Search

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.

To quantify the absolute risks of adverse fetal outcomes and maternal mortality following non-obstetric abdominopelvic surgery in pregnancy.Surgery is often necessary in pregnancy, but absolute measures of risk required to guide perioperative management are lacking.We systematically searched MEDLINE, EMBASE, and Evidence-Based Medicine Reviews from January 1, 2000, to December 9, 2020, for observational studies and randomized trials of pregnant patients undergoing non-obstetric abdominopelvic surgery. We determined the pooled proportions of fetal loss, preterm birth, and maternal mortality using a generalized linear random/mixed effects model with a logit link.We identified 114 observational studies (52 [46%] appendectomy, 34 [30%] adnexal, 8 [7%] cholecystectomy, 20 [17%] mixed types) reporting on 67,111 pregnant patients. Overall pooled proportions of fetal loss, preterm birth, and maternal mortality were 2.8% (95% CI 2.2-3.6), 9.7% (95% CI 8.3-11.4), and 0.04% (95% CI 0.02-0.09; 4/10,000), respectively. Rates of fetal loss and preterm birth were higher for pelvic inflammatory conditions (e.g. appendectomy, adnexal torsion) than for abdominal or non-urgent conditions (e.g. cholecystectomy, adnexal mass). Surgery in the second and third trimester was associated with lower rates of fetal loss (0.1%) and higher rates of preterm birth (13.5%) than surgery in the first and second trimester (fetal loss 2.9%, preterm birth 5.6%).Absolute risks of adverse fetal outcomes after non-obstetric abdominopelvic surgery vary with gestational age, indication, and acuity. Pooled estimates derived here identify high-risk clinical scenarios, and can inform implementation of mitigation strategies and improve preoperative counselling.

Hand hygiene is key to preventing health care-associated infections. Human observation is the gold standard for measuring compliance, but its utility is increasingly being questioned with calls for the use of video monitoring approaches. The utility of video-based systems to measure compliance according to the WHO 5 moments is largely unexamined, as is its acceptability amongst health care workers (HCW) and patients. This study examined HCW acceptability of video monitoring for hand hygiene auditing.Following trial of a video monitoring system (reported elsewhere), 5 participating HCW attended 2 in-depth group interviews where they reviewed the footage and explored responses to the approach. Transcripts were analyzed using thematic analysis.Four themes were identified: 1) Fears; 2) Concerns for patients; 3) Changes to feedback; and 4) Behavioral responses to the cameras. HCWs expressed fears of punitive consequences, data security, and confidentiality. For patients, HCWs raised issues regarding invasion of privacy, ethics, and consent. HCWs suggested that video systems may result in less immediate feedback but also identified potential to use the footage for feedback. They also suggested that the Hawthorne Effect was less potent with video systems than human observation.The acceptability of video monitoring systems for hand hygiene compliance is complex and has the potential to complicate practical implementation. Additionally, exploration of the acceptability to patients is warranted.COREQ.

Biologic medications have revolutionized treatment of psoriasis; however, there remains uncertainty in which medications should be used to maximize efficacy based on race/ethnicity. The purpose was to determine if efficacy of biological medications differs based on race/ethnicity. A systematic review identified all clinical trials focused on biologic treatment outcomes from inception of database until March 5th, 2021. Included studies provided data on racial/ethnic differences in biologic skin clearance efficacy using the Psoriasis Area and Severity Index (PASI) and "clear/almost clear" scores. There were 1220 studies identified, and 24 included in the review. The races/ethnicities included were Asian (n = 2740), White (n = 9745), Black (n = 138), and Latino (n = 728). Ixekizumab provided the highest "clear/almost clear" score (90.7%, 89.4%) and PASI 75 (98.8%, 96.6%) for Asian and Latino patients, respectively. Guselkumab had the highest "clear/almost clear" score for White (86.8%) patients, while Black patients had highest "clear/almost clear" (75.0%) and PASI 75 (91.7%) scores to brodalumab. Limitations included lack of studies reporting outcome data based on race/ethnicity and lack of patients of color within psoriasis clinical trials. For treatment of plaque psoriasis, there is evidence of differences in efficacy of biologics improving clinical disease severity between different races or ethnicities.

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.

