Association Between Surgeon Sex and Days Alive at Home Following Surgery: A Population-Based Cohort Study.

Objective: The objective of this study was to measure potential associations between surgeon sex and number of days alive and at home (DAH). Background: Patients treated by female surgeons appear to have lower rates of mortality, complications, readmissions, and healthcare costs when compared with male surgeons. DAH is a validated measure, shown to better capture the patient experience of postoperative recovery. Methods: We conducted a retrospective study of adults (≥18 years of age) undergoing common surgeries between January 01, 2007 and December 31, 2019 in Ontario, Canada. The outcome measures were the number of DAH within 30-, 90-, and 365-days. The data was summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results: During the study period, 1,165,711 individuals were included, of which 61.9% (N = 721,575) were female. Those managed by a female surgeon experienced a higher mean number of DAH when compared with male surgeons at 365 days (351.7 vs. 342.1 days; P < 0.001) and at each earlier time point. This remained consistent following adjustment for covariates, with patients of female surgeons experiencing a higher number of DAH at all time points, including at 365 days (343.2 [339.5-347.1] vs. 339.4 [335.9-343.0] days). Multivariable regression modeling revealed that patients of male surgeons had a significantly lower number of DAH versus female surgeons. Conclusions: Patients of female surgeons experienced a higher number of DAH when compared with those treated by male surgeons at all time points. More time spent at home after surgery may in turn lower costs of care, resource utilization, and potentially improve quality of life. Further studies are needed to examine these findings across other care contexts.

HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.

CD8+ T cells destroy insulin-producing pancreatic ß cells in type 1 diabetes through HLA class I-restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele HLA A*24:02. Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02-peptide-TCR structure by crystal seeding. TCR binding to the PPI epitope was strongly focused on peptide residues Arg4 and Leu5, with more flexibility at other positions, allowing the TCR to strongly engage many peptides derived from pathogenic bacteria. We confirmed an epitope from Klebsiella that was recognized by PPI-reactive T cells from 3 of 3 HLA A*24:02+ patients. Remarkably, the same epitope selected T cells from 7 of 8 HLA A*24+ healthy donors that cross-reacted with PPI, leading to recognition and killing of HLA A*24:02+ cells expressing PPI. These data provide a mechanism by which molecular mimicry between pathogen and self-antigens could have resulted in the breaking of self-tolerance to initiate disease.

Impact of continuous topical oxygen therapy on biofilm gene expression in a porcine tissue model.

OBJECTIVE: The effect of continuous topical oxygen therapy (cTOT) on Pseudomonas aeruginosa biofilm gene transcription profiles following inoculation onto porcine skin, using a customised molecular assay was determined. METHOD: Sterilised porcine skin explants were inoculated with Pseudomonas aeruginosa in triplicate: 0 hours as negative control; 24 hours cTOT device on; 24 hours cTOT device off. The oxygen delivery system of the cTOT device was applied to the inoculated tissue and covered with a semi-occlusive dressing. All samples were incubated at 37±2°C for 24 hours, with the 0 hours negative control inoculated porcine skin samples recovered immediately. Planktonic suspensions and porcine skin biopsy samples were taken at 0 hours and 24 hours. Samples were processed and quantifiably assessed using gene specific reverse transcription-quantitative polymerase chain reaction assays for a panel of eight Pseudomonas aeruginosa genes (16S, pelA, pslA, rsaL, pcrV, pscQ, acpP, cbrA) associated with biofilm formation, quorum sensing, protein secretion/translocation and metabolism. RESULTS: Transcriptional upregulation of pelA, pcrV and acpP, responsible for intracellular adhesion, needletip protein production for type-3 secretion systems and fatty acid synthesis during proliferation, respectively, was observed when the cTOT device was switched on compared to when the device was switched off. Data suggest increased metabolic activity within bacterial cells following cTOT treatment. CONCLUSION: cTOT is an adjunctive therapy that supports faster healing and pain reduction in non-healing hypoxic wounds. Oxygen has previously been shown to increase susceptibility of biofilms to antibiotics through enhancing metabolism. Observed gene expression changes highlighted the impact of cTOT on biofilms, potentially influencing antimicrobial treatment success in wounds. Further in vitro and clinical investigations are warranted.

