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Contrast-associated AKI may result in higher morbidity and mortality. Intravenous fluid administration remains the mainstay for prevention. There is a lack of consensus on the optimal administration strategy. We studied the association of periprocedure fluid administration with contrast-associated AKI, defined as an increase in serum creatinine of at least 25% or 0.5 mg/dl from baseline at 3-5 days after angiography, and 90-day need for dialysis, death, or a 50% increase in serum creatinine.We conducted a secondary analysis of 4671 PRESERVE participants who underwent angiographic procedures. Although fluid type was randomized, strategy of administration was at the discretion of the clinician. We divided the study cohort into quartiles by total fluid volume. We performed multivariable logistic regression, adjusting for clinically important covariates. We tested for the interaction between fluid volume and duration of fluid administration, categorized as6 or ≥6 hours.The mean (SD) age was 70 (8) years, 94% of participants were male, and median (interquartile range) eGFR was 60 (41-60) ml/min per 1.73 mWe found that administration of a total volume of 1000 ml, starting at least 1 hour before contrast injection and continuing postcontrast for a total of 6 hours, is associated with a similar risk of adverse outcomes as larger volumes of intravenous fluids administered for periods6 hours. Mean fluid volumes964 ml may be associated with a higher risk for the primary outcome, although residual confounding cannot be excluded.

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Next-generation genomic sequencing has identified multiple novel molecular alterations in cancer. Since the identification of DNA methylation and histone modification, it has become evident that genes encoding epigenetic modifiers that locally and globally regulate gene expression play a crucial role in normal development and cancer progression. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is the enzymatic catalytic subunit of the polycomb-repressive complex 2 (PRC2) that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). EZH2 is involved in global transcriptional repression, mainly targeting tumor-suppressor genes. EZH2 is commonly overexpressed in cancer and shows activating mutations in subtypes of lymphoma. Extensive studies have uncovered an important role for EZH2 in cancer progression and have suggested that it may be a useful therapeutic target. In addition, tumors harboring mutations in other epigenetic genes such as ARID1A, KDM6, and BAP1 are highly sensitive to EZH2 inhibition, thus increasing its potential as a therapeutic target. Recent studies also suggest that inhibition of EZH2 enhances the response to tumor immunotherapy. Many small-molecule inhibitors have been developed to target EZH2 or the PRC2 complex, with some of these inhibitors now in early clinical trials reporting clinical responses with acceptable tolerability. In this review, we highlight the recent advances in targeting EZH2, its successes, and potential limitations, and we discuss the future directions of this therapeutic subclass.

Background Multisite practical clinical trials evaluate treatments in real-world practice. A multisite randomized Veterans Health Administration (VHA) cooperative study (CSP#555) published in 2011 compared the first long-acting injectable (LAI) second-generation antipsychotic (SGA), Risperidone Consta®, in veterans with a diagnosis of schizophrenia or schizoaffective disorder, to oral antipsychotics, with unexpected null results for effectiveness and cost-effectiveness. Whether null results of this type could change VHA practice has not been studied. Methods A longitudinal observational analysis was used to evaluate the impact of the trial findings on VHA clinical practices. National administrative data compared new starts on LAI risperidone during the 4 years before the publication of CSP#555 in 2011 to new starts on LAI risperidone during the 4 years after. Results Among 119,565 Veterans with the indicated diagnoses treated with antipsychotics from 2007 to 2015, the number and proportion of new starts on LAI risperidone declined significantly following the study publication, as did the total number of annual users and drug expenditures. However, data from 2007 to 2010 showed the decline in new starts actually preceded the publication of CSP#555. This change was likely explained by the increase in new starts, total use, and expenditures on a newer medicine, LAI paliperidone, a 4-week LAI treatment, in the 2 years prior to the publication of CSP#555. Conclusions The declining use of LAI risperidone likely primarily reflects the substitution of a longer-acting LAI SGA, paliperidone, that came to market 2 years before the study publication, a substitution that may have been reinforced by null CSP#555 study results for LAI risperidone.

