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Background: Parent engagement in child-focused interventions is increasingly recognised as an important aspect of effective intervention delivery. While several fields have an emerging literature around parent engagement, no reviews currently exist which combine findings across allied health literatures. Objective: This review aimed to explore factors relevant to understanding parent engagement in child-focused interventions, as described in qualitative literature across allied health disciplines, toward informing the clinical practice of helping professionals in effectively engaging parents. Methods: A systematised qualitative literature review was carried out, with a comprehensive search of five online databases (CINAHL, Embase, MEDLINE, PsycINFO, Scopus) for allied health literature (specifically: behaviour analysis, occupational therapy, psychology, and speech-language therapy) using parent engagement key words. Reference searching and citation tracking steps supported the search. Thematic synthesis was used as the overarching framework and analysis approach. Results: 8824 unique studies were generated in the search. Of the 71 studies which met inclusion criteria, 38 reported qualitative findings and were included in the analysis. Five themes were identified including: societal context, interpersonal context, clinician features, family features, and relationship as engagement. Conclusions: Findings support conceptual explanations of parent engagement as a complex and dynamic process, emphasising the joint contributions of parents and clinicians in developing therapeutic relationships which promote engagement. Across allied health research there are consistency of understandings around parent engagement, supporting the conclusion that clinicians can look to literatures from various helping fields to inform clinical practice around engaging parents in interventions.

IntroductionProstate multiparametric magnetic resonance imaging (mpMRI) has greatly improved the detection of clinically significant prostate cancer (csPCa). However, the limited number of expert sub-specialist radiologists capable of interpreting conventional prostate mpMRI is a bottleneck for universal access to this healthcare advance. A reliable and reproducible quantitative imaging biomarker could facilitate implementation of accurate prostate MRI at clinical sites with limited experience, thus ensuring more equitable patient care. Restriction Spectrum Imaging restriction score (RSIrs) is an MRI biomarker that has shown the ability to enhance the qualitative and quantitative interpretation of prostate MRI. However, patient-level factors (age, race, ethnicity, prostate volume, and 5-alpha-reductase inhibitor (5-ARI) use) and acquisition-level factors (scanner manufacturer/model and protocol parameters) can affect prostate mpMRI, and their impact on quantitative RSIrs is unknown.MethodsRSI data from patients with known or suspected csPCa were collected from seven centers. We estimated effects of patient and acquisition factors on prostate voxels overall (Method 1: benign patients only) and on only the maximum RSIrs within each prostate (RSIrsmax; Method 2: benign and csPCa patients) using linear models. We then tested whether adjusting for any estimated systematic biases would improve performance of RSIrs for patient-level detection of csPCa, as measured by area under the ROC curve (AUC).ResultsUsing both Method 1 and Method 2, we observed statistically significant effects on RSIrs of age and acquisition group (p < 0.05). Prostate volume had significant effects using only Method 2. All of these effects were small, and adjusting for them did not improve csPCa detection performance (p ≥ 0.05). AUC of RSIrsmaxfor patient-level csPCa detection was 0.77 (95% CI: 0.75, 0.79) unadjusted, compared to 0.77 (0.76, 0.79) and 0.74 (0.72, 0.76) after adjustment using Method 1 and 2 respectively.ConclusionAge, prostate volume, and imaging acquisition factors may lead to systematic differences in RSIrs, but these effects are small and have minimal impact on performance of RSIrs for detection of csPCa. RSIrs can be used as a reliable biomarker across a wide range of patients, centers, scanners, and acquisition factors.

