Longitudinal effects of dog ownership, dog acquisition, and dog loss on children's movement behaviours: findings from the PLAYCE cohort study.

INTRODUCTION: Regular physical activity is important for children's physical and mental health, yet many children do not achieve recommended amounts of physical activity. Dog ownership has been associated with increased physical activity in children, however, there have been no longitudinal studies examining this relationship. This study used data from the Play Spaces and Environments for Children's Physical Activity (PLAYCE) cohort study to examine the longitudinal effects of dog ownership status on children's movement behaviours. METHODS: Change in dog ownership from preschool (wave 1, age 2-5) to fulltime school (wave 2, age 5-7) was used as a natural experiment with four distinct dog ownership groups: continuing non-dog owners (n = 307), continuing dog owners (n = 204), dog acquired (n = 58), and dog loss (n = 31; total n = 600). Daily movement behaviours, including physical activity, sedentary time, sleep, and screen time, were measured using accelerometry and parent-report surveys. Differences between groups over time and by sex were tested using linear mixed effects regression models. RESULTS: Girls who acquired a dog increased their light intensity activities and games by 52.0 min/day (95%CI 7.9, 96.0) and girls who lost a dog decreased their light intensity activities and games by 62.1 min/day (95%CI -119.3, -4.9) compared to no change among non-dog owners. Girls and boys who acquired a dog increased their unstructured physical activity by 6.8 (95%CI 3.2, 10.3) and 7.1 (95%CI 3.9, 10.3) occasions/week, compared to no changes among non-dog owners. Girls and boys who lost a dog reduced their unstructured physical activity by 10.2 (95%CI -15.0, -5.3) and 7.7 (95%CI -12.0, -3.5) occasions/week. Girls who lost a dog decreased their total physical activity by 46.3 min/day (95%CI -107.5, 14.8) compared to no change among non-dog owners. Continuing dog ownership was typically not associated with movement behaviours. Dog ownership group was not associated with changes in sleep and had mixed associations with screen time. CONCLUSION: The positive influence of dog ownership on children's physical activity begins in early childhood and differs by child sex. Further research should examine the specific contributions dog-facilitated physical activity makes to children's overall physical activity, including the intensity and duration of dog walking and play.

Reliability and validity of rapid assessment tools for measuring 24-hour movement behaviours in children aged 0-5 years: the Movement Behaviour Questionnaire Baby (MBQ-B) and child (MBQ-C).

BACKGROUND: The development of validated "fit-for-purpose" rapid assessment tools to measure 24-hour movement behaviours in children aged 0-5 years is a research priority. This study evaluated the test-retest reliability and concurrent validity of the open-ended and closed-ended versions of the Movement Behaviour Questionnaire for baby (MBQ-B) and child (MBQ-C). METHODS: 300 parent-child dyads completed the 10-day study protocol (MBQ-B: N = 85; MBQ-C: N = 215). To assess validity, children wore an accelerometer on the non-dominant wrist (ActiGraph GT3X+) for 7 days and parents completed 2 × 24-hour time use diaries (TUDs) recording screen time and sleep on two separate days. For babies (i.e., not yet walking), parents completed 2 × 24-hour TUDs recording tummy time, active play, restrained time, screen time, and sleep on days 2 and 5 of the 7-day monitoring period. To assess test-retest reliability, parents were randomised to complete either the open- or closed-ended versions of the MBQ on day 7 and on day 10. Test-retest intraclass correlation coefficients (ICC's) were calculated using generalized linear mixed models and validity was assessed via Spearman correlations. RESULTS: Test-retest reliability for the MBQ-B was good to excellent with ICC's ranging from 0.80 to 0.94 and 0.71-0.93 for the open- and closed-ended versions, respectively. For both versions, significant positive correlations were observed between 24-hour diary and MBQ-B reported tummy time, active play, restrained time, screen time, and sleep (rho = 0.39-0.87). Test-retest reliability for the MBQ-C was moderate to excellent with ICC's ranging from 0.68 to 0.98 and 0.44-0.97 for the open- and closed-ended versions, respectively. For both the open- and closed-ended versions, significant positive correlations were observed between 24-hour diary and MBQ-C reported screen time and sleep (rho = 0.44-0.86); and between MBQ-C reported and device-measured time in total activity and energetic play (rho = 0.27-0.42). CONCLUSIONS: The MBQ-B and MBQ-C are valid and reliable rapid assessment tools for assessing 24-hour movement behaviours in infants, toddlers, and pre-schoolers. Both the open- and closed-ended versions of the MBQ are suitable for research conducted for policy and practice purposes, including the evaluation of scaled-up early obesity prevention programs.