Reflex genetic testing of tumor tissue is being completed to direct cancer treatment; however, the patient impact of this genetic testing model is unknown. This survey study evaluates psychological outcomes following tumor and germline genetic testing in individuals with a new diagnosis of high-grade serous ovarian cancer (HGSOC). Individuals were recruited from two hospitals in Toronto, Canada. Participants completed surveys 1 week after receiving tumor results and 1 week after receiving germline results (which included genetic counseling). Outcomes included cancer-related distress (Impact of Events Scale: IES), genetic testing-related distress (Multidimensional Impact of Cancer Risk Assessment: MICRA), and patient satisfaction. Paired t-tests were used to evaluate differences in outcomes following each genetic test result; Cohen's d was used to evaluate effect size. Subgroup analyses were undertaken according to age at diagnosis (60 years vs. ≥60 years) and test results (any positive vs. both negative). McNemar's test assessed differences in satisfaction. Fifty-two individuals were included in the analyses. Mean IES scores were similar following disclosure of tumor and germline results (27.39 vs. 26.14; p = 0.481; d = 0.101). Compared to following tumor result disclosure, MICRA scores were significantly lower following receipt of germline results with genetic counseling (27.23 vs. 22.69; p = 0.007; d = 0.435). Decreases in MICRA scores from tumor to germline result disclosure were greater for those diagnosed60 years or those who received only negative test results. Most individuals were satisfied/highly satisfied following tumor (85.7%) and germline (89.8%) results disclosure (p = 0.774). Reflex tumor, and subsequent germline, genetic testing is a new model of care for cancer patients. In our cohort, genetic testing-related distress decreased significantly following receipt of germline results with genetic counseling, especially for individuals diagnosed under 60 years and those receiving only negative results. Most individuals were satisfied with this model of care.

National policies have targeted widespread exclusionary discipline in schools which is associated with negative academic outcomes. Principals play an important role in making disciplinary decisions, yet little is understood about how their mindsets might impact disciplinary decisions. We hypothesized that principals' mindsets regarding the purpose of discipline (exclusion versus prevention) would predict their responses to misbehavior. In a random nation-wide sample (N=234), principals responded to misbehavior by a hypothetical Black or White student. Exclusion beliefs predicted more severe discipline, while prevention beliefs predicted greater endorsement of referring the student to a school counselor. Principal prevention mindsets also predicted less exclusionary discipline in real-world contexts.

Background With the advent of COVID-19, many healthcare workers (HWs) in Australia requested access to powered air purifying respirators (PAPR) for improved respiratory protection, comfort and visibility. The urgency of the response at our hospital required rapid deployment of innovative training to ensure the safe use of PAPRs, in particular, a video-feedback training option to prepare HWs for PAPR competency. Aim To explore the feasibility, acceptability, and utility of video-feedback in PAPR training and competency assessment. Methods Semi-structured interviews were conducted with 12 HWs, including clinicians from Intensive Care, Anaesthetics and Respiratory Medicine, at a large teaching hospital in Australia. Findings Participants believed that the use of video-feedback in PAPR training was feasible, acceptable and useful. They described a variety of benefits to learning and retention, from a variety of ways in which they engaged with the personal video-feedback. Participants also described the impact of reviewing personalised practice footage, compared to generic footage of an ideal performance. Conclusion By conceptualising video-feedback using a pedagogical approach, this study contributes to knowledge around optimising methods for training HWs in PPE use, particularly when introducing a new and complex PPE device during an infectious disease outbreak.

