Temporal dissipative Kerr solitons in optical microresonators enable the generation of ultrashort pulses and low-noise frequency combs at microwave repetition rates. They have been demonstrated in a ...growing number of microresonator platforms, enabling chip-scale frequency combs, optical synthesis of low-noise microwaves and multichannel coherent communications. In all these applications, accessing and maintaining a single-soliton state is a key requirementone that remains an outstanding challenge. Here, we study the dynamics of multiple-soliton states and report the discovery of a simple mechanism that deterministically switches the soliton state by reducing the number of solitons one by one. We demonstrate this control in Si3N4 and MgF2 resonators and, moreover, we observe a secondary peak to emerge in the response of the system to a pump modulation, an eect uniquely associated with the soliton regime. Exploiting this feature, we map the multi-stability diagram of a microresonator experimentally. Our measurements show the physical mechanism of the soliton switching and provide insight into soliton dynamics in microresonators. The technique provides a method to sequentially reduce, monitor and stabilize an arbitrary state with solitons, in particular allowing for feedback stabilization of single-soliton states, which is necessary for practical applications.
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IJS, NUK, SBMB, UL, UM, UPUK
Cell-surface expressed contactin 1 and neurofascin 155 control wiring of the nervous system and interact across cells to form and maintain paranodal myelin-axon junctions. The molecular mechanism of ...contactin 1 - neurofascin 155 adhesion complex formation is unresolved. Crystallographic structures of complexed and individual contactin 1 and neurofascin 155 binding regions presented here, provide a rich picture of how competing and complementary interfaces, post-translational glycosylation, splice differences and structural plasticity enable formation of diverse adhesion sites. Structural, biophysical, and cell-clustering analysis reveal how conserved Ig1-2 interfaces form competing heterophilic contactin 1 - neurofascin 155 and homophilic neurofascin 155 complexes whereas contactin 1 forms low-affinity clusters through interfaces on Ig3-6. The structures explain how the heterophilic Ig1-Ig4 horseshoe's in the contactin 1 - neurofascin 155 complex define the 7.4 nm paranodal spacing and how the remaining six domains enable bridging of distinct intercellular distances.
Background Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with ...laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. Methods We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. Results Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2 DS2 VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07–1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. Conclusions In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly ...visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.
IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.
The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across ...Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists. In total, 223 centres from 26 countries reported 1,009 patients aged < 20 yrs. Reported cases per million children (for 5-14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% had situs inversus. Median age at diagnosis was 5.3 yrs, lower in children with situs inversus (3.5 versus 5.8 yrs; p < 0.001) and in children treated in large centres (4.1 versus 4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p < 0.001). This strongly correlated with general government expenditures on health (p < 0.001). This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.
National Day of Service (NDS) volunteering events have become common, yet little is known about how the design of such events affects volunteer satisfaction. This relationship is important because ...volunteer satisfaction ensures a strong volunteer base for special events and promotes sustained volunteerism. We explore how the design of NDS projects promotes volunteer job satisfaction. Our approach to the research question is informed by work design theory. Based on interview, participant observation, and focus group data from an NDS in the Netherlands, the findings suggest that nonprofit organizations can elicit volunteer job satisfaction by designing NDS projects that create a sense of added value, support productivity, and make volunteers feel comfortable. Designing NDS projects that incorporate task significance, symbolic social support, feedback from others, beneficiary contact, task identity, project preparation, physically demanding work, social support, and limited autonomy help to achieve these goals.
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NUK, OILJ, PRFLJ, SAZU, UKNU, UL, UM, UPUK
There is worldwide concern about the environmental costs of conventional intensification of agriculture. Growing evidence suggests that ecological intensification of mainstream farming can safeguard ...food production, with accompanying environmental benefits; however, the approach is rarely adopted by farmers. Our review of the evidence for replacing external inputs with ecosystem services shows that scientists tend to focus on processes (e.g., pollination) rather than outcomes (e.g., profits), and express benefits at spatio-temporal scales that are not always relevant to farmers. This results in mismatches in perceived benefits of ecological intensification between scientists and farmers, which hinders its uptake. We provide recommendations for overcoming these mismatches and highlight important additional factors driving uptake of nature-based management practices, such as social acceptability of farming.
Ecological intensification aims to harness ecosystem services to sustain agricultural production while minimising adverse effects on the environment.
Ecological intensification is championed by scientists as a nature-based alternative to high-input agriculture but meets with little interest from growers.
Scientific evidence underlying ecological intensification is often unconvincing to growers, as it is based on small-scale studies of ecological processes unlinked from agricultural production.
Grower interest can be enhanced by evidence of the agronomic and economic benefits most relevant to farmers and measured at the scales of operation of farm enterprises.
In addition to concrete benefits, concerns of the general public about adverse effects of industrial farming can promote adoption of ecological intensification, both directly and indirectly, by enhancing political will to use regulatory instruments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D 25(OH)D levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the ...contribution of these factors to the latitudinal gradient in FDE incidence in Australia.
This was a multicenter incident case-control study. Cases (n = 216) were aged 18-59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status.
Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval CI 0.53-0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m(2) (range 508-6,397 kJ/m(2)). Higher actinic skin damage (AOR = 0.39 95% CI 0.17-0.92, highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 95% CI 0.86-1.00 per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions.
Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.
Patients with confirmed or suspected Covid-19 were randomly assigned to receive hydroxychloroquine with azithromycin, hydroxychloroquine alone, or usual care. The primary outcome was clinical status ...at 15 days, assessed on a seven-level ordinal scale. There were no significant differences between groups in the primary outcome.
Supergeneralists, defined as species that interact with multiple groups of species in ecological networks, can act as important connectors of otherwise disconnected species subsets. In Brazil, there ...are two supergeneralist bees: the honeybee Apis mellifera, a non-native species, and Trigona spinipes, a native stingless bee. We compared the role of both species and the effect of geographic and local factors on networks by addressing three questions: 1) Do both species have similar abundance and interaction patterns (degree and strength) in plant-bee networks? 2) Are both species equally influential to the network structure (nestedness, connectance, and plant and bee niche overlap)? 3) How are these species affected by geographic (altitude, temperature, precipitation) and local (natural vs. disturbed habitat) factors? We analyzed 21 plant-bee weighted interaction networks, encompassing most of the main biomes in Brazil. We found no significant difference between both species in abundance, in the number of plant species with which each bee species interacts (degree), and in the sum of their dependencies (strength). Structural equation models revealed the effect of A. mellifera and T. spinipes, respectively, on the interaction network pattern (nestedness) and in the similarity in bee's interactive partners (bee niche overlap). It is most likely that the recent invasion of A. mellifera resulted in its rapid settlement inside the core of species that retain the largest number of interactions, resulting in a strong influence on nestedness. However, the long-term interaction between native T. spinipes and other bees most likely has a more direct effect on their interactive behavior. Moreover, temperature negatively affected A. mellifera bees, whereas disturbed habitats positively affected T. spinipes. Conversely, precipitation showed no effect. Being positively (T. spinipes) or indifferently (A. mellifera) affected by disturbed habitats makes these species prone to pollinate plant species in these areas, which are potentially poor in pollinators.
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