Goal-directed therapeutic exercise for paediatric posterior fossa brain tumour survivors: a qualitative analysis of experiences.

PURPOSE: To explore child and parent experiences of a 12-week goal-directed therapeutic exercise intervention in paediatric posterior fossa brain tumours survivors and to identify features of the program that influenced program adherence and acceptability. METHODS: Eleven interviews were conducted; five parent-child dyads (mothers = 83%) and one parent only (mean child age = 10.6 ± 3.0 years; 83% male). Posterior fossa brain tumour survivors, who participated in a weekly goal-directed exercise program for 12 weeks, completed semi-structured interviews to discuss their experience of the program. An inductive content analysis was undertaken. Interviews were transcribed, imported into NVivo and independently coded by two reviewers. Code and content categories were iteratively discussed and refined. RESULTS: Five content categories were generated: (1) perceived improvements, (2) program logistics, (3) activity selection, (4) connection with the therapist and (5) options for technology. All participants valued the tailored exercise program and described improvements in movement competence. Children and their parents discussed preferring home- and community-based locations and favoured face-to-face delivery. Occasionally, parents reported difficulty completing the home program due to low child motivation or family time restrictions. Multiple families suggested an interactive digital application would be an effective delivery channel for the supplemental home-based program. CONCLUSION: A goal-directed exercise program delivered at home and in community-based locations was considered valuable and helpful for improving movement competence in paediatric survivors of posterior fossa brain tumour. TRIAL REGISTRATION: ACTRN12619000841178 June 12, 2019.

Neonatal seizures during extra corporeal membrane oxygenation support.

To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1-20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1-7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4-103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8-41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7-52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97-20.5, p = 0.002)Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: • Patients on ECMO are at a higher risk of seiures. • Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: • In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. • Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? • This study reports a 33% incidence of neonatal seizures during ECMO. • Neonates with seizures were 11 times more likely to have an abnormal brain scan. • The study captures the real-time approach of EEG monitoring. • Recommended cEEG monitoring should last at least 24 h for ECMO patients. • This is the first study to assess this in neonates only.

Stroke Prevention by Antihyperglycemic Drugs in Type 2 Diabetes Mellitus.

OBJECTIVES: The American Heart Association/American Stroke Association and the American Association of Clinical Endocrinology provided guidelines for patients with transient ischemic attacks or strokes (TIA/stroke) and diabetes mellitus with the use of glucose-lowering agents (GLA) effective in preventing major adverse cardiovascular events (MACE). This review evaluated GLA for specific differences in TIA/stroke prevention. METHODS: Previous reviews and meta-analyses were evaluated for outcomes of MACE, cardiovascular death (CVD), hospitalization for heart failure, and TIA/stroke. The GLA were glucagon-like peptide 1-receptor agonists (GLP-1RA, 6-trials, n = 46 541), sodium-glucose transport 2 inhibitors (SGLT2i, 5-trials, n = 46 959), insulin-providing regimens (IP, 4-trials, n = 26 223), and thiazolidinediones (TZD, 1-trial, n = 5238). RESULTS: There were reductions in MACE for each class. Relative risk (rr) reductions for TIA/stroke were found with GLP-1RA (rr = 0.840, 95% CI: 0.759, 0.936, P =.001) but not with SGLT2i, IP, or TZD. Cardiovascular deaths were decreased with GLP-1RA (rr = 0.873, CI: 0.804, 0.947, P =.001) and SGLT2i (rr = 0.835, CI: 0.706, 0.987, P =.034), but not with TZD or IP. Hospitalizations for heart failure were decreased only with SGLT2i (rr = 0.699, CI: 0.626, 0.781, P <.001). Increased CVD correlated with aggressive lowering of A1c (r = -0.611, P =.012) and showed a trend with the relative risk of hypoglycemia (r = 0.447, P =.08). For GLP-1RA, there was no increase in hypoglycemia and a direct correlation with a decreased rr for stroke with decreases in A1c (r = 0.917, P =.010). CONCLUSION: Improvements in A1c with GLP-1RA were associated with stroke prevention in patients with diabetes and with TIA or stroke. Reductions in cardiovascular mortality include therapy with GLP-1RA and SGLT2i. Aggressive lowering of A1c, however, was associated with increased CVD.