Abstract: Background: Multiparametric MRI (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, major limitations of mpMRI are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric MRI (bpMRI) and advanced, quantitative MRI techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Purpose: To evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs, and to evaluate characteristics of RSIrs as a stand-alone, quantitative biomarker. Design, setting, and participants: ART-Pro is a multisite, multinational trial that will be conducted in two stages, evaluating bpMRI, mpMRI, and RSIrs on accuracy of expert (ART-Pro-1) and non-expert (ART-Pro-2) radiologists’ detection of csPCa. Additionally, RSIrs will be evaluated as a stand-alone, quantitative, objective biomarker (ART-Pro-1). This study will include a total of 500 patients referred for a multiparametric prostate MRI with a clinical suspicion of prostate cancer at any of the five participating sites (100 patients per site). Intervention: In ART-Pro-1, patients receive standard of care mpMRI, with addition of the RSI sequence, and subsets of the patients’ images are read separately by two expert radiologists, one of whom is the standard of care radiologist (Reader 1). Three research reports are generated using: bpMRI only (Reader 1), mpMRI (Reader 1), and bpMRI + RSIrs (Reader 2). The clinical report is submitted by Reader 1. Patients’ future prostate cancer management will be recorded and used to evaluate the performance of the MRI techniques being tested. In ART-Pro-2, the dataset created in ART-Pro-1 will be retrospectively reviewed by radiologists of varying experience level (novice, basic, and expert). Radiologists will be assigned to read cases and record research reports while viewing subsets of either mpMRI only or RSIrs + mpMRI. Patient cases will be read by two readers from each experience level (6 reads total), and findings will be evaluated against the expertly created dataset from ART-Pro-1. Outcome measurements and statistical analysis: The primary endpoint is to evaluate if bpMRI is non-inferior to mpMRI among expert radiologists (ART-Pro-1) and non-expert radiologists (ART-Pro-2) for detection of grade group (GG) ≥2 csPCa. We will conduct one-sided non-inferiority tests of correlated proportions (ART-Pro-1) and use McNemar’s test and AUC to test the null hypothesis of non-inferiority (ART-Pro-1 and ART-Pro-2). Conclusions: This trial is registered in the US National Library of Medicine Trial Registry (NCT number:NCT06579417) atClinicalTrials.gov. Patient accrual at the first site (UC San Diego) began in December 2023. The expected trial timeline is three years to complete accrual with a six-month endpoint.

Abstract: Background and Objective: Positive predictive value of PI-RADS for clinically significant prostate cancer (csPCa, grade group [GG]≥2) varies widely between institutions and radiologists. The Restriction Spectrum Imaging restriction score (RSIrs) is a metric derived from diffusion MRI that could be an objectively interpretable biomarker for csPCa. Methods: In patients scanned for suspected or known csPCa at 7 centers, we calculated patient-level csPCa probability based on maximum RSIrs in the prostate, without relying on subjectively defined lesions. We used area under the ROC curve (AUC) to compare patient-level csPCa detection for RSIrs, ADC, and PI-RADS. Finally, we combined RSIrs with clinical risk factors via multivariable regression, training in a single-center cohort and testing in an independent, multi-center dataset. Key Findings and Limitations: Among all patients (n=1892), probability of csPCa increased with higher RSIrs . GG≥4 csPCa was most common in patients with very high RSIrs. Among biopsy-naïve patients (n=877), AUCs for GG≥2 vs. non-csPCa were 0.73 (0.69-0.76), 0.54 (0.50-0.57), and 0.75 (0.71-0.78) for RSIrs, ADC, and PI-RADS, respectively. RSIrs significantly outperformed ADC (p

Abstract Habitual consumption of low-calorie sweeteners (LCS) during juvenile-adolescence can lead to greater sugar intake later in life. Here, we investigated if exposure to the LCS Acesulfame Potassium (Ace-K) during this critical period of development reprograms the taste system in a way that would alter hedonic responding for common dietary compounds. Results revealed that early-life LCS intake not only enhanced the avidity for a caloric sugar (fructose) when rats were in a state of caloric need, it increased acceptance of a bitterant (quinine) in Ace-K-exposed rats tested when middle-aged. These behavior shifts, which endured months after the end of Ace-K exposure, were accompanied by widespread changes in the peripheral taste system. The anterior tongue had fewer fungiform taste papillae, and the circumvallate papillae had a reduced anterior to posterior span and diminished expression of genes involved in sweet reception, sweet and bitter intracellular signaling, fructose transport, and cellular progeneration in the Ace-K-exposed rats. Ace-K exposure also led to a significant reduction in dopamine-producing cells of the ventral tegmental area. The collective findings reveal that LCS intake early in life alters the taste-brain axis and the behavioral responsiveness to both positive and negative tastants that are important determinants of dietary preferences.

