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Institutions of higher education are increasingly highlighting community engagement activities to make the benefits of higher education more visible. The most transformational community engagement is linked to curriculum, so it is faculty who must incorporate community-engaged pedagogy. This content analysis of faculty narratives about community engagement reveals motivations for faculty to engage in this work. These findings connect to social capital theory and suggest a new direction for faculty development efforts to promote community engagement.

This music score was submitted for Resonate 2024: An Open Access Call for Scores by the UCLA Music Library with Bent Frequency and Jan Berry Baker.

Ultrafast electron diffraction (UED) stands as a powerful technique for real-time observation of structural dynamics at the atomic level. In recent years, the use of MeV electrons from radio frequency guns has been widely adopted to take advantage of the relativistic suppression of the space charge effects that otherwise limit the temporal resolution of the technique. Nevertheless, there is not a clear choice for the optimal energy for a UED instrument. Scaling to beam energies higher than a few MeV does pose significant technical challenges, mainly related to the inherent increase in diffraction camera length associated with the smaller Bragg angles. In this study, we report a solution by using a compact post-sample magnetic optical system to magnify the diffraction pattern from a crystal Au sample illuminated by an 8.2 MeV electron beam. Our method employs, as one of the lenses of the optical system, a triplet of compact, high field gradients (>500 T/m), small-gap (3.5 mm) Halbach permanent magnet quadrupoles. Shifting the relative position of the quadrupoles, we demonstrate tuning the magnification by more than a factor of two, a 6× improvement in camera length, and reciprocal space resolution better than 0.1 Å-1 in agreement with beam transport simulations.

Abstract Leukocytes interact with other cells using cell surface receptors. The largest group of such receptors are non-catalytic tyrosine phosphorylated receptors (NTRs), also called immunoreceptors. NTR signalling requires phosphorylation of cytoplasmic tyrosine residues by SRC-family tyrosine kinases. How ligand binding to NTRs induces this phosphorylation, also called NTR triggering, remains controversial, with roles suggested for size-based segregation, clustering, and mechanical force. Here we exploit a recently developed cell-surface generic ligand system to explore the ligand requirements for NTR triggering. We examine the effect of varying the ligand’s length, mobility and valency on the activation of representative members of four NTR families: SIRPβ1, Siglec 14, NKp44 and TREM-1. Increasing the ligand length impairs activation via NTRs, despite enhancing cell-cell conjugation, while varying ligand mobility has little effect on either conjugation or activation. Increasing the valency of the ligand, while enhancing cell-cell conjugation, does not enhance activation at equivalent levels of conjugation. These findings are more consistent with a role for size-based segregation, rather than mechanical force or clustering, in NTR triggering, suggesting a role for the kinetic-segregation model.

Abstract Background Multiple sclerosis (MS) is a chronic neurological condition and the leading cause of non-traumatic disability in young adults. MS pathogenesis leads to the death of oligodendrocytes, demyelination, and progressive central nervous system neurodegeneration. Endogenous remyelination occurs in people with MS (PwMS) but is insufficient to repair the damage. Our preclinical studies in mice indicate that endogenous remyelination can be supported by the delivery of repetitive transcranial magnetic stimulation (rTMS). Our phase I trial concluded that 20 sessions of rTMS, delivered over 5 weeks, are safe and feasible for PwMS. This phase II trial aims to investigate the safety and preliminary efficacy of rTMS for PwMS. Methods Participants must be aged 18–65 years, diagnosed with MS by a neurologist, stable and relapse free for 6 months, have an Extended Disability Status Scale (EDSS) between 1.5 and 6 (inclusive), willing to travel to a study site every weekday for 4 consecutive weeks, and able to provide informed consent and access the internet. Participants from multiple centres will be randomised 2:1 (rTMS to sham) stratified by sex. The intervention will be delivered with a Magstim Rapid2 stimulator device and circular 90-mm coil or MagVenture MagPro stimulator device with C100 circular coil, positioned to stimulate a broad area including frontal and parietal cortices. For the rTMS group, pulse intensity will be set at 18% (MagVenture) or 25% (Magstim) of maximum stimulator output (MSO), and rTMS applied as intermittent theta burst stimulation (iTBS) (~ 3 min per side; 600 pulses). For the sham group, the procedure will be the same, but the intensity is set at 0%. Each participant will attend 20 intervention sessions over a maximum of 5 weeks. Outcome measures include MS Functional Composite Score (primary), Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Quality of Life, and Pittsburgh Sleep Quality Index/Numeric Rating Scale and adverse events (secondary) and advanced MRI metrics (tertiary). Outcomes will be measured at baseline and after completing the intervention. Discussion This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in PwMS. Trial registration Registered with Australian New Zealand Clinical Trials Registry, 20 January 2022; ACTRN12622000064707.

