Therapeutic drug monitoring of antimicrobial drugs in neonates. An opinion paper

Neonatal infections are associated with high morbidity and mortality rates. Optimal treatment of these infections requires knowledge of neonatal pharmacology and integration of neonatal developmental pharmacokinetics (PKs) of antimicrobial drugs in the design of dosing regimens for use with different gestational and postnatal ages. Population PK and pharmacodynamic models are used to personalize the use of these drugs in these fragile patients. The final step to further minimize variability in an individual patient is therapeutic drug monitoring (TDM), where the same population PK/pharmacodynamic models are used in concert with optimally drawn blood samples to further fine-tune therapy. The purpose of this article is to describe the present status and future role of model-based precision dosing and TDM of antimicrobial drugs in neonates. METHODS: PubMed was searched for clinical trials or clinical studies of TDM in neonates. RESULTS: A total of 447 articles were retrieved, of which 19 were concerned with antimicrobial drugs. Two articles (one aminoglycoside and one vancomycin) addressed the effects of TDM in neonates. We found that, in addition to aminoglycosides and vancomycin, TDM also plays a role in beta-lactam antibiotics and antifungal drugs. CONCLUSIONS: There is a growing awareness that, in addition to aminoglycosides and vancomycin, the use of beta-lactam antibiotics, such as amoxicillin and meropenem, and other classes of antimicrobial drugs, such as antifungal drugs, may benefit from TDM. However, the added value must be shown. New analytical techniques and software development may greatly support these novel developments

Brownian modulated optical nanoprobes

Brownian modulated optical nanoprobes (Brownian MOONs) are fluorescent micro- and nanoparticles that resemble moons: one hemisphere emits a bright fluorescent signal, while an opaque metal darkens the other hemisphere. Brownian motion causes the particles to tumble and blink erratically as they rotate literally through the phases of the moon. The fluctuating probe signals are separated from optical and electronic backgrounds using principal components analysis or images analysis. Brownian MOONs enable microrheological measurements on size scales and timescales that are difficult to study with other methods. Local chemical concentrations can be measured simultaneously, using spectral characteristics of indicator dyes embedded within the MOONs. © 2004 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70496/2/APPLAB-84-1-154-1.pd

Boosting the Figure Of Merit of LSPR-based refractive index sensing by phase-sensitive measurements

Localized surface plasmon resonances possess very interesting properties for a wide variety of sensing applications. In many of the existing applications only the intensity of the reflected or transmitted signals is taken into account, while the phase information is ignored. At the center frequency of a (localized) surface plasmon resonance, the electron cloud makes the transition between in- and out-of-phase oscillation with respect to the incident wave. Here we show that this information can experimentally be extracted by performing phase-sensitive measurements, which result in linewidths that are almost one order of magnitude smaller than those for intensity based measurements. As this phase transition is an intrinsic property of a plasmon resonance, this opens up many possibilities for boosting the figure of merit (FOM) of refractive index sensing by taking into account the phase of the plasmon resonance. We experimentally investigated this for two model systems: randomly distributed gold nanodisks and gold nanorings on top of a continuous gold layer and a dielectric spacer and observed FOM values up to 8.3 and 16.5 for the respective nanoparticles

Spatial Modulation Microscopy for Real-Time Imaging of Plasmonic Nanoparticles and Cells

Spatial modulation microscopy is a technique originally developed for quantitative spectroscopy of individual nano-objects. Here, a parallel implementation of the spatial modulation microscopy technique is demonstrated based on a line detector capable of demodulation at kHz frequencies. The capabilities of the imaging system are shown using an array of plasmonic nanoantennas and dendritic cells incubated with gold nanoparticles.Comment: 3 pages, 4 figure

Interaction of matter-wave gap solitons in optical lattices

We study mobility and interaction of gap solitons in a Bose-Einstein condensate (BEC) confined by an optical lattice potential. Such localized wavepackets can exist only in the gaps of the matter-wave band-gap spectrum and their interaction properties are shown to serve as a measure of discreteness imposed onto a BEC by the lattice potential. We show that inelastic collisions of two weakly localized near-the-band-edge gap solitons provide simple and effective means for generating strongly localized in-gap solitons through soliton fusion.Comment: 12 pages, 7 figure

Lp Fourier multipliers on compact Lie groups

In this paper we prove Lp multiplier theorems for invariant and non-invariant operators on compact Lie groups in the spirit of the well-known Hormander-Mikhlin theorem on Rn and its variants on tori Tn. We also give applications to a-priori estimates for non-hypoelliptic operators. Already in the case of tori we get an interesting refinement of the classical multiplier theorem.Comment: 22 pages; minor correction

Designing verbal autopsy studies

<p>Abstract</p> <p>Background</p> <p>Verbal autopsy analyses are widely used for estimating cause-specific mortality rates (CSMR) in the vast majority of the world without high-quality medical death registration. Verbal autopsies -- survey interviews with the caretakers of imminent decedents -- stand in for medical examinations or physical autopsies, which are infeasible or culturally prohibited.</p> <p>Methods and Findings</p> <p>We introduce methods, simulations, and interpretations that can improve the design of automated, data-derived estimates of CSMRs, building on a new approach by King and Lu (2008). Our results generate advice for choosing symptom questions and sample sizes that is easier to satisfy than existing practices. For example, most prior effort has been devoted to searching for symptoms with high sensitivity and specificity, which has rarely if ever succeeded with multiple causes of death. In contrast, our approach makes this search irrelevant because it can produce unbiased estimates even with symptoms that have very low sensitivity and specificity. In addition, the new method is optimized for survey questions caretakers can easily answer rather than questions physicians would ask themselves. We also offer an automated method of weeding out biased symptom questions and advice on how to choose the number of causes of death, symptom questions to ask, and observations to collect, among others.</p> <p>Conclusions</p> <p>With the advice offered here, researchers should be able to design verbal autopsy surveys and conduct analyses with greatly reduced statistical biases and research costs.</p

Spherical Spectral Synthesis and Two-Radius Theorems on Damek-Ricci Spaces

We prove that spherical spectral analysis and synthesis hold in Damek-Ricci spaces and derive two-radius theorems

Refractive-index sensing with ultra-thin plasmonic nanotubes

We study the refractive-index sensing properties of plasmonic nanotubes with a dielectric core and ultra-thin metal shell. The few-nm thin metal shell is described by both the usual Drude model and the nonlocal hydrodynamic model to investigate the effects of nonlocality. We derive an analytical expression for the extinction cross section and show how sensing of the refractive index of the surrounding medium and the figure-of-merit are affected by the shape and size of the nanotubes. Comparison with other localized surface plasmon resonance sensors reveals that the nanotube exhibits superior sensitivity and comparable figure-of-merit