Influence of servant leadership on the life satisfaction of basic education teachers: the mediating role of satisfaction with job resources.

Background: Life satisfaction is essential for teachers' work performance and student learning. Additionally, servant leadership has been shown to be one of the best leadership practices as it promotes employee well-being and satisfaction. Moreover, satisfaction with job resources acts as a mediator in the relationship between servant leadership and life satisfaction by influencing individual and collective performance in the organization. Objective: This research aimed to evaluate the mediating role of satisfaction with job resources in the relationship between servant leadership and life satisfaction. Methods: The study was cross-sectional and explanatory. 620 teachers aged between 20 and 62 years (M = 35 and SD = 9.49) participated in the study. Structural Equation Modeling (SEM) was used to measure life satisfaction, service leadership, and job resource satisfaction through the use of questionnaires. Results: The results indicated that the model obtained an adequate fit, χ2 = 2,658, df = 551, p < 0.001, CFI = 0.941, TLI = 0.936, RMSEA = 0.079, SRMR = 0.070. The results confirm the positive influence of leadership on satisfaction with resources and life satisfaction. Additionally, a positive influence of satisfaction with job resources on life satisfaction was observed. Moreover, the mediation of job resources in servant leadership and life satisfaction was confirmed. Conclusion: Servant leadership, supported by satisfaction with job resources, can reduce effort and associated costs, stimulate personal growth and learning, and improve the well-being of teachers.

Critical Thinking, Generalized Anxiety in Satisfaction with Studies: The Mediating Role of Academic Self-Efficacy in Medical Students.

BACKGROUND: The academic and emotional challenges faced by medical students can affect critical thinking and may also contribute to the development of increased generalized anxiety. Similarly, critical thinking and generalized anxiety can impact study satisfaction through the mediating mechanism of academic self-efficacy. OBJECTIVE: The aim of this study was to assess the mediating role of academic self-efficacy between critical thinking and generalized anxiety in study satisfaction among medical students. METHODS: A cross-sectional and explanatory study was conducted involving 259 Peruvian medical students aged between 18 and 35 (M = 20.29, SD = 2.84). The evaluation was based on self-reported questionnaires covering critical thinking, generalized anxiety, academic self-efficacy, and study satisfaction. Furthermore, a structural equation modeling (SEM) and mediation approach was employed to examine the relationships between variables. RESULTS: The results showed an adequate fit of the model [χ2 (87) = 155, p < 0.001, CFI = 0.93, TLI = 0.92, RMSEA = 0.05 (CI: 0.04-0.07), SRMR = 0.07], demonstrating the impact of critical thinking and generalized anxiety. It was confirmed that academic self-efficacy has a positive effect on study satisfaction. Moreover, the mediating role of academic self-efficacy was confirmed between critical thinking and study satisfaction, as well as between generalized anxiety and study satisfaction. CONCLUSIONS: Due to the high academic load on medical students, academic self-efficacy plays a mediating role in the relationship between critical thinking, generalized anxiety, and satisfaction with studies. The development of educational strategies will help to promote critical thinking and academic self-efficacy, as well as provide support to students with generalized anxiety, to enhance study satisfaction.

Work-related injuries and attendance at a Canadian regional emergency department.

BACKGROUND: Monitoring trends in the burden of illness and injury attributable to work is key in assessing occupational health hazards; however, New Brunswick does not participate in the Canadian National Ambulatory Care Reporting System which itself does not collect details of occupation and industry. AIMS: We set out to determine the proportion of emergency department attendances that were attributable to a work-related cause. We also wanted to evaluate the recording of occupation in the electronic health record system, and to describe the characteristics of patients with a work-related presentation. METHODS: A retrospective observational study over a 1-year period was conducted using an administrative database obtained from Canadian Emergency Department Information System. Descriptive statistics are used to present the analysis of categorical and continuous data. RESULTS: A total of 49 365 patients were included for analysis. Two per cent of patients presented with a self-reported work-related condition. Health care and social assistance, construction, retail trade and manufacturing were the most common industries reported by patients. CONCLUSIONS: This study found the rate of work-related medical conditions to be substantially less than expected, and that occupation was not captured for any patients presenting to the emergency department with a work-related condition, despite a field being available in the electronic health record registration system. We were able to analyse the industry sectors for work-related presentations. The recording and coding of occupation and industry would significantly benefit occupational epidemiology in emergency medicine as well as potentially improving patient outcomes and health system efficiencies.