A great way to bring up health behaviour topics at playgroup: a qualitative evaluation of the Healthy Conversations @ Playgroup program.

BACKGROUND: The early years is a critical stage to establish optimal nutrition and movement behaviours. Community playgroups are a relaxed environment for parents with a focus on social connection and supporting parents in their role as 'First Teachers'. Playgroups are therefore an opportunistic setting to promote health behaviours in the early years. To support parents with young children around healthy lifestyle behaviours, the Healthy Conversations @ Playgroup program was delivered in urban and regional areas, across three Australian jurisdictions between 2021-2023. OBJECTIVE: This qualitative evaluation aimed to understand how the Healthy Conversations @ Playgroup program was experienced by parents, playgroup coordinators and peer facilitators. DESIGN: Semi-structured virtual interviews and focus groups were conducted with parents, playgroup coordinators (i.e., person responsible for coordinating the playgroup) and peer facilitators (i.e., trained facilitator for the program) that participated in the Healthy Conversations @ Playgroup study. Transcripts were analysed following a thematic analysis approach. RESULTS: Twenty-eight playgroup parents, coordinators or peer facilitators participated in one of 8 focus groups or 5 interviews. Four themes were developed: Program strengths and challenges; Setting strengths and challenges; Factors that impact program delivery; Participant's suggestions for future program delivery. CONCLUSIONS: The Healthy Conversations @ Playgroup program was valued by parents, providing validation and normalisation of parenting practices, and fostering a shared experience of parenting. Playgroups are a convenient setting for families to attend. The dynamic and distracting nature of the playgroup setting were carefully considered when designing the program. Strategies to further enhance program engagement could include use of coordinator or parent champions, tailored delivery, and extending the reach to other family members. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621000055808, registered 22 January 2021, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380890.

Construct Validity of the Both Hands Assessment Using Wrist-Worn Accelerometers.

AIM: The aim of this study was to evaluate the construct validity of the Both Hands Assessment (BoHA) using activity of the upper limbs as detected by accelerometry in children with bilateral cerebral palsy (CP). METHODS: Observational study of children with CP (n = 44, n = 27 boys, aged 9.1 ± 1.6 years; Manual Ability Classification Scale I: n = 15, II: n = 22, III: n = 7) completing a BoHA assessment while wearing a triaxial accelerometer on each wrist. BoHA Each-Hand sub-scores, BoHA percentage difference between hands, BoHA Units, mean activity for each hand, mean activity asymmetry index and total mean activity were calculated. Linear regressions were used to analyze associations between measures. RESULTS: There were significant, positive associations between BoHA Units and total mean activity (B = 0.86, 95%CI: 0.32, 1.40), BoHA Percentage difference between hands and mean activity asymmetry index (B = 0.95, 95%CI: 0.75,1.15), and BoHA Each-Hand sub-score and mean activity for the non-dominant hand (B = 1.71, 95%CI: 1.16, 2.28), but not the dominant hand (B = 0.50, 95%CI: -0.45, 1.45). CONCLUSIONS: This study provides further evidence for the construct validity of the BoHA as a measure of upper limb performance. Wearable wrist sensors such as accelerometers capture and quantify gross upper limb movement in children with CP but cannot measure fine finger movements captured by the BoHA. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616001488493 and ACTRN12618000164291).

High BMP7 expression is associated with poor prognosis in ovarian cancer.

