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The authors present a case report for an adolescent student with a learning disability who has academic, behavioral, and intensive mental health needs. A therapeutic package to support and maintain student progress is discussed. The case report outlines specifically how the student's mental health needs were supported through the implementation of Acceptance Commitment Therapy and a Check-In, Check-Out procedure. The authors discuss how the interventions are applied to the student's academic engagement, emotional stability, and improved quality of life. Major takeaways and implications for school teams are discussed.

Abstract Neuronal activity undergoes significant changes during vigilance states, accompanied by an accommodation of energy demands. While the astrocyte-neuron lactate shuttle has shown that lactate is the primary energy substrate for sustaining neuronal activity in multiple brain regions, its role in regulating sleep/wake architecture is not fully understood. Here we investigated the involvement of astrocytic lactate supply in maintaining consolidated wakefulness by downregulating, in a cell-specific manner, the expression of monocarboxylate transporters (MCTs) in the lateral hypothalamus of transgenic mice. Our results demonstrate that reduced expression of MCT4 in astrocytes disrupts lactate supply to wake-promoting orexin neurons, impairing wakefulness stability. Additionally, we show that MCT2-mediated lactate uptake is necessary for maintaining tonic firing of orexin neurons and stabilizing wakefulness. Our findings provide both in vivo and in vitro evidence supporting the role of astrocyte-to-orexinergic neuron lactate shuttle in regulating proper sleep/wake stability.

Online interventions that elicit kindness may enhance well-being. We tested the efficacy of three kindness interventions among breast cancer survivors. Participants (N = 137, M age = 62.65 years) were randomized to perform acts of kindness for others, acts of kindness for self, self-kindness meditation, or a daily-activities-writing control and completed three activities each week for 4 weeks. Primary (well-being, depressive symptoms) and secondary outcomes (social support, self-kindness) were assessed pre- and post-intervention. No differences emerged in the primary outcomes. However, relative to controls, participants in the acts of kindness to others condition reported greater increases in social support, and participants in the self-kindness meditation condition reported greater decreases in self-kindness. Among breast cancer survivors, performing prosocial acts may enhance feelings of social support. The two self-kindness conditions yielded either null or detrimental effects, suggesting that further research is needed on best practices for conducting self-focused kindness interventions.

The authors present a three-year case report for an adolescent student with Autism who has academic, behavioral, and mental health needs requiring collaborative school-based intervention. The case report outlines specifically how the student's mental health needs were supported through the application of a relationship-building framework. The authors discuss how elements of the Establish, Maintain, Restore intervention were applied to the therapist-student relationship. Results of the intervention consisted of stable connections with school staff and academic support for the student's educational success. Major takeaways and implications for school teams are discussed.

Abstract Campylobacter is a leading cause of food-borne gastroenteritis worldwide, linked to the consumption of contaminated poultry meat. Targeting this pathogen at source, vaccines for poultry can provide short-term caecal reductions in Campylobacter numbers in the chicken intestine. However, this approach is unlikely to reduce Campylobacter in the food chain or human incidence. This is likely as vaccines typically target only a subset of the high genomic strain diversity circulating among chicken flocks, and rapid evolution diminishes vaccine efficacy over time. To address this, we used a genomic approach to develop a whole-cell autogenous vaccine targeting isolates harbouring genes linked to survival outside of the host. We hyper-immunised a whole major UK breeder farm to passively target offspring colonisation using maternally-derived antibody. Monitoring progeny, broiler flocks revealed a near-complete shift in the post-vaccination Campylobacter population with an ~50% reduction in isolates harbouring extra-intestinal survival genes and a significant reduction of Campylobacter cells surviving on the surface of meat. Based on these findings, we developed a logistic regression model that predicted that vaccine efficacy could be extended to target 65% of a population of clinically relevant strains. Immuno-manipulation of poultry microbiomes towards less harmful commensal isolates by competitive exclusion, has major potential for reducing pathogens in the food production chain.

Synchrotron light sources can provide the required spatial coherence, stability and control to support the development of advanced lithography at the extreme ultraviolet and soft X-ray wavelengths that are relevant to current and future fabricating technologies. Here an evaluation of the optical performance of the soft X-ray (SXR) beamline of the Australian Synchrotron (AS) and its suitability for developing interference lithography using radiation in the 91.8 eV (13.5 nm) to 300 eV (4.13 nm) range are presented. A comprehensive physical optics model of the APPLE-II undulator source and SXR beamline was constructed to simulate the properties of the illumination at the proposed location of a photomask, as a function of photon energy, collimation and monochromator parameters. The model is validated using a combination of experimental measurements of the photon intensity distribution of the undulator harmonics. It is shown that the undulator harmonics intensity ratio can be accurately measured using an imaging detector and controlled using beamline optics. Finally, the photomask geometric constraints and achievable performance for the limiting case of fully spatially coherent illumination are evaluated.