To compare the immediate operating room (OR), inpatient, and overall costs between three surgical modalities among women with endometrial cancer (EC) and Class III obesity or higher.A multicentre prospective observational study examined outcomes of women, with early stage EC, treated surgically. Resource use was collected for OR costs including OR time, equipment, and inpatient costs. Median OR, inpatient, and overall costs across surgical modalities were analyzed using an Independent-Samples Kruskal-Wallis Test among patients with BMI ≥ 40.Out of 520 women, 103 had a BMI ≥ 40. Among women with BMI ≥ 40: median OR costs were $4197.02 for laparotomy, $5524.63 for non-robotic assisted laparoscopy, and $7225.16 for robotic-assisted laparoscopy (p 0.001) and median inpatient costs were $5584.28 for laparotomy, $3042.07 for non-robotic assisted laparoscopy, and $1794.51 for robotic-assisted laparoscopy (p 0.001). There were no statistically significant differences in the median overall costs: $10 291.50 for laparotomy, $8412.63 for non-robotic assisted laparoscopy, and $9002.48 for robotic-assisted laparoscopy (p = 0.185).There was no difference in overall costs between the three surgical modalities in patient with BMI ≥ 40. Given the similar costs, any form of minimally invasive surgery should be promoted in this population.

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.

Practice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients.This was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS).We identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1-7 days, 95% CI 1.61-4.51, and HR death 1.96 for 8-14 days, 95% CI 1.50-2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46-60 days, 95% CI 1.04-1.36, and HR death 1.42 for 61-75 days, 95% CI 1.11-1.83).Regionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival.

Objective: To evaluate health care professional (HCP) documentation of elevated patient-reported symptoms and subsequent intervention in gynecologic oncology clinics. Methods: This was a retrospective chart review of gynecologic oncology patients within a single institution. Prior to their clinical encounter, patients complete the validated Edmonton Symptom Assessment System revised (ESAS-r) questionnaire. Patients with any ESAS-r symptom score ≥4 (moderate-severe) were eligible for analysis. A stratified sampling method was used: 100 patients were randomly selected with 20 patients per year from 2012 to 2016. Patient, tumor and treatment characteristics were extracted from medical records. Health care provider (HCP) documentation of elevated symptoms and subsequent intervention were evaluated. Descriptive statistics were used to report symptom prevalence, HCP documentation and intervention. Fisher’s exact test evaluated documentation and intervention rates according to symptom severity and total ESAS-r score. Results: Between January 2012 and December 2016, 5849 patients completed the ESAS-r. Symptoms scores were ≥ 4 in 3216 patients (55%). In our sample of 100, ovarian (42%) and endometrial (34%) malignancies were most common. Median age was 55 years (range 47-63). Median ESAS-r score was 24 (range: 5-84), with tiredness being the most prevalent symptom reported by patients. HCP documented at least one elevated symptom in 50 patients (50%), most commonly for pain (71%) and least commonly for nausea (4%). Subsequent interventions were offered to only 32 patients (32%), most commonly for pain (56%). Higher median total ESAS-r score was associated with higher rate of documentation (p=0.004) and higher rate of intervention (pConclusions: A significant proportion of gynecologic oncology patients report symptom that should prompt an intervention. However, HCPs documented symptoms in only half of patients and reported interventions in only one third. These results highlight gaps and opportunities for improving symptom screening and response in the “real-world” setting.

Introduction We describe a case of botulism and its differentiation from acute neurological presentations. Case A 35 year-old man presented with dysphagia, subjective jaw numbness, dyspnoea and vertigo. He denied alcohol intake but had injected methamphetamines and developed symptoms shortly after. 48 hours post-injection, he was drowsy and developed a complete internal and external ophthalmoplegia, an absent gag reflex with slow tongue movements and facial diplegia with sparing of distal muscle groups. His reflexes were initially present but became absent five hours later. There were no sensory or cerebellar findings. Blood cultures were taken given his history of intravenous drug use. Neuroimaging did not note the presence of a posterior circulation infarct. A lumbar puncture did not demonstrate cytoalbuminological dissociation, and antibody testing for myasthenia gravis and Guillain Barre Syndrome variants were negative, although he was commenced on empirical IVIg prior to these results. He required intubation on day three of admission due to hypoxia secondary to aspiration but needed minimal ventilatory support. Neurophysiological findings were consistent with a presynaptic neuromuscular junction disorder. Blood cultures noted clostridium botulinum with detection of clostridium botulinum toxin B. Antitoxin was administered on day four of presentation with slow but gradual improvement in his neurology and he was extubated on day 16. Conclusion Acute causes of bilateral ophthalmoplegia include Wernicke’s encephalopathy, Miller-Fisher Syndrome (MFS) variant of Guillain Barre Syndrome, brainstem stroke, myasthenia gravis and botulism. Of these, only MFS and botulism will cause both internal and external ophthalmoplegia.

