Margin Size Research Articles

ESTRO-EANO guideline on target delineation and radiotherapy for IDH-mutant WHO CNS grade 2 and 3 diffuse glioma

PurposeThis guideline will discuss radiotherapeutic management of IDH-mutant grade 2 and grade 3 diffuse glioma, using the latest 2021 WHO (5th) classification of brain tumours focusing on: imaging modalities, tumour volume delineation, irradiation dose and fractionation. MethodsThe ESTRO Guidelines Committee, CNS subgroup, nominated 15 European experts who identified questions for this guideline. Four working groups were established addressing specific questions concerning imaging, target volume delineation, radiation techniques and fractionation. A literature search was performed, and available literature was discussed. A modified two-step Delphi process was used with majority voting resulted in a decision or highlighting areas of uncertainty. ResultsKey issues identified and discussed included imaging needed to define target definition, target delineation and the size of margins, and technical aspects of treatment including different planning techniques such as proton therapy. ConclusionsThe GTV should include any residual tumour volume after surgery, as well as the resection cavity. Enhancing lesions on T1 imaging should be included if they are indicative of residual tumour. In grade 2 tumours, T2/FLAIR abnormalities should be included in the GTV. In grade 3 tumours, T2/FLAIR abnormalities should also be included, except areas that are considered to be oedema which should be omitted from the GTV. A GTV to CTV expansion of 10 mm is recommended in grade 2 tumours and 15 mm in grade 3 tumours. A treatment dose of 50.4 Gy in 28 fractions is recommended in grade 2 tumours and 59.4 Gy in 33 fractions in grade 3 tumours. Radiation techniques with IMRT are the preferred approach.

Evaluation of a Musculoskeletal Digital Assessment Routing Tool (DART): Crossover Noninferiority Randomized Pilot Trial.

Musculoskeletal conditions account for 16% of global disability, resulting in a negative effect on patients and increasing demand for health care use. Triage directing patients to appropriate level intervention improving health outcomes and efficiency has been prioritized. We developed a musculoskeletal digital assessment routing tool (DART) mobile health (mHealth) system, which requires evaluation prior to implementation. Such innovations are rarely rigorously tested in clinical trials-considered the gold standard for evaluating safety and efficacy. This pilot study is a precursor to a trial assessing DART performance with a physiotherapist-led triage assessment. The study aims to evaluate trial design, assess procedures, and collect exploratory data to establish the feasibility of delivering an adequately powered, definitive randomized trial, assessing DART safety and efficacy in an NHS primary care setting. A crossover, noninferiority pilot trial using an integrated knowledge translation approach within a National Health Service England primary care setting. Participants were patients seeking assessment for a musculoskeletal condition, completing a DART assessment and the history-taking element of a face-to-face physiotherapist-led triage in a randomized order. The primary outcome was agreement between DART and physiotherapist triage recommendation. Data allowed analysis of participant recruitment and retention, randomization, blinding, study burden, and potential barriers to intervention delivery. Participant satisfaction was measured using the System Usability Scale. Over 8 weeks, 129 patients were invited to participate. Of these, 92% (119/129) proceeded to eligibility assessment, with 60% (78/129) meeting the inclusion criteria and being randomized into each intervention arm (39/39). There were no dropouts and data were analyzed for all 78 participants. Agreement between physiotherapist and DART across all participants and all primary triage outcomes was 41% (32/78; 95% CI 22-45), intraclass correlation coefficient 0.37 (95% CI 0.16-0.55), indicating that the reliability of DART was poor to moderate. Feedback from the clinical service team led to an adjusted analysis yielding of 78% (61/78; 95% CI 47-78) and an intraclass correlation coefficient of 0.57 (95% CI 0.40-0.70). Participant satisfaction was measured quantitively using amalgamated System Usability Scale scores (n=78; mean score 84.0; 90% CI +2.94 to -2.94), equating to an "excellent" system. There were no study incidents, and the trial burden was acceptable. Physiotherapist-DART agreement of 78%, with no adverse triage decisions and high patient satisfaction, was sufficient to conclude DART had the potential to improve the musculoskeletal pathway. Study validity was enhanced by the recruitment of real-world patients and using an integrated knowledge translation approach. Completion of a context-specific consensus process is recommended to provide definitive definitions of safety criteria, range of appropriateness, noninferiority margin, and sample size. This pilot demonstrated an adequately powered definitive trial is feasible, which would provide evidence of DART safety and efficacy, ultimately informing potential for DART implementation. ClinicalTrials.gov NCT04904029; http://clinicaltrials.gov/ct2/show/NCT04904029. RR2-10.2196/31541.

