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Background: Mental health concerns prevent positive well-being and are key challenges for Australian children and young people. Arts organisations play a role in enhancing the positive mental health of children and young people. This paper describes the involvement of young people and their parents in the development of a resource for arts organisation's intentional support of social and emotional well-being. Methods: Six focus groups were conducted with 19 young people who participate in dance, drama, and circus programs, and 17 of their parents. Questions explored how the arts currently, and potentially, support their social and emotional well-being. Results: Three overarching themes: "Connecting with Others;" "Being Myself;" and "Teaching Methods," plus 14 sub-themes were identified. Conclusion: A framework of well-being factors and pedagogies was developed to guide the creation of a resource to help support the social and emotional well-being of young people participating in arts programs.

Developing as a scholar is a critical aspect of graduate school. In this article, we use an autoethnographic approach to explore our experiences in a newly redeveloped interdisciplinary graduate course. The course was designed to emphasize interdisciplinary scholarship and to encourage students' awareness of their own developing epistemological, ontological, and axiological commitments. In this paper, we identify themes that arose from the final class paper, in which the students/researchers reflected on our development as emerging scholars. Through this course we developed an understanding of the value of interdisciplinarity, the cultural embeddedness of knowledge, and our own responsibilities as researchers in relation to social structures of power and marginalization. Our analyses of our experiences suggests that reflections on our own positionality and axiology are important for developing our identities as emerging scholars and that becoming a scholar may be more about the process than an end goal. We conclude with a discussion of how our learning in this course may be relevant for other instructors and emerging scholars.

Little research has been done on conceptualizing gender-based violence (GBV) against immigrant and refugee women as a continuum of violence. The objective of the larger study was to understand gender-based violence in migration and analyze the ways in which discriminations and inequalities interact to increase vulnerability and decrease access to supports and services for some women. Using (a) the concept of continuum of [sexual] violence and (b) intersectionality, we demonstrate the need to both document the range of violence in women’s lives and the tactics of victimization among immigrant and refugee women and show how they are different than the cumulated literature showing victimization tactics against the Canadian-born population. Using semi-structured interviews via phone or video, we asked professionals (N = 43) who worked with migrant women across Canada about forms of GBV experienced in the immigrant and refugee populations they worked with. Participants reported that non-physical forms of violence are more normalized, but also more commonly experienced than physical forms of violence in Canada. Additionally, intersecting social identities impact both the distinct and amplified forms of GBV immigrant and refugee women experienced. Results contribute theoretically and empirically to the conceptualization of the GBV experiences by immigrant and refugee women in Canada.

Abstract Background Congenital Heart Disease (CHD) is the most common congenital abnormality. Survival rates are over 90%, however infants with CHD remain at high risk of attention and executive function impairments. These abilities are difficult to assess in toddlers because clinical assessments rely on language abilities which are commonly delayed in CHD. Our aim was to characterise visual attention in toddlers with CHD compared to controls and identify associations with parent‐rated effortful control. Methods Thirty toddlers with CHD (19 male, median (IQR) age at assessment 22.2 (22–23.1) months) and 66 controls from the developing human connectome project (36 male, age at assessment 22 (21.5–23.8) months) using eye‐tracking tasks designed to assess multiple components of visual attention. Analyses of co‐variance and regressions were used to identify differences between groups and relationships between gaze behaviours and parent‐rated effortful control. Results Toddlers with CHD were less accurate when switching behaviours (set‐shifting) [median (IQR) 79%, (28–100)] compared to controls [100% (86–100), pFDR = 0.032], with worse accuracy associated with lower parent‐rated effortful control in CHD but not controls (interaction pFDR = 0.028). Reaction times were slower during selective [CHD 1243 ms (986–1786), controls 1065 ms (0851–1397), pFDR

Abstract Targeted therapy remains the future of anti‐cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility. Here, ICT10336 is reported, a newly developed hypoxia‐responsive prodrug of ATR inhibitor, AZD6738, which is hypoxia‐activated and specifically releases AZD6738 only in hypoxic conditions, in vitro. This hypoxia‐selective release of AZD6738 inhibited ATR activation (T1989 and S428 phosphorylation) and subsequently abrogated HIF1a‐mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. Importantly, in normal tissues, ICT10336 is demonstrated to be metabolically stable and less toxic to normal cells than its active parent agent, AZD6738. In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor‐targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index.

