A Tool for Automated Reasoning about Traces Based on Configurable Formal Semantics

We present Tarski, a tool for specifying configurable trace semantics to facilitate automated reasoning about traces. Software development projects require that various types of traces be modeled between and within development artifacts. For any given artifact (e.g., requirements, architecture models and source code), Tarski allows the user to specify new trace types and their configurable semantics, while, using the semantics, it automatically infers new traces based on existing traces provided by the user, and checks the consistency of traces. It has been evaluated on three industrial case studies in the automotive domain (https://modelwriter.github.io/Tarski/)

Within-Field Rice Yield Estimation Based on Sentinel-2 Satellite Data

[EN] Rice is considered one of the most important crops in the world. According to the Food and Agriculture Organization of the United Nations (FAO), rice production has increased significantly (156%) during the last 50 years, with a limited increase in cultivated area (24%). With the recent advances in remote sensing technologies, it is now possible to monitor rice crop production for a better understanding of its management at field scale to ultimately improve rice yields. In this work, we monitor within-field rice production of the two main rice varieties grown in Valencia (Spain) JSendra and Bomba during the 2020 season. The sowing date of both varieties was May 22-25, while the harvesting date was September 15-17 for Bomba and October 5-8 for JSendra. Rice yield data was collected over 66.03 ha (52 fields) by harvesting machines equipped with onboard sensors that determine the dry grain yield within irregular polygons of 3-7 m width. This dataset was split in two, selecting 70% of fields for training and 30% for validation purposes. Sentinel-2 surface reflectance spectral data acquired from May until September 2020 was considered over the test area at the two different spatial resolutions of 10 and 20 m. These two datasets were combined assessing the best combination of spectral reflectance bands (SR) or vegetation indices (VIs) as well as the best timing to infer final within-field yields. The results show that SR improves the performance of models with VIs. Furthermore, the correlation of each spectral band and VIs with the final yield changes with the dates and varieties. Considering the training data, the best correlation with the yields is obtained on July 4, with R-2 for JSendra of 0.72 at 10 m and 0.76 at 20 m resolution, while the R-2 for Bomba is 0.87 at 10 m and 0.92 at 20 m resolution. Based on the validation dataset, the proposed models provide within-field yield modelling Mean Absolute Error (MAE) of 0.254 t.ha(-1) (Mean Absolute Percentage Error, MAPE, of 3.73%) for JSendra at 10 m (0.240 t.ha(-1); 3.48% at 20 m) and 0.218 t.ha(-1) (MAPE 5.82%) for Bomba (0.223 t.ha(-1); 5.78% at 20 m) on July 4, that is three months before harvest. At parcel level the model's MAE is 0.176 t.ha(-1) (MAPE 2.61%) for JSendra and 0.142 t.ha(-1) (MAPE 4.51%) for Bomba. These results confirm the close correlation between the rice yield and the spectral information from satellite imagery. Additionally, these models provide a timeliness overview of underperforming areas within the field three months before the harvest where farmers can improve their management practices. Furthermore, it highlights the importance of optimum agronomic management of rice plants during the first weeks of rice cultivation (40-50 days after sowing) to achieve high yields.This research was partially funded by the program Generacio Talent of Generalitat Valenciana (CIDEGENT/2018/009).Franch-Gras, B.; San Bautista Primo, A.; Fita-Silvestre, D.; Rubio Michavila, C.; Tarrazó-Serrano, D.; Sánchez, A.; Skakun, S.... (2021). Within-Field Rice Yield Estimation Based on Sentinel-2 Satellite Data. Remote Sensing. 13(20). https://doi.org/10.3390/rs13204095132

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis

BackgroundDespite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune‐related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life‐threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment‐related encephalitis, and provide practical guidance on diagnosis and management.MethodsWe searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8‐year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol‐Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned.ResultsIn our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5), encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1–170) and to resolution was 32 days (2–809+). Median time to onset of encephalitis was 55.5 days (range 18–297); four cases resolved and one was fatal.ConclusionBoth oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs.Implications for PracticeWith increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune‐related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab.Melanoma is a particularly immunogenic cancer, and immune checkpoint inhibitors have been extensively studied in this tumor type. This review focuses on the incidence of serious neurologic immune‐related adverse events, specifically encephalitis, in patients with advanced melanoma treated with nivolumab alone or in sequence or combination with ipilimumab. Practical guidance is provided for the diagnosis and management of treatment‐related encephalitis associated with nivolumab and ipilimumab.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139998/1/onco12130.pd

