Influence of Previous Exposure to Antibiotic Therapy on the Susceptibility Pattern of Pseudomonas aeruginosa Bacteremic Isolates

Many patients who present with Pseudomonas aeruginosa bacteremia have been previously exposed to antibiotics. To assess whether resistance of bacteremic strains to antipseudomonal antibiotics (piperacillin, ceftazidime, imipenem, ciprofloxacin, or aminoglycosides) is associated with previous exposure to these drugs, a case-control study including 267 cases of P. aeruginosa bacteremia was conducted. Twenty-five percent of the episodes had been preceded by the exposure to an antipseudomonal antibiotic. Eighty-one strains were resistant to at least 1 antibiotic; 186 were susceptible to all drugs. Via univariate analysis, the risks of resistance to ceftazidime and imipenem were found to be significantly associated with previous receipt of these agents. Using multivariate analysis, exposure to any antipseudomonal antibiotic as a monotherapy was found to be associated with an increased risk of subsequent resistance to itself (odds ratio, 2.5; P = .006). Therefore, clinicians should avoid readministering previously prescribed antibiotics when initiating empiric therapies for possible P. aeruginosa bacteremia, especially when they have been given as monotherapie

An uncertain future, deep uncertainty, scenarios, robustness and adaptation: How do they fit together?

A highly uncertain future due to changes in climate, technology and socio-economics has led to the realisation that identification of “best-guess” future conditions might no longer be appropriate. Instead, multiple plausible futures need to be considered, which requires (i) uncertainties to be described with the aid of scenarios that represent coherent future pathways based on different sets of assumptions, (ii) system performance to be represented by metrics that measure insensitivity (i.e. robustness) to changes in future conditions, and (iii) adaptive strategies to be considered alongside their more commonly used static counterparts. However, while these factors have been considered in isolation previously, there has been a lack of discussion of the way they are connected. In order to address this shortcoming, this paper presents a multidisciplinary perspective on how the above factors fit together to facilitate the devel- opment of strategies that are best suited to dealing with a deeply uncertain future

Alertness, movement, and affective behaviour of people with profound intellectual and multiple disabilities (PIMD) on introduction of a playful interactive product:Can we get your attention?

Background: New technology may stimulate active leisure activities for people with profound intellectual and multiple disabilities (PIMD). We conducted a study of an interactive ball that responded to gross body movement, focus of attention, and vocalisations of users with PIMD. The aim was to increase alertness and body movement and elicit more expressions of positive, or fewer of negative affect.Method: Nine participants with PIMD played during 8–10 sessions. The movement was analysed automatically. Alertness and affective behaviour were coded manually. We analysed the last 5 sessions for each participant and compared 15 min of interaction with 15 min of rest.Results: Clearly positive effects were seen for three participants. Effects were seen in the unexpected direction for four participants. No strong effects were found for the remaining three participants.Conclusions: Interactive technologies may provide suitable activities for people with PIMD but individual differences play an important role

Amplitude noise and RF response analysis of 1 GHz mode-locked pulses from an InP-based laser chip at 1550 nm

In this work, we investigate a 1 GHz InP-based hybrid mode-locked laser chip and find an amplitude noise of 0.036 percent. An RF response simulation of its custom-designed mounting PCB is performed providing power transmission between 86 and 92 percent

RF Analysis of a Sub-GHz InP-Based 1550 nm Monolithic Mode-Locked Laser Chip

We report a monolithic sub-GHz repetition rate mode-locked laser with record low pulse-to-pulse RMS timing jitter of 3.65 ps in the passive mode locking regime. We analyse the optical pulse generation in passive and hybrid mode-locking operating regimes, finding narrower RF tone linewidth in the passive regime, attributed to the improved contact structure of the gain sections. The noise performance is also characterized in passive and hybrid regimes, showing RMS integrated timing jitter of approximately 600 fs. For hybrid modelocking, the repetition rate can be varied over a large range from 880 to 990 MHz. We observe broad pulse widths of few hundred picoseconds attributed to the (long folded) waveguide architecture and on-chip multimode interference mirrors. This device subjects a stand-alone, ultra-compact, mode-locking based clock source to realize frequency synthesizers operating over a frequency range from sub-GHz up to approximately 15 GHz

Quorum Sensing Inhibition Selects for Virulence and Cooperation in Pseudomonas aeruginosa

With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research. Possible innovative strategies include the inhibition of bacterial virulence. However, consideration must be given to the evolutionary and environmental consequences of such new interventions. Virulence and cooperative social behaviour of the bacterium Pseudomonas aeruginosa rely on the quorum-sensing (QS) controlled production of extracellular products (public goods). Hence QS is an attractive target for anti-virulence interventions. During colonization, non-cooperating (and hence less virulent) P. aeruginosa QS-mutants, benefiting from public goods provided by wild type isolates, naturally increase in frequency providing a relative protection from invasive infection. We hypothesized that inhibition of QS-mediated gene expression removes this growth advantage and selection of less virulent QS-mutants, and maintains the predominance of more virulent QS-wild type bacteria. We addressed this possibility in a placebo-controlled trial investigating the anti-QS properties of azithromycin, a macrolide antibiotic devoid of bactericidal activity on P. aeruginosa, but interfering with QS, in intubated patients colonized by P. aeruginosa. In the absence of azithromycin, non-cooperating (and hence less virulent) lasR (QS)-mutants increased in frequency over time. Azithromycin significantly reduced QS-gene expression measured directly in tracheal aspirates. Concomitantly the advantage of lasR-mutants was lost and virulent wild-type isolates predominated during azithromycin treatment. We confirmed these results in vitro with fitness and invasion experiments. Azithromycin reduced growth rate of the wild-type, but not of the lasR-mutant. Furthermore, the lasR-mutant efficiently invaded wild-type populations in the absence, but not in the presence of azithromycin. These in vivo and in vitro results demonstrate that anti-virulence interventions based on QS-blockade diminish natural selection towards reduced virulence and therefore may increase the prevalence of more virulent genotypes in the Hospital environment. More generally, the impact of intervention on the evolution of virulence of pathogenic bacteria should be assessed

Information heat engine: converting information to energy by feedback control

In 1929, Leo Szilard invented a feedback protocol in which a hypothetical intelligence called Maxwell's demon pumps heat from an isothermal environment and transduces it to work. After an intense controversy that lasted over eighty years; it was finally clarified that the demon's role does not contradict the second law of thermodynamics, implying that we can convert information to free energy in principle. Nevertheless, experimental demonstration of this information-to-energy conversion has been elusive. Here, we demonstrate that a nonequilibrium feedback manipulation of a Brownian particle based on information about its location achieves a Szilard-type information-energy conversion. Under real-time feedback control, the particle climbs up a spiral-stairs-like potential exerted by an electric field and obtains free energy larger than the amount of work performed on it. This enables us to verify the generalized Jarzynski equality, or a new fundamental principle of "information-heat engine" which converts information to energy by feedback control.Comment: manuscript including 7 pages and 4 figures and supplementary material including 6 pages and 8 figure