Early childhood educator's emotional socialization may contribute crucially to young children's social-emotional competence. Here, we examined the contributions of self-reported reactions to children's emotions and beliefs about emotional socialization of 90 teachers to the social-emotional competence of 334 pre-schoolers. Teacher-reported emotion socialization, especially as moderated by classroom socioeconomic risk, often predicted pre-schoolers' end-of-year social-emotional behaviours, independent of child covariates, including children's beginning-of-year premeasures. Only three findings resembled the parent emotion socialization literature, however, and two appeared unique to the pre-school environment. Most were specific to classrooms where children experienced socioeconomic risk. The pattern of moderation findings highlights the importance of context in teachers' emotional socialization. Suggestions are given for expanded research on the topic and potential applications to assist teachers in their role as emotion socializers.

Mental rotation is the ability to mentally rotate two-dimensional and three-dimensional objects in one's mind. Previous studies have examined the relationship between mental rotation abilities and embodied cognition. However, conflicting findings underscore the necessity for further investigation. This study aims to investigate how different levels of embodiment in mental rotation training affect mental rotation training. Three versions of mental rotation training with different levels of embodiment (keyboard, touchpad and augmented reality) were developed for this study. A quasi-experimental study was conducted with a total of 125 university students to explore how different training versions affect participants' training performances, perception of the usability of the training and mental rotation ability. The results suggest those who used the versions with higher levels of bodily engagement performed better than those who used the versions with lower levels of bodily engagement (p < 0.001). Participants' mental rotation ability also improved significantly after training with the augmented reality (AR1) version compared to those in the keyboard group (p = 0.01). The learning analytics results provide additional clarity by indicating that the participants' mental rotation ability can be predicted by their training performance in the AR condition (p < 0.001). This study has significant implications for the potential of using embodied AR training to improve mental rotation ability.

BackgroundWhile vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection.MethodsIn this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures.FindingsPrevious infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease.InterpretationPrevious infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection.FundingNational Institutes of Health.

Background: High intensity statin therapy (HIST) is the gold standard therapy for decreasing the risk of recurrent atherosclerotic cardiovascular disease (ASCVD); however, little is known about the use of HIST in older adults with ASCVD. Objectives: The aim of this cross-sequential study was to determine trends in statin intensity in older adults over a 10-year timeframe. Methods: The study was conducted in an integrated healthcare delivery system. Patients were 76 years or older with validated coronary ASCVD. Data were collected from administrative databases. Statin intensity level was assessed in eligible patients on January 1st and July 1st from January 1, 2007 to December 31, 2016. Results: Overall, a total of 5,453 patients were included with 2,119 (38.9%) and 3,334 (61.1%) categorized as HIST and Non-HIST, respectively. Included patients had a mean age of 79.8 years and were primarily male and white and had a cardiac intervention. The rate of HIST use increased from 14.5% to 41.3% over the study period (p

Integrating learning analytics in digital game-based learning has gained popularity in recent decades. The interactive nature of educational games creates an ideal environment for learning analytics data collection. However, past research has limited success in producing accessible and effective assessments using game learning analytics. In this study, a mathematics educational game called The Nomads was designed and developed to train learners' adaptive expertise in rational number arithmetic. Players' game log data were captured and fitted to a cognitive diagnostic model (CDM)--CCM (continuous conjunctive model). CCM lends itself well to the complex and dynamic nature of game learning analytics. Unlike traditional CDMs, CCM generates parameters at an attribute level and offers more parsimonious diagnoses using continuous variables. The findings suggest that learners' attribute mastery improved during the gameplay and that learners benefit from using the scaffolds for three of the attributes instructed by the game. This study presents the application of a powerful new tool for game learning analytics. Future studies can benefit from more generalized analytics models and more specified learning attributes and game tasks.

