COVID-19 and haematological malignancy: navigating a narrow strait

Patients with haematological malignancies face unique infectious risks. Not only do their cancers typically directly affect the immune system, but therapies can cause severe myelosuppression and lymphodepletion, especially in curative settings. Vigilance to avoid life-threatening infection is a part of life for these patients and is crucial in medical decision making. With this context, the COVID-19 pandemic has understandably shaken this community, and more data to guide management are needed

Phenome-Based Analysis as a Means for Discovering Context-Dependent Clinical Reference Ranges

Abstract Robust electronic medical records (EMR's

Normalization of drug and therapeutic concepts with Thera-Py

OBJECTIVE: The diversity of nomenclature and naming strategies makes therapeutic terminology difficult to manage and harmonize. As the number and complexity of available therapeutic ontologies continues to increase, the need for harmonized cross-resource mappings is becoming increasingly apparent. This study creates harmonized concept mappings that enable the linking together of like-concepts despite source-dependent differences in data structure or semantic representation. MATERIALS AND METHODS: For this study, we created Thera-Py, a Python package and web API that constructs searchable concepts for drugs and therapeutic terminologies using 9 public resources and thesauri. By using a directed graph approach, Thera-Py captures commonly used aliases, trade names, annotations, and associations for any given therapeutic and combines them under a single concept record. RESULTS: We highlight the creation of 16 069 unique merged therapeutic concepts from 9 distinct sources using Thera-Py and observe an increase in overlap of therapeutic concepts in 2 or more knowledge bases after harmonization using Thera-Py (9.8%-41.8%). CONCLUSION: We observe that Thera-Py tends to normalize therapeutic concepts to their underlying active ingredients (excluding nondrug therapeutics, eg, radiation therapy, biologics), and unifies all available descriptors regardless of ontological origin

Natural language processing to automatically extract the presence and severity of esophagitis in notes of patients undergoing radiotherapy

Radiotherapy (RT) toxicities can impair survival and quality-of-life, yet remain under-studied. Real-world evidence holds potential to improve our understanding of toxicities, but toxicity information is often only in clinical notes. We developed natural language processing (NLP) models to identify the presence and severity of esophagitis from notes of patients treated with thoracic RT. We fine-tuned statistical and pre-trained BERT-based models for three esophagitis classification tasks: Task 1) presence of esophagitis, Task 2) severe esophagitis or not, and Task 3) no esophagitis vs. grade 1 vs. grade 2-3. Transferability was tested on 345 notes from patients with esophageal cancer undergoing RT. Fine-tuning PubmedBERT yielded the best performance. The best macro-F1 was 0.92, 0.82, and 0.74 for Task 1, 2, and 3, respectively. Selecting the most informative note sections during fine-tuning improved macro-F1 by over 2% for all tasks. Silver-labeled data improved the macro-F1 by over 3% across all tasks. For the esophageal cancer notes, the best macro-F1 was 0.73, 0.74, and 0.65 for Task 1, 2, and 3, respectively, without additional fine-tuning. To our knowledge, this is the first effort to automatically extract esophagitis toxicity severity according to CTCAE guidelines from clinic notes. The promising performance provides proof-of-concept for NLP-based automated detailed toxicity monitoring in expanded domains.Comment: 17 pages, 6 tables, 1figure, submiting to JCO-CCI for revie

Collaborative, Multidisciplinary Evaluation of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices.

PURPOSE: The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics to support case review and treatment planning. METHODS: In this review, we evaluate and summarize the landscape of available tools, resources, and evidence used in the evaluation of somatic and germline tumor variants within the context of molecular tumor boards. RESULTS: Molecular tumor boards (MTBs) are collaborative efforts of multidisciplinary cancer experts equipped with genomic interpretation resources to aid in the delivery of accurate and timely clinical interpretations of complex genomic results for each patient, within an institution or hospital network. Virtual MTBs (VMTBs) provide an online forum for collaborative governance, provenance, and information sharing between experts outside a given hospital network with the potential to enhance MTB discussions. Knowledge sharing in VMTBs and communication with guideline-developing organizations can lead to progress evidenced by data harmonization across resources, crowd-sourced and expert-curated genomic assertions, and a more informed and explainable usage of artificial intelligence. CONCLUSION: Advances in cancer genomics interpretation aid in better patient and disease classification, more streamlined identification of relevant literature, and a more thorough review of available treatments and predicted patient outcomes

