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| 2. |
- Krulichova, I. S., et al.
(author)
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Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study
- 2022
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In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 31:10, s. 1046-1055
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Journal article (peer-reviewed)abstract
- Purpose The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. Methods We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. Results In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. Conclusions The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.
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| 3. |
- Smid, Marcel, et al.
(author)
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Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.
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| 4. |
- Anchordoqui, Luis A., et al.
(author)
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The Forward Physics Facility : Sites, experiments, and physics potential
- 2022
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In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 968, s. 1-50
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Journal article (peer-reviewed)abstract
- The Forward Physics Facility (FPF) is a proposal to create a cavern with the space and infrastructure to support a suite of far-forward experiments at the Large Hadron Collider during the High Luminosity era. Located along the beam collision axis and shielded from the interaction point by at least 100 m of concrete and rock, the FPF will house experiments that will detect particles outside the acceptance of the existing large LHC experiments and will observe rare and exotic processes in an extremely low-background environment. In this work, we summarize the current status of plans for the FPF, including recent progress in civil engineering in identifying promising sites for the FPF and the experiments currently envisioned to realize the FPF's physics potential. We then review the many Standard Model and new physics topics that will be advanced by the FPF, including searches for long-lived particles, probes of dark matter and dark sectors, high-statistics studies of TeV neutrinos of all three flavors, aspects of perturbative and non-perturbative QCD, and high-energy astroparticle physics.
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| 5. |
- Singh, Jagmeet P., et al.
(author)
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Phased target trial design and meta-analysis in a head-to-head treatment comparison
- 2023
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In: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:Suppl. 1, s. 444-444
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Journal article (other academic/artistic)abstract
- Background: For conditions with rare clinical outcomes, real-world treatment comparisons are challenging to design and prone to confounding.Objectives: To present a robust methodologic approach for rigorous and transparent assessment of rare outcomes using real-world data.Methods: We emulated a target trial using an active comparator, new-user design to compare dronedarone to sotalol for rhythm control in atrial fibrillation (AF) as both are recommended for similar patient phenotypes. Using one protocol, a pre-specified stepwise approach was implemented across 4 datasets (Optum CDM; IBM MarketScan; Veterans Affairs Electronic Health Records; Swedish National Patient Register). Meta-analysis was used to ensure sufficient capture of specific, rare primary outcomes (cardiovascular (CV) hospitalization and ventricular proarrhythmia) and to evaluate consistency of findings across patient populations. Steps 1–3 focused on cohort selection, propensity score matching (PSM), baseline equipoise and residual confounding assessment via negative control outcome analyses. In steps 4–6, outcomes in the individual cohorts were analyzed using an as-treated approach and Cox proportional hazards models. Step 7 included a heterogeneity assessment, meta-analysis using fixed effects models, and hypothesis testing using a hierarchical approach. In step 8, sensitivity analyses, including E-values and Inverse Probability of Censoring Weighting, were conducted to verify the robustness of findings.Results: In step 1, 35,467 sotalol and 27,955 dronedarone patients with AF who were antiarrhythmic drug-naive were identified across databases. In steps 2–3, 23,275 dronedarone patients were PS-matched to 23,275 sotalol patients. Baseline covariates were well-balanced and little-to-no residual confounding was observed via the negative control analyses. Individual HRs were estimated in steps 4–6, and, when no significant heterogeneity between databases was observed, hazard ratios (HRs) were pooled across datasets in step 7. For example, for CV hospitalization, dronedarone was superior to sotalol with no heterogeneity (HR: 0.91; 95% CI: 0.85, 0.97; Cochran Q p-value: 0.32). Eleven sensitivity analyses were conducted in step 8 and confirmed that findings were generally robust.Conclusions: An active comparator, new-user design using the target trial approach coupled with meta-analysis generated consistent findings across databases and countries using one protocol. Similar methods, including a pre-specified stepwise approach, negative control outcome, and tests for robustness should be considered for real-world studies where specific, rare outcomes need to be examined in a rigorous and transparent way.
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| 6. |
- Xiao, S., et al.