Background: Successful catheter ablation of ventricular tachycardia (VT) in repaired tetralogy of Fallot (TOF) can be achieved by targeting 1 or more anatomical isthmuses. However, significant interindividual variability in the size and location of surgical patches means careful mapping is required to design ablation lines to block the isthmus. Intracardiac echocardiography (ICE) may assist ablation by accurate identification of individual TOF anatomy. Objectives: The authors hypothesized ICE-guided VT ablation improved isthmus recognition, ablation, and procedural outcomes. Methods: Retrospective study of adults with repaired TOF undergoing VT ablation between January 1, 2017 and December 31, 2022. ICE integration was compared to a strategy using electroanatomical mapping only to identify anatomic boundaries. All cases underwent ablation and had proven isthmus block as the procedural endpoint. Results: Twenty-three patients (age 47 ± 14 years; 61% male) underwent 27 VT ablations (ICE: 16/27 [59%]; no ICE: 11/27 [41%]). ICE improved the ability to localize and ablate the anatomical isthmus (ICE: 13/15 [87%] vs no ICE: 4/11 [36%]; P = 0.014); however, there was no difference in long-term freedom from VT (ICE: 9/12 [75%] vs no ICE: 8/11 [73%]; P = 0.901). ICE had no impact on procedural times (ICE: 173 ± 48 minutes vs no ICE: 157 ± 47 minutes; P = 0.399), fluoroscopy time (ICE: 30 ± 16 minutes vs no ICE: 29 ± 10 minutes; P = 0.864), or major complications (ICE: 1/16 [6%] vs no ICE 0/11; P = 1.000). Conclusions: ICE improves ablation of the anatomical isthmus for sustaining VT in patients with repaired TOF by demonstrating the individual anatomy but does not improve long-term outcomes.

Background: To determine any differences in clinical outcomes between patients in the supine vs the lateral position during anterior-based muscle sparing (ABMS) total hip arthroplasty (THA). Methods: A retrospective review was performed of 368 patients undergoing THA via the ABMS approach (201 lateral vs 167 supine position) at our institution (2015-2019) with a minimum follow-up of 12 months. Inclusion criteria were all patients undergoing primary THA. Exclusion criteria were any revision surgeries and patients who did not undergo the ABMS THA. Outcomes assessed were postoperative complication rates, ambulation distance, length of stay, and Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, and physical function scores at 3 time periods (preoperative, 3 months postoperative, and 1 year postoperative). Results: The supine group had significantly greater postoperative day 0 ambulation distance (150 vs 60 meters; P < .001), while no difference was observed on postoperative day 1 (210 meters in supine vs 200 in lateral; P = .921). Median length of stay was significantly shorter in the supine group (1; interquartile range 0-1) with respect to the lateral group (1; interquartile range 0-2; P < .001). The in-hospital complication rates (2.4% in supine vs 1.5% in lateral; P = .780), return to operating room rates (2.4% in supine vs 1.5% in lateral; P = .780), and readmission rates (5.4% in supine vs 5.0% in lateral; P = .631) were not significantly different between the groups. No significant differences were observed across any Western Ontario and McMaster Universities Osteoarthritis Index scores. Conclusions: Both supine and lateral patient positioning provide acceptable early surgical outcomes, suggesting that satisfactory results can be obtained via both positions in THAs.

BackgroundMajor histocompatibility complex class-1-related protein (MR1), unlike human leukocyte antigen (HLA) class-1, was until recently considered to be monomorphic. MR1 presents metabolites in the context of host responses to bacterial infection. MR1-restricted TCRs specific to tumor cells have been described, raising interest in their potential therapeutic application for cancer treatment. The diversity of MR1-ligand biology has broadened with the observation that single nucleotide variants (SNVs) exist within MR1 and that allelic variants can impact host immunity.MethodsThe TCR from a MR1-restricted T-cell clone, MC.7.G5, with reported cancer specificity and pan-cancer activity, was cloned and expressed in Jurkat E6.1 TCRαβ− β2M− CD8+ NF-κB:CFP NFAT:eGFP AP-1:mCherry cells or in human donor T cells. Functional activity of 7G5.TCR-T was demonstrated using cytotoxicity assays and by measuring cytokine release after co-culture with cancer cell lines with or without loading of previously described MR1 ligands. MR1 allele sequencing was undertaken after the amplification of the MR1 gene region by PCR. In vivo studies were undertaken at Labcorp Drug Development (Ann Arbor, MI, USA) or Epistem Ltd (Manchester, UK).ResultsThe TCR cloned from MC.7.G5 retained MR1-restricted functional cytotoxicity as 7G5.TCR-T. However, activity was not pan-cancer, as initially reported with the clone MC.7.G5. Recognition was restricted to cells expressing a SNV of MR1 (MR1*04) and was not cancer-specific. 7G5.TCR-T and 7G5-like TCR-T cells reacted to both cancer and healthy cells endogenously expressing MR1*04 SNVs, which encode R9H and H17R substitutions. This allelic specificity could be overcome by expressing supraphysiological levels of the wild-type MR1 (MR1*01) in cell lines.ConclusionsHealthy individuals harbor T cells reactive to MR1 variants displaying self-ligands expressed in cancer and benign tissues. Described “cancer-specific” MR1-restricted TCRs need further validation, covering conserved allomorphs of MR1. Ligands require identification to ensure targeting MR1 is restricted to those specific to cancer and not normal tissues. For the wider field of immunology and transplant biology, the observation that MR1*04 may behave as an alloantigen warrants further study.

