Large oligoclonal outbreak due to Klebsiella pneumoniae ST14 and ST26 producing the FOX-7 AmpC ß-lactamase in a neonatal intensive care unit.

A large outbreak caused by expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae (ESCRKP) was observed in a neonatal intensive care unit (NICU) in central Italy. The outbreak involved 127 neonates (99 colonizations and 28 infections, with seven cases of sepsis and two deaths) over a period of more than 2 years (February 2008 to April 2010). Characterization of the 92 nonredundant isolates that were available for further investigation revealed that all of them except one produced the FOX-7 AmpC-type ß-lactamase and belonged to either sequence type 14 (ST14) or ST26. All of the FOX-7-positive isolates were resistant to cefotaxime, ceftazidime, and piperacillin-tazobactam, while 76% were susceptible to cefepime, 98% to ertapenem, 99% to meropenem, and 100% to imipenem. The two carbapenem-nonsusceptible isolates had alterations in the genes encoding outer membrane proteins K35 and K36, which resulted in truncated and likely nonfunctional proteins. The outbreak was eventually controlled by the reinforcement of infection control measures based on a multitiered interventional approach. This is the first report of a large NICU outbreak caused by ESCRKP producing an AmpC-type enzyme. This study demonstrates that AmpC-type enzyme-producing strains can cause large outbreaks with significant morbidity and mortality effects (the mortality rate at 14 days was 28.5% for episodes of sepsis), and it underscores the role of laboratory-based surveillance and infection control measures to contain similar episodes.

Prestrain-induced contraction in one-dimensional random elastic chains.

Prestrained elastic networks arise in a number of biological and technological systems ranging from the cytoskeleton of cells to tensegrity structures. Motivated by this observation, we here consider a minimal model in one dimension to set the stage for understanding the response of such networks as a function of the prestrain. To this end we consider a chain [one-dimensional (1D) network] of elastic springs upon which a random, zero mean, finite variance prestrain is imposed. Numerical simulations and analytical predictions quantify the magnitude of the contraction as a function of the variance of the prestrain, and show that the chain always shrinks. To test these predictions, we vary the topology of the chain, consider more complex connectivity and show that our results are relatively robust to these changes.

Thermodynamic entropy and chaos in a discrete hydrodynamical system.

We show that the thermodynamic entropy density is proportional to the largest Lyapunov exponent (LLE) of a discrete hydrodynamical system, a deterministic two-dimensional lattice gas automaton. The definition of the LLE for cellular automata is based on the concept of Boolean derivatives and is formally equivalent to that of continuous dynamical systems. This relation is justified using a Markovian model. In an irreversible process with an initial density difference between both halves of the system, we find that Boltzmann's H function is linearly related to the expansion factor of the LLE although the latter is more sensitive to the presence of traveling waves.

Quantifying fairness to overcome selfishness: A behavioural model to describe the evolution and stabilization of inter-group bias using the Ultimatum Game.

The ability to form groups to overcome problems has been crucial for the evolution of human beings. To favour the formation of cooperating groups, one of the mechanisms developed is the inter-group bias, namely the tendency of individuals to favour members of their group and hinder the external ones. It is the cognitive equivalent of the "green beard effect" in evolutionary biology, introduced by Hamilton and popularized by Dawkins, for which a group can profit of the altruistic be-haviour of its members. Here, we use a behavioural model based on the Ultimatum Game, to shed ligh on how this behaviour cloud has been stabilized in the human population, estimating the magnitude of favouritism needed to overcome selfish individuals. Through both numerical simulations and analytic approaches, we study how a community of collectivist and individualist agents evolves. The key factor is the mechanism for the evolution of the population, i.e., the replacement of the poor-performing in-dividuals. In the case of replacement by the reproduction of existing individuals, we observe a smooth phase transition and no coexistence. If the replacement is random, the transition smooths, and coex-istence is possible. We developed analytical approaches for these two cases and performed numerical simulations. Although analytical calculations support the behaviour emerging from simulations, some differences ask for more refined treatments.

Humans best judge how much to cooperate when facing hard problems in large groups.

We report the results of a game-theoretic experiment with human players who solve problems of increasing complexity by cooperating in groups of increasing size. Our experimental environment is set up to make it complicated for players to use rational calculation for making the cooperative decisions. This environment is directly translated into a computer simulation, from which we extract the collaboration strategy that leads to the maximal attainable score. Based on this, we measure the error that players make when estimating the benefits of collaboration, and find that humans massively underestimate these benefits when facing easy problems or working alone or in small groups. In contrast, when confronting hard problems or collaborating in large groups, humans accurately judge the best level of collaboration and easily achieve the maximal score. Our findings are independent on groups' composition and players' personal traits. We interpret them as varying degrees of usefulness of social heuristics, which seems to depend on the size of the involved group and the complexity of the situation.

Plasma cortisol and ACTH levels in 416 VLBW preterm infants during the first month of life: distribution in the AGA/SGA population.

