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In a study involving women undergoing breast-conserving therapy, the group that had the cavity of tumor resection shaved had a significantly lower rate of positive margins than the no-shave group (19% vs. 34%). Half as many such patients required second surgery for margin clearance. Many women who receive a diagnosis of early-stage breast cancer opt for breast-conserving surgery with partial mastectomy. 1 Although the survival rate with such surgery is equivalent to that with total mastectomy, margin status is a critical determinant of local recurrence. 2 Approximately 20 to 40% of patients have positive margins (margins positive for tumor) after partial mastectomy and require a second operation for margin clearance. 3 , 4 Retrospective studies have shown that taking additional tissue circumferentially around the cavity left by partial mastectomy (also known as cavity shave margins) may reduce the rate of positive margins. However, others have argued that it . . .

Background Tumor-infiltrating lymphocyte (TIL) count in breast cancer carries prognostic information and represents a potential predictive marker for emerging immunotherapies. However, the distribution of the lymphocyte subpopulations is not well defined. The goals of this study were to examine intratumor heterogeneity in TIL subpopulation counts in different fields of view (FOV) within each section, in different sections from the same biopsy, and between biopsies from different regions of the same cancer using quantitative immunofluorescence (QIF). Methods We used multiplexed QIF to quantify cytokeratin-positive epithelial cells, and CD3-positive, CD8-positive and CD20-positive lymphocytes in tissue sections from multiple biopsies obtained from different areas of 31 surgically resected primary breast carcinomas (93 samples total). Log2-transformed QIF scores or concordance and variance component analyses with linear mixed-effects models were used. Cohen’s kappa index [k] of high versus low scores, defined as above and below the median, was used to measure sample similarity between areas. Results We found a strong positive correlation between CD3 and CD8 levels across all patients (Pearson correlation coefficient [CC] = 0.827). CD3 and CD8 showed a weaker but significant association with CD20 (CC = 0.446 and 0.363, respectively). For each marker, the variation between different FOVs in the same section was higher than the variation between sections or between biopsies of the same cancer. The intraclass correlation coefficients (ICC) were 0.411 for CD3, 0.324 for CD8, and 0.252 for CD20. In component analysis, 66–69 % of the variance was attributable to differences between FOVs in the same section and 30–33 % was due to differences between biopsies from different areas of the same cancer. Section to section differences were negligible. Concordance for low versus high marker status assignment in single biopsies compared to all three biopsies combined yielded k = 0.705 for CD3, k = 0.655 for CD8, and k = 0.603 for CD20. Conclusions T and B lymphocytes show more heterogeneity across the dimensions of a single section than between different sections or regions of a given breast tumor. This observation suggests that the average lymphocyte score from a single biopsy of a tumor is reasonably representative of the whole cancer.

Background Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. Results Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank ( n  = 25) and from non-cancer-related breast surgery specimens ( n  = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the “Epigenetic Clock,” a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age ( r  = 0.712, p  < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue ( p  = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue ( p  = 0.012). Conclusions Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

Gastrointestinal nematodes (GINs) are a common threat faced by pastoral livestock. Since their major introduction to the UK in the early 1990s, South American camelids have been cograzed with sheep, horses, and other livestock, allowing exposure to a range of GIN species. However, there have been no molecular-based studies to investigate the GIN populations present in these camelids. In the current study, we sampled nine alpaca herds from northern England and southern Scotland and used high-throughput metabarcoded sequencing to describe their GIN species composition. A total of 71 amplicon sequence variants (ASVs) were identified representing eight known GIN species. Haemonchus contortus was the most prevalent species found in almost all herds in significant proportions. The identification of H. contortus in other livestock species is unusual in the northern UK, implying that alpacas may be suitable hosts and potential reservoirs for infection in other hosts. In addition, the camelid-adapted GIN species Camelostrongylus mentulatus was identified predominantly in herds with higher faecal egg counts. These findings highlight the value of applying advanced molecular methods, such as nemabiome metabarcoding to describe the dynamics of gastrointestinal nematode infections in novel situations. The results provide a strong base for further studies involving cograzing animals to confirm the potential role of alpacas in transmitting GIN species between hosts.

Background Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins. Patients and Methods The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0–3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins. Results A total of 631 patients participated. Median age was 64 (range 29–94) years, with a median tumor size of 1.3 cm (range 0.1–9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant ( p  = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status ( p  = 0.110). Rather, age ( p  = 0.032) and tumor size ( p  = 0.040) were the only factors associated with margin status. Conclusion These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors.

