A breakthrough in macro-scale circularity and eco-efficiency assessment: A case study of OECD countries.

Countries' circularity performance and CO2 emissions should be addressed as a part of the UN net-zero Sustainable Development Goals (SDGs) 2030. Macro-scale circularity assessment is regarded as a helpful tool for tracking and adjusting nations' progress toward the sustainable Circular Economy (CE) and SDGs. However, practical frameworks are required to address the shortage of real-world circularity assessments at the macro level. The establishment of CE benchmarks is also essential to enhance circularity in less sustainable nations. Further, monitoring the extent to which nations' circularity activities are sustainable and in line with the SDGs is an area that lacks sufficient practical research. The current research aims to develop a macro-level framework and benchmarks for national sustainable circularity assessments. Methodologically, we develop a dynamic network data envelopment analysis (DN-DEA) framework for multi-period circularity and eco-efficiency assessment of OECD countries. To do so, we incorporate dual-role and bidirectional carryovers in our macro-scale framework. From a managerial perspective, we conduct a novel comparative analysis of the circularity and eco-efficiency of the nations to monitor macro-scale sustainable CE trends. Research results reveal a significant performance disparity in circularity, eco-efficiency, and benchmarking patterns. Accordingly, circularly efficient nations cannot necessarily be considered eco-friendly and sustainable. Although Germany (as a superior circular nation) can be regarded as a circularity benchmark, it cannot serve as an eco-efficiency benchmark for less eco-efficient nations. Hence, the new method allows decision-makers not only to identify the nations' circularity outcome but also to distinguish sustainable nations from less sustainable ones. This, on the one hand, provides policymakers with a multi-faceted sustainability analysis, beyond the previous unidimensional analysis. On the other, it proposes improvement benchmarks for planning and regulating nations' future circularity in line with real sustainability goals. The capabilities of our innovative approach are demonstrated in the case study.

Intravital imaging of the human cornea reveals the differential effects of season on innate and adaptive immune cell morphodynamics.

PURPOSE: While the external environment has been shown to shape the systemic human immune landscape, defining the in vivo immune status of peripheral tissues has remained a technical challenge. We recently developed functional in vivo confocal microscopy (Fun-IVCM) for dynamic, longitudinal imaging of corneal immune cells in living humans. This study investigated the effect of seasonal-driven environmental factors on the density, morphology and dynamic behavior of human corneal immune cell subsets. DESIGN: Longitudinal, observational clinical study. PARTICIPANTS: Sixteen healthy participants (18-40 years) attended two visits in distinct seasons in Melbourne, Australia (Visit 1: Spring/Summer: November-December 2021; Visit 2: Autumn/Winter: April-June 2022). METHODS: Environmental data were collected over each period. Participants underwent ocular surface examinations and corneal Fun-IVCM (Heidelberg HRT-3, Rostock Corneal Module). Volume scans (80µm) were acquired at 5.5±1.5 minute intervals, for up to five timepoints. Time-lapse videos were created to analyze corneal immune cells, comprising epithelial T cells and dendritic cells (DCs), and stromal macrophages. Tear cytokines were analyzed using multiplex bead-based immunoassay. MAIN OUTCOME MEASURES: Difference in the density, morphological and dynamic parameters of corneal immune cell subsets over the study periods. RESULTS: Visit 1 was characterized by higher temperature, lower humidity, and higher air particulate and pollen levels than Visit 2. Clinical ocular surface parameters, and the density of immune cell subsets were similar across visits. At Visit 1 (Spring/Summer), corneal epithelial DCs were larger and more elongated, with a lower dendrite probing speed (0.38±0.21 vs 0.68±0.33µm/min, p<0.001) relative to Visit 2; stromal macrophages were more circular and had less dynamic activity (Visit 1: 7.2±1.9 vs Visit 2: 10.3±3.7 'dancing index', p<0.001). T cell morphology and dynamics were unchanged across periods. Basal tear levels of IL-2 and CXCL10 were lower during Spring/Summer. CONCLUSION: This novel study shows that the in vivo morphodynamics of innate corneal immune cells (DCs, macrophages) are modified by environmental factors, but such effects are not evident for adaptive immune cells (T cells). The cornea is a potential non-invasive, in vivo 'window' to season-dependent changes to the human immune system, with capacity to yield new insight into environmental influences on immune regulation.

TIM-3+ CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies.

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (TPHEX), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ+ TPHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ+ TPHEX. We also observed IFN-γ+ TPHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19+ leukemia cells. An IFN-γ+ TPHEX gene signature was recapitulated in TEX cells from human cancers, including myeloma and lymphoma. Here, we characterize a TEX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional TEX found in chronic viral infections. Thus, IFN-γ+ TPHEX represent a potential target for immunotherapy of blood cancers.

