Thermal performance under constant temperatures can accurately predict insect development times across naturally variable microclimates.

External conditions can drive biological rates in ectotherms by directly influencing body temperatures. While estimating the temperature dependence of performance traits such as growth and development rate is feasible under controlled laboratory settings, predictions in nature are difficult. One major challenge lies in translating performance under constant conditions to fluctuating environments. Using the butterfly Pieris napi as model system, we show that development rate, an important fitness trait, can be accurately predicted in the field using models parameterized under constant laboratory temperatures. Additionally, using a factorial design, we show that accurate predictions can be made across microhabitats but critically hinge on adequate consideration of non-linearity in reaction norms, spatial heterogeneity in microclimate and temporal variation in temperature. Our empirical results are also supported by a comparison of published and simulated data. Conclusively, our combined results suggest that, discounting direct effects of temperature, insect development rates are generally unaffected by thermal fluctuations.

Evaluating the implementation and use of the regional cancer plan in Western Sweden through concept mapping.

QUALITY PROBLEM OR ISSUE: Within healthcare, policy documents are often used to strategically standardize, streamline or change how general health issues are managed for a specific patient group or treatment. Despite significant effort in developing policy and strategic planning documents, these may not have the intended impact and their value has long been questioned by practitioners. CHOICE OF SOLUTION: To identify barriers and affordances for the implementation and use of a strategic plan for cancer care in the Western Sweden Healthcare Region, we used Concept Mapping; a participatory mixed method approach to inquiry consisting of both qualitative and quantitative tasks intended to elicit and integrate the diverse perspectives of multiple stakeholders. IMPLEMENTATION: The study was carried out between April and October 2017 and consisted of several sequential data collection steps: idea generation, sorting and rating ideas for importance and feasibility. Stakeholders from different levels and professions in cancercare participated, but the number varied in the separate steps of data collection: idea generation (n = 112), sorting (n = 16) and rating (n = 38). EVALUATION: A concept map visualized seven areas that stakeholders throughout the cancer-care process considered necessary to address in order to enable the implementation of the plan. Skills provision was considered the most important cluster but also rated as least feasible. A consistent theme emerged that information, or lack thereof, might be a barrier for the plan being put into action to a greater extent in the cancer-care units. Nine actionable ideas rated highly on both importance and feasibility were presented as a go-zone. LESSONS LEARNED: Our results suggest that efforts might be better spent on ensuring information about and accessibility to strategic documents throughout the organization, rather than frequently updating them or producing new ones. Having sufficient skills provision seems to be the prerequisite for successful implementation.

A population-based cohort study on adherence to practice guidelines for adjuvant chemotherapy in colorectal cancer.

BACKGROUND: The value of adjuvant chemotherapy in colorectal cancer is well studied, and guidelines have been established. Little is known about how treatment guidelines are implemented in the everyday clinical setting. METHODS: This national population-based study on nearly 34,000 patients with colorectal cancer evaluates the adherence to present clinical guidelines for adjuvant chemotherapy. Virtually all patients with colorectal cancer in Sweden during the years 2007-2012 and data from the Swedish Colorectal Cancer Registry were included. RESULTS: In colon cancer stage III, adherence to national guidelines was associated with lower age, presence of multidisciplinary team (MDT) conference, low co-morbidity, and worse N stage. The MDT forum also affected whether or not high-risk stage II colon cancer patients were considered for adjuvant chemotherapy. Rectal cancer patients both in stage II and III were considered for adjuvant chemotherapy less often than colon cancer patients, but the same factors influenced the decision. Adjuvant chemotherapy was started later than eight weeks after surgery in 30% of colon cancer patients and in 38% of rectal cancer patients. CONCLUSIONS: In Sweden, the adherence to national guidelines for adjuvant chemotherapy in colon cancer stage III is acceptable in younger and healthier patients. MDT conferences are of major importance and affect whether patients are recommended for adjuvant chemotherapy. Special consideration needs to be given to certain subgroups of patients, particularly older patients and patients with poorly differentiated tumors. There is a need to shorten the waiting time until start of chemotherapy.

Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome.

BACKGROUND: Breast cancer is a potentially fatal malignancy in females despite the improvement in therapeutic techniques. The identification of novel molecular signatures is needed for earlier detection, monitoring effects of treatment, and predicting prognosis. We have previously used microarray analysis to identify differentially expressed genes in aggressive breast tumors. The purpose of the present study was to investigate the prognostic value of the candidate biomarkers CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 in breast cancer. METHODS: The expression levels and subcellular localization of the CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 proteins were measured using immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Furthermore, the mRNA levels of CCNB2, KIAA0101, and SLC27A2 were subsequently examined by qRT-PCR to validate IHC results. Patient disease-specific survival (DSS) was evaluated in correlation to protein levels using the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of aberrant protein expression of the candidate biomarkers on patient DSS and to estimate the hazard ratio at 8-year follow-up. RESULTS: Elevated cytoplasmic CCNB2 protein levels were strongly associated with short-term disease-specific survival of breast cancer patients (≤ 8 years; P<0.001) and with histological tumor type (P= 0.04). However, no association with other clinicopathological parameters was observed. Multivariate Cox regression analysis specified that CCNB2 protein expression is an independent prognostic marker of DSS in breast cancer. The predictive ability of several classical clinicopathological parameters was improved when used in conjunction with CCNB2 protein expression (C-index = 0.795) in comparison with a model without CCNB2 expression (C-index = 0.698). The protein levels of ASPM, CDCA7, KIAA0101, and SLC27A2 did not correlate with any clinicopathological parameter and had no influence on DSS. However, a significant correlation between the expression of the CCNB2 and ASPM proteins was detected (P = 0.03). CONCLUSION: These findings suggest that cytoplasmic CCNB2 may function as an oncogene and could serve as a potential biomarker of unfavorable prognosis over short-term follow-up in breast cancer.

Seasonal specialization drives divergent population dynamics in two closely related butterflies.

Seasons impose different selection pressures on organisms through contrasting environmental conditions. How such seasonal evolutionary conflict is resolved in organisms whose lives span across seasons remains underexplored. Through field experiments, laboratory work, and citizen science data analyses, we investigate this question using two closely related butterflies (Pieris rapae and P. napi). Superficially, the two butterflies appear highly ecologically similar. Yet, the citizen science data reveal that their fitness is partitioned differently across seasons. Pieris rapae have higher population growth during the summer season but lower overwintering success than do P. napi. We show that these differences correspond to the physiology and behavior of the butterflies. Pieris rapae outperform P. napi at high temperatures in several growth season traits, reflected in microclimate choice by ovipositing wild females. Instead, P. rapae have higher winter mortality than do P. napi. We conclude that the difference in population dynamics between the two butterflies is driven by seasonal specialization, manifested as strategies that maximize gains during growth seasons and minimize harm during adverse seasons, respectively.

Exploring the meaning, role and experiences of a patient-led social innovation for people affected by cancer: a new collaborative care model complementing traditional cancer rehabilitation in Sweden.

OBJECTIVE: Kraftens Hus is the first support centre in Sweden designed by and for people affected by cancer, including patients, family, friends, staff members and local community representatives (collectively 'stakeholders'). The purpose of this study was to explore the meaning, role and experiences of Kraftens Hus stakeholders using a patient and public involved methodology. METHODS: To understand and map the experiences of visitors to Kraftens Hus, we applied concept mapping (CM), a mixed methods approach where data are collected and analysed in four structured steps designed to capture the diverse perspectives of multiple stakeholders. Qualitative interviews with relevant stakeholders supplemented the CM findings. RESULTS: The final concept map contained six clusters of ideas. Within the clusters, there was a recurring theme that cancer-affected people value accessible and long-term psychosocial support (PSS). The intended emotional, social and practical needs identified in a previous design process seem to have been addressed and appreciated by Kraftens Hus visitors. CONCLUSION: Kraftens Hus is an example of a new patient-led social innovation based on a life-event perspective and integration of resources from different sectors in society. By focusing on life, not the disease, the care continuum expands, and long-term PSS is provided alongside cancer treatment. The evaluation confirms that PSS should focus on health and well-being in the broadest sense.