PURPOSE: Malignant bowel obstruction (MBO) is a common and distressing complication in women with advanced gynecologic cancer. A pilot, interprofessional MBO program was launched in 2016 at a large Canadian tertiary cancer center to integrate these patients’ complex care needs across multiple disciplines and support women with MBO. METHOD: Retrospective analysis to evaluate the outcomes of women with advanced gynecologic cancer who were admitted to hospital because of MBO, before (2014 to 2016: baseline group) and after (2016 to 2018) implementation of the MBO program. RESULTS: Of the 169 women evaluated, 106 and 63 were in the baseline group and MBO program group, respectively. Most had ovarian cancer (n = 124; 73%) and had small-bowel obstruction (n = 131; 78%). There was a significantly shorter cumulative hospital length of stay (LOSsum) within the first 60 days of MBO diagnosis in the MBO program group compared with the baseline group (13 v 22 days, respectively; adjusted P = .006). The median overall survival for women treated in the MBO program was also significantly longer compared with the baseline group (243 v 99 days, respectively; adjusted P = .002). Using the interprofessional MBO care platform, a greater proportion of patients received palliative chemotherapy (83% v 56%) and less surgery (11% v 21%) in the MBO program group than in the baseline group, respectively. A subgroup of women (n = 11) received total parenteral nutrition for longer than 6 months. CONCLUSION: Implementation of a comprehensive, interprofessional MBO program significantly affects patient care and may improve outcomes. Unique to this MBO program is an integrated outpatient model of care and education that empowers patients to recognize MBO symptoms for early intervention.

This study documents the collective capacity of the external support providers working to improve K-3 reading outcomes in New York City. Interviews and social network surveys with a sample of the 112 providers at work in this “reading improvement sector” showed that they serve as a conduit for sharing reading-related resources and expertise throughout a large part of New York City. However, the collective impact of the sector remains limited because their goals vary widely; support is unevenly distributed; and many programs work in isolation and are informed by funders and sources of expertise that are unlikely to be connected.

Cancer cells utilize vitamin folate to fulfill their excessive demand for nucleotides and amino acids. Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids. DHFR inhibitors are used as a chemotherapeutic agent. Cancer sequencing analysis has identified additional enzymes in folate metabolism that are dysregulated in cancer. Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), one such enzyme is overexpressed in bladder cancer. MTHFD1L is a mitochondrial enzyme involved in the folate cycle by catalyzing the reaction of formyl-tetrahydrofolate to formate and tetrahydrofolate (THF). THF is crucial for de novo purine and thymidylate synthesis and is also involved in the regeneration of methionine. Cancer cells rely on purines derived from the de novo pathway for the nucleotides whereas normal cells favor the salvage pathway. In this study we examined MTHFD1L expression in bladder cancer. By using publicly available cancer transcriptome data analysis web-portal UALCAN, we found overexpression of MTHFD1L in bladder cancer and expression was associated with overall survival. RT-PCR and immunoblot analysis confirmed the overexpression of MTHFD1L in muscle invasive bladder cancer tissues compared to normal urothelium. Furthermore, our investigations suggested a critical role for MTHFD1L in bladder cancer cell proliferation, colony formation and invasion. Thus, in this study, we show the significance of the folate metabolic enzyme MTHFD1L in aggressive bladder cancers and suggest that being an enzyme, MTHFD1L serves as a valuable therapeutic target.

