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DOE OSTI2025

The Arctic

The Arctic environment in 2024 continued on a trajectory that has put it in a state far different from that of the twentieth century. Ongoing accumulation of greenhouse gases in the atmosphere continues to quickly warm the Arctic, resulting in rapid changes in the cryosphere that are driving cascading impacts to climate, ecological, and societal systems. Many weather- and climate-related impacts in the Arctic are the result of compounding change, such as increased riverbank erosion, which is proximately due to increased river discharge from higher seasonal precipitation, yet is also exacerbated by thawing permafrost. However, even individual storms occur within very different ocean and ice conditions than were typically present in the late twentieth century. As a result, the impacts, including high winds, excessive precipitation, and coastal inundation, may be quite different nowadays, as exemplified by the October 2024 storm in northwest Alaska that produced severe coastal flooding in several communities. To share some of these impacts with a wider audience, select extreme weather impacts around the greater Arctic have been highlighted through the inclusion of sidebars in recent State of the Climate Arctic chapters (e.g., Benestad et al. 2023; Thoman et al. 2024).

Thoman, Richard L. [Univ. of Alaska, Fairbanks, AK↗

DOE OSTI2019

Safety of Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Liver Metastases from Ocular Melanoma Using the Delcath Systems’ Second-Generation Hemofiltration System: A Prospective Non-randomized Phase II Trial

Purpose: To investigate the safety and toxicity of percutaneous hepatic perfusion with melphalan (M-PHP) with the Delcath Systems’ second-generation (GEN 2) filter and compare the outcomes with historical data from studies using the first-generation filter. Materials and Methods: A prospective, single-arm, single-center phase II study was carried out including 35 patients with unresectable, histologically confirmed liver metastases from ocular melanoma between February 2014 and June 2017. Main exclusion criteria were extrahepatic disease and age > 75 years. M-PHP was performed with melphalan 3 mg/kg (maximum dose 220 mg). Safety and toxicity were assessed according to the Common Terminology Criteria for Adverse Events version 4.03. Results: A total of 67 M-PHPs were performed in 35 patients (median 2 procedures). Although hematologic grade 3/4 events were seen in the majority of patients (thrombocytopenia 54.5%, leukopenia 75.6%, neutropenia 66.7%, anemia (only grade 3) 18.1%), these were all well manageable or self-limiting. Of the non-hematologic grade 3 events (n = 14), febrile neutropenia (n = 3), pulmonary emboli (n = 2) and post-procedural hemorrhage (n = 2) were most common. A case of sepsis with bacterial pharyngitis was the only non-hematologic grade 4 event. Prior therapy for liver metastases was found to be a predictor of late grade 3/4 neutropenia with an odds ratio of 5.5 (95% CI 1.4–21.7). Conclusions: M-PHP using the GEN 2 filter has an acceptable safety and toxicity profile, and seems to reduce hematologic toxicity when compared to M-PHP with a first-generation filter. Prior therapy of liver metastases is a possible predictive factor in developing grade 3/4 hematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2023

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’s regional difference and global difference, were used to test for regional differences that diverge from the global difference. For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

15q11.2 BP1-BP2↗

DOE OSTI2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Integration of RNTuple in ATLAS Athena

After using ROOT’s TTree I/O subsystem for over two decades and storing more than an exabyte of compressed High Energy Physics (HEP) data, advances in technology have motivated a complete redesign, RNTuple, which breaks backward-compatibility to take better advantage of these storage options. The RNTuple I/O subsystem has been designed to address performance bottlenecks and other shortcomings of TTree. Specifically, RNTuple comes with an updated, more compact binary data format that can be stored both in ROOT files and natively in object stores. It is designed for modern storage hardware (e.g. high-throughput low-latency NVMe SSDs), and provides robust and easy to use interfaces. The binary format of RNTuple is scheduled to become production grade in 2024, and recently has become mature enough to start exploring the integration into software used by HEP experiments. In this contribution, we discuss the developments to support the features as required by the ATLAS analysis Event Data Model (EDM) in RNTuple, which will enable its integration into the Athena software framework. With these developments in place, we evaluate the performance of the current most recent versions of RNTuple-based ATLAS data sets and compare this to that of TTree.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