Prevalence of pain phenotypes and co-morbidities of chronic pain in Parkinson's Disease.

OBJECTIVE: The prevalence of chronic pain in Parkinson's disease (PD) in neurology practices ranges from 24 % to 83 %. To determine whether this prevalence is accurate across patients with PD, we leveraged data from electronic medical records in 80 inpatient and outpatient general practice settings. METHODS: We explored the prevalence of chronic pain in patients with PD relative to age and sex-matched controls in a large international database with electronic medical records from over 250 million patients (TriNetX Cambridge, MA, USA). We described demographics, co-morbid conditions and medication differences between patients with PD and without PD who have chronic pain. RESULTS: Extracted data included 4510 patients with PD and 4,214,982 age-matched control patients without Parkinson's Disease. A chronic pain diagnosis was identified in 19.3 % of males and 22.8 % of females with PD. This differed significantly from age-matched patients without PD who had a significantly lower prevalence of chronic pain 3.78 % and 4.76 %. Significantly more PD patients (both male and females) had received tramadol, oxycodone, and neuropathic agents (p<0.001) than patients without PD. Females with PD more often received anti-depressants than males with PD (p<0.05), corresponding with a significantly higher prevalence of depression. CONCLUSION: Chronic pain in patients with PD is five times as common as in age-matched controls in general practice settings. Patients with PD have a greater prevalence of comorbid conditions that affect development of chronic pain. Whether the pain or the PD is causative to those conditions remains to be elucidated.

Transmission potential of Streptococcus pyogenes during a controlled human infection trial of pharyngitis.

Controlled human infection (CHI) models can provide insights into transmission of pathogens such as Streptococcus pyogenes (Strep A). As part of the Controlled Human Infection with Penicillin for Streptococcus pyogenes (CHIPS) trial, we explored the potential for transmission among participants deliberately infected with the Strep A emm75 strain. Three approaches to understanding transmission were employed: the use of agar settle plates to capture possible droplet or airborne spread of Strep A; measurement of distance droplets could spread during conversation; and environmental swabbing of high-touch items to detect Strep A on surfaces. Of the 60 (27%) CHIPS trial participants across five cohorts, 16 were enrolled in this sub-study; availability of study staff was the primary reason for selection. In total, 189 plates and 260 swabs were collected. Strep A was grown on one settle plate from a participant on the second day, using plates placed 30 cm away. This participant received the placebo dose of penicillin and had met the primary endpoint of pharyngitis. Whole-genome sequencing identified this to be the challenge strain. Strep A was not detected on any swabs. In this small sample of CHI participants, we did not find evidence of Strep A transmission by the airborne route or fomites, and just one instance of droplet spread while acutely symptomatic with streptococcal pharyngitis. Although these experiments provide evidence of minimal transmission within controlled clinical settings, greater efforts are required to explore Strep A transmission in naturalistic settings.IMPORTANCEStreptococcus pyogenes remains a significant driver of morbidity and mortality, particularly in under-resourced settings. Understanding the transmission modalities of this pathogen is essential to ensuring the success of prevention methods. This proposed paper presents a nascent attempt to determine the transmission potential of Streptococcus pyogenes nested within a larger controlled human infection model.

Child Maltreatment, Mental Health Disorders, and Health Risk Behaviors in People With Diverse Gender Identities.

This study examined rates of mental health disorders and health risk behaviors in people with diverse gender identities and associations with five types of child maltreatment. We used data from the Australian Child Maltreatment Study (ACMS), a nationally representative survey of Australian residents aged 16 years and more, which was designed to understand the experience of child maltreatment (physical abuse, sexual abuse, emotional abuse, neglect, exposure to domestic violence). Mental disorders-major depressive disorder, generalized anxiety disorder (GAD), alcohol use disorder, post-traumatic stress disorder (PTSD), and health risk behaviors-smoking, binge drinking, cannabis dependence, self-harm, and suicide attempt in the past 12 months were assessed. People with diverse gender identities who experienced child maltreatment were significantly more likely to have GAD (43.3%; 95% CI [30.3, 56.2]) than those who had experienced child maltreatment who were either cisgender men (13.8%; [12.0, 15.5]) or cisgender women (17.4%; [15.7, 19.2]). Similarly, higher prevalence was found for PTSD (21.3%; [11.1, 31.5]), self-harm (27.8%; [17.1, 38.5]) and suicide attempt (7.2%; [3.1, 11.3]) for people with diverse gender identities. Trauma-informed approaches, attuned to the high likelihood of any child maltreatment, and the co-occurrence of different kinds may benefit people with diverse gender identities experiencing GAD, PTSD, self-harm, suicidal behaviors, or other health risk behaviors.

