Background: Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Results: Six children underwent NAc-DBS without any serious adverse events. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.

Background: Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) based cerebrovascular reactivity (CVR) indicies have enable the entirely non-invasive continuous monitoring. This study aims to compare CVR in those recovering from moderate/severe TBI to a health control group. Methods: In this prospective cohort study the cerebral oxygen CVR index, COx_a (using rSO2 and arterial blood pressure), was measured in subjects with moderate/severe TBI at follow-up. COx_a was also measured in a group of healthy controls. CVR was compared within and between these groups using conventional statistics. Results: A total of 101 heathy subject were recruited for this study along with 29 TBI patients. In the health cohort COx_a was not statistically different between males and females or in the dominate and non-dominate hemisphere. The TBI cohort, COx_a was not statistically different between first and last available follow up. Surprisingly, CVR as measured by COx_a was statistically better in those recovering from TBI than in the healthy cohort. Conclusions: In the prospective cohort study, CVR as measured by NIRS based methods, was found to be more active in those recovering from TBI than in a healthy cohort. This study may indicate that, in those that survive TBI, CVR may be enhanced as a neuroprotective measure.

Background: Over the past decade, worldwide stroke incidence has been increasing among young adults (≤65years), which has implications during the most dynamic period of their life. There is a dearth of research exploring young adults stroke patients’ experiences, healthy lifestyle habits, preferences, and recommendations for brain care-related initiatives. The study aimed to gain knowledge and a deeper understanding of young adult stroke patients’ experiences, lifestyle habits, and support needs for brain care-related education and interventions. Methods: A descriptive qualitative study was used. Participants who took part in the quantitative phase of a larger mixed methods study (n=103 that expressed an interest in the qualitative phase, were invited to take part in semi-structured focus groups. Simultaneous data collection and analysis are being conducted. Data are being analyzed using inductive thematic analysis outlined by Braun and Clarke (2006). Results: Findings will be available by May 20, 2024. Conclusions: Study findings will be essential to 1) mobilize an understanding of young adult stroke patients’ lived experience; 2) reconceptualize the current model of stroke care and services that is traditionally geared towards older adults; and 3) inform the development of brain care-related education and interventions to meet the unique needs, priorities, and preferences of young adult stroke patients.

This study compared the likelihood of long-term sequelae following infection with SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. Participants (n=5,630) were drawn from Virus Watch, a prospective community cohort investigating SARS-CoV-2 epidemiology in England. Using logistic regression, we compared predicted probabilities of developing long-term symptoms (>2 months) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. SARS-CoV-2 infection during early variant periods up to Omicron BA.1 was associated with greater probability of long-term sequalae (adjusted predicted probability (PP) range 0.27, 95% CI = 0.22–0.33 to 0.34, 95% CI = 0.25–0.43) compared with later Omicron sub-variants (PP range 0.11, 95% CI 0.08–0.15 to 0.14, 95% CI 0.10–0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04–0.11 to 0.23, 95% CI 0.18–0.28) varied by period, all post-infection estimates substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00, 0.02 to 0.03, 95% CI 0.01–0.06). Variant was an important predictor of SARS-CoV-2 post-infection sequalae, with recent Omicron sub-variants demonstrating similar probabilities to other contemporaneous ARIs. Further aetiological investigation including between-pathogen comparison is recommended.

Trichinellosis is a serious foodborne zoonosis. It poses a serious risk to public health worldwide. Early serological diagnosis of trichinellosis is influenced by an immunological ‘silent’ phase following infection. This highlights the necessity for developing sensitive diagnostic approaches to be employed when antibodies cannot be detected. In this work, the validity of traditional ELISA, Nano-ELISA and real time polymerase chain reaction (PCR) were evaluated in early diagnosis of Trichinella spiralis. Swiss albino mice were orally infected with 100 and 300 muscle larvae/mouse. Mice were sacrificed 4, 6, 8, 10, 15, and 28 days post-infection (dpi). Blood samples were tested for circulating antigen by traditional ELISA and Nano-ELISA using anti-rabbit polyclonal IgG conjugated with AgNPs and for Rep gene by SYBR green real-time PCR. Rep gene detection by SYBR green real-time PCR could detect T. spiralis with 100% sensitivity in the mild infection group at 8 dpi, while in the severe infection group it reached 100% sensitivity at 4 dpi. Nano-ELISA could detect T. spiralis circulating antigen from 4 dpi in both mild and severe infection and reached 100% sensitivity at 8 dpi and 6 dpi in mild and severe infection, respectively. However, traditional ELISA could detect T. spiralis circulating antigen from 6 dpi and reached maximum sensitivity at 15 dpi in the mild infection group, while in the severe infection group detection began at 4 dpi and reached 100% sensitivity at 8 dpi. Nano-ELISA and real time PCR, using Rep gene, are useful tools for the detection of early T. spiralis infection even in its mild infection state.

