| 1. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 2. |
- Guidolin, Andrea, et al.
(författare)
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Geometry of spiking patterns in early visual cortex : a topological data analytic approach
- 2022
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 19:196
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Tidskriftsartikel (refereegranskat)abstract
- In the brain, spiking patterns live in a high-dimensional space of neurons and time. Thus, determining the intrinsic structure of this space presents a theoretical and experimental challenge. To address this challenge, we introduce a new framework for applying topological data analysis (TDA) to spike train data and use it to determine the geometry of spiking patterns in the visual cortex. Key to our approach is a parametrized family of distances based on the timing of spikes that quantifies the dissimilarity between neuronal responses. We applied TDA to visually driven single-unit and multiple single-unit spiking activity in macaque V1 and V2. TDA across timescales reveals a common geometry for spiking patterns in V1 and V2 which, among simple models, is most similar to that of a low-dimensional space endowed with Euclidean or hyperbolic geometry with modest curvature. Remarkably, the inferred geometry depends on timescale and is clearest for the timescales that are important for encoding contrast, orientation and spatial correlations.
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| 3. |
- Kang, M. S., et al.
(författare)
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Preclinical in vivo longitudinal assessment of KG207-M as a disease-modifying Alzheimer's disease therapeutic
- 2022
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 42:5, s. 788-801
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Tidskriftsartikel (refereegranskat)abstract
- In vivo biomarker abnormalities provide measures to monitor therapeutic interventions targeting amyloid-beta pathology as well as its effects on downstream processes associated with Alzheimer's disease pathophysiology. Here, we applied an in vivo longitudinal study design combined with imaging and cerebrospinal fluid biomarkers, mirroring those used in human clinical trials to assess the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in the McGill-R-Thy1-APP transgenic rat model. The bi-functional fusion protein consisted of a blood-brain barrier crossing single domain antibody (FC5) fused to an amyloid-beta oligomer-binding peptide (ABP) via Fc fragment of mouse IgG (FC5-mFc2a-ABP). A five-week treatment with FC5-mFc2a-ABP (loading dose of 30 mg/Kg/iv followed by 15 mg/Kg/week/iv for four weeks) substantially reduced brain amyloid-beta levels as measured by positron emission tomography and increased the cerebrospinal fluid amyloid-beta(42/40) ratio. In addition, the 5-week treatment rectified the cerebrospinal fluid neurofilament light chain concentrations, resting-state functional connectivity, and hippocampal atrophy measured using magnetic resonance imaging. Finally, FC5-mFc2a-ABP (referred to as KG207-M) treatment did not induce amyloid-related imaging abnormalities such as microhemorrhage. Together, this study demonstrates the translational values of the designed preclinical studies for the assessment of novel therapies based on the clinical biomarkers providing tangible metrics for designing early-stage clinical trials.
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| 4. |
- McNaughton, Candace D., et al.
(författare)
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Quality of life assessed 6 months after hospitalisation for acute heart failure: an analysis from REPORT-HF (international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure)
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 1020-1029
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Tidskriftsartikel (refereegranskat)abstract
- Aims Recovery of well-being after hospitalisation for acute heart failure (AHF) is a measure of the success of interventions and the quality of care but has rarely been quantified. Accordingly, we measured health status after discharge in an international registry (REPORT-HF) of AHF. Methods and results The analysis included 4606 patients with AHF who survived to hospital discharge, had known vital status at 6 months, and were enrolled in the United States of America, Russian Federation, or Western Europe, where the Kansas City Cardiomyopathy Questionnaire (KCCQ) was administered. Median age was 69 years (quartiles 59-78), 40% were women, and 34% had a left ventricular ejection fraction (LVEF) <40%, and 12% patients died by 6 months. Of 2475 patients with a follow-up KCCQ, 28% were alive and well (KCCQ >75), while 43% had poor health status (KCCQ <= 50). Being alive and well was associated with new-onset AHF, LVEF <40%, younger age, higher baseline KCCQ, country, and race. Associations were similar for increasing health status, with the exception of country and addition of comorbidities. Conclusion In this international global registry, health status recovery after AHF hospitalisation was highly variable. Those with the best health status at 6 months were younger, had new-onset heart failure, and higher baseline KCCQ; nearly one-third of survivors were alive and well. Investigating reasons for changes in KCCQ after hospitalisation might identify new therapeutic targets to improve patient-centred outcomes.