Standard two-dimensional (2D) specimen radiography may guide intraoperative re-excision of margins in patients undergoing breast conserving surgery. We sought to determine the impact of three-dimensional (3D) specimen imaging in further reducing positive margin rates. A prospective study of 100 patients in which both 2D and 3D specimen radiographies were performed. The impact of orthogonal view on intraoperative surgical management and final margins was assessed. Ten patients had no residual tumor; therefore, 90 patients formed the cohort of interest. Of them, 21 patients (23.3%) had ductal carcinoma in situ; 18 (20.0%) had invasive cancer; and 51 (56.7%) had both. Median tumor size was 1.7 cm (range, .2 to 8.1 cm). On the basis of 2D imaging, surgeons stated they would take more tissue in 26 patients (28.9%). Three-dimensional imaging changed management in 4 patients (6.3%). One of these patients would have had positive margins if the intraoperative resection done on the basis of the 3D imaging would have been omitted. Three-dimensional specimen imaging results in further intraoperative re-excision in 6.3% of patients and may reduce re-excision rates in 2.2%. •Two dimensional specimen radiography reduces positive margin rates by 7.8%.•Adding orthogonal (3D) images reduces positive margin rates by another 1.1%.

Using a consensual qualitative research (CQR) approach, this study investigated the experience of nontenured, tenure track faculty (NTTTF) members involved in gatekeeping with students for non-academic concerns from American Psychological Association (APA)- and The Council for the Accreditation of Counseling and Related Educational Programs (CACREP)-accredited programs. The study investigated the emotional and cognitive reactions, factors supportive/facilitative and discouraging/hindering of the decision to intervene, the impact the gatekeeping process had on NTTTF relationships and what the NTTTF learned from the gatekeeping intervention. Participants were five female faculty members. Results indicated participants had little to no training in gatekeeping beyond informal training from mentors/colleagues, but suggested that faculty should receive a fact-based training/orientation and be provided with mentoring. The NTTTF cared for the gatekept student’s wellbeing, but the student rejected the relationship. Supportive/facilitative factors for the faculty in intervening were a) support offered by other faculty; b) support sought from mentors; c) a sense of responsibility to protect future clients and the profession; d) confidence in their own experience, competence and evidence; and e) concern for the student. Hindering/discouraging factors were a) experience of negative affect, self-doubt, or anxiety; b) lack of support or engagement from other faculty members; c) lack of support from University officials; d) and departmental policies and procedures. Professionally, participants lost time and energy for publication and other professional responsibilities during the gatekeeping experience. After the intervention, they are faster to intervene with concerns, have more conversations with students about gatekeeping prior to problems, and are seen as the “go-to” faculty in their department for future gatekeeping and policy development. The intervention led to increased trust and connection with other faculty, increased communication and partnership with support staff, and increased stress in family relationships. Other students in participants’ programs had questions about enforcement of training/professional standards related to the gatekept student. Results’ relationship to Social Cognitive Career Theory are investigated. Implications for training and practice, as well as future directions for research, are discussed.

Premature infant mortality and poor neurodevelopmental outcomes are great concerns worldwide as well as in South African Neonatal Intensive Care Units (NICUs). The Neurodevelopmental Supportive Care (NDSC) approach focuses on the improvement of neurodevelopmental outcomes by promoting a uterinelike environment by limiting noxious stimuli provided by the NICU environment. It is evident that developmental outcomes in the NICU need to be optimised and this can occur through further education and training of the multi-disciplinary team (MDT) on the application of NDSC guidelines in these units.In order to develop and implement such a programme, it is vital to first determine the perceptions of the MDT on the current standards of NDSC before a training programme can be developed and implemented. The aim of this study was to determine the self-reported perceptions of the MDT regarding the current standards of developmental care in two public-sector NICUs in Gauteng.A quantitative, cross sectional survey design was used to describe the selfreported perceptions of the MDT (qualified specialists, doctors, nurses and all therapists) working in the NICUs. Data was collected by making use of an existing checklist, the Instrument for Neurodevelopmental Supportive Care.The quantitative data gained from the questionnaire was studied manually, ultimately portraying a great deal of optimal as well as high-risk practices. The prevalence of high-risk practices for both hospitals was found to be evidently higher compared to the optimally applied elements. It included the categories of NICU design, family-centred philosophy, environmental stimulation, pain management, knowledge of preterm infant development as well as feeding. Very few significant differences were identified between the two participating hospitals, thus making it apparent that the participating MDT members perceive that a lot of room for improvement is present regarding the application of NDSC in the NICUs of the two participating hospitals.

