Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

PURPOSE: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. METHODS: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). RESULTS: A total of 49 patients were evaluated with a median age of 81 years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50 Gy (range, 40-50 Gy) in 5 fractions. 1 Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6 months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. CONCLUSIONS: A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

Percutaneous pelvic fixation model: an affordable and realistic simulator for pelvic trauma training.

PURPOSE: To describe the construction and use of a percutaneous pelvic fixation model, evaluate its translational validity among fellowship-trained orthopedic trauma surgeons, and investigate the importance of specific criteria for effective competency-based assessment of pelvic fixation techniques. METHODS: Five orthopedic trauma surgeons were asked to place percutaneous wires on a pelvic fixation model, including anterior column (antegrade/retrograde), posterior column (antegrade/retrograde), supra-acetabular, transsacral, and iliosacral. Evaluation criteria included successful wire placement, redirections, cortical breaches, procedure duration, radiation exposure, and quality of fluoroscopic views. Following completion, participants were provided a survey to rate the model. RESULTS: There were no differences between approaches on successful screw placement, wire redirections, or fluoroscopic quality. Antegrade approaches to the anterior and posterior columns took longer (p = 0.008) and used more radiation (p = 0.02). There was also a trend toward more cortical breaches with the antegrade anterior column approach (p = 0.07). Median ratings among surgeons were 4 out of 5 for their overall impression and its accuracy in tactile response, positioning constraints, and fluoroscopic projections. Learning parameters considered most important to the progression of trainees (most to least important) were successful screw placement, corridor breaches, wire redirections, quality of fluoroscopic views, radiation exposure, and procedure duration. CONCLUSION: In being affordable, accessible, and realistic, this percutaneous pelvic fixation model represents an opportunity to advance orthopedic surgery education globally. Future research is needed to validate the findings of this pilot study and to expand upon how trainees should be evaluated within simulations and the operating room to optimize skill progression.

Largest neurosurgical social media group and its impact on communication and research.

BACKGROUND: The use of social media to communicate and disseminate knowledge has increased exponentially, especially in the field of neurosurgery. 'Neurosurgery cocktail' (NC) was developed by a group of young neurosurgeons as a means of sharing didactic materials and clinical experiences via social media. It connects 35.000 neurosurgeons worldwide on multiple platforms, primarily Facebook and Twitter. Given the rising utilization of social media in neurosurgery, the popularity of NC has also increased since its inception. In this study, the authors surveyed the social media analytics of NC for both Facebook and Twitter. Besides, we reviewed the literature on the use of social media in neurosurgery. METHODS: Facebook and Twitter metrics were extracted through each respective platform's analytics tools from December 2020 (earliest available date for data analysis) through January 2021. A literature search was conducted using PubMed (MEDLINE) and Scopus databases. RESULTS: On Facebook, as of January 2021, the group had a total of 25.590 members (87.6% male), most commonly (29%) between 35 and 44 years of age with over 100 countries were represented. As of January 2021, they had amassed 6457 followers on Twitter. During the last 28 d between December 2020 and January 2021, the account published 65 tweets that garnered a total of 196,900 impressions. Twelve articles were identified in our literature review on the use of social media within the neurosurgical community. CONCLUSIONS: NC is one of the most widely utilized neurosurgical social media resources available. Sharing knowledge has been broadened thanks to the recent social media evolution, and NC has become a leading player in disseminating neurosurgical knowledge.

Traceless Benzylic C-H Amination via Bifunctional N-Aminopyridinium Intermediates.

C-H amination reactions provide the opportunity to streamline the synthesis of nitrogen-containing organic small molecules. The impact of intermolecular C-H amination methods, however, is currently limited the frequent requirement for the amine precursors to bear activating groups, such as N-sulfonyl substituents, that are both challenging to remove and not useful synthetic handles for subsequent derivatization. Here, we introduce traceless nitrogen activation for C-H amination-which enables application of selective C-H amination chemistry to the preparation of diverse N-functionalized products-via sequential benzylic C-H N-aminopyridylation followed by Ni-catalyzed C-N cross-coupling with aryl boronic acids. Unlike many C-H amination reactions that provide access to protected amines, the current method installs an easily diversifiable synthetic handle that serves as a lynchpin for C-H amination, deaminative N-N functionalization sequences.