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| 5. |
- Tromp, Jasper, et al.
(författare)
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A global perspective of racial differences and outcomes in patients presenting with acute heart failure
- 2022
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 243, s. 11-14
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Important racial differences in characteristics, treatment, and outcomes of patients with acute heart failure (AHF) have been described. The objective of this analysis of the International Registry to assess medical Practice with longitudinal observation for Treatment of Heart Failure (REPORT-HF) registry was to investigate racial differences in patients with AHF according to country income level.
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| 6. |
- Tromp, Jasper, et al.
(författare)
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Global disparities in prescription of guideline-recommended drugs for heart failure with reduced ejection fraction
- 2022
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 43:23, s. 2224-2234
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Tidskriftsartikel (refereegranskat)abstract
- Background Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines. Methods and results This analysis assessed prescription rates and doses of renin-angiotensin system (RAS) inhibitors, beta-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias. Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on >= 50% of guideline-recommended doses of RAS inhibitors, and beta-blockers were independently associated with better 1-year survival, regardless of country income level. Conclusion Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.
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| 7. |
- Tromp, Jasper, et al.
(författare)
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Regional differences in precipitating factors of hospitalization for acute heart failure: insights from the REPORT-HF registry
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:4, s. 645-652
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Tidskriftsartikel (refereegranskat)abstract
- Aims Few prior studies have investigated differences in precipitants leading to hospitalizations for acute heart failure (AHF) in a cohort with global representation. Methods and results We analysed the prevalence of precipitants and their association with outcomes in 18 553 patients hospitalized for AHF in REPORT-HF (prospective international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) according to left ventricular ejection fraction subtype (reduced [HFrEF] and preserved ejection fraction [HFpEF]) and presentation (new-onset vs. decompensated chronic heart failure [DCHF]). Patients were enrolled from 358 centres in 44 countries stratified according to Latin America, North America, Western Europe, Eastern Europe, Eastern Mediterranean and Africa, Southeast Asia, and Western Pacific. Precipitants were pre-with mutually exclusive categories and selected according to the local investigators discretion. Outcomes included in-hospital and 1-year mortality. The median age was 67 (interquartile range 57-77) years, and 39% were women. Acute coronary syndrome (ACS) was the most common precipitant in patients with new-onset heart failure in all regions except for North America and Western Europe, where uncontrolled hypertension and arrhythmia, respectively, were the most common precipitants, independent of confounders. In patients with DCHF, non-adherence to diet/medication was the most common precipitant regardless of region. Uncontrolled hypertension was a more likely precipitant in HFpEF, non-adherence to diet/medication, and ACS were more likely precipitants in HFrEF. Patients admitted due to worsening renal function had the worst in-hospital (5%) and 1-year post-discharge (30%) mortality rates, regardless of region, heart failure subtype and admission type (p(interaction) >0.05 for all). Conclusion Data on global differences in precipitants for AHF highlight potential regional differences in targets for preventing hospitalization for AHF and identifying those at highest risk for early mortality.
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| 8. |
- Baxter, Amanda L., et al.
