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Root infinitives on Twitter
(2017)
Editorial
(2017)
We develop a simple two-zone interpretation of the broadband baseline Crab nebula spectrum between 10(-5) eV and similar to 100 TeV by using two distinct log-parabola energetic electrons distributions. We determine analytically the very-high energy photon spectrum as originated by inverse-Compton scattering of the far-infrared soft ambient photons within the nebula off a first population of electrons energized at the nebula termination shock. The broad and flat 200 GeV peak jointly observed by Fermi/LAT and MAGIC is naturally reproduced. The synchrotron radiation from a second energetic electron population explains the spectrum from the radio range up to similar to 10 keV. We infer from observations the energy dependence of the microscopic probability of remaining in proximity of the shock of the accelerating electrons.
Since the Shallow Structure Hypothesis (SSH) was first put forward in 2006, it has inspired a growing body of research on grammatical processing in nonnative (L2) speakers. More than 10 years later, we think it is time for the SSH to be reconsidered in the light of new empirical findings and current theoretical assumptions about human language processing. The purpose of our critical commentary is twofold: to clarify some issues regarding the SSH and to sketch possible ways in which this hypothesis might be refined and improved to better account for L1 and L2 speakers’ performance patterns.
Photonic sensing in highly concentrated biotechnical processes by photon density wave spectroscopy
(2017)
Photon Density Wave (PDW) spectroscopy is introduced as a new approach for photonic sensing in highly concentrated biotechnical processes. It independently quantifies the absorption and reduced scattering coefficient calibration-free and as a function of time, thus describing the optical properties in the vis/NIR range of the biomaterial during their processing. As examples of industrial relevance, enzymatic milk coagulation, beer mashing, and algae cultivation in photo bioreactors are discussed.
Background: Infliximab (IFX), an anti-TNF monoclonal antibody approved for the treatment of inflammatory bowel disease, is dosed per kg body weight (BW). However, the rationale for body size adjustment has not been unequivocally demonstrated [1], and first attempts to improve IFX therapy have been undertaken [2]. The aim of our study was to assess the impact of different dosing strategies (i.e. body size-adjusted and fixed dosing) on drug exposure and pharmacokinetic (PK) target attainment. For this purpose, a comprehensive simulation study was performed, using patient characteristics (n=116) from an in-house clinical database.
Methods: IFX concentration-time profiles of 1000 virtual, clinically representative patients were generated using a previously published PK model for IFX in patients with Crohn's disease [3]. For each patient 1000 profiles accounting for PK variability were considered. The IFX exposure during maintenance treatment after the following dosing strategies was compared: i) fixed dose, and per ii) BW, iii) lean BW (LBW), iv) body surface area (BSA), v) height (HT), vi) body mass index (BMI) and vii) fat-free mass (FFM)). For each dosing strategy the variability in maximum concentration Cmax, minimum concentration Cmin (= C8weeks) and area under the concentration-time curve (AUC), as well as percent of patients achieving the PK target, Cmin=3 μg/mL [4] were assessed.
Results: For all dosing strategies the variability of Cmin (CV ≈110%) was highest, compared to Cmax and AUC, and was of similar extent regardless of dosing strategy. The proportion of patients reaching the PK target (≈⅓ was approximately equal for all dosing strategies.
As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.