Pediatric Cardiology Fellowship Standards for Training in Exercise Medicine and Curriculum Outline.

Over the past 2 decades, fundamentals of exercise medicine, including clinical exercise testing, assessment and promotion of physical activity, exercise prescription, and supervised exercise training/rehabilitation programming have demonstrated considerable clinical value in the management of children and adolescents with congenital and acquired heart disease. Although the principles of exercise medicine have become an integral component in pediatric cardiology, there are no standardized training recommendations for exercise physiology during pediatric cardiology fellowship at this time. Thus, the Pediatric Cardiology Exercise Medicine Curriculum Committee (PCEMCC) was formed to establish core and advanced exercise physiology training recommendations for pediatric cardiology trainees. The PCEMCC includes a diverse group of pediatric cardiologists, exercise physiologists, and fellowship program directors. The expert consensus training recommendations are by no means a mandate and are summarized herein, including suggestions for achieving the minimum knowledge and training needed for general pediatric cardiology practice.

Regional differences in the reduction in cerebral FDG uptake induced by the ketogenic diet.

BACKGROUND: The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18F-FDG uptake as a surrogate marker. METHODS: A retrospective audit was conducted of the brain 18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels. RESULTS: The expected negative association between serum glucose levels and whole brain 18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain. CONCLUSION: In a real-world clinical PET setting, cerebral 18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.

Comparison of actionable events detected in cancer genomes by whole-genome sequencing, in silico whole-exome and mutation panels.

BACKGROUND: Next-generation sequencing is used in cancer research to identify somatic and germline mutations, which can predict sensitivity or resistance to therapies, and may be a useful tool to reveal drug repurposing opportunities between tumour types. Multigene panels are used in clinical practice for detecting targetable mutations. However, the value of clinical whole-exome sequencing (WES) and whole-genome sequencing (WGS) for cancer care is less defined, specifically as the majority of variants found using these technologies are of uncertain significance. PATIENTS AND METHODS: We used the Cancer Genome Interpreter and WGS in 726 tumours spanning 10 cancer types to identify drug repurposing opportunities. We compare the ability of WGS to detect actionable variants, tumour mutation burden (TMB) and microsatellite instability (MSI) by using in silico down-sampled data to mimic WES, a comprehensive sequencing panel and a hotspot mutation panel. RESULTS: We reveal drug repurposing opportunities as numerous biomarkers are shared across many solid tumour types. Comprehensive panels identify the majority of approved actionable mutations, with WGS detecting more candidate actionable mutations for biomarkers currently in clinical trials. Moreover, estimated values for TMB and MSI vary when calculated from WGS, WES and panel data, and are dependent on whether all mutations or only non-synonymous mutations were used. Our results suggest that TMB and MSI thresholds should not only be tumour-dependent, but also be sequencing platform-dependent. CONCLUSIONS: There is a large opportunity to repurpose cancer drugs, and these data suggest that comprehensive sequencing is an invaluable source of information to guide clinical decisions by facilitating precision medicine and may provide a wealth of information for future studies. Furthermore, the sequencing and analysis approach used to estimate TMB may have clinical implications if a hard threshold is used to indicate which patients may respond to immunotherapy.

Care of Seniors with Breast Cancer - Treatment Received and Refining Decision Making.