(author)
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Talking through the continuum : New manifestations of Fano-resonance phenomenology realized with mesoscopic nanostructures
- 2013
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In: Fortschritte der Physik. - : Wiley. - 0015-8208 .- 1521-3978. ; 61:2-3, s. 348-359
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Journal article (peer-reviewed)abstract
- The focus of this review is recent work in which we have demonstrated a highly-flexible approach to the study of Fano-resonance phenomena, by making use of the mesoscopic devices known as quantum point contacts (QPCs). Utilizing the ability of these structures to function as an on-demand quantum state, we demonstrate a highly-flexible system for the investigation of Fano resonances. Our approach involves making measurements of non-locally coupled pairs of QPCs, one of which is used to form the discrete state needed for the Fano resonance, while the other serves as a detector whose conductance is sensitive to the energy of this state. As a demonstration of the flexibility of this approach, we show how it can be used to implement a multi-state Fano resonance, in which two discrete states undergo a robust interaction that is achieved by coupling them to each other through a common continuum.
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| 7. |
- Yoon, Y., et al.
(author)
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Coupling Quantum States through a Continuum : A Mesoscopic Multistate Fano Resonance
- 2012
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In: Physical Review X. - 2160-3308. ; 2:2, s. 021003-
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Journal article (peer-reviewed)abstract
- We demonstrate a fully tunable realization of a multistate Fano resonance, in which a pair of remote quantum states experience an effective coupling due to their mutual overlap with a continuum. Our mesoscopic implementation of this system exploits the ability of the semiconductor nanostructures known as quantum point contacts (QPCs) to serve, in the low-density limit close to pinch-off, as an on-demand localized state. By coupling the states formed on two separate QPCs, through a two-dimensional electron gas that serves as a continuum, we observe a robust effective interaction between the QPCs. To explain this result, we develop a theoretical formulation, based on the ideas of the Schrieffer-Wolff transformation, which is able to reproduce our key experimental findings. According to this model, the robust character of the interaction between the two remote states arises from the fact that the interaction is essentially mediated by a large number of degenerate continuum states. While the continuum is often viewed as a source of decoherence, our experiment therefore instead suggests the possibility of using this medium to support the interaction of quantum states, a result that may allow new approaches to coherently couple nanostructures in extended geometries.
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| 8. |
- Filla, Reno, et al.
(author)
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A Case Study on Quantifying the Workload of Working Machine Operators by Means of Psychophysiological Measurements
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Other publication (other academic/artistic)abstract
- In this study of eighteen wheel loader operators, test-driving a machine in three different traction force settings, we examine if a workload index derived from psychophysiological measurements of heart rate, finger temperature, skin conductance, respiration rate and end-tidal CO2-concentration in exhaled air can be used to assess operator workload in sufficient detail to use it as a complement to traditional subjective evaluations, and also to use such measurements in a workload-adaptive operator assistance system in a longer perspective.
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| 9. |
- Fransson, Jonas, et al.
(author)
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Tuning the Fano Resonance with an Intruder Continuum
- 2014
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In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 14:2, s. 788-793
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Journal article (peer-reviewed)abstract
- Through a combination of experiment and theory we establish the possibility of achieving strong tuning of Fano resonances (FRs), by allowing their usual two-path geometry to interfere with an additional, "intruder", continuum. As the coupling strength to this intruder is varied, we predict strong modulations of the resonance line shape that, in principle at least, may exceed the amplitude of the original FR itself. For a proof-of-concept demonstration of this phenomenon, we construct a nanoscale interferometer from nonlocally coupled quantum point contacts and utilize the unique features of their density of states to realize the intruder. External control of the intruder coupling is enabled by means of an applied magnetic field, in the presence of which we demonstrate the predicted distortions of the FR. This general scheme for resonant control should be broadly applicable to a Variety of wave-based systems, opening up the possibility of new applications in areas such as chemical and biological sensing and secure communications.
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| 10. |
- Huisman, Elise S., et al.
(author)
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Regional molecular and cellular differences in the female rabbit Achilles tendon complex : potential implications for understanding responses to loading
- 2014
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In: Journal of Anatomy. - : Wiley. - 0021-8782 .- 1469-7580. ; 224:5, s. 538-547
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Journal article (peer-reviewed)abstract
- The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon.
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