Hasil untuk "astro-ph.CO"

Y. Lievens, M. Guckenberger, D. Gomez et al.

BACKGROUND Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. CONCLUSION While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.

S. Shaitelman, Bethany M. Anderson, D. Arthur et al.

PURPOSE This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS The American Society for Radiation Oncology (ASTRO) convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS PBI delivered using 3-D conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy and single-entry brachytherapy result in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared to WBI. A daily or every other day external beam PBI regimen is preferred over twice daily regimens due to late toxicity concerns. CONCLUSIONS Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI.

P. Iyengar, S. All, M. Berry et al.

PURPOSE This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent. METHODS ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology. RESULTS Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation. CONCLUSIONS Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances.

Todd M. Morgan, S. Boorjian, M. Buyyounouski et al.

Purpose: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. Materials and Methods: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. Results: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. Conclusions: Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

L. Peyrin-Biroulet, J. Allegretti, S. Danese et al.

Guselkumab (GUS) is a selective dual-acting IL-23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23. GUS demonstrated efficacy in patients (pts) with ulcerative colitis (UC) who received GUS intravenous (IV) induction and subcutaneous (SC) maintenance (QUASAR). We evaluated the efficacy and safety of GUS SC induction in ASTRO, a phase 3, randomised, double-blind, placebo (PBO)-controlled, parallel-group, multicenter trial in pts with moderately to severely active UC. Eligible pts had a history of inadequate response or intolerance to corticosteroids, immunosuppressants, biologics, Janus kinase inhibitors, and/or sphingosine 1-phosphate inhibitors (BIO/JAKi/S1Pi-IR) or were BIO/JAKi/S1Pi naïve. Randomisation was stratified by baseline (BL) BIO/JAKi/S1Pi status and Mayo endoscopic subscore (MES) with 418 pts allocated 1:1:1 to GUS 400 mg SC q4w (x3)→GUS 200 mg SC q4w (N=140), GUS 400 mg SC q4w (x3)→GUS 100 mg SC q8w (N=139), or PBO (N=139). The primary endpoint was clinical remission (Mayo stool frequency subscore 0/1 not increased from BL, rectal bleeding subscore 0, MES 0/1 with no friability) at week (W) 12. Multiplicity-controlled W12 secondary endpoints are clinical response, symptomatic remission, endoscopic improvement, and histo-endoscopic mucosal improvement (HEMI). The prespecified analysis plan compared the combined GUS 400 mg SC treatment group to PBO at W12, and safety was assessed throughout. BL characteristics were similar across treatment groups (overall mean age, 41.7 years; mean UC duration, 7.6 years; mean modified Mayo score, 6.7; MES=3, 56.0%; BIO/JAKi/S1Pi-IR, 40.2%). The primary endpoint and all secondary endpoints were met. At W12, significantly greater proportions of pts treated with GUS 400 mg SC induction than PBO achieved clinical remission (27.6% vs 6.5%, respectively; adj Δ: 21.1%; P<0.001), clinical response (65.6% vs 34.5%; adj Δ: 31.0%; P<0.001), symptomatic remission (51.3% vs 20.9%; adj Δ: 30.4%; P<0.001), endoscopic improvement (37.3% vs 12.9%; adj Δ: 24.3%; P<0.001), and HEMI (30.5% vs 10.8%; adj Δ: 19.6%; P<0.001). In prespecified analyses of subpopulations defined by prior BIO/JAKi/S1Pi history, greater proportions of GUS-treated versus PBO-treated pts achieved the endpoints (Figure). The proportions of GUS-treated pts with ≥1 adverse event (AE), serious AE, or AE leading to treatment discontinuation were not greater than PBO (Table). ASTRO established the efficacy of GUS SC induction in UC, with no new safety concerns identified. These results build on the QUASAR IV induction data, demonstrating that both GUS IV and SC induction are highly efficacious in pts with moderately to severely active UC.

