The effects of tibial tuberosity avulsion and repair on tibial plateau angle in dogs.

AIMS: To assess whether tibial tuberosity avulsion injury and subsequent surgical repair in skeletally immature dogs are associated with changes in tibial plateau angle (TPA) at skeletal maturity. METHODS: Skeletally mature (> 18 months of age) dogs that had previously undergone unilateral surgery when 4-8 months of age to repair tibial tuberosity avulsion were enrolled. Bilateral, mediolateral stifle radiographs were taken. TPA was measured digitally from the radiographs independently by two readers and compared between sides within dogs. As the number of dogs that would be enrolled for the main part of the study was unknown, to understand how the variation between left and right stifles within dogs would affect the power of the main study, 29 client-owned, skeletally mature dogs without stifle pathology were recruited prior to the main study for bilateral, mediolateral projection stifle radiographs. Variation in the differences in TPA between left and right stifles was used to estimate the likely power of the major part of the study for different numbers of enrolled dogs. RESULTS: From 29 dogs enrolled in the power assessment, the SD of the differences between left and right stifles was 2.1°. With 10 dogs (20 stifles) enrolled within the main part of the study, and if the SD of the differences between operated and non-operated stifles within a dog was the same as the SD of the differences between non-operated stifles within a dog (2.1°), the study would have power ≥ 0.8 if the mean difference in TPA between operated and non-operated stifles was ≥ 2.1°.Ten dogs were enrolled in phase II of the study. In 8/10 of these dogs, the TPA in the operated stifle was less than in the non-operated stifle. The mean TPA on the operated stifle was 6.4° less than on the non-operated stifle (95% CI = 2.4-10.3° less; p = 0.002). For surgery between 4 and 8 months of age, TPA at maturity increased by 2.7° (95% CI = 1.1-4.3°; p = 0.001) for each additional month of age at surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Based on this study, surgical repair of tibial tuberosity avulsion in skeletally immature dogs is associated with a smaller TPA at skeletal maturity. However, causality cannot be established from this cross-sectional study, and this association may be because stifles with a smaller TPA are predisposed to tibial tuberosity avulsion.

Principal Accompaniment in Australian Faith-Based Schools: A Salutogenesis Approach.

A program designed to provide accompaniment reflects a salutogenesis emphasis aimed at sustaining the professional well-being of experienced principals. A mixed methods pilot study focused on participant (N = 12) orientation, principles of accompaniment, mission-aligned processes, leadership agency, structured conversations, and nominated outcomes. Data were collected over twelve months at three stages using online survey. Australian Catholic principals reported a positive orientation experience, professional well-being, the comprehensiveness of the program, and the manageability of its implementation. Discussion confirmed design elements contributed to the wholistic nature of accompaniment linking body, mind, and spirit in conversational processes and the transformative effects of these exchanges on professional practice and well-being.

Impact of fetal growth restriction on pregnancy outcome in women undergoing expectant management for preterm pre-eclampsia.

OBJECTIVES: To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management. Secondary outcomes assessed were indication for delivery, mode of delivery and rate of serious adverse maternal and perinatal outcomes. METHODS: We conducted a secondary analysis of the Pre-eclampsia Intervention (PIE) and the Pre-eclampsia Intervention 2 (PI2) trial data. These randomized controlled trials evaluated whether esomeprazole and metformin could prolong gestation of women diagnosed with pre-eclampsia between 26 and 32 weeks of gestation undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or reaching 34 weeks' gestation. FGR (defined by Delphi consensus) at the time of pre-eclampsia diagnosis was examined as a predictor of outcome. Only placebo data from PI2 were included, as the trial showed that metformin use was associated with prolonged gestation. All outcome data were collected prospectively from diagnosis of pre-eclampsia to 6 weeks after the expected due date. RESULTS: Of the 202 women included, 92 (45.5%) had FGR at the time of pre-eclampsia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days; adjusted 0.49-fold change (95% CI, 0.33-0.74); P < 0.001). FGR pregnancies were less likely to reach 34 weeks' gestation (12.0% vs 30.9%; adjusted relative risk (aRR), 0.44 (95% CI, 0.23-0.83)) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%; aRR, 1.84 (95% CI, 1.36-2.47)). More women with FGR underwent a prelabor emergency Cesarean section (66.3% vs 43.6%; aRR, 1.56 (95% CI, 1.20-2.03)) and were less likely to have a successful induction of labor (4.3% vs 14.5%; aRR, 0.32 (95% CI, 0.10-1.00)), compared to those without FGR. The rate of maternal complications did not differ significantly between the two groups. FGR was associated with a higher rate of infant death (14.1% vs 4.5%; aRR, 3.26 (95% CI, 1.08-9.81)) and need for intubation and mechanical ventilation (15.2% vs 5.5%; aRR, 2.97 (95% CI, 1.11-7.90)). CONCLUSION: FGR is commonly present in women with early preterm pre-eclampsia and outcome is poorer. FGR is associated with shorter pregnancy latency, more emergency Cesarean deliveries, fewer successful inductions and increased rates of neonatal morbidity and mortality. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Reimagining Rural: Shifting Paradigms About Health and Well-Being in the Rural United States.