Wilderness Therapy Programs have recently become a formal alternative treatment for adolescents with emotional and behavioral disorders (Hinkle, 1999; Russell & Hendee, 1999; Russell, Hendee, & Phillips-Miller, 2000; Russell, 2003a, 2003b). Adolescent populations are unique in that traditional forms of psychotherapy, including “talk-therapies,” are often inadequate for adolescents' stage of development. Despite improvements in mental health awareness, there continues to be barriers to service, including a lack of education and awareness about psychological concerns of children and adolescents, stigma associated with mental health issues, and a staggering rise in health care costs (Department of Health and Human Services [DHHS], 1999; National Advisory Mental Health Council Workgroup, 2001; Russell, 2003a, 2003b). An extraordinary number of children and adolescents in need of psychological services are not being adequately treated (Bryson, 1997; Davis-Berman, & Berman, 1994a; DHHS; Harris, Leiberman, & Marans, 2007; National Advisory Mental Health Council Workgroup, 2001; Reid & Eddy, 2002; Russell, 2003a). With growing rates of mental health issues among children and adolescents, this population in particular needs access to quality and appropriate therapeutic treatments. Wilderness Therapy has become a popular alternative because various components that are unique to this therapeutic intervention are particularly effective with adolescent populations, and notably less stigma is attached to this form of treatment (Crisp, 1998; Davis-Berman & Berman, Gass, 1995; Hinkle; Russell, 1999; Russell & Farnum, 2004; Russell & Hendee; Russell, Hendee, & Phillips-Miller; Russell, 2003a; 2003b). Wilderness Therapy Programs have successfully improved qualities in adolescents. Historically, however, these programs are used as a final treatment option, mostly because of the lack of familiarity of programs, sensationalized boot camp views of the programs, and the inaccurate assumption that these programs are more expensive than traditional treatment (Russell, 2003b; Russell & Farnum). Wilderness Therapy Programs offer children and adolescents an experience that challenges dysfunctional beliefs and coping skills, provides them with a stronger skills set, and improves their ability effectively communicate with others. Wilderness Therapy Programs developed for healthy populations have demonstrated an increase in overall personal enhancement (Crisp, 1998; Davis-Berman & Berman, 1994a; Ewert, McCormick, & Voight, 2001; Fletcher & Hinkle, 2002; Gass, 1993; Gillis & Thomsen, 1996; Kelley et al., 1997). These positive effects found in wilderness therapy programs could be adapted and used in a preventative form for youth at risk of developing emotional and behavioral disorders. One difficulty inherent in studying the effectiveness of wilderness therapy programs is the lack of strong empirical support for its use. Although the field of wilderness therapy has campaigned for clearer definitions and descriptions of interventions categorized under the umbrella of adventure or recreation therapy, barriers still exist for gathering empirical data Wilderness therapy occurs with a wide variety of populations and settings, and there continues to be a lack of validated measurement tools and control groups making empirical studies flawed. These methodological flaws limit the few studies in existence into general anecdotal reports with ungeneralizable results. Recently, the works of Michael Gass, Jennifer Davis-Berman, Dene Berman, and Keith Russell have progressed the field towards gathering more qualitative and quantitative data. Over the past two decades, their works have outlined theoretical foundations and the process of change that guides wilderness therapy programs. The work of these authors have laid the foundation for this dissertation and without their contributions to the field, this dissertation would not be possible. The purpose of this dissertation is to examine the research on wilderness therapy programs in order to outline the therapeutic process of change, identify various components, and highlight the current understanding of these programs. A comprehensive review of the literature will also identify areas of growth and need in the field of wilderness therapy, which will be included in developing this program. Simultaneously, current research on prevention programming will be examined to understand and incorporate programming guidelines. By combining effective wilderness therapy program components with modified program needs and best practice in prevention programming, a model prevention program for youth will be developed. In doing so, a model wilderness therapy prevention program for at-risk youth will be generated, in the hopes of providing a base model from which future models may elaborate, and researchers may empirically study across various settings and populations. (Abstract shortened by UMI.)

  Lining the walls of the first hangar are glass cases containing World War I uniforms, an actual flight book from WWI and even a pencil rubbing taken from the table where the armistice was signed on 1918.