Bone Morphogenetic Protein 7 (BMP7) is an extracellular signalling protein that belongs to the transforming growth factor-ß (TGF- ß) superfamily. Previous transcriptomic data suggested that BMP7 expression may be disrupted in ovarian carcinoma and may play an important role in the aggressiveness of the disease. However, the protein expression in patient tumours has not been well studied. The current study aimed to assess BMP7 protein expression in a large cohort of ovarian carcinoma patient tumour samples to establish its associations with different clinical endpoints. Ovarian carcinoma tissue samples from 575 patients who underwent surgery for different subtypes of ovarian cancer were used. BMP7 protein expression was analysed by immunohistochemistry using tissue microarray and full face tumour sections. High BMP7 expression is associated with aggressive ovarian cancer clinicopathological variables including advanced FIGO stage, high grade, residual disease and poor overall survival. Elevated cytoplasmic and nuclear BMP7 expression was significantly associated with advanced FIGO stage, high tumour grade, presence of residual tumours and high-grade serous carcinomas (p = 0.001, 0.005, 0.004, <0.001 and p < 0.001, <0.001, 0.002, 0.001 respectively). Increased cytoplasmic and nuclear BMP7 expression was also significantly associated with an adverse overall survival (p = 0.001 and 0.046 respectively). The study highlights the potential of BMP7 as a prognostic tool and as a potential novel target for ovarian cancer therapies to limit disease progression.

Tumor microenvironment in a minipig model of spinal cord glioma.

BACKGROUND: Spinal cord glioma (SCG) is considered an orphan disease that lacks effective treatment options with margins that are surgically inaccessible and an overall paucity of literature on the topic. The tumor microenvironment is a critical factor to consider in treatment and modeling design, especially with respect to the unresectable tumor edge. Recently, our group developed a high-grade spinal cord glioma (SCG) model in Göttingen minipigs. METHODS: Immunofluorescence and ELISA were performed to explore the microenvironmental features and inflammation cytokines in this minipig SCG model. Protein carbonyl assay and GSH/GSSG assay were analyzed in the core and edge lesions in the minipig SCG model. The primary core and edge cells proliferation rate were shown in vitro, and the xenograft model in vivo. RESULTS: We identified an elevated Ki-67 proliferative index, vascular and pericyte markers, CD31 and desmin in the tumor edge as compared to the tumor core. In addition, we found that the tumor edge demonstrated increased pro-inflammatory and gliomagenic cytokines including TNF-α, IL-1ß, and IL-6. Furthermore, the mediation of oxidative stress is upregulated in the tumor edge. Hypoxic markers had statistically significant increased staining in the tumor core, but were notably still present in the tumor edge. The edge cells cultures derived from SCG biopsy also demonstrated an increased proliferative rate compared to core cell cultures in a xenotransplantation model. CONCLUSIONS: Our study demonstrates heterogeneity in microenvironmental features in our minipig model of high-grade SCG, with a phenotype at the edge showing increased oxidative stress, proliferation, inflammatory cytokines, neovascularization, and decreased but present staining for hypoxic markers. These findings support the utility of this model as a means for investigating therapeutic approaches targeting the more aggressive and surgically unresectable tumor border.

Adaptations to scale-up an early childhood education and care physical activity intervention for real-world availability - Play Active.

