Pulmonary metastasectomy versus continued active monitoring in colorectal cancer (PulMiCC): a multicentre randomised clinical trial

BACKGROUND: Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT). METHODS: Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%. RESULTS: Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56). CONCLUSIONS: Because of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23-62%) for metastasectomy patients and 29% (16-52%) in the well-matched controls. That is the new and important finding of this RCT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01106261. Registered on 19 April 2010

Inflexible Youngsters: Psychological and Psychopathological Correlates of the Avoidance and Fusion Questionnaire for Youths in Nonclinical Dutch Adolescents

The present study examined psychological and psychopathological correlates of psychological inflexibility as measured by the Avoidance and Fusion Questionnaire for Youth (AFQ-Y) in two independent samples of nonclinical Dutch adolescents aged between 12 and 18 years (Ns being 184 and 157). Participants completed a survey containing the AFQ-Y and scales assessing mindfulness, thought suppression, self-compassion, self-worth, self-efficacy, and internalizing/externalizing symptoms. In both samples, the AFQ-Y was found to be a reliable measure of psychological inflexibility that correlated in a theoretically meaningful way with other psychological constructs. Most importantly, AFQ-Y scores correlated positively with internalizing and externalizing symptoms, and in most cases, these associations remained significant when controlling for other measures. These findings suggest that psychological inflexibility is an important factor in youth psychopathology that needs to be further investigated in future research

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

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

How Corporates in South Africa Are Using Serious Games in Business

It has been shown that serious games are useful in the military, healthcare, and education sectors. Meanwhile corporate interest in serious gaming in business has rapidly grown internationally. However the level of awareness and adoption of serious gaming among South African corporates in business is still unclear.This interpretive study explores South African corporate awareness of serious gaming in business and the barriers to its adoption. Semi-structured interviews were used to collect qualitative data from managers in Johannesburg Stock Exchange-listed companies. Eight participants were interviewed across four different industries. Data analysis was guided by the general inductive approach.The absence of serious gaming adopters among the participants, and the general lack of awareness of serious gaming in business were identified as the most salient features. The analysis suggests that corporates currently use technologies related to serious games (e-learning, collaborative tools, and simulation tools), and that there is a demand for the greater promotion and use of serious gaming.While the findings provide new insights into the level of serious gaming awareness, caution should be exercised when attempting to generalize these findings due to the small sample and the scarcity of prior research

A Protective Factor Against Mental Health Problems in Youths?: A Critical Note on the Assessment of Self-Compassion

Self-compassion, which refers to the tendency of being kind and understanding to oneself when confronted with personal failings and difficulties, is increasingly investigated as a protective factor within the context of mental health problems. In this invited paper, I will briefly introduce the concept of self-compassion and give an overview of the research that has examined its relationship with psychopathology in youth. Then I will make my critical point regarding the assessment of self-compassion: the scales that are currently used for measuring this construct include a large number of reversely scored, negative items that measure the precise opposite of having compassion with oneself. I present evidence (partly on the basis of own data) that these negative items do not reflect the true protective nature of self-compassion and tend to inflate the relation with psychopathology. My recommendation is to remove the negative items from the scales and to assess self-compassion by means of a set of items that truly reflect its protective nature