Margin status, adjuvant treatment and recurrence in buccal cancer

ObjectiveTo assess the prognostic importance of margin in resected buccal cancer within a framework of risk factor-driven postoperative adjuvant treatment. Materials and MethodsConsecutive, treatment naïve patients undergoing primary surgical treatment for buccal cancer. Margin was defined as clear (≥5 mm), close (1–4 mm) and involved (<1 mm). Main outcome was association of margin with local recurrence free survival (LRFS). Subgroup analysis of close margin was performed according to receipt or no receipt of adjuvant treatment. A numerical margin cut-off in mm that could independently predict LRFS was sought to be identified. ResultsOf the 167 patients included, the frequency of clear, close and involved margins was 50 (30 %), 78 (47 %) and 39 (23 %) respectively, among whom 52 %, 44 % and 98 % received postoperative adjuvant treatment respectively. Clear and close margins had similar 3-year LRFS (89 % and 96 % respectively), while involved margin had worse 3-year LRFS at 65 %. Involved margin was confirmed to be strongly and independently associated with worse LRFS. Within close margin, receipt and no receipt of adjuvant treatment had similar 3-year LRFS (92 % and 100 % respectively). A margin cut-off of 2 mm was identified at or above which LRFS approximated that of clear margin. ConclusionsThis single center cohort study of patients with resected buccal cancer suggests that close margin is distinct from and has a better LRFS than involved margin. A subset of close margin, with margin size ≥ 2 mm and no other adverse features, might be spared adjuvant treatment without compromising outcomes.

The Influence of Cash Ratio, Net Profit Margin, and Company Size on Dividend Policy

The purpose of this study was to determine the effect of cash ratio, net profit margin and company size on dividend policy in consumer non-cyclicals companies listed on the Indonesia Stock Exchange in 2018-2022. The research method used in this research is quantitative. The population in this study were 58 main board consumer non-cyclicals companies listed on the Indonesia Stock Exchange for the period 2018-2022. The sampling technique used in this study was purposive sampling. So that the sample obtained was 21 consumer non-cyclicals companies listed on the IDX for the 2018-2022 period. The results showed that partially cash ratio and net profit margin had no effect on dividend policy. Meanwhile, company size partially has a significant effect on dividend policy. It can be concluded that cash ratio, net profit margin and company size have an effect on dividend policy. And the Adjusted R-Squared value is 0.736174, which means that the dividend policy is influenced by the Cash Ratio, Net Profit Margin and Company Size by 73.62% and 26.38% is influenced by other variables not examined in this study.

Optimizing loss functions for improved energy demand prediction in smart power grids

In this paper, our aim is to improve the accuracy and effectiveness of energy demand forecasting, particularly within modern electricity transmission systems and smart grid technology. To achieve this, we developed a hybrid approach that combines machine learning, representation learning, and other deep learning techniques. This approach is based on extracting essential features, including time-based attributes, identifiable trends, and optimal lags. The outcome of our investigation is the observation that triplet losses demonstrate remarkable accuracy, particularly when employed with a larger margin size and for longer prediction lengths. This finding signifies a substantial improvement in the precision and reliability of energy demand forecasting within modern electricity transmission systems. Our research not only improves predictive modeling in the power grid but also demonstrates the practical use of advanced analytics in addressing renewable energy integration challenges, refining energy demand forecasting for efficient management, system operation, and market analysis.