Background: First-line treatment of epithelial ovarian cancer (EOC) consists of a combination of cytoreductive surgery and platinum-based chemotherapy. Recently, targeted therapies such as bevacizumab have been shown to improve oncologic outcomes in a subset of a high-risk population. The objective of this study is to evaluate the patterns of practice and outcomes of first-line systemic treatment of advanced EOC, focusing on the adoption of bevacizumab. Methods: A population cohort study was conducted using administrative data in Ontario, Canada. Patients diagnosed with advanced stage non-mucinous EOC between 2014 and 2018 were identified. Datasets were linked to obtaining information on first-line treatment including surgery, systemic therapy, providers of care, systemic therapy facilities, and acute care utilization (emergency department (ED) visits and hospitalizations) during systemic treatment. Multivariate logistic regression was used to determine factors associated with systemic therapy utilization. Results: Among 3726 patients with advanced EOC, 2838 (76%) received chemotherapy: 1316 (47%) received neoadjuvant chemotherapy, 1060 (37%) underwent primary cytoreductive surgery followed by chemotherapy, and 462 (16%) received chemotherapy only. The median age was 67 (range: 20–100). Most chemotherapies were prescribed by gynecologic oncologists (60%) and in level 1 academic cancer centres (58%). Only 54 patients (3.1%) received bevacizumab in the first-line setting after its approval in Ontario in 2016. Bevacizumab was more likely to be administered by medical oncologists compared to gynecologic oncologists (OR 3.95, 95% CI 2.11–7.14). In total, 1561 (55%) and 1594 (56%) patients had at least one ED visit and/or hospitalization during systemic treatment, respectively. The most common reasons for ED visits were fever and bowel obstruction. Conclusion: Patterns of care for EOC in Ontario differed between care providers. The uptake of bevacizumab for first-line treatment of EOC was low. Acute care utilization related to EOC was high.

Introduction The COVID-19 pandemic has had significant impact on clinical care and traditional clinical trial operations, but it is unclear whether these impacts persist in pragmatic trials with a centralized study design. The Diuretic Comparison Project (DCP) is a Point-of Care pragmatic trial testing the hypothesis that chlorthalidone is superior to hydrochlorothiazide at the prevention of major cardiovascular (CV) events and non-cancer death. DCP relies on telephone consent, data collection from the electronic health record and Medicare, forgoes study visits, and limits provider time beyond usual care. DCP paused recruitment on VA directive in response to COVID-19 from 3/17/2020 until 7/1/2020. We assessed the impact of the COVID-19 pandemic on the centralized recruitment, patient follow-up, data collection, and outcome ascertainment performed in the DCP. Methods To assess clinical activity level and trial metrics, we compared data from two 8-month time periods: Pre-Pandemic (July 2019 – February 2020) and Mid-Pandemic (July 2020 – February 2021). Consent and randomization rates, study medication adherence, blood pressure (BP) and electrolyte follow-up rates, VA records of CV events, all-cause hospitalization, and death rates were compared for these two periods. Results Providers agreed to participate at a lower rate mid-pandemic (71%) than pre-pandemic (65%), but more patients were contacted (5,363 vs. 7,622) and consented (3,048 vs. 3,718) mid-pandemic. Patients refilled medications and remained on their randomized diuretic at the same frequency (90%) in both periods. Overall, rates of BP, electrolyte measurements, and hospitalizations decreased mid-pandemic while deaths increased. Conclusions While recruitment, enrollment, and adherence did not suffer during the pandemic, documented blood pressure checks and laboratory evaluations decreased, likely due to fewer in-person visits during the pandemic. All-cause VA hospitalizations decreased, despite a considerable number of COVID-related hospitalizations. While this suggests some changes in clinical care during the pandemic, the overall impact on DCP’s ability to operate mostly unimpacted during a global pandemic is another important strength of Point of Care clinical trials. Clinical Trial Registration NCT02185417 Registered 9 July 9 2014 https://clinicaltrials.gov/ct2/show/NCT02185417

Objectives: The aim of the study was to examine the unique contributions of age to objectively measure driving frequency and dangerous driving behaviors in healthy older adults after adjusting for executive function (EF). Method: A total of 28 community-dwelling older adults (mean age = 82.0 years, standard deviation [SD] = 7.5) without dementia who were in good physical health and enrolled in a longitudinal aging study completed several EF and clinical self-report measures at baseline. Participants subsequently had a sensor installed in their vehicle for a mean of 208 (SD = 38, range = 127–257) days. Results: Participants drove for an average of 54 min per day. Mixed-effects models indicated that after controlling for EF, older age was associated with less time driving per day, decreased number of trips, and less nighttime driving. Age was not associated with hard brakes or hard accelerations. Discussion: After accounting for EF, greater age is associated with higher driving self-regulation but not dangerous driving behaviors in healthy older adults. Future studies should recruit larger samples and collect sensor-measured driving data over a more extended time frame to better determine how and why these self-regulation changes take place.