Incorporating climate change in flood estimation guidance.

Research into potential implications of climate change on flood hazard has made significant progress over the past decade, yet efforts to translate this research into practical guidance for flood estimation remain in their infancy. In this commentary, we address the question: how best can practical flood guidance be modified to incorporate the additional uncertainty due to climate change? We begin by summarizing the physical causes of changes in flooding and then discuss common methods of design flood estimation in the context of uncertainty. We find that although climate science operates across aleatory, epistemic and deep uncertainty, engineering practitioners generally only address aleatory uncertainty associated with natural variability through standards-based approaches. A review of existing literature and flood guidance reveals that although research efforts in hydrology do not always reflect the methods used in flood estimation, significant progress has been made with many jurisdictions around the world now incorporating climate change in their flood guidance. We conclude that the deep uncertainty that climate change brings signals a need to shift towards more flexible design and planning approaches, and future research effort should focus on providing information that supports the range of flood estimation methods used in practice. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes.

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius-Clapeyron (CC) rate (6-7% K-1), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

Sargassum landings have not compromised nesting of loggerhead and green sea turtles in the Mexican Caribbean.

The Mexican Caribbean is a vital nesting destination for loggerhead (Caretta caretta) and green (Chelonia mydas) sea turtles. Since 2015, massive periodical landings of pelagic Sargassum species (sargasso) have affected coastal ecosystems. Dense accumulations of sargasso on the shoreline may preclude access to sea turtles' preferred nesting areas and compromise hatching. In this study, we assess whether the number of nests and hatches of loggerhead and green sea turtles has been affected by the massive influx of sargasso. We compare data from before (2010-2014) and after (2015-2019) the first sargasso event, obtained from the same 17 marine turtle camps, which collectively account for 72.3 km of sampling distance over a 210 km section of shoreline. No differences in preferences on nesting beaches were recorded between periods for the two species. The mean number of nests per kilometer of coastline remained without statistically significant changes between periods in 16 camps and increased significantly in one camp for each species. Overall, the mean annual number of nests per kilometer of beach was 37% higher in the period after massive landings of sargasso began. The mean number of hatchlings increased significantly in one camp for C. mydas and in three for C. caretta. Periodical massive landings of sargasso from 2015 to 2019 do not appear to have compromised nesting and hatching of loggerhead and green sea turtles along the Mexican Caribbean coast.

Analysis of time-varying signals using continuous wavelet and synchrosqueezed transforms.

The continuous wavelet transform (CWT) has played a key role in the analysis of time-frequency information in many different fields of science and engineering. It builds on the classical short-time Fourier transform but allows for variable time-frequency resolution. Yet, interpretation of the resulting spectral decomposition is often hindered by smearing and leakage of individual frequency components. Computation of instantaneous frequencies, combined by frequency reassignment, may then be applied by highly localized techniques, such as the synchrosqueezing transform and ConceFT, in order to reduce these effects. In this paper, we present the synchrosqueezing transform together with the CWT and illustrate their relative performances using four signals from different fields, namely the LIGO signal showing gravitational waves, a 'FanQuake' signal displaying observed vibrations during an American football game, a seismic recording of the Mw 8.2 Chiapas earthquake, Mexico, of 8 September 2017, followed by the Irma hurricane, and a volcano-seismic signal recorded at the Popocatépetl volcano showing a tremor followed by harmonic resonances. These examples illustrate how high-localization techniques improve analysis of the time-frequency information of time-varying signals.This article is part of the theme issue 'Redundancy rules: the continuous wavelet transform comes of age'.

Six Sessions of Sprint Interval Training Improves Running Performance in Trained Athletes.

