526 research outputs found
Effects of intraduodenal protein on appetite, energy intake, and antropyloroduodenal motility in healthy older compared with young men in a randomized trial
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Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis
Background: Costâeffective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decisionâmaking. A concentrationâresponse relationship for ustekinumab at trough is uncertain owing to the contradictory results reported.
Objectives: To investigate the relationship between 4âweek postinjection ustekinumab concentrations and clinical response in patients with psoriasis.
Methods: Fortyânine patients with moderateâtoâsevere psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for â„ 16 weeks were included. Ustekinumab serum concentrations and antiâustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI).
Results: At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5·9 ÎŒg mLâ1 (Ï = â0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI †2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 ÎŒg mLâ1, P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 ÎŒg mLâ1 (area under the curve 0·71, sensitivity 86%, specificity 63%). Only one patient (2%) had antiâustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0·003 and P = 0·048, respectively).
Conclusions: A concentrationâresponse relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4âweek postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization
Distribution of the invasive ctenophore <i>Mnemiopsis leidyi</i> in the Belgian part of the North Sea
The invasive ctenophore Mnemiopsis leidyi A. Agassiz, 1865 was recorded for the first time in Northern Europe in summer 2005, while the first records in the North Sea date back to summer 2006. The first sightings in the Belgian part of the North Sea were made in August 2007 in the port of Zeebrugge, but most probably M. leidyi had already been present for a longer period in this area. The high densities in the port of Zeebrugge suggest that M. leidyi entered the Belgian marine waters via ballast water transport, comparable with the invasion in the Black and Caspian Seas and the Dutch part of the North Sea. In the period 2009â2011, M. leidyi was found in all ports and all along the Belgian coastline, up to 27 km offshore. Further offshore, no M. leidyi were found in zooplankton samples and small meshed otter trawl samples. Sightings of adult individuals in the coldest winter months imply that the species can survive Belgian winters. Highest densities (17 ind.m-3) were found in the Sluice dock in the port of Oostende. Along the coastline, average densities of 0.4 ind.m 3 were recorded. As M. leidyi might previously have been misidentified on the basis of morphological features alone, we also determined the species with genetic identification tools. Taking into account the notorious impact of this species in its native and in other invaded waters, it is recommended to continue the monitoring of M. leidyi populations in the Belgian part of the North Sea
The role of lateral magnetic reconnection in solar eruptive events
On 10â11 December 2005 a slow CME occurred in between two coronal streamers in the Western Hemisphere. SOHO/MDI magnetograms show a multipolar magnetic configuration at the photosphere consisting of a complex of active regions located at the CME source and two bipoles at the base of the lateral coronal streamers. White light observations reveal that the expanding CME affects both of the lateral streamers and induces the release of plasma within or close to them. These transient phenomena are possibly due to magnetic reconnections induced by the CME expansion that occurs either inside the streamer current sheet or between the CME flanks and the streamer. Our observations show that CMEs can be associated to not only a single reconnection process at a single location in the corona, but also to many reconnection processes occurring at different times and locations around the flux rope. Numerical simulations are used to demonstrate that the observed lateral reconnections can be reproduced. The observed secondary reconnections associated to CMEs may facilitate the CME release by globally decreasing the magnetic tension of the corona. Future CME models should therefore take into account the lateral reconnection effect
Weight-loss induced changes in physical activity and activity energy expenditure in overweight and obese subjects before and after energy restriction
Activity energy expenditure (AEE) is the component of daily energy expenditure that is mainly influenced by the amount of physical activity (PA) and by the weight of the body displaced. This study aimed at analyzing the effect of weight loss on PA and AEE. The body weight and PA of 66 overweight and obese subjects were measured at baseline and after 12 weeks of 67% energy restriction. PA was measured using a tri-axial accelerometer for movement registration (Tracmor) and quantified in activity counts. Tracmor recordings were also processed using a classification algorithm to recognize 6 common activity types engaged in during the day. A doubly-labeled water validated equation based on Tracmor output was used to estimate AEE. After weight loss, body weight decreased by 13±4%, daily activity counts augmented by 9% (95% CI: +2%, +15%), and this increase was weakly associated with the decrease in body weight (R(2)â=â7%; P<0.05). After weight loss subjects were significantly (P<0.05) less sedentary (-26 min/d), and increased the time spent walking (+11 min/d) and bicycling (+4 min/d). However, AEE decreased by 0.6±0.4 MJ/d after weight loss. On average, a 2-hour/day reduction of sedentary time by increasing ambulatory and generic activities was required to restore baseline levels of AEE. In conclusion, after weight loss PA increased but the related metabolic demand did not offset the reduction in AEE due to the lower body weight. Promoting physical activity according to the extent of weight loss might increase successfulness of weight maintenance.Alberto G. Bonomi, Stijn Soenen, Annelies H. C. Goris, Klaas R. Westerter
PAM-4 VCSEL driver with selective falling-edge pre-emphasis
Data centre optical links are migrating to four-level pulse amplitude modulation (PAM-4) as a method to extend the data rate while covering longer distances. Vertical-cavity surface-emitting lasers (VCSELs) enable the integration of low-power transmitters, but their non-linear and bias-dependent behaviour makes conventional feed-forward equalisation less effective. This Letter presents a 0.13 mu m SiGe BiCMOS PAM-4 driver that boosts the falling-edge to the bottom level through a selective pre-emphasis technique. Experiments at 25 GBd (50 Gb/s) reveal that adding selective pre-emphasis to a 4-tap equalised current driving a 20.6 GHz 1.5 mu m VCSEL, relaxes the critical PAM-4 link budget requirements by >1 dB at the KP4 forward error correction threshold of 2.2 x 10(-4). The potential of PAM-4 VCSEL transmitters can be significantly enhanced by including selective pre-emphasis to the equalisation topology while requiring minimal overhead
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