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Advanced Restriction imaging and reconstruction Technology for Prostate MRI (ART-Pro) is a multisite, multinational trial that aims to evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs. Additionally, RSIrs will be evaluated as a stand-alone, quantitative, objective biomarker. ART-Pro will be conducted in two stages and will include a total of 500 patients referred for multiparametric prostate MRI with a clinical suspicion of prostate cancer at the participating sites. ART-Pro-1 will evaluate bpMRI, mpMRI, and RSIrs on the accuracy of expert radiologists’ detection of csPCa and will evaluate RSIrs as a stand-alone, quantitative, objective biomarker. ART-Pro-2 will evaluate the same MRI techniques on the accuracy of nonexpert radiologists’ detection of csPCa, and findings will be evaluated against the expertly created dataset from ART-Pro-1. The primary endpoint is to evaluate whether bpMRI is noninferior to mpMRI among expert (ART-Pro-1) and nonexpert (ART-Pro-2) radiologists for the detection of grade group ≥2 csPCa. This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT06579417) at ClinicalTrials.gov. Patient accrual at the first site (UC San Diego) began in December 2023. Initial results are anticipated by the end of 2026.

Abstract Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children. In this study, we developed an in silico model describing the pulmonary immune response to a common allergen, house dust mite, to investigate its downstream impact on the pathophysiology of asthma, including airway eosinophilic inflammation, remodelling, and lung function. We hypothesised that altered epithelial function following allergen exposure determines the onset of airway remodelling and abnormal lung function, which are irreversible with current asthma therapies. We calibrated the in silico model using age appropriate in vivo data from neonatal and adult mice. We validated the in silico model using in vivo data from mice on the effects of current treatment strategies. The in silico model recapitulates experimental observations and provides an interpretable in silico tool to assess airway pathology and the underlying immune responses upon allergen exposure. The in silico model simulations predict the extent of bronchial epithelial barrier damage observed when allergen sensitisation occurs and demonstrate that epithelial barrier damage and impaired immune maturation are critical determinants of reduced lung function and asthma development. The in silico model demonstrates that both epithelial barrier repair and immune maturation are potential targets for therapeutic intervention to achieve successful asthma prevention.

Most students acknowledge shared responsibility, with the university, for their employability development. Many academics use assessments as the main driver for motivating students to learn. At the intersection between employability, assessment and learning, the emergent research question is -- what are the mechanisms by which course-based employability is fostered? Prior research reveals that although academics identified course-based assessment as the key employability mechanism, neither students nor employers registered this conceptualisation, and thus purpose of assessment. The aim of this research was to stimulate and communicate the direct connection between assessment and employability to students and interpret their response. Over 100 first-year students, across a metropolitan and regional Australian university, participated. Students were directed to use a simple reflective tool, dubbed iASK by the researchers, that probed employability elements of identity, Attributes, Skills, and Knowledge. The research revealed the resulting student view that regular course-based assessment can develop their employability skills in communication and independence, but not in critical thinking and global citizenship.