Rural health disparities have attracted increased national attention, compelling an expanded focus on rural health research. In this article, we deconstruct the definitions and narratives of "rural" communities and suggest that a paradigm shift is needed that centers the complexity and strength of rural places. We discuss the relevance of health equity frameworks, implementation science, and community-engaged approaches to promote rural well-being. Focusing on rural in its own right will lead to intervention innovations and reinvention with implications beyond rural areas. We conclude with suggestions for research and practice to inspire renewed interest in partnering with rural communities to promote health equity.

Delivery outcomes in women with morbid obesity, where induction of labour was planned to prevent post-term complications.

Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. We conducted a retrospective observational study on otherwise uncomplicated women with a body mass index (BMI) ≥ 40 kg/m2 where, having reached term, induction of labour (IOL) was planned, to prevent prolonged pregnancy. The primary aim was to describe delivery outcomes and short-term maternal and perinatal adverse events. Of 117 cases included, 69 (59%) laboured spontaneously before the induction date, while 48 (41%) required an IOL. Of 48 patients that underwent an IOL, 22 (45.8%) achieved vaginal delivery, compared to 55 (79.7%) who laboured spontaneously (p = <.001). Twenty-two (18.8%) of the 117 babies weighed more than 4000 g, with 13 of these delivered vaginally. Overall, term patients with morbid obesity who laboured spontaneously before requiring induction, had a high rate of vaginal delivery. However, when IOL was required, the rate of caesarean delivery rose dramatically.Impact statementWhat is already known on this subject? Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. Induction of labour (IOL) increases the workload in busy units.What do the results of this study add? These results help inform accurate counselling on delivery outcomes, which is integral to respectful care, for the continuously increasing numbers of morbidly obese pregnant women.What the implications are of these findings for clinical practice and/or further research? It is preferable to avoid semi- or urgent caesarean deliveries in morbidly obese women after IOL. The outcomes of earlier induction of labour from 39- or 40-weeks' gestation requires investigation. Earlier induction may reduce the numbers of caesarean deliveries for abnormal cardiotocograph during the process.

Children's Understanding of Proper Names and Descriptions.

This research addressed the question of whether children understand proper names differently from descriptions. We examined how children extend these two types of expressions from an initial object (a truck) owned by the experimenter to two identical objects created by transforming the initial object, both owned by the experimenter. Adults and 5/6-year-olds extended a name ("Tommy") to only one post-transformation object, but extended a description ("my truck") to both objects. Adults and 7-year-olds (but not 5/6-year-olds) also extended a description modeled as a name ("called My Truck") to only one object. Like adults, children understand that proper names identify unique individuals, but that descriptions identify properties.

Improving the Quality of Paediatric ECG Interpretation.

Aims Our aim was to complete an audit loop and identify whether implementing a paediatric ECG checklist improved the documentation and therefore the quality of paediatric ECG interpretation. We designed a paediatric ECG and education proforma in a Paediatric Emergency Department and incorporated it into daily practice. Methods We audited the medical records of children presenting with clinical indications for ECG. We included 40 records before and 40 records after the introduction of a paediatric ECG interpretation checklist. Results We assessed 10 items of documentation of which 8 related to the wave-form. Recording of these ranged from 0-65% before and from 95-100% after the checklist. Conclusion An intervention to introduce a paediatric ECG checklist, including education proforma, demonstrated significant improvement in the interpretation and documentation of a paediatric ECG. We recommend the use of this checklist in primary care and hospital settings.

