The survival benefit associated with complete macroscopic resection in epithelial ovarian cancer is histotype-specific

Background: Complete macroscopic resection (CMR) is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high grade serous ovarian carcinoma (HGSOC), and the benefit of CMR in other histotypes is poorly characterised. We sought to determine which histotypes derive the greatest benefit from CMR to better inform future decisions on radical cytoreductive efforts. Methods: We performed multivariable analysis of disease-specific survival (DSS) across two independent patient cohorts to determine the magnitude of benefit associated with CMR within each histotype. Results: Across both cohorts (Scottish, n=1622; SEER, n=18947), CMR was associated with prolonged DSS; this was more marked in the Scottish cohort (multivariable HR 0.44, 95%CI 0.37-0.52 vs 0.59, 95%CI 0.57-0.62 in SEER). In both cohorts, clear cell ovarian carcinoma (CCOC) was among the histotypes to benefit most from CMR (multivariable HR 0.23 and 0.50 in Scottish and SEER cohorts); HGSOC cases demonstrated highly significant and clinically meaningful survival benefit, but this was of lower magnitude than in CCOC and endometrioid ovarian carcinoma (EnOC) across both cohorts. The benefit derived in low grade serous ovarian carcinoma is also high (multivariable HR 0.27 in Scottish cohort). CMR was associated with prolonged survival in mucinous ovarian carcinoma (MOC) patients in the SEER cohort (multivariable HR 0.65), but the associated failed to reach statistical significance in the Scottish cohort. Conclusions: The overall ovarian cancer patient population demonstrates significant survival benefit associated with CMR; however, the magnitude of benefit differs between histotypes. <br/

Behavioral family intervention for children with developmental disabilities and behavioral problems

The outcomes of a randomized clinical trial of a new behavioral family intervention, Stepping Stones Triple P, for preschoolers with developmental and behavior problems are presented. Forty-eight children with developmental disabilities participated, 27 randomly allocated to an intervention group and 20 to a wait-list control group. Parents completed measures of parenting style and stress, and independent observers assessed parent-child interactions. The intervention was associated with fewer child behavior problems reported by mothers and independent observers, improved maternal and paternal parenting style, and decreased maternal stress. All effects were maintained at 6-month follow-up

Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy

Self-Compassion, emotion regulation and stress among australian psychologists: Testing an emotion regulation model of self-compassion using structural equation modeling

Psychologists tend to report high levels of occupational stress, with serious implications for themselves, their clients, and the discipline as a whole. Recent research suggests that selfcompassion is a promising construct for psychologists in terms of its ability to promote psychological wellbeing and resilience to stress; however, the potential benefits of self-compassion are yet to be thoroughly explored amongst this occupational group. Additionally, while a growing body of research supports self-compassion as a key predictor of psychopathology, understanding of the processes by which self-compassion exerts effects on mental health outcomes is limited. Structural equation modelling (SEM) was used to test an emotion regulation model of self-compassion and stress among psychologists, including postgraduate trainees undertaking clinical work (n = 198). Self-compassion significantly negatively predicted emotion regulation difficulties and stress symptoms. Support was also found for our preliminary explanatory model of self-compassion, which demonstrates the mediating role of emotion regulation difficulties in the self-compassion-stress relationship. The final self-compassion model accounted for 26.2% of variance in stress symptoms. Implications of the findings and limitations of the study are discussed

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

Genomics-informed outbreak investigations of SARS-CoV-2 using civet

The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 13 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different ’catchments’ and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health