Does attachment anxiety mediate the persistence of anxiety and depressive symptoms from adolescence to early adulthood?

OBJECTIVES: Depression and anxiety often emerge in adolescence and persist into early adulthood. Developing a greater understanding of the factors that influence their persistence may inform psychological interventions. Their association with an insecure attachment style is well established although the mediating role of attachment anxiety in the persistence of depression and anxiety over time has not been examined. This study aimed to examine if anxious attachment mediated depression and anxiety from adolescence to early adulthood. METHODS: Data from 3,436 participants in a longitudinal birth cohort study were examined. At 14-years and 21-years, participants completed the Achenbach Youth Self Report (YSR) and the Achenbach Young Adult Self-Report (YASR) respectively. At 21-years, participants completed the Attachment Style Questionnaire (ASQ). Attachment anxiety as a mediator for the persistence of anxiety/depressive symptoms from 14- to 21-years was examined. RESULTS: Attachment anxiety accounted for approximately 60% of the persistence of anxiety and depressive symptoms at 14- and 21- years after adjusting for covariates. Results were similar when stratifying by males and females. CONCLUSIONS: Attachment anxiety significantly contributes to the persistence of anxiety and depressive symptoms from adolescence into early adulthood for both males and females. Incorporating interventions that address attachment anxiety in adolescents may improve the response to therapy for anxiety and depression.

Poor compliance and exemptions facilitate ongoing deforestation.

Many nations are struggling to reduce deforestation, despite having extensive environmental protection laws in place and commitments to international agreements that address the biodiversity and climate crises. We developed a novel framework to quantify the extent to which contemporary deforestation is being captured under national and subnational laws. We then applied this framework to northern Australia as a case study, a development and deforestation hotspot with ecosystems of global significance. First, deforestation may be compliant under all relevant legislation, either through assessment and approval or because of exemptions in the legislation. Second, deforestation may be compliant under at least one relevant law, but not all. Third, there may be no evidence of deforestation assessment or exemption from assessment, despite their apparent requirement, which could mean the deforestation is potentially noncompliant. Finally, deforestation may occur in an area or under circumstances that are beyond the intended scope of any relevant legislation. All deforestation that we analyzed was hypothetically covered by one or more laws. However, 65% of deforestation was potentially noncompliant with at least one law. Because multiple laws could be relevant to a given clearing event, the majority of clearing was still compliant with at least one law, but of these events, only a small proportion was explicitly approved (19%). The remaining were permitted under various exemptions. Of all the legislation we analyzed, most of the exempt clearing occurred under one subnational law and most potentially noncompliant clearing occurred under one national law. Our results showed that even a nation with a suite of mature environmental protection laws is falling well short of achieving international commitments regarding deforestation. Our framework can be used to pinpoint the pathways of policy change required for nations to align local laws with these international accords.