OBJECTIVE: The aim of this study is to establish the serum level distribution of cortisol and ACTH in VLBW preterm newborns and determine which neonates are ideal candidates for the stimulation test for adrenal insufficiency. METHODS: Plasma cortisol and ACTH levels were evaluated in 416 VLBW newborns on days 1, 7, and 30 of life. Gender, gestational age, weight, type of delivery, RDS prophylaxis, and perinatal morbidities were considered as potential variability factors. RESULTS: Cortisol and ACTH levels significantly decreased between 1, 7, and 30 days. Significantly higher cortisol levels were found at lower gestational ages and in infants born by vaginal delivery, whereas lower levels were observed in those born after maternal corticosteroid treatment. The distribution of cortisol and ACTH levels in healthy infants born by cesarian section is presented. CONCLUSION: Even if high or low levels were not frequently linked to illness, the presented distribution data may indicate that the newborns are ideal candidates for the stimulation test.

Modeling HIV quasispecies evolutionary dynamics.

BACKGROUND: During the HIV infection several quasispecies of the virus arise, which are able to use different coreceptors, in particular the CCR5 and CXCR4 coreceptors (R5 and X4 phenotypes, respectively). The switch in coreceptor usage has been correlated with a faster progression of the disease to the AIDS phase. As several pharmaceutical companies are starting large phase III trials for R5 and X4 drugs, models are needed to predict the co-evolutionary and competitive dynamics of virus strains. RESULTS: We present a model of HIV early infection which describes the dynamics of R5 quasispecies and a model of HIV late infection which describes the R5 to X4 switch. We report the following findings: after superinfection (multiple infections at different times) or coinfection (simultaneous infection by different strains), quasispecies dynamics has time scales of several months and becomes even slower at low number of CD4+ T cells. Phylogenetic inference of chemokine receptors suggests that viral mutational pathway may generate a large variety of R5 variants able to interact with chemokine receptors different from CXCR4. The decrease of CD4+ T cells, during AIDS late stage, can be described taking into account the X4-related Tumor Necrosis Factor dynamics. CONCLUSION: The results of this study bridge the gap between the within-patient and the inter-patients (i.e. world-wide) evolutionary processes during HIV infection and may represent a framework relevant for modeling vaccination and therapy.

Inter-observer reliability of two pain scales for newborns.

AIM: To assess inter-observer reliability of two of the most widely used pain scales for newborns. BACKGROUND: More than 30 scales exist to assess neonatal pain, but they are rarely used because they are too complicated or unreliable. METHOD: We scored pain level in two groups of babies during a heelprick. The first group of 20 premature babies (mean gestational age: 34.2+/-1.2 weeks) was studied using the PIPP scale, and the second group of 20 term babies (mean gestational age: 39.5+/-0.9 weeks) with the NIPS scale. We compared the pain scores assigned by the nurse who took the blood sample (nurse A) and those assigned by another who was present during heelprick (nurse B) with those assigned by a nurse who later watched the video clip of the procedure (nurse C). We chose the latter as "objective" score, because in this case the scorer could watch the recorded event several times, timing and scoring it thoroughly. FINDING: NIPS: 8/20 scores were different between nurse A and nurse C, but only in one case was this difference greater than 2 (Cohen's K=0.60). In the case of nurse B, there were 12/20 differences with respect to the score assigned by nurse C but only one baby was assigned a score that differed by more than 2 (Cohen's K=0.30). PIPP: 16/20 scores were different between nurse A and nurse C; in 9 cases this difference was more than 2 (Cohen's K=0.10). In the case of nurse B, differences with respect to the score assigned by nurse C occurred in 17/20 cases and for six babies the difference in score was more than 2 (Cohen's K=0.16). CONCLUSION: Our results indicate a higher inter-observer reliability of NIPS than PIPP, though NIPS did not have a very high inter-observer agreement score. Caregivers who use them to assess pain in real time at the cribside should be aware of the limits we have highlighted in this study.

Risk perception in epidemic modeling.

We investigate the effects of risk perception in a simple model of epidemic spreading. We assume that the perception of the risk of being infected depends on the fraction of neighbors that are ill. The effect of this factor is to decrease the infectivity, that therefore becomes a dynamical component of the model. We study the problem in the mean-field approximation and by numerical simulations for regular, random, and scale-free networks. We show that for homogeneous and random networks, there is always a value of perception that stops the epidemics. In the "worst-case" scenario of a scale-free network with diverging input connectivity, a linear perception cannot stop the epidemics; however, we show that a nonlinear increase of the perception risk may lead to the extinction of the disease. This transition is discontinuous, and is not predicted by the mean-field analysis.

Dynamical affinity in opinion dynamics modeling.

We propose here a model to simulate the process of opinion formation, which accounts for the mutual affinity between interacting agents. Opinion and affinity evolve self-consistently, manifesting a highly nontrivial interplay. A continuous transition is found between single and multiple opinion states. Fractal dimension and signature of critical behavior are also reported. A rich phenomenology is presented and discussed with reference to corresponding psychological implications.