Abstract. In this commentary, I seek to join the ongoing conversation about evidence-informed educational practice that has been threaded through this special issue. I do so by drawing on related insights from the fields of teachers' beliefs and epistemic cognition and considering the roles of teacher education and educational research in improving (preservice) teachers' use of educational research. In particular, I focus on the merits of explicit research-based practice in teacher educators' teaching and ways that they can encourage preservice teachers' interactions with educational research in class, and methods of changing the beliefs that may underlie (preservice) teachers' engagement with educational research evidence, and finally, the need for clearly communicated research, including details of implementation.

Objective: To provide recommendations on systemic therapy options in consolidation or maintenance therapy for women with newly diagnosed stage II, III, or IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma including all histological types. Methods: Consistent with the Program in Evidence-based Program’s standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO (the international prospective register of systematic reviews) databases, and four relevant conferences were systematically searched. The Working Group drafted recommendations and revised them based on the comments from internal and external reviewers. Results: We have one recommendation for consolidation therapy and eight recommendations for maintenance therapy. Overall, consolidation therapy with chemotherapy should not be recommended in the target population. For maintenance therapy, we recommended olaparib (Recommendation), niraparib (Weak Recommendation), veliparib (Weak Recommendation), and bevacizumab (Weak Recommendation) for certain patients with newly diagnosed stage III–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, respectively. We do not recommend some agents as maintenance therapy in four recommendations. We are unable to specify the patient population by histological types for different maintenance therapy recommendations. When new evidence that can impact the recommendations is available, the recommendations will be updated as soon as possible.

Clinical testing for mismatch repair (MMR) deficiency often entails serial testing of tumor and constitutional DNA using multiple assays. To minimize cost and specimen requirements of MMR testing, we developed an integrated targeted sequencing protocol (termed MultiMMR) that tests for promoter methylation, mutations, copy number alterations, copy neutral loss of heterozygosity, and microsatellite instability from a single aliquot of DNA. Hybrid capture of DNA-sequencing libraries constructed with methylated adapters was performed on 142 samples (60 tumors and 82 constitutional samples) from 82 patients with MMR-associated colorectal, endometrial, and brain cancers as well as a synthetic DNA mix with 11 known mutations. The captured material was split to enable parallel bisulfite and conventional sequence analysis. The panel targeted microsatellite regions and 13 genes associated with MMR, hypermutation, and hereditary colorectal cancer. MultiMMR recapitulated clinical testing results in 23 of 24 cases, was able to explain MMR loss in an additional 29 of 48 patients with incomplete or inconclusive testing, and identified all 11 MMR variants within the synthetic DNA mix. Promoter methylation and microsatellite instability analysis found 95% and 97% concordance with clinical testing, respectively. We report the feasibility for amalgamation of the current stepwise and complex clinical testing workflow into an integrated test for hereditary and somatic causes of MMR deficiency.

Small-scale fisheries and aquaculture (SSFA) provide livelihoods for over 100 million people and sustenance for ~1 billion people, particularly in the Global South. Aquatic foods are distributed through diverse supply chains, with the potential to be highly adaptable to stresses and shocks, but face a growing range of threats and adaptive challenges. Contemporary governance assumes homogeneity in SSFA despite the diverse nature of this sector. Here we use SSFA actor profiles to capture the key dimensions and dynamism of SSFA diversity, reviewing contemporary threats and exploring opportunities for the SSFA sector. The heuristic framework can inform adaptive governance actions supporting the diversity and vital roles of SSFA in food systems, and in the health and livelihoods of nutritionally vulnerable people—supporting their viability through appropriate policies whilst fostering equitable and sustainable food systems.