Preoperative Differentiation of HER2-Zero and HER2-Low from HER2-Positive Invasive Ductal Breast Cancers Using BI-RADS MRI Features and Machine Learning Modeling.

Accurate determination of human epidermal growth factor receptor 2 (HER2) is important for choosing optimal HER2 targeting treatment strategies. HER2-low is currently considered HER2-negative, but patients may be eligible to receive new anti-HER2 drug conjugates. To use breast MRI BI-RADS features for classifying three HER2 levels, first to distinguish HER2-zero from HER2-low/positive (Task-1), and then to distinguish HER2-low from HER2-positive (Task-2). Retrospective. 621 invasive ductal cancer, 245 HER2-zero, 191 HER2-low, and 185 HER2-positive. For Task-1, 488 cases for training and 133 for testing. For Task-2, 294 cases for training and 82 for testing. 3.0 T; 3D T1-weighted DCE, short time inversion recovery T2, and single-shot EPI DWI. Pathological information and BI-RADS features were compared. Random Forest was used to select MRI features, and then four machine learning (ML) algorithms: decision tree (DT), support vector machine (SVM), k-nearest neighbors (k-NN), and artificial neural nets (ANN), were applied to build models. Chi-square test, one-way analysis of variance, and Kruskal-Wallis test were performed. The P values <0.05 were considered statistically significant. For ML models, the generated probability was used to construct the ROC curves. Peritumoral edema, the presence of multiple lesions and non-mass enhancement (NME) showed significant differences. For distinguishing HER2-zero from non-zero (low + positive), multiple lesions, edema, margin, and tumor size were selected, and the k-NN model achieved the highest AUC of 0.86 in the training set and 0.79 in the testing set. For differentiating HER2-low from HER2-positive, multiple lesions, edema, and margin were selected, and the DT model achieved the highest AUC of 0.79 in the training set and 0.69 in the testing set. BI-RADS features read by radiologists from preoperative MRI can be analyzed using more sophisticated feature selection and ML algorithms to build models for the classification of HER2 status and identify HER2-low. Stage 2.

Diminishing Safety Margins of Telescoping-Boom Aerial Lifts

Abstract As the height of telescoping-boom aerial lifts increase, the severity of tip-over accidents obviously increases. To reduce the probability of tip-over accidents, manufacturers use countermeasures such as outriggers and wheel axels that expand in width to provide a more stable base, counterweights to offset the moments generated by the telescoping boom, and controllers that limit the machine configurations to within stable envelopes. The size of stability margins is determined by industry standards that set the approved load capacity of the machine to less than the load that would induce tip-over. This paper investigates the effectiveness of such load-based safety margins for very tall aerial lifts with telescoping-booms. The results indicate that the industry standards result in both inconsistent and often low safety margins.

Surgical margins and outcomes for eyelid melanoma: a systematic review and meta-analysis.

No randomized trials exist to inform the peripheral surgical margins or depth of wide excision for eyelid melanoma. We performed a meta-analysis examining surgical margins and Breslow depth for eyelid melanomas. A systematic review was performed in August 2022 using PubMed, Cochrane, and Medline databases (1/1/1990 to 8/1/2022). Inclusion criteria included studies reporting surgical treatment of primary cutaneous melanomas of the eyelid with reported surgical margins. Ten articles were included. The studies were examined by surgical margin size (group 1: ≤ 0.5cm; group 2 > 0.5cm and ≤ 1.5cm) and Breslow depth (group 1: ≤ 1mm; group 2: > 1mm). The odds ratio (OR) for local recurrence was 2.55 [95% CI 0.36-18.12], p = 0.18; regional metastasis was 0.70 [95% CI 0.00-23671.71], p = 0.48; and distant metastasis was 2.47 [95% CI 0.00-1687.43], p = 0.66. When examining by Breslow depth, the OR for local recurrence was 0.53 [95% CI 0.14-1.94], p = 0.34; regional metastasis was 0.14 [0.00-176.12], p = 0.54; and the OR for distant metastasis was 0.24 [95% CI 0.01-8.73], p = 0.46. There was a trend toward higher likelihood of recurrence and metastasis in the ≤ 0.5cm group. Similarly, there is a trend toward higher likelihood of recurrence and metastasis with Breslow depth > 1mm. A surgical margin of at least 0.5cm and achievement of negative margins via permanent sections or MMS are likely needed to prevent adverse outcomes. En face sectioning may be a superior method of histological processing for eyelid melanoma.

