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Abstract Image-based deformation estimation is an important tool used in a variety of engineering problems, including crack propagation, fracture, and fatigue failure. These tools have been important in biomechanics research where measuring in vitro and in vivo tissue deformations are important for evaluating tissue health and disease progression. However, accurately measuring tissue deformation in vivo is particularly challenging due to limited image signal-to-noise ratio. Therefore, we created a novel deep-learning approach for measuring deformation from a sequence of images collected in vivo called StrainNet. Utilizing a training dataset that incorporates image artifacts, StrainNet was designed to maximize performance in challenging, in vivo settings. Artificially generated image sequences of human flexor tendons undergoing known deformations were used to compare benchmark StrainNet against two conventional image-based strain measurement techniques. StrainNet outperformed the traditional techniques by nearly 90%. High-frequency ultrasound imaging was then used to acquire images of the flexor tendons engaged during contraction. Only StrainNet was able to track tissue deformations under the in vivo test conditions. Findings revealed strong correlations between tendon deformation and applied forces, highlighting the potential for StrainNet to be a valuable tool for assessing rehabilitation strategies or disease progression. Additionally, by using real-world data to train our model, StrainNet was able to generalize and reveal important relationships between the effort exerted by the participant and tendon mechanics. Overall, StrainNet demonstrated the effectiveness of using deep learning for image-based strain analysis in vivo.

Mechanical testing is a valuable tool for assessing intervertebral disc health, but the wide range of testing protocols makes it difficult to compare results from different studies. Normalizing mechanical properties by disc geometry allows for such comparisons, but there is little consistency in the methods by which disc geometry is measured. As such, we hypothesized that methods used to measure disc geometry would impact reported mechanical properties. Disc height and area were measured using computed tomography (CT), digital calipers, and ImageJ to yield three different measurements for disc height and six for disc area. Disc heights measured by digital calipers ex situ were >30% less than disc heights measured in situ by CT, and disc areas measured ex situ using ImageJ were >30% larger than those measured by CT. This significantly affected reported mechanical properties, leading to a 65% reduction in normalized compressive stiffness in the most extreme case. Though we cannot quantitatively correct between methods, results presented in this study suggest that disc geometry measurement methods have a significant impact on normalized mechanical properties and should be accounted for when comparing results.

The intervertebral disc is a complex structure that experiences multiaxial stresses regularly. Disc failure through herniation is a common cause of lower back pain, which causes reduced mobility and debilitating pain, resulting in heavy socioeconomic burdens. Unfortunately, herniation etiology is not well understood, partially due to challenges in replicating herniation in vitro. Previous studies suggest that flexion elevated risks of herniation. Thus, the objective of this study was to use a multiscale and multiphasic finite element model to evaluate the risk of failure under torque- or muscle-driven flexion. Models were developed to represent torque-driven flexion with the instantaneous center of rotation (ICR) located on the disc, and the more physiologically representative muscle-driven flexion with the ICR located anterior of the disc. Model predictions highlighted disparate disc mechanics regarding bulk deformation, stress-bearing mechanisms, and intradiscal stress-strain distributions. Specifically, failure was predicted to initiate at the bone-disc boundary under torque-driven flexion, which may explain why endplate junction failure, instead of herniation, has been the more common failure mode observed in vitro. By contrast, failure was predicted to initiate in the posterolateral annulus fibrosus under muscle-driven flexion, resulting in consistent herniation. Our findings also suggested that muscle-driven flexion combined with axial compression could be sufficient for provoking herniation in vitro and in silico. In conclusion, this study provided a computational framework for designing in vitro testing protocols that can advance the assessment of disc failure behavior and the performance of engineered disc implants.

