Measuring And Understanding Health-Related Quality Of Life Among Adult Patients With Hemophilia

Objectives: The objectives of this study are to: 1) examine the psychometric properties of the Medical Outcomes Study Short Form-12 Version 2 (SF-12v2); 2) assess the measurement invariance of the SF-12v2 with respect to age, disease severity, and treatment regimen; 3) identify psychosocial predictors of health-related quality (HRQOL) among adults with hemophilia in the United States. Methods: This cross-sectional study was conducted using both a web-based and paper-based self-administered survey. Adults with hemophilia were recruited using an online panel, a Facebook community of hemophilia patients, and at the University of Mississippi Medical Center hemophilia treatment clinic. Psychometric properties of the SF-12v2 were established in terms of its construct validity and internal consistency reliability using confirmatory factor analysis (CFA). The measurement invariance of the scale was examined using a multi-group CFA based approach. Finally, structural equation modeling (SEM) was used to test a theory driven model to identify psychosocial predictors of HRQOL in the study sample. Results A total of 218 adults with hemophilia completed the survey. The SF-12v2 was found to be psychometrically valid in the study population. The CFA revealed a two-factor model for the SF-12v2 instrument similar to what has been previously established in the literature. The instrument was found to invariant with respect to age, disease severity, and treatment regimen. Results from the SEM analysis suggested that disability, social support, maladaptive coping, and self-efficacy were key predictors of HRQOL among adults with hemophilia. Conclusions The study results indicated that the SF-12v2 is a psychometrically sound instrument to assess HRQOL of adults with hemophilia. Considering that the assumption of measurement invariance was met, future studies can consider that sub-group comparisons among hemophilia patients in terms of HRQOL reflect true differences between groups and are not artifacts of measurement bias. Clinicians and caregivers of hemophilia patients should consider factors such as improving social support provided, emphasizing on the reduction of maladaptive coping strategies, and increasing patient self-efficacy while making key treatment decisions

Assessing the Value of Environmental Observations in a Changing World: Nonstationarity, Complexity, and Hierarchical Dependencies

This paper explores three related propositions for designing environmentalobservation systems: (1) Nonstationarity in environmental data series has the consequentimpact of making observation network design itself a nonstationary, stochastic planningproblem where the value of alternative observation strategies should be evaluated based onplanners’ evolving conception of Pareto efficiency given new knowledge, technologies,and policies over long time-scales. (2) Real-world budgetary constraints within observationnetwork design problems yield resource allocation conflicts across space, time, andcompeting foci that are equivalent in form to the multiobjective d-dimensional knapsackproblem (MO-dKP). Consequently, the Pareto efficiency of observation networks can onlybe determined approximately for non-trivial problem instances. (3) Multiobjectivehierarchical Bayesian optimization provides a very promising tool for identifyingobservation alternatives that are approximately Pareto efficient while simultaneouslyproviding insights into the emergent dependencies of our decisions (both science andmanagement oriented) on critical observations

Assessing the Value of Environmental Observations in a Changing World: Nonstationarity, Complexity, and Hierarchical Dependencies

This paper explores three related propositions for designing environmentalobservation systems: (1) Nonstationarity in environmental data series has the consequentimpact of making observation network design itself a nonstationary, stochastic planningproblem where the value of alternative observation strategies should be evaluated based onplanners’ evolving conception of Pareto efficiency given new knowledge, technologies,and policies over long time-scales. (2) Real-world budgetary constraints within observationnetwork design problems yield resource allocation conflicts across space, time, andcompeting foci that are equivalent in form to the multiobjective d-dimensional knapsackproblem (MO-dKP). Consequently, the Pareto efficiency of observation networks can onlybe determined approximately for non-trivial problem instances. (3) Multiobjectivehierarchical Bayesian optimization provides a very promising tool for identifyingobservation alternatives that are approximately Pareto efficient while simultaneouslyproviding insights into the emergent dependencies of our decisions (both science andmanagement oriented) on critical observations

