The detection of life on rocky exoplanets in the habitable zones of nearby stars would be a paradigm-shifting advance, and it is one of the greatest scientific challenges of our time. There is no single spectral feature that is an unambiguous sign of life on a given exoplanet. Instead, the current state-of-the-art approach involves detecting multiple molecular atmospheric features that should not exist together in equilibrium, e.g. simultaneous detection of O$_2$ and CH$_4$. Spectra across a wide wavelength (0.3-1.7 $μ$m) range are necessary to cover multiple spectral features per molecule of interest and to contextualise the suite of molecular features detected. While the US will lead the optical arm of the Habitable Worlds Observatory (HWO) coronagraph, a UK-led contribution of a near-infrared Integral Field Spectrograph (IFS) for the infrared arm will ensure UK leadership in the flagship scientific goal of HWO - to search for signatures of life on potentially habitable exoplanets.
PURPOSE This guideline provides evidence-based recommendations for palliative external beam radiation therapy (RT) in symptomatic bone metastases. METHODS The American Society for Radiation Oncology (ASTRO) convened a task force to address 5 key questions regarding palliative RT in symptomatic bone metastases. Based on a systemic review by the Agency for Health Research and Quality, recommendations using predefined consensus-building methodology were established; evidence quality and recommendation strength were also assessed. RESULTS For palliative RT for symptomatic bone metastases, RT is recommended for managing pain from bone metastases and spine metastases with or without spinal cord or cauda equina compression. Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone. Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression. Patients with non-spine bone metastases requiring surgery are recommended postoperative RT. Symptomatic bone metastases treated with conventional RT are recommended 800 cGy in 1 fraction (800 cGy/1fx), 2000 cGy/5fx, 2400 cGy/6fx, or 3000 cGy/10fx. Spinal cord or cauda equina compression in patients ineligible for surgery and receiving conventional RT are recommended 800 cGy/1fx, 1600 cGy/2fx, 2000 cGy/5fx, or 3000 cGy/10fx. Symptomatic bone metastases in selected patients with good performance status without surgery or neurological symptoms/signs are conditionally recommended SBRT over conventional palliative RT. Spine bone metastases re-irradiated with conventional RT are recommended 800 cGy/1fx, 2000 cGy/5fx, 2400 cGy/6fx, or 2000 cGy/8fx; non-spine bone metastases re-irradiated with conventional RT are recommended 800 cGy/1fx, 2000 cGy/5fx, or 2400 cGy/6fx. Determination of an optimal RT approach/regimen requires whole person assessment, including prognosis, previous RT dose if applicable, risks to normal tissues, quality of life, cost implications, and patient goals and values. Relatedly, for patient-centered optimization of treatment-related toxicities and quality of life, shared decision-making is recommended. CONCLUSIONS Based on published data, the ASTRO task force's recommendations inform best clinical practices on palliative RT for symptomatic bone metastases.
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.
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.
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.
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.
Cosmic and planetary dust hold vital clues to the chemical evolution of the solar system, yet in situ analysis of their molecular and elemental composition remains technically challenging. Here we present laboratory results from HANKA (High-resolution mass Analyzer for Nano-scale Kinetic Astro materials), a compact Orbitrap-based mass spectrometer developed towards the goal of a universal dust detector for space applications. Using infrared laser ablation and plasma formation under vacuum, we analyzed solid-state samples representative of Lunar, Martian, and Meteoritic material. The resulting mass spectra - recorded at resolving powers of R=60000 - reveal complex, but characteristic element mixtures. These results demonstrate the single event sensitivity of HANKA, and its mass resolution with the ability to resolve complex mass spectra and possibly differentiate geochemical signatures across planetary bodies. The dynamic range of 3-4 orders of magnitude enables even the detection of trace compounds. The minimalistic impact sampling approach enables fast, high-precision compositional mass analysis without complex sample preparation, making the instrument well-suited for orbital, surface, or flyby missions with expected dust impacts. Our system consists of an IR-laser system that simulates impacts of nano to micron sized solid-state dust and ice particles from space. It therefore allows to perform so called analogue experiments in the laboratory. We conclude that IR- laser pulses on a solid-state material are not only well suited for ice particle impact analogues but also a good analogue experiment for solid state particle impacts on a dust detector electrode in space. Moreover, the IR laser is employed only for an optimal analogue experiment simulating the impact event - it is not necessary in space on a spacecraft detecting space dust.