DOE OSTI2024

ROOT’s RNTuple I/O Subsystem: The Path to Production

The RNTuple I/O subsystem is ROOT’s future event data file format and access API. It is driven by the expected data volume increase at upcoming HEP experiments, e.g. at the HL-LHC, and recent opportunities in the storage hardware and software landscape such as NVMe drives and distributed object stores. RNTuple is a redesign of the TTree binary format and API and has shown to deliver substantially faster data throughput and better data compression both compared to TTree and to industry standard formats. In order to let HENP computing workflows benefit from RNTuple’s superior performance, however, the I/O stack needs to connect efficiently to the rest of the ecosystem, from grid storage to (distributed) analysis frameworks to (multithreaded) experiment frameworks for reconstruction and ntuple derivation. With the RNTuple binary format soon arriving at its first production release, we present RNTuple’s feature set, integration efforts, and its performance impact on the time-to-solution. We show the latest performance figures of RDataFrame analysis code of realistic complexity, comparing RNTuple and TTree as data sources. We discuss RNTuple’s approach to functionality critical to the HENP I/O (such as multithreaded writes, fast data merging, schema evolution) and we provide an outlook on the road to its use in production.

Blomer, Jakob↗

DOE OSTI2025

On-the-fly data set combinations with RNTuple

With the expected data volume increase for HL-LHC and the even more complex computing challenges set by future colliders, the need for efficient data storage and processing becomes more pressing. ROOT’s next-generation data format and I/O subsystem, RNTTuple, is designed to address these challenges. RNTTuple already demonstrates a clear improvement in storage and I/O efficiency, as well as overall stability and robustness with respect to its predecessor, TTTree. These improvements provide a solid baseline to introduce novel extensions to common high-energy and nuclear physics (HENP) workflows. Notably, many workflows could benefit from the ability to arbitrarily join and chain data set samples at runtime, which could reduce overall storage requirements and improve application runtime and ergonomics. In this paper, we present the RNTupleProcessor, which enables HENP data set combinations with RNTuple. We will discuss the main design considerations, present the interfaces to support data set combinations and show how they integrate in typical workflows.

de Geus, Florine Willemijn [CERN; Twente U., Ensch↗

DOE OSTI2025

ROOT RNTuple and EOS: The Next Generation of Event Data I/O

For several years, the ROOT team is developing the new RNTuple I/O subsystem in preparation of the next generation of collider experiments. Both HL-LHC and DUNE are expected to start data taking by the end of this decade. They pose unprecedented challenges to event data I/O in terms of data rates, event sizes, and event complexity. At the same time, the I/O landscape is becoming more diverse. HPC cluster file systems and object stores, NVMe disk cache layers in analysis facilities, and S3 storage on cloud resources are mixing with traditional XRootD-managed spinning disk pools.The ROOT team will finalize a first production version of the RNTuple binary format by the end of 2024. After this point, ROOT will provide backward compatibility for RNTuple data. This contribution provides an overview of the RNTuple feature set, the related R&D activities and the long-term vision for RNTuple. We report on performance, interface design, tooling, robustness, integration with experiment frameworks, and validation results, as well as recent R&D on parallel reading and writing and exploitation of modern hardware and storage systems. We will give an outlook on possible future features after a first production release.Collaboratively, the IT and EP departments at CERN have launched a formal project within the Research and Computing sector to evaluate the novel data format for physics analysis data utilized in LHC experiments and other fields. This part of the project focuses on validating the scalability of the EOS storage backend during the transition from the over 25 years old TTree production format to the newly developed RNTuple format, using both replicated and erasure-coded storage profiles.

Blomer, Jakob [CERN]↗