To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
A landmark result of Erdős, Ginzburg, and Ziv (EGZ) states that any sequence of $2n-1$ elements in ${\mathbb {Z}}/n$ contains a zero-sum subsequence of length n. While algebraic techniques have predominated in deriving many deep generalizations of this theorem over the past sixty years, here we introduce topological approaches to zero-sum problems which have proven fruitful in other combinatorial contexts. Our main result is a topological criterion for determining when any ${\mathbb {Z}}/n$-coloring of an n-uniform hypergraph contains a zero-sum hyperedge. In addition to applications for Kneser hypergraphs, for complete hypergraphs our methods recover Olson’s generalization of the EGZ theorem for arbitrary finite groups. Furthermore, we give a fractional generalization of the EGZ theorem with applications to balanced set families and provide a constrained EGZ theorem which imposes combinatorial restrictions on zero-sum sequences in the original result.
Electronic Health Record (EHR) data are critical for advancing translational research and AI technologies. The ENACT network offers access to structured EHR data across 57 CTSA hubs. However, substantial information is contained in clinical narratives, requiring natural language processing (NLP) for research. The ENACT NLP Working Group was formed to make NLP-derived clinical information accessible and queryable across the network.
Methods:
We established the ENACT NLP Working Group with 13 sites selected based on criteria including clinical notes access, IT infrastructure, NLP expertise, and institutional support. We divided sites into five focus groups targeting clinical tasks within disease contexts. Each focus group consisted of two development sites and two validation sites. We extended the ENACT ontology to standardize NLP-derived data and conducted multisite evaluations using the Open Health Natural Language Processing (OHNLP) Toolkit.
Results:
The working group achieved 100% site retention and deployed NLP infrastructure across all sites. We developed and validated NLP algorithms for rare disease phenotyping, social determinants of health, opioid use disorder, sleep phenotyping, and delirium phenotyping. Performance varied across sites (F1 scores 0.53–0.96), highlighting data heterogeneity impacts. We extended the ENACT common data model and ontology to incorporate NLP-derived data while maintaining Shared Health Research Informatics NEtwork (SHRINE) compatibility.
Conclusion:
This demonstrates feasibility of deploying NLP infrastructure across large, federated networks. The focus group approach proved more practical than general-purpose approaches. Key lessons include the challenge of data heterogeneity and importance of collaborative governance. This work also provides a foundation that other networks can build on to implement NLP capabilities for translational research.
Objectives/Goals: Manual skin assessment in chronic graft-versus-host disease (cGVHD) can be time consuming and inconsistent (>20% affected area) even for experts. Building on previous work we explore methods to use unmarked photos to train artificial intelligence (AI) models, aiming to improve performance by expanding and diversifying the training data without additional burden on experts. Methods/Study Population: Common to many medical imaging projects, we have a small number of expert-marked patient photos (N = 36, n = 360), and many unmarked photos (N = 337, n = 25,842). Dark skin (Fitzpatrick type 4+) is underrepresented in both sets; 11% of patients in the marked set and 9% in the unmarked set. In addition, a set of 20 expert-marked photos from 20 patients were withheld from training to assess model performance, with 20% dark skin type. Our gold standard markings were manual contours around affected skin by a trained expert. Three AI training methods were tested. Our established baseline uses only the small number of marked photos (supervised method). The semi-supervised method uses a mix of marked and unmarked photos with human feedback. The self-supervised method uses only unmarked photos without any human feedback. Results/Anticipated Results: We evaluated performance by comparing predicted skin areas with expert markings. The error was given by the absolute difference between the percentage areas marked by the AI model and expert, where lower is better. Across all test patients, the median error was 19% (interquartile range 6 – 34) for the supervised method and 10% (5 – 23) for the semi-supervised method, which incorporated unmarked photos from 83 patients. On dark skin types, the median error was 36% (18 – 62) for supervised and 28% (14 – 52) for semi-supervised, compared to a median error on light skin of 18% (5 – 26) for supervised and 7% (4 – 17) for semi-supervised. Self-supervised, using all 337 unmarked patients, is expected to further improve performance and consistency due to increased data diversity. Full results will be presented at the meeting. Discussion/Significance of Impact: By automating skin assessment for cGVHD, AI could improve accuracy and consistency compared to manual methods. If translated to clinical use, this would ease clinical burden and scale to large patient cohorts. Future work will focus on ensuring equitable performance across all skin types, providing fair and accurate assessments for every patient.