Cumplimiento deficiente y exenciones que facilitan la deforestación Resumen Muchos países luchan por reducir la deforestación, a pesar de contar con amplias leyes de protección del medio ambiente y de sus compromisos con los acuerdos internacionales que abordan la crisis de la biodiversidad y el clima. Por ello desarrollamos un novedoso marco para cuantificar hasta qué punto la deforestación actual se recopila en las leyes nacionales y subnacionales. Después aplicamos este marco al norte de Australia como estudio de caso, un punto caliente de desarrollo y deforestación con ecosistemas de importancia mundial. En primer lugar, la deforestación puede ser compatible con toda la legislación pertinente, ya sea mediante evaluación y aprobación o debido a exenciones en la legislación. En segundo lugar, la deforestación puede ser compatible con al menos una ley pertinente, pero no con todas. En tercer lugar, puede que no haya pruebas de evaluación de la deforestación o de exención de la evaluación, a pesar de su aparente requisito, lo que podría significar que la deforestación es potencialmente no conforme. Por último, la deforestación puede producirse en una zona o en circunstancias que quedan fuera del ámbito de aplicación de la legislación pertinente. Toda la deforestación analizada era hipotéticamente legal según una o más leyes. Sin embargo, el 65% de la deforestación no cumplía potencialmente al menos una ley. Dado que varias leyes podían ser pertinentes para un determinado caso de deforestación, la mayoría de las deforestaciones seguían cumpliendo al menos una ley, pero de estos casos, sólo una pequeña proporción estaba explícitamente aprobada (19%). El resto estaba permitido en virtud de diversas exenciones. De toda la legislación que analizamos, la mayor parte de la compensación exenta se produjo en virtud de una ley subnacional y la mayor parte de la compensación potencialmente no conforme se produjo en virtud de una ley nacional. Nuestros resultados muestran que incluso un país con un conjunto de leyes maduras de protección del medio ambiente está muy lejos de cumplir los compromisos internacionales en materia de deforestación. Nuestro marco puede utilizarse para determinar las vías de cambio político necesarias para que los países adapten su legislación local a los acuerdos internacionales.

The prevalence of child sexual abuse perpetrated by leaders or other adults in religious organizations in Australia.

BACKGROUND: Numerous national public inquiries have highlighted the problem of child sexual abuse in religious organizations. Despite this, evidence of population-wide prevalence is scarce. OBJECTIVE: To provide the first nationally representative prevalence estimates of child sexual abuse perpetrated by adults in religious organizations in Australia. METHODS: The Australian Child Maltreatment Study (ACMS) surveyed 8503 people aged 16 and over about their experiences of child maltreatment. Weighted prevalence estimates were calculated based on responses to the child sexual abuse questions from the Juvenile Victimization Questionnaire-R2: Adapted Version (ACMS). RESULTS: One in 250 people reported being sexually abused as a child by an adult in a religious organization (0.4 %, 95 % CI, 0.3-0.6 %). Men reported significantly higher rates of child sexual abuse by these perpetrators (0.8 %, 95 % CI, 0.5-1.2 %), compared to women (0.1 %, 95 % CI, 0-0.3 %). This type of sexual abuse was overwhelmingly perpetrated by men (0.4 %, 95 % CI, 0.3-0.6 %), compared to women (0 %, 95 % CI, 0-0.1 %), and was substantially more often experienced in Catholic organizations (71.9 %) than other Christian denominations or other religions. Prevalence of child sexual abuse in religious organizations has declined over time (2.2 % of men 65 years and older, compared with 0.2 % of 16-24-year-old men). CONCLUSIONS: Child sexual abuse has been widespread in religious organizations in Australia. A decline over time indicates progress has been made in preventing sexual abuse of children. Religious organizations must take all reasonable measures to prevent child sexual abuse, with a particular need for interventions targeting male leaders, and organizational cultures.

PP2A B55α inhibits epithelial-mesenchymal transition via regulation of Slug expression in non-small cell lung cancer.

PP2A B55α, encoded by PPP2R2A, acts as a regulatory subunit of the serine/threonine phosphatase PP2A. Despite a frequent loss of heterozygosity of PPP2R2A in cases of non-small cell lung cancer (NSCLC), research on PP2A B55α's functions remains limited and controversial. To investigate the biological roles of PP2A B55α, we conducted bulk RNA-sequencing to assess the impact of PPP2R2A knockdown using two shRNAs in a NSCLC cell line. Gene set enrichment analysis (GSEA) of the RNA-sequencing data revealed significant enrichment of the epithelial-mesenchymal transition (EMT) pathway, with SNAI2 (the gene encoding Slug) emerging as one of the top candidates. Our findings demonstrate that PP2A B55α suppresses EMT, as PPP2R2A deficiency through knockdown or homozygous or hemizygous depletion promotes EMT and metastatic behavior in NSCLC cells, as evidenced by changes in EMT biomarkers, invasion and migration abilities, as well as metastasis in a tail vein assay. Mechanistically, PP2A B55α inhibits EMT by downregulating SNAI2 expression via the GSK3ß-ß-catenin pathway. Importantly, PPP2R2A deficiency also slows cell proliferation by disrupting DNA replication, particularly in PPP2R2A-/- cells. Furthermore, PPP2R2A deficiency, especially PPP2R2A-/- cells, leads to an increase in the cancer stem cell population, which correlates with enhanced resistance to chemotherapy. Overall, the decrease in PP2A B55α levels due to hemizygous/homozygous depletion heightens EMT and the metastatic or stemness/drug resistance potential of NSCLC cells despite their proliferation disadvantage. Our study highlights the significance of PP2A B55α in EMT and metastasis and suggests that targeting EMT/stemness could be a potential therapeutic strategy for treating PPP2R2A-deficient NSCLC.