As more states in the USA require elementary schools to offer computer science (CS) education, teachers are expected to master the knowledge and skills to teach CS by integrating computational thinking (CT) into content areas. This study presented a research-practice partnership approach to support elementary teachers in a local school district with CT integration. Professional development (PD) followed the technological, pedagogical, and content knowledge (TPACK) framework, and three elementary teachers' PD and classroom implementation experiences were examined and reported as a multiple case study. Interviews, observations, and teacher artifacts and reflections were collected and analyzed. The cross-case analysis revealed that the teachers (1) had an improved understanding of how CS/CT connects with content areas and how to make alignments across content standards, (2) demonstrated concrete strategies for designing and implementing CT-integrated instruction with various coding tools, and (3) provided students with engaging and inclusive learning experiences using a range of pedagogies. The paper discussed the implications for CS education at the elementary level.

For many years I cared for Joe, following him through diagnoses of strokes, end-stage renal disease, and metastatic prostate cancer. Gaining his trust, coordinating his care across specialist visits and hospitalizations, and helping him and his family clarify goals of care took an investment of time and relationship-building. I was able to spend this time with Joe, and all of my medically complex patients, because I had taken a job in a Program of All-Inclusive Care for the Elderly (PACE), a fully capitated model of care. With care organized around the patient instead of the visit, this payment model transformed my work life. As I reflect on the care that I provided for Joe over the years, I consider how health care organization and finance can either help or hinder our ability to provide patient-centered, coordinated, continuous care for our patients. Evolving payment models can help make space for family physicians to provide the robust primary care we are trained to deliver. Key words: health care finance; physician-patient relationship; geriatrics, One afternoon when I was in clinic, I received a call from the ICU of a local hospital. The hospitalist caring for a patient of mine, I'll call him Joe, [...]

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

Methods Semi-structured interviews were conducted with purposively sampled participants to explore their perspectives about the implementation of the programme, interventions tested as part of the ‘change package’ provided and the pandemic’s impact.Results A total of seven participants were interviewed, including acute ward managers, a charge nurse (deputy ward manager), a wound healing community nurse and a team leader community nurse. Interview durations varied from 9 min to 28 min. The interviews were kept short and stopped when data saturation was achieved as it was an extremely pressurised time for the organisation where the highest escalation alert was triggered on numerous occasions.Conclusion A sustained reduction in PUs was achieved during the evaluation period and participants felt that the approach helped to achieve this, regardless of the adaptations made to the delivery method due to the pandemic. To support improvements, it is vital to ensure systems such as data collection are accurate and timely. The necessity for building strong foundations for QI capability must not be underestimated, as greater QI knowledge leads to better engagement and outcomes.

As climate change impacts human systems, associated adaptation efforts are beginning to shape the quality of life in cities and other places. How the work of climate change adaptation is being undertaken, by whom, where and for whose benefit, has important justice and equity outcomes. Increasingly, adaptation work is being formalised into paid jobs. This emerging field of work has been rarely studied, but it is important to understand because the disciplinary backgrounds, organisational positions, roles, responsibilities and spatial locations involved are likely to have a disproportionate influence on wider approaches to climate change risk and adaptation, including societal understandings of what actually is climate change adaptation. This paper commences the investigation into paid adaptation work by analysing Australian job advertisements for adaptation roles, and interviewing associated hiring managers. It identifies three biases in the jobs of adaptation on offer towards: well-resourced and urban-based positions; professional services; and a climate risk management interpretation of adaptation. These biases indicate that urban adaptation has the potential to ossify, if not exacerbate, unjust urban geographies. To help moderate this risk of maladaptation, investment is required into other forms of adaptation work, particularly within the public sector. Policy relevance The biases within the emerging work of adaptation towards consulting firms and local government in larger cities, as well as few jobs addressing vulnerability, indicates the need for government to undertake the work of inclusive and just climate change adaptation. This work would minimise the potential for existing socio-economic disparities to be exacerbated though climate change adaptation.

IntroductionParkinson’s disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia.MethodsA forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices.ResultsTwenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future.DiscussionInvestment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.

