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Since their first demonstration in 2001 [Gol’tsman et al., Appl. Phys. Lett. 79, 705-707 (2001)], superconducting-nanowire single-photon detectors (SNSPDs) have witnessed two decades of great developments. SNSPDs are the detector of choice in most modern quantum optics experiments and are slowly finding their way into other photon-starved fields of optics. Until now, however, in nearly all experiments, SNSPDs were used as “binary” detectors, meaning that they could only distinguish between 0 and > = 1 photons, and photon number information was lost. Recent research has demonstrated proof-of-principle photon-number resolution (PNR) SNSPDs counting 2-5 photons. The photon-number-resolving capability is highly demanded in various quantum-optics experiments, including Hong-Ou-Mandel interference, photonic quantum computing, quantum communication, and non-Gaussian quantum state preparation. In particular, PNR detectors at the wavelength range of 850-950 nm are of great interest due to the availability of high-quality semiconductor quantum dots (QDs) [Heindel et al., Adv. Opt. Photonics 15, 613-738 (2023)] and high-performance cesium-based quantum memories [Ma et al., J. Opt. 19, 043001 (2017)]. In this paper, we demonstrate NbTiN-based SNSPDs with >94% system detection efficiency, sub-11 ps timing jitter for one photon, and sub-7 ps for 2 photons. More importantly, our detectors resolve up to 7 photons using conventional cryogenic electric readout circuitry. Through theoretical analysis, we show that the PNR performance of demonstrated detectors can be further improved by enhancing the signal-to-noise ratio and bandwidth of our readout circuitry. Our results are promising for the future of optical quantum computing and quantum communication., QC 20240626

Item does not contain fulltext, AIMS: The contribution of adverse ventricular interdependence remains undervalued in heart failure or pulmonary vascular disease, and not much is known about its dynamic nature during exercise and respiration. In this study, we evaluated ventricular interaction during exercise in patients with heart failure with preserved ejection fraction (HFpEF) and patients with chronic thromboembolic pulmonary hypertension (CTEPH) as compared with healthy controls. METHODS AND RESULTS: Forty-six subjects (10 controls, 19 CTEPH patients, and 17 HFpEF patients) underwent cardiac magnetic resonance imaging during exercise. Ventricular interaction was determined through analysis of the septal curvature (SC) of a mid-ventricular short-axis slice at end-diastole, end-systole, and early-diastole, both in expiration and inspiration. Exercise amplified ventricular interaction in CTEPH patients and to a lesser extent in HFpEF patients (P < 0.05 for decrease in SC with exercise). Adverse interaction was most profound in early-diastole and most pronounced in CTEPH patients (P < 0.05 interaction group * exercise) because of a disproportionate increase RV afterload (P < 0.05 to both controls and HFpEF) and diastolic pericardial restraint (P < 0.001 for interaction group * exercise) during exercise. Inspiration enhanced diastolic interdependence in CTEPH and HFpEF patients (P < 0.05 vs. expiration). Both at rest and during exercise, SC strongly correlated with RV volumes and pulmonary artery pressures (all P < 0.05). CONCLUSIONS: Exercise amplifies adverse right-left ventricular interactions in CTEPH, while a more moderate effect is observed in isolated post-capillary HFpEF. Given the strong link with RV function and pulmonary hemodynamic, assessing ventricular interaction with exCMR might be valuable from a diagnostic or therapeutic perspective.

Contains fulltext : 300044.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM). METHODS: The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model. RESULTS: A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15-2.01, p < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61-1.25) in participants with T2DM and 0.64 (0.51-0.80) in participants without diabetes (p(interaction )= 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group (p = 0.10). DISCUSSION: In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.

Single photon detectors are indispensable tools in optics, from fundamental measurements to quantum information processing. The ability of superconducting nanowire single photon detectors (SNSPDs) to detect single photons with unprecedented efficiency, short dead time, and high time resolution over a large frequency range enabled major advances in quantum optics. However, combining near-unity system detection efficiency (SDE) with high timing performance remains an outstanding challenge. In this work, we fabricated novel SNSPDs on membranes with 99.5-2.07+0.5% SDE at 1350 nm with 32 ps timing jitter (using a room-temperature amplifier), and other detectors in the same batch showed 94%-98% SDE at 1260-1625 nm with 15-26 ps timing jitter (using cryogenic amplifiers). The SiO2/Au membrane enables broadband absorption in small SNSPDs, offering high detection efficiency in combination with high timing performance. With low-noise cryogenic amplifiers operated in the same cryostat, our efficient detectors reach a timing jitter in the range of 15-26 ps. We discuss the prime challenges in optical design, device fabrication, and accurate and reliable detection efficiency measurements to achieve high performance single photon detection. As a result, the fast developing fields of quantum information science, quantum metrology, infrared imaging, and quantum networks will greatly benefit from this far-reaching quantum detection technology.