Provider Implicit Racial Bias in Pediatric Sickle Cell Disease.

BACKGROUND/OBJECTIVES: This study is to (1) assess implicit racial bias among pediatric providers and (2) use virtual patient (VP) vignettes to determine the impact of implicit racial bias on clinical decision-making in pediatric sickle cell disease (SCD) pain care. DESIGN/METHODS: This cross-sectional study was conducted at a mid-sized, freestanding children's hospital in the northeast. Participants (N = 52) were pediatric SCD providers (87% cisgender female, 90% White, M age = 38.78). Providers completed a demographic questionnaire, the race Implicit Association Test (IAT) with adult and child faces, and a measure of SCD explicit bias (5-point Likert scale). Providers also made clinical decisions for four VP vignettes depicting Black and White youth in the emergency department (ED) with either SCD or cancer pain. Frequency tables were calculated. RESULTS: On the race IAT, providers demonstrated a pro-White implicit bias for both adult (81%) and child (89%) faces. Responses to the explicit bias measure reflected low levels of agreement with negative stereotypes about SCD patients. No significant differences emerged in providers' pain treatment decisions for Black vs. White, or SCD vs. cancer VPs. CONCLUSIONS: Findings indicate pediatric providers harbor implicit racial bias similar to the general population. Findings from VP vignettes did not demonstrate that pain treatment decision-making differed based on race or diagnosis. This may be due to standardized protocols and procedures in the pediatric emergency setting. Future research is needed to clarify the role of implicit bias in clinical decision-making and the potential efficacy of treatment protocols in preventing biases from interfering with pediatric SCD pain care.

Community emergency medical services approaches to fall prevention: a systematic review.

BACKGROUND: Falls are a leading cause of morbidity and mortality among older adults in the USA. Current approaches to fall prevention often rely on referral by primary care providers or enrolment during inpatient admissions. Community emergency medical services (CEMS) present a unique opportunity to rapidly identify older adults at risk for falls and provide fall prevention interventions in the home. In this systematic review, we seek to assess the efficacy and qualitative factors determining success of these programs. METHODS: Studies reporting the outcomes of fall prevention interventions delivered by EMS were identified by searching the electronic databases PubMed, Embase, Web of Science Core Collection, CINAHL and the Cochrane Central Register of Controlled Trials through 11 July 2023. RESULTS: 35 studies including randomised and non-randomised experimental trials, systematic reviews and qualitative research primarily from Western Europe, the USA, Australia and Canada were included in our analysis. Current fall prevention efforts focus heavily on postfall referral of at-risk community members. CEMS fall prevention interventions reduced all-cause and fall-related emergency department encounters, subsequent falls and EMS calls for lift assist. These interventions also improved patient health-related quality of life, independence with activities of daily living, and secondary health outcomes. CONCLUSIONS: CEMS programmes provide an opportunity for direct, proactive fall prevention on the individual level. Addressing barriers to implementation in the context of current emergency medical systems in the USA is the next step toward widespread implementation of these novel fall prevention interventions.

Understanding the Burden of Pediatric Traumatic Injury in Uganda: A Multicenter, Prospective Study.