D. Yeboa, S. Braunstein, Alvin R. Cabrera et al.

PURPOSE The central nervous system World Health Organization (WHO) grade 4 adult-type diffuse glioma represents one of the most aggressive and challenging primary brain tumors. This guideline aims to provide evidence-based recommendations for the multidisciplinary management of these tumors, focusing on diagnosis, initial treatment, reirradiation, and health disparities, while acknowledging that present literature primarily represents historical histological grade 4 glioblastoma. METHODS The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications for radiation therapy (RT) and/or adjunctive therapies (eg, systemic therapy, alternating electric field therapy), appropriate regimens for external beam RT after initial biopsy/resection including variables such as pretreatment characteristics, target volumes, technique, dose, reirradiation indications and techniques, and health disparities. Recommendations are based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS Following maximum safe resection, molecular and pathologic diagnosis, and prognostic stratification of WHO grade 4 adult-type diffuse glioma, concurrent RT with temozolomide followed by adjuvant temozolomide is recommended for eligible patients and incorporation of alternating electric field therapy is conditionally recommended. In elderly patients, hypofractionated RT with concurrent and adjuvant temozolomide is conditionally recommended. In frail patients, supportive and palliative care is conditionally recommended following multidisciplinary, patient-centered discussion. Appropriate reirradiation techniques, with or without additional systemic therapies, can be considered and are conditionally recommended in patients following pathologic or advanced imaging confirmation of WHO grade 4 diffuse glioma recurrence. Health disparities exist in patients with WHO grade 4 adult-type diffuse glioma and attention is necessary to improve outcomes and increase clinical trial enrollment for underserved populations. CONCLUSIONS These evidence-based recommendations and current practice adoption patterns inform best clinical practices on the management of WHO grade 4 adult-type diffuse glioma. Future advancements in personalized medicine, biomarker discovery, and novel therapies are essential to improving outcomes. The integration of multidisciplinary care and participation in future clinical trials, especially in underserved populations, is crucial in addressing the poor outcomes among WHO grade 4 adult-type diffuse glioma.

L. Tang, Cheng Huang, Shao-Jun Lin et al.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, the Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology collaboratively developed evidence-based guidelines and a comprehensive contouring atlas for neck target volume delineation in nasopharyngeal carcinoma. These guidelines address five key challenges in modern radiotherapy practice: margin design of clinical target volume; nodal target volume delineation after induction chemotherapy; delineation of equivocal nodes evident on imaging; low-risk clinical target volume delineation based on regional stepwise extension patterns; and modifications for anatomical boundaries of lymphatic areas. Developed through a rigorous systematic review and expert appraisal process by a panel of 50 international, multidisciplinary members from 17 countries and regions, these guidelines incorporate the latest advances in nasopharyngeal carcinoma diagnosis and treatment. They reflect contemporary therapeutic concepts and elaborate on current practice variations. These guidelines aim to standardise global practice, substantially improving consistency and reducing variability in nasopharyngeal carcinoma radiotherapy target delineation.

D. Rochman, A. Koning, S. Goriely et al.

In this work, we are presenting a new database of astrophysical interest, based on calculations performed with the nuclear reaction code TALYS. Four quantities are systematically calculated for over 8000 nuclides: cross sections, reaction rates, Maxwellian Averaged Cross Sections (or MACS) at 30 keV and partition functions. For cross sections and reaction rates, nine reactions are considered, induced by neutron, proton or alpha. The main complement of this database compared to existing ones is that the impact of reaction models ({\it e.g.} level density, gamma strength function, and optical model) is estimated by varying 9 different models, and by proposing calculated values for each of them, together with averages, standard deviations and other statistical quantities. This new database, called TENDL-astro, version 2023, is available online (https://tendl.web.psi.ch/tendl\_2023/astro/astro.html) and linked to the well-known TENDL database, used in a variety of applications.