Koral, J, Oranchuk, DJ, Herrera, R, and Millet, GY. Six sessions of sprint interval training improves running performance in trained athletes. J Strength Cond Res 32(3): 617-623, 2018-Sprint interval training (SIT) is gaining popularity with endurance athletes. Various studies have shown that SIT allows for similar or greater endurance, strength, and power performance improvements than traditional endurance training but demands less time and volume. One of the main limitations in SIT research is that most studies were performed in a laboratory using expensive treadmills or ergometers. The aim of this study was to assess the performance effects of a novel short-term and highly accessible training protocol based on maximal shuttle runs in the field (SIT-F). Sixteen (12 male, 4 female) trained trail runners completed a 2-week procedure consisting of 4-7 bouts of 30 seconds at maximal intensity interspersed by 4 minutes of recovery, 3 times a week. Maximal aerobic speed (MAS), time to exhaustion at 90% of MAS before test (Tmax at 90% MAS), and 3,000-m time trial (TT3000m) were evaluated before and after training. Data were analyzed using a paired samples t-test, and Cohen's (d) effect sizes were calculated. Maximal aerobic speed improved by 2.3% (p = 0.01, d = 0.22), whereas peak power (PP) and mean power (MP) increased by 2.4% (p = 0.009, d = 0.33) and 2.8% (p = 0.002, d = 0.41), respectively. TT3000m was 6% shorter (p < 0.001, d = 0.35), whereas Tmax at 90% MAS was 42% longer (p < 0.001, d = 0.74). Sprint interval training in the field significantly improved the 3,000-m run, time to exhaustion, PP, and MP in trained trail runners. Sprint interval training in the field is a time-efficient and cost-free means of improving both endurance and power performance in trained athletes.

Synthesis of Secondary Amines via Self-Limiting Alkylation.

N-centered nucleophilicity increases upon alkylation, and thus selective partial alkylation of ammonia and primary amines can be challenging: Poor selectivity and overalkylation are often observed. Here we introduce N-aminopyridinium salts as ammonia surrogates for the synthesis of secondary amines via self-limiting alkylation chemistry. Readily available N-aryl-N-aminopyridinium salts engage in N-alkylation and in situ depyridylation to afford secondary aryl-alkyl amines without any overalkylation products. The method overcomes classical challenges in selective amine alkylation by accomplishing alkylation via transient, highly nucleophilic pyridinium ylide intermediates and can be applied in the context of complex molecular scaffolds. These findings establish N-aminopyridinium salts as ammonia synthons in synthetic chemistry and a strategy to control the extent of amine alkylation.

Multi-institutional experience of MR-guided stereotactic body radiation therapy for adrenal gland metastases.

Purpose: While dose escalation is associated with improved local control (LC) for adrenal gland metastases (AGMs), the proximity of gastrointestinal (GI) organs-at-risk (OARs) limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The advantages of magnetic resonance-guided SBRT (MRgSBRT), including tumor tracking and online plan adaptation, facilitate safe dose escalation. Methods: This is a multi-institutional review of 57 consecutive patients who received MRgSBRT on a 0.35-T MR linac to 61 AGMs from 2019 to 2021. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and LC, and the Cox proportional hazards model was utilized for univariate analysis (UVA). Results: Median follow up from MRgSBRT was 16.4 months (range [R]: 1.1-39 months). Median age was 67 years (R: 28-84 years). Primary histologies included non-small cell lung cancer (N = 38), renal cell carcinoma (N = 6), and melanoma (N = 5), amongst others. The median maximum diameter was 2.7 cm (R: 0.6-7.6 cm), and most AGMs were left-sided (N = 32). The median dose was 50 Gy (R: 30-60 Gy) in 5-10 fractions with a median BED10 of 100 Gy (R: 48-132 Gy). 45 cases (74 %) required adaptation for at least 1 fraction (median: 4 fractions, R: 0-10). Left-sided AGMs required adaptation in at least 1 fraction more frequently than right-sided AGMs (88 % vs 59 %, p = 0.018). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N = 1) and 40 Gy in 5 fractions (N = 2). One-year LC, PFS, and OS were 92 %, 52 %, and 78 %, respectively. On UVA, melanoma histology predicted for inferior 1-year LC (80 % vs 93 %, p = 0.012). There were no instances of grade 3+ toxicity. Conclusions: We demonstrate that MRgSBRT achieves favorable early LC and no grade 3 + toxicity despite prescribing a median BED10 of 100 Gy to targets near GI OARs.

Surgically targeted radiation therapy versus stereotactic radiation therapy: A dosimetric comparison for brain metastasis resection cavities.