Background We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib‐induced vulnerability to VA that can be modulated for cardioprotection remains unclear. Methods and Results The effects of ibrutinib on cardiac electrical activity and Ca2+ dynamics were investigated in Langendorff‐perfused hearts using optical mapping. We also conducted Western blotting analysis to evaluate the impact of ibrutinib on various regulatory and Ca2+‐handling proteins in rat cardiac tissues. Treatment with ibrutinib (10 mg/kg per day) for 4 weeks was associated with an increased VA inducibility (72.2%±6.3% versus 38.9±7.0% in controls, P

Chromatography combined with mass spectrometry is a gold standard technique for steroid measurement, however the type of sample preparation, the dynamic range and reliability of the calibration curve, the chromatographic separation and mass spectrometry settings ultimately determine the success of the method. The steroid biosynthetic pathway is conserved in higher mammals and literature demonstrates that the concentration ranges of different steroid groups are relatively comparable across species. We sought to develop a robust and reliable multi steroid targeted analysis method for blood that would have wide application across higher mammals. The method was developed following bioanalytical method validation guidelines to standards typically applied to human clinical studies, including isotopically labelled internal standards where at all possible. Here we describe the practical approach to a 96-well supported liquid extraction (SLE) method of extraction from plasma (200 µL) using an Extrahera liquid handling robot (Biotage, Sweden), including quality control samples, followed by a comprehensive separation and targeted LC-MS/MS analysis of 18 steroids in plasma (pregnenolone, progesterone, 17α-hydroxyprogesterone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycortisol, 21-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, 5α-dihydrotestosterone, dehydroepiandrosterone, estrone, 17β-estradiol and estriol). • SLE in a 96-well format of up to 74 biological plasma samples, enriched with multiple isotopically labelled internal standards, a 12-point aqueous calibration curve, and 6 serum quality controls, designed to monitor long-term performance of the method • Chromatographic separation of multiple steroids along the gradient, with ammonium fluoride mobile phase additive to improve sensitivity, followed by electrospray ionisation and constant polarity switching • Aqueous calibration standards that cover physiologically relevant ranges - high nanomolar glucocorticoids, low nanomolar androgens and picomolar ranges for estrogens and steroid intermediates.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P

Abstract Modern healthcare focuses on patient‐centred care where patients' needs, beliefs, choices and preferences are valued and lead to better health outcomes. Children and young persons in out of home care (OOHC) require more health care services compared with children from similar social and economic backgrounds. Each state and territory government are responsible for statutory child protection in Australia. If a child is unsafe in their current environment, they may be removed and placed into OOHC where they have ongoing case management with either a government or non‐government agency. Complex trauma is the prolonged and uncontrolled exposure to traumatic events, like those experienced by maltreated children. Complex trauma can create a toxic stress response that produces biological alteration to the developing brain and affects the lives of the child, other family members and their descendants. Children with complex trauma often do not have the ability to regulate their responses to stimuli, reacting to minor triggers with disproportionate reactions. Many of these children will present with challenging behaviours. Trauma‐informed care is a method of service delivery that seeks to actively minimise re‐traumatisation. Creating a safe space is an essential element of trauma‐informed care. Children with a history of complex trauma have life experiences that may be re‐lived in a healthcare setting. There are ethical and legal considerations like privacy, consent and mandatory reporting when dealing with children in OOHC. By practising trauma‐informed care Medical Radiation Practitioners can minimise further trauma to one of the most vulnerable population groups in Australia.

Abstract Magnetic resonance imaging (MRI) is being integrated into routine radiation therapy (RT) planning workflows. To reap the benefits of this imaging modality, patient positioning, image acquisition parameters and a quality assurance programme must be considered for accurate use. This paper will report on the implementation of a retrofit MRI Simulator for RT planning, demonstrating an economical, resource efficient solution to improve the accuracy of MRI in this setting.

Abstract Current differentiation protocols for generating mesencephalic dopaminergic (mesDA) neurons from human pluripotent stem cells result in grafts containing only a small proportion of mesDA neurons when transplanted in vivo. In this study, we develop lineage-restricted undifferentiated stem cells (LR-USCs) from pluripotent stem cells, which enhances their potential for differentiating into caudal midbrain floor plate progenitors and mesDA neurons. Using a ventral midbrain protocol, 69% of LR-USCs become bona fide caudal midbrain floor plate progenitors, compared to only 25% of human embryonic stem cells (hESCs). Importantly, LR-USCs generate significantly more mesDA neurons under midbrain and hindbrain conditions in vitro and in vivo. We demonstrate that midbrain-patterned LR-USC progenitors transplanted into 6-hydroxydopamine-lesioned rats restore function in a clinically relevant non-pharmacological behavioral test, whereas midbrain-patterned hESC-derived progenitors do not. This strategy demonstrates how lineage restriction can prevent the development of undesirable lineages and enhance the conditions necessary for mesDA neuron generation.