Objectives/Goals: Lung transplant is a life-saving surgery for patients with advanced lung diseases yet long-term survival remains poor. The clinical features and lung injury patterns of lung transplant recipients who die early versus those who survive longer term remain undefined. Here, we use cell-free DNA and rejection parameters to help elucidate this further. Methods/Study Population: Lung transplant candidacy prioritizes patients who have a high mortality risk within 2 years and will likely survive beyond 5 years. We stratified patients who died within 2 years of transplant as early death (n = 50) and those who survived past 5 years as long-term survivors (n = 53). Lung transplant recipients had serial blood collected as part of two prospective cohort studies. Cell-free DNA (cfDNA) was quantified using relative (% donor-derived cfDNA {%ddcfDNA}) and absolute (nuclear-derived {n-cfDNA}, mitochondrial-derived {mt-cfDNA}) measurements. As part of routine posttransplant clinical care, all patients underwent pulmonary function testing (PFT), surveillance bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy (TBBx), and donor-specific antibody testing (DSA). Results/Anticipated Results: Over the first 2 years after transplant, the number of episodes of antibody-mediated rejection (p) Discussion/Significance of Impact: Clinically, early-death patients perform worse on routine surveillance PFTs and experience a worse degree of CLAD. These patients also have higher levels of cfDNA as quantified by n-cfDNA and mt-cfDNA. These results provide preliminary evidence that early-death patients have worse allograft rejection, dysfunction, and molecular injury.
The effective reproduction number $ R $ was widely accepted as a key indicator during the early stages of the COVID-19 pandemic. In the UK, the $ R $ value published on the UK Government Dashboard has been generated as a combined value from an ensemble of epidemiological models via a collaborative initiative between academia and government. In this paper, we outline this collaborative modelling approach and illustrate how, by using an established combination method, a combined $ R $ estimate can be generated from an ensemble of epidemiological models. We analyse the $ R $ values calculated for the period between April 2021 and December 2021, to show that this $ R $ is robust to different model weighting methods and ensemble sizes and that using heterogeneous data sources for validation increases its robustness and reduces the biases and limitations associated with a single source of data. We discuss how $ R $ can be generated from different data sources and show that it is a good summary indicator of the current dynamics in an epidemic.
Most medical diagnostic tests are expensive, involve slow turnaround times from centralized laboratories and require highly specialized equipment with seasoned technicians to carry out the assay. To facilitate realization of precision medicine at the point of care, we have developed a mixed-scale nanosensor chip featuring high surface area pillar arrays where solid-phase reactions can be performed to detect and identify nucleic acid targets found in diseased patients. Products formed can be identified and detected using a polymer nanofluidic channel. To guide delivery of this platform, we discuss the operation of various components of the device and simulations (COMSOL) used to guide the design by investigating parameters such as pillar array loading, and hydrodynamic and electrokinetic flows. The fabrication of the nanosensor is discussed, which was performed using a silicon (Si) master patterned with a combination of focused ion beam milling and photolithography with deep reactive ion etching. The mixed-scale patterns were transferred into a thermoplastic via thermal nanoimprint lithography, which facilitated fabrication of the nanosensor chip making it appropriate for in vitro diagnostics. The results from COMSOL were experimentally verified for hydrodynamic flow using Rhodamine B as a fluorescent tracer and electrokinetic flow using single fluorescently labelled oligonucleotides (single-stranded DNAs, ssDNAs).