Joongwon Kim, Anirudh Goyal, Liang Tan et al.

We introduce ASTRO, the"Autoregressive Search-Taught Reasoner", a framework for training language models to reason like search algorithms, explicitly leveraging self-reflection, backtracking, and exploration in their outputs. Recently, training large language models (LLMs) via reinforcement learning (RL) has led to the advent of reasoning models with greatly enhanced reasoning capabilities. Open-source replications of reasoning models, while successful, build upon models that already exhibit strong reasoning capabilities along with search behavior observed even before RL. As a result, it is yet unclear how to boost the reasoning capabilities of other non-reasoner models including Llama 3. ASTRO teaches such models to internalize structured search behavior through a synthetic dataset derived from Monte Carlo Tree Search (MCTS) over mathematical problem-solving trajectories. By converting search traces into natural language chain-of-thoughts that capture both successes and recoveries from failure, ASTRO bootstraps models with a rich prior for exploration during RL. We finetune our models on these search-derived traces and further improve performance via RL with verifiable rewards. We apply ASTRO to the Llama 3 family of models and achieve absolute performance gains of 16.0% on MATH-500, 26.9% on AMC 2023, and 20.0% on AIME 2024, especially improving upon challenging problems that require iterative correction. Our results demonstrate that search-inspired training offers a principled way to instill robust reasoning capabilities into open LLMs.

R. Jimenez, Y. Abdou, Penny Anderson et al.

PURPOSE This guideline provides evidence-based recommendations on the use of postmastectomy radiation therapy (PMRT) in the treatment of breast cancer. PMRT refers to the treatment of the chest wall and ipsilateral regional nodes, including at-risk axillary, supra/infraclavicular, and internal mammary nodes. Updated recommendations detail indications for PMRT in the upfront surgical setting and after neoadjuvant systemic therapy, and provide guidance on appropriate target volumes, dosing, and treatment techniques. METHODS The American Society for Radiation Oncology, American Society of Clinical Oncology, and the Society of Surgical Oncology convened a multidisciplinary task force to address 4 key questions focused on radiation therapy (RT) in patients with breast cancer who undergo mastectomy including (1) indications for PMRT after upfront surgery, (2) indications for PMRT after neoadjuvant systemic therapy followed by surgery, (3) appropriate PMRT treatment volumes and dose-fractionation regimens, and (4) treatment techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS After upfront mastectomy, PMRT is indicated for most patients with node-positive breast cancer and select patients with node-negative disease. PMRT is also recommended after neoadjuvant systemic therapy, both for patients presenting with locally advanced disease and for those with residual nodal disease at the time of surgery. PMRT is conditionally recommended for patients with cT1-3N1 or cT3N0 breast cancer with pathologically negative nodes after neoadjuvant systemic therapy (ypN0). When PMRT is delivered, treatment to the ipsilateral chest wall/reconstructed breast and regional lymphatics is recommended, with moderate hypofractionation preferred, but with conventional fractionation approaches acceptable in rare cases. Computed tomography-based volumetric treatment planning with 3-dimensional conformal RT is recommended, with intensity modulated RT advised when 3-dimensional conformal RT is unable to achieve treatment goals. Deep inspiration breath hold techniques are also recommended for normal tissue sparing. For patients with skin involvement, positive superficial margins, and/or lymphovascular invasion, the use of a bolus is recommended, but the routine use of tissue-equivalent bolus is not recommended. CONCLUSIONS These evidence-based recommendations guide clinical practice on the use of PMRT in patients with breast cancer.

D. Margalit, C. Anker, M. Aristophanous et al.

PURPOSE Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management. METHODS ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and posttreatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins or extranodal extension. Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without positive surgical margins and extranodal extension, 5600 to 6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-dimensional techniques with reduction in dose to critical organs at risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography is recommended approximately 3 months after definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal positron emission tomography-computed tomography findings, either neck dissection or repeat imaging is recommended. CONCLUSIONS The role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.