BACKGROUND: Adaptations for scale-up are ubiquitous but are rarely described in detail. Adaptations may be a key reason for the "scale-up penalty" which is when there is a reduction in intervention effect size following scale-up. The Play Active intervention consists of a physical activity policy for early childhood education and care (ECEC) services, with accompanying implementation support strategies. It was first implemented with 81 ECEC services in Perth, Western Australia, in 2021 - with significant positive changes in physical activity practice uptake. The aim of this paper is to describe the extent, type, fidelity consistency, goals, size, scope, and proposed impact of proposed adaptations to the implementation support strategies for scaling-up Play Active. METHODS: Proposed adaptations were defined as planned changes, made prior to making the intervention available. The authors created a list of adaptations from a comparison of the Play Active implementation support strategies, before and after adaptation for proposed statewide availability across Western Australia, Queensland and South Australia, Australia. We used the Framework for Reporting Adaptations and Modifications-Enhanced Implementation Strategies (FRAME-IS) to code adaptations to implementation support strategies. Three authors coded each adaptation and rated their size, scope and proposed impact. RESULTS: Fifty-three adaptations to Play Active were identified. Most (68%) were proposed for the 'content' of implementation strategies, including aspects of their delivery. In practice, this involved changing the delivery mode of implementation support strategies from phone call and email support, to website-based delivery. More than half (56%) of adaptations involved 'adding elements' for scale-up. Most adaptations were 'fidelity consistent' (95%). The main goals for adaptations were related to 'increasing the acceptability, appropriateness, or feasibility' (45%), 'decreasing the costs' (19%) and 'increasing adoption of the evidence-based practice' (19%). Adaptations were small to medium in size, with most proposed to have a positive (87%) or neutral (8%) effect on the effectiveness of the intervention, rather than negative (4%). CONCLUSIONS: A large number of small, fidelity-consistent, adaptations were proposed for Play Active scale-up. Overall, the process of reporting adaptations was found to be feasible. To understand the impact of these adaptations, it will be important to re-evaluate implementation, effectiveness and process outcomes, at-scale.

Play Active physical activity policy intervention and implementation support in early childhood education and care: results from a pragmatic cluster randomised trial.

BACKGROUND: Policy interventions to increase physical activity in early childhood education and care (ECEC) services are effective in increasing physical activity among young children. However, a large proportion of ECEC services do not have nor implement a physical activity policy. Play Active is an evidence-informed physical activity policy intervention with implementation support strategies to enable ECEC services to successfully implement their policy. This study examined the effectiveness, implementation, and process outcomes of Play Active. METHODS: A pragmatic cluster randomised trial in 81 ECEC services in Perth, Western Australia was conducted in 2021. Services implemented their physical activity policy over a minimum of three months. The effectiveness outcomes were changes in educator practices related to daily time provided for total physical activity and energetic play. Implementation outcomes included changes in director- and educator-reported uptake of policy practices and director-reported uptake of high impact and low effort policy practices. Process evaluation outcomes included awareness, fidelity, reach, and acceptability of the intervention and implementation strategies. Analysis involved descriptive statistics and generalised linear mixed effects models. RESULTS: There was a significant increase in the uptake of director-reported policy practices (p = 0.034), but no change in the uptake of the subset of high impact and low effort policy practices. Intervention group educators reported high awareness of the Play Active policy recommendations (90%). Play Active acceptability was high among educators (83%) and directors (78%). Fidelity and reach were high for most implementation support strategies (> 75%). There were no significant changes in the amount of physical activity or energetic play educators provided to children or in the proportion of educators providing the policy recommended ≥ 180 min of physical activity/day or ≥ 30 min of energetic play/day for intervention compared to wait-listed comparison services. CONCLUSIONS: Play Active resulted in significantly higher uptake of physical activity practices. However, there was no change in the amount of physical activity provided to children, which may be explained by the relatively short policy implementation period. Importantly, Play Active had high awareness, fidelity, reach, and acceptability. Future research should investigate the effectiveness of Play Active over longer implementation periods and its scalability potential. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (reference number 12620001206910, registered 13/11/2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378304&isReview=true ).

Sleep homeostasis, seizures, and cognition in children with focal epilepsy.

AIM: To investigate the link between sleep disruption and cognitive impairment in childhood epilepsy by studying the effect of epilepsy on sleep homeostasis, as reflected in slow-wave activity (SWA). METHOD: We examined SWA from overnight EEG-polysomnography in 19 children with focal epilepsy (mean [SD] age 11 years 6 months [3 years], range 6 years 6 months-15 years 6 months; 6 females, 13 males) and 18 age- and sex-matched typically developing controls, correlating this with contemporaneous memory consolidation task scores, full-scale IQ, seizures, and focal interictal discharges. RESULTS: Children with epilepsy did not differ significantly from controls in overnight SWA decline (p = 0.12) or gain in memory performance with sleep (p = 0.27). SWA was lower in patients compared to controls in the first hour of non-rapid eye movement sleep (p = 0.021), although not in those who remained seizure-free (p = 0.26). Full-scale IQ did not correlate with measures of SWA in patients or controls. There was no significant difference in SWA measures between focal and non-focal electrodes. INTERPRETATION: Overnight SWA decline is conserved in children with focal epilepsy and may underpin the preservation of sleep-related memory consolidation in this patient group. Reduced early-night SWA may reflect impaired or immature sleep homeostasis in those with a higher seizure burden. WHAT THIS PAPER ADDS: The decline in slow-wave activity (SWA) across the night, reflecting global synaptic downscaling, was preserved in children with focal lesional epilepsies. Sleep benefited memory consolidation in this group of patients, as in typically developing children. Reduced early-night SWA was associated with increased likelihood of a subsequent seizure.