BackgroundPatients with recurrent clear cell ovarian cancer have poor prognosis and limited effective systemic treatment options.ObjectivesTo characterize patterns of recurrence and compare overall survival and post-recurrence survival parameters in patients with recurrent ovarian clear cell carcinoma.MethodsClinical data on patients with ovarian clear cell carcinoma between June 1995 and August 2014 were collected. Patients with clear cell ovarian cancer recurrence were included in this study. Patients with different histologic sub-type, persistent or progressive disease on completion of the initial treatment were excluded. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to quantify survival differences on univariable analysis. To search for significant covariates related to the overall survival and post-recurrence survival, a univariable Cox proportional hazard model was performed.ResultsA total of 209 patients met inclusion criteria. Of these, 61 (29%) patients who were free of disease at completion of the initial treatment had recurrence. Patterns of recurrence were as follows: 38 (62%) patients had multiple-site recurrence, 12 (20%) had single-site recurrence, and 11 (18%) had nodal recurrence only. The median overall survival was 44.7 months (95% CI 33.4 to 64.2) and was significantly associated with pattern of recurrence (p=0.005). The median post-recurrence survival was 18.4 months (95% CI 12.5 to 26.7): 54.4 months (95% CI 11 to 125.5) in single-site recurrence, 13.7 months (95% CI 6.8 to 16.5) in multiple-site recurrence, and 30.1 (95% CI 7.2 to 89) months in nodal recurrence (p=0.0002). In the multivariable analysis, pattern of recurrence was a predictor of post-recurrence survival.Six patients (9.8%) had a prolonged disease-free interval after recurrence (disease-free for more than 30 months after completion of treatment for recurrence). Prolonged recurrences were noted in 4 (33%) of 12 patients with single-site recurrence, 1 (9%) of 11 patients with nodal recurrence, and in 1 (2.7%) of 38 patients with multiple-site recurrence. Three of the six patients with a prolonged disease-free interval after recurrence were treated surgically at the time of recurrence.ConclusionOvarian clear cell carcinoma predominantly recurs in multiple sites and it is associated with a high mortality rate and short post-recurrence survival. When recurrences are limited to a single site, or only to lymph nodes, the median post-recurrence survival is longer. Disease-free interval after recurrence is longer in patients with single-site recurrence who are treated surgically at the time of recurrence.

We previously demonstrated protection against high fat-induced obesity in female but not male p47phox−/− mice lacking NADPH oxidase NOX1/2 activity. To test the role of estradiol (E2)-NOX crosstalk in development of this sexually dimorphic phenotype, we fed diets containing 42% fat/0.5% cholesterol to intact and ovariectomized wild type female C57BL/6 mice and female p47phox−/− mice and to ovariectomized mice where the diet was supplemented with an 1 mg/kg 17β estradiol (E2) for 12 weeks from PND28. Weight gain, gonadal fat pad weight, serum leptin and adiponectin, and adipose tissue inflammation were greater in intact wild type vs. p47 mice ( P phox−/− mice mice ( P Impact statement Estrogens are known to regulate body composition. In addition, reactive oxygen species (ROS) produced by the action of NADPH oxidase (NOX) enzymes have been linked to obesity development. We examined development of obesity and adipose tissue injury in response to feeding “Western” diets high in fat and cholesterol in intact, ovariectomized (OVX), and estrogen-replaced (OVX + E2) wild type and p47phox−/− female mice where NOX2 activity is inhibited. Weight gain, gonadal fat pad weight, and adipose tissue inflammation were greater in intact WT vs. p47phox−/− mice. Genotype effects on body weight/fat mass were abolished after OVX and restored in OVX + E2 mice. These data indicate adipose tissue responses to feeding the “Western” diet is regulated by negative cross-talk between NOX-dependent ROS signaling and E2-signaling during development. Loss of estrogens post menopause may increase the risk of obesity and metabolic syndrome as the result disinhibition of ROS signaling.

Summary: Sarcomatoid urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARC and 84 cases of conventional urothelial carcinoma (UC), with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference. SARCs show a distinct mutational landscape, with enrichment of TP53, RB1, and PIK3CA mutations. They are related to the basal molecular subtype of conventional UCs and could be divided into epithelial-basal and more clinically aggressive mesenchymal subsets on the basis of TP63 and its target gene expression levels. Other analyses reveal that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of the EMT network, and nearly half exhibit a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer. : Guo et al. report that sarcomatoid carcinoma of the bladder evolves by the progression of the basal subtype of conventional urothelial carcinoma with the enrichment of mutagenesis signature 1 and mutations of TP53, RB1, and PIK3CA. It is driven by the dysregulation of the EMT network and shows increased immune infiltrate with overexpression of PD-L1. Keywords: bladder cancer, sarcomatoid carcinoma, urothelial carcinoma, epithelial-mesenchymal transformation, genomic expression, chromatin remodeling, microRNA expression, molecular classification, basal subtype, immune phenotype