Strain-induced phonon shifts in tungsten disulfide nanoplatelets and nanotubes

The relationship between structure and properties has been followed for different nanoscale forms of tungsten disulfide (2H-WS2) namely exfoliated monolayer and few-layer nanoplatelets, and nanotubes. The similarities and differences between these nanostructured materials have been examined using a combination of optical microscopy, scanning and high-resolution transmissionelectron microscopy (SEM and HRTEM) and atomic force microscopy (AFM). Photoluminescence (PL) and Raman spectroscopy have also been used to distinguish between monolayer and few-layer material. Strain induced phonon shifts have been followed from the changes in the positions of the A1g and E2g1 Raman bands during uniaxial deformation. This has been modelled for monolayer using density functional theory (DFT) with excellent agreement between the measured and predicted behaviour. It has been found that as the number of WS2 layers increases for few-layer crystals or nanotubes, the A1g mode hardens whereas the E2g1 mode softens. This is believed to be due to theA1g mode, which involves out of plane atomic movements, being constrained by the increasing number of WS2 layers whereas easy sliding reduces stress transfer to the individual layers for the E2g1mode, involving only in-plane vibrations. This finding has enabled the anomalous phonon shift behaviour in earlier pressure measurements on WS2 to be resolved, as well as similar effects in othertransition metal dichalcogenides, such as molybdenum disulfide (MoS2), to be explained. <br/

Diameter-dependent wetting of tungsten disulfide nanotubes

The simple process of a liquid wetting a solid surface is controlled by a plethora of factors—surface texture, liquid droplet size and shape, energetics of both liquid and solid surfaces, as well as their interface. Studying these events at the nanoscale provides insights into the molecular basis of wetting. Nanotube wetting studies are particularly challenging due to their unique shape and small size. Nonetheless, the success of nanotubes, particularly inorganic ones, as fillers in composite materials makes it essential to understand how common liquids wet them. Here, we present a comprehensive wetting study of individual tungsten disulfide nanotubes by water. We reveal the nature of interaction at the inert outer wall and show that remarkably high wetting forces are attained on small, open-ended nanotubes due to capillary aspiration into the hollow core. This study provides a theoretical and experimental paradigm for this intricate problem

Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights

Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating a schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium with expression data from brain, blood, and adipose tissues across 3,693 primarily control individuals. We identified 157 TWAS-significant genes, of which 35 did not overlap a known GWAS locus. Of these 157 genes, 42 were associated with specific chromatin features measured in independent samples, thus highlighting potential regulatory targets for follow-up. Suppression of one identified susceptibility gene, mapk3, in zebrafish showed a significant effect on neurodevelopmental phenotypes. Expression and splicing from the brain captured most of the TWAS effect across all genes. This large-scale connection of associations to target genes, tissues, and regulatory features is an essential step in moving toward a mechanistic understanding of GWAS

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia

AbstractCombinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia

Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, N=240) and in myelodysplastic syndrome (MK+MDS, N=221) on hematopoietic cell transplantation (HCT) outcomes compared to other cytogenetically defined groups (AML, N=3,360; MDS, N=1,373) as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1998 to 2011. MK+AML was associated with higher disease relapse (hazard ratio [HR] 1.98, p<0.01), similar transplant related mortality (TRM, HR 1.01, p=0.9) and worse survival (HR 1.67, p<0.01) compared to other cytogenetically defined AML. Among patients with MDS, MK+MDS was associated with higher disease relapse (HR 2.39, p<0.01), higher TRM (HR 1.80, p<0.01) and worse survival (HR 2.02, p<0.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (HR 1.72, p<0.01) and MDS (HR1.79, p<0.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes for acute myeloid leukemia (AML) patients. We evaluated 8709 AML patients from the CIBMTR database and, after selection and manual curation of cytogenetics data, 3779 patients in CR1 were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis compared to intermediate-risk patients detected an increased risk of relapse for KMT2A-rearranged and adverse-risk patients (HR 1.27, p = 0.01 and HR 1.71, p < 0.001, respectively). Leukemia-free survival (LFS) was similar for KMT2A and adverse-risk patients (HR 1.26, p = 0.002 and HR 1.47, p < 0.001), as was overall survival (OS) (HR 1.32, p < 0.001 and HR 1.45, p < 0.001). No differences in outcome could be detected when patients were stratified by KMT2A fusion partner. This is the largest study conducted to date on post-HCT outcomes in AML using manually curated cytogenetics for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A rearrangements and adverse-risk disease