Rural libraries implementing walking groups or walking groups plus civic engagement for walkability in rural communities: a comparative effectiveness trial study protocol.

BACKGROUND: Rural residents generally lack adequate physical activity to benefit health and reduce disparities in chronic diseases, such as cardiovascular disease and certain cancers. The Socioecological Model describes physical activity as involving a dynamic and reciprocal interaction between individual, social, and community factors. Community group-based walking programs and civic engagement interventions aimed at enhancing physical activity have been successful in rural communities but have not targeted all three socioecological levels. Public libraries can act as innovative public health partners in rural communities. However, challenges remain because rural libraries often lack the capacity to implement evidence-based health promotion programming. The goals of this study are (1) build the capacity for rural libraries to implement evidence-based health promotion programs, (2) compare changes in physical activity between a group-based walking program and a combined group-based walking and civic engagement program with rural residents, and (3) conduct an implementation evaluation. METHODS: We will conduct a comparative effectiveness study of a group-based walking (standard approach) versus a group-based walking plus civic engagement program (combined approach) aimed at enhancing walkability to increase physical activity among rural adults. Key mediators between the program effects and change in outcomes will also be identified. Finally, we will evaluate program implementation, conduct a cost effectiveness evaluation, and use a positive deviance analysis to understand experiences of high and low changers on key outcomes. Twenty towns will be matched and randomized to one of the two conditions and our aim is to enroll a total of 350-400 rural residents (15-20 per town). Study outcomes will be assessed at baseline, and 6, 12, and 24 months. DISCUSSION: This study will build the capacity of rural libraries to implement evidence-based walking programs as well as other health promotion programs in their communities. The study results will answer questions regarding the relative effectiveness and cost effectiveness of two multilevel physical activity interventions targeting rural communities. We will learn what works and how these multilevel interventions can be implemented in rural populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05677906.

Attenuation of Rayleigh waves due to three-dimensional surface roughness: A comprehensive numerical evaluation.

The phenomenon of Rayleigh wave attenuation due to surface roughness has been well studied theoretically in the literature. Three scattering regimes describing it have been identified-the Rayleigh (long wavelength), stochastic (medium wavelength), and geometric (short wavelength)-with the attenuation coefficient exhibiting a different behavior in each. Here, in an extension to our previous work, we gain further insight with regard to the existing theory, in three dimensions, using finite element (FE) modeling, under a unified approach, where the same FE modeling techniques are used regardless of the scattering regime. We demonstrate good agreement between our FE results and the theory in all scattering regimes. Additionally, following this demonstration, we extend the results to cases that lie outside the limits of validity of the theory.

Human Serum Alters the Metabolism and Antibiotic Susceptibility of Staphylococcus aureus.

Staphylococcus aureus is a common source of hospital-acquired bacterial infections, where the emergence of antibiotic resistance is a serious human health concern. Most investigations into S. aureus virulence and antibiotic resistance have relied on in vitro cultivation conditions and optimized media formulations. However, S. aureus can survive and adapt to a hostile host environment or antibiotic treatments by rapidly adjusting its metabolic activity. To assess this metabolic response, S. aureus strains susceptible and nonsusceptible to daptomycin were cultivated in medium supplemented with 55% serum to more closely approximate in vivo conditions. Growth analyses, MIC testing, and NMR-based metabolomics determined that serum decreased daptomycin susceptibility and altered metabolism in S. aureus. Both S. aureus strains exhibited altered amino acid biosynthesis and catabolism, enhanced fermentation, and a modified salt tolerance response. The observation that growth conditions defined an adaptive metabolic response to antibiotics by S. aureus may be a critical consideration for designing an effective drug discovery study.