INTRODUCTION: Traumatic injury is responsible for eight million childhood deaths annually. In Uganda, there is a paucity of comprehensive data describing the burden of pediatric trauma, which is essential for resource allocation and surgical workforce planning. This study aimed to ascertain the burden of non-adolescent pediatric trauma across four Ugandan hospitals. METHODS: We performed a descriptive review of four independent and prospective pediatric surgical databases in Uganda: Mulago National Referral Hospital (2012-2019), Mbarara Regional Referral Hospital (2015-2019), Soroti Regional Referral Hospital (SRRH) (2016-2019), and St Mary's Hospital Lacor (SMHL) (2016-2019). We sub-selected all clinical encounters that involved trauma. The primary outcome was the distribution of injury mechanisms. Secondary outcomes included operative intervention and clinical outcomes. RESULTS: There was a total of 693 pediatric trauma patients, across four hospital sites: Mulago National Referral Hospital (n = 245), Mbarara Regional Referral Hospital (n = 29), SRRH (n = 292), and SMHL (n = 127). The majority of patients were male (63%), with a median age of 5 [interquartile range = 2, 8]. Chiefly, patients suffered blunt injury mechanisms, including falls (16.2%) and road traffic crashes (14.7%) resulting in abdominal trauma (29.4%) and contusions (11.8%). At SRRH and SMHL, from which orthopedic data were available, 27% of patients suffered long-bone fractures. Overall, 55% of patients underwent surgery and 95% recovered to discharge. CONCLUSIONS: In Uganda, non-adolescent pediatric trauma patients most commonly suffer injuries due to falls and road traffic crashes, resulting in high rates of abdominal trauma. Amid surgical workforce deficits and resource-variability, these data support interventions aimed at training adult general surgeons to provide emergency pediatric surgical care and procedures.

Can Pretreatment MRI and Planning CT Radiomics Improve Prediction of Complete Pathological Response in Locally Advanced Rectal Cancer Following Neoadjuvant Treatment?

OBJECTIVE(S): The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before the start of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT. METHODS: Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals. RESULTS: One hundred and fifty patients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66. CONCLUSION: Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies.

Tonsils at Telethon: developing a standardised collection of tonsil photographs for group A streptococcal (GAS) research.

Introduction: Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon. This study aimed to develop a standardised set of tonsil photographs and determine tonsil size distribution from an urban paediatric population. Methods: A prospective cohort of children aged 3-15 years were recruited at the public events "Discover Day" and "Telethon Weekend" (October 2017) in Perth, Western Australia, Australia. Tonsil photographs, symptomatology, and GAS rapid antigen detection tests (RADT) were collected. Tonsil size was graded from the photographs using the Brodsky Grading Scale of tonsillar hypertrophy (Brodsky) by two independent clinicians, and inter-rater reliability calculated. Pharyngitis symptoms and GAS RADT were correlated, and immediate results provided. Results: Four hundred and twenty-six healthy children participated in the study over three days. The median age was seven years [interquartile range (IQR) 5.9-9.7 years]. Tonsil photographs were collected for 92% of participants, of which 62% were rated as good-quality photographs and 79% were deemed of adequate quality for assessment by both clinicians. When scored by two independent clinicians, 57% received the same grade. Average Brodsky grades (between clinicians) were 11%, 35%, 28%, 22% and 5% of grades 0,1,2,3 and 4, respectively. There was moderate agreement in grading using photographs, and minimal to weak agreement for signs of infection. Of 394 participants, 8% reported a sore throat. Of 334 GAS RADT performed, <1% were positive. Discussion: We report the first standardised use of paediatric tonsil photographs to assess tonsil size in urban-living Australian children. This provides a proof of concept from an urban-living cohort that could be compared with children in other settings with high risk of GAS pharyngitis or rheumatic fever such as remote-living Australian Indigenous populations.

A two-generation study of attachment in mothers and their young adult offspring: Latent classes of attachment and associations with anxiety and depression.

BACKGROUND: Evidence supports the conceptualization of adult attachment as existing along a continuum of attachment security and insecurity; however, ongoing debates persist regarding the use of categorical versus continuous approaches to studying attachment. Attachment data collected from a large community sample of mothers and their offspring in young adulthood were used to examine i) latent classes of adult attachment, ii) associations between mother and offspring attachment, iii) the relationship between adult attachment and mental health symptoms. METHODS: Mothers and offspring were each administered the Attachment Style Questionnaire when offspring were aged 21-years. Latent class analyses (LCA) were performed to examine response patterns across ASQ items. Associations between mothers' and offspring attachment, and correlations between attachment domains and depression/anxiety subscales were examined. RESULTS: LCA identified four latent classes across a continuum of secure and insecure attachment rather than four distinct adult attachment styles. Anxious attachment subscales correlated strongly with depression/anxiety symptoms in both cohorts. Mothers' attachment was significantly but weakly correlated with their young adult offspring attachment. LIMITATIONS: Attachment was measured at one time point and as such, a causal maternal-offspring attachment relationship could not be established. CONCLUSIONS: Findings support a dimensional view of attachment security and insecurity over a four-category model of adult attachment. Attachment correlated with anxiety and depressive symptoms and highlights the importance of considering adult attachment when addressing mental health. There was limited evidence of a relationship between middle aged mothers and their offspring in young adulthood, suggesting other factors influence attachment in adulthood.