AIMS: Treatment decisions for older patients with breast cancer are complex and evidence is largely extrapolated from younger populations. Frailty and comorbidity need to be considered. We studied the baseline characteristics and treatment decisions in older patients in Christchurch with breast cancer and assessed survival outcomes and prognostic/discriminatory performance of several tools. MATERIALS AND METHODS: We searched the Canterbury Breast Cancer Registry and identified patients aged 70 years or older at diagnosis with invasive, non-metastatic breast cancer between 1 June 2009 and 30 June 2015. We retrieved demographics, treatment and outcome information. Overall survival and breast cancer-specific survival were estimated. Tools analysing performance status and comorbidity were assessed for their prognostic and discriminatory power. RESULTS: In total, 440 patients were identified. Primary surgery was carried out for 362 patients (82.3%): breast-conserving surgery in 114 (of whom 88.6% received radiation therapy); mastectomy in 248 (of whom 24.6% received radiation). Hormone therapy was given for 265 (71.1%) patients with oestrogen receptor-positive cancers. Two hundred and seventy-four (62.3%) patients received full standard treatment, which was associated with significantly improved 5-year survival and 5-year breast cancer-specific survival. The median estimated overall survival was 8.2 years (95% confidence interval 7.3-9.1 years). Of those who died, 71.3% of deaths were due to causes other than breast cancer or unknown causes. The comorbidity-adjusted life expectancy (CALE) showed partial prognostic accuracy. CALE, Charlson and Eastern Cooperative Oncology Group tools all showed discriminatory value. CONCLUSION: In this population-based series of older patients with breast cancer, showing high levels of primary and adjuvant treatment, patients were more likely to die of causes other than breast cancer. Performance status and comorbidity tools showed prognostic and discriminatory potential in this population supporting their use in treatment decision making. CALE showed the most potential to improve treatment decisions but requires validation in this population to improve prognostic accuracy.

Profile of soluble factors in pleural effusions predict prognosis in mesothelioma.

BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual feature of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease. OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma. METHODS: We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively "soluble factors") involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients.Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n= 51) using a separate assay system. RESULTS: Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis. CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients.

Intermediate ice scour disturbance is key to maintaining a peak in biodiversity within the shallows of the Western Antarctic Peninsula.

Climate-related disturbance regimes are changing rapidly with profound consequences for ecosystems. Disturbance is often perceived as detrimental to biodiversity; however, the literature is divided on how they influence each other. Disturbance events in nature are diverse, occurring across numerous interacting trophic levels and multiple spatial and temporal scales, leading to divergence between empirical and theoretical studies. The shallow Antarctic seafloor has one of the largest disturbance gradients on earth, due to iceberg scouring. Scour rates are changing rapidly along the Western Antarctic Peninsula because of climate change and with further changes predicted, the Antarctic benthos will likely undergo dramatic shifts in diversity. We investigated benthic macro and megafaunal richness across 10-100 m depth range, much of which, 40-100 m, has rarely been sampled. Macro and megafauna species richness peaked at 50-60 m depth, a depth dominated by a diverse range of sessile suspension feeders, with an intermediate level of iceberg disturbance. Our results show that a broad range of disturbance values are required to detect the predicted peak in biodiversity that is consistent with the Intermediate Disturbance Hypothesis, suggesting ice scour is key to maintaining high biodiversity in Antarctica's shallows.

Malignant struma ovarii with a robust response to radioactive iodine.

SUMMARY: Struma ovarii is a rare, usually benign ovarian tumour with malignancy occurring in <5% of cases. Metastases, particularly seeding to bone, are extremely rare. Presentation is variable but often features local pain and/or ascites and hyperthyroidism may occur. It is not established how to best treat and follow patients with extensive disease. Case reports of radioiodine (I131) ablative therapy following thyroidectomy have shown reduced recurrence. We describe the case of a 33-year-old woman who presented with bone pain and was diagnosed with skeletal metastases with features of follicular thyroid carcinoma. However, thyroid pathology was benign. She recalled that 5 years prior, an ovarian teratoma was excised, classified at that time as a dermoid cyst. Retrospective review of this pathology confirmed struma ovarii without obvious malignant features. The patient was found to have widespread metastases to bone and viscera and her thyroglobulin was >3000 µg/L following recombinant TSH administration prior to her first dose of I131. At 25 months following radioiodine treatment, she is in remission with an undetectable thyroglobulin and clear I131 surveillance scans. This case demonstrates an unusual presentation of malignant struma ovarii together with challenges of predicting metastatic disease, and demonstrates a successful radioiodine regimen inducing remission. LEARNING POINTS: Malignant transformation of struma ovarii (MSO) is extremely rare and even rarer are metastatic deposits in bone and viscera. MSO can be difficult to predict by initial ovarian pathology, analogous to the difficulty in some cases of differentiating between follicular thyroid adenoma and carcinoma. No consensus exists on the management for post operative treatment of MSO; however, in this case, three doses of 6Gbq radioiodine therapy over a short time period eliminated metastases to viscera and bone. Patients should continue to have TSH suppression for ~5 years. Monitoring thyroglobulin levels can predict recurrence.

