Role of Metastasis-Directed Therapy in Genitourinary Cancers.

OPINION STATEMENT: The treatment of oligometastatic genitourinary cancers is a rapidly advancing field with ablative radiotherapy as one of the critical treatment components. The oligometastatic disease state, which can be defined as 1-5 metastatic sites with a controlled primary, represents a distinct clinical state where comprehensive ablative local therapies may provide improved outcomes. Enhanced imaging has increased the number of patients identified with oligometastatic disease. Evidence for improved outcomes with metastasis-directed therapy (MDT) in oligometastatic genitourinary cancers is increasing, and previously published outcome data continues to mature with an increasing body of prospective data to inform the role of MDT in histology-specific settings or in the context of systemic therapy. In select patients, MDT can offer benefits beyond improved local control and allow for time off of systemic therapy, prolonged time until next therapy, or even the hope of cure. However, treatment decisions for locally ablative therapy must be balanced with consideration towards safety. There are exciting advances in technologies to target and adapt treatment in real-time which have expanded options for safer delivery and dose escalation to metastatic targets near critical organs at risk. The role of systemic therapies in conjunction with MDT and incorporation of tumor genetic information to further refine prognostication and treatment decision-making in the oligometastatic setting is actively being investigated. These developments highlight the evolving field of treatment of oligometastatic disease. Future prospective studies combining MDT with enhanced imaging and integrating MDT with evolving systemic therapies will enable the optimal selection of patients most likely to benefit from this "all-or-none" approach and reveal settings in which a combination of therapies could result in synergistic outcomes.

Determining the prevalence of Escherichia coli, Salmonella, and shiga toxin-producing Escherichia coli in manure of dairy lagoons.

AIM: The aim of this study was to determine the prevalence of microbial pathogens in manure of dairy lagoons in California. METHODS AND RESULTS: To determine pathogens in dairy manure stored in anaerobic lagoons of dairy farm, an extensive field study was conducted across California to sample manure from 20 dairy farms. Samples were analyzed to determine the prevalence of indicator E. coli, Shiga toxin producing E. coli (STEC), Salmonella, and E. coli O157:H7. To test the E. coli, STEC, and Salmonella, we used agar culture-based method followed by polymerase chain reaction (PCR) method. In addition, a real- time PCR based method was used to determine the presence of E coli O157:H7. Study demonstrated that the prevalence of Salmonella in manure sample is lower than E. coli. The presence of Salmonella was found in 2.26% of the samples, and both the culture-based and PCR methods yielded comparable outcomes in detecting Salmonella. Moreover, approximately 11.30% of the total samples out of the 177 were identified as positive for STEC by qPCR. CONCLUSION: These findings demonstrate that indicator E. coli are abundantly present in anaerobic lagoons. However, the presence of STEC, and Salmonella is substantially low.

A protocol for annotation of total body photography for machine learning to analyze skin phenotype and lesion classification.

Introduction: Artificial Intelligence (AI) has proven effective in classifying skin cancers using dermoscopy images. In experimental settings, algorithms have outperformed expert dermatologists in classifying melanoma and keratinocyte cancers. However, clinical application is limited when algorithms are presented with 'untrained' or out-of-distribution lesion categories, often misclassifying benign lesions as malignant, or misclassifying malignant lesions as benign. Another limitation often raised is the lack of clinical context (e.g., medical history) used as input for the AI decision process. The increasing use of Total Body Photography (TBP) in clinical examinations presents new opportunities for AI to perform holistic analysis of the whole patient, rather than a single lesion. Currently there is a lack of existing literature or standards for image annotation of TBP, or on preserving patient privacy during the machine learning process. Methods: This protocol describes the methods for the acquisition of patient data, including TBP, medical history, and genetic risk factors, to create a comprehensive dataset for machine learning. 500 patients of various risk profiles will be recruited from two clinical sites (Australia and Spain), to undergo temporal total body imaging, complete surveys on sun behaviors and medical history, and provide a DNA sample. This patient-level metadata is applied to image datasets using DICOM labels. Anonymization and masking methods are applied to preserve patient privacy. A two-step annotation process is followed to label skin images for lesion detection and classification using deep learning models. Skin phenotype characteristics are extracted from images, including innate and facultative skin color, nevi distribution, and UV damage. Several algorithms will be developed relating to skin lesion detection, segmentation and classification, 3D mapping, change detection, and risk profiling. Simultaneously, explainable AI (XAI) methods will be incorporated to foster clinician and patient trust. Additionally, a publicly released dataset of anonymized annotated TBP images will be released for an international challenge to advance the development of new algorithms using this type of data. Conclusion: The anticipated results from this protocol are validated AI-based tools to provide holistic risk assessment for individual lesions, and risk stratification of patients to assist clinicians in monitoring for skin cancer.

