Optical fibre communication is the backbone of the internet. As essential core technologies are approaching their limits of size, speed and energy-efficiency, there is a need for new technologies ...that offer further scaling of data transmission capacity. Here we show that a single optical frequency-comb source based on a silicon nitride ring resonator supports data capacities in the petabit-per-second regime. We experimentally demonstrate transmission of 1.84 Pbit s–1 over a 37-core, 7.9-km-long fibre using 223 wavelength channels derived from a single microcomb ring resonator producing a stabilized dark-pulse Kerr frequency comb. We also present a theoretical analysis that indicates that a single, chip-scale light source should be able to support 100 Pbit s–1 in massively parallel space-and-wavelength multiplexed data transmission systems. Our findings could mark a shift in the design of future communication systems, targeting device-efficient transmitters and receivers.A microcomb source based on a silicon nitride ring resonator is shown to support petabit-per-second data transmission over a multicore optical fibre.
Background: Both sublingual allergen‐specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.
...Objective: To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side‐effects.
Methods: A 3‐year randomized, placebo‐controlled, double‐blind, double‐dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age.
Results: Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one‐half and SCIT to one‐third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side‐effects, while SCIT resulted in few serious systemic side‐effects.
Conclusion: Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored.
Summary Objectives To recommend a consensus-derived set of performance-based tests of physical function for use in people diagnosed with hip or knee osteoarthritis (OA) or following joint ...replacement. Methods An international, multidisciplinary expert advisory group was established to guide the study. Potential tests for consideration in the recommended set were identified via a survey of selected experts and through a systematic review of the measurement properties for performance-based tests. A multi-phase, consensus-based approach was used to prioritize and select performance-based tests by applying decision analysis methodology (1000Minds software) via online decision surveys. The recommended tests were chosen based on available measurement-property evidence, feasibility of the tests, scoring methods and expert consensus. Results Consensus incorporated the opinions of 138 experienced clinicians and researchers from 16 countries. The five tests recommended by the advisory group and endorsed by Osteoarthritis Research Society International (OARSI) were the 30-s chair-stand test, 40 m fast-paced walk test, a stair-climb test, timed up-and-go test and 6-min walk test. The first three were recommended as the minimal core set of performance-based tests for hip or knee OA. Conclusion The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements. These tests are complementary to patient-reported measures and are recommended as prospective outcome measures in future OA research and to assist decision-making in clinical practice. Further research should be directed to expanding the measurement-property evidence of the recommended tests.
The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is ...unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)κB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.
Aims: To determine the proportion of children admitted with difficult to treat paroxysmal events to a tertiary epilepsy centre who did not have epilepsy. Methods: In an observational retrospective ...study, all case notes of 223 children admitted in 1997 were examined. The referral was made from the local paediatric department in 51% of cases, other departments in 27%, and from general or specialist practitioners in 22%. Doubt regarding the diagnosis of epilepsy was expressed in the referral note in 17%. On admission, 86% were on antiepileptic drug treatment. During admission all children were subjected to a comprehensive intensive observation and 62% had EEG monitoring. Results: In total, 39% (87/223) were found not to have epilepsy. In 30% of children (55/184) referred without any doubts about the epilepsy diagnosis, the diagnosis was disproved. Of the 159 children admitted for the first time, 75 (47%) were discharged with a diagnosis of non-epileptic seizures. Of 125 children admitted for the first time with no doubts about the diagnosis of epilepsy, 44 (35%) did not have epilepsy. Staring episodes were the most frequently encountered non-epileptic paroxysmal event. Psychogenic non-epileptic seizures were found in 12 children. A total of 34 (15%) had their medication tapered off; a further 22 (10%) had tapered off medication before admission. Conclusion: The present study supports the view that misdiagnosis of epilepsy is common. The treating physician should be cautious in diagnosis, especially of staring episodes. A diagnostic re-evaluation should be undertaken in difficult cases with continuing paroxysmal events in order to avoid unnecessary drug treatment and restrictions on the child’s lifestyle.
Background
Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release ...assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy.
Methods
BAT, HR, and passive HR were performed on 11 peanut‐allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti‐IgE and tests were performed as follows: BAT—CD63 upregulation was assessed by flow cytometry; HR—released histamine was quantified by a glass fiber‐based fluorometric method; passive HR—IgE‐stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR.
Results
CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min).
Conclusion
BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR.