Oral Cavity Squamous Cell Carcinoma: Impact of Clear Margin Distance on Locoregional Control in Patients Undergoing Postoperative Radiotherapy.

Postoperative radiotherapy can improve locoregional control (LC) in oral cavity squamous cell carcinoma (OCSCC) patients with positive resection margins. The present study aimed to evaluate the impact of surgical margin size on LC in this patient population. This retrospective study involved 162 patients with OCSCC who underwent postoperative radiotherapy between 2000 and 2020 at the Department of Radiation Oncology, University Hospital Heidelberg and the German Cancer Research Center. The study aimed to determine the impact of different resection margins on LC, as well as overall survival (OS), progression-free survival (PFS), and treatment-related toxicity (CTCAE 4.03). Seventy-seven patients (47.5%) had involved (<1 mm) margins, 22 patients (13.6%) close (≤5 mm) margins, and 63 patients (38.9%) clear (>5 mm) margins. A surgical margin ≤ 5 mm was a significant predictor for worse LC (HR 2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2, 0.7, 2.0). Patients who have narrow resection margins (1-5 mm) experience poor local control and should receive postoperative radiotherapy. It is necessary to conduct further prospective studies to determine whether a narrower margin window could be achieved to better determine the appropriate indication for adjuvant radiotherapy.

Comparison of Standard and Vacuum Specimen Mammography in the Detection of Margin Status in Conservative Surgery for Breast Cancer: a Cross-Sectional Diagnostic Study

Background: One of the most important factors that increases breast cancer (BC) recurrence after Breast-conserving surgery (BCS) is the positivity of the margins, which is found in permanent histological exams. Intra-operative specimen mammography (SM) can reduce the rate of margin positivity and re-operation. Our aim was to examine whether vacuum SM (VSM) is more accurate than standard SM (SSM) in detecting the positivity of the margins. Methods: For this cross-sectional study, in the operating room, excised specimens of 55 women with breast cancer who underwent lumpectomy were oriented by metallic staples and sutures for radiologic and histological assessment, respectively. In the radiology ward, SSM was first taken; then, the specimen was vacuum packed and VSM was performed. Afterwards, the specimen was sent for histopathological analysis as a gold standard for the assessment of surgical margins. Specimens’ margins were classified according to the size of clear margins in millimeters as zero or &gt;0; and ≤1 or &gt;1. Results: The mean age of all participants was 51.22 ± 10.58 years. Totally, 220 margins were assessed. According to classified margins (zero and 1 mm), for the detection of affected margins, the accuracy values of the VSM method were 90.52%, and 87.20% while these figures were 91.51% and 88.68% for SSM. There was substantial agreement between the two methods of detecting the affected margins (VSM and SSM), with Cohen's κ =0.66, 95% CI: 0.34-0.97, P-value &lt;0.001). Finally, there was not a statistically significant difference in the proportion of detecting margin between SSM and VSM (McNemar test P-value =0.63). Conclusion: Specimen mammography with an adequate orientation of the tissue is an accurate and practical method for immediate intraoperative examination of the margin status in BCS, and VSM is not superior to SSM in the detection of affected margins.

Prospective Margin Estimates Predict Local Tumor Progression Following Microwave Ablation of Small Renal Masses.