In vitro radiosensitization of breast cancer with hypoxia-activated prodrugs.

KP167 is a novel hypoxia-activated prodrug (HAP), targeting cancer cells via DNA intercalating and alkylating properties. The single agent and radiosensitizing efficacy of KP167 and its parental comparator, AQ4N, were evaluated in 2D and 3D cultures of luminal and triple negative breast cancer (TNBC) cell lines and compared against DNA damage repair inhibitors. 2D normoxic treatment with the DNA repair inhibitors, Olaparib or KU-55933 caused, as expected, substantial radiosensitization (sensitiser enhancement ratio, SER0.01 of 1.60-3.42). KP167 induced greater radiosensitization in TNBC (SER0.01 2.53 in MDAMB-231, 2.28 in MDAMB-468, 4.55 in MDAMB-436) and luminal spheroids (SER0.01 1.46 in MCF-7 and 1.76 in T47D cells) compared with AQ4N. Significant radiosensitization was also obtained using KP167 and AQ4N in 2D normoxia. Although hypoxia induced radioresistance, radiosensitization by KP167 was still greater under 2D hypoxia, yielding SER0.01 of 1.56-2.37 compared with AQ4N SER0.01 of 1.13-1.94. Such data show KP167 as a promising single agent and potent radiosensitiser of both normoxic and hypoxic breast cancer cells, with greater efficacy in TNBCs.

Adherence to 24-hour movement guidelines among rural Brazalian preschool children: associations with parenting practices.

BACKGROUND: Young children residing in rural areas of low-and-middle income countries (LMICs) such as Brazil are at greater risk of obesity and related chronic health conditions. Yet, the extent to which rural preschool children from Brazil aged 3- to 6-years meet the World Health Organisation (WHO) 24-hour movement guidelines is unknown. Parents play a central role in the development of children's movement behaviors with logistic support, co-participation, modelling, and setting rules and limits recognized as influential parenting practices. However, the bulk of parenting research has been conducted in families from high income countries (HICs) and little is known about the relationship between parenting practices and children's movement behaviors in LMIC communities. Therefore, the aims of this study were two-fold: (1) report the proportion of preschool children from low-income families in rural Brazil meeting the WHO 24-hour movement guidelines; and (2) determine associations with theory-based parenting practices related to physical activity, screen time, and sleep. METHODS: A representative sample of 324 families from a rural district in north-eastern Brazil completed a validated, culturally adapted interviewer-administered survey assessing child physical activity, screen time and sleep, and associated parenting practices. The proportion of children meeting the physical activity, screen time, and sleep recommendations and all combinations of these recommendations was calculated. Forward selection logistic regression was used to determine which parenting practices were associated with meeting the individual recommendations and the 24-hour movement guidelines. RESULTS: Less than half of the children (47.5%) met the physical activity recommendation, 22% met the screen time recommendation, 62% met the sleep recommendation, with just over 10% meeting all three recommendations in the 24-h movement guidelines. Having fewer rules and restrictions around indoor and outdoor play, limiting, or monitoring screen time, and maintaining a consistent bedtime routine were key parenting practices associated with children´s adherence to the 24-hour movement guidelines. CONCLUSION: Only 1 in 10 rural Brazilian preschool children meet the 24-hour movement guidelines. These findings underscore the need for family-based interventions targeting parenting practices to support healthful movement behaviors in young children from LMICs.

Ancient DNA confirmation of lepromatous leprosy in a skeleton with concurrent osteosarcoma, excavated from the leprosarium of St. Mary Magdalen in Winchester, Hants., UK.