We all love the ecstasy that comes with submitting papers to journals or arXiv. Some have described it as yeeting their back-breaking products of labor into the void, wishing they could never deal with them ever again. The very act of yeeting papers onto arXiv contributes to the expansion of the arXiverse; however, we have yet to quantify our contribution to the cause. In this work, I investigate the expansion of the arXiverse using the arXiv astro-ph submission data from 1992 to date. I coin the term "the arXiverse constant", $a_0$, to quantify the rate of expansion of the arXiverse. I find that astro-ph as a whole has a positive $a_0$, but this does not always hold true for the six subcategories of astro-ph. I then investigate the temporal changes in $a_0$ for the astro-ph subcategories and astro-ph as a whole, from which I infer the fate of the arXiverse.
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.
C. Deville, Sophia C. Kamran, Scott C. Morgan
et al.
PURPOSE Our purpose was to develop a summary of recommendations regarding the management of patients with clinically localized prostate cancer based on the American Urologic Association/ ASTRO Guideline on Clinically Localized Prostate Cancer. METHODS The American Urologic Association and ASTRO convened a multidisciplinary, expert panel to develop recommendations based on a systematic literature review using an a priori defined consensus-building methodology. The topics covered were risk assessment, staging, risk-based management, principles of management including active surveillance, surgery, radiation, and follow-up after treatment. Presented are recommendations from the guideline most pertinent to radiation oncologists with an additional statement on health equity, diversity, and inclusion related to guideline panel composition and the topic of clinically localized prostate cancer. SUMMARY Staging, risk assessment, and management options in prostate cancer have advanced over the last decade and significantly affect shared decision-making for treatment management. Current advancements and controversies discussed to guide staging, risk assessment, and treatment recommendations include the use of advanced imaging and tumor genomic profiling. An essential active surveillance strategy includes prostate-specific antigen monitoring and periodic digital rectal examination with changes triggering magnetic resonance imaging and possible biopsy thereafter and histologic progression or greater tumor volume prompting consideration of definitive local treatment. The panel recommends against routine use of adjuvant radiation therapy (RT) for patients with prostate cancer after prostatectomy with negative nodes and an undetectable prostate-specific antigen, while acknowledging that patients at highest risk of recurrence were relatively poorly represented in the 3 largest randomized trials comparing adjuvant RT to early salvage and that a role may exist for adjuvant RT in selected patients at highest risk. RT for clinically localized prostate cancer has evolved rapidly, with new trial results, therapeutic combinations, and technological advances. The recommendation of moderately hypofractionated RT has not changed, and the updated guideline incorporates a conditional recommendation for the use of ultrahypofractionated treatment. Health disparities and inequities exist in the management of clinically localized prostate cancer across the continuum of care that can influence guideline concordance.
The Astro 2020 Decadal Survey "Pathways to Discovery in Astronomy and Astrophysics for the 2020s" has recommended that "after a successful mission and technology maturation program, NASA should embark on a program to realize a mission to search for biosignatures from a robust number of about ~25 habitable zone planets and to be a transformative facility for general astrophysics," and prescribing that the high-contrast direct imaging mission would have "a target off-axis inscribed diameter of approximately 6 meters." The Decadal Survey assumed an exo-Earth frequency of ~25%, requiring that approximately 100 cumulative habitable zones of nearby stars should be surveyed. Surveying the nearby bright stars, and taking into account inputs from the LUVOIR and HabEx mission studies (but without being overly prescriptive in the required starlight suppression technology or requirements), we compile a list of 164 stars whose exo-Earths would be the most accessible for a systematic imaging survey of habitable zones with a 6-m-class space telescope in terms of angular separation, planet brightness in reflected light, and planet-star brightness ratio. We compile this star list to motivate observations and analysis to help inform observatory design (mission-enabling "precursor science") and enhance the science return of the Habitable Worlds Observatory (HWO) survey for exo-Earths (mission-enhancing "preparatory science"). It is anticipated that this list of target stars and their properties will be updated periodically by the NASA Exoplanet Exploration Program.