The following Key Messages comprise the salient findings of this study:1. Ambient energy (from sun, air, ground, and sky) can heat and cool buildings; provide hot water, ventilation, and daylighting; dry clothes; and cook food. These services account for about three-quarters of building energy consumption and a third of total US demand. Biophilic design (direct and indirect connections with nature) is an intrinsic adjunct to ambient energy systems, and improves wellness and human performance.2. The current strategy of electrification and energy efficiency for buildings will not meet our climate goals, because the transition to an all-renewable electric grid is too slow. Widespread adoption of ambient energy is needed. Solar-heated buildings also flatten the seasonal demand for electricity compared to all-electric buildings, reducing required production capacity and long-term energy storage. In addition, ambient-conditioned buildings improve resilience by remaining livable during power outages.3. National policies, incentives, and marketing should be enacted to promote ambient energy use. Federal administrative priorities should reflect the importance of ambient energy for buildings. Use of ambient energy should be encouraged through existing and new building codes and standards.4. Ambient energy system design tools are needed for architects, engineers, builders, building scientists, realtors, appraisers, and consumers. PVWatts is used over 100 million times per year for photovoltaic system design. A similar, simple, and accessible tool for ambient design is crucial.5. Training on ambient energy is needed throughout secondary, post-secondary, and continuing education for workforce development. Currently, only about 10% of colleges teach courses on passive heating and cooling systems.6. Ambient-conditioned buildings should be demonstrated in all US climate zones. Performance should be monitored and reported, with quantitative case studies made widely available.7. While current technology is sufficient to build high-performance ambient buildings now, research is needed to develop new technologies to harness ambient energy more effectively and more economically. Such advancements will facilitate adoption of ambient energy technologies in a wider range of buildings, including retrofits. Examples include windows with much lower thermal losses, use of the building shell for thermal storage, alternative light-weight thermal storage systems, sky-radiation cooling systems, automated controls for solar gains and passive cooling, and ground coupling.

Abstract Identifying factors linked to autism traits in the general population may improve our understanding of the mechanisms underlying divergent neurodevelopment. In this study we assess whether factors increasing the likelihood of childhood autism are related to early autistic trait emergence, or if other exposures are more important. We used data from 536 toddlers from London (UK), collected at birth (gestational age at birth, sex, maternal body mass index, age, parental education, parental language, parental history of neurodevelopmental conditions) and at 18 months (parents cohabiting, measures of socio-economic deprivation, measures of maternal parenting style, and a measure of maternal depression). Autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) at 18 months. A multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). In order to address variable collinearity we used principal component analysis, finding that a component which was positively correlated with Q-CHAT was also correlated to measures of parenting style and socio-economic deprivation. Our results show that parenting style and socio-economic deprivation correlate with the emergence of autism traits at age 18 months as measured with the Q-CHAT in a community sample.

Abstract In the study, we report an in situ corrosion and mass transport monitoring method developed using a radionuclide tracing technique for the corrosion study of 316L stainless steel (316L SS) in a NaCl–MgCl2 eutectic molten salt natural circulation loop. This method involves cyclotron irradiation of a small tube section with 16 MeV protons, later welds at the hot leg of the molten salt flow loop, generating radionuclides 51Cr, 52Mn, and 56Co at the salt–alloy interface. By measuring the activity variations of these radionuclides at different sections along the loop, both the in situ monitoring of the corrosion attack depth of 316L SS and corrosion product transport and its precipitation in flowing NaCl–MgCl2 molten salt are achieved. While 316L SS is the focus of this study, the technique reported herein can be extended to other structural materials being used in a wide range of industrial applications.

Abstract Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

Abstract Introduction Clinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia’s new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care. Methods and analysis The Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level. Discussion The EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 — retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx .

Summary: Background: According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment. Here we compare oncologic outcome by TMMR + tLND or ST. Methods: In this observational cohort study, women treated according to international guidelines were identified in the population-based registries from Sweden and women treated with TMMR were identified in the Leipzig Mesometrial Resection (MMR) Study Database (DRKS 0001517) 2011–2020. Relevant clinical and tumour related variables were extracted. Recurrence-free survival (RFS) and overall survival (OS) by ST or TMMR was analysed with log-rank test, cumulative incidence function and proportional hazard regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders. Findings: Between 2011 and 2020, 1007 women were included in the final analysis. 733 women were treated according to ST and 274 with TMMR. RFS at five years was 77.9% (95% CI 74.3–81.1) and 82.6% (95% CI 77.2–86.9) for the ST and TMMR cohorts respectively (p = 0.053). In early-stage CC, RFS was higher after TMMR as compared to ST, 91.2% vs 81.8% (p = 0.002). In the adjusted analysis, TMMR was associated with a lower hazard of recurrence (HR 0.39; 95% CI 0.22–0.69) and death (HR 0.42; 95% CI 0.21–0.86) compared to ST. The absolute difference in risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7) in favor of TMMR. In locally advanced CC, no significant differences in RFS or OS was observed. Interpretation: Compared to ST, TMMR without radiation therapy was associated with superior oncologic outcomes in women with early-stage cervical cancer whereas no difference was observed in locally advanced disease. Our findings together with previous evidence suggest that TMMR may be considered the primary option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment. Funding: This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden).

