TraceSim: An alignment method for computing stack trace similarity

ABSTRACT: Software systems can automatically submit crash reports to a repository for investigation when program failures occur. A significant portion of these crash reports are duplicate, i.e., they are caused by the same software issue. Therefore, if the volume of submitted reports is very large, automatic grouping of duplicate crash reports can significantly ease and speed up analysis of software failures. This task is known as crash report deduplication. Given a huge volume of incoming reports, increasing quality of deduplication is an important task. The majority of studies address it via information retrieval or sequence matching methods based on the similarity of stack traces from two crash reports. While information retrieval methods disregard the position of a frame in a stack trace, the existing works based on sequence matching algorithms do not fully consider subroutine global frequency and unmatched frames. Besides, due to data distribution differences among software projects, parameters that are learned using machine learning algorithms are necessary to provide more flexibility to the methods. In this paper, we propose TraceSim – an approach for crash report deduplication which combines TF-IDF, optimum global alignment, and machine learning (ML) in a novel way. Moreover, we propose a new evaluation methodology for this task that is more comprehensive and robust than previously used evaluation approaches. TraceSim significantly outperforms seven baselines and state-of-the-art methods in the majority of the scenarios. It is the only approach that achieves competitive results on all datasets regarding all considered metrics. Moreover, we conduct an extensive ablation study that demonstrates the importance of each TraceSim’s element to its final performance and robustness. Finally, we provide the source code for all considered methods and evaluation methodology as well as the created datasets

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study

© 2023 The Author(s). This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in The Lancet Oncology. To access the final edited and published work see https://doi.org/10.1016/S1470-2045(23)00268-1Background The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer. Methods In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a–c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0–1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1–14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1–21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete. Findings Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0–68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0–67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was –75% (95% CI –80 to –70) with giredestrant and –67% (–73 to –59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3–4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction). Interpretation Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

BACKGROUND: In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib. METHODS: We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety. RESULTS: A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups. CONCLUSIONS: Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.)

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

A Radionuclide Generator of High-Purity Bi-213 for Instant Labeling

A new two-column 225Ac/213Bi generator was developed specifically for using 225Ac containing an impurity of long lived 227Ac. The parent 225Ac was retained on the first Actinide Resin column, while 213Bi was accumulated on the second column filled with AG MP-50 resin via continuous elution and decay of intermediate 221Fr. The 213Bi accumulation was realized in circulation mode which allowed a compact generator design. It was demonstrated that 213Bi could be quickly and effectively extracted from AG MP-50 in form of complexes with various chelating agents including DTPA and DOTA. The performance of the generator presented and a conventional single-column generator on the base of AG MP-50 was tested and both generators were loaded with 225Ac containing 227Ac impurity. The 213Bi generation efficiencies were comparable and greater than 70%, whereas the developed generator provided a deeper degree of purification of 213Bi from Ac isotopes and decay products of 227Ac

Rapid Elution of ²²⁶Th from a Two-Column ²³⁰U/²²⁶Th Generator with Diluted and Buffer Solutions

A radionuclide generator of the short-lived alpha emitter 226Th was proposed. An original scheme consisting of two in-series chromatographic columns was developed for rapidly producing a neutral citric-buffered eluate of high purity 226Th. The first column filled with TEVA resin retained the parent 230U, while 226Th was eluted with 7 M HCl solution to be immediately adsorbed on the second column containing DGA resin or UTEVA resin. Having substituted the strongly acidic medium of second column with neutral salt solution, 226Th was desorbed with diluted citric buffer solution. One cycle of generator milking took 5–7 min and produced >90% of 226Th in 1.5 mL of eluate (pH 4.5–5.0) appropriate for direct use in radiopharmaceutical synthesis. The 230U impurity in 226Th eluate was less than 0.01%. The proposed two-column 230U/226Th generator was tested over 2 months including a second loading of 230U additionally accumulated from 230Pa