Measuring perceived fitness interdependence between humans and non-humans.

Conservation ethics (i.e. moral concern for non-human organisms) are widespread, but we lack a comprehensive explanation for why people care about other species at all, and why they express strong moral concern for some species but not others. Recent theory suggests that conservation ethics might be rooted in cooperation between humans and members of other species. Building on central predictions of this eco-evolutionary theory, we conducted an online study (N = 651) and exploratory factor analysis to develop two scales that independently measure perceived fitness interdependence (PFI) and conservation ethics. The PFI scale measures perceived shared fate as a proximate indicator of human fitness interdependence with non-human organisms (i.e. the degree to which humans and other organisms influence each other's evolutionary success, that is, survival and reproduction). We designed the conservation ethics scale to measure moral beliefs and attitudes regarding those organisms. Both scales are composed of two factors and demonstrate good internal reliability. By combining insights from various branches of the evolutionary human sciences, including evolutionary anthropology, evolutionary psychology and human behavioural ecology, we offer empirical tools to investigate eco-evolutionary foundations of conservation ethics and behaviour.

How CPC+ supported patient care during the COVID-19 pandemic: Lessons for alternative payment models.

BACKGROUND: A growing literature documents how primary care practices adapted to the COVID-19 pandemic. We examine a topic that has received less attention-how participants in an advanced alternative payment model perceive the model influenced their ability to meet patients' care needs during the pandemic. METHODS: Analysis of closed- and open-ended questions from a 2021 survey of 2496 practices participating in the Comprehensive Primary Care Plus (CPC+) model (92% response rate) and a 2021 survey of 993 randomly selected primary care physicians from these practices (55% response rate). Both surveys asked whether respondents agreed or disagreed that they or their practice was "better positioned to meet patients' care needs during the coronavirus pandemic" because of participation in CPC+. Both also included an open-ended question about CPC+'s effects. RESULTS: Half of practices and one-third of physicians agreed or strongly agreed that participating in CPC+ better positioned them to meet patients' care needs during the pandemic. One in 10 practices and 2 in 10 physicians, disagreed or strongly disagreed, while 4 in 10 practices and slightly more than half of physicians neither agreed nor disagreed (or, for physicians, didn't know). The most commonly identified CPC+ activities that facilitated meeting patient care needs related to practices' work on care management (e.g., risk stratification), access (e.g., telehealth), payment outside of fee-for-service (FFS), and staffing (e.g., supporting care managers). CONCLUSIONS: Most CPC+ practices and physicians were positive or neutral about participating in CPC+ in the context of COVID-19, indicating more benefit than risk to payment alternatives to FFS.

Impact of zinc supplementation on phenotypic antimicrobial resistance of fecal commensal bacteria from pre-weaned dairy calves.

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96-2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03-0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15-0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR.

The effect of vibrotactile stimulation on hypoxia-induced irregular breathing and apnea in preterm rabbits.

BACKGROUND: Manual tactile stimulation is used to counteract apnea in preterm infants, but it is unknown when this intervention should be applied. We compared an anticipatory to a reactive approach using vibrotactile stimulation to prevent hypoxia induced apneas. METHODS: Preterm rabbit kittens were prematurely delivered and randomized to either group. All kittens breathed spontaneously with a positive airway pressure of 8 cmH2O while they were imaged using phase contrast X-ray. Irregular breathing (IB) was induced using gradual hypoxia. The anticipatory group received stimulation at the onset of IB and the reactive group if IB transitioned into apnea. Breathing rate (BR), heart rate (HR) and functional residual capacity (FRC) were compared. RESULTS: Anticipatory stimulation significantly reduced apnea incidence and maximum inter-breath intervals and increased BR following IB, compared to reactive stimulation. Recovery in BR but not HR was more likely with anticipatory stimulation, although both BR and HR were significantly higher at 120 s after stimulation onset. FRC values and variability were not different. CONCLUSIONS: Anticipated vibrotactile stimulation is more effective in preventing apnea and enhancing breathing when compared to reactive stimulation in preterm rabbits. Stimulation timing is likely to be a key factor in reducing the incidence and duration of apnea. IMPACT: Anticipated vibrotactile stimulation can prevent apnea and stimulate breathing effort in preterm rabbits. Anticipated vibrotactile stimulation increases the likelihood of breathing rate recovery following hypoxia induced irregular breathing, when compared to reactive stimulation. Automated stimulation in combination with predictive algorithms may improve the treatment of apnea in preterm infants.

Navigation abilities and spatial anxiety in individuals with and without Developmental Coordination Disorder (DCD/Dyspraxia).

BACKGROUND: Navigation skills are essential for independent living as they allow us to explore our environment; find our way to new locations, refine pathways to familiar locations and retrace our route home. Alongside motor coordination difficulties, there is evidence that individuals with Developmental Coordination Disorder (DCD/Dyspraxia) experience spatial processing difficulties, which are known to negatively affect navigation abilities. However, although self-reports indicate that adults with DCD have difficulties with sense of direction and navigation, no known studies have measured navigation abilities and strategies in adults with DCD. Furthermore, given evidence that individuals with DCD report higher levels of anxiety, we will additionally investigate associations between anxiety and navigation in this group. AIMS: This study compares navigation abilities, navigation strategies and spatial anxiety in adults with and without DCD. METHODS: Participants include 226 Adults aged 18-55 years, across two groups 1) DCD (N = 138, 111 F:25 M; 2:Other) 2); Typically Developing (N = 88, 77 F: 11 M). In this cross-sectional study, participants completed a series of tasks on the online Qualtrics platform. This included the Adult Developmental Coordination Disorder Checklist, the State-Trait Anxiety Inventory, the Wayfinding Anxiety Measure, the Wayfinding Questionnaire, the Wayfinding Strategy Questionnaire, and a navigation task. RESULTS: Our analysis shows that 1) compared to those with typical development, individuals with DCD have similar navigation performance but lower navigation and orientation scores, and distance estimation scores. 2) Movement co-ordination difficulties were only a significant predictor of landmark recognition and egocentric path route knowledge, and played no role for other aspects of navigation performance. 3) For wayfinding strategy use the DCD group used orientation strategies significantly less often than those with typical development, however there was no group difference in the use of route strategies. 4) The DCD group had significantly higher spatial anxiety scores across navigation, manipulation and imagery spatial sub-domains, even after controlling for general anxiety. 5) Spatial navigation anxiety was a significant predictor of navigational skill for all three wayfinding measures (navigation & orientation, distance estimation and spatial anxiety). CONCLUSIONS: The findings establish benchmarks of navigational skills in DCD and highlight spatial anxiety and route strategies as factors that may inhibit navigation success and could help specify suitable intervention targets.

Sustained inflation improves initial lung aeration in newborn rabbits with a diaphragmatic hernia.

BACKGROUND: Infants with a congenital diaphragmatic hernia (DH) have underdeveloped lungs and require mechanical ventilation after birth, but the optimal approach is unknown. We hypothesised that sustained inflation (SI) increases lung aeration in newborn kittens with a DH. METHODS: In pregnant New Zealand white rabbits, a left-sided DH was induced in two fetal kittens per doe at 24-days gestation (term = 32 days); litter mates acted as controls. DH and control kittens were delivered by caesarean section at 30 days, intubated and mechanically ventilated (7-10 min) with either an SI followed by intermittent positive pressure ventilation (IPPV) or IPPV throughout. The rate and uniformity of lung aeration was measured using phase-contrast X-ray imaging. RESULTS: Lung weights in DH kittens were ~57% of controls. An SI increased the rate and uniformity of lung aeration in DH kittens, compared to IPPV, and increased dynamic lung compliance in both control and DH kittens. However, this effect of the SI was lost when ventilation changed to IPPV. CONCLUSION: While an SI improved the rate and uniformity of lung aeration in both DH and control kittens, greater consideration of the post-SI ventilation strategy is required to sustain this benefit. IMPACT: Compared to intermittent positive pressure ventilation (IPPV), an initial sustained inflation (SI) increased the rate and uniformity of lung aeration after birth. However, this initial benefit is rapidly lost following the switch to IPPV. The optimal approach for ventilating CDH infants at birth is unknown. While an SI improves lung aeration in immature lungs, its effect on the hypoplastic lung is unknown. This study has shown that an SI greatly improves lung aeration in the hypoplastic lung. This study will guide future studies examining whether an SI can improve lung aeration in infants with a CDH.

