary practices over time. Data indicates that knowledge and use of symptom minimization precautions are poor. Little is known about how breast cancer survivors perceive their LE nsk and the cognitive- affective factors that promote the uptake and adherence to LEsymptom minimization precautions. Guided by the Cognitive-Social Health Information Processing (C-SHIP) model we conducted a longitudinal study to assess barriers and facilitators associated with knowledge and adherence to LE symptom-minimization practices among breast cancer survivors. We are exploring the mediating role of cognitive- affective variables and the moderating role of attentional style on knowledge uptake and adherence of symptom minimization precautions at baseline 6- and 12-month follow-up post treatment. Little is known about how individuals understand and make sense of these issues and few resources have been developed to address this problem. Through systematic investigation of these factors we will be able to develop a profile of the role of cognitive-emotional processing in the management of lymphedema. These data will ultimately be used to design and evaluate enhanced management protocols tailored to the individual%s cognitive-emotional signature.

The Behavioral Center of Excellence (BCE) in Breast Cancer was established to provide a comprehensive, multidisciplinary approach for studying the process of, and methods for facilitating, successful adaptation in the context of breast cancer risk, treatment, and recovery. The four ongoing studies are derived from and integrated by a unifying theoretical framework, and ere supported by four care facilities ( i . e . , Administrative, Communication, Genetic Testing and Bioinformatics Core). The four projects are: 1) development of an intervention to promote utilization of breast cancer risk assessment programs and adherence to screening recommendations and underserved African-American women; 21 use of a "teachable moments and tailored communication materials to g r a t e utilization of risk assessment and adherence to screening amen0 daughters of diagnosed breast cancer patients 3) the g r m t i o n of psychological and physical adaptation among breast cancer patients at the completion of active treatments., during the re-entry phase); 4) promotion of psychological adaptation among metastatic breast cancer patients. The overarching goal is to develop theoretically guided, tailored, and transportable breast cancer communications to enhance screening adherence, decision-making, and quality of life across the spectrum of disease ( i . e . , from risk through treatment to survivorship).

Approximately 20-30% of women develop lymphedema (LE) following breast cancer treatment. Effective symptom management requires that women recognize early signs of lymphedema, and maintain precautionary practices over time. Data indicates that knowledge and use of symptom minimization precautions are poor. Little is known about how breast cancer survivors perceive their LE risk, and the cognitive-affective factors that promote the uptake and adherence to LE symptom minimization precautions. Guided by the Cognitive-Social Health Information Processing (C-SHIP) model, we are conducting a longitudinal study, to assess barriers and facilitators associated with knowledge and adherence to LE symptom-minimization practices among breast cancer survivors. We are exploring the mediating role of cognitive-affective variables, and the moderating role of attentional style, on knowledge, uptake and adherence. Our preliminary analysis shows a correlation between high monitoring and more knowledge of lymphedema risks compared to low-monitoring styles. We are surveying levels of knowledge, and practice of symptom minimization precautions at baseline, 6-, and 12-month follow-up. Although many women are aware of LE minimization practices, data suggest that they are not incorporating the recommendations into their daily lives. Further, psychosocial factors play a role in the uptake of LE symptom-minimization practices, and sustained adherence over time.

Prostate cancer is the second leading cause of cancer death in men. Like other forms, prostate cancer exists in both sporadic and hereditary forms. A family history of prostate cancer and African-American ethnicity are two key factors that have been found to place men at increased risk for developing the disease. However, at-risk men exhibit low levels of prostate cancer risk-related knowledge, despite their increased risk as a group. Prostate cancer risk assessment provides an opportunity to weigh available information and make decisions about screening options; it also provides a window of opportunity to offer concrete instruction in specific prevention behaviors. While there is controversy over the benefits and liabilities associated with prostate cancer screening, there is agreement that at-risk men need to understand the issues related to prostate cancer risk management. Family members can help facilitate health-related behavior and may serve as an important, but underutilized, gateway into the health care system. Thus, guided by the Cognitive-Social Health Information Processing (C-SHIP) model, the current study will evaluate the impact of a communication message intervention tailored to the partners of at-risk men enrolling in prostate cancer risk assessment to facilitate screening adherence.