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is an established test to identify Lynch syndrome (LS) in patients with colorectal cancer and is being increasingly used to identify LS in women with endometrial and/or nonserous ovarian cancer (OC). We assessed interobserver agreement in the interpretation of MMR-IHC on endometrial and ovarian carcinomas. The study consisted of 73 consecutive endometrial cancers (n=48) and nonserous, nonmucinous epithelial OCs (n=25). Six pathologists from 2 cancer centers, one with and the other without, previous experience in interpreting MMR-IHC, evaluated MLH1, MSH2, MSH6, and PMS2 stains. Before the study, an experienced pathologist led a review of 9 teaching cases. A decision tool was developed as a guide in MMR-IHC interpretation. Staining was interpreted as intact, deficient, or equivocal for each protein. Interobserver agreement for the patient MMR status was categorized as "almost perfect" with κ=0.919 (95% CI, 0.863-0.976). All observers were in agreement in 66 (92%) tumors. Four of the less experienced pathologists had at least 1 discrepant interpretation. There were 6 discordant cases: 3 MMR-deficient cases and 2 MMR-intact cases by majority opinion were called equivocal by at least 1 observer, and 1 MMR-deficient case by majority opinion was interpreted as MMR intact by 1 pathologist. Only the latter case (1/73 patients, 1.4%) had an unequivocal disagreement that could affect patient management. Issues associated with discordant interpretation included heterogeneous staining, intratumoral lymphocytes, regional reduced internal control tissue staining, and scattered absent/weak staining adjacent to tumor cells with strong nuclear staining.

Introduction: To determine whether maternal human papillomavirus (HPV) infection is associated with preterm premature rupture of membranes (PPROM). Materials and Methods: We conducted a re...

What are the ethical responsibilities of doing and teaching qualitative inquiry at a time when Black and Brown bodies are under assault, an expression of White supremacy that has become ever more visible in the wake of the election of Donald Trump? And how might scholars who “think with” posthumanist theories respond to the call for more “humanizing” methodologies being made by African American and Latinx researchers? This article responds to this moment by presenting a conversation among three literacy scholars about the ethical challenges they have encountered in their own engagements with posthumanist theories, and the implications this has for doing/teaching qualitative inquiry. We call for more openness about the limits as well as the possibilities of posthumanisms, and more attention to ethics for justice. The entanglements of human/nonhuman assemblages in these dangerous times call on us to act, not only think, with theory.

The annual average cost of maintaining a racehorse will typically outweigh its earning, making it important that the horse performs above average. The goal of this study was to investigate if the age or experience level of a racehorse could be associated with performance. This study observed pre-racing Quarter Horses (n = 1,033) behavior during one racing season at Delta Downs racetrack (Vinton, LA). The horses were placed into groups based on race experience (0-2, 3-10, and 11+ total races). Horse pre-race before saddling (BSAD), saddling (SAD), after saddling (ASAD) and post-parade (POST) behaviors (calm, ready or nervous) were observed to identify if the horse was calm, ready, or nervous. The behavior types were recorded as categorical variables in this study and were analyzed using proc FREQ, and the finish was recorded as a quantitative variable and were analyzed using proc GLM with (P < 0.05) being statistically different. Horses with 11+ races had a mean±SE finish (4.9±0.1), better (P< 0.05), than horses with 3 to 10 races (4.8±0.2) and both were better (P< 0.05) than horses with 0 to 2 races experience (5.5±0.2). Race experience was also associated with pre-race behaviors. There were more (P< 0.05) horses with 0 to 2 races experience that were classified as nervous during the BSAD (39/326, 11.9%), SAD (29/326, 8.9%), ASAD (13/325, 4.0%) and POST (17/320, 5.3%) compared with horses with 11 plus races experience; BSAD (5/343, 1.5%), SAD (16/343, 4.7%), ASAD (4/343, 1.2%) and POST (1/341, 0.3%). The improvement in race finish among horses with more experience could be that they have been placed in more suitable levels of racing competition compared with unexperienced horses. However, the additional racing experience was associated with less stress or fear-full behaviors pre-race that can result in a reduction of available energy to possibly prolonged elevated cortisol concentrations.