Objective This study compares the rate and time to genetic referral, and patient uptake of germline genetic services, before and after implementation of reflex BRCA1/2 tumor testing for high-grade serous ovarian cancer (HGSOC) in a universal healthcare system. Methods A retrospective chart review of HSGOC patients diagnosed in the year before (PRE) and after (POST) implementation of reflex BRCA1/2 tumor testing was conducted. Clinical information (date/age at diagnosis, personal/family history of breast/ovarian cancer, cancer stage, primary treatment, tumor results) and dates of genetics referral, counseling, and germline testing were obtained. Incident rate ratios (IRR) and 95% CI were calculated using negative binomial regression. Time to referral was evaluated using Kaplan-Meier survival analysis. Fisher Exact tests were used to evaluate uptake of genetic services. Results 175 HGSOC patients were identified (81 PRE; 94 POST). Post-implementation of tumor testing, there was a higher rate of genetics referral (12.88 versus 7.10/1000 person-days; IRR = 1.60, 95% CI: 1.07–2.42) and a shorter median time from diagnosis to referral (59 days PRE, 33 days POST; p = .04). In the POST cohort, most patients were referred prior to receiving their tumor results (n = 63/77; 81.8%). Once referred, most patients attended genetic counseling (94.5% PRE, 97.6% POST; p = .418) and pursue germline testing (98.6% PRE; 100% POST; p = .455). Conclusions Following implementation of reflex BRCA1/2 tumor testing for HGSOC, significant improvements to the rate and time to genetics referral were identified. Additional studies are needed to evaluate physician referral practices and the long-term impact of reflex tumor testing.

Background For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS. Methods Women with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result. Results Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR‐deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1‐deficient tumors) followed by MSI for nonmethylated and/or MMR‐intact patients was the most sensitive (92.3%; 95% confidence interval, 64%‐99.8%) and specific (97.7%; 95% confidence interval, 94.2%‐99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%. Conclusions Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost‐effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS., Although the incidence of mismatch repair deficiency (MMRd) is low (13%) in patients with nonserous and/or nonmucinous ovarian cancer, the likelihood of having Lynch syndrome is high in patients with MMRd (39%). In the current study, immunohistochemistry for mismatch repair proteins (with MLH1 promoter methylation analysis performed on MLH1‐deficient tumors) is found to be highly sensitive (85%) and specific (98%), missing only 2 patients of Lynch syndrome.

Objective Women with advanced gynecologic cancer and malignant bowel obstruction (MBO) undergo repeated hospitalizations, experience feelings of isolation and abandonment, and often die in acute settings. Innovative outpatient models of care are needed to address the unmet needs of this population at the end-of-life. We implemented a novel supported self-management (SMS) program focused on increasing patients' skill and confidence in managing MBO proactively in the ambulatory setting. Methods We performed a qualitative descriptive study embedded in a prospective single-arm evaluative trial ( Clinicaltrials.gov ID: NCT03260647 ) to understand the impact of this program on patients' sense of support, degree of distress, quality of care, and capacity to self-manage. Semi-structured interviews were completed and analysed using the Chronic Care Model as a theoretical framework. Data saturation was confirmed after 15 interviews. Results Fifteen patients (age range: 47–82) with diagnoses of advanced ovarian, endometrial, and cervical cancer were interviewed; 10 had died by end of follow-up, with a median interval from interview to death of 5 months. Patients were able to self-manage the: (i) medical aspects; (ii) psychological consequences, and (iii) changes in life roles and expectations resulting from their condition. Patients felt greatly supported, less isolated, and secure in their knowledge and ability to access care due to SMS. While patients understood their disease was not curative they did not fully appreciate that MBO signalled a significantly poorer prognosis. Conclusion Outpatient SMS interventions can be successfully implemented even for rapidly fatal conditions at the end-of-life and offer significant benefit to gynecologic cancer patients with MBO. Counselling should focus on the specific trajectory of MBO, and early palliative care referrals should be standard practice.