Breast cancer and cytomegalovirus.

PURPOSE: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. METHODS: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. RESULTS: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. CONCLUSIONS: Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.

Neo-antigen specific T cell responses indicate the presence of metastases before imaging.

Non-small cell lung cancer (NSCLC) causes 19% of all Australian cancer deaths, with a 5-year survival post-resection of around 60%. Post-operative recurrence is due to metastases that were undetectable pre-operatively, or growth of microscopic locoregional residual disease. However, post-operative imaging modalities typically only detect more advanced tumours; where PET-CT has a detection limit of 6-7 mm. Detection of small deposits of lung metastatic disease is of importance in order to facilitate early and potentially more effective treatment. In this study, in a murine model of lung metastatic disease, we explore whether neo-antigen specific T cells are a sensitive marker for the detection of lung cancer after primary tumour resection. We determine lung metastatic disease by histology, and then compare detection by PET-CT and neo-antigen specific T cell frequency. Detection of lung metastatic disease within the histology positive group by PET-CT and neo-antigen specific T cell frequency were 22.9% and 92.2%, respectively. Notably, neo-antigen specific T cells in the lung draining lymph node were indicative of metastatic disease (82.8 ± 12.9 spots/105 cells; mean ± SE), compared to healthy lung control (28.5 ± 8.6 spots/105 cells; mean ± SE). Potentially, monitoring tumour neo-antigen specific T cell profiles is a highly sensitive method for determining disease recurrence.

A Fibromyxoid Stromal Response is Associated with Muscle Invasion in Canine Urothelial Carcinoma.

Canine urothelial carcinoma (UC) is the most common type of cancer of the lower urinary tract and tends to affect elderly neutered female dogs, with a high predisposition for Scottish terriers. Tumour stroma, inflammation and necrosis are poorly characterized in canine UC and their role as prognostic factors is unknown. The aims of this study were to (1) assess histologically 381 canine UCs, with emphasis on myxoid tumour stroma, inflammation and necrosis and (2) assess possible associations between these features and the available epidemiological data as well as bladder wall muscle invasion. In 103 of 381 (27%) cases, the stroma was mixed collagenous and myxoid (fibromyxoid), which was strongly associated with invasive growth of muscle (P <0.0001). Peritumoural and intratumoural inflammation was present in 308 of 345 (89%) and 287 of 381 (75%) cases, respectively, and was mostly mild and lymphoplasmacytic. One hundred and fifteen of the 381 (30%) cases showed a variable eosinophilic inflammation and 58 of 381 (15%) presented with formations of one or several lymphoid follicles. Twenty-four percent (91 of 381) of cases had tumour necrosis, which was typically mild. In 83 of 91 (91%) cases, the necrosis was comedo-like. Moderate to severe tumour necrosis was associated with the presence of moderate to predominant fibromyxoid tumour stroma (P <0.02). The results of this study indicate that fibromyxoid stroma is common in canine UC and is a strong indicator for invasive growth of muscle, which is consistent with a poor prognosis. Based on histomorphology, tumour necrosis in canine UC is best described as comedonecrosis.

Cadmium uptake by onions, lettuce and spinach in New Zealand: Implications for management to meet regulatory limits.