Abstract
We present the ion composition in the coma of comet 67P with newly detected ion species over the 28–37 u mass range, probed by Rosetta Orbiter Spectrometer for Ion and Neutral Analysis ...(ROSINA)/Double Focusing Mass Spectrometer (DFMS). In summer 2015, the nucleus reached its highest outgassing rate and ion-neutral reactions started to take place at low cometocentric distances. Minor neutrals can efficiently capture protons from the ion population, making the protonated version of these neutrals a major ion species. So far, only $\mathrm{NH_4^+}$ has been reported at comet 67P. However, there are additional neutral species with proton affinities higher than that of water (besides NH3) that have been detected in the coma of comet 67P: CH3OH, HCN, H2CO and H2S. Their protonated versions have all been detected. Statistics showing the number of detections with respect to the number of scans are presented. The effect of the negative spacecraft potential probed by the Rosetta Plasma Consortium/LAngmuir Probe on ion detection is assessed. An ionospheric model has been developed to assess the different ion density profiles and compare them to the ROSINA/DFMS measurements. It is also used to interpret the ROSINA/DFMS observations when different ion species have similar masses, and their respective densities are not high enough to disentangle them using the ROSINA/DFMS high-resolution mode. The different ion species that have been reported in the coma of 67P are summarized and compared with the ions detected at comet 1P/Halley during the Giotto mission.
The objectives of this study were to estimate variance components and identify regions of the genome associated with traits related to embryo transfer in Holsteins. Reproductive technologies are used ...in the dairy industry to increase the reproductive rate of superior females. A drawback of these methods remains the variability of animal responses to the procedures. If some variability can be explained genetically, selection can be used to improve animal response. Data collected from a Holstein dairy farm in Florida from 2008 to 2015 included 926 superovulation records (number of structures recovered and number of good embryos), 628 in vitro fertilization records (number of oocytes collected, number of cleaved embryos, number of high- and low-quality embryos, and number of transferrable embryos), and 12,089 embryo transfer records (pregnancy success). Two methods of transformation (logarithmic and Anscombe) were applied to count variables and results were compared. Univariate animal models were fitted for each trait with the exception of pregnancy success after embryo transfer. Due to the binary nature of the latter trait, a threshold liability model was fitted that accounted for the genetic effect of both the recipient and the embryo. Both transformation methods produced similar results. Single-step genomic BLUP analyses were performed and SNP effects estimated for traits with a significant genetic component. Heritability of number of structures recovered and number of good embryos when log-transformed were 0.27 ± 0.08 and 0.15 ± 0.07, respectively. Heritability estimates from the in vitro fertilization data ranged from 0.01 ± 0.08 to 0.21 ± 0.15, but were not significantly different from zero. Recipient and embryo heritability (standard deviation) of pregnancy success after embryo transfer was 0.03 (0.01) and 0.02 (0.01), respectively. The 10-SNP window explaining the largest proportion of variance (0.37%) for total structures collected was located on chromosome 8 beginning at 55,663,248 bp. Similar regions were identified for number of good embryos, with the largest proportion of variance (0.43%) explained by a 10-SNP window on chromosome 14 beginning at 26,713,734 bp. Results indicate that there is a genetic component for some traits related to superovulation and that selection should be possible. Moreover, the genetic component for superovulation traits involves some genomic regions that are similar to those for other fertility traits currently evaluated.
Clustering of magnetic nanoparticles can drastically change their collective magnetic properties, which in turn may influence their performance in technological or biomedical applications. Here, we ...investigate a commercial colloidal dispersion (FeraSpinTMR), which contains dense clusters of iron oxide cores (mean size around 9 nm according to neutron diffraction) with varying cluster size (about 18-56 nm according to small angle x-ray diffraction), and its individual size fractions (FeraSpinTMXS, S, M, L, XL, XXL). The magnetic properties of the colloids were characterized by isothermal magnetization, as well as frequency-dependent optomagnetic and AC susceptibility measurements. From these measurements we derive the underlying moment and relaxation frequency distributions, respectively. Analysis of the distributions shows that the clustering of the initially superparamagnetic cores leads to remanent magnetic moments within the large clusters. At frequencies below 105 rad s−1, the relaxation of the clusters is dominated by Brownian (rotation) relaxation. At higher frequencies, where Brownian relaxation is inhibited due to viscous friction, the clusters still show an appreciable magnetic relaxation due to internal moment relaxation within the clusters. As a result of the internal moment relaxation, the colloids with the large clusters (FS-L, XL, XXL) excel in magnetic hyperthermia experiments.
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