The NASA Atmospheric Tomography (ATom) mission built a photochemical climatology of air parcels based on in situ measurements with the NASA DC-8 aircraft along objectively planned profiling transects through the middle of the Pacific and Atlantic oceans. In this paper we present and analyze a data set of 10s (2km) merged and gap-filled observations of the key reactive species driving the chemical budgets of O3 and CH4 (O3, CH4, CO, H2O, HCHO, H2O2, CH3OOH, C2H6, higher alkanes, alkenes, aromatics, NOx, HNO3, HNO4, peroxyacetyl nitrate, and other organic nitrates), consisting of 146494 distinct air parcels from ATom deployments 1 through 4. Six models calculated the O3 and CH4 photochemical tendencies from this modeling data stream for ATom 1. We find that 80%-90% of the total reactivity lies in the top 50% of the parcels and 25%-35% in the top 10%, supporting previous model-only studies that tropospheric chemistry is driven by a fraction of all the air. Surprisingly, the probability densities of species and reactivities averaged on a model scale (100 km) differ only slightly from the 2km ATom 10s data, indicating that much of the heterogeneity in tropospheric chemistry can be captured with current global chemistry models. Comparing the ATom reactivities over the tropical oceans with climatological statistics from six global chemistry models, we find generally good agreement with the reactivity rates for O3 and CH4. Models distinctly underestimate O3 production below 2km relative to the mid-troposphere, and this can be traced to lower NOx levels than observed. Attaching photochemical reactivities to measurements of chemical species allows for a richer, yet more constrained-to-what-matters, set of metrics for model evaluation. This paper presents a corrected version of the paper published under the same authors and title (sans "corrected") as 10.5194/acp-21-13729-2021.

Abstract Pregnancy represents a period of immense maternal physiological adaptation, with progressive increases in lipid storage potential and insulin resistance to support fetal/placental growth. This requires significant change in the adipose tissue. Women living with obesity/overweight are more susceptible to these changes causing complications such as gestational diabetes. This is particularly worrying as up to 60% of European women are living with overweight/obesity at the onset of pregnancy. Furthermore, less than 1% meet all nutrition guidelines. There is now evidence that these deep metabolic changes can result in a predisposition to metabolic disease in both the mother and child in later life. Health and nutrition status during this period therefore represents a window to future health. This period offers a valuable opportunity for intervention to prevent the negative consequences of poor in utero environments and increases the long‐term quality of life for mother and offspring. This review will examine a range of in utero factors which determine adipose tissue development, the impact of these factors on later‐life obesity and metabolic health and the therapeutic value of dietary anti‐inflammatory nutritional interventions during pregnancy and early life. When it comes to early life nutrition, a ‘one size fits all’ approach is not always appropriate. Understanding the mechanisms of adipose tissue development in response to differing nutritional strategies may be important in the context of complicated or adverse in utero environments and represents a substantial step towards a more personalised nutritional approach for the prevention of obesity, metabolic syndrome and related non‐communicable diseases in future generations.

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

Summary: Leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme, with dual activities critical in defining the scale of tissue inflammation and pathology. LTA4H classically operates intracellularly, primarily within myeloid cells, to generate pro-inflammatory leukotriene B4. However, LTA4H also operates extracellularly to degrade the bioactive collagen fragment proline-glycine-proline to limit neutrophilic inflammation and pathological tissue remodeling. While the dichotomous functions of LTA4H are dictated by location, the cellular source of extracellular enzyme remains unknown. We demonstrate that airway extracellular LTA4H concentrations are governed by the level of pulmonary vascular permeability and influx of an abundant repository of blood-borne enzyme. In turn, blood LTA4H originates from liver hepatocytes, being released constitutively but further upregulated during an acute phase response. These findings have implications for our understanding of how inflammation and repair are regulated and how perturbations to the LTA4H axis may manifest in pathologies of chronic diseases.

BackgroundMen with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer.MethodsIn this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting.FindingsBetween May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths.Interpretation24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term.FundingInsightec and the National Cancer Institute.

The mammalian airways and lungs are exposed to a myriad of inhaled particulate matter, allergens, and pathogens. The immune system plays an essential role in protecting the host from respiratory pathogens, but a dysregulated immune response during respiratory infection can impair pathogen clearance and lead to immunopathology. Furthermore, inappropriate immunity to inhaled antigens can lead to pulmonary diseases. A complex network of epithelial, neural, stromal, and immune cells has evolved to sense and respond to inhaled antigens, including the decision to promote tolerance versus a rapid, robust, and targeted immune response. Although there has been great progress in understanding the mechanisms governing immunity to respiratory pathogens and aeroantigens, we are only beginning to develop an integrated understanding of the cellular networks governing tissue immunity within the lungs and how it changes after inflammation and over the human life course. An integrated model of airway and lung immunity will be necessary to improve mucosal vaccine design as well as prevent and treat acute and chronic inflammatory pulmonary diseases. Given the importance of immunology in pulmonary research, the American Thoracic Society convened a working group to highlight central areas of investigation to advance the science of lung immunology and improve human health.