Exponential growth of private coastal infrastructure influenced by geography and race in South Carolina, USA.

Homeowners in coastal environments often augment their access to estuarine ecosystems by building private docks on their personal property. Despite the commonality of docks, particularly in the Southeastern United States, few works have investigated their historical development, their distribution across the landscape, or the environmental justice dimensions of this distribution. In this study, we used historic aerial photography to track the abundance and size of docks across six South Carolina counties from the 1950s to 2016. Across our roughly 60-year study period, dock abundance grew by two orders of magnitude, mean length of newly constructed docks doubled, and the cumulative length of docks ballooned from 34 to 560 km. Additionally, we drew on census data interpolated into consistent 2010 tract boundaries to analyze the racial and economic distribution of docks in 1994, 1999, 2011, and 2016. Racial composition, measured as the percentage of a tract's population that was White, positively correlated with dock abundance in each year. Median household income and dock abundance were only correlated in 2011. Taken together, these metrics indicate the growing desire for direct estuary access, however, that access does not appear to be equally spread across racial groups. Because docks enhance estuarine access and demarcate private property, our study provides longitudinal insights into environmental justice concerns related to disparate private property ownership. We found a persistent correlation between the racial characteristics of an area and dock abundance, strongly indicating that White South Carolinians have had disproportionately greater private water access for the past two decades.

Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation.

Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective anti-leukemic effect post-HCT. We conducted a phase I clinical trial employing a novel TCR-T product targeting the minor H antigen HA-1 to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms. The primary objective was to evaluate the feasibility and safety of administration of HA-1 TCR-T post-HCT. CD8+ and CD4+ T cells expressing the HA-1 TCR and a CD8-co-receptor were successfully manufactured from HA-1 disparate HCT donors. One or more infusions of HA-1 TCR-T following lymphodepleting chemotherapy were administered to nine HCT recipients who had developed disease recurrence post-HCT. TCR-T cells expanded and persisted in vivo after adoptive transfer. No dose-limiting toxicities occurred. Although the study was not designed to assess efficacy, four patients achieved or maintained complete remissions following lymphodepletion and HA-1 TCR-T, with one ongoing at >2 years. Single-cell RNA sequencing of relapsing/progressive leukemia after TCR-T therapy identified upregulated molecules associated with T cell dysfunction or cancer cell survival. HA-1 TCR-T therapy appears feasible and safe and shows preliminary signals of efficacy. This clinical trial is registered at clinicaltrials.gov as NCT03326921.

IL-6-mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation.

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.

Lifileucel, an Autologous Tumor-infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1-6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung. The objective response rate was 21.4% (6/28). Responses occurred in tumors with profiles typically resistant to immunotherapy, such as PD-L1-negative, low tumor mutational burden, and STK11 mutation. Two responses were ongoing at the time of data cutoff, including one complete metabolic response in a PD-L1-negative tumor. Adverse events were generally as expected and manageable. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy.

Protocol for the isolation of the mouse sympathetic splanchnic-celiac-superior mesenteric ganglion complex.

Neurons that originate from pre-vertebral sympathetic ganglia, the splanchnic-celiac-superior mesenteric ganglion complex (SCSMG) in mouse, have important roles in control of organs of the upper abdomen. Here, we present a protocol for the isolation of the mouse sympathetic SCSMG. We describe steps for surgical incision, ganglia isolation, ganglia fine dissection, and whole-mount SCSMG after clearing-enhanced 3D (Ce3D) clearing method and immunohistochemistry. Given the importance of mice in studies of that control, this protocol aims to assist biomedical researchers in the dissection of the mouse SCSMG.

The transcription factor SpiB regulates the fibroblastic reticular cell network and CD8+ T-cell responses in lymph nodes.

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs. Conditional ablation of SpiB in FRCs impaired the FRC network in the T-cell zone of LNs, leading to reduced numbers of FRCs and altered homeostatic functions including reduced CCL21 and interleukin-7 expression. The size and cellularity of LNs remained intact in the absence of SpiB but the space between the reticular network increased, indicating that although FRCs were reduced in number they stretched to maintain network integrity. Following virus infection, antiviral CD8+ T-cell responses were impaired, suggesting a role for SpiB expression in FRCs in orchestrating immune responses. Together, our findings reveal a new role for SpiB as an important regulator of FRC functions and immunity in LNs.

Myelin Oligodendrocyte Glycoprotein Antibody Disease Optic Neuritis: A Structure-Function Paradox?