PURPOSE: Surgically targeted radiation therapy (STaRT) with Cesium-131 seeds embedded in a collagen tile is a promising treatment for recurrent brain metastasis. In this study, the biological effective doses (BED) for normal and target tissues from STaRT plans were compared with those of external beam radiotherapy (EBRT) modalities. METHODS: Nine patients (n = 9) with 12 resection cavities (RCs) who underwent STaRT (cumulative physical dose of 60 Gy to a depth of 5 mm from the RC edge) were replanned with CyberKnifeⓇ (CK), Gamma KnifeⓇ (GK), and intensity modulated proton therapy (IMPT) using an SRT approach (30 Gy in 5 fractions). Statistical significance comparing D95% and D90% in BED10Gy (BED10Gy95% and BED10Gy90%) and to RC + 0 to + 5 mm expansion margins, and parameters associated with radiation necrosis risk (V83Gy, V103Gy, V123Gy and V243Gy) to the normal brain were evaluated by a Wilcoxon-signed rank test. RESULTS: For RC + 0 mm, median BED10Gy 90% for STaRT (90.1 Gy10, range: 64.1-140.9 Gy10) was significantly higher than CK (74.3 Gy10, range:59.3-80.4 Gy10, p = 0.04), GK (69.4 Gy10, range: 59.8-77.1 Gy10, p = 0.005), and IMPT (49.3 Gy10, range: 49.0-49.7 Gy10, p = 0.003), respectively. However, for the RC + 5 mm, the median BED10Gy 90% for STaRT (34.1 Gy10, range: 22.2-59.7 Gy10) was significantly lower than CK (44.3 Gy10, range: 37.8-52.4 Gy10), and IMPT (46.6 Gy10, range: 45.1-48.5 Gy10), respectively, but not significantly different from GK (34.1 Gy10, range: 22.8-47.0 Gy10). The median V243Gy was significantly higher in CK (11.7 cc, range: 4.7-20.1 cc), GK(6.2 cc, range: 2.3-11.9 cc) and IMPT (19.9 cc, range: 11.1-36.6 cc) compared to STaRT (1.1 cc, range: 0.0-7.8 cc) (p < 0.01). CONCLUSIONS: This comparative analysis suggests a STaRT approach may treat recurrent brain tumors effectively via delivery of higher radiation doses with equivalent or greater BED up to at least 3 mm from the RC edge as compared to EBRT approaches.

Perioperative management of aortic stenosis in patients undergoing non-cardiac surgery.

Aortic stenosis is one of the most common cardiac valve pathologies in the world and its prevalence increases with age. Although previously associated with increased perioperative mortality, more recent studies suggest that mortality rates may be decreasing. Recent guidelines suggest that major non-cardiac surgery can be performed safely in asymptomatic severe aortic stenosis patients with close hemodynamic monitoring. Among symptomatic patients, the guidelines recommend aortic valve intervention prior to major non-cardiac surgery because of a reduction in the incidence of postoperative heart failure and improved rates of long-term overall survival. This review provides a comprehensive and contemporary review of the perioperative management of patients with severe aortic valve stenosis.

Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer.

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

Surgically targeted radiation therapy (STaRT) for recurrent brain metastases: Initial clinical experience.

PURPOSE: This study evaluates the outcomes of recurrent brain metastasis treated with resection and brachytherapy using a novel Cesium-131 carrier, termed surgically targeted radiation therapy (STaRT), and compares them to the first course of external beam radiotherapy (EBRT). METHODS: Consecutive patients who underwent STaRT between August 2020 and June 2022 were included. All patients underwent maximal safe resection with pathologic confirmation of viable disease prior to STaRT to 60 Gy to a 5-mm depth from the surface of the resection cavity. Complications were assessed using CTCAE version 5.0. RESULTS: Ten patients with 12 recurrent brain metastases after EBRT (median 15.5 months, range: 4.9-44.7) met the inclusion criteria. The median BED10Gy90% and 95% were 132.2 Gy (113.9-265.1 Gy) and 116.0 Gy (96.8-250.6 Gy), respectively. The median maximum point dose BED10Gy for the target was 1076.0 Gy (range: 120.7-1478.3 Gy). The 6-month and 1-year local control rates were 66.7% and 33.3% for the prior EBRT course; these rates were 100% and 100% for STaRT, respectively (p < 0.001). At a median follow-up of 14.5 months, there was one instance of grade two radiation necrosis. Surgery-attributed complications were observed in two patients including pseudomeningocele and minor headache. CONCLUSIONS: STaRT with Cs-131 presents an alternative approach for operable recurrent brain metastases and was associated with superior local control than the first course of EBRT in this series. Our initial clinical experience shows that STaRT is associated with a high local control rate, modest surgical complication rate, and low radiation necrosis risk in the reirradiation setting.

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy.

Purpose: Nearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and Materials: A single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. Results: A total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. Conclusions: To our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

Treatment of glioblastoma using MRIdian® A3i BrainTx™: Imaging and treatment workflow demonstration.

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes.

Diversification of Amidyl Radical Intermediates Derived from C-H Aminopyridylation.

The N-activating substituents typically encountered in C-H amination chemistry are challenging to remove and have limited scope for synthetic elaboration. Here, we demonstrate that N-benzylaminopyridinium species provide a platform for synthetic elaboration via reductive N-N bond activation to unveil electrophilic N-centered radicals. These reactive intermediates can be trapped either via anti-Markovnikov olefin carboamination to provide access to tetrahydroisoquinolines or via aza-Rubottom chemistry with silyl enol ethers to provide α-amino ketones.

[Transnasal endoscopic skull base surgery: analysis of complications in the first 120 procedures]. / Cirugía endoscópica transnasal de base de cráneo: Análisis de las complicaciones en los primeros 120 procedimientos.

Background: The endonasal endoscopic approach (EEA) has potential advantages over traditional open approaches. However, complications such as cerebrospinal fluid (CFS) leak, visual disturbances, and postoperative meningitis have been described. The aim was to present the experience accumulated in 120 cases of skull base EEA performed by the same surgical team and describe and analyze the main postoperative complications according to the complexity of the cases. Methods: Retrospective study on our database of patients undergoing skull base EEA for various pathologies between July 2011 and March 2022. Results: 120 skull base EEA surgeries were analyzed. 57.14% were performed on women. The median age was 44 years. 26.66% were reinterventions. The most frequent pathology was pituitary adenoma (49.17%) followed by CSF leak (8.33%). The most used EEA was the transelar 65.83%. 26 complications were recorded, with no differences according to complexity. There were 13 cases of diabetes insipidus (DI) and 8 of CSF leak. This was more frequent in patients with intraoperative CSF leak. The median hospital stay was 5.5 days. Conclusion: Skull base EEA has become increasingly common for the surgical management of skull base pathology, with a low frequency of immediate postoperative complications and low mortality. The improvement of the technique and the improvement in postoperative care are associated with a shorter hospital stay.

Sub-hourly resolution quality control of rain-gauge data significantly improves regional sub-daily return level estimates.

This research demonstrates how the use of high-resolution rain-gauge data for quality control (QC) significantly changes extreme rainfall estimates, with implications in scientific, meteorological and engineering applications. Current open QC algorithms only consider data at hourly or daily accumulations. Here we present the first open QC algorithm utilising sub-hourly rain-gauge data from official networks at a national, multi-decade scale. We use data from 1,301 rain-gauges in Great Britain (GB) to develop a threshold-based methodology for sub-hourly QC that can be used to complement existing, freely available hourly QC methods by developing an algorithm for sub-hourly QC that uses monthly thresholds for 1 hr, 15 min and 1 min rainfall totals. We then evaluated the effect of combining these QC procedures on rainfall distributions using graphical and statistical methods, with an emphasis on extreme value analysis. We demonstrate that the additional information in sub-hourly rainfall allows our new QC to remove spuriously large values undetected by existing methods which generate errors in extreme rainfall estimates. This results in statistically significant differences between extreme rainfall estimates for 15 min and 1 hr accumulations, with smaller differences found for 6 and 24 hr totals. We also find that extremes in the distributions of 15 min and 1 hr rainfall accumulations tend to grow more rapidly with return period than for longer accumulation periods. We observe similarities between the shape parameter populations for 15 min and 1 hr rainfall accumulations, suggesting that hourly records may be used to improve shape parameter estimates for extreme sub-hourly rainfall in GB. Sub-hourly QC moderates unrealistically large return level estimates for short-duration rainfall, with beneficial impacts on data required for the design of urban drainage infrastructure and the validation of high-resolution climate models.