Abstract Background A precipitous decline in health status among people recently released from prison is common. In Victoria, Australia, opioid agonist treatment (OAT) in the community involves frequent contact with primary care, potentially facilitating broader use of primary healthcare services. Among a cohort of men who injected drugs regularly pre-imprisonment, we estimated differences in rates of primary healthcare use and medication dispensation between people who did and did not receive OAT post-release. Methods Data came from the Prison and Transition Health Cohort Study. Three-month post-release follow-up interviews were linked with primary care and medication dispensation records. Generalised linear models were fit with one exposure (OAT: none/partial/complete) for 13 outcomes relating to primary healthcare use, pathology testing, and medication dispensation, adjusted for other covariates. Coefficients were reported as adjusted incidence rate ratios (AIRR). Results Analyses included 255 participants. Compared to no OAT use, both partial and complete OAT use were associated with increased rates of standard (AIRR: 3.02, 95%CI: 1.88–4.86; AIRR: 3.66, 95%CI: 2.57–5.23), extended (AIRR: 2.56, 95%CI: 1.41–4.67; AIRR: 2.55, 95%CI: 1.60–4.07) and mental health-related (AIRR: 2.71, 95%CI: 1.42–5.20; AIRR: 2.27, 95%CI: 1.33–3.87) general practitioner (GP) consultations, total medication (AIRR: 1.88, 95%CI: 1.19–2.98; AIRR: 2.40, 95%CI: 1.71–3.37), benzodiazepine (AIRR: 4.99, 95%CI: 2.81–8.85; AIRR: 8.30, 95%CI: 5.28–13.04) and gabapentinoid (AIRR: 6.78, 95%CI: 3.34–13.77; AIRR: 4.34, 95%CI: 2.37–7.94) dispensations, respectively. Partial OAT use was also associated with increased after-hours GP consultations (AIRR: 4.61, 95%CI: 2.24–9.48) and complete OAT use? with increased pathology utilisation (e.g. haematological, chemical, microbiological or immunological tissue/sample testing; AIRR: 2.30, 95%CI: 1.52–3.48). Conclusion We observed higher rates of primary healthcare use and medication dispensation among people who reported partial and complete OAT use post-release. Findings suggest that access to OAT post-release may have a collateral benefit in supporting broader health service utilisation, underscoring the importance of retention in OAT after release from prison.

Abstract Background Australian needle and syringe distribution occurs via a mix of modalities, including syringe dispensing machines (SDMs). SDMs are electronic vending machines providing (often) 24-h access to needles/syringes and may attract greater numbers of people who are younger, female, and/or have limited connection to health care services compared to individuals accessing fixed-site needle and syringe programs (NSPs). However, validating the demographic characteristics of SDM clients has proven difficult in previous research. Methods In this paper, we analyse SDM order and client demographic data from four SDMs located in South-East Melbourne, Australia, and compare this against the managing fixed-site NSP between May 2017 and December 2020. SDM data were collected via a novel 0–9 numeric keypad input tool. Via the tool, SDM clients were requested to input their categorised age, gender and postcode. Given the novelty of the tool, we evaluate the feasibility of the data collection method. We analysed data according to: (1) total SDM orders made, (2) estimated ‘unique SDM presentations’ and (3) describing the demographics of unique SDM clients. Importantly, we noted substantial invalid demographic data, and consequently, severely restricted data for analysis. Results There were 180,989 SDM orders made across the four SDMs to an estimated 90,488 unique SDM presentations. There was little variation in unique presentations across days of the week, but 69% occurred out of NSP operating hours. Across the study period, the SDMs distributed 66% of the number of syringes distributed by the fixed-site NSP. Due to invalid demographic data, our restriction method provided only 10,914 (6% of all data) unique presentations for analysis. There were some demographic differences between SDM and NSP client, but these should be treated with caution. Conclusions The data collection tool provides a novel means of comparing SDM and fixed-site presentations, demonstrating the substantial expansion of service via the SDMs. However, the validity of the demographic data was highly questionable and requires significant data coding, meaning it is not feasible for community NSPs. While we recommend the inclusion of automatically collected SDM order data, the use of a 0–9 numeric keypad to collect demographic data—while an innovation—requires alteration to support NSP data.

Abstract Background Australian harm reduction services are provided via a mix of modalities, including fixed-site needle and syringe programmes (NSP) and syringe-dispensing machines (SDMs). SDMs are cost-effective and provide 24-h anonymous access to needles/syringes, often to underserved geographic areas, and can attract clientele who may choose not to use NSPs. The introduction of COVID-19 control measures saw disruptions and adaptations to the provision of harm reduction services. It is possible that SDMs filled the gap in otherwise disrupted harm reduction services in Melbourne. In this paper, we use data from four SDMs and an NSP to explore changes to harm reduction usage during periods of COVID-19 lockdowns in Melbourne, Australia, in 2020. Methods Our data span September 2017–December 2020. We analysed daily counts of SDM use and monthly counts of NSP use, according to unique presentations to both. Auto-regressive integrated moving average (ARIMA) time-series models were fitted to the data with the effects of lockdowns estimated via a step function. Results Across the study period, we estimated 85,851 SDM presentations and 29,051 NSP presentations. Usage across both the SDMs and the NSP declined during the COVID-19 lockdowns, but only the decline in SDM usage was significant in ARIMA analysis. Conclusions The slight, but significant decline in SDM use suggests barriers to access, though this may have been mitigated by SDM users acquiring needles/syringes from other sources. The decline, however, may be a concern if it led to lowered needle/syringe coverage and a subsequent increase in injecting risk. Further work is needed to properly explore potential changes in preference for needle/syringe acquisition site and associated barriers. Importantly, this work adds to the body of literature around the impacts of COVID-19 on harm reduction provision and potential areas of improvement.

