Establishing the tolerability and performance of tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of a clinical study

BACKGROUND: One of the problems arising from available preparations for dry eye syndrome is the limited residence time of products on the ocular surface. In this paper, we look at an innovative new treatment for dry eye, tamarind seed polysaccharide (TSP). TSP possesses mucomimetic, mucoadhesive and pseudoplastic properties. The 'mucin-like' molecular structure of TSP is similar to corneal and conjunctival mucin 1 (MUC1), a transmembrane glycoprotein thought to play an essential role in protecting and wetting the corneal surface and may explain its increased retention on the eye surface. METHODS: The activity of TSP and hyaluronic acid (HA) in the treatment of dry eye syndrome was compared in an open-label, randomised, single-centre clinical study. Thirty patients were randomised to receive three or more applications per day of either TSP 0.5%, TSP 1% or HA 0.2% (Hyalistil™) over a period of 90 days. The primary objective of tolerability was assessed by visual analogue scale (VAS), scoring of specific symptoms and the incidence of adverse events. Secondary objectives included improvement in stability of the precorneal tear film, subjective symptoms and corneal and conjunctival staining. RESULTS: TSP 0.5% and 1% were comparable to HA 0.2% with regard to both primary and secondary objective parameters. TSP 1% showed benefits over HA 0.2% for the subjective symptoms; trouble blinking, ocular burning and foreign body sensation. CONCLUSION: This study suggests that TSP 0.5% and 1% offer at least equivalent relief to HA 0.2% for dry eye syndrome. All treatments demonstrated optimal tolerability and are suitable for frequent use in the therapy of dry eye. TSP 1% produced promising results in terms of improvements in certain patient symptoms and suggests benefits of the TSP formulation. This study paves the way for a larger study to further establish the performance and safety of TSP compared with HA and highlights the need to expand this therapeutic agent to a wider dry eye population

Magnetic Energy Powers the Corona: How We Can Understand its 3D Storage & Release

The coronal magnetic field is the prime driver behind many as-yet unsolved mysteries: solar eruptions, coronal heating, and the solar wind, to name a few. It is, however, still poorly observed and understood. We highlight key questions related to magnetic energy storage, release, and transport in the solar corona, and their relationship to these important problems. We advocate for new and multi-point co-optimized measurements, sensitive to magnetic field and other plasma parameters, spanning from optical to $\gamma$-ray wavelengths, to bring closure to these long-standing and fundamental questions. We discuss how our approach can fully describe the 3D magnetic field, embedded plasma, particle energization, and their joint evolution to achieve these objectives.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 16 pages, 3 figure

COMPLETE: A flagship mission for complete understanding of 3D coronal magnetic energy release

COMPLETE is a flagship mission concept combining broadband spectroscopic imaging and comprehensive magnetography from multiple viewpoints around the Sun to enable tomographic reconstruction of 3D coronal magnetic fields and associated dynamic plasma properties, which provide direct diagnostics of energy release. COMPLETE re-imagines the paradigm for solar remote-sensing observations through purposefully co-optimized detectors distributed on multiple spacecraft that operate as a single observatory, linked by a comprehensive data/model assimilation strategy to unify individual observations into a single physical framework. We describe COMPLETE's science goals, instruments, and mission implementation. With targeted investment by NASA, COMPLETE is feasible for launch in 2032 to observe around the maximum of Solar Cycle 26.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 10 pages, 6 figures, 1 tabl

Improving Multi-Dimensional Data Formats, Access, and Assimilation Tools for the Twenty-First Century

Heliophysics image data largely relies on a forty-year-old ecosystem built on the venerable Flexible Image Transport System (FITS) data standard. While many in situ measurements use newer standards, they are difficult to integrate with multiple data streams required to develop global understanding. Additionally, most data users still engage with data in much the same way as they did decades ago. However, contemporary missions and models require much more complex support for 3D multi-parameter data, robust data assimilation strategies, and integration of multiple individual data streams required to derive complete physical characterizations of the Sun and Heliospheric plasma environment. In this white paper we highlight some of the 21$^\mathsf{st}$ century challenges for data frameworks in heliophysics, consider an illustrative case study, and make recommendations for important steps the field can take to modernize its data products and data usage models. Our specific recommendations include: (1) Investing in data assimilation capability to drive advanced data-constrained models, (2) Investing in new strategies for integrating data across multiple instruments to realize measurements that cannot be produced from single observations, (3) Rethinking old data use paradigms to improve user access, develop deep understanding, and decrease barrier to entry for new datasets, and (4) Investing in research on data formats better suited for multi-dimensional data and cloud-based computing.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 9 pages, 3 figure

Significance of Pelvic Fluid Observed during Ovarian Cancer Screening with Transvaginal Sonogram

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters. Measured outcomes were the presence and duration of fluid over successive screening encounters. Of the 48,925 women surveyed, 2001 (4.1%) had pelvic fluid present during a TVS exam. The odds ratio (OR) of detecting fluid in the comparison group (TN screen; OR = 1) significantly differed from that of the FP cases (benign pathology; OR: 13.4; 95% confidence interval (CI): 9.1–19.8), the TP cases with a low malignant potential (LMP; OR: 28; 95% CI: 26.5–29.5), TP ovarian cancer cases (OR: 50.4; 95% CI: 27.2–93.2), and FN ovarian cancer cases (OR: 59.3; 95% CI: 19.7–178.1). The mean duration that pelvic fluid was present for women with TN screens was 2.2 ± 0.05 encounters, lasting 38.7 ± 1.3 months. In an asymptomatic screening population, free fluid identified in TVS exams was more associated with ovarian malignancy than in the control group or benign ovarian tumors. While pelvic free fluid may not solely discriminate malignancy from non-malignancy, it appears to be clinically relevant and warrants thoughtful consideration

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Innovative methods to analyse the impact of gender norms on adolescent health using global health survey data.

BACKGROUND: Understanding how gender norms affect health is an important entry point into designing programs and policies to change norms and improve gender equality and health. However, it is rare for global health datasets to include questions on gender norms, especially questions that go beyond measuring gender-related attitudes, thus limiting gender analysis. METHODS: We developed five case studies using health survey data from six countries to demonstrate approaches to defining and operationalising proxy measures and analytic approaches to investigating how gender norms can affect health. Key findings, strengths and limitations of our norms proxies and methodological choices are summarised. FINDINGS: Case studies revealed links between gender norms and multiple adolescent health outcomes. Proxys for norms were derived from data on attitudes, beliefs, and behaviours, as well as differences between attitudes and behaviours. Data were cross-sectional, longitudinal, census- and social network-based. Analytic methods were diverse. We found that gender norms affect: 1) Intimate partner violence in Nigeria; 2) Unhealthy weight control behaviours in Brazil and South Africa; 3) HIV status in Zambia; 4) Health and social mobility in the US; and 5) Childbirth in Honduras. INTERPRETATION: Researchers can use existing global health survey data to examine pathways through which gender norms affect health by generating proxies for gender norms. While direct measures of gender norms can greatly improve the understanding of how gender affects health, proxy measures for norms can be designed for the specific health-related outcome and normative context, for instance by either aggregating behaviours or attitudes or quantifying the difference (dissonance) between them. These norm proxies enable evaluations of the influence of gender norms on health and insights into possible reference groups and sanctions for non-compliers, thus informing programmes and policies to shape norms and improve health