Putting Mutual Exclusivity in Context: Speaker Race Influences Monolingual and Bilingual Infants' Word-Learning Assumptions.

Previous work indicates mutual exclusivity in word learning in monolingual, but not bilingual toddlers. We asked whether this difference indicates distinct conceptual biases, or instead reflects best-guess heuristic use in the absence of context. We altered word-learning contexts by manipulating whether a familiar- or unfamiliar-race speaker introduced a novel word for an object with a known category label painted in a new color. Both monolingual and bilingual infants showed mutual exclusivity for a familiar-race speaker, and relaxed mutual exclusivity and treated the novel word as a category label for an unfamiliar-race speaker. Thus, monolingual and bilingual infants have access to similar word-learning heuristics, and both use nonlinguistic social context to guide their use of the most appropriate heuristic.

Observation of Dirac monopoles in a synthetic magnetic field.

Magnetic monopoles--particles that behave as isolated north or south magnetic poles--have been the subject of speculation since the first detailed observations of magnetism several hundred years ago. Numerous theoretical investigations and hitherto unsuccessful experimental searches have followed Dirac's 1931 development of a theory of monopoles consistent with both quantum mechanics and the gauge invariance of the electromagnetic field. The existence of even a single Dirac magnetic monopole would have far-reaching physical consequences, most famously explaining the quantization of electric charge. Although analogues of magnetic monopoles have been found in exotic spin ices and other systems, there has been no direct experimental observation of Dirac monopoles within a medium described by a quantum field, such as superfluid helium-3 (refs 10-13). Here we demonstrate the controlled creation of Dirac monopoles in the synthetic magnetic field produced by a spinor Bose-Einstein condensate. Monopoles are identified, in both experiments and matching numerical simulations, at the termini of vortex lines within the condensate. By directly imaging such a vortex line, the presence of a monopole may be discerned from the experimental data alone. These real-space images provide conclusive and long-awaited experimental evidence of the existence of Dirac monopoles. Our result provides an unprecedented opportunity to observe and manipulate these quantum mechanical entities in a controlled environment.

Decay of a Quantum Knot.

We experimentally study the dynamics of quantum knots in a uniform magnetic field in spin-1 Bose-Einstein condensates. The knot is created in the polar magnetic phase, which rapidly undergoes a transition toward the ferromagnetic phase in the presence of the knot. The magnetic order becomes scrambled as the system evolves, and the knot disappears. Strikingly, over long evolution times, the knot decays into a polar-core spin vortex, which is a member of a class of singular SO(3) vortices. The polar-core spin vortex is stable with an observed lifetime comparable to that of the condensate itself. The structure is similar to that predicted to appear in the evolution of an isolated monopole defect, suggesting a possible universality in the observed topological transition.

A comparison between point-of-care testing and venous glucose determination for the diagnosis of diabetes mellitus 6-12 weeks after gestational diabetes.

AIM: To evaluate point-of-care-testing (POCT) for the diagnosis of Type 2 diabetes mellitus 6-12 weeks post-partum in women with gestational diabetes (GDM). METHODS: Post-partum glucose assessment (75-mg oral glucose tolerance test, OGTT) was performed prospectively in 122 women with GDM (1 November 2015 to 1 November 2017) at Tygerberg Hospital, Cape Town, South Africa. Individuals with known pre-existing diabetes were excluded. The accuracy and clinical utility of POCT (capillary finger-prick) were compared with laboratory plasma glucose (hexokinase and glucokinase methods). The OGTT consisted of two time points (fasting and 2 h) during which concurrent glucose samples (POCT and laboratory) were obtained. Bland-Altman plots and paired analysis were used to assess the analytical accuracy of POCT, whereas its diagnostic performance was determined using positive and negative predictive values to calculate specificity and sensitivity. RESULTS: Spearman's ranked correlation analysis indicated a strong association between POCT and laboratory glucose values at both OGTT time points (fasting, r = 0.95, P < 0.0001; 2 h, r = 0.88, P < 0.0001). Thirty-six women were diagnosed with Type 2 diabetes based on gold standard laboratory glucose levels (fasting > 7 mmol/l; 2 h > 11.1 mmol/l). POCT correctly identified Type 2 diabetes in 78% of women (28 of 36) with a positive predictive value of 89.3% and a negative predictive value of 96.7% at the fasting time point. The sensitivity and specificity of POCT to diagnose Type 2 diabetes were 89% (fasting), 85.7% (2 h) and 96.7% (fasting), 98.5% (2 h) respectively. POCT proved less sensitive to diagnose pre-diabetes (69%) but displayed satisfactory specificity (92%) at both time points assessed. CONCLUSION: POCT accurately identifies women with Type 2 diabetes 6-12 weeks after GDM.

Knowledge, help-seeking and efficacy to find respite services: an exploratory study in help-seeking carers of people with dementia in the context of aged care reforms.

BACKGROUND: Research highlights the need for carers of people with dementia to acquire relevant and timely information to assist them to access appropriate respite services. Unfortunately, negative experiences of information-seeking can create additional stress for carers and contribute to delays in up-take, or not using respite services at all. METHODS: Cross-sectional survey data was collected from a convenience sample of n = 84 carers of older people with dementia living in the Illawarra-Shoalhaven region of NSW, Australia. We assessed knowledge, attitudes, information seeking behaviours, and unmet need for respite services in 2016, following national aged care reforms. RESULTS: Over the previous 12 months, 86% of carers sought respite service information. The majority (73%) of all carers reported an unmet need for respite services, and were relying on personal networks to provide support for respite information. Few utilised the new government gateway 'My Aged Care' phone line (11%) or website (25%). However, 35% used a pre-existing helpline to access short term or emergency respite. We found a preference for interpersonal information sources, including local doctor (65%), professionally and volunteer led carer support groups (49%), and family and friends (46%). Those using four or more information sources showed higher capacity to name local respite services. Respite service information seekers were more likely to be caring for someone with behavioural problems, to have received assistance to access services, and to have used respite services in the past 3 to 6 months. CONCLUSIONS: New reforms in the Australian aged care sector have not adequately responded to the needs of carers of people with dementia for respite service information and support. Wider, community-based messaging promoting positive service options and the provision of active personal support is required to address the unmet need for respite in carers of people with dementia.

Evaluation of the Bactericidal Activity of Plazomicin and Comparators against Multidrug-Resistant Enterobacteriaceae.

The next-generation aminoglycoside plazomicin, in development for infections due to multidrug-resistant (MDR) Enterobacteriaceae, was evaluated alongside comparators for bactericidal activity in minimum bactericidal concentration (MBC) and time-kill (TK) assays against MDR Enterobacteriaceae isolates with characterized aminoglycoside and ß-lactam resistance mechanisms. Overall, plazomicin and colistin were the most potent, with plazomicin demonstrating an MBC50/90 of 0.5/4 µg/ml and sustained 3-log10 kill against MDR Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp.

Toxicogenomic module associations with pathogenesis: a network-based approach to understanding drug toxicity.

Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP'). Accounting for the overall transcriptional activity resulting from treatment, we explain mechanisms of toxicity and predict distinct toxicity phenotypes using module associations. We demonstrate that early network responses complement traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury derived using rat translate to human. Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.

Dose-dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor.

AIMS: LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety and tolerability profile. METHODS: Healthy subjects were randomized to receive LY3031207 (25, 75 and 275 mg), placebo or celecoxib (400 mg) once daily for 28 days. The safety, tolerability and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated. RESULTS: The study was terminated when two subjects experienced drug-induced liver injury (DILI) after they had received 225 mg LY3031207 for 19 days. Liver biopsy from these subjects revealed acute liver injury with eosinophilic infiltration. Four additional DILI cases were identified after LY3031207 dosing had been stopped. All six DILI cases shared unique presentations of hepatocellular injury with hypersensitivity features and demonstrated a steep dose-dependent trend. Prompt discontinuation of the study drug and supportive medical care resulted in full recovery. Metabolites from metabolic activation of the imidazole ring were observed in plasma and urine samples from all subjects randomized to LY3031207 dosing. CONCLUSIONS: This study emphasized the importance of careful safety monitoring and serious adverse events management in phase I trials. Metabolic activation of the imidazole ring may be involved in the development of hepatotoxicity of LY3031207.