A growing volume of research suggests that religion protects against late-life suicide, but it remains unclear whether effects are relevant to clinical samples, which facets of religion are most relevant, and variations over the course of mood disorders (e.g. during periods of euthymia, depression, and/or heightened suicidality).
Method
Eighty adults aged 55–85 years with mood disorders completed assessments of religion (affiliation, service attendance, importance of religion, belief and faith in God), depression, and suicidality over time (M = 7.31 measurements over M = 727 days). We computed metrics to identify mean and maximum levels of depression and suicidality, and the number of episodes of significant depression and suicidality experienced by each participant.
Results
Religious affiliation and importance of religion, but not service attendance, belief, or faith in God, were associated with lower mean and maximum depression. Conversely, all facets of religion predicted significantly lower mean and maximum levels of suicidality (rs ranging from −0.24 to −0.39), and substantially less likelihood of experiencing significant suicidality during the study (ORs ranging from 0.19 to 0.33). Service attendance, belief, and faith in God predicted less suicidality even among individuals who did not affiliate with a religious group.
Conclusions
Religious factors, particularly faith in God, are associated with substantially less suicidality over time among older adults with mood disorders, irrespective of religious affiliation.
Background: Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, California (SHIELD OC) was a CDC-funded regional decolonization intervention from April 2017 through July 2019 involving 38 hospitals, nursing homes (NHs), and long-term acute-care hospitals (LTACHs) to reduce MDROs. Decolonization in NH and LTACHs consisted of universal antiseptic bathing with chlorhexidine (CHG) for routine bathing and showering plus nasal iodophor decolonization (Monday through Friday, twice daily every other week). Hospitals used universal CHG in ICUs and provided daily CHG and nasal iodophor to patients in contact precautions. We sought to evaluate whether decolonization reduced hospitalization and associated healthcare costs due to infections among residents of NHs participating in SHIELD compared to nonparticipating NHs. Methods: Medicaid insurer data covering NH residents in Orange County were used to calculate hospitalization rates due to a primary diagnosis of infection (counts per member quarter), hospital bed days/member-quarter, and expenditures/member quarter from the fourth quarter of 2015 to the second quarter of 2019. We used a time-series design and a segmented regression analysis to evaluate changes attributable to the SHIELD OC intervention among participating and nonparticipating NHs. Results: Across the SHIELD OC intervention period, intervention NHs experienced a 44% decrease in hospitalization rates, a 43% decrease in hospital bed days, and a 53% decrease in Medicaid expenditures when comparing the last quarter of the intervention to the baseline period (Fig. 1). These data translated to a significant downward slope, with a reduction of 4% per quarter in hospital admissions due to infection (P < .001), a reduction of 7% per quarter in hospitalization days due to infection (P < .001), and a reduction of 9% per quarter in Medicaid expenditures (P = .019) per NH resident. Conclusions: The universal CHG bathing and nasal decolonization intervention adopted by NHs in the SHIELD OC collaborative resulted in large, meaningful reductions in hospitalization events, hospitalization days, and healthcare expenditures among Medicaid-insured NH residents. The findings led CalOptima, the Medicaid provider in Orange County, California, to launch an NH incentive program that provides dedicated training and covers the cost of CHG and nasal iodophor for OC NHs that enroll.
Funding: None
Disclosures: Gabrielle M. Gussin, University of California, Irvine, Stryker (Sage Products): Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes.