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a demyelinating disorder that most commonly presents with optic neuritis (ON) and affects children more often than adults. We report 8 pediatric patients with MOG-associated ON and characterize focal optical coherence tomography (OCT) abnormalities over time that help distinguish this condition from the trajectories of other demyelinating disorders. These OCT findings are examined in the context of longitudinal visual function testing. METHODS: This is a retrospective case series of 8 pediatric patients with MOG-associated ON who were referred for neuro-ophthalmic evaluation. Longitudinal data for demographics, clinical history, physical examination, and OCT obtained in the course of clinical evaluations were collected through retrospective medical record review. RESULTS: Patients demonstrated acute peripapillary retinal nerve fiber layer (RNFL) thickening in one or both eyes, consistent with optic disc swelling. This was followed by steady patterns of average RNFL thinning, with 9 of 16 eyes reaching significantly low RNFL thickness using OCT platform reference databases ( P < 0.01), accompanied by paradoxical recovery of high-contrast visual acuity (HCVA) in every patient. There was no correlation between HCVA and any OCT measures, although contrast sensitivity (CS) was associated with global thickness, PMB thickness, and nasal/temporal (N/T) ratio, and color vision was associated with PMB thickness. There was a lower global and papillomacular bundle (PMB) thickness ( P < 0.01) in clinically affected eyes compared with unaffected eyes. There was also a significantly higher N:T ratio in clinically affected eyes compared with unaffected eyes in the acute MOG-ON setting ( P = 0.03), but not in the long-term setting. CONCLUSIONS: MOG shows a pattern of prominent retinal atrophy, as demonstrated by global RNFL thinning, with remarkable preservation of HCVA but remaining deficits in CS and color vision. These tests may be better clinical markers of vision changes secondary to MOG-ON. Of the OCT parameters measured, PMB thickness demonstrated the most consistent correlation between structural and functional measures. Thus, it may be a more sensitive marker of clinically significant retinal atrophy in MOG-ON. The N:T ratio in acute clinically affected MOG-ON eyes in our study was higher than the N:T ratio of neuromyelitis optica (NMO)-ON eyes and similar to the N:T ratio in multiple sclerosis (MS)-ON eyes as presented in the prior literature. Therefore, MOG may share a more similar pathophysiology to MS compared with NMO.

Single high-energy arc proton therapy with Bragg peak boost (SHARP).

INTRODUCTION: Because of the co-location of critical organs at risk, base of skull tumours require steep dose gradients to achieve the prescribed dosimetric criteria. When available, proton beam therapy (PBT) is often considered a desirable modality for these cases, but in many instances, compromises in target coverage are still required to achieve critical organ at risk (OAR) tolerance doses. A number of techniques have been proposed to further improve the penumbra of PBT. In the current study, we propose a novel, collimator-free treatment planning technique that combines high-energy shoot-through proton beams with conventional Bragg peak spot placement. The small spot size of the high-energy pencil beams provides a sharp penumbra at the target boundary, and the Bragg peak spots provide a higher linear energy transfer (LET) boost to the target centre. METHODS: Three base of skull chordoma patients were retrospectively planned with three different PBT treatment planning techniques: (1) conventional intensity-modulated proton therapy (IMPT); (2) high-energy proton arc therapy (HE-PAT); and (3) the novel technique combining HE-PAT and IMPT, referred to as single high-energy arc with Bragg peak boost (SHARP). The Monaco 6 treatment planning system was used. RESULTS: SHARP was found to improve the PBT penumbra in the plane perpendicular to the HE-PAT beams. Minimal penumbra differences were observed in the plane of the HE-PAT beams. SHARP reduced dose-averaged LET to surrounding organs at risk. CONCLUSION: A novel PBT treatment planning technique was successfully implemented. Initial results indicate the potential for SHARP to improve the penumbra of PBT treatments for base of skull tumours.

Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks.

The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.

Long-term follow-up of acceptance-enhanced behavior therapy for trichotillomania.

Acceptance-enhanced behavior therapy for trichotillomania (AEBT-TTM) is effective in reducing trichotillomania (TTM) symptoms, but the durability of treatment effects remains in question. This study analyzed 6-month follow-up data from a large randomized clinical trial comparing AEBT-TTM to an active psychoeducation and supportive therapy control (PST). Adults with TTM (N=85; 92% women) received 10 sessions of AEBT-TTM or PST across 12 weeks. Independent evaluators assessed participants at baseline, post-treatment, and 6 months follow-up. For both AEBT-TTM and PST, self-reported and evaluator-rated TTM symptom severity decreased from baseline to follow-up. TTM symptoms did not worsen from post-treatment to follow-up. At follow-up, AEBT-TTM and PST did not differ in rates of treatment response, TTM diagnosis, or symptom severity. High baseline TTM symptom severity was a stronger predictor of high follow-up severity for PST than for AEBT-TTM, suggesting AEBT-TTM may be a better option for more severe TTM. Results support the efficacy of AEBT-TTM and show that treatment gains were maintained over time. Although AEBT-TTM yielded lower symptoms at post-treatment, 6-month follow-up outcomes suggest AEBT-TTM and PST may lead to similar symptom levels in the longer term. Future research should examine mechanisms that contribute to long-term gain maintenance.