ObjectivesOpioids are routinely prescribed after minimally invasive gynecologic oncology surgery, with minimal data to inform the ideal dose. The aim of this study was to evaluate the impact of a restrictive opioid prescription protocol on the median morphine milligram equivalents prescribed and pain control in patients undergoing minimally invasive surgery.MethodsA restrictive opioid prescription protocol was implemented from January through December 2020 at a single tertiary cancer center in Ontario, Canada. Consecutive patients undergoing minimally invasive hysterectomy for suspected malignancy were included. Simultaneously, we implemented use of multimodal analgesia, patient and provider education, pre-printed standardized prescriptions, and tracking of opioid prescriptions. Total median morphine milligram equivalents prescribed were compared between pre- and post-intervention cohorts. Patients were surveyed regarding opioid use and pain control at 30 days post-surgery.ResultsA total of 101 women in the post-intervention cohort were compared with 92 consecutive pre-intervention controls. Following protocol implementation, median morphine milligram equivalents prescribed decreased from 50 (range 9–100) to 25 (range 8–75) (pConclusionsImplementation of a restrictive opioid prescription protocol led to a significant reduction in opioid use after minimally invasive gynecologic oncology surgery, with over 50% of patients requiring no opioids postoperatively.

Background Machine learning techniques are increasingly being applied in health research. It is not clear how useful these approaches are for modeling continuous outcomes. Child quality of life is associated with parental socioeconomic status and physical activity and may be associated with aerobic fitness and strength. It is unclear whether diet or academic performance is associated with quality of life. Objective The purpose of this study was to compare the predictive performance of machine learning techniques with that of linear regression in examining the extent to which continuous outcomes (physical activity, aerobic fitness, muscular strength, diet, and parental education) are predictive of academic performance and quality of life and whether academic performance and quality of life are associated. Methods We modeled data from children attending 9 schools in a quasi-experimental study. We split data randomly into training and validation sets. Curvilinear, nonlinear, and heteroscedastic variables were simulated to examine the performance of machine learning techniques compared to that of linear models, with and without imputation. Results We included data for 1711 children. Regression models explained 24% of academic performance variance in the real complete-case validation set, and up to 15% in quality of life. While machine learning techniques explained high proportions of variance in training sets, in validation, machine learning techniques explained approximately 0% of academic performance and 3% to 8% of quality of life. With imputation, machine learning techniques improved to 15% for academic performance. Machine learning outperformed regression for simulated nonlinear and heteroscedastic variables. The best predictors of academic performance in adjusted models were the child’s mother having a master-level education (P Conclusions Linear regression was less prone to overfitting and outperformed commonly used machine learning techniques. Imputation improved the performance of machine learning, but not sufficiently to outperform regression. Machine learning techniques outperformed linear regression for modeling nonlinear and heteroscedastic relationships and may be of use in such cases. Regression with splines performed almost as well in nonlinear modeling. Lifestyle variables, including physical exercise, television and computer use, and parental education are predictive of academic performance or quality of life. Academic performance is associated with quality of life after adjusting for lifestyle variables and may offer another promising intervention target to improve quality of life in children.

Examine feasibility and acceptability of a group-mediated cognitive-behavioral (GMCB) intervention targeting planned, self-managed physical activity (PA).Sequential mixed methods, single arm pre-/post-test design with a 4-week follow-up.Post-treatment gynecologic cancer survivors.Participants attended 8 weekly facilitator-led group sessions and completed assessments at baseline, post-intervention and follow-up. Feasibility was assessed by recruitment rate, retention rate, capture of outcomes, intervention usability and intervention fidelity. Acceptability was examined via qualitative interviews. Preliminary estimates of intervention effectiveness (PA, PA social cognitions and sleep) were collected.355 participants were approached and 38 consented. Twenty took part in the study and 17 (85%) completed the intervention. Thematic content analysis revealed positive group experiences. Cognitive-behavioral strategies were beneficial. Goal-setting and shared cancer recovery experience facilitated connection among group members.Program acceptability was high among a diverse sample of gynecologic cancer survivors and delivery of the program is feasible to this group of gynecologic cancer survivors. Recruitment challenges were present but study retention was high.