Anthocyanins and bromelain have gained significant attention due to their antioxidative and anti-inflammatory properties. Both have been shown to improve endothelial function, blood pressure (BP) and oxygen utility capacity in humans; however, the combination of these two and the impacts on endothelial function, BP, total antioxidant capacity (TAC) and oxygen utility capacity have not been previously investigated. The purpose of this study was to investigate the impacts of a combined anthocyanins and bromelain supplement (BE) on endothelial function, BP, TAC, oxygen utility capacity and fatigability in healthy adults. Healthy adults (n 18, age 24 (sd 4) years) received BE or placebo in a randomised crossover design. Brachial artery flow-mediated dilation (FMD), BP, TAC, resting heart rate, oxygen utility capacity and fatigability were measured pre- and post-BE and placebo intake. The BE group showed significantly increased FMD, reduced systolic BP and improved oxygen utility capacity compared with the placebo group (P < 0·05). Tissue saturation and oxygenated Hb significantly increased following BE intake, while deoxygenated Hb significantly decreased (P < 0·05) during exercise. Additionally, TAC was significantly increased following BE intake (P < 0·05). There were no significant differences for resting heart rate, diastolic BP or fatigability index. These results suggest that BE intake is an effective nutritional therapy for improving endothelial function, BP, TAC and oxygen utility capacity, which may be beneficial to support vascular health in humans.
Early career investigators have few opportunities for targeted training in supportive oncology research. To address this need, we developed, implemented, and evaluated an intensive, six-day workshop on methods in supportive oncology research for trainees and junior faculty across multiple disciplines.
Method
A multidisciplinary team of supportive oncology researchers developed a workshop patterned after the clinical trials workshop offered jointly by the American Society of Clinical Oncology and American Association of Cancer Research. The curriculum included lectures and a mentored experience of writing a research protocol. Each year since 2015, the workshop has accepted and trained 36 early career investigators. Over the course of the workshop, participants present sections of their research protocols daily in small groups led by senior researchers, and have dedicated time to write and revise these sections. Primary outcomes for the workshop included the frequency of completed protocols by the end of the workshop, a pre- and posttest assessing participant knowledge, and follow-up surveys of the participants and their primary mentors.
Result
Over three years, the workshop received 195 applications; 109 early career researchers were competitively selected to participate. All participants (109/109, 100%) completed writing a protocol by the end of their workshop. Participants and their primary mentors reported significant improvements in their research knowledge and skills. Each year, participants rated the workshop highly in terms of satisfaction, value, and likelihood of recommending it to a colleague. One year after the first workshop, most respondents (29/30, 96.7%) had either submitted their protocol or written at least one other protocol.
Significance of results
We developed a workshop on research methods in supportive oncology. More early career investigators applied for the workshop than capacity, and the workshop was fully attended each year. Both the workshop participants and their primary mentors reported improvement in research skills and knowledge.
Multiple studies have elucidated the antioxidant properties of Se, which are now well known among the nutrition and biomedical science communities. Recently, considerable interest has been focused on the possible association between Se exposure and risk of metabolic disease, such as lipid dysregulation; however, there is limited epidemiological data on this topic. The present study aimed to investigate associations between toenail Se levels and dyslipidaemia or individual lipid levels, and to examine the effect of dietary supplement use on these associations. We analysed baseline data from a cohort in the Yeungnam area, including 232 men and 269 women. Information on demographic, dietary and lifestyle characteristics was obtained through a self-reported questionnaire. Se levels in toenail specimens were measured using neutron activation analysis. Fasting blood lipid levels were measured during medical examinations. After adjusting for multiple confounding variables, we observed no association between toenail Se levels and dyslipidaemia or individual lipid profiles. However, the association was modified by dietary supplement use. Among the supplement users, higher toenail Se levels were associated with a higher prevalence of lipid dysregulation, whereas non-users exhibited a lower prevalence of lipid dysregulation. Associations between toenail Se levels, lipid levels and dyslipidaemia may be influenced by taking dietary supplements. Future large-scale, prospective cohort studies should be conducted to further evaluate the association between Se levels in the body and metabolic health effects in light of increasing rates of dietary supplement use.
