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While vasculopathies are a known complication of radiation therapy, the exact mechanism and dose-dependency of damage are not fully understood. Several published studies have tried to identify a relationship between carotid artery radiation dose and subsequent stenosis, but dosimetric parameters predictive of this outcome remain unclear. The purpose of this study is to generate hypotheses about the relationship between clinical factors and risk of carotid stenosis and carotid events (TIA and CVA) in patients who received radiotherapy to the neck. A retrospective case-control study was performed, by identifying patients who had received head and neck RT and subsequently underwent screening carotid ultrasounds. Of these patients, those with carotid stenosis on post-RT ultrasounds were compared to patients without stenosis. Data from the cohort were analyzed to assess the association between clinical and carotid dosimetric variables and carotid stenosis severity as well as the occurrence of carotid events. Logistic regression was employed to explore factors contributing to carotid events, while linear regression was used to evaluate severity scores. Univariate and multivariate analyses were conducted to identify significant predictors. Among the patients who had carotid stenosis post RT, only a small proportion experienced carotid events (7/43). No dosimetric variables (max carotid dose, mean carotid dose, dose to relative and absolute volumes of carotid) were correlated with carotid events or carotid stenosis severity. Logistic regression revealed age as the sole statistically significant variable associated with carotid events (p = 0.02). For severity scores, univariate analyses identified several significant predictors: patient age was significantly correlated with left- and right-sided carotid stenosis severity after RT (p = 0.001 and 0.02 respectively), but pre-existing carotid artery calcifications on either side of the neck were significantly correlated with only the severity of left-sided stenosis after RT, via linear regression (r = 0.44 for calcifications on the left side (p = 0.05) vs r = 0.57 for the right (p = 0.01)). These findings suggest that patient age prior to neck RT may increase the risk of carotid events, whereas pre-existing calcifications are associated with the severity of carotid stenosis on the left side. Previous studies have shown that left carotids have a higher prevalence of intraplaque hemorrhage than the right; further research is needed to clarify possible mechanisms of the asymmetrical impact of prior calcifications on post-RT carotid stenosis. While we did not identify any dosimetric variables associated with post-RT carotid stenosis or carotid events, clinical factors such as age and pre-existing calcifications may help identify patients at risk, and could be used to tailor surveillance. [ABSTRACT FROM AUTHOR]

Despite advancements in the treatment of high-risk neuroblastoma, overall survival (OS) remains poor in patients who experience relapse after multimodal upfront therapy. Few studies have investigated outcomes in this cohort. Our study aims to characterize clinical outcomes for patients with relapsed high-risk neuroblastoma following definitive upfront treatment and identify factors that are associated with OS. This study was a multi-institutional retrospective cohort analysis of patients who had relapsed high-risk neuroblastoma after definitive upfront treatment, including ≥1 autologous stem cell transplant and external beam radiation therapy. Follow-up time was defined as time from the end of radiotherapy. Kaplan-Meier methods and log-rank test were used to assess OS. Cox proportional hazards models were used for univariate (UVA) and multivariable (MVA) analyses. All continuous variables were dichotomized at the median of the cohort for UVA and MVA. We identified 87 patients with relapsed high-risk neuroblastoma after upfront definitive treatment with 25 experiencing local or local and distant relapse (LLDR) and 62 experiencing distant-only relapse. The median age at diagnosis for the LLDR cohort was 3.54 years (range = 0.56-15.18) and 3.75 years for the distant-only cohort (range = 0.62-19.73). Patients with LLDR had higher rates of MYCN amplification compared to patients with distant-only relapse (66.7% vs. 34.5%, p = 0.038), with no differences in other variables. The median time to first relapse was 1.74 years (range = 0.61-4.38) for the LLDR cohort and 2.03 years (0.71-10.05) for the distant-only relapse cohort. At time of relapse, similar proportions of LLDR and distant-only relapse patients received chemotherapy (88.0% vs. 91.2%, p = 0.684), but the receipt of radiotherapy (33.3% vs. 61.7%, p = 0.049) and surgery (28.0% vs. 5.1%, p = 0.005) was significantly different between the two groups. Patients with LLDR had decreased median OS with a trend to significance (1.05 vs. 1.68 years, p = 0.056). On UVA, age at first recurrence (HR = 0.59, 95% CI = 0.36-0.98, p<0.05) and time to relapse (HR = 0.48, 95% CI = 0.29-0.81, p<0.05) were significant predictors of OS. On MVA, time relapse was a significant predictor of OS (HR = 0.53, 95% CI = 0.31-0.92, p<0.05) when controlling for recurrence type (LLDR vs. distant-only) and age at diagnosis. Longer time to first relapse is associated with improved OS in patients with relapsed high-risk neuroblastoma. There is a trend for patients with local relapse to have decreased OS. Future prospective studies are needed to confirm these findings and identify novel therapies to improve outcomes for patients with relapsed high-risk neuroblastoma. [ABSTRACT FROM AUTHOR]