Abstract Mechanical testing is a valuable tool for assessing intervertebral disc health, but the wide range of testing protocols makes it difficult to compare results from different studies. Normalizing mechanical properties by disc geometry allows for such comparisons, but there is little consistency in the methods by which disc geometry is measured. As such, we hypothesized that methods used to measure disc geometry would impact reported mechanical properties. Disc height and area were measured using computed tomography (CT), digital calipers, and ImageJ to yield three different measurements for disc height and six for disc area. Disc heights measured by digital calipers ex situ were >30% less than disc heights measured in situ by CT, and disc areas measured ex situ using ImageJ were >30% larger than those measured by CT. This significantly affected reported mechanical properties, leading to a 65% reduction in normalized compressive stiffness in the most extreme case. Though we cannot quantitatively correct between methods, results presented in this study suggest that disc geometry measurement methods have a significant impact on normalized mechanical properties and should be accounted for when comparing results.

Solid‐state emission is pivotal for the functionality of organic compounds in opto‐electronic applications. Yet, tailoring the emission characteristics of existing solid‐state emissive organic frameworks is a challenging task, primarily due to their intricate structure‐activity interplay. In this study, an innovative family of solid‐state luminogens, centered around the dibenzosuberenylidene core are introduced. These luminogens are characterized by a remarkable excited‐state aromatization‐induced structural planarization (ESAISP) behavior. This unique feature allows for the modulation of their fluorescence properties, including color and intensity, through simple structural alterations, opening new avenues in the development of organic advanced functional materials. [ABSTRACT FROM AUTHOR]

Image-based deformation estimation is an important tool used in a variety of engineering problems, including crack propagation, fracture, and fatigue failure. These tools have been important in biomechanics research where measuring in vitro and in vivo tissue deformations are important for evaluating tissue health and disease progression. However, accurately measuring tissue deformation in vivo is particularly challenging due to limited image signal-to-noise ratio. Therefore, we created a novel deep-learning approach for measuring deformation from a sequence of images collected in vivo called StrainNet. Utilizing a training dataset that incorporates image artifacts, StrainNet was designed to maximize performance in challenging, in vivo settings. Artificially generated image sequences of human flexor tendons undergoing known deformations were used to compare benchmark StrainNet against two conventional image-based strain measurement techniques. StrainNet outperformed the traditional techniques by nearly 90%. High-frequency ultrasound imaging was then used to acquire images of the flexor tendons engaged during contraction. Only StrainNet was able to track tissue deformations under the in vivo test conditions. Findings revealed strong correlations between tendon deformation and applied forces, highlighting the potential for StrainNet to be a valuable tool for assessing rehabilitation strategies or disease progression. Additionally, by using real-world data to train our model, StrainNet was able to generalize and reveal important relationships between the effort exerted by the participant and tendon mechanics. Overall, StrainNet demonstrated the effectiveness of using deep learning for image-based strain analysis in vivo. [ABSTRACT FROM AUTHOR]

Loot boxes are a popular mechanic within many video games, but it remains unclear if some forms of loot boxes can be seen of as gambling. However, the perspectives of players are often neglected, such as whether they see them as ‘fair’ game elements and how closely they feel this aligns with gambling. In this paper, we synthesise a conceptualisation for loot boxes through players’ actual experience and explore if there are any parallels with gambling. Twenty-one participants who played video games took part in the research through either an interview or online survey. Thematic analysis suggested that six themes were core to exploring loot boxes: Random Chance Effects, Attitudes Towards Content, Implementation, Parallels with Gambling, Game Design, and The Player. The results suggested both indirect and direct parallels with gambling from the players experiences. Implications of game design and classifying loot boxes as gambling are discussed in relation to game design and risk factors of gambling and purchasing behaviour.