Carriers can remarkably reduce transportation costs and emissions when they collaborate, for example through a platform. Such gains, however, have only been investigated for relatively small problem instances with low numbers of carriers. We develop auction-based methods for large-scale dynamic collaborative pickup and delivery problems, combining techniques of multi-agent systems and combinatorial auctions. We evaluate our approach in terms of both solution quality and possibilities of strategic behaviour using a real-world data set of over 12,000 orders. Hence, this study is (to the best of our knowledge) the first to assess the benefits of large-scale carrier cooperation and to propose an approach for it. First, we use iterative single-order auctions to investigate possible collaboration gains for increasing numbers of carriers. Our results show that travel costs can be reduced by up to 77% when 1000 carriers collaborate, largely increasing the gains that were previously observed in smaller-scale collaboration. We also ensure that individual rationality is guaranteed in each auction. Next, we compare this approach of multiple local auctions with an established central combinatorial auction mechanism and observe that the proposed approach performs better on large-scale instances. Furthermore, to improve solution quality, we integrate the two approaches by allowing small bundle auctions in the multi-agent system. We analyze the circumstances under which bundling is beneficial in a large-scale decentralized system and demonstrate that travel cost gains of up to 13% can be obtained for 1000 carriers. Finally, we investigate whether the system is vulnerable to cheating: we show that misrepresentation of true values by individual participants sometimes can benefit them at the cost of the collective. Although such strategic behaviour is not straightforward, we also discuss different means to prevent it., Transport Engineering and Logistics, Algorithmics

Item does not contain fulltext, Elevated LDL-cholesterol (LDL-C) plays a major role in atheroma formation and inflammation. Medical therapy to lower elevated LDL-C is the cornerstone for reducing the progression of atherosclerotic cardiovascular disease. Statin therapy, and more recently, other drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven efficacy in long-term lowering of LDL-C and therefore diminish cardiovascular risk. During an acute coronary syndrome (ACS), a systemic inflammatory response can destabilize other non-culprit atherosclerotic plaques. Patients with these vulnerable plaques are at high risk of experiencing recurrent cardiovascular events in the first few years post-ACS. Initiating intensive LDL-C lowering therapy in these patients with statins or PCSK9 inhibitors can be beneficial via several pathways. High-intensity statin therapy can reduce inflammation by directly lowering LDL-C, but also through its pleiotropic effects. PCSK9 inhibitors can directly lower LDL-C to recommended guideline thresholds, and could have additional effects on inflammation and plaque stability. We discuss the potential role of early implementation of statins combined with PCSK9 inhibitors to influence these cascades and to mediate the associated cardiovascular risk, over and above the well-known long-term beneficial effects of chronic LDL-C lowering.

Ultra-high system detection efficiency (SDE) s uperconducting nanowire single-photon detectors are demonstrated for a broad range of wavelengths, from UV to mid-infrared, opening novel possibilities in the fields of quantum photonics, neuroimaging and astronomy., QC 20230602

The trends of autonomous transportation and mobility on demand in line with large numbers of requests increasingly call for decentralized vehicle routing optimization. Multi-agent systems (MASs) allow to model fully autonomous decentralized decision making, but are rarely considered in current decision support approaches. We propose a multi-agent approach in which autonomous vehicles are modeled as independent decision makers that locally interact with auctioneers for transportation orders. The developed MAS finds solutions for a realistic routing problem in which multiple pickup and delivery alternatives are possible per order. Although information sharing is significantly restricted, the MAS results in better solutions than a centralized Adaptive Large Neighborhood Search with full information sharing on large problem instances where computation time is limited., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Transport Engineering and Logistics, Algorithmics

Collaboration in transportation is important to reduce costs and emissions, but carriers may have incentives to bid strategically in decentralized auction systems. We investigate what the effect of the auction strategy is on the possible cheating benefits in a dynamic context, such that we can recommend a method with lower chances for carriers to cheat. We consider both a first-price auction system and a second-price auction scheme. Contrary to what was expected, a second-price auction scheme gives more room for successful strategic behaviour, while it also results in more rejected orders. A first-price auction scheme might be useful in practice if the profit shares that are allocated to the winner of an auction are selected carefully., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Transport Engineering and Logistics, Algorithmics