Reproducibility in Radiomics: A Comparison of Feature Extraction Methods and Two Independent Datasets.

Radiomics involves the extraction of information from medical images that are not visible to the human eye. There is evidence that these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations, namely the MATLAB toolkit and Pyradiomics, when applied to independent datasets of CT scans of patients: (i) the open access RIDER dataset containing a set of repeat CT scans taken 15 min apart for 31 patients (RIDER Scan 1 and Scan 2, respectively) treated for lung cancer; and (ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV), manually outlined by an experienced observer available on both datasets, was used. The 43 common radiomics features available in MATLAB and Pyradiomics were calculated using two intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters, and the Spearman's rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset, and vice versa. A total of 29 out of the 43 reported stable features were found to be highly reproducible between MATLAB and Pyradiomics implementations, having a consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs > 0.8). 18/43 reported features were common in the RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Short-term high-calorie high-fat feeding induces hyperinsulinemia and blunts skeletal muscle microvascular blood flow in healthy humans.

Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention (+52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P = 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses.NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow.

Graft incompatibility between pepper and tomato can be attributed to genetic incompatibility between diverged immune systems.

Graft compatibility is the capacity of two plants to form cohesive vascular connections. Tomato and pepper are incompatible graft partners; however, the underlying cause of graft rejection between these two species remains unknown.We diagnosed graft incompatibility between tomato and diverse pepper varieties based on weakened biophysical stability, decreased growth, and persistent cell death using trypan blue and TUNEL assays. Transcriptomic analysis of cell death in the junction was performed using RNA-sequencing, and molecular signatures for incompatible graft response were characterized based on meta-transcriptomic comparisons with other biotic processes.We show that tomato is broadly incompatible with diverse pepper cultivars. These incompatible graft partners activate prolonged transcriptional changes that are highly enriched for defense processes. Amongst these processes was broad NLR upregulation and hypersensitive response. Using transcriptomic datasets for a variety of biotic stress treatments, we identified a significant overlap in the genetic profile of incompatible grafting and plant parasitism. In addition, we found over 1000 genes that are uniquely upregulated in incompatible grafts.Based on NLR overactivity, DNA damage, and prolonged cell death we have determined that tomato and pepper graft incompatibility is likely caused by a form of genetic incompatibility, which triggers a hyperimmune-response.

The unique role of adolescent internalizing and externalizing problems, and maternal-adolescent communication in their association with attachment in early adulthood.

Attachment styles influence mental health and relationships through life. Few studies examine the adolescent factors associated with adult attachment styles. This paper examines the association between adolescent emotional and behavioral problems and maternal-adolescent communication with attachment style in early adulthood. Data from 3423 participants in a birth cohort study were examined. At 14-years, participants' mothers completed the Parent-Adolescent Communication Scale. Participants completed the Youth Self-Report at 14-years which measures internalizing and externalizing symptoms, and the Attachment Style Questionnaire (ASQ) at 21-years. The ASQ comprises five domains of internal working models of interpersonal relationships and attachment style: confidence (security), discomfort with closeness and relationships as secondary (avoidance), need for approval and preoccupation with relationships (anxiety). Associations were examined using general linear models. After adjustments, internalizing symptoms score was associated with all domains of attachment and externalizing symptoms score was associated with four domains of attachment insecurity, but not attachment security. Low openness in maternal-adolescent communication was most strongly associated with decreased confidence and high problem maternal-adolescent communication was associated with viewing relationships as secondary. Adolescents with emotional and behavioral problems and maternal-adolescent communication may benefit from attachment-based interventions to support the development of healthy relationships and attachments in young adulthood.