Microbial diversity and nitrogen-metabolizing gene abundance in backyard food waste composting systems.

AIMS: The microbial diversity of backyard compost piles is poorly understood compared to large-scale, highly regulated composting systems. The purpose of this study was the identification of the microbial community composition and associated change over time among three different backyard composting styles. METHODS AND RESULTS: Food waste was composted in a household backyard compost bin, a small-scale aerated windrow or a semi-aerated static pile. Samples were obtained from each sequential phase of the composting process for 16s rRNA sequencing and relationships between temperature, moisture and microbial communities were examined. The Bacilli dominated in the early phases of composting then transitioned to Proteobacteria in the later stages. Different bacterial species increased and decreased dramatically in different composting systems and at different phases of the composting process. We performed qPCR to quantify gene abundance of nirS to profile the nitrogen-metabolizing bacteria present in each composting system. Gene abundance of nirS varied with temperature, but peaked during the cooling phase in the aerated windrow. CONCLUSIONS: Although the phases of decomposition were not as distinct as large-scale regulated piles, the microbial diversity mirrored the appropriate phases. Interestingly, different backyard composting styles were marked by the predominance of certain bacterial species. In particular, nitrogen-metabolizing bacterial communities peaked in the later stages of decomposition. SIGNIFICANCE AND IMPACT OF THE STUDY: A profile of the compost microbiome yields important clues about how differences in backyard food waste composting systems influence bacterial species that may facilitate or hinder nitrogen metabolism.

Second label learning in bilingual and monolingual infants.

Mutual exclusivity is the assumption that each object has only one category label. Prior research suggests that bilingual infants, unlike monolingual infants, fail to adhere to this assumption to guide word learning. Yet previous work has not addressed whether bilingual infants systematically interpret a novel word for a familiar object (i.e. an object with a known category label) as a second category label. We addressed this question by exploring bilingual and monolingual infants' use of mutual exclusivity in a task in which they heard a novel label for a familiar object with a salient color (e.g. an aqua-colored dog). They were subsequently tested with two trials that probed whether they interpreted the word as a second category label for the object (e.g. another word meaning dog) or as a label for one of the object's salient properties, namely its color (e.g. a word meaning aqua). Bilingual infants failed to adhere to mutual exclusivity and interpreted the novel word systematically as a second object category label for the familiar object. In contrast, consistent with their use of mutual exclusivity, monolingual infants rejected the novel word as a second category label, and instead showed some evidence of interpreting it as a property (color) term for the familiar object. The findings suggest that both bilingual and monolingual infants are systematic in their interpretation of a novel label for a familiar object, but that they show different interpretations of that label. We thus argue that theoretical accounts of early word learning must consider the crucial role of linguistic experience.

Sampling random directions within an elliptical cone.

This work extends the spherical surface sampling algorithm in order to uniformly generate random directions within an elliptical cone. This has applications in Monte Carlo particle transport simulations, for example modeling asymmetric beam divergence or scattering interactions. Two methods are presented. The first obeys the strict boundary of the elliptical cone. The second relaxes this requirement, increasing the range of generated directions by up to 10% for elliptical cones of extreme eccentricity. However, the second method is able to generate directions beyond the equator.

Neurological and endocrine phenotypes of fragile X carrier women.

Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions frequently report neurological or endocrine symptoms and prior studies have predominantly focused on questionnaire report of medical issues. Premutation carrier (PMC) women (n = 33) and non-carrier controls (n = 13) were recruited and evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and skin biopsies were collected for molecular measures. Scales for movement disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and quality of life were completed. The average age of the women was 51 years (n = 46) and average CGG repeat size was 91 ± 24.9 in the FMR1 PMC women. Seventy percent of the PMC women had an abnormal neurological examination. PMC women had significantly higher scores on the Fragile X-Associated Tremor Ataxia Syndrome (FXTAS) rating scale, more neuropathy, and difficulty with tandem gait compared to controls. Central sensitivity syndromes, a neuroticism profile on the NEO Personality Profile, and sleep disorders were also prevalent. Discrepancies between subject report and examination findings were also seen. This pilot study suggests that women with the FMR1 premutation may have a phenotype that overlaps with that seen in FXTAS. Additional research with larger sample sizes is warranted to better delineate the clinical features.