Sulfur cinquefoil is an exotic, perennial forb that invades a wide range of ecosystems in western North America. It forms dense populations and often threatens native plant species and communities. In this study, we address the following questions: (1) what herbicides, rates, and application times are most effective at reducing sulfur cinquefoil abundance while having the least impact on native plants; and (2) does postherbicide seeding with native grass species increase native plant abundance? In 2002, we experimentally examined the effects of five herbicides (dicamba + 2,4-D; metsulfuron-methyl; triclopyr; glyphosate; and picloram) at two rates of application (low and high), three application times (early summer, fall, and a combined early summer–fall treatment), and two postherbicide seed addition treatments (seeded or not seeded) on sulfur cinquefoil abundance, plant community composition, and species richness. Experimental plots were monitored through 2005. Picloram was the most effective herbicide at reducing sulfur cinquefoil density, the proportion of remaining adult plants, and seed production. The effects of picloram continued to be evident after 3 yr, with 80% reduction of sulfur cinquefoil in 2005. In addition, seeding of native grass seeds alone (no herbicide application) reduced the proportion of sulfur cinquefoil plants that were reproductively active. Despite reductions in sulfur cinquefoil abundance, all treatments remained dominated by exotic species because treated areas transitioned from exotic forb- to exotic grass-dominated communities. However, a one-time herbicide application controlled sulfur cinquefoil for at least 3 yr, and therefore might provide a foundation to begin ecological restoration. Herbicide applications alone likely are to be insufficient for long-term sulfur cinquefoil control without further modification of sites through native grass or forb seeding. Integrating herbicides with native plant seeding to promote the development of plant communities that are resistant to sulfur cinquefoil invasion is a promising management approach to ecological restoration.
Herbicides are the primary method used to control exotic, invasive plants. This study evaluated restoration efforts applied to grasslands dominated by an invasive plant, sulfur cinquefoil, 6 yr after treatments. Of the five herbicides we evaluated, picloram continued to provide the best control of sulfur cinquefoil over 6 yr. We found the timing of picloram applications to be important to the native forb community. Plots with picloram applied in the fall had greater native forb cover. However, without the addition of native perennial grass seeds, the sites became dominated by exotic grasses. Seeding resulted in a 20% decrease in exotic grass cover. Successful establishment of native perennial grasses was not apparent until 6 yr after seeding. Our study found integrating herbicide application and the addition of native grass seed to be an effective grassland restoration strategy, at least in the case where livestock are excluded.
We examine excess emission at high positive and negative velocities toward known Galactic supernova remnants (SNRs) in the “Inner-Galaxy Arecibo L-band Feed Array (I-GALFA)” Hi 21-cm survey data. The I-GALFA survey covers ℓ = 32° to 77°, and has a velocity range of ±700 km s−1 with high angular and velocity resolutions (4′ and 0.18 km s−1, respectively) and good sensitivity (0.2 K). The excess emission which is thought to be part of a fast-expanding Hi shell of a SNR is detected from four among 39 SNRs in the I-GALFA area: W44, G54.4–0.3, W51C, and CTB 80. Although the Hi shells of the four SNRs were already reported in low-resolution studies, the first detection of both sides of an expanding Hi shell associated with W44 is very inspiring. We discuss physical properties of these four SNRs and their statistical nature.
We show evidence of electrical and thermal conductivity percolation in polymer based carbon nanotube (CNT) composites, which follow power law variations with respect to the CNT concentrations in the matrix. The experimentally obtained percolation thresholds, i.e., ~ 0.074 vol % for single walled CNTs and ~ 2.0 vol % for multi-walled CNTs, were found to be aspect ratio dependent and in accordance with those determined theoretically from excluded volume percolation theory. A much greater enhancement, over 10 orders of magnitude, was obtained in the electrical conductivity at the percolation threshold, while a smaller increase of ~ 100 % was obtained in the thermal conductivity values. Such a difference is qualitatively explained on the basis of the respective conductivity contrast between the CNT filler and the polymer matrix.