Til tross for fokus på kritisk tenkning som en nødvendig ferdighet, er det få som har kommet med tiltak for hvordan lærere kan støtte utvikling av denne typen tenkning blant elever i den norske skolen. Vi tar et grep om denne utfordringen. Først foreslår vi et teoretisk rammeverk for å forstå sentrale deler innen kritisk tenkning. Deretter presenterer vi nyere forskning som fremmer forslag til hvordan kritisk tenkning kan stimuleres i grunnskolen. Vårt fokus er på argumentasjon, kildevurderingsferdigheter og kunnskapssyn. Basert på vår gjennomgang av relevant litteratur identifiserer vi implikasjoner for læreres praksis. Despite focus on critical thinking as a necessary skill, few have suggested specific ways for teachers to support its development in Norwegian school pupils. We address this challenge: We first suggest a theoretical framework for understanding critical thinking’s central components, then we present recent research that forms the basis for suggestions for how critical thinking can be promoted in primary and secondary school. Our focus is on argumentation, strategic source evaluation and views of knowledge. Based on this review we identify implications for teachers’ practice.

OBJECTIVE: The study aims to evaluate the differences in ovarian cancer survival by age and stage at diagnosis within and across seven high-income countries.METHODS: We analyzed data from 58,161 women diagnosed with ovarian cancer during 2010-2014, followed until 31 December 2015, from 21 population-based cancer registries in Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. Comparisons of 1-year and 3-year age- and stage-specific net survival (NS) between countries were performed using the period analysis approach.RESULTS: Minor variation in the stage distribution was observed between countries, with most women being diagnosed with 'distant' stage (ranging between 64% in Canada and 71% in Norway). The 3-year all-ages NS ranged from 45 to 57% with Australia (56%) and Norway (57%) demonstrating the highest survival. The proportion of women with 'distant' stage was highest for those aged 65-74 and 75-99 years and varied markedly between countries (range:72-80% and 77-87%, respectively). The oldest age group had the lowest 3-year age-specific survival (20-34%), and women aged 65-74 exhibited the widest variation across countries (3-year NS range: 40-60%). Differences in survival between countries were particularly stark for the oldest age group with 'distant' stage (3-year NS range: 12% in Ireland to 24% in Norway).CONCLUSIONS: International variations in ovarian cancer survival by stage exist with the largest differences observed in the oldest age group with advanced disease. This finding endorses further research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease.

Background Reflex (automatic) BRCA1 and BRCA2 (BRCA1/2) genetic testing of tumour tissue is being completed for all newly diagnosed high-grade serous ovarian cancer (HGSOC) in the province of Ontario, Canada. The objective of this study was to measure the psychological impact of tumour genetic testing among individuals with a new diagnosis of HGSOC. Methods Participants had a new diagnosis of HGSOC and received reflex BRCA1/2 tumour genetic testing as a component of their care. Eligible individuals were recruited from two oncology centres in Toronto, Canada. One week after disclosure of tumour genetic test results, consenting participants were asked to complete a questionnaire that measured cancer-related distress, dispositional optimism, knowledge of hereditary breast/ovarian cancer, recall of tumour genetic test results, satisfaction, and the psychological impact of receiving tumour genetic test results. The Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire was used to measure the psychological impact of tumour genetic testing. Results 76 individuals completed the study survey; 13 said they did not receive their tumour test results. Of the remaining 63 participants, the average MICRA score was 26.8 (SD = 16.3). Higher total MICRA scores were seen among those with children (p = 0.02), who received treatment with primary surgery (p = 0.02), and had higher reported cancer-related distress (p p p = 0.03) were associated with lower total MICRA scores. Most (83.5%) participants reported being satisfied/highly satisfied with having tumour testing completed; however, 40.8% could not accurately recall their tumor test results. Conclusions This study is the first to assess psychological outcomes following reflex BRCA1/2 tumour genetic testing in women newly diagnosed with HGSOC. Increased dispositional optimism provided a protective effect, while increased cancer-related distress increased the psychological impact of tumour genetic testing. Educational resources are needed to help increase patient understanding and recall of tumour results, particularly when tumour genetic testing includes analysis of genes that may have implications for hereditary cancer risk. Additional research is required to better understand the patient experience of reflex tumour genetic testing.