Early childhood education (ECE) settings play a crucial role in promoting physical and social development among children aged 3–7 years. This systematic review sought to examine the associations between characteristics of ECE outdoor environments, social interactions, physical activity, and motor competence. The secondary aim examines previously applied methods to capture children’s behaviour in the context of their social and physical environment. Methods: This review used the PRISMA framework and study quality was assessed using the mixed-methods appraisal tool (MMAT). Keyword searches were conducted in seven databases. Studies were eligible if children were aged 3–7 years in ECE; physical activity, social interactions and/or motor competence were measured; location and/or social context were measured. Results were synthesised using an effect direct plot, a table of associations, and narrative synthesis. Results: Twenty-three studies from eight countries met the inclusion criteria. Intervention and controlled cross-sectional studies (n = 9) favoured high-quality outdoor environments rich in affordances, portable play equipment, and natural features to increase children’s physical activity, social interactions, and cooperative play. Cross-sectional and descriptive studies (n = 14) positively associated open grassy space, portable and fixed equipment, wheeled toys, and paths with physical activity (p < 0.05). Based on limited evidence, playground size and active games in small groups were associated with greater MC. Conclusions: The findings highlight the benefit of creating diverse affordance rich outdoor environments in early childhood settings to promote physical and social development. Limitations include variability in study designs and protocols for conducting systematic observations, thus emphasising the need for standardised approaches to future research.

Background: Physical literacy (PL) is increasingly recognised as essential for fostering lifelong engagement in physical activity (PA), particularly when nurtured in early childhood. Yet there remains limited understanding of how stakeholders in early years (EY) education perceive, value, and implement a PL-informed approach. This study aims to explore knowledge and beliefs regarding PL and PA in relation to 3–5-year-olds, investigating key questions around perceived importance, current practices, and barriers to implementation. Methods: A concurrent mixed-methods approach was used, incorporating semi-structured expert interviews (n = 11), focus groups (n = 22), and a survey (n = 210). Thematic analysis was used to identify key themes from qualitative data, and survey data were analysed to complement and triangulate the qualitative findings. Results: The findings revealed variation in stakeholders’ awareness of PA recommendations and confusion over terminology. Whilst stakeholders acknowledged the importance of PL, there remains uncertainty about the connection between theory and practical application. Identified barriers included resource limitations, conflicting priorities, and insufficient training and policy support. Feedback on an educational PL-EY model was generally positive, suggesting strong potential as a tool to support PL understanding and application in early childhood contexts. Conclusions: Given the pivotal role of EY education in shaping children’s behaviours, health, and wellbeing, this study highlights the necessity of a holistic approach to interventions, strong stakeholder involvement, and evidence-based practices to foster PL in EY children. The PL-EY model presents a promising direction for future resources and education and raises critical questions about what effective interventions to develop PL in this age group should consider and look like.

This paper reports on the development and piloting of a new model of multiplechoice question (MCQ) assessment used in two undergraduate degree modules at a tertiary university. The new model was purposefully designed to promote deeper learning closely aligned with the SOLO taxonomy. Students were invited to participate in an exploratory qualitative study exploring their experience of learning using this new assessment. In total, 13 students completed an online open-ended qualitative questionnaire. Data was analyzed thematically. Four themes were generated: (a) empowered choice, (b) iterative reading, (c) forcing comparison, and (d) justified understandings. Findings suggest that the new model MCQ assessment promoted wider and more prolonged engagement with learning materials and fostered critical comparisons resulting in deeper learning. Limitations in study design mean that further research is merited to develop our model of MCQ assessment and enhance our understanding of students' learning experience.