PurposeThe combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma.MethodsPatients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis.ResultsOverall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm.ConclusionT-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

Elliot John Teo,1,2 Sigrid Petautschnig,1,2 Jack Hellerstedt,1 Sally A Grace,1 Jacqui S Savage,1 Brendan Fafiani,1 Paul Daniel Smith,3,4 Ashu Jhamb,5 Timothy Haydon,2,6 Barry Dixon1,5,6 1Cyban Pty Ltd, Melbourne, Victoria, Australia; 2Department of Critical Care Medicine, St Vincent’s Hospital, Melbourne, Victoria, Australia; 3Department of Neurosurgery, St Vincent’s Hospital, Melbourne, Victoria, Australia; 4University of Melbourne Medical School, Melbourne, VIC, Australia; 5Department of Medical Imaging, St Vincent’s Hospital, Melbourne, Victoria, Australia; 6Department of Critical Care, the University of Melbourne, Melbourne, VIC, AustraliaCorrespondence: Barry Dixon, Department of Critical Care Medicine, St Vincent’s Hospital (Melbourne), 41 Victoria Parade, Fitzroy, VIC, 3065, Australia, Tel +61 439 618 815 ; +61 3 9231 4425, Email barry.dixon@cyban.com.auAbstract: Subarachnoid haemorrhage (SAH) can trigger a range of poorly understood cerebrovascular responses that may play a role in delayed cerebral ischemia. The brain pulse monitor is a novel non-invasive device that detects a brain photoplethysmography signal that provides information on intracranial pressure (ICP), compliance, blood flow and tissue oxygen saturation. We monitored the cerebrovascular responses in a patient with Lundberg B waves following a SAH. The patient presented with a Fischer grade 4 SAH that required urgent left posterior communicating artery aneurysm coiling and ventricular drain insertion. On hospital day 4 oscillations or spikes on the invasive ICP were noted, consistent with Lundberg B waves. Brain pulse monitoring demonstrated concurrent pulse waveform features consistent with reduced brain compliance and raised ICP over both brain hemispheres. Oxygen levels also demonstrated slow oscillations correlated with the ICP spikes. Brief infrequent episodes of reduced and absent brain pulses were also noted over the right hemisphere. Our findings suggest that the brain pulse monitor holds promise for early detection of delayed cerebral ischemia and could offer insights into the vascular mechanisms at play.Plain Language Summary: In this study, we examined a patient with a serious brain bleed, known as subarachnoid hemorrhage (SAH). Patients with SAH can suffer from vasospasm and consequent delayed cerebral ischemia (DCI), which can happen from 4 to 14 days after the initial bleeding. Detecting and treating DCI early is difficult because methods are imperfect, discontinuous and technically difficult.We used a new, non-invasive device that can monitor various features of brain health. This device helps us understand the pressure inside the skull, blood flow, and the oxygen saturation on the surface of the brain. In this patient, we found evidence of:Brain pulse signals that were directly related to acute changes in the invasive intracranial pressure.Specific brain pulse patterns that may indicate a local reduction in brain blood flow.Signs of a breakdown in the brain’s ability to regulate blood flow in the injured hemisphere.The oxygen saturation levels in the brain that related to pressure changes.These results are promising because they suggest the new device could help us identify when someone’s brain condition is getting worse. This ability could guide the development of improved care protocols, and aid clinical decision-making. Further research is needed in this patient population with additional forms of monitoring to understand the generalizability of our findings.Keywords: near infra-red, spreading depolarisation, vasoconstriction, intracranial pressure, brain compliance, brain oxygen

NUT carcinomas (NCs) are a group of rare tumors that can occur anywhere in the body and are defined by the fusion of the nuclear protein in testis (NUTM1) resulting in increased transcription of proto-oncogenes. NCs have a poor prognosis that varies according to the site of origin with an urgent need to develop new treatment strategies. Case reports on immunotherapy in pulmonary NC have been published, and bromodomain and extraterminal (BET) inhibitors have shown activity in NC in phase I/II trials. We present the case of a 27-year-old woman with an unresectable sinonasal NC who had a sustained clinical response to both immunotherapy and BET inhibitor therapy. This is the first reported case of immunotherapy in sinonasal NC, and it highlights the different responses to a range of treatments including BET inhibitor therapy. This case supports the theory that NCs arising from different primary sites have differing prognoses.

Wnt signaling plays a major role in regulating cell proliferation and differentiation. The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either through β-catenin in the canonical pathway or through a series of other proteins in the noncanonical pathway. Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body, establishing the complex interplay between Wnt signaling and other signaling pathways. This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes. Dysregulation of this system has been implicated in many diseases affecting a wide array of organ systems, including cancer and embryological defects, and can even cause embryonic lethality. The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments. However, both stimulatory and inhibitory treatments come with potential risks that need to be addressed. This review synthesized much of the current knowledge on the Wnt signaling pathway, beginning with the history of Wnt signaling. It thoroughly described the different variants of Wnt signaling, including canonical, noncanonical Wnt/PCP, and the noncanonical Wnt/Ca2+ pathway. Further description involved each of its components and their involvement in other cellular processes. Finally, this review explained the various other pathways and processes that crosstalk with Wnt signaling.