This study evaluated the efficacy of a patient-spouse centered cognitive-affective counseling session (CARE: cognitive-affective reactions and expectations), to facilitate treatment decision-making for localized prostate cancer (PrCa). Methods: CARE identified treatment-related values and goals and focused on improving knowledge about treatment options. A time and attention matched General Health Information (GHI) session provided nutrition information. Couples (N=300) were enrolled after diagnosis with PrCa, but before a definite treatment decision was made. Data were assessed separately for patients and spouses at baseline, at 6-months, and at 12 months post intervention. Results: Both sessions were well accepted among participants. The goal of CARE to facilitate treatment decision making was best achieved for spouses and among those patient/partners who chose a non-invasive treatment option. Partners were more distressed about the treatment decision compared to patients, especially in the CARE condition and when considering invasive procedures. We interpret this result as an indication that participants in CARE processed the relevant information and that momentarily higher levels of distress were the cost of such processing. At 6-mo this effect disappears, underscoring its temporal nature. Conclusions: The results demonstrate the usefulness of integrating a brief counseling session into the decision-making process, and that increases in perceived difficulty of decision-making are short-term., The original document contains color images.

We reviewed the empirical literature on psychosocial factors influencing women’s decisions to undergo prophylactic surgery. A total of 34 studies were identified. The majority of studies found that women’s cancer-specific worries and risk perceptions exerted considerable influence in decision making about prophylactic surgery. Higher levels of cancerspecific anxiety were positively associated with interest in and intention to undergo surgery. In addition, greater perceived risk was also associated with greater interest and uptake of prophylactic surgery. Women also cited issues concerning body image and sexuality, familial responsibilities, and cultural norms as influencing the decision-making process. Several studies have begun to evaluate the impact of decision aids and counseling interventions, but additional studies are still needed to evaluate the long-term psychosocial, behavioral, and medical implications of these interventions. Decision counseling and preference clarification may be useful in facilitating the selection between different behavioral alternatives and in enhancing patient outcomes.

Approximately 20-30% of women develop lymphedema (LE) following breast cancer treatment; this condition has been associated with psychological distress and diminished quality of life. Effective symptom management requires that women not only recognize early signs of this condition, but that they uptake and maintain precautionary practices over their lifetime. Yet, the limited data available indicate that knowledge and use of symptom minimization precautions are poor, particularly over time. Unfortunately, little is known about how breast cancer survivors perceive their LE risk status, and the cognitive-affective factors that promote the uptake of; and adherence to, LE symptom minimization precautions. Further, the moderating role of individual differences in attentional style has not been explored. Guided by the Cognitive-Social Health Information Processing (C-SHIP) model, we will conduct a longitudinal study, to assess the barriers and facilitators associated with knowledge about, and adherence to, LE symptom-minimization practices among breast cancer survivors currently unaffected by LE. We will explore the mediating role of cognitive-affective variables, and the moderating role of attentional style, on knowledge, uptake and adherence over time. Toward this end, we will survey levels of knowledge, and the practice of symptom minimization precautions at baseline, and again at 6-, and 12-month follow-up.

Breast cancer represents a serious health concern for women across the disease spectrum. First, despite the advances in technology used for intensive disease surveillance and innovative preventative options, interest in and utilization of these technologies is less than optimal, especially among low-income, African-American women. Second, among women who have completed cancer treatment, psychological after-effects that can have a negative impact on adjustment and adherence to further screening practices are prevalent. Finally, for those cancer patients whose disease has metastasized, clinically relevant psychosocial adjustment problems need to be recognized and managed. It is for these reasons that research leading to improvements in quality of life throughout the disease spectrum is necessary. The Behavioral Center for Excellence, through the coordination of four projects, seeks to understand and evaluate psychosocial approaches for promoting psychological and physical adaptation to cancer risk, treatment, and survival. Each project systematically assesses and addresses barriers to, and facilitators of, adjustment and adherence and evaluates interventions designed for this cause. With support from four core facilities, the BCE has assembled a multi-disciplinary research team to conduct an interrelated set of studies that are theoretically guided, thematically convergent, and synergistic in the impact on the behavioral aspects of breast cancer.

This paper documents some of the challenges and risks facing programs or organizations trying to help small manufacturing enterprises (SMEs). The Technology Insertion, Demonstration, and Evaluation (TIDE) Program performed seven demonstration projects with SMEs. While the companies differed in size, technology needs, and in-house capabilities, they are typical of the companies to be found in the SME sector. This report examines the effort to help SMEs through demonstration projects. It describes the challenges that the TIDE Program personnel faced, and presents recommendations to help organizations in similar situations address or avoid those challenges.