The latest results from our ongoing multiplicity study of (Community) TESS Objects of Interest are presented, using astro- and photometric data from the ESA-Gaia mission, to detect stellar companions of these stars and characterize their properties. A total of 124 binary and 7 hierarchical triple star systems were detected among 2175 targets, whose multiplicity was investigated in the course of our survey, which are located at distances closer than about 500pc around the Sun. The detected companions and the targets are located at the same distance and share a common proper motion, as expected for components of gravitationally bound stellar systems, as proven with their accurate Gaia EDR3 astrometry. The companions have masses in the range between about 0.09 and 2.5$M_\odot$ and are most frequently found in the mass range between 0.15 and 0.8$M_\odot$. The companions exhibit projected separations to the targets between about 50 to 9700au and their frequency is the highest and constant up to about 500au, while it decreases for larger projected separations. In addition to mainly mid M to early K dwarfs, 4 white dwarf companions were detected in this survey, whose true nature could be identified with their photometric properties.
We present the latest results of our ongoing multiplicity study of (Community) TESS Objects of Interest, using astro- and photometric data from the ESA-Gaia mission, to detect stellar companions of these stars and to characterize their properties. In total, 113 binary, 5 hierarchical triple star systems, as well as one quadruple system were detected among 585 targets surveyed, which are all located at distances closer than about 500pc around the Sun. As proven with their accurate Gaia EDR3 astrometry the companions and the targets are located at the same distance and share a common proper motion, as it is expected for components of gravitationally bound stellar systems. The companions exhibit masses in the range between about 0.09$M_\odot$ and 4.5$M_\odot$ and are most frequently found in the mass range between 0.15 and 0.6$M_{\odot}$. The companions are separated from the targets by about 120 up to 9500au and their frequency is the highest and constant within about 500au while it continually decreases for larger separations. Beside mainly early to mid M dwarfs, also 5 white dwarf companions were identified in this survey, whose true nature was revealed by their photometric properties.
To address the the problem of calibration of instrument systematics in transit light curves, we present the Python package ExoTiC-ISM. Transit spectroscopy can reveal many different chemical components in exoplanet atmospheres, but such results depend on well-calibrated transit light curve observations. Each transit data set will contain instrument systematics that depend on the instrument used and will need to be calibrated out with an instrument systematic model. The proposed solution in Wakeford et al. (2016) (arXiv:1601.02587 [astro-ph.EP]) is to use a marginalisation across a grid of systematic models in order to retrieve marginalised transit parameters. Doing this over observations in multiple wavelengths yields a robust transmission spectrum of an exoplanet. ExoTiC-ISM provides tools to perform this analysis, and its current capability contains a systematic grid that is applicable to the Wide Field Camera 3 (WFC3) detector on the Hubble Space Telescope (HST), particularly for the two infrared grisms G141 and G102. By modularisation of the code and implementation of more systematic grids, ExoTiC-ISM can be used for other instruments, and an implementation for select detectors on the James Webb Space Telescope (JWST) will provide robust transit spectra in the future.