Assessing the impact of LEGO® construction training on spatial and mathematical skills.

Lego construction ability is associated with a variety of spatial skills and mathematical outcomes. However, it is unknown whether these relations are causal. We aimed to establish the causal impact of Lego construction training on: Lego construction ability; a broad range of spatial skills; and on mathematical outcomes in 7-9-year-olds. We also aimed to identify how this causal impact differs for digital versus physical Lego construction training. One-hundred and ninety-eight children took part in a six-week training programme, delivered twice weekly as a school lunch time club. They completed either physical Lego training (N = 59), digital Lego training (N = 64), or an active control condition (crafts; N = 75). All children completed baseline and follow-up measures of spatial skills (disembedding, visuo-spatial working memory, spatial scaling, mental rotation, and performance on a spatial-numerical task, the number line task), mathematical outcomes (geometry, arithmetic, and overall mathematical skills) and Lego construction ability. Exploratory analyses revealed evidence for near transfer (Lego construction ability) and some evidence for far transfer (arithmetic) of Lego training, but overall transfer was limited. Despite this, we identified key areas for further development (explicit focus on spatial strategies, training for teachers, and embedding the programme within a mathematical context). The findings of this study can be used to inform future development of Lego construction training programmes to support mathematics learning.

Assessing the genetic risk of nodular melanoma using a candidate gene approach.

BACKGROUND: Nodular melanoma (NM) is a challenge to diagnose early due to its rapid growth and more atypical clinical presentation, making it the largest contributor to melanoma mortality. OBJECTIVES: Our study aim was to perform a rare-variant allele (RVA) analysis of whole-exome sequencing of patients with NM and non-NM (minor allele frequency ≤ 1% non-Finnish European) for a set of 500 candidate genes potentially implicated in melanoma. METHODS: This study recruited 131 participants with NM and 194 with non-NM from South-east Queensland and patients with NM from Victoria to perform a comparative analysis of possible genetic differences or similarities between the two melanoma cohorts. RESULTS: Phenotypic analysis revealed that a majority of patients diagnosed with NM were older males with a higher frequency of fair skin and red hair than is seen in the general population. The distribution of common melanoma polygenic risk scores was similar in patients with NM and non-NM, with over 28% in the highest quantile of scores. There was also a similar frequency of carriage of familial/high-penetrant melanoma gene and loss-of-function variants. We identified 39 genes by filtering 500 candidate genes based on the greatest frequency in NM compared with non-NM cases. The genes with RVAs of greatest frequency in NM included PTCH1, ARID2 and GHR. Rare variants in the SMO gene, which interacts with PTCH1 as ligand and receptor, were also identified, providing evidence that the Hedgehog pathway may contribute to NM risk. There was a cumulative effect in carrying multiple rare variants in the NM-associated genes. A 14.8-fold increased ratio for NM compared with non-NM was seen when two RVAs of the 39 genes were carried by a patient. CONCLUSIONS: This study highlights the importance of considering frequency of RVA to identify those at risk of NM in addition to known high penetrance genes.

MITF E318K: A rare homozygous case with multiple primary melanoma.

MITF E318K moderates melanoma risk. Only five MITF E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total-body-photography (TBP) to describe the dermatological phenotype of a homozygous MITF E318K individual. The case, a 32-year-old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre-existing naevi and one was a rare naevoid melanoma. 3D-TBP revealed a high naevus count (n = 162) with pigmentation varying from light to dark. Most naevi generally (n = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (n = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the MITF E318K homozygosity, there was heterozygosity for four other moderate-risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance.

The Skin Molecular Ecosystem Holds the Key to Nevogenesis and Melanomagenesis.

Early detection of melanoma is critical to good patient outcomes, but we still know little about the mechanisms of early melanoma development. Normal epidermis has many of the sequence variants and genetic architecture disruptions found in both benign nevi, melanomas, and other skin cancers, yet continues to behave more or less normally. One hypothesis is that many melanocytes in this context are "tumor competent" but are regulated by the microenvironment provided by the surrounding keratinocytes to inhibit progress to nevi or melanoma. There is evidence of accumulating disorder in several measures of the genomic and epigenomic landscape from normal skin through nevi to melanoma that may be key to promoting nevogenesis and melanomagenesis.

Building Numeracy Skills: Associations between DUPLO® Block Construction and Numeracy in Early Childhood.

Research shows that children's block construction skills are positively associated with their concurrent and later mathematics performance. Furthermore, there is evidence that block construction training is particularly beneficial for improving early mathematics skills in children from low-Socio Economic Status (SES) groups who are known to have lower maths performance than their peers. The current study investigates (a) the association between block construction and mathematics in children just before the start of formal schooling (4 years-of-age in the UK) and (b) whether the association between block construction and mathematics differs between children from more compared to less affluent families. Participants in this study included 116 children (M = 3 years 11 months, SD = 3 months) who all completed numeracy, block construction, and receptive vocabulary tasks. Socio-economic status and demographic information (child age, gender, ethnicity) were also obtained from parents. Findings show a strong positive association between block construction and early numeracy skills. Block construction skills explained approximately 5% of the variation in numeracy, even after controlling for age in months, household income, and child receptive vocabulary. When separated by SES group, for children from less affluent families, block construction explained a significant amount of variability (14.5%) in numeracy performance after covariates. For children from more affluent families, block construction did not explain a significant amount of variation in numeracy. These findings suggest that, interventions involving block construction skills may help to reduce SES-based attainment gaps in UK children's mathematics achievement.

Hands-On: Investigating the role of physical manipulatives in spatial training.

Studies show that spatial interventions lead to improvements in mathematics. However, outcomes vary based on whether physical manipulatives (embodied action) are used during training. This study compares the effects of embodied and non-embodied spatial interventions on spatial and mathematics outcomes. The study has a randomized, controlled, pre-post, follow-up, training design (N = 182; mean age 8 years; 49% female; 83.5% White). We show that both embodied and non-embodied spatial training approaches improve spatial skills compared to control. However, we conclude that embodied spatial training using physical manipulatives leads to larger, more consistent gains in mathematics and greater depth of spatial processing than non-embodied training. These findings highlight the potential of spatial activities, particularly those that use physical materials, for improving children's mathematics skills.

Prevalence and antimicrobial resistance profiles of Vibrio spp. and Enterococcus spp. in retail shrimp in Northern California.

Shrimp is one of the most consumed seafood products globally. Antimicrobial drugs play an integral role in disease mitigation in aquaculture settings, but their prevalent use raises public health concerns on the emergence and spread of antimicrobial resistant microorganisms. Vibrio spp., as the most common causative agents of seafood-borne infections in humans, and Enterococcus spp., as an indicator organism, are focal bacteria of interest for the monitoring of antimicrobial resistance (AMR) in seafood. In this study, 400 samples of retail shrimp were collected from randomly selected grocery stores in the Greater Sacramento, California, area between September 2019 and June 2020. The prevalence of Vibrio spp. and Enterococcus spp. was 60.25% (241/400) and 89.75% (359/400), respectively. Subsamples of Vibrio (n = 110) and Enterococcus (n = 110) isolates were subjected to antimicrobial susceptibility testing (AST). Vibrio isolates had high phenotypic resistance to ampicillin (52/110, 47.27%) and cefoxitin (39/110, 35.45%). Enterococcus were most frequently resistant to lincomycin (106/110, 96.36%), quinupristin-dalfopristin (96/110, 87.27%), ciprofloxacin (93/110, 84.55%), linezolid (86/110, 78.18%), and erythromycin (58/110, 52.73%). For both Vibrio and Enterococcus, no significant associations were observed between multidrug resistance (MDR, resistance to ≥3 drug classes) in isolates from farm raised and wild caught shrimp (p > 0.05) and in isolates of domestic and imported origin (p > 0.05). Whole genome sequencing (WGS) of a subset of Vibrio isolates (n = 42) speciated isolates as primarily V. metschnikovii (24/42; 57.14%) and V. parahaemolyticus (12/42; 28.57%), and detected 27 unique antimicrobial resistance genes (ARGs) across these isolates, most commonly qnrVC6 (19.05%, 8/42), dfrA31 (11.90%, 5/42), dfrA6 (9.5%, 4/42), qnrVC1 (9.5%, 4/42). Additionally, WGS predicted phenotypic resistance in Vibrio isolates with an overall sensitivity of 11.54% and specificity of 96.05%. This study provides insights on the prevalence and distribution of AMR in Vibrio spp. and Enterococcus spp. from retail shrimp in California which are important for food safety and public health and exemplifies the value of surveillance in monitoring the spread of AMR and its genetic determinants.