In "network neuropsychology", network modelling and graph theory is applied to the neuropsychological test scores of patients with neurological disorders to investigate cognitive functioning. This review identifies the emerging literature across several disorders before focusing on the assumptions about cognition underlying the studies; specifically, that cognition can be thought of as a network of interrelated variables and that changes in these interrelationships, or cognitive rearrangement, can occur in neurological disorders. Next the review appraises how well network models can provide a "map" of this cognitive "territory". In particular, the review considers issues of a lack of correspondence between the variables and properties of network models and cognitive functioning. The challenges of explicitly accounting for latent cognitive constructs and drawing inferences about cognition based on associative, as opposed to dissociative, methods are also discussed. It is concluded that the validity of network neuropsychological models is yet to be established and that cognitive theory and experiments, as well as network models, are needed to develop and interpret better maps.

Sentinel lymph node (SLN) mapping is becoming an acceptable alternative to full lymphadenectomy for evaluating lymphatic spread in clinical stage I endometrial cancer (EC). While the assessment of pelvic and para-aortic lymph nodes is part of the surgical staging of EC, there is a long-standing debate over the therapeutic value of full lymphadenectomy in this setting. Although lymphadenectomy offers critical information on lymphatic spread and prognosis, most patients will not derive oncologic benefit from this procedure as the majority of patients do not have lymph node involvement. SLN mapping offers prognostic information while simultaneously avoiding the morbidity associated with an extensive and often unnecessary lymphadenectomy. A key factor in the decision making when planning for EC surgery is the histologic subtype. Since the risk of lymphatic spread is less than 5% in low-grade EC, these patients might not benefit from lymph node assessment. Nonetheless, in high-grade EC, the risk for lymph node metastases is much higher (20–30%); therefore, it is crucial to determine the spread of disease both for determining prognosis and for tailoring the appropriate adjuvant treatment. Studies on the accuracy of SLN mapping in high-grade EC have shown a detection rate of over 90%. The available evidence supports adopting the SLN approach as an accurate method for surgical staging. However, there is a paucity of prospective data on the long-term oncologic outcome for patients undergoing SLN mapping in high-grade EC, and more trials are warranted to answer this question.

This study investigated the effects of a refutation text intervention on Norwegian teacher education students’ (n = 150) beliefs about justification for knowing and their subsequent performance on a multiple document literacy task. Participants were randomly assigned to one of three conditions in which they read a refutation text that promoted the conception that an appropriate way to judge the trustworthiness of information about educational topics is to rely on personal understanding and practical experience, the expertise of the author, or comparison of multiple sources. Results showed that participants’ beliefs about epistemic justification were strongly influenced by the intervention. Beyond effects on self-reported justification beliefs, effects on participants’ selection of documents varying in terms of the expertise of the author and the stance toward the issue discussed across the documents were observed, as well as effects on how participants justified their document selections, processed the selected documents, and finally used them in their written task products. As such, the effects of the intervention targeting beliefs about epistemic justification transferred to various stages of the multiple document task.

Contains fulltext : 283074.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG). METHODS: A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion. RESULTS: Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%-97.9%) and 76.5% (95% CI=68.1%-84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%-15.2%) in patients with grade 1-2 endometrial cancer and 11.8% (95% CI=8.1%-16.1%) in patients with grade 1-3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%-100%) in studies that included grade 1-2 endometrial cancer and 99.2% (95% CI=97.9%-99.9%) in studies that also included grade 3. CONCLUSION: SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer.

We set out to investigate preservice teachers’ beliefs about sources of teaching knowledge and their motivation to learn from practice and theory in teacher education in a longitudinal study ( n = 96, at the beginning of the study). Participants placed more trust in experiential knowledge sources compared with formalized sources and participants’ beliefs about sources of teaching knowledge generally predicted their motivation to learn from different sources. Quantitative results were further supported and elaborated by qualitative interview data that suggested development of preservice teachers’ beliefs about sources of teaching knowledge and their understanding of the relation between theoretical and practical knowledge over time. The findings extend existing literature by providing a window on how (preservice) teachers may articulate their views about sources of teaching knowledge and relations between theory and practice, with expected consequences for teaching practice. Implications for teacher educators’ practice are also discussed.