Purpose To assess US radiation oncologists’ views on practice scope and the ideal role of the radiation oncologist (RO), the American Society for Radiation Oncology (ASTRO) conducted a scope of practice survey. Methods and Materials In spring 2019, ASTRO distributed an online survey to 3822 US RO members. The survey generated 984 complete responses (26% response rate) for analysis. Face validity testing confirmed respondents were representative of ASTRO’s RO membership. Results Nearly all respondents agreed that “ROs should be leaders in oncologic care.” Respondents indicated the ideal approach to patient care was to provide “an independent opinion on radiation therapy and other treatment options” (82.5%) or “an independent opinion on radiation therapy but not outside of it” (16.1%), with only 1.4% favoring provision of “radiation therapy at the request of the referring physician” as the ideal approach. Actual practice fully matched the ideal approach in 18.2% of respondents. For the remaining majority, actual practice did not always match the ideal and comprised a mix of approaches that included providing radiation at the referring physician’s request 24.0% of the time on average. Reasons for the mismatch included fear of alienating referring physicians and concern for offering an unwelcome opinion. One-fifth of respondents expressed a desire to expand the scope of service though interspecialty politics and insufficient training were potential barriers. Respondents interested in expanding scope of practice were on average earlier in their career (average years in practice 13.3) than those who were not interested (average years in practice 17.2, P < .001). Radiopharmaceuticals administration, medical marijuana and anticancer medications prescribing, and RO inpatient service represented areas of interest for expansion but also knowledge gaps. Conclusions These results provide insight regarding US ROs’ scope of practice and attitudes on the ideal role of the RO. For most ROs, to provide an independent opinion on treatment options represented the ideal approach to care, but barriers such as concern of alienating referring physicians prevented many from fully adhering to their ideal in practice. Actual practice commonly comprised a mixed approach, including the least favored scenario of delivering radiation at the referring physician’s request one-quarter of the time, highlighting the influence of interspecialty politics on practice behavior. Advocacy for open communication and meaningful interdisciplinary collaboration presents an actionable solution toward a more balanced relationship with other specialties as ROs strive to better fulfill the vision of being leaders in oncologic care and being our best for our patients. The study also identified interest in expanding into nontraditional domains that offer opportunities to address unmet needs in the cancer patient’s journey and elevate radiation oncology within the increasingly value-based US health care system.
AbstractHere we demonstrate the simultaneous recovery of multiplexed physical information of surface‐enhanced Raman scattering (SERS) nanoparticles (pH and depth) using deep Raman spectroscopy. As has been shown previously and in accordance with theory, inelastically scattered photons arising from spectral peaks that are suitably separated can exhibit different optical properties in the media through which they travel. These differences can impact the relative intensities of the Raman peaks as a function of the transmission path length; thereby, the depth of signal generation is inherently encoded in the spectra; assuming the target is clustered at a single depth or location, its depth can be readily determined. Moreover, Raman spectroscopy is very sensitive to chemistry of a sample, and changes in pH are observed not only as changes in peak intensity through relevant protonation and deprotonation but also as shifts in spectral features. Here, we show it is possible to precisely predict the depth (root‐mean‐square error [RMSE] 5 %) of SERS nanoparticles in scattering media (0.5% intralipid) while also being able to noninvasively monitor simultaneously the pH levels (RMSE ~0.2 pH units) of the media surrounding the nanoparticles. This is important as it demonstrates that nanoparticles can be used to report on multiple physical properties including their depth. This opens avenues for a range of new applications including the noninvasive diagnosis and localisation of cancer lesions in clinical environment in vivo.
ESPRESSO is the new high-resolution spectrograph of ESO's Very-Large Telescope (VLT). It was designed for ultra-high radial-velocity precision and extreme spectral fidelity with the aim of performing exoplanet research and fundamental astrophysical experiments with unprecedented precision and accuracy. It is able to observe with any of the four Unit Telescopes (UT) of the VLT at a spectral resolving power of 140,000 or 190,000 over the 378.2 to 788.7 nm wavelength range, or with all UTs together, turning the VLT into a 16-m diameter equivalent telescope in terms of collecting area, while still providing a resolving power of 70,000. We provide a general description of the ESPRESSO instrument, report on the actual on-sky performance, and present our Guaranteed-Time Observation (GTO) program with its first results. ESPRESSO was installed on the Paranal Observatory in fall 2017. Commissioning (on-sky testing) was conducted between December 2017 and September 2018. The instrument saw its official start of operations on October 1st, 2018, but improvements to the instrument and re-commissioning runs were conducted until July 2019. The measured overall optical throughput of ESPRESSO at 550 nm and a seeing of 0.65 arcsec exceeds the 10% mark under nominal astro-climatic conditions. We demonstrate a radial-velocity precision of better than 25 cm/s during one night and 50 cm/s over several months. These values being limited by photon noise and stellar jitter show that the performanceis compatible with an instrumental precision of 10 cm/s. No difference has been measured across the UTs neither in throughput nor RV precision. The combination of the large collecting telescope area with the efficiency and the exquisite spectral fidelity of ESPRESSO opens a new parameter space in RV measurements, the study of planetary atmospheres, fundamental constants, stellar characterisation and many other fields.