During the COVID crisis, the incidence of food insecurity worsened around the globe. We were reminded that: food insecurity existed before COVID, worsened during this crisis, and will unfortunately be a persistent phenomenon in the post-COVID world. It is evident that to counter this public health threat, systematic changes will need to happen. In this short communication, we introduce the notion of a systems-oriented framework that can guide appropriate actions for us to disrupt future food insecurity crises. This short communication identifies preliminary observations based on relevant past studies that documented the impact of COVID-19 on food insecurity, and the researchers' conceptualization of a framework on how we may address future crisis-driven food insecurity challenges. Systems-oriented framework was conceptualized based on preliminary observations in studies that investigated food insecurity during the COVID-19 pandemic. This short communication explores the notion of a systems-oriented framework as a guide to future action to prevent crisis-driven food insecurity. The systems-oriented framework emphasizes the importance of action across macro, meso, and micro levels, and synchronization to maximize synergies. [ABSTRACT FROM AUTHOR]

The temperature-dependent (T -dependent) linewidth (Γ G) and frequency shift (Δ ω G) of the G mode provide valuable information on the phonon anharmonicity of graphene-based materials. In contrast to the negligible contribution from electron-phonon coupling (EPC) to the linewidth of a Raman mode in semiconductors, Γ G in pristine graphene is dominated by EPC contribution at room temperature due to its semimetallic characteristics. This leads to difficulty in resolving intrinsic contribution from phonon anharmonicity to Γ G. Here, we probed the intrinsic phonon anharmonicity of heavily-doped graphene by T -dependent Raman spectra based on FeCl 3 -based stage-1 graphite intercalation compound (GIC), in which the EPC contribution is negligible due to the large Fermi level (E F) shift. The Δ ω G and Γ G exhibit a nonlinear decrease and noticeable broadening with increasing temperature, respectively, which are both dominated by phonon anharmonicity processes. The contribution of phonon anharmonicity to Γ G of heavily-doped graphene decreases as the E F approaches to the Dirac point. However, the T dependence of Δ ω G is almost independent on E F and qualitatively agrees with the theoretical result of pristine graphene. These results provide a deeper understanding of the role of phonon anharmonicity on the Raman spectra of heavily doped graphene. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection.Design: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP.Results: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings.Conclusion: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values. [ABSTRACT FROM AUTHOR]

Standard of care radiotherapy for locally advanced cervical cancer includes large margins to ensure the uterocervix remains within the treatment fields over the course of treatment. Daily online cone-beam adaptive radiotherapy corrects for interfractional changes by adjusting the plan to match the target position during each treatment session, thus allowing for significantly reduced clinical target volume (CTV) to planning target volume (PTV) margins. We hypothesise that reduced margins from daily online adaptive radiotherapy will reduce organ at risk dose without compromising target coverage. Ten patients with cervical cancer (stage IIB–IIIC2) were treated with definitive chemoradiation using daily online cone-beam adaptive radiotherapy in 25–27 fractions. Initial and all adapted treatment plans were generated with CTV to PTV margins versus standard of care image-guided radiotherapy (IGRT) plans as follows: cervix/uterus/gross tumour volume (0.5 versus 1.5 cm), parametria/vagina (0.5 versus 1.0 cm) and nodal chains and gross nodes (0.5 versus 0.5 cm). IGRT plans were created and copied to synthetic computed tomography scans and contours generated from each daily adapted fraction. The dosimetry of each clinically treated online adapted fraction was compared with emulated IGRT plans. Statistical significance was defined as P < 0.05. Daily online cone-beam adaptive radiotherapy significantly improves bowel bag dosimetry compared with IGRT, with a reduction in V40 by an average of 91.3 cm3 [V40 (–6.2%) and V45 (–6.1%)]. The daily adapted plans showed significant improvements in bladder and rectum [V40 (–25.2% and –36.0%) and V30 (–9.7% and –17.1%), respectively]. Additionally, bone marrow had a significantly reduced dose [V10 (–2.7%) and V20 (–3.3%)]. Daily online cone-beam adaptive radiotherapy improved uterocervix CTV coverage and reduced hotspots compared with IGRT [D95% (+1.6%) and Dmax (–0.9%)]. Reduced CTV to PTV margins achievable with daily online adaptive radiotherapy improves organ at risk dosimetry and target coverage when compared with standard of care IGRT for locally advanced cervical cancer. The clinical impact of improved dosimetry is currently undergoing investigation. • Adaptive radiotherapy accounts for changes in anatomy and improves radiation delivery. • Daily online adaptive radiotherapy allows for reduced CTV to PTV margins. • Daily online adaptive radiotherapy improves CTV coverage and OAR sparing. • Daily online adaptive therapy takes about 41 min on average. [ABSTRACT FROM AUTHOR]