Swift X-Ray Observations of Classical Novae. II. The Super Soft Source sample

The Swift GRB satellite is an excellent facility for studying novae. Its rapid response time and sensitive X-ray detector provides an unparalleled opportunity to investigate the previously poorly sampled evolution of novae in the X-ray regime. This paper presents Swift observations of 52 Galactic/Magellanic Cloud novae. We included the XRT (0.3-10 keV) X-ray instrument count rates and the UVOT (1700-8000 Angstroms) filter photometry. Also included in the analysis are the publicly available pointed observations of 10 additional novae the X-ray archives. This is the largest X-ray sample of Galactic/Magellanic Cloud novae yet assembled and consists of 26 novae with super soft X-ray emission, 19 from Swift observations. The data set shows that the faster novae have an early hard X-ray phase that is usually missing in slower novae. The Super Soft X-ray phase occurs earlier and does not last as long in fast novae compared to slower novae. All the Swift novae with sufficient observations show that novae are highly variable with rapid variability and different periodicities. In the majority of cases, nuclear burning ceases less than 3 years after the outburst begins. Previous relationships, such as the nuclear burning duration vs. t_2 or the expansion velocity of the eject and nuclear burning duration vs. the orbital period, are shown to be poorly correlated with the full sample indicating that additional factors beyond the white dwarf mass and binary separation play important roles in the evolution of a nova outburst. Finally, we confirm two optical phenomena that are correlated with strong, soft X-ray emission which can be used to further increase the efficiency of X-ray campaigns.Comment: Accepted to ApJ Supplements. Full data for Table 2 and Figure 17 available in the electronic edition. New version of the previously posted paper since the earlier version was all set in landscape mod

Governance and Shareholder Value in Delegated Portfolio Management: The Case of Closed-End Funds

Based on the records of 1183 individual fund managers from 1985 to 2010, we investigate the compensation and discipline mechanisms in the closed-end fund industry and their implications for manager performance and fund premium. We find that managers generating high surplus, as proxied by fund premium, capture rents on their skills by expansions of assets under management and increases in management fees; however, managers with a high discount are not penalized accordingly. Managers with poor NAV performance suffer from asset contractions, but such discipline is insignificant for managers with long tenure. Consistent with manager entrenchment and decreasing returns to scale, NAV performance and premium decline with manager tenure and the size of assets under management. Finally, in support of the notion that adjustments of assets under management and management fees in response to extreme performance break the premium-performance relation, we find that the fund premium responds positively only to the medium-range NAV performance

Doing masculinity, not doing health? a qualitative study among dutch male employees about health beliefs and workplace physical activity

<p>Abstract</p> <p>Background</p> <p>Being female is a strong predictor of health promoting behaviours. Workplaces show great potential for lifestyle interventions, but such interventions do not necessarily take the gendered background of lifestyle behaviours into account. A perspective analyzing how masculine gender norms affect health promoting behaviours is important. This study aims to explore men's health beliefs and attitudes towards health promotion; in particular, it explores workplace physical activity in relation to masculine ideals among male employees.</p> <p>Methods</p> <p>In the Fall of 2008, we interviewed 13 white Dutch male employees aged 23-56 years. The men worked in a wide range of professions and occupational sectors and all interviewees had been offered a workplace physical activity program. Interviews lasted approximately one to one-and-a-half hour and addressed beliefs about health and lifestyle behaviours including workplace physical activity, as well as normative beliefs about masculinity. Thematic analysis was used to analyze the data.</p> <p>Results</p> <p>Two normative themes were found: first, the ideal man is equated with being a winner and real men are prepared to compete, and second, real men are not whiners and ideally, not vulnerable. Workplace physical activity is associated with a particular type of masculinity - young, occupied with looks, and interested in muscle building. Masculine norms are related to challenging health while taking care of health is feminine and, hence, something to avoid. Workplace physical activity is not framed as a health measure, and not mentioned as of importance to the work role.</p> <p>Conclusions</p> <p>Competitiveness and nonchalant attitudes towards health shape masculine ideals. In regards to workplace physical activity, some men resist what they perceive to be an emphasis on muscled looks, whereas for others it contributes to looking self-confident. In order to establish a greater reach among vulnerable employees such as ageing men, worksite health promotion programs including workplace physical activity may benefit from greater insight in the tensions between health behaviours and masculinity.</p

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure