Stochastic processes that are randomly reset to an initial condition serve as a showcase to investigate non-equilibrium steady states. However, all existing results have been restricted to the ...special case of memoryless resetting protocols. Here, we obtain the general solution for the distribution of processes in which waiting times between reset events are drawn from an arbitrary distribution. This allows for the investigation of a broader class of much more realistic processes. As an example, our results are applied to the analysis of the efficiency of constrained random search processes.
Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir ...(GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses.
, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.
Spare parts are a particularly interesting application for switching production from traditional manufacturing (TM) to additive manufacturing (AM). Research assessing AM has primarily addressed cost ...models centering on the production process or the operations management of separate spare parts. By combining case study, modeling, and design science elements, we adopt a holistic perspective and develop a design to examine the systematic leverage of AM in spare parts operations. Contextually grounded in problems faced by a leading material handling equipment manufacturer that is challenged by common characteristics of after-sales operations, we engage with practice to propose a portfolio level analysis examining the switchover share from TM to AM. Using a data set of 53,457 spare parts over 9 years, we find that up to 8% of stock keeping units (SKUs) and 2% of total units supplied could be produced using AM, even if unit production costs are four times those of TM. This result is driven by low demand, high fixed costs, and minimum order quantities in TM. Finally, we present the evaluation by the case company's management and highlight five areas of opportunity and challenge.
The growing incidence of skeletal fractures poses a significant challenge to ageing societies. Since a major part of physiological loading in the lower limbs is carried by cortical bone, it would be ...desirable to better understand the structure-mechanical property relationships and scale effects in this tissue. This study aimed at assessing whether microindentation properties combined with chemical and morphological information are usable to predict macroscopic elastic and strength properties in a donor- and site-matched manner. Specimens for quasi-static macroscopic tests in tension, compression, and torsion and microindentation were prepared from a cohort of 19 male and 20 female donors (46 to 99 years). All tests were performed under fully hydrated conditions. The chemical composition of the extra-cellular matrix was investigated with Raman spectroscopy. The results of the micro-mechanical tests were combined with morphological and compositional properties using a power law relationship to predict the macro-mechanical results. Microindentation properties were not gender dependent, remarkably constant over age, and showed an overall small variation with standard deviations of approximately 10 %. Similar results were obtained for chemical tissue composition. Macro-mechanical stiffness and strength were significantly related to porosity for all load cases (p<0.05). In case of macroscopic yield strain and work-to-failure this was only true in torsion and compression, respectively. The correlations of macro-mechanical with micro-mechanical, morphological, and chemical properties showed no significance for cement line density, mineralisation, or variations in the microindentation results and were dominated by porosity with a moderate explanatory power of predominately less than 50 %. The results confirm that age, with minor exceptions gender, and small variations in average mineralisation have negligible effect on the tissue microindentation properties of human lamellar bone in the elderly. Furthermore, our findings suggest that microindentation experiments are suitable to predict macroscopic mechanical properties in the elderly only on average and not on a one to one basis. The presented data may help to form a better understanding of the mechanisms of ageing in bone tissue and of the length scale at which they are active. This may be used for future prediction of fracture risk in the elderly.
Model-based decomposition of polarimetric radar covariance matrices holds the promise that specific scattering mechanisms can be isolated for further quantitative analysis. In this paper, we show ...that current algorithms suffer from a fatal flaw in that some of the scattering components result in negative powers. We propose a simple modification that ensures that all covariance matrices in the decomposition will have nonnegative eigenvalues. We further combine our nonnegative eigenvalue decomposition with eigenvector decomposition to remove additional assumptions that have to be made before the current algorithms can be used to estimate all the scattering components. Our results are illustrated using Airborne Synthetic Aperture Radar data and show that current algorithms typically overestimate the canopy scattering contribution by 10%-20%.
Many new ventures position themselves along the additive manufacturing (AM) value chain to benefit from the quickly maturing technology. Yet, their business models and sources of value creation are ...largely unidentified. We compile a unique dataset with 160 entrepreneurial AM-firms using a leading crowd-sourced database and organize the data in a card file system. We code the data along multiple dimensions and apply a Latent Class Analysis to identify unique segments of firms that focus on different complementary activities along the AM value chain. By using the NICE framework, we additionally reveal the value creation mechanisms of each identified class. We identify four unique segments of AM-firms that focus on different complementary activities: (i) hardware providers, (ii) software and data experts, (iii) full-service providers, and (iv) manufacturing orchestrators. While a lot of value creation across these segments is currently still driven by novelty and innovation, AM-firms also introduce lock-in and complementary products and services to capture value beyond production. In characterizing value chain structures, we outline how firms can position themselves in this emerging industry.
PurposeA current technological trend, which has gained even more traction recently due to the COVID-19 pandemic, is the use of augmented reality (AR) in shopping environments. AR is addressing ...contemporary challenges rooted in online shopping (e.g. in terms of experientiality and try-on) and is fundamentally reshaping consumers' experiences. The purpose of this study is to provide a synthesized and structured overview of the state-of-the-art research focused on AR shopping.Design/methodology/approachThe authors conduct a systematic literature review of the empirical academic corpus focused on shopping via AR technology.FindingsThe review reveals the diverse psychological (cognitive, affective, and social) as well as behavioral outcomes related to the use of AR in the shopping context. The authors integrate the results into a framework for AR induced consumer behavior in shopping, thereby providing an important overview of the dynamics in AR-related shopping and the factors influencing the adoption of the technology by consumers. Specifically, the authors encountered that the technological abilities of AR (e.g. in terms of interactivity, vividness, informativeness, etc.) are a source for enhanced utilitarian and hedonic shopping experiences that can support intentions to purchase a product, reuse an AR app, or recommend it to others. Importantly, our review reveals the demand for several avenues for future research.Originality/valueThe authors provide an overview and synthesis of how and where AR is employed in shopping contexts, what theories and technological characteristics of AR are commonly analyzed, and what psychological and behavioral outcomes AR has been found to evoke. Based on our findings, the authors derive a framework that illustrates the dynamics in AR shopping and give an in-depth discourse on 13 future research agenda points related to thematic, theoretical, methodological, and technological matters.
The ongoing SARS‐CoV‐2 pandemic stresses the need for effective antiviral drugs that can quickly be applied in order to reduce morbidity, mortality, and ideally viral transmission. By repurposing of ...broadly active antiviral drugs and compounds that are known to inhibit viral replication of related viruses, several advances could be made in the development of treatment strategies against COVID‐19. The nucleoside analog remdesivir, which is known for its potent in vitro activity against Ebolavirus and other RNA viruses, was recently shown to reduce the time to recovery in patients with severe COVID‐19. It is to date the only approved antiviral for treating COVID‐19. Here, we provide a mechanism and evidence‐based comparative review of remdesivir and other repurposed drugs with proven in vitro activity against SARS‐CoV‐2.
This comprehensive review discusses preclinical and clinical outcomes of remdesivir and other repurposed antiviral drugs against SARS‐CoV‐2.
Arctic landscapes are changing rapidly in response to warming, but future predictions are hindered by difficulties in scaling ecological relationships from plots to biomes. Unmanned aerial systems ...(hereafter 'drones') are increasingly used to observe Arctic ecosystems over broader extents than can be measured using ground-based approaches and are facilitating the interpretation of coarse-grained remotely sensed data. However, more information is needed about how drone-acquired remote sensing observations correspond with ecosystem attributes such as aboveground biomass. Working across a willow shrub-dominated alluvial fan at a focal study site in the Canadian Arctic, we conducted peak growing season drone surveys with an RGB camera and a multispectral multi-camera array. We derived photogrammetric reconstructions of canopy height and normalised difference vegetation index (NDVI) maps along with in situ point-intercept measurements and aboveground vascular biomass harvests from 36, 0.25 m2 plots. We found high correspondence between canopy height measured using in situ point-intercept methods compared to drone-photogrammetry (concordance correlation coefficient = 0.808), although the photogrammetry heights were positively biased by 0.14 m relative to point-intercept heights. Canopy height was strongly and linearly related to aboveground biomass, with similar coefficients of determination for point-intercept (R2 = 0.92) and drone-based methods (R2 = 0.90). NDVI was positively related to aboveground biomass, phytomass and leaf biomass. However, NDVI only explained a small proportion of the variance in biomass (R2 between 0.14 and 0.23 for logged total biomass) and we found moss cover influenced the NDVI-phytomass relationship. Vascular plant biomass is challenging to infer from drone-derived NDVI, particularly in ecosystems where bryophytes cover a large proportion of the land surface. Our findings suggest caution with broadly attributing change in fine-grained NDVI to biomass differences across biologically and topographically complex tundra landscapes. By comparing structural, spectral and on-the-ground ecological measurements, we can improve understanding of tundra vegetation change as inferred from remote sensing.
Abstract
Background
The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear.
Methods
We conducted a systematic review until 1 November 2022 searching for randomized ...controlled trials (RCTs) involving COVID-19 patients comparing molnupiravir ±standard of care (SoC) versus SoC and/or placebo. Data were pooled in random-effects meta-analyses. Certainty of evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations approach.
Results
Nine RCTs were identified, eight investigated outpatients (29 254 participants) and one inpatients (304 participants). Compared with placebo/SoC, molnupiravir does not reduce mortality risk ratio (RR) 0.27, 95% CI 0.07–1.02, high-certainty evidence and probably does not reduce the risk for ‘hospitalization or death’ (RR 0.81, 95% CI 0.55–1.20, moderate-certainty evidence) by Day 28 in COVID-19 outpatients. We are uncertain whether molnupiravir increases symptom resolution by Day 14 (RR 1.20, 95% CI 1.02–1.41, very-low-certainty evidence) but it may make no difference by Day 28 (RR 1.05, 95% CI 0.92–1.19, low-certainty evidence). In inpatients, molnupiravir may increase mortality by Day 28 compared with placebo (RR 3.78, 95% CI 0.50–28.82, low-certainty evidence). There is little to no difference in serious adverse and adverse events during the study period in COVID-19 inpatients/outpatients treated with molnupiravir compared with placebo/SoC (moderate- to high-certainty evidence).
Conclusions
In a predominantly immunized population of COVID-19 outpatients, molnupiravir has no effect on mortality, probably none on ‘hospitalization or death’ and effects on symptom resolution are uncertain. Molnupiravir was safe during the study period in outpatients although a potential increase in inpatient mortality requires careful monitoring in ongoing clinical research. Our analysis does not support routine use of molnupiravir for COVID-19 treatment in immunocompetent individuals.
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