The freight transportation sector is one of the major contributors to air pollution. An important way to reduce emissions consists of collective route planning. Although unloaded trips and inefficient routes could not always be prevented by individual carriers, more efficient operations could often be obtained if multiple carriers collaborate by exchanging part of their shipments. The resulting vehicle mileage reductions not only lower the costs for the cooperating carriers, but also reduce emissions and decrease the level of congestion. Achieving a successful collaboration between carriers, however, is a difficult problem. On top of the NP-hardness of the vehicle routing problem, the collaborative variants suffer from different carriers each having their individual policies, objectives, and preferences. Whereas information is generally assumed to be available in fleet management problems for individual carriers, this is problematic in collaborative cases: carriers might be hesitant to share confidential information with each other or with a platform that coordinates the cooperation. Furthermore, carriers might be more interested in increasing their own profits than in reducing the overall costs. Hence, they might try to exploit a cooperative approach. This thesis explores how the above problems can be approached in the context of dynamic large-scale collaborative pickup and delivery problems. Earlier, centralized collaboration approaches have been proposed, but these are only applicable to problems of limited size: computation times increase with the number of orders, and hence, quick adaptations in a dynamic world will be hindered. Furthermore, information is assumed to be always available in centralized approaches, and carriers need to give up their autonomy. To avoid the last two problems, decentralized approaches with central auctions have been used, but these still suffer from scalability issues due to the role of a central auctioneer. This thesis ther, Transport Engineering and Logistics

Single photon detectors are indispensable tools in optics, from fundamental measurements to quantum information processing. The ability of superconducting nanowire single photon detectors (SNSPDs) to detect single photons with unprecedented efficiency, short dead time, and high time resolution over a large frequency range enabled major advances in quantum optics. However, combining near-unity system detection efficiency (SDE) with high timing performance remains an outstanding challenge. In this work, we fabricated novel SNSPDs on membranes with 99.5-2.07+0.5% SDE at 1350 nm with 32 ps timing jitter (using a room-temperature amplifier), and other detectors in the same batch showed 94%-98% SDE at 1260-1625 nm with 15-26 ps timing jitter (using cryogenic amplifiers). The SiO2/Au membrane enables broadband absorption in small SNSPDs, offering high detection efficiency in combination with high timing performance. With low-noise cryogenic amplifiers operated in the same cryostat, our efficient detectors reach a timing jitter in the range of 15-26 ps. We discuss the prime challenges in optical design, device fabrication, and accurate and reliable detection efficiency measurements to achieve high performance single photon detection. As a result, the fast developing fields of quantum information science, quantum metrology, infrared imaging, and quantum networks will greatly benefit from this far-reaching quantum detection technology., ImPhys/Optics

Background Healthcare costs related to ESRD are well-described, but broader societal costs of ESRD are less known. This study aimed to estimate patient and family costs, including informal care costs and out-of-pocket costs, and costs due to productivity loss related to ESRD, for patients receiving dialysis and living with a kidney transplant, using a bottom-up approach. Methods A total of 655 patients were asked to complete a digital questionnaire consisting of two standardised instruments (iMCQ and iPCQ) from November 2016 through January 2017. We applied a retrospective bottom-up cost estimation by combining data from the questionnaire with unit prices from the Dutch costing manual. Results Our study sample consisted of 230 patients, of which 165 were kidney transplant recipients and 65 received dialysis. The total annual non-healthcare related costs were estimated at €8284 (SD: €14,266) for transplant recipients and €23,488 (SD: €39,434) for dialysis patients. Costs due to productivity loss contributed most to the total non-healthcare costs (66% for transplant recipients and 65% for dialysis patients), followed by informal care costs (26% resp. 29%) and out-of-pocket costs, such as medication and travel expenses (8% resp. 6%). Conclusion By exposing patient, family and productivity costs, our study revealed that dialysis and transplantation are not only costly within the healthcare system, but also incur high non-healthcare costs (18–23% resp. 35% of the total societal costs). It is important to reveal these types of non-healthcare costs in order to understand the full burden of ESRD for society and the potential impact of new therapies.

A broad range of scientific and industrial disciplines require precise optical measurements at very low light levels. Single-photon detectors combining high efficiency and high time resolution are pivotal in such experiments. By using relatively thick films of NbTiN (8-11 nm) and improving the pattern fidelity of the nanostructure of the superconducting nanowire single-photon detectors (SNSPD), we fabricated devices demonstrating superior performance over all previously reported detectors in the combination of efficiency and time resolution. Our findings prove that small variations in the nanowire width, in the order of a few nanometers, can lead to a significant penalty on their temporal response. Addressing these issues, we consistently achieved high time resolution (best device 7.7 ps, other devices similar to 10-16 ps) simultaneously with high system detection efficiencies (80-90%) in the wavelength range of 780-1000 nm, as well as in the telecom bands (1310-1550 nm). The use of thicker films allowed us to fabricate large-area multipixel devices with homogeneous pixel performance. We first fabricated and characterized a 100 x 100 mu m(2) 16-pixel detector and showed there was little variation among individual pixels. Additionally, to showcase the power of our platform, we fabricated and characterized 4-pixel multimode fiber-coupled detectors and carried out photon-correlation experiments on a nanowire quantum dot resulting in g(2) (0) values lower than 0.04. The multipixel detectors alleviate the need for beamsplitters and can be used for higher order correlations with promising prospects not only in the field of quantum optics, but also in bioimaging applications, such as fluorescence microscopy and positron emission tomography.