FiNER-ORD: Financial Named Entity Recognition Open Research Dataset

Over the last two decades, the development of the CoNLL-2003 named entity recognition (NER) dataset has helped enhance the capabilities of deep learning and natural language processing (NLP). The finance domain, characterized by its unique semantic and lexical variations for the same entities, presents specific challenges to the NER task; thus, a domain-specific customized dataset is crucial for advancing research in this field. In our work, we develop the first high-quality English Financial NER Open Research Dataset (FiNER-ORD). We benchmark multiple pre-trained language models (PLMs) and large-language models (LLMs) on FiNER-ORD. We believe our proposed FiNER-ORD dataset will open future opportunities to use FiNER-ORD as a benchmark for financial domain-specific NER and NLP tasks. Our dataset, models, and code are publicly available on GitHub and Hugging Face under CC BY-NC 4.0 license

Case Report: Diagnosis of Gaucher disease in a toddler with acute respiratory failure

A 22-month-old male infant presented with cyanosis and stridor after a trivial fall and then developed acute respiratory distress. The respiratory status of the patient progressed rapidly to severe acute respiratory distress syndrome. Additional findings of hypersplenism prompted a comprehensive multidisciplinary approach and consideration of an inborn error of metabolism. Rapid whole-genome sequence showed a compound heterozygote mutation in the GBA1 gene involving a maternally inherited known pathogenic variant, p.L484P, and a paternally inherited novel likely pathogenic variant, p.P358l. The diagnosis of Gaucher disease was confirmed with low leukocyte acid β-glucosidase activity and the patient received recombinant macrophage-targeted enzyme replacement therapy. The patient eventually recovered, but subsequent work-up demonstrated severe bulbar dysfunction with evidence of aspiration. Two months after discharge, the patient arrived at the hospital in a condition of cardiac arrest after a suspected aspiration event associated with hemoptysis. This case illustrates a previously undescribed presentation of Gaucher disease and a new likely pathogenic genetic variant for Gaucher disease. It highlights the role of a multidisciplinary approach, including rapid whole-genome sequencing, to establish timely diagnosis and provide appropriate therapy for Gaucher disease

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial

Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo. Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib (n = 487) or placebo (n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019). Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd (n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9–8.9] and 4.1 [95% CI, 2.2–5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5–8.6] and 3.5 [95% CI, 1.7–5.6] months, respectively) in the HRd and ITT populations. Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure. Trial registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016 Plain language summary: Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patients’ quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA. Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses: ● The first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life. ● The second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects. Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib – they are known as homologous recombination deficiency (HRd) patients. ● When information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo. ● Using the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo. Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patients’ quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib.publishedVersionPeer reviewe

Characterization of a new collagen-like protein from trichodesmium erythraeum

In order to meet the exponentially rising demands of collagen in the fields of tissue engineering, cosmetic surgery and drug delivery systems, there is an increasing demand to find novel sources. Recently, an intron-free collagen-like gene found in Trichodesmium erythraeum, a colonial marine cyanobacterium, was reported. This thesis aims at characterizing this new collagen-like sequence and theoretically comparing it with human collagens (especially type I human collagen) and few other bacterial proteins in terms of amino acid composition, flexibility, hydropathicity and charge density. Enzyme degradation and polarized light microscopy were utilized to support the hypothesis of presence of collagen-like protein in T. erythraeum’s cell. The initial step of analysis involved running the blastp algorithm using this new sequence as the query sequence and studying its resemblance to various proteins in RefSeq protein database. Comparison with type I human collagen revealed that the assumed homotrimer molecule of Trichodesmium erythraeum’s collagen-like protein is almost as relatively stable as the former. The alternate flexible and rigid domains in the molecular structure can be predicted to coincide and form a highly flexible fibrillar structure that may aid the aggregates to survive stresses from ocean. It is suggested that this collagen-like protein is primarily responsible for transmission of energy during loading and not as much for storage of elastic energy. This new sequence was found to be highly hydrophobic and sparsely charged unlike any of the other sequences used in analyses. Based on this unusual hydrophobic nature, this collagen-like protein may find its applications for procedures like guided tissue reconstruction in dentistry as also in hernia repair and topical wound dressings. In order to determine the potential of the collagen gene of Trichodesmium erythraeum for tissue engineering, further studies will be required that include experimentally measuring its thermal stability, enzymatic stability of the triglycine repeat region and the globular N and C termini and its ability to undergo fibrillogenesis using established methods.M.S.Includes bibliographical referencesby Ruchit Girishchandra Sha