(författare)
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Collaborative experience between scientific software projects using Agile Scrum development
- 2022
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Ingår i: Software, practice & experience. - : John Wiley & Sons. - 0038-0644 .- 1097-024X. ; 52:10, s. 2077-2096
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Tidskriftsartikel (refereegranskat)abstract
- Developing sustainable software for the scientific community requires expertise in software engineering and domain science. This can be challenging due to the unique needs of scientific software, the insufficient resources for software engineering practices in the scientific community, and the complexity of developing for evolving scientific contexts. While open-source software can partially address these concerns, it can introduce complicating dependencies and delay development. These issues can be reduced if scientists and software developers collaborate. We present a case study wherein scientists from the SuperNova Early Warning System collaborated with software developers from the Scalable Cyberinfrastructure for Multi-Messenger Astrophysics project. The collaboration addressed the difficulties of open-source software development, but presented additional risks to each team. For the scientists, there was a concern of relying on external systems and lacking control in the development process. For the developers, there was a risk in supporting a user-group while maintaining core development. These issues were mitigated by creating a second Agile Scrum framework in parallel with the developers' ongoing Agile Scrum process. This Agile collaboration promoted communication, ensured that the scientists had an active role in development, and allowed the developers to evaluate and implement the scientists' software requirements. The collaboration provided benefits for each group: the scientists actuated their development by using an existing platform, and the developers utilized the scientists' use-case to improve their systems. This case study suggests that scientists and software developers can avoid scientific computing issues by collaborating and that Agile Scrum methods can address emergent concerns.
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| 9. |
- Busto, David, et al.
(författare)
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Probing electronic decoherence with high-resolution attosecond photoelectron interferometry
- 2022
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Ingår i: European Physical Journal D. - : Springer Science and Business Media LLC. - 1434-6060 .- 1434-6079. ; 76:7
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Quantum coherence plays a fundamental role in the study and control of ultrafast dynamics in matter. In the case of photoionization, entanglement of the photoelectron with the ion is a well-known source of decoherence when only one of the particles is measured. Here, we investigate decoherence due to entanglement of the radial and angular degrees of freedom of the photoelectron. We study two-photon ionization via the 2s2p autoionizing state in He using high spectral resolution photoelectron interferometry. Combining experiment and theory, we show that the strong dipole coupling of the 2s2p and 2p2 states results in the entanglement of the angular and radial degrees of freedom. This translates, in angle-integrated measurements, into a dynamic loss of coherence during autoionization. Graphic Abstract: [Figure not available: see fulltext.]. © 2022, The Author(s).
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| 10. |
- Demers-Mathieu, Veronique, et al.
(författare)
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Functional Antibodies Against SARS-CoV-2 Receptor Binding Domain Variants with Mutations N501Y or E484K in Human Milk from COVID-19-Vaccinated, -Recovered, and -Unvaccinated Women
- 2022
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Ingår i: Breastfeeding Medicine. - : Mary Ann Liebert Inc. - 1556-8253 .- 1556-8342. ; 17:2, s. 163-172
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Tidskriftsartikel (refereegranskat)abstract
- Background: New variants are evolving in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and receptor binding domain (RBD) mutations have been associated with a higher capacity to evade neutralizing antibodies (NAbs). We aimed at determining the impact of COVID-19 vaccine and infection on human milk antibody titers and activity against the RBD mutations from SARS-CoV-2 variants of concern. Materials and Methods: Milk samples were collected from 19 COVID-19 vaccinated women, 10 women who had a positive COVID-19 PCR test, and 13 unvaccinated women. The titers and NAbs of secretory IgA (SIgA)/IgA, secretory IgM (IgM)/IgM, and IgG against SARS-CoV-2 RBD with mutations N501Y or E484K were measured by using ELISA and a surrogate virus neutralization assay. Results: The titers of human milk IgG against N501Y were higher in the COVID-19 vaccine group than in the no-vaccine group but comparable with the COVID-19 PCR group. Other antibody titers did not differ between the three groups. The titers of SIgA/IgA were higher than those of SIgM/IgM and IgG in all three groups. The titers of SIgM/IgM and the inhibition of NAbs were higher against the mutation E484K than N501Y. Milk NAb did not differ between the three groups, but the inhibition of NAb against binding of the two mutant RBD proteins to their receptor was higher in the COVID-19 vaccine and PCR groups than in milk from prepandemic women. Conclusions: COVID-19 vaccination and exposure of mothers to SARS-CoV-2 influenced the titers and NAbs in breast milk against the variants of concern.
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