Examining the prevalence and type of technology-use in people with Down syndrome: Perspectives from parents and caregivers.

Familiarity with technology has become a requirement for independent living, however there is limited information on technology access and use for people with Down syndrome (DS). The aim of this study is to describe technology, gaming, and social-media use in people with DS. Parents/caregivers (N = 220) of individuals with DS aged 5-35 years (49% female) completed an online questionnaire. They felt that technology and social media use, and to a lesser extent gaming, played an important role in their son/daughter's life. However, many had concerns about their son/daughter's safety online, and identified challenges they faced with using technology, such as using a mouse and speech recognition. We also found substantial parental interest in learning more about technology-use in DS, particularly the impact of using social media. This paper summarises important details about technology-use in people with DS, providing foundational information for the design of effective technology-based activities and support.

Associations and indirect effects between LEGO® construction and mathematics performance.

There is a known association between LEGO® construction ability and mathematics achievement, yet the mechanisms which drive this association are largely unknown. This study investigated the spatial mechanisms underlying this association, and whether this differs for concrete versus digital construction. Between January 2020 and July 2021, children aged 7-9 years (N = 358, 189 female, ethnicity not recorded) completed spatial and mathematics tasks, and either a concrete or digital Lego construction task. Mediation analyses examining direct and indirect pathways (through spatial skills) between Lego construction ability and mathematics explained 8.4% to 26.6% of variance in mathematics scores. Exploratory moderated mediation analyses revealed that only the indirect path through mental rotation differed between Lego conditions. Findings are discussed in relation to theories of spatial-numerical associations and the potential of Lego training for mathematics improvement.

Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes.

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students' understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship.

Assessment of Prevalence and Diversity of Antimicrobial Resistant Escherichia coli from Retail Meats in Southern California.

Retail meat products may serve as reservoirs and conduits for antimicrobial resistance, which is frequently monitored using Escherichia coli as indicator bacteria. In this study, E. coli isolation was conducted on 221 retail meat samples (56 chicken, 54 ground turkey, 55 ground beef, and 56 pork chops) collected over a one-year period from grocery stores in southern California. The overall prevalence of E. coli in retail meat samples was 47.51% (105/221), with E. coli contamination found to be significantly associated with meat type and season of sampling. From antimicrobial susceptibility testing, 51 isolates (48.57%) were susceptible to all antimicrobials tested, 54 (51.34%) were resistant to at least 1 drug, 39 (37.14%) to 2 or more drugs, and 21 (20.00%) to 3 or more drugs. Resistance to ampicillin, gentamicin, streptomycin, and tetracycline were significantly associated with meat type, with poultry counterparts (chicken or ground turkey) exhibiting higher odds for resistance to these drugs compared to non-poultry meats (beef and pork). From the 52 E. coli isolates selected to undergo whole-genome sequencing (WGS), 27 antimicrobial resistance genes (ARGs) were identified and predicted phenotypic AMR profiles with an overall sensitivity and specificity of 93.33% and 99.84%, respectively. Clustering assessment and co-occurrence networks revealed that the genomic AMR determinants of E. coli from retail meat were highly heterogeneous, with a sparsity of shared gene networks.