Background COVID-19 has placed unprecedented demands on infection control professionals (ICPs) and infectious disease (ID) physicians. This study examined their knowledge, preparedness, and experiences managing COVID-19 in the Australian healthcare settings. Methods A cross-sectional study of ICPs and ID physician members of the Australasian College for Infection Prevention and Control (ACIPC) and the Australasian Society for Infectious Diseases (ASID) was conducted using an online survey. Descriptive statistics were used to summarise and report data. Results A total of 103 survey responses were included in the analysis for ICPs and 45 for ID physicians. A majority of ICPs (78.7%) and ID physicians (77.8%) indicated having ‘very good' or ‘good' level of knowledge of COVID-19. Almost all ICPs (94.2%) relied on state or territory's department of health websites to source up-to-date information While most ID physicians (84.4%) used scientific literature and journals. A majority of ICPs (96%) and ID physicians (73.3%) reported feeling ‘moderately prepared' or ‘extremely prepared' for managing COVID-19. Most respondents had received specific training about COVID-19 within their workplace (ICPs: 75%; ID physicians: 66.7%), particularly training/certification in PPE use, which made them feel ‘mostly or entirely confident' in using it. Most ICPs (84.5%) and ID physicians (76.2%) reported having ‘considerably' or ‘moderately more' work added to their daily duties. Their biggest concerns included the uncertainties under a rapidly changing landscape, PPE availability, and the community's compliance. Conclusion Harmonised information, specific COVID-19 training and education, and adequate support for front-line workers are key to successfully managing COVID-19 and other future outbreaks.

IntroductionSentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance.MethodsA Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability.ResultsSeventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; PConclusionSpecific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Background Despite recommendations for reflex immunohistochemistry (IHC) for mismatch repair (MMR) proteins to identify Lynch syndrome (LS), the uptake of genetic assessment by those who meet referral criteria is low. The authors implemented a comprehensive genetic navigation program to increase the uptake of genetic testing for LS in patients with endometrial cancer (EC) or nonserous/nonmucinous ovarian cancer (OC). Methods Participants with newly diagnosed EC or OC were prospectively recruited from 3 cancer centers in Ontario, Canada. Family history questionnaires were used to assess LS‐specific family history. Reflex IHC for MMR proteins was performed with the inclusion of clinical directives in pathology reports. A trained genetic navigator initiated a genetic referral on behalf of the treating physician and facilitated genetic referrals to the closest genetics center. Results A total of 841 participants (642 with EC, 172 with OC, and 27 with synchronous EC/OC) consented to the study; 194 (23%) were MMR‐deficient by IHC. Overall, 170 women (20%) were eligible for a genetic assessment for LS: 35 on the basis of their family history alone, 24 on the basis of their family history and IHC, 82 on the basis of IHC alone, and 29 on the basis of clinical discretion. After adjustments for participants who died (n = 6), 149 of 164 patients (91%) completed a genetic assessment, and 111 were offered and completed genetic testing. Thirty‐four women (4.0% of the total cohort and 30.6% of those with genetic testing) were diagnosed with LS: 5 with mutL homolog 1 (MLH1), 9 with mutS homolog 2 (MSH2), 15 with mutS homolog 6 (MSH6), and 5 with PMS2. Conclusions The introduction of a navigated genetic program resulted in a high rate of genetic assessment (>90%) in patients with gynecologic cancer at risk for LS., A navigated genetic system significantly increases the uptake of genetic assessment for women with endometrial and nonserous/nonmucinous ovarian cancers at high risk of Lynch syndrome.

OBJECTIVE: To compare gynecologic oncology surgical treatment modifications and delays during the first wave of the COVID-19 pandemic between a publicly funded Canadian versus a privately funded American cancer center. METHODS: This is a retrospective cohort study of all planned gynecologic oncology surgeries at University Health Network (UHN) in Toronto, Canada and Brigham and Women's Hospital (BWH) in Boston, USA, between March 22,020 and July 302,020. Surgical treatment delays and modifications at both centers were compared to standard recommendations. Multivariable logistic regression was performed to adjust for confounders. RESULTS: A total of 450 surgical gynecologic oncology patients were included; 215 at UHN and 235 at BWH. There was a significant difference in median time from decision-to-treat to treatment (23 vs 15 days, p < 0.01) between UHN and BWH and a significant difference in treatment delays (32.56% vs 18.29%; p < 0.01) and modifications (8.37% vs 0.85%; p < 0.01), respectively. On multivariable analysis adjusting for age, race, treatment site and surgical priority status, treatment at UHN was an independent predictor of treatment modification (OR = 9.43,95% CI 1.81-49.05, p < 0.01). Treatment delays were higher at UHN (OR = 1.96,95% CI 1.14-3.36 p = 0.03) and for uterine disease (OR = 2.43, 95% CI 1.11-5.33, p = 0.03). CONCLUSION: During the first wave of COVID-19 pandemic, gynecologic oncology patients treated at a publicly funded Canadian center were 9.43 times more likely to have a surgical treatment modification and 1.96 times more likely to have a surgical delay compared to an equal volume privately funded center in the United States.