To establish a biological profile and disease aetiologies for one of four burials recovered during a Time Team dig at the St. Mary Magdalen leprosarium, Winchester, UK in AD 2000. Osteological techniques were applied to estimate age at death, biological sex, stature and pathology. Visual assessment of the material was supplemented by radiographic examination. Evidence for leprosy DNA was sought using ancient DNA (aDNA) analysis. The remains are those of a male individual excavated from a west-east aligned grave. The skeleton shows signs of two pathologies. Remodelling of the rhino-maxillary area and degenerative changes to small bones of the feet and reactive bone on the distal lower limbs suggest a multibacillary form of leprosy, whereas the right tibia and fibula show the presence of a primary neoplasm identified as an osteosarcoma. The aDNA study confirmed presence of Mycobacterium leprae in several skeletal elements, and the strain was genotyped to the 3I lineage, one of two main SNP types present in mediaeval Britain and ancestral to extant strains in America. This is a rare documentation of leprosy in association with a primary neoplasm.

Contributions of side effects to contraceptive discontinuation and method switch among Kenyan women: a prospective cohort study.

OBJECTIVE: To determine the contribution of specific contraceptive side effects to method switch and modern-method discontinuation among Kenyan women. DESIGN: A prospective cohort study. SETTING: Five counties in Western Kenya. PARTICIPANTS: Women aged ≥18 years old and emancipated female minors ≥14 years old using modern, reversible contraception were recruited while attending 10 public health facilities. METHODS: Patient-reported adverse effect symptoms, method switch and discontinuation were reported through weekly text message-based surveys for 24 weeks. MAIN OUTCOME MEASUREMENTS: Prevalence, hazards ratio (HR). RESULTS: Among 825 women, 44% were using implants, 43% injectables, 7% an intrauterine device and 6% oral contraceptive pills at enrolment. Most (61%) women were continuing a method used in the previous month. During the 24-week follow up, incidence of contraceptive switch was 61.3 per 100 person-years (95% confidence interval [CI] 52.4-71.8) and incidence of discontinuation was 38.5 per 100 person-years (95% CI 31.6-47.0). On average, one-quarter (prevalence [Pr] 0.24, 95% CI 0.22-0.26) of participants reported side effects or method problems weekly, with sexual side effects the most prevalent symptom (Pr 0.15, 95% CI 0.13-0.16). Lack of expected bleeding was associated with higher risk of method switch (adjusted hazard ratio [aHR] 2.36, 95% CI 1.22-4.57). Risk of all-modern method discontinuation was higher among women experiencing irregular bleeding (aHR 2.39, 95% CI 1.20-4.77), weight changes (aHR 2.72, 95% CI 1.47-4.68) and sexual side effects (aHR 2.42, 95% CI 1.40-4.20). CONCLUSIONS: Addressing irregular bleeding, weight changes and sexual side effects through development of new products that minimise these specific side effects and anticipatory counseling may reduce method-related discontinuation. TWEETABLE ABSTRACT: Bleeding, weight changes, sexual problems associated with discontinuation of #contraception, but many continue despite side effects.

Feeding practices in Australian early childhood education and care settings.

OBJECTIVE: Feeding practices used by educators in Early Childhood Education and Care (ECEC) settings can influence the diet quality of young children. However, Australian data is scarce and limited to describing barriers to responsive feeding. This study describes the use of feeding practices amongst a group of Australian educators. DESIGN: Direct observation of feeding practices and assessment of centre policy were conducted using the 'Environment and Policy Assessment and Observation' tool. Self-reported feeding practices and demographic data were collected via online survey using the Childcare Food and Activity Practices Questionnaire. SETTING: Ten centre-based ECEC services in South East Queensland, Australia. PARTICIPANTS: Educators working in ECEC. RESULTS: A total of 120 meals were observed and 88 educators provided self-report data (n 84 female). Centre policy supported the use of responsive feeding practices, and this was reflected in the high frequency with which children could decide what and how much to eat, across both observed and self-report data as well as low levels of pressure to eat and use of food as a reward (observed at 19·9 % and 0 % of meals). The only apparent discrepancy was regarding modelling. Median score for self-reported role-modelling was 5·0 (4·3-5·0) and educators were observed to sit with children at 75 % of meals, however observed occasions of enthusiastic role modelling was only 22 % (0-33·3) of meals. CONCLUSIONS: Research addressing how educators conceptualise feeding practices, as well under what circumstances they are used, particularly in centres with different models of food provision, may shed light on why modelling is rarely implemented in practice.