Objectives Endometrial cancer (EC) or atypical hyperplasia (AH) in young women with obesity is often the first significant obesity-related comorbidity they experience. Significant, sustained weight loss through bariatric surgery may result in a durable response by addressing obesity directly, and subsequently improve oncologic and reproductive outcomes. However, it is not known whether bariatric surgery is acceptable to this patient population. Methods We performed a qualitative study to understand the acceptability of bariatric surgery among women of reproductive age with BMI ≥ 35 and grade 1 EC/AH. Semi-structured interviews were used to explore participant perceptions towards their weight, fertility, and the possibility of bariatric surgery as part of the treatment strategy for their EC/AH. Results Eleven participants with median age of 33 years (range 27–38) and BMI of 42.1 (35.1–56.9) were interviewed. Two (18%) participants had grade 1 EC, and 9 (82%) had AH. Patients were reluctant to accept bariatric surgery as a treatment option due to 1) lack of knowledge about the procedure, 2) stigma attached to bariatric surgery, and 3) fear of the unknown. The desire to conceive was highlighted as the strongest motivator for patients to consider bariatric surgery. Their perception towards their weight, fertility and diagnosis of EC/AH were characterized by concepts of ‘helplessness’, ‘isolation’, ‘frustration’ and ‘guilt’. We observed a significant gap in participant understanding of the complex interplay between their cancer, fertility and obesity. Conclusions We need to provide patient-oriented counseling on implication of their weight on their cancer and fertility, before presenting bariatric surgery as a treatment option.

Metastatic urothelial carcinoma is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, with ARID1A-inactivating mutations present in about 20% of tumors. EZH2, a histone methyltransferase, acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling is activated in more than 20% of bladder cancers. Using a combination of in vitro and in vivo data, including patient-derived xenografts, we show that ARID1A-mutant tumors were more sensitive to EZH2 inhibition than ARID1A WT tumors. Mechanistic studies revealed that (a) ARID1A deficiency results in a dependency on PI3K/AKT/mTOR signaling via upregulation of a noncanonical PI3K regulatory subunit, PIK3R3, and downregulation of MAPK signaling and (b) EZH2 inhibitor sensitivity is due to upregulation of PIK3IP1, a protein inhibitor of PI3K signaling. We show that PIK3IP1 inhibited PI3K signaling by inducing proteasomal degradation of PIK3R3. Furthermore, ARID1A-deficient bladder cancer was sensitive to combination therapies with EZH2 and PI3K inhibitors in a synergistic manner. Thus, our studies suggest that bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K and revealed mechanistic insights into the role of noncanonical PI3K constituents in bladder cancer biology.

BACKGROUND Seborrheic dermatitis is a common fungal infection of the scalp that may potentially affect depth electrode placement for intracranial seizure monitoring. No cases documenting the safety of proceeding with depth electrode placement in the setting of seborrheic dermatitis have been reported. OBSERVATIONS A 19-year-old man with a history of drug-resistant epilepsy was taken to the operating room for placement of depth electrodes for long-term seizure monitoring. Annular patches of erythema with trailing scales were discovered after shaving the patient’s head. Dermatology service was consulted, and surgery was cancelled because of the uncertainty of his diagnosis and possible intracranial spreading. He was diagnosed with severe seborrheic dermatitis and treated with topical ketoconazole. Surgery was rescheduled, and the patient received successful placement and removal of depth electrodes without any complications. LESSONS Seborrheic dermatitis is a common skin infection that, in the authors’ experience, is unlikely to lead to any intracranial spread after treatment. However, surgeons should use clinical judgment and engage dermatology colleagues regarding any uncertain skin lesions.

Objective The purpose of this guideline is to make recommendations regarding the care of women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2. Methods Draft recommendations were formulated based on evidence obtained through a systematic review of RCTs, comparative retrospective studies and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners. Results The literature search yielded 1 guideline, 5 systematic reviews, and 15 studies that met the eligibility criteria. Conclusions In women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 screening for ovarian cancer is not recommended. Risk-reducing surgery is recommended to reduce the risk of ovarian cancer. In the absence of contraindications, premenopausal women undergoing RRSO should be offered hormone therapy until menopause. Systemic hormone replacement therapy, is not recommended for women who have had a personal history of breast cancer. RRSO should be considered for breast cancer risk reduction in women younger than 50 years. After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. Following RRSO, it is not recommended to do surveillance for peritoneal cancer.