The accumulation of heavy metals in the edible tissue of the white spot sea cucumber, Holothuria poli, revealed the transfer of metal contaminants to sea cucumbers when produced below fish cages in a Mediterranean port area. Sea cucumbers were cultured on the seafloor directly below a fish cage at 0 m, then at 10 m and at 25 m away from the cage, as part of an open-water integrated multi-trophic aquaculture (IMTA) system, and then at a reference site over 1 km from the fish farm, over a one-year period. At the end of the study, sea cucumbers and seafloor sediments were sampled from the IMTA sites near the fish cages, except at 0 m due to mass sea cucumber mortalities within the first month of the study, and again at the reference site. The concentrations of cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), and zinc (Zn) were significantly higher in sediments near fish cages than the reference site. Localised enrichment from marine aquaculture could explain the significant concentration of metals in sediments below fish cages that are typically ascribed to their use in aquaculture. Arsenic (As), lead (Pb) and mercury (Hg), which are not associated with commercial fish diets, did not vary between sites. Concentrations of iron (Fe), which is available in commercial diets, were similar near fish cages and at the reference site. The body wall/muscle tissue of the sea cucumber. H. poli revealed high concentrations of the essential metals Fe and Zn near fish cages and in natural sediments at the reference site. H. poli can regulate these essential metals that characterised the edible tissue of the sea cucumbers. Non-essential metals like Hg and Cd had the lowest concentrations of all analysed metals in the sea cucumber tissue. However, the bioaccumulation of toxic metals, Hg and As, reveal the bioavailability of these contaminants in sediments and the propensity of bottom-dwelling sea cucumbers to bioconcentrate these metals, when cultured under a commercial fish cage in IMTA and elsewhere in natural sediments in this industrial environment. Holothuria poli did not exhibit bioaccumulation of Cu, Cr, Fe, Ni, Pb and Zn in its body wall/muscle tissue. The bioaccumulation of Hg and As reveal the need to account for the potential effects of farm-level variability throughout longer production cycles and bay-wide dynamics on sediment contamination and bioaccumulation in sea cucumbers until harvest. Site-specific dynamics in ports, whether natural or anthropogenic, can be expected to influence bioaccumulation of metal contaminants and therefore require long-term and fine resolution monitoring for better representation in open-water IMTA production.

Classically, ATM is known for its role in sensing double-strand DNA breaks, and subsequently signaling for their repair. Non-canonical roles of ATM include transcriptional silencing, ferroptosis, autophagy and angiogenesis. Angiogenesis mediated by ATM signaling has been shown to be VEGF-independent via p38 signaling. Independently, p38 signaling has been shown to upregulate metalloproteinase expression, including MMP-2 and MMP-9, though it is unclear if this is linked to ATM. Here, we demonstrate ATM regulates aminopeptidase-N (CD13/APN/ANPEP) at the protein level. Positive correlation was seen between ATM activity and CD13 protein expression using both “wildtype” (WT) and knockout (KO) ataxia telangiectasia (AT) cells through western blotting; with the same effect shown when treating neuroblastoma cancer cell line SH-SY5Y, as well as AT-WT cells, with ATM inhibitor (ATMi; KU55933). However, qPCR along with publically available RNAseq data from Hu et al. (J. Clin. Invest., 2021, 131, e139333), demonstrated no change in mRNA levels of CD13, suggesting that ATM regulates CD13 levels via controlling protein degradation. This is further supported by the observation that incubation with proteasome inhibitors led to restoration of CD13 protein levels in cells treated with ATMi. Migration assays showed ATM and CD13 inhibition impairs migration, with no additional effect observed when combined. This suggests an epistatic effect, and that both proteins may be acting in the same signaling pathway that influences cell migration. This work indicates a novel functional interaction between ATM and CD13, suggesting ATM may negatively regulate the degradation of CD13, and subsequently cell migration.

This study examines implications of a rights-based perspective among honors students through the lens of healthcare. Students (n = 71) surveyed in April 2019 were asked to consider issues relating to health entitlement and government responsibility. Perspectives on local, regional, national, and global access to health care; state and national government fiscal responsibility; and rights-based approaches to health entitlement were elicited. Data indicate a propensity for understanding health as a human right among honors students. Probit regressions show a more inclusive stance on healthcare policy and a general preference toward a universal healthcare system. Acknowledging that innovative curricula can help students comprehend and tackle complex issues, the authors suggest that honors programs and practitioners are uniquely poised to help illumine political issues associated with healthcare, which are often abundant and perplexing.

Abstract Background Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT’s sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen. Methods We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool. Results For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3–38%) and 86% (95% CrI 59–96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0–90%) and 86% (95% CrI 9–100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32–92%) and 75% (95% CrI 45–93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2–100%) and 75% (2–100%). Conclusions Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.

Abstract Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.