Background: Epilepsy is associated with a high disease burden, impacting the lives of people with epilepsy and their caregivers and family. Persons with medically refractory epilepsy experience the greatest burden, suffering from profound physical, psychological, and social consequences. Anecdotal evidence suggests these persons may benefit from a seizure dog. As the training of a seizure dog is a substantial investment, their accessibility is limited in the absence of collective reimbursement as is seen in the Netherlands. Despite sustained interest in seizure dogs, scientific knowledge on their benefits and costs remains scarce. To substantiate reimbursement decisions stronger evidence is required. The EPISODE study aims to provide this evidence by evaluating the effectiveness and cost-effectiveness of seizure dogs in adults with medically refractory epilepsy. Methods: The study is designed as a stepped wedge randomized controlled trial that compares the use of seizure dogs in addition to usual care, with usual care alone. The study includes adults with epilepsy for whom current treatment options failed to achieve seizure freedom. Seizure frequency of participants should be at least two seizures per week, and the seizures should be associated with a high risk of injury or dysfunction. During the 3 year follow-up period, participants receive a seizure dog in a randomized order. Outcome measures are taken at multiple time points both before and after receiving the seizure dog. Seizure frequency is the primary outcome of the study and will be recorded continuously using a seizure diary. Questionnaires measuring seizure severity, quality of life, well-being, resource use, productivity, social participation, and caregiver burden will be completed at baseline and every 3 months thereafter. The study is designed to include a minimum of 25 participants. Discussion: This protocol describes the first randomized controlled trial on seizure dogs. The study will provide compre

While collaborative vehicle routing has a significant potential to reduce transportation costs and emissions, current approaches are limited in terms of applicability, unrealistic assumptions, and low scalability. Centralized planning generally assumes full information and full control, which is often unacceptable for individual carriers. Combinatorial auctions with one central auctioneer overcome this problem and provide good results, but are limited to small static problems. Multi-agent approaches have been proposed for large dynamic problems, but do not directly take the advantages of bundling into account. We propose an approach where participants can individually outsource orders, while a platform can suggest bundles of the offered requests to improve solutions. We consider bundles of size 2 and 3 and show that travel costs can be decreased with 1.7% compared to the scenario with only single order auctions. Moreover, experiments on data from a Dutch transportation platform company show that large-scale collaboration through a platform results in system-wide savings of up to 79% for 1000 carriers., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Transport Engineering and Logistics, Algorithmics

Cooperation is important in order to find efficient vehicle routing solutions for the growing transportation market. Increasingly, platforms emerge as facilitators for this kind of collaborative transportation. However, individual actors connected to a platform might refuse to share (parts of) their information due to reasons of competition. Though the need for realistic information sharing models is widely acknowledged by transportation researchers and practitioners, the precise value of such information is mostly unknown. We investigate the quality of solutions that can be obtained when different types and levels of carrier data are available. We consider an auction-based Multi-Agent System to solve large-scale, dynamic pickup and delivery problems, and vary whether carriers’ positions or route plans are available, and whether carriers are fully cooperative or more competitive in placing their bids by sharing or hiding their marginal costs. In total, we evaluate 9 different information sharing policies. The availability of vehicle position and route plan information turns out to be important for decreasing total route costs, and sharing marginal costs has a positive impact on service level. We provide detailed insights into trade-offs of carriers’ confidentiality concerns and a range of system performance objectives (service level, travel costs, and carrier profits) under different circumstances (various numbers of auctions, penalties for rejected orders, emission or congestion fees, and different problem characteristics). Based on these results, platform providers can stimulate sharing of certain information to improve the total system efficiency., Transport Engineering and Logistics, Algorithmics

The transportation market requires collaboration to improve efficiency and reduce emissions. Individual carriers, however, might be hesitant to share their private information on a transportation platform. Although a few articles have investigated the value of information sharing, they assume identical behaviour of all carriers. In practice, nonetheless, some carriers are open to share more information than others. We consider such a hybrid information sharing setting and investigate the value of information sharing dependent on what other carriers are willing to share. We propose a Multi-Agent System in which carriers and customers interact and vary carriers’ willingness to share information about vehicle locations and marginal costs. The results show that sharing full route plans is always beneficial for individual carriers, independent of what position information other carriers share. However, to increase the total profit in scenarios with limited interaction, at least 50% of the carriers need to share full plans instead of only current positions. Furthermore, about 60% of the carriers need to be stimulated to share full cost information for solutions with maximal service level, although it might be unprofitable for themselves., Transport Engineering and Logistics, Algorithmics