S. Neibart, Lilie L. Lin, Mark H Einstein et al.

Baptiste Cecconi, L. Debisschop, S'ebastien Derriere et al.

The astronomy communities are widely recognised as mature communities for their open science practices. However, while their data ecosystems are rather advanced and permit efficient data interoperability, there are still gaps between these ecosystems. Semantic artefacts (SAs) -- e.g., ontologies, thesauri, vocabularies or metadata schemas -- are a means to bridge that gap as they allow to semantically described the data and map the underlying concepts. The increasing use of SAs in astronomy presents challenges in description, selection, evaluation, trust, and mappings. The landscape remains fragmented, with SAs scattered across various registries in diverse formats and structures -- not yet fully developed or encoded with rich semantic web standards like OWL or SKOS -- and often with overlapping scopes. Enhancing data semantic interoperability requires common platforms to catalog, align, and facilitate the sharing of FAIR (Findable, Accessible, Interoperable and Reusable) SAs. In the frame of the FAIR-IMPACT project, we prototyped a SA catalogue for astronomy, heliophysics and planetary sciences. This exercise resulted in improved vocabulary and ontology management in the communities, and is now paving the way for better interdisciplinary data discovery and reuse. This article presents current practices in our discipline, reviews candidate SAs for such a catalogue, presents driving use cases and the perspective of a real production service for the astronomy community based on the OntoPortal technology, that will be called OntoPortal-Astro.

Kiyam Lin, Alicja Polanska, Davide Piras et al.

A core motivation of science is to evaluate which scientific model best explains observed data. Bayesian model comparison provides a principled statistical approach to comparing scientific models and has found widespread application within cosmology and astrophysics. Calculating the Bayesian evidence is computationally challenging, especially as we continue to explore increasingly more complex models. The Savage-Dickey density ratio (SDDR) provides a method to calculate the Bayes factor (evidence ratio) between two nested models using only posterior samples from the super model. The SDDR requires the calculation of a normalised marginal distribution over the extra parameters of the super model, which has typically been performed using classical density estimators, such as histograms. Classical density estimators, however, can struggle to scale to high-dimensional settings. We introduce a neural SDDR approach using normalizing flows that can scale to settings where the super model contains a large number of extra parameters. We demonstrate the effectiveness of this neural SDDR methodology applied to both toy and realistic cosmological examples. For a field-level inference setting, we show that Bayes factors computed for a Bayesian hierarchical model (BHM) and simulation-based inference (SBI) approach are consistent, providing further validation that SBI extracts as much cosmological information from the field as the BHM approach. The SDDR estimator with normalizing flows is implemented in the open-source harmonic Python package.

Heinrich Steigerwald

We set up and perform collision rate simulations between dark matter in the form of asteroid-mass primordial black holes (PBHs) and white dwarf stars. These encounters trigger prompt detonations and could be the key to solving the ignition mystery of type Ia supernovae. Our framework is flexible enough to cover the full range of progenitor white dwarf masses, host galaxy stellar masses, galactocentric radial offsets, and cosmic time. The rate distribution pattern is consistent with exhaustive literature observational determinations for a slightly extended log-normal PBH mass spectrum. Most strikingly, the so far unexplained brightness distribution comes out without finetuning. We find no severe contradictions, except that the inferred PBH mass scale is unpredicted from first principles.

Todd M. Morgan, S. Boorjian, M. Buyyounouski et al.

Purpose: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part III of a three-part series focusing on evaluation and management of suspected non-metastatic recurrence after radiotherapy (RT) and focal therapy, evaluation and management of regional recurrence, management for molecular imaging metastatic recurrence, and future directions. Please refer to Part I for discussion of treatment decision-making and Part II for discussion of treatment delivery for non-metastatic biochemical recurrence (BCR) after radical prostatectomy (RP). Materials and Methods: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. Results: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Guideline Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. Conclusions: Continuous and deliberate efforts for multidisciplinary care in prostate cancer will be required to optimize and improve the oncologic and functional outcomes of patients treated with salvage therapies in the future.

Todd M. Morgan, S. Boorjian, M. Buyyounouski et al.

Purpose: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part II of a three-part series focusing on treatment delivery for non-metastatic biochemical recurrence (BCR) after primary radical prostatectomy (RP). Please refer to Part I for discussion of treatment decision-making and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. Materials and Methods: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. Results: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. Conclusions: Optimizing and personalizing the approach to salvage therapy remains an ongoing area of work in the field of genitourinary oncology and represents an area of research and clinical care that requires well-coordinated, multi-disciplinary efforts.

Alicja Polanska, Matthew A. Price, Davide Piras et al.

We present the learned harmonic mean estimator with normalizing flows - a robust, scalable and flexible estimator of the Bayesian evidence for model comparison. Since the estimator is agnostic to sampling strategy and simply requires posterior samples, it can be applied to compute the evidence using any Markov chain Monte Carlo (MCMC) sampling technique, including saved down MCMC chains, or any variational inference approach. The learned harmonic mean estimator was recently introduced, where machine learning techniques were developed to learn a suitable internal importance sampling target distribution to solve the issue of exploding variance of the original harmonic mean estimator. In this article we present the use of normalizing flows as the internal machine learning technique within the learned harmonic mean estimator. Normalizing flows can be elegantly coupled with the learned harmonic mean to provide an approach that is more robust, flexible and scalable than the machine learning models considered previously. We perform a series of numerical experiments, applying our method to benchmark problems and to a cosmological example in up to 21 dimensions. We find the learned harmonic mean estimator is in agreement with ground truth values and nested sampling estimates. The open-source harmonic Python package implementing the learned harmonic mean, now with normalizing flows included, is publicly available.

Jenny Wagner

In our current best cosmological model, the vast majority of matter in the Universe is dark, consisting of yet undetected, non-baryonic particles that do not interact electro-magnetically. So far, the only significant evidence for dark matter has been found in its gravitational interaction, as observed in galaxy rotation curves or gravitational lensing effects. The inferred dark matter agglomerations follow almost universal mass density profiles that can be reproduced well in simulations, but have eluded an explanation from a theoretical viewpoint. Forgoing standard (astro-)physical methods, I show that it is possible to derive these profiles from an intriguingly simple mathematical approach that directly determines the most likely spatial configuration of a self-gravitating ensemble of collisionless dark matter particles.

Pietro Bergamini, Piero Rosati, Eros Vanzella et al.

We present a new high-precision parametric strong lensing model of the galaxy cluster MACS J0416.1-2403, at z=0.396, which takes advantage of the MUSE Deep Lensed Field (MDLF), with 17.1h integration in the northeast region of the cluster, and Hubble Frontier Fields data. We spectroscopically identify 182 multiple images from 48 background sources at 0.9<z<6.2, and 171 cluster member galaxies. Several multiple images are associated to individual clumps in multiply lensed resolved sources. By defining a new metric, which is sensitive to the gradients of the deflection field, we show that we can accurately reproduce the positions of these star-forming knots despite their vicinity to the model critical lines. The high signal-to-noise ratio of the MDLF spectra enables the measurement of the internal velocity dispersion of 64 cluster galaxies, down to m(F160W)=22. This allowed us to independently estimate the contribution of the subhalo mass component of the lens model from the measured Faber-Jackson scaling relation. Our best reference model, which represents a significant step forward compared to our previous analyses, was selected from a comparative study of different mass parametrizations. The root-mean-square displacement between the observed and model-predicted image positions is only 0.40", which is 33% smaller than in all previous models. The mass model appears to be particularly well constrained in the MDLF region. We characterize the robustness of the magnification map at varying distances from the model critical lines and the total projected mass profile of the cluster.