To evaluate the relationship between prospectively generated ablative margin estimates and local tumor progression (LTP) among patients undergoing microwave ablation (MWA) of small renal masses (SRMs). Between 2017 and 2020, patients who underwent MWA for SRM were retrospectively identified. During each procedure, segmented kidney and tumor shapes were coregistered with intraprocedural helical CT images obtained after microwave antenna placement. Predicted ablation zone shape and size were then overlaid onto the resultant model, and a model-to-model distance algorithm was employed to calculate multiple ablative margin estimates. LTP was modeled as a function of each margin estimate by hazard regression. Models were evaluated using hazard ratios and Akaike information criterion. Receiver operating characteristic curve area under the curve was also estimated using Harrell's and Uno's C indices (HI and UI, respectively). One hundred and twenty-eight patients were evaluated (median age 72.1years). Mean tumor diameter was 2.4 ± 0.9cm. LTP was observed in nine (7%) patients. Analysis showed that decreased estimated margin size as measured by first quartile (Q1; 25th percentile), maximum, and average ablative margin metrics was significantly associated with risk of LTP. For every one millimeter increase in Q1, maximum, and mean ablative margin, the hazard of LTP increased 67% (HR: 1.67; 95% CI = 1.25-2.20, UI = 0.93, HI = 0.77), 32% (HR: 1.32; 95% CI 1.09-1.60; UI = 0.93; HI = 0.76), and 48% (HR: 1.48; 95% CI 1.18-1.85; UI = 0.83; HI = 0.75), respectively. Prospectively generated ablative margin estimates can be used to predict the risk of local tumor progression following microwave ablation of small renal masses. LEVEL OF EVIDENCE 3: Retrospective cohort study.

Pendampingan Penetapan Harga Pokok Produksi Untuk Menentukan Harga Jual Susu Pada KPS-Bogor

This research aims to review the cost of production (HPP) for milk and determine the appropriate selling price in livestock cooperatives. The research was conducted using quantitative descriptive methods and a case study approach on Milk Production Cooperatives and Livestock Businesses. Data collection was carried out through interviews, field observations, and financial report documents for certain periods from the previous year to the month when the final assignment was written. The cost-plus pricing method is used to determine the selling price of pasteurized milk products. Based on this analysis, the results obtained show that the ideal profit margin that can be obtained by each product is between 20-30%. The results of this research can provide an idea of the size of the profit margin on each product so that it can help livestock businesses in calculating HPP accurately and getting maximum profits without harming consumers. Therefore, it is recommended that livestock cooperatives continue to evaluate production costs and determine selling prices in order to increase profits and strengthen competitiveness in the market. Keywords: Cost of Production, Selling Price, Milk, Cost-Plus Pricing

Pengaruh Rasio Keuangan dan Ukuran Perusahaan terhadap Return Saham Jakarta Islamic Index 70

Sharia-based investments are increasingly in demand by investors. An example of this phenomenon is the emergence of a new Islamic stock index, namely the Jakarta Islamic Index (JII) 70. One of the aims of investors is to expect a good rate of return on what they have invested. This study aims to analyze whether JII 70 stock returns can be influenced by financial ratios and company size variables with objects namely companies that have been listed on the index from 2018-2020. The population in this study was 101 companies through purposive sampling, 21 companies were used as samples. There are nine variables used in this study with the results showing that stock returns can be influenced by three variables, namely debt to equity ratio, price earning ratio, dividend per share. Meanwhile, stock returns cannot be influenced by six other independent variables including return on assets, earnings per share, economic value added, total asset turnover, net profit margin and company size.

