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IntroductionMammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as ‘overdiagnosed’ cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL (Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers.MethodsSMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.Ethics and disseminationEthical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.Trial registration numberISRCTN12240119.

With the continued emergence of SARS-CoV-2 variants and concerns of waning immunity, there is a need for better defined correlates of protection to aid future vaccine and therapeutic developments. Whilst neutralising antibody titres are associated with protection, these are typically determined in the absence of the complement system, which has the potential to enhance neutralisation titres and strengthen correlates with protection in vivo. Here we show that replenishment of the complement system in neutralisation assays can significantly enhance neutralisation titres, with up to an ~83-fold increase in neutralisation of the BA.1.1.529 strain using cross-reactive sera from vaccination against the ancestral strain. The magnitude of enhancement significantly varies between individuals, viral strains (wild-type/VIC01 and Omicron/BA.1), and cell lines (Vero E6 and Calu-3), and is abrogated following heat-inactivation of the complement source. Utilising ACE2 competition assays, we show that the mechanism of action is partially mediated by reducing ACE2-spike interactions. Through the addition of compstatin (a C3 inhibitor) to live virus neutralisation assays, the complement protein C3 is shown to be required for maximum efficiency. These findings further our understanding of SARS-CoV-2 immunity and neutralisation, with implications for protection against emerging variants and assessing future vaccine and therapeutic developments. It is important to understand the correlates of protection against SARS-CoV-2 and its variants for future vaccine design. Here, the authors show that the complement system enhances the antibody-mediated neutralisation of SARS-CoV-2 via increased inhibition of virus-host interactions.

The main goal of this paper is to conceptualize a theory of optimal motivation for talent development. According to this theory, a lack of motivation can seriously undermine talent development. Optimal motivation is necessary for the full development of talent. Optimal motivation is described as a “flow” experience in which students become so absorbed in a task that they lose track of time and their efforts seem “effortless.” A generalized expectancy-value theory is used to analyze 3 ideal conditions under which students are most likely to experience flow: (a) optimal challenge, (b) undivided interest, and (c) optimal arousal. These conditions are further analyzed by reversal theory to show how each is composed of two complementary motivational processes: (a) “serious-minded” process and (b) “fun-minded” process. The balanced interaction of these two processes creates the optimal motivation of “serious fun” (Rea, 1995, p. 22). With serious fun, students are able to sustain high levels of talent development without burnout or dropout.

The main goals of this article are to explain how the theory of the motivated mind conceptualizes the productive interaction of intelligence, creativity, and achievement motivation and to show how this theory can help educators to maximize students' emergent potential for giftedness. According to this theory, students' motivated minds are complex-adaptive systems comprised of two co-evolving psychological subsystems: cold-order thinking expressed as serious intelligence and hot-chaotic thinking expressed as fun creativity. When these co-evolving subsystems become fully differentiated and integrated, students' complex capacity for giftedness emerges as fluid-adaptive thinking. This enhanced thinking capacity is both seriously intelligent and playfully creative at the same time. Students' optimal motivation for self-regulating and educators' ideal leadership style for promoting fluid-adaptive thinking are operationally described. The motivated mind is also compared and contrasted with Renzulli's three rings of giftedness, Gardner's multiple intelligences, Stemberg's successful intelligence, and Csikszentmihalyi's optimal experience of flow.

Proposes that both formal and informal tests of literature comprehension at the secondary level should be congruent with the latest research on the dynamic complexity of reading comprehension. Provides a conceptual framework and literary examples on how to design \"transformative\" tests (learning activities used for the purposes of testing). (RS)

Advocates the use of serious play in the middle school classroom to provide students with motivating, creative, hands-on activities. Considers the pedagogical benefits and themes of fun and play, and ways to overcome teacher reluctance. Provides four examples of class activities. (JPB)

The Serious-Fun model is presented. The model proposes a balanced interaction of fun and seriousness in order to promote optimal learning.