Background: Hypothalamic hamartomas (HH) are a challenging cause of seizure in children, partly because the neural circuitry involved in ictogenesis is incompletely understood. We review our institutions’ use of magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) to treat hypothalamic hamartoma (HH) with resting-state fMRI performed immediately before and after ablation. Methods: Seed-based whole brain connectivity to thalamic regions of interest was performed immediately pre- and post- MRgLITT. Multivariable generalized linear models were used to correlate resting-state data with seizure outcomes. Results: Eight patients underwent MRgLITT treatments for HH, with a mean follow up of 29 months. Four patients (50%) were seizure free at 12 months and two (25%) had a significant improvement in seizure frequency. We identified reduced thalamocortical connectivity involving the anterior cingulate and posterior parietal regions, consistent with disconnection of the mammillothalamic tract and interruption of Papez circuit. Large-scale thalamocortical connectivity changes were driven by children who subsequently became seizure free. Conclusions: Disconnection of the mammillothalamic tract and interruption of thalamic circuitry in patients undergoing MRgLITT for HH appears to be associated with improved seizure outcomes. The ability to assess network changes immediately post- MRgLITT could enable operative adjustments to be made mid-procedure to optimize seizure outcome in real time.

OBJECTIVES/GOALS: The goal of this study was to develop a clinically applicable technique to increase the precision of in vivo dose monitoring during radiation therapy by mapping the dose deposition and resolving the temporal dose accumulation while the treatment is being delivered in real time. METHODS/STUDY POPULATION: Ironizing radiation acoustic imaging (iRAI) is a novel imaging concept with the potential to map the delivered radiation dose on anatomic structure in real time during external beam radiation therapy without interrupting the clinical workflow. The iRAI system consisted of a custom-designed two-dimensional (2D) matrix transducer array with integrated preamplifier array, driven by a clinic-ready ultrasound imaging platform. The feasibility of iRAI volumetric imaging in mapping dose delivery and real-time monitoring of temporal dose accumulation in a clinical treatment plan were investigated with a phantom, a rabbit model, and a cancer patient. RESULTS/ANTICIPATED RESULTS: The total dose deposition and temporal dose accumulation in 3D space of a clinical C-shape treatment plan in a targeted region were first imaged and optimized in a phantom. Then, semi-quantitative iRAI measurements were achieved in an in vivo rabbit model. Finally, for the first time, real-time visualization of radiation dose delivered deep in a patient with liver metastases was performed with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the radiation dose deposition during treatment. DISCUSSION/SIGNIFICANCE: Described here is the pioneering role of an iRAI system in mapping the 3D radiation dose deposition of a complex clinical radiotherapy treatment plan. iRAI offers a cost-effective and practical solution for real-time visualization of 3D radiation dose delivery, potentially leading to personalized radiotherapy with optimal efficacy and safety.

Effective stakeholder interviewing is a critical component of a design process. However, interviewing is a complex skill that is difficult for novice designers to learn and incorporate into their design practices. Few studies have investigated how novice designers apply recommended practices for interviewing stakeholders during the development of product requirements. In this research, we studied how novice designers elicited information to inform the development of product requirements during stakeholder interviews. Results included the establishment of a coding methodology developed from a systematic literature review of recommended interviewing practices that was used to reliably evaluate the use of recommended practices in novice designers’ interviews. A correlation existed between the use of recommended practices and the extent to which information gathered from interviews was incorporated into the requirements. Additionally, specific recommended practices, such as encouraging deep thinking and being flexible and opportunistic, differentiated performance among novice designers. The coding methodology could be adapted to guide the development of stakeholder interview protocols and assessment of design interview skills.

The Royal Commission into Aged Care Quality and Safety has again focussed attention on the failings of the Australian aged care system. Residential aged care in Australia has become increasingly market-driven since the major reforms of 1997. The aims of increased marketisation include providing residents with greater choice, higher quality services, and increasing providers’ efficiency and innovation. However, marketisation is not meeting these aims, predominantly due to asymmetries of knowledge and power between residents and aged care providers. These asymmetries arise from inadequate provision of information, geographic disparities, urgency for care as needs arise acutely, and issues surrounding safety, including cultural safety. We propose a human rights framework, supported by responsive regulation, to overcome the failings of the current system and deliver an improved aged care system which is fit for purpose.

This review provides an overview of the composition, structure, and biological activities of milk fat globule membrane (MFGM) compounds with focus on the future application of this compound as a food ingredient. MFGM is a particular component of mammalian milks and is comprised of a tri-layer of polar lipids, glycolipids and proteins. In recent years, MFGM has been extensively studied for the purpose of enhancing the efficacy of infant nutrition formula. For example, infant formulas supplemented with bovine MFGM have shown promising results with regard to neurodevelopment and defense against infections. Components of MFGM have been shown to present several health benefits as the proteins of the membrane have shown antiviral activity and a reduction in the incidence of diarrhea. Moreover, the presence of sphingomyelin, a phospholipid, implies beneficial effects on human health such as enhanced neuronal development in infants and the protection of neonates from bacterial infections. The development of a lipid that is similar to human milk fat would represent a significant advance for the infant formula industry and would offer high technology formulas for those infants that depend on infant formula. The complexity of the structure of MFGM and its nutritional and technological properties is critically examined in this review with a focus on issues relevant to the dairy industry.

Not all patients who acquire carbapenemase-producing Enterobacteriaceae (CPE) develop infections by these organisms; many remain only colonized. Of 54 CPE-colonized patients, 16 (30%) developed CPE infections. We identified indwelling urinary catheter exposure, exposure to intravenous colistin, and overseas transfer as variables associated with CPE infection development among colonized patients.