Breast cancer represents a serious health concern for women, across the disease spectrum. First, despite advances in technology used for intensive disease surveillance and innovative preventive options, interest in and utilization of these technologies is less than optimal, especially among low-income, African-American women and first-degree relatives. Second, among women who have completed cancer treatment, psychological after-effects that can have a negative impact on adjustment and adherence to screening practices are prevalent. Finally, for those cancer patients whose disease has metastasized, clinically relevant psychosocial adjustment problems need to be recognized and managed. It is for these reasons that research leading to improvements in quality of life throughout the disease spectrum is necessary. The Behavioral Center for Excellence, through the coordination of four projects, seeks to understand and evaluate psychosocial approaches for promoting psychological and physical adaptation to cancer risk, treatment and survival. Each project systematically assesses and addresses barriers to, and facilitators of, adjustment and adherence and evaluates interventions designed for this cause. With support from four core facilities, the BCE has assembled a multi-disciplinary research team to conduct an interrelated set of studies that are theoretically-guided, thematically convergent. and synergistic in the impact on the behavioral aspects of breast cancer., The original document contains color images. All DTIC reproductions will be in black and white.

Approximately 20-30% of women develop lymphedema (LE) following breast cancer treatment; this condition has been associated with psychological distress and diminished quality of life. Effective symptom management requires that women not only recognize early signs of this condition, but that they uptake and maintain precautionary practices over their lifetime. Yet, the limited data available indicate that knowledge and use of symptom minimization precautions are poor, particularly over time. Unfortunately, little is known about how breast cancer survivors perceive their LE risk status, and the cognitive- affective factors that promote the uptake of, and adherence to, LE symptom minimization precautions. Further, the moderating role of individual differences in attentional style has not been explored. Guided by the Cognitive-Social Health Information Processing (C- SHIP) model, we will conduct a longitudinal study, to assess the barriers and facilitators associated with knowledge about, and adherence to, LE symptom-minimization practices among breast cancer survivors currently unaffected by LE. We will explore the mediating role of cognitive-affective variables, and the moderating role of attentional style, on knowledge, uptake and adherence over time. Toward this end, we will survey levels of knowledge, and the practice of symptom minimization precautions at baseline, and again at 6-, and 12- month follow-up.

Breast cancer represents a serious health concern for women, across the disease spectrum. First despite advances in technology used for intensive disease surveillance and innovative preventive options, interest in and utilization of these technologies is less than optimal, especially among low-income, African-American women and first-degree relatives. Second, among women who have completed cancer treatment, psychological after-effects that can have a negative impact on adjustment and adherence to screening practices are prevalent. Finally, for those cancer patients whose disease has metastasized, clinically relevant psychosocial adjustment problems need to be recognized and managed. It is for these reasons that research leading to improvements in quality of life throughout the disease spectrum is necessary. The Behavioral Center for Excellence, through the coordination of four projects, seeks to understand and evaluate psychosocial approaches for promoting psychological and physical adaptation to cancer risk, treatment and survival. Each project systematically assesses and addresses barriers to, and facilitators of, adjustment and adherence and evaluates interventions designed for this cause. With support from four core facilities, the BCE has assembled a multi-disciplinary research team to conduct an interrelated set of studies that are theoretically-guided, thematically convergent, and synergistic in the impact on the behavioral aspects of breast cancer.

Previous research shows that women often lack knowledge regarding the kinds of information required to determine inherited risk as well as on the process and content of risk assessment/genetic testing. This lack of information leads them to feel unprepared for risk assessment/genetic testing, if they choose to seek it. This pilot study developed an enhanced intervention to increase a woman's knowledge of: 1) the factors that determine a genetic predisposition to breast/ovarian cancer, 2) personal family history and other risk factors, 3) the benefits and drawbacks of genetic testing for breast/ovarian cancer, 4) the range of surveillance and preventive behaviors available, and 5) the actual process of risk assessment/genetic testing. Participants were 279 women who contacted the Atlantic Region of the National Cancer Institute's (NCI) Cancer Information Service (CIS) requesting information about risk for breast/ovarian cancer and/or information about risk assessment services and genetic testing. Women were randomly assigned to either the standard or enhanced intervention. The study, comparing the standard and enhanced interventions, tested the effectiveness of the CIS in increasing a woman's knowledge of inherited breast/ovarian cancer and the process of risk assessment/genetic testing as well as her sense of preparation and intention to pursue such services.