Paired soil and plant samples collected from the main commercial growing areas for onions (Allium cepa), lettuce (Lactuca sativa) and spinach (Spinacia olearacea) in New Zealand were used to assess the influence of plant and soil factors on cadmium (Cd) uptake in these crops. Differences in Cd concentration between eight lettuce sub-types were not consistent across sites, nor were differences in Cd concentrations in three crisphead cultivars assessed at two sites. Similarly, differences in Cd concentrations between four onion cultivars were inconsistent across sites. Mean lettuce Cd concentrations in eight lettuce varieties (range 0.005-0.034 mg∙kg-1 (fresh weight, FW) were markedly lower than those in baby leaf and bunching spinach, (range 0.005-0.19 mg∙kg-1 FW). Significant regional variation was observed in Cd concentrations in one onion cultivar (mean range 0.007-0.05 mg∙kg-1 FW). Soil Cd concentration, pH and region were statistically significant predictors of onion Cd concentration, explaining low (38% for soil Cd and pH) to moderate (50% for all three parameters) percentage of the variation. Soil Cd concentration and exchangeable magnesium or total carbon were statistically significant predictors of Cd concentration in baby leaf and bunching spinach, respectively, explaining a moderate percentage (49% and 42%) of the variation in Cd concentration. Increasing pH and soil carbon may assist in minimising Cd uptake in onion and bunching spinach, respectively. The low to moderate proportion of explained variation is partly attributable to the narrow range in some measured soil properties and indicates factors other than those assessed are influencing plant uptake. This highlights a challenge in using these relationships to develop risk-based soil guideline values to support compliance with food standards. Similarly, the inconsistency in Cd concentrations in different cultivars across sites highlights the need for multi-site assessments to confirm the low Cd accumulation status of different cultivars.

Biowastes to augment the essential oil production of Leptospermum scoparium and Kunzea robusta in low-fertility soil.

Biowastes are unwanted materials of biological origin. They include biosolids, dairy shed effluent, and sawdust. When applied to soil, biowastes can provide plant nutrients, but also introduce heavy metals, pathogens, or xenobiotics. Biowastes could improve degraded or low-fertility soils and generate revenue through the production of non-food products such as essential oils. We grew New Zealand native plants, manuka (Leptospermum scoparium J.R. Forst & G. Forst) and kanuka (Kunzea robusta de Lange & Toelken) in series of greenhouse experiments in low-to-medium-fertility soils (Bideford clay loam, Lismore stony silt loam, and Pawson silt loam) amended with either biosolids (up to 13500 kg N ha-1 equiv.), biosolids + sawdust (1:0.5-1250 kg N ha-1 equiv.) and dairy shed effluent (200 kg N ha-1 equiv.). Two types of biosolids from Kaikoura (KB) and Christchurch City Council (CB) were used in the experiments. CB (1500 kg N ha-1 equiv.) and dairy shed effluent (200 kg N ha-1 equiv.) increased the biomass of L. scoparium by up to 120% and 31%, and K. robusta by up to 170% and 34%, respectively. Adding sawdust to KB increased the biomass of L. scoparium and K. robusta although it offset the L. scoparium growth increase in the KB-only treatment. The growth response of K. robusta to biowastes was greater than L. scoparium with oil production in K. robusta increasing by up to 211% when 1500 kg N ha-1 equiv. of CB was applied to Lismore stony silt loam. Generally, the treatments had a negligible effect on oil concentration in all the soil types, except for the KB + sawdust treatment, which increased the oil concentration by 82%. Most of the EOs' major components were unaffected by biowaste addition in the soils, although some components increased in the Bideford clay loam following KB and KB + sawdust application. Biosolids increased foliar concentrations of Zn, Cu, and Cd, but these were below risk-threshold concentrations. Applying CB (up to 1500 kg N ha-1 equiv.) to low-fertility soils is recommended to establish ecosystems dominated by L. scoparium and K. robusta that annually would produce ca. 100 kg ha-1 of EOs worth US$ 26k and 24k, respectively. Adding sawdust to CB could have environmental benefits through reduction of N leaching. Field trials are warranted to elucidate critical ecological variables and production economics in biowaste management.

Outcomes for Patients with Non-metastatic Triple-negative Breast Cancer in New Zealand.