The influence of resource availability on ecosystem function varies spatially and temporally, among and within ecosystems. Dramatic shifts in moisture‐driven resources can drive bottom‐up effects on animal behaviours and distributions. Further, complexity arises when landscapes are influenced by large mammalian grazers and predator‐induced trophic cascades, such as those mediated by the dingo (Canis familiaris (Dingo)) in the eastern arid Strzelecki Desert in Australia. During the driest two‐year period on record for this region, we investigated the persistence of avian communities associated with structurally distinct dunes and swale habitats, and across two different land management regimes (pastoral land with livestock and dingoes, and Sturt National Park managed for conservation without these animals). We grouped all birds into dietary functional groups to infer patterns of habitat use associated with available resources. We also compared incidental observations of the 'winter' bird community in part of the study region between the extended dry period of 2018/2019 and wet period of 2020/2021. Despite habitat partitioning, the avian community did not differ between land management regimes except in species richness during the dry period, likely driven by the low numbers of birds present during the surveys. Incidental observations indicated that insectivorous and omnivorous species dominated the bird community in the dry period, with granivorous species forming a greater proportion of the bird community during wet times. Birds with completely or partially insectivorous diets dominated avian species composition on surveys in the dry period, but there were distinct structural vegetation associations among functional groups, indicating that heterogeneity in vegetation structure was likely important for the conservation of refuges, which enable the persistence of avifauna during extended dry periods. Distinct habitat type, structure and available resources shaped avian communities in this landscape, during the extremely resource‐limited extended dry period, with implications for conservation and management, particularly given the increasing drying effects of climate change. [ABSTRACT FROM AUTHOR]

Background: Australian harm reduction services are provided via a mix of modalities, including fixed-site needle and syringe programmes (NSP) and syringe-dispensing machines (SDMs). SDMs are cost-effective and provide 24-h anonymous access to needles/syringes, often to underserved geographic areas, and can attract clientele who may choose not to use NSPs. The introduction of COVID-19 control measures saw disruptions and adaptations to the provision of harm reduction services. It is possible that SDMs filled the gap in otherwise disrupted harm reduction services in Melbourne. In this paper, we use data from four SDMs and an NSP to explore changes to harm reduction usage during periods of COVID-19 lockdowns in Melbourne, Australia, in 2020. Methods: Our data span September 2017–December 2020. We analysed daily counts of SDM use and monthly counts of NSP use, according to unique presentations to both. Auto-regressive integrated moving average (ARIMA) time-series models were fitted to the data with the effects of lockdowns estimated via a step function. Results: Across the study period, we estimated 85,851 SDM presentations and 29,051 NSP presentations. Usage across both the SDMs and the NSP declined during the COVID-19 lockdowns, but only the decline in SDM usage was significant in ARIMA analysis. Conclusions: The slight, but significant decline in SDM use suggests barriers to access, though this may have been mitigated by SDM users acquiring needles/syringes from other sources. The decline, however, may be a concern if it led to lowered needle/syringe coverage and a subsequent increase in injecting risk. Further work is needed to properly explore potential changes in preference for needle/syringe acquisition site and associated barriers. Importantly, this work adds to the body of literature around the impacts of COVID-19 on harm reduction provision and potential areas of improvement. [ABSTRACT FROM AUTHOR]