The aim of the present qualitative interview study was to explore how teachers working at an alternative education setting serving students with emotional and behavioral disorders (EBD) build relationships with their students. In-depth interviews with five instructors resulted in the development of seven interrelated themes concerning the key attitudes, process, context, and outcomes associated with developing quality relationships with students with EBD. The authors present and thoroughly describe each of these themes. They then discuss how the study adds to the limited knowledge about the student teacher relationship for students with EBD and how practitioners working with this population of students can use this knowledge. Finally, they address what next steps are needed to improve this influential aspect of the learning environment for these students.

Different terms are used to describe pedagogy that moves away from the transmission of content and moves towards teaching and learning that builds from the learner's own experiences in a more responsive and interactive manner. We understand this as developing "cultural relationships for responsive pedagogy". Rongohia te Hau processes were developed to understand how effectively culturally responsive pedagogy was being introduced or maintained in early childhood settings or schools. The Rongohia te Hau processes of walkthrough observations and surveys ask teachers, students, and whanau critical questions about their learning experiences. This article discusses these processes and provides examples of the data produced to help understand how the pedagogy is being understood across the setting to inform strategic direction.

Background: Malignancy is a long-term complication of lung transplantation (LTx); however, contemporary Australian data and detailed evaluation of nonreportable cancers are lacking. Methods: Retrospective review of LTx recipients’ medical records and registry data linkage were performed to identify histologically proven malignancies. Baseline clinico-demographic variables were collected, and cancer incidence was compared with reported data for the general Australian population. Results: There were 1,715 LTx in 1,631 patients between 1989 and 2021, with a follow-up of 9,696 person-years. Eight hundred and ninety-three (54.8%) patients were male, and the median age at first LTx was 54.7 years. There were 886 deaths with a median overall survival of 7.5 years (95% confidence intervals (CI) 6.8-8.3 years). One thousand seven hundred and seventy-four separate invasive cancer events occurred across 407 patients, of which, 1,588 (89.5%) were nonmelanoma skin cancers (NMSCs). This translated to a 9-fold increased incidence of NMSCs and a 4-fold increased incidence of other cancers compared with the general population. Cancer mortality reached parity with chronic lung allograft dysfunction 10 years postfirst transplant and was independently associated with age (hazard ratios (HR) per year increase in age 1.02 [95% CI 1.01-1.03], p = 0.001), Epstein-Barr virus primary mismatch (HR 3.24 [95% CI 1.68-6.25], vs nonmismatch, p = 0.002), and cancer count (HR per cancer event 1.19 [95% CI 1.13-1.24], p

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues. This includes but is not limited to embryonic, hematopoietic, mesenchymal, gut, neural, and epidermal stem cells. Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties. Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders. Not surprisingly, aberrant Wnt signaling is also associated with a wide variety of diseases, including cancer. Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation, epithelial–mesenchymal transition, and metastasis. Altogether, advances in the understanding of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway. Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt, this review aims to summarize the current knowledge of Wnt signaling in stem cells, aberrations to the Wnt pathway associated with diseases, and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.

BackgroundAmbulance-based telemedicine is an innovative strategy through which transport time can be used to rapidly and accurately triage stroke patients (i.e., mobile telestroke). The acute phase of stroke is a time-sensitive emergency, and delays in care during this phase worsen outcomes. In this literature review, we analyzed studies that investigated the feasibility and reliability of ambulance based telestroke.MethodsWe followed PRISMA guidelines to perform a keyword-based search of PubMed, Web of Science, CINHAL, and Academic Search Complete databases. We reviewed references of search-identified articles to screen for additional articles. Articles for inclusion were selected according to author consensus in consideration of the studies' investigation of feasibility, reliability, or validity of ambulance-based telestroke.ResultsWe identified 67 articles for secondary screening from which 19 articles were selected for full text review. The selected studies reported diverse methods of development, implementation, and assessment of ambulance-based telestroke systems. Although the methods and results varied among these studies, most concluded that the implementation of ambulance based telestroke is feasible.ConclusionThis topical review suggests that ambulance based telestroke is a feasible method for enhanced prehospital stroke care in a variety of settings. Further prospective research is needed to assess the real-world challenges and to identify additional strategies that bolster rapid and accurate prehospital assessment of acute stroke patients.

SUMMARY: A total of 3 broiler diets were pelleted to determine the effects of diet formulation on pellet quality. Dietary treatments consisted of corn and soybean meal-based control, the control with crystalline valine (Val), and the control with crystalline Val and isoleucine (Ile). As crystalline amino acids (AA) increased in the diets, corn concentrations increased as soybean meal and the fat source were removed to balance for nitrogen-corrected metabolizable energy (MEn). There were 3 replicates per treatment with time of processing as a blocking factor and treatment order randomized within each block. Cooled pellet samples were collected to determine pellet fines, standard pellet durability index (PDI), modified PDI, and Holmen NHP100. Pellet mill kW increased (P < 0.05) in pelleted Val + Ile diets compared to the control and Val diets. Pellet fines decreased (P < 0.01) and PDI increased (P < 0.01) as crystalline AA increased and added fat decreased in the diet. In conclusion, diets with increasing crystalline AA, Val, and Val + Ile, led to improved pellet quality which can be explained by the 0.4% or 0.6% reduction in added fat with increasing crystalline AA and balancing for MEn in the diet.