Previous research has shown that women often lack knowledge regarding the kinds of information that are required to determine inherited risk as well as on the process and content of risk assessment/genetic testing. This lack of information leads them to feel unprepared for risk assessment/genetic testing, if they choose to seek it. The present study will evaluate an enhanced intervention's ability to increase a women's knowledge of: 1) the factors that determine genetic predisposition to breast/ovarian cancer; 2) their personal family history and other risk factors; 3) the benefits and drawbacks of genetic testing for breast/ovarian cancer; 4) the range of surveillance and preventive behaviors available; and 5) the actual process of risk assessment/genetic testing. Participants are 200 women who contact the Cancer Information Service (CIS) requesting information on inheritable breast/ovarian cancer, risk assessment and/or genetic testing. Women are randomly assigned to either the standard or enhanced intervention. A randomized study in which the two interventions are compared will test the effectiveness of the CIS in increasing women's knowledge of inheritable breast/ovarian cancer and the process of risk assessment/genetic testing.

Previous research has shown that women often lack knowledge regarding the kinds of information that are required to determine inherited risk as well as on the process and content of risk assessment/genetic testing. This lack of information leads them to feel unprepared for risk assessment/genetic testing, if they choose to seek it. The present study will evaluate an enhanced intervention's ability to increase a woman's knowledge of: 1) the factors that determine genetic predisposition to breast/ovarian cancer, 2) their personal family history and other risk factors, 3) the benefits and drawbacks of genetic testing for breast/ovarian cancer, 4) the range of surveillance and preventive behaviors available, and 5) the actual process of risk assessment/genetic testing. Participants are 200 women who contact the Cancer Information Service (CIS) requesting information on inheritable breast/ovarian cancer, risk assessment and/or genetic testing. Women are randomly assigned to either the standard or enhanced intervention. A randomized study in which the two interventions are compared will test the effectiveness of the CIS in increasing women's knowledge of inheritable breast/ovarian cancer and the process of risk assessment/genetic testing.

The present study aims to increase a woman's knowledge of: (1) the factors that determine genetic predisposition to breast/ovarian cancer, (2) personal family history and other risk factors, (3) the benefits and drawbacks of genetic testing for breast/ovarian cancer, (4) the range of surveillance and preventive behaviors available and, (5) the process of genetic testing. Participants will be 200 women who have contacted the Cancer Information Service (CIS) requesting information on inherited breast/ovarian cancer. Women will be randomly assigned to a standard or enhanced intervention testing the effectiveness of the CIS in increasing a woman's knowledge of inherited disease, risk assessment and genetic testing. As planned, this first year was dedicated to a formative evaluation of the informational/emotional needs of women pursuing risk assessment services. The structured interviews and focus groups conducted with women from the lay population, women at high risk and genetic counselors informed the development of the enhanced intervention. The interviews/groups supported previous research demonstrating that women are unprepared for and have limited knowledge about the process and outcomes of risk assessment for genetic predisposition to breast/ovarian cancer. A comprehensive training program and formalized standard protocol will ensure competence and consistency when accrual begins in the Pall.

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Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of extra cellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases and we hypothesised that the ECM in IPF is abnormally cross-linked which enhances fibroblast growth and resistance to normal ECM turnover. We used a combination of in vitro ECM preparations and in vivo assays to examine the expression of cross-linking enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover. Lysyl oxidase like 1, 2, 3 and 4 were expressed equally in control and IPF derived fibroblasts. Transglutaminase 2 was more strongly expressed in IPF fibroblasts. Lysyl oxidase like 2, transglutaminase 2 and transglutaminase generated cross-links were strongly expressed in IPF lung tissue. Fibroblasts grown on IPF ECM had higher LOXL3 protein expression and transglutaminase activity compared with those grown on control ECM. IPF derived ECM also enhanced fibroblast adhesion and proliferation compared with control ECM. Inhibition of lysyl oxidase and transglutaminse activity during ECM formation affected ECM structure as visualised by electron microscopy and reduced the enhanced fibroblast adhesion and proliferation of IPF ECM to control levels. Inhibition of transglutaminase, but not lysyl oxidase activity, enhanced the turnover of ECM in vitro. In bleomycin treated mice, during the post-inflammatory fibrotic phase, inhibition of transglutaminases was associated with a reduction in whole lung collagen. Our findings suggest that the ECM in IPF may enhance pathological cross-linking which contributes to increased fibroblast growth, resistance to normal ECM turnover to drive lung fibrosis.