CEF is superior to CMF for tumours with TOP2A aberrations: a Subpopulation Treatment Effect Pattern Plot (STEPP) analysis on Danish Breast Cancer Cooperative Group Study 89D.

The aim of this study was to examine TOP2A gene copy number changes as a means to identify groups of breast cancer patients with superior benefit from treatment with anthracyclines. Tumour tissue was retrospectively collected and successfully analysed for TOP2A in 773 of 980 Danish patients randomly assigned to receive intravenous CMF (cyclophosphamide, methotrexate and fluorouracil) or CEF (cyclophosphamide, epirubicin and fluorouracil) in DBCG trial 89D. Subgroup analyses on this material published by Knoop et al. (J Clin Oncol 23:7483-7490, 2005) and updated by Nielsen et al. (Acta Oncol 47:725-734, 2008) demonstrated that superiority of CEF over CMF is limited to patients with TOP2A aberrations, defined as patients whose tumours have TOP2A ratio below 0.8 or above 2.0. The Subpopulation Treatment Effect Pattern Plot (STEPP) technique was applied to these data to explore the pattern of treatment effect relative to TOP2A and to compare that pattern to the ranges previously used to define 'aberrations'. The pattern of treatment effect illustrated by the STEPP analysis confirmed that the superiority of CEF over CMF is indeed limited to patients whose tumours have high or low TOP2A ratios. The hypothesis of no treatment effect-covariate interaction was rejected (P = 0.02). Furthermore, results indicated that the interval of TOP2A ratios hitherto denoted as 'normal' could be narrower than previously assumed. A more optimal separation of TOP2A subgroups could be obtained by altering cut-points currently used to define TOP2A amplified and TOP2A deleted tumours by narrowing the TOP2A normal interval, and consequently enlarging the population with TOP2A aberrated tumours.

retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group.

PURPOSE: The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. PATIENTS AND METHODS: In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. RESULTS: HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). CONCLUSION: TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.

Effect of obesity on prognosis after early-stage breast cancer.

PURPOSE: This study was performed to characterize the impact of obesity on the risk of breast cancer recurrence and death as a result of breast cancer or other causes in relation to adjuvant treatment. PATIENTS AND METHODS: Information on body mass index (BMI) at diagnosis was available for 18,967 (35%) of 53,816 women treated for early-stage breast cancer in Denmark between 1977 and 2006 with complete follow-up for first events (locoregional recurrences and distant metastases) up to 10 years and for death up to 30 years. Information was available on prognostic factors and adjuvant treatment for all patients. Univariate analyses were used to compare the associations of known prognostic factors and risks of recurrence or death according to BMI categories. Cox proportional hazards regression models were used to assess the influence of BMI after adjusting for other factors. RESULTS: Patients with a BMI of 30 kg/m(2) or more were older and had more advanced disease at diagnosis compared with patients with a BMI below 25 kg/m(2) (P < .001). When data were adjusted for disease characteristics, the risk of developing distant metastases after 10 years was significantly increased by 46%, and the risk of dying as a result of breast cancer after 30 years was significantly increased by 38% for patients with a BMI of 30 kg/m(2) or more. BMI had no influence on the risk of locoregional recurrences. Both chemotherapy and endocrine therapy seemed to be less effective after 10 or more years for patients with BMIs greater than 30 kg/m(2). CONCLUSION: Obesity is an independent prognostic factor for developing distant metastases and for death as a result of breast cancer; the effects of adjuvant therapy seem to be lost more rapidly in patients with breast cancer and obesity.