Objective A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). Data Sources We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. Study Eligibility Criteria We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. Methods We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44–82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4–43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%–95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%–73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%–34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%–96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%–16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%–99%; I2=0%). Conclusion Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Individuals with amputations often experience phantom limb pain (PLP) that can limit their participation in rehabilitation, prosthesis training, desired activities, and roles. One nonpharmacological rehabilitation intervention for PLP is graded motor imagery (GMI). There are several components to GMI, including right/left discrimination or laterality, motor imagery, sensory retraining, and mirror therapy. Successful implementation of GMI requires a range of cognitive skills, such as attention span, working memory, abstract reasoning, and planning. For individuals with PLP who concurrently display cognitive impairments, GMI protocols can be adapted using strategies derived from clinical practice.The purpose of this technical clinical report was to discuss the application of clinically implemented cognitive compensation techniques to GMI instruction.Not applicable.Clinical expert opinion to explore adaptations for GMI.Graded motor imagery can be an effective tool for pain treatment; however, some clients may need greater clinician support due to existing cognitive difficulties.For clients to be successful, active engagement in learning about and implementing GMI techniques is necessary.When serving the lifetime amputation care needs of patients with cognitive deficits, we find that targeted learning strategies and accommodations can be helpful when introducing GMI concepts and skill development. Enhanced patient education techniques support client learning.

Background On 31 December 2019, the World Health Organization recognised clusters of pneumonia‐like cases due to a novel coronavirus disease (COVID‐19). COVID‐19 became a pandemic 71 days later. Aim To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID‐19 in Australia. Methods This is a retrospective, multi‐centre case series. All patients with confirmed COVID‐19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. Results The median age of our patient cohort was 42 years (IQR, 24–53 years) with six men and five women. Eight patients (72.7%) had returned from Wuhan, one from Shenzhen, one from Japan, and one from Europe. Possible human‐to‐human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co‐morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75–21), all patients were discharged. Conclusions This is a historical record of the first COVID‐19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID‐19 models of care and informing the management of COVID‐19 overtime as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection. This article is protected by copyright. All rights reserved.

Recent US guidelines recommend chlorthalidone over other thiazide-type diuretics for the treatment of hypertension based on its long half-life and proven ability to reduce CVD events. Despite recommendations most clinicians prescribe hydrochlorothiazide (HCTZ) over chlorthalidone (CTD). No randomized controlled data exist comparing these two diuretics on cardiovascular outcomes.The Diuretic Comparison Project (DCP) is a multicenter, two-arm, parallel, Prospective Randomized Open, Blinded End-point (PROBE) trial testing the primary hypothesis that CTD is superior to HCTZ in the prevention of non-fatal CVD events and non-cancer death. Patients with hypertension taking HCTZ 25 or 50 mg were randomly assigned to either continue their current HCTZ or switch to an equipotent dose of CTD. The primary outcome is time to the first occurrence of a composite outcome consisting of a non-fatal CVD event (stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, or hospitalization for acute heart failure) or non-cancer death. The trial randomized 13,523 patients at 72 VA medical centers. The study is conducted by a centralized research team with site procedures embedded in the electronic health record and all data collected through administrative claims data, with no study related visits for participants. The trial will have 90% power to detect an absolute reduction in the composite event rate of 2.4%.Enrollment ended in November 2021. There are 4128 participting primary care providers and 16,595 patients individually consented to participate, 13,523 of whom were randomized.DCP should provide much needed evidence as to whether CTD is superior to HCTZ in preventing cardiovascular events in hypertensive patients.NCT02185417 [https://clinicaltrials.gov/ct2/show/NCT02185417].