Background: Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature., Methods: We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022., Results: The median age was 46 years old (range: 25.6-50). Most patients fell into the R-ISS II category (72.7%), and 24.1% had high-risk cytogenetics. The majority of patients (89.9%) received a proteasome inhibitor-based first-line treatment, 92.1% received a stem cell transplant, and 65.6% had maintenance therapy post-autologous stem cell transplant (ASCT). Median follow-up from initial treatment to patients' last follow-up was 48.5 (range: 0-155) months. Median progression-free survival (PFS) was 45.0 months (95% CI: 40.2-50.0). Maintenance therapy post-ASCT improved median PFS to 52.3 months (95% CI: 43.1-68.2), compared to 23.6 months (95% CI: 20.0-34.8) without maintenance [p < 0.001]., Conclusion: Although the overall survival has not yet been reached in this young population, our reported median PFS of only 45 months highlights the urgent need to develop innovative treatments to induce more profound and durable responses., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Talquetamab is the first GPRC5D-targeting bispecific antibody approved for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). This matching-adjusted indirect comparison (MAIC) study was conducted to compare the effectiveness of talquetamab vs selinexor-dexamethasone (sel-dex) and vs belantamab mafodotin (belamaf) in patients with TCE RRMM., Methods: An unanchored MAIC was performed using individual patient-level data from patients treated with subcutaneous talquetamab 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W) from MonumenTAL-1 (NCT03399799/NCT04636552) and published summary data for sel-dex from STORM (NCT02336815) and belamaf from DREAMM-2 (NCT0325678). Patients from MonumenTAL-1 who met key eligibility criteria for STORM and DREAMM-2 were included. Outcomes of interest were overall response rate (ORR), complete response or better (≥CR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS)., Results: After adjustment for cross-trial differences, patients treated with both dosing schedules of talquetamab showed significantly better ORR, ≥CR, and DOR vs sel-dex and significantly higher ORR and ≥ CR vs belamaf; DOR was relatively similar to belamaf. PFS was significantly improved with talquetamab Q2W and numerically in favor of talquetamab QW vs sel-dex and significantly improved with both dosing schedules of talquetamab vs belamaf. OS was significantly improved with both dosing schedules of talquetamab vs sel-dex and was numerically in favor of both dosing schedules of talquetamab vs belamaf., Conclusion: These analyses show superior effectiveness of both talquetamab dosing schedules vs sel-dex and vs belamaf for most outcomes and highlight talquetamab as an effective treatment option for patients with TCE RRMM.

Given the early use of triplet and quadruplet regimens, most patients with multiple myeloma (MM) will be exposed and/or refractory to PIs, IMiDs, and anti-CD38 mAbs after first- or second-line treatment. Effective treatment for this group of triple class exposed/refractory (TCE/R) patients is crucial. Here we present a post-hoc subgroup analysis of TCE/R patients treated on the ALGONQUIN study of belantamab mafodotin plus pomalidomide-dexamethasone (belamaf-Pd) for relapsed MM. Of the 99 patients treated on the ALGONQUIN study, 69 were TCE and 56 were TCR and were included in this analysis. Patients had a median of three prior lines of therapy. The ORR was 86.4% in TCE patients and 84.9% in TCR patients, with ≥ very good partial response rates of 64% and 68% respectively. The median progression free survival was 18.3 months in TCE patients and 19.6 months in TCR patients, with overall survival not yet reached and 34.4 months, respectively for TCE and TCR patients. No new safety signals were identified. The most common Grade ≥ 3 AEs were keratopathy (48%), decreased visual acuity (42%), neutropenia (36%), thrombocytopenia (27%), and infection (25%). In this subgroup analysis of the ALGONQUIN study, patients with TCE/TCR disease treated with belamaf-Pd achieved high clinical response rates with durable remissions, comparable to other novel therapeutics in this space., (© 2024. The Author(s).)

In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial. This is particularly true in the era of novel agent induction and post-transplant maintenance therapy. The aim of this study was to use the Canadian Myeloma Research Group database and examine a large cohort of real-world patients comparing the outcomes of tandem versus single ASCT specifically in high-risk patients receiving novel agent-based induction and post-transplant maintenance. The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with MM. High-risk cytogenetics was defined as presence of del17p, t(4;14), or t(14;16). Those receiving allogeneic transplant were excluded. Tandem transplantation was defined as a second ASCT performed consecutively without interim relapse or progression after first ASCT. Those with relapse or progressive disease within 3 months of completing a first transplant were excluded. We compared response depth, progression-free, and overall survival (OS) based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. A total of 381 patients with high-risk cytogenetics were identified. A total of 242 received single and 139 patients received tandem transplants. All received post-transplant maintenance. The most common induction regimen for these patients was cyclophosphamide, bortezomib, and steroids (CyBorD, 87%). Forty-one patients (10.8%) required reinduction prior to first ASCT. The best overall responses at any time were 98.3% (90.5% ≥ very good partial response [VGPR]) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups, respectively. Survival outcomes were similar with the median progression-free survival for single or tandem ASCT of 35.2 and 35.3 months (P = .88) and the median OS were 92.6 and 88.9 months, respectively (P = .72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. In the real-world setting, tandem ASCT does not improve outcomes for MM patients with high-risk cytogenetics. This may be driven by the use of effective pre- and post-ASCT therapies. The development of more potent induction and consolidation along with current nearly ubiquitous continuous maintenance therapies until disease progression does not support the use of a second high-dose procedure., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)