Molecular phylogeny and character-mapping support the synonymy of Cordobia and Gallardoa in Mionandra (Malpighiaceae)

Background and aims – Cordobia, Gallardoa, Mionandra, and Peixotoa (Stigmaphylloid clade, Malpighiaceae) are four small, closely related genera comprising shrubs or lianas endemic to South American savannas, dry forests, and temperate steppes. Their generic limits have significantly changed in the last century, and past molecular phylogenetic studies of Malpighiaceae have not tested the morphological characters of this group to identify synapomorphies supporting these clades/genera. Material and methods – We sampled the monospecific Cordobia and Gallardoa, one species of Mionandra (out of 2 spp.), nine species of Peixotoa (out of 29 spp.), and a single species of Camarea and Janusia as outgroups. Bayesian and Maximum Likelihood analyses were carried out for this clade based on five molecular markers (i.e. ETS, ITS, PHYC, matK, and ndhF). A set of 16 macromorphological characters was scored and coded for identifying synapomorphies under the Maximum Likelihood criteria. Key results – Our molecular phylogeny recovered Peixotoa as monophyletic and sister to the clade comprising Cordobia + Gallardoa + Mionandra, strongly corroborating previous phylogenetic studies of Malpighiaceae. The character-mapping analyses recovered two synapomorphies supporting the Cordobia + Gallardoa + Mionandra + Peixotoa clade, six supporting Mionandra s.l. (i.e. Cordobia + Gallardoa + Mionandra), and five supporting Peixotoa. Cordobia and Gallardoa are proposed as synonyms of Mionandra, alongside the necessary combinations, typifications, and identification keys. Conclusions – Morphological characters related to the degree of connation of the stipules, leaf indumentum type, petiole length, inflorescence architecture, number of flowers per inflorescence, presence of a peduncle in the 1-flowered cincinni, sepal connation, posture and texture, petal width and margin integrity, staminode presence, shape and size, and the shape of the apex of styles were key in circumscribing these lineages. Mionandra s.l. is proposed and characterised, including a new combination, an identification key to distinguish its species, a distribution map, and taxonomy notes.

Recurrence rate and survival implications of surgical margins in patients with acral melanoma. Is a wide margin necessary?

Appropriate size of resection margins in acral melanoma is not clearly established. To investigate whether narrow-margin excision is appropriate for thick acral melanoma. Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm). Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003). A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma.

Efficiency, Margin And Channel Analysis Corn (Zea mays L.)

The development of corn crops that began in the 1990s is considered by many parties to have brought significant changes to improve the welfare of farmers. For Indonesia, corn is the second food crop after rice. Even in some places, corn is the main staple food substitute for rice or as a mixture of rice. The research was conducted in Sumber Lor Village, Babakan District, Cirebon Regency, from January to March 2023. This study aims to find out: (1) The size of corn trading margin in Sumber Lor Village, Babakan District, Cirebon Regency and, (2) The efficiency of corn trading channels created in Sumber Lor Village, Babakan District, Cirebon Regency. The research design used in this study is a quantitative method, with a survey approach, with a sample of 42 farmers, 9 collecting traders, 3 wholesalers and 7 retailers. The data collected are primary data and secondary data that have to do with the research problem. The resulting data is analyzed descriptively and statistically. Descriptive analysis is used to determine the channel of commerce and the function of tataniaga. While statistical analysis is used to determine trade margins and to determine corn farming analysis. The results showed that: (1) The largest trade margin was in marketing channel II which was Rp. 2,550 per kg and the smallest in commerce channel I which was Rp. 1,945 per kg, and (2) The efficiency of corn trading in trade channels I and II was efficient, with a value of tatangiaga efficiency of 6.78% and 9.47%, (3) There were two systems of commerce channels corn in Sumber Lor Village, Babakan District, namely Farmers - Collecting Traders - Retailers - Consumers, and Farmers - Collecting Traders - Wholesalers - Retailers - Consumers, and (4) The efficiency of corn trading in trade channel I is more efficient than commercial channel II. The shorter the configuration channel, the more efficient the value. Because the longer the commercial channel, the more costs are incurred.

Critical Appraisal of Histologic Grading for Mucoepidermoid Carcinoma of Salivary Gland: Is an Objective Prognostic 2-tiered Grading System Possible?

Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative border, lymphovascular invasion, perineural invasion, atypical mitosis, mitotic index (MI) ≥4/2mm 2 (4/10HPFs), necrosis, and pT4 stage were associated with increased risk of nodal metastasis. The 5-year recurrence-free survival (RFS) was 95%. Significant prognostic factors for RFS included infiltrative border, tumor-associated lymphoid stroma, architectural patterns (macrocystic, microcystic, and noncystic), anaplasia, atypical mitosis, MI, necrosis, lymphovascular invasion, margin, pT stage, and tumor size. Nuclear anaplasia, high mitotic rate, and ≥25% microcystic component were significant independent prognostic factors on multivariate survival analysis. There was no significant difference between low-grade (LG) and intermediate-grade (IG) MECs in terms of risk of nodal metastasis and outcomes using all 4 known grading systems. Rather, high-grade MEC was consistently associated with an increased risk of nodal metastasis at presentation and decreased RFS and distant metastasis-free survival (DMFS) compared with the LG/IG MECs. We therefore recommend simplifying MEC grading to a 2-tiered grading scheme using MI and/or tumor necrosis. Using a 2-tiered grading, high-grade histology independently predict RFS, and is associated with a 25% risk of nodal metastasis, a 5-year RFS of 76%, and a 5-year DMFS of 76%, whereas LG MEC has a nodal metastasis rate of 7.0%, 5-year RFS of 97% and 5-year DMFS of 99%.

Improved sub-milimeter range-verification method for proton therapy using a composite hadron tumour marker (HTM)

Objective. The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented. Approach. The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring the γ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery. Main results. Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure the γ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate the γ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm. Significance. Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.

Trade Preference Utilization Post-Brexit: The Role of Rules of Origin

AbstractThe degree to which firms make use of preferences in exporting to a partner country under a Free Trade Agreement will in good part depend on the restrictiveness of the underlying Rules of Origin (ROOs). Focusing on the post-Brexit Trade and Cooperation Agreement (TCA) signed by the United Kingdom and the European Union, we examine how access to zero preferential tariffs has been impacted by ROOs. We do so by constructing a ROO restrictiveness index which varies across products. We find that the TCA has an overall moderate degree of ROO restrictiveness. Using product-country level trade data, we find that preference utilization under the TCA has risen over time, and exhibits a positive correlation at the product level with the EU Common External Tariff. Regressions on the determinants of preference utilization indicate that more restrictive ROOs are associated with a lower degree of preference utilization by UK firms in the EU market and this effect is more evident for consumption goods. Preference utilization is also driven by the size of the preferential margin, the size of the trade flows, and the extent to which exports are undertaken by producers as opposed to distributors, as well as the degree of firms’ engagement in value chains.

Sol-Gel-Processed Y2O3-Al2O3 Mixed Oxide-Based Resistive Random-Access-Memory Devices.

Herein, sol-gel-processed Y2O3-Al2O3 mixed oxide-based resistive random-access-memory (RRAM) devices with different proportions of the involved Y2O3 and Al2O3 precursors were fabricated on indium tin oxide/glass substrates. The corresponding structural, chemical, and electrical properties were investigated. The fabricated devices exhibited conventional bipolar RRAM characteristics without requiring a high-voltage forming process. With an increase in the percentage of Al2O3 precursor above 50 mol%, the crystallinity reduced, with the amorphous phase increasing owing to internal stress. Moreover, with increasing Al2O3 percentage, the lattice oxygen percentage increased and the oxygen vacancy percentage decreased. A 50% Y2O3-50% Al2O3 mixed oxide-based RRAM device exhibited the maximum high-resistance-state/low-resistance-state (HRS/LRS) ratio, as required for a large readout margin and array size. Additionally, this device demonstrated good endurance characteristics, maintaining stability for approximately 100 cycles with a high HRS/LRS ratio (>104). The HRS and LRS resistances were also retained up to 104 s without considerable degradation.