Intimate Partner Violence: A Stochastic Model.

Intimate partner violence (IPV) has been a well-studied problem in the past psychological literature, especially through its classical methodology such as qualitative, quantitative and mixed methods. This article introduces two basic stochastic models as an alternative approach to simulate the short and long-term dynamics of a couple at risk of IPV. In both models, the members of the couple may assume a finite number of states, updating them in a probabilistic way at discrete time steps. After defining the transition probabilities, we first analyze the evolution of the couple in isolation and then we consider the case in which the individuals modify their behavior depending on the perceived violence from other couples in their environment or based on the perceived informal social support. While high perceived violence in other couples may converge toward the own presence of IPV by means a gender-specific transmission, the gender differences fade-out in the case of received informal social support. Despite the simplicity of the two stochastic models, they generate results which compare well with past experimental studies about IPV and they give important practical implications for prevention intervention in this field.

Control of multidimensional systems on complex network.

Multidimensional systems coupled via complex networks are widespread in nature and thus frequently invoked for a large plethora of interesting applications. From ecology to physics, individual entities in mutual interactions are grouped in families, homogeneous in kind. These latter interact selectively, through a sequence of self-consistently regulated steps, whose deeply rooted architecture is stored in the assigned matrix of connections. The asymptotic equilibrium eventually attained by the system, and its associated stability, can be assessed by employing standard nonlinear dynamics tools. For many practical applications, it is however important to externally drive the system towards a desired equilibrium, which is resilient, hence stable, to external perturbations. To this end we here consider a system made up of N interacting populations which evolve according to general rate equations, bearing attributes of universality. One species is added to the pool of interacting families and used as a dynamical controller to induce novel stable equilibria. Use can be made of the root locus method to shape the needed control, in terms of intrinsic reactivity and adopted protocol of injection. The proposed method is tested on both synthetic and real data, thus enabling to demonstrate its robustness and versatility.

High maternal and fetal plasma urocortin levels in pregnancies complicated by hypertension.

OBJECTIVE: We evaluated maternal and fetal plasma levels and placental mRNA expression of urocortin, a placental vasoactive neuropeptide, in singleton pregnancies (n = 70) complicated by hypertensive disorders classified as gestational hypertension (n = 36), pre-eclampsia (n = 19), and pre-eclampsia complicated by intrauterine growth restriction (PE/IUGR, n = 15), and in 70 healthy normotensive singleton pregnancies. METHODS: Plasma levels were assayed by radioimmunoassay, fetal biometry by ultrasound scans, utero-placental and fetal perfusion by Doppler velocimetry, and placental urocortin mRNA expression by quantitative real time reverse transcriptase-polymerase chain reaction. The main outcome measures were the correlation of urocortin concentrations with patterns of the utero-placental and fetal circulation, and the early prediction of a poor neonatal outcome such as the occurrence of perinatal death and intraventricular hemorrhage. RESULTS: Maternal and fetal urocortin levels were significantly (both P < 0.001) higher in gestational hypertension, pre-eclampsia and PE/IUGR women than in controls, and correlated with Doppler velocimetry patterns. Fetal concentrations were significantly (P < 0.0001) higher than and significantly (P < 0.0001) correlated to maternal levels. Placental mRNA expression did not change. Ten out of 140 newborns had a poor neonatal outcome, with an overall prevalence of 7.14% (pretest probability). Using the receiver operator characteristics curve analysis cut-off values, the probability of a poor neonatal outcome was 66.7% when urocortin was used, and was 0% if levels were unaltered. CONCLUSIONS: Maternal and fetal urocortin levels are increased in hypertensive disorders of pregnancy. Since urocortin has vasoactive properties, the evidence of increased urocortin levels in hypertensive disorders may represent an adaptive fetal response.

Synchronization universality classes and stability of smooth coupled map lattices.

We study two problems related to spatially extended systems: the dynamical stability and the universality classes of the replica synchronization transition. We use a simple model of one-dimensional coupled map lattices and show that chaotic behavior implies that the synchronization transition belongs to the multiplicative noise universality class, while stable chaos implies that the synchronization transition belongs to the directed percolation universality class.

Stochastic bifurcations in the nonlinear parallel Ising model.

We investigate the phase transitions of a nonlinear, parallel version of the Ising model, characterized by an antiferromagnetic linear coupling and ferromagnetic nonlinear one. This model arises in problems of opinion formation. The mean-field approximation shows chaotic oscillations, by changing the couplings or the connectivity. The spatial model shows bifurcations in the average magnetization, similar to that seen in the mean-field approximation, induced by the change of the topology, after rewiring short-range to long-range connection, as predicted by the small-world effect. These coherent periodic and chaotic oscillations of the magnetization reflect a certain degree of synchronization of the spins, induced by long-range couplings. Similar bifurcations may be induced in the randomly connected model by changing the couplings or the connectivity and also the dilution (degree of asynchronism) of the updating. We also examