Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell

Measurement properties of quality of life measurement instruments for infants, children and adolescents with eczema: protocol for a systematic review

Background: Eczema is a common chronic or chronically relapsing skin disease that has a substantial impact on quality of life (QoL). By means of a consensus-based process, the Harmonising Outcome Measures in Eczema (HOME) initiative has identified QoL as one of the four core outcome domains to be assessed in all eczema trials. Few measurement instruments exist to measure QoL in infants and children with eczema, but there is a great variability in both content and quality (for example, reliability and validity) of the instruments used, and it is not always clear if the best instrument is being used. Therefore, the aim of the proposed research is a comprehensive systematic assessment of the measurement properties of the existing measurement instruments that were developed and/or validated for the measurement of patient-reported QoL in infants and children with eczema. Methods/Design: This study is a systematic review of the measurement properties of patient-reported measures of QoL developed and/or validated for infants and children with eczema. Medline via PubMed and EMBASE will be searched using a selection of relevant search terms. Eligible studies will be primary empirical studies evaluating, describing, or comparing measurement properties of QoL instruments for infants and children with eczema. Eligibility assessment and data abstraction will be performed independently by two reviewers. Evidence tables will be generated for study characteristics, instrument characteristics, measurement properties, and interpretability. The adequacy of the measurement properties will be assessed using predefined criteria. Methodological quality of studies will be assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A best evidence synthesis will be undertaken if more than one study has investigated a particular measurement property. Discussion: The proposed systematic review will produce a comprehensive assessment of measurement properties of existing QoL instruments in infants and children with eczema. We aim to identify one best currently available instrument to measure QoL in infants and/or children with eczema

In the Shadow of the Transiting Disk: Imaging epsilon Aurigae in Eclipse

Eclipses of the single-line spectroscopic binary star, epsilon Aurigae, provide an opportunity to study the poorly-defined companion. We used the MIRC beam combiner on the CHARA array to create interferometric images during eclipse ingress. Our results demonstrate that the eclipsing body is a dark disk that is opaque and tilted, and therefore exclude alternative models for the system. These data constrain the geometry and masses of the components, providing evidence that the F-star is not a massive supergiant star.Comment: As submitted to Nature. Published in Nature April 8, 2010

Goal setting and self-efficacy among delinquent, at-risk and not at-risk adolescents

Setting clear achievable goals that enhance self-efficacy and reputational status directs the energies of adolescents into socially conforming or non-conforming activities. This present study investigates the characteristics and relationships between goal setting and self-efficacy among a matched sample of 88 delinquent (18 % female), 97 at-risk (20 % female), and 95 not at-risk adolescents (20 % female). Four hypotheses related to this were tested. Findings revealed that delinquent adolescents reported fewest goals, set fewer challenging goals, had a lower commitment to their goals, and reported lower levels of academic and self-regulatory efficacy than those in the at-risk and not at-risk groups. Discriminant function analysis indicated that adolescents who reported high delinquency goals and low educational and interpersonal goals were likely to belong to the delinquent group, while adolescents who reported high educational and interpersonal goals and low delinquency goals were likely to belong to the not at-risk group. The at-risk and not at-risk groups could not be differentiated. A multinomial logistic regression also revealed that adolescents were more likely to belong to the delinquent group if they reported lower self-regulatory efficacy and lower goal commitment. These findings have important implications for the development of prevention and intervention programs, particularly for those on a trajectory to delinquency. Specifically, programs should focus on assisting adolescents to develop clear self-set achievable goals and support them through the process of attaining them, particularly if the trajectory towards delinquency is to be addressed

Low-risk Prostate Cancer: Identification, Management, and Outcomes.

ContextThe incidence of low-risk prostate cancer (PCa) has increased as a consequence of prostate-specific antigen testing.ObjectiveIn this collaborative review article, we examine recent literature regarding low-risk PCa and the available prognostic and therapeutic options.Evidence acquisitionWe performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms: prostate cancer, low risk, active surveillance, focal therapy, radical prostatectomy, watchful waiting, biomarker, magnetic resonance imaging, alone or in combination.Evidence synthesisProspective randomized trials have failed to show an impact of radical treatments on cancer-specific survival in low-risk PCa patients. Several series have reported the risk of adverse pathologic outcomes at radical prostatectomy. However, it is not clear if these patients are at higher risk of death from PCa. Long-term follow-up indicates the feasibility of active surveillance in low-risk PCa patients, although approximately 30% of men starting active surveillance undergo treatment within 5 yr. Considering focal therapies, robust data investigating its impact on long-term survival outcomes are still required and therefore should be considered experimental. Magnetic resonance imaging and tissue biomarkers may help to predict clinically significant PCa in men initially diagnosed with low-risk disease.ConclusionsThe incidence of low-risk PCa has increased in recent years. Only a small proportion of men with low-risk PCa progress to clinical symptoms, metastases, or death and prospective trials have not shown a benefit for immediate radical treatments. Tissue biomarkers, magnetic resonance imaging, and ongoing surveillance may help to identify those men with low-risk PCa who harbor more clinically significant disease.Patient summaryLow-risk prostate cancer is very common. Active surveillance has excellent long-term results, while randomized trials have failed to show a beneficial impact of immediate radical treatments on survival. Biomarkers and magnetic resonance imaging may help to identify which men may benefit from early treatment

Neck pain and anxiety do not always go together

Chronic pain and psychosocial distress are generally thought to be associated in chronic musculoskeletal disorders such as non-specific neck pain. However, it is unclear whether a raised level of anxiety is necessarily a feature of longstanding, intense pain amongst patient and general population sub-groups. In a cohort of 70 self-selected female, non-specific neck pain sufferers, we observed relatively high levels of self-reported pain of 4.46 (measured on the 11 point numerical pain rating scale (NRS-101)) and a longstanding duration of symptoms (156 days/year). However, the mean anxiety scores observed (5.49), fell well below the clinically relevant threshold of 21 required by the Beck Anxiety Inventory. The cohort was stratified to further distinguish individuals with higher pain intensity (NRS>6) and longer symptom duration (>90 days). Although a highly statistically significant difference (p = 0.000) was subsequently observed with respect to pain intensity, in the resulting sub-groups, none such a difference was noted with respect to anxiety levels. Our results indicate that chronic, intense pain and anxiety do not always appear to be related. Explanations for these findings may include that anxiety is not triggered in socially functional individuals, that individual coping strategies have come into play or in some instances that a psychological disorder like alexithymia could be a confounder. More studies are needed to clarify the specific role of anxiety in chronic non-specific musculoskeletal pain before general evidence-driven clinical extrapolations can be made

Utilization of focal therapy for patients discontinuing active surveillance of prostate cancer: Recommendations of an international Delphi consensus

BACKGROUND: With the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS). METHODS: A 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement. RESULTS: Fifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community. CONCLUSIONS: FT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS

Animal cultures matter for conservation

This is the author accepted manuscript. The final version is available from AAAS via the DOI in this record.No abstrac

Registration accuracy for MR images of the prostate using a subvolume based registration protocol

<p>Abstract</p> <p>Background</p> <p>In recent years, there has been a considerable research effort concerning the integration of magnetic resonance imaging (MRI) into the external radiotherapy workflow motivated by the superior soft tissue contrast as compared to computed tomography. Image registration is a necessary step in many applications, e.g. in patient positioning and therapy response assessment with repeated imaging. In this study, we investigate the dependence between the registration accuracy and the size of the registration volume for a subvolume based rigid registration protocol for MR images of the prostate.</p> <p>Methods</p> <p>Ten patients were imaged four times each over the course of radiotherapy treatment using a T2 weighted sequence. The images were registered to each other using a mean square distance metric and a step gradient optimizer for registration volumes of different sizes. The precision of the registrations was evaluated using the center of mass distance between the manually defined prostates in the registered images. The optimal size of the registration volume was determined by minimizing the standard deviation of these distances.</p> <p>Results</p> <p>We found that prostate position was most uncertain in the anterior-posterior (AP) direction using traditional full volume registration. The improvement in standard deviation of the mean center of mass distance between the prostate volumes using a registration volume optimized to the prostate was 3.9 mm (p < 0.001) in the AP direction. The optimum registration volume size was 0 mm margin added to the prostate gland as outlined in the first image series.</p> <p>Conclusions</p> <p>Repeated MR imaging of the prostate for therapy set-up or therapy assessment will both require high precision tissue registration. With a subvolume based registration the prostate registration uncertainty can be reduced down to the order of 1 mm (1 SD) compared to several millimeters for registration based on the whole pelvis.</p