CNS PNET and pineoblastomas are highly malignant embryonal brain tumours of poor prognosis. Current treatment strategies are based on the histologically similar medulloblastoma; however, patients with CNS PNET and pineoblastoma have significantly worse outcomes. Specific therapies based on the underlying biology and genetics of CNS PNET and pineoblastoma are needed. To provide evidence of the fundamental genetics driving tumour pathogenesis and to identify novel targets for therapy, 46 CNS PNETs and pineoblastomas were analysed using the Affymetrix 100K/500K mapping sets to identify genome-wide copy number alterations and loss of heterozygosity. Overall, frequent gains of 1q, 2p and 21q and frequent loss of 16q were identified. Unsupervised hierarchical clustering showed marked differences in the frequency of genetic imbalance in the CNS PNETs and pineoblastomas, with pineoblastomas containing fewer genomic changes clustering separately to the CNS PNETs. Novel gene copy number alterations were identified; gain of PCDHGA3 (5q31.3) and FAM129A (1q25) and losses of OR4C12 (11p11.12), CADPS (3p14.2), and SALL1 (16q12.1). Loss of CDKN2A and CDKN2B was also identified, in keeping with previous genetic studies of CNS PNET. Linking gene copy number data with patient clinical information, loss of CADPS was associated with poor prognosis in patients with primary CNS PNETs (p = 0.033 and p = 0.046, by SNP array and real time qPCR analyses, respectively). On comparison of 5 primary and recurrent CNS PNET pairs, gain of 2p21 was the most common alteration maintained in 80% of cases. Immunohistochemistry for p15INK4B (encoded by CDKN2B) was performed which demonstrated the loss in gene copy number had lowered the expression of the encoded protein. Finally an immunohistochemical and mutational screen for INI1 (commonly lost in the malignant embryonal brain tumour, ATRT) was performed in the CNS PNET/pineoblastoma cohort which showed the loss of INI1 protein expression in the tumou

Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of extra cellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases and we hypothesised that the ECM in IPF is abnormally cross-linked which enhances fibroblast growth and resistance to normal ECM turnover. We used a combination of in vitro ECM preparations and in vivo assays to examine the expression of cross-linking enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover. Lysyl oxidase like 1, 2, 3 and 4 were expressed equally in control and IPF derived fibroblasts. Transglutaminase 2 was more strongly expressed in IPF fibroblasts. Lysyl oxidase like 2, transglutaminase 2 and transglutaminase generated cross-links were strongly expressed in IPF lung tissue. Fibroblasts grown on IPF ECM had higher LOXL3 protein expression and transglutaminase activity compared with those grown on control ECM. IPF derived ECM also enhanced fibroblast adhesion and proliferation compared with control ECM. Inhibition of lysyl oxidase and transglutaminse activity during ECM formation affected ECM structure as visualised by electron microscopy and reduced the enhanced fibroblast adhesion and proliferation of IPF ECM to control levels. Inhibition of transglutaminase, but not lysyl oxidase activity, enhanced the turnover of ECM in vitro. In bleomycin treated mice, during the post-inflammatory fibrotic phase, inhibition of transglutaminases was associated with a reduction in whole lung collagen. Our findings suggest that the ECM in IPF may enhance pathological cross-linking which contributes to increased fibroblast growth, resistance to normal ECM turnover to drive lung fibrosis.

Introduction Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model. Methods Immunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells. Gene expression array data was used to identify AGER expression during lung development in 38 fetal lung samples. RNA-Seq was used to identify AGER transcripts in lung cells. sRAGE levels were assessed in cells and patient serum by ELISA. BEAS2B-R1 cells were transfected to overexpress RAGE protein with either the Gly82 or Ser82 variant and sRAGE levels identified. Results Immunohistochemical assessment of 6 adult lung samples identified high RAGE expression in the alveoli of healthy adults and individuals with COPD. AGER/RAGE expression increased across developmental stages in human fetal lung at both the mRNA (38 samples) and protein levels (20 samples). Extensive AGER splicing was identified. The rs2070600T (Ser82) allele is associated with higher FEV1, FEV1/FVC and lower serum sRAGE levels in UK smokers. Using an airway epithelium model overexpressing the Gly82 or Ser82 variants we found that HMGB1 activation of the RAGE-Ser82 receptor results in lower sRAGE production. Conclusions This study provides new information regarding the expression profile and potential role of RAGE in the human lung and shows a functional role of the Gly82Ser variant. These findings advance our understanding of the potential mechanisms underlying COP