AIMS: Triple-negative breast cancer (TNBC) has inferior outcomes to other subtypes of breast cancer. We studied the demographics and baseline breast cancer characteristics of patients in New Zealand with TNBC and assessed survival outcomes and prognostic/predictive factors. MATERIALS AND METHODS: We searched the New Zealand breast cancer registry database and identified patients with TNBC without distant metastatic disease. We retrieved demographic, tumour characteristic and treatment information. Locoregional recurrence-free survival, breast cancer-specific survival (BSS), metastasis-free survival (MRFS) and overall survival were determined. Predefined univariate and multivariate analyses were carried out investigating the association of survival outcomes with treatment and tumour characteristics. RESULTS: In total, 1390 patients were identified, with a median follow-up of 3.5 years. The median age was 55 years. Thirty-eight per cent were node positive and 79% were grade III. Mastectomy was carried out in 53%, adjuvant radiation delivered in 66% and chemotherapy in 69%. The significant predictive factors for overall survival, BSS and MRFS were radiotherapy, chemotherapy and neoadjuvant chemotherapy. The significant prognostic indicators were lymphovascular invasion, nodal status and tumour size. On Kaplan-Meier analysis, the 5 year overall survival was 72%. The median time to death for those who died was 3.55 years with 92% of deaths within 5 years. Seventy-four per cent of patients had distant metastasis as a first recurrence and isolated local recurrences occurred in only 4.5%. Metastatic disease occurred in lung (55.9%) and was in multiple sites in 51%. CONCLUSION: We report a large population-based series of TBNC without distant metastatic disease at diagnosis highlighting the unique behavioural characteristics of TNBC. Traditional therapies are positively associated with survival outcomes, and yet, particularly in the setting of recurrent disease, prognosis remains poor. Increased research into more effective systemic agents and the most effective timing of delivery of these may result in improved outcomes.

Medullary Thyroid Carcinoma: Survival Analysis and Evaluation of Mutation-Specific Immunohistochemistry in Detection of Sporadic Disease.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare tumour of neuroendocrine origin with a more aggressive profile than differentiated thyroid cancer. Familial cases of MTC are associated with RET mutations whilst RAS mutations appear to be a frequent finding in RET negative tumours. The aims of this study were to analyse survival outcomes in MTC and to evaluate the role of RAS immunohistochemistry in the identification of sporadic disease. MATERIALS AND METHODS: A retrospective cohort study of consecutive patients with MTC was undertaken. The primary outcome measures were overall survival and disease-free survival. Survival analysis was performed on the basis of sporadic and familial disease. Patients had routine RET testing using the capillary (Sanger) sequencing method. Histopathological MTC slides from 100 patients were tested for HRASQ61R, a common somatic RAS mutation in MTC, with mutation-specific immunohistochemistry (IHC). RESULTS: A total of 195 patients had surgical treatment of MTC in the period 1980 to 2016. There were 83 males and 112 females with a mean age of 53.0 years. A total of 39 (20%) patients had familial disease. Sporadic cases had a higher median pre-op calcitonin (969.5 vs. 257.5 pg/ml), greater mean primary tumour size (23.5 vs. 12.5 mm) and more distant metastases (12.8 vs. 10.3%). Multivariate analysis showed age (p = 0.005), Multiple Endocrine Neoplasia Type 2 (MEN2) status (p = 0.021) and distant metastasis (p = 0.002) to be significant independent predictors of survival. Significant independent predictors for disease-free survival were age (p = 0.015), MEN2 (p = 0.002), pre-op calcitonin (p = 0.033) and venous invasion (p = 0.001). The overall 5-year survival was 100% for familial MTC and 78% for sporadic MTC. The 10-year disease-free survival was 94% for familial MTC and 61% for sporadic cases. A total of 100 cases of MTC underwent mutation-specific IHC for HRASQ61R. Of these, 18 had confirmed MEN2. IHC had 100% specificity in excluding MEN2. Twelve (12%) of 100 patients stained positive for HRASQ61R mutation. CONCLUSION: In the era of genetic testing, RET status significantly influences disease-specific survival in MTC. Mutation-specific IHC for HRASQ61R may have a role in the identification of patients presenting with sporadic disease.

Adherence to Adjuvant Endocrine Therapy in Christchurch Women with Early Breast Cancer.