Accessory Extensor Pollicis Longus Tendon Incidentally Discovered During Dorsal Distal Radius Plating.

Anatomical variations of the extensor pollicis longus (EPL) tendon are rare. Variations are typically asymptomatic, yet knowledge of these variations poses significance in the setting of dorsal approaches to wrist surgery. We present a case of an accessory EPL tendon that was discovered intraoperatively in the fourth dorsal compartment during open repair of a distal radius fracture with a dorsal spanning plate. If not correctly identified, the accessory EPL could have been entrapped beneath the plate, resulting in limited thumb extension and potentially tendon rupture.

Relapsing White Matter Disease and Subclinical Optic Neuropathy: From the National Multiple Sclerosis Society Case Conference Proceedings

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Increasing trend in Brazilian Jiu Jitsu injuries presenting to U.S. emergency departments - a 10-year analysis and injury profile.

OBJECTIVE: Evaluate injury trends in Brazilian Jiu Jitsu (BJJ) participation by presenting to U.S. emergency departments over a 10-year period and formulate an injury profile. METHODS: The U.S. Consumer Product Safety Commission's (CPSC) National Electronic Injury Surveillance System (NEISS) database was queried for martial arts related injuries from 1 January 2012 to 31 December 2021. Codes and narratives were examined to compile data for patients sustaining BJJ-related injuries. RESULTS: From 1 January 2012 to 31 December 2021 there were 7,722 (NE = 282,315) ED-diagnosed martial arts related injuries with 911 (NE = 36,023) BJJ-related injuries identified. Regression analysis demonstrated an increasing trend in the annual incidence of Brazilian Jiu Jitsu injuries presenting to the ED (R2 = 0.934; SE = 2.069: p < .0001). Average age was 25.68 years of age (range 4-83). The most common injury diagnoses were sprains/strains and other/not listed at 27.68% and 26.39%. The most commonly injured body parts were the upper trunk, and the shoulder comprising 13.66% and 12.14% of injured body parts, respectively. The most commonly fractured region was toes, at 14.15% of all fractures. The most common dislocations occurred at the shoulder and knee, at 32.49% and 28.45% of dislocations, respectively. The most common mechanisms of injury specifically identified were indeterminate contact between players, fall onto ground, or fall onto another player comprising 18.62% and 17.17%, of injuries, respectively. CONCLUSION: There was an increasing trend of BJJ-related injuries presenting to U.S. Emergency Departments. The most common diagnoses and body parts injured were sprains/strains and upper trunk and shoulder, respectively. The most commonly fractured and dislocated regions were toes and shoulder, respectively. The most common mechanisms of injury were indeterminate contact or falling. This study provides novel information concerning trends in injury and injury profiles for Brazilian Jiu Jitsu related injuries.

Dosimetric comparison of gantry and horizontal fixed-beam proton therapy treatment plans for base of skull chordoma.

INTRODUCTION: Australia's first proton beam therapy (PBT) centre will house a fixed-beam room and two gantry rooms. As the only PBT facility in Australia for at least the short term, there is a need to efficiently allocate treatment appointments between the gantry and fixed-beam rooms. This planning study assesses the dosimetric differences between fixed-beam and gantry-based treatment plans for base of skull chordoma, one of the core indications likely to be referred for PBT in Australia. METHODS: Retrospective gantry-based and fixed-beam treatment plans were generated for five patients with base of skull chordoma. Fixed-beam plans were generated with a conventional horizontal patient positioning system. Robust intensity modulated proton therapy (IMPT) optimisation and evaluation techniques were used for both delivery systems. Plans were designed to maximise target coverage while adhering to maximum dose constraints to neighbouring critical organs at risk. RESULTS: Robust target coverage and integral dose were found to be approximately equivalent for the gantry-based and fixed-beam plans. Doses to specific organs at risk could be reduced with the gantry-based geometry; however, the gantry-based plans did not exhibit a general decrease in doses to organs at risk. CONCLUSION: A fixed-beam treatment plan was found to be non-inferior to a gantry-based treatment plan for all base of skull patients included in the current study.