AIMS: To assess adherence to adjuvant endocrine therapy by a real-world cohort of women in Christchurch and to determine any associated factors. MATERIALS AND METHODS: Records were retrieved of all women newly diagnosed with early breast cancer and registered on the Christchurch Breast Cancer Patient Register over 4 years from June 2009. Demographic and pathological factors, dates of starting and stopping endocrine therapies and reported side-effects were collected. The proportion remaining on endocrine therapy was analysed by Kaplan-Meier curve; Cox regression analysis was used to identify independent factors influencing adherence. RESULTS: Of 1213 women, 1018 (83.9%) had oestrogen receptor-positive tumours, of whom 674 (66.2%) started adjuvant endocrine therapy, including 62 (9.2%) neoadjuvantly. Uptake was 52.4% of those with T1 tumours, 89% with T2 tumours, 93% with T3/T4 tumours, 92.7% with node-positive tumours and 49.7% with node-negative tumours. The initial endocrine therapy was an aromatase inhibitor in 254 (38%) and tamoxifen for 412 (61%). At 1 year, 90% remained adherent, at 2 years 84%, at 3 years 81%, at 4 years 76%, at 4.5 years 71% and at 5 years 50%, with a median duration of 60 months (56-64 months, 95% confidence interval) and a median follow-up of 33 months. Overall, 135 (20%) women stopped treatment for adverse events or poor tolerability. A longer persistence with endocrine therapy was associated with node-positive tumours (hazard ratio 1.38, P = 0.003), but not first hormone used; aromatase inhibitor compared with tamoxifen, P = 0.76. CONCLUSION: Adjuvant endocrine therapy use fell to 50% by 5 years, limiting possible survival benefits, providing support for efforts to increase compliance.

Molecular alterations in prostate cancer and association with MRI features.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly used for prostate cancer (PCa). Recent studies identified distinct molecular subclasses of PCa with recurrent genomic alterations. However, the associations between molecular alterations in PCa and characteristics on mpMRI are unknown. Therefore, the objective of this study was to investigate recurrent molecular alterations in PCa and their associations with mpMRI features. METHODS: Sixty-two PCa nodules >0.5 cm had a preoperative mpMRI. Nodules were evaluated for ERG rearrangement, PTEN deletion, SPINK1 overexpression, SPOP mutation and CHD1 deletion. Each PCa focus was matched to the corresponding location on mpMRI. Lesions were scored by single observer according to the PI-RADSv2 scale. RESULTS: Of the 62 nodules, 22 (35.5%) were ERG positive, 6 (9.7%) had SPINK1 overexpression, 6 (9.7%) had SPOP mutations, 4 (6.5%) had CHD1 deletions and 1 (1.6%) had PTEN deletion. All of the nodules with CHD1 deletions were not visible on mpMRI (P=0.037). All of the nodules with SPINK1 overexpression were visible on mpMRI, although the association was not statistically significant (P=0.06). There were no significant associations between any molecular alteration with the severity of the PI-RADS scores (all P>0.05). CONCLUSIONS: This investigation represents the first description of an association between recurrent molecular alterations and the characterization of PCa nodules on mpMRI. This study can be considered hypothesis-generating for future studies to rigorously evaluate the association of specific PCa molecular subclasses with imaging features and potentially define specific subsets of PCa for which the utility of MRI is higher or lower.

Flexible mate choice may contribute to ecotype assortative mating in pumpkinseed sunfish (Lepomis gibbosus).

Gene flow is expected to limit adaptive divergence, but the ecological and behavioural factors that govern gene flow are still poorly understood, particularly at the earliest stages of population divergence. Reduced gene flow through mate choice (sexual isolation) can evolve even under conditions of subtle population divergence if intermediate phenotypes have reduced fitness. We indirectly tested the hypothesis that mate choice has evolved between coexisting littoral and pelagic ecotypes of polyphenic pumpkinseed sunfish (Lepomis gibbosus) that have diverged in morphology and resource use and where intermediate phenotypes have reduced performance. We assessed the ecotype of nesting males and females using stable isotope estimates of diet and a divergent male morphological trait, oral jaw width. We found positive assortative mating between ecotypes in a common spawning habitat along exposed lake shorelines, but contrary to expectations, assortative mating was variably expressed between two sampling years. Although the factors that influence variable assortative mating remain unclear, our results are consistent with mate choice being expressed by ecotypes. Despite being variably expressed, mate choice will reduce gene flow between ecotypes and could contribute to further adaptive divergence depending on its frequency and strength in the population. Our findings add to a growing body of evidence indicating mate choice behaviour can be a plastic trait, an idea that should be more explicitly considered in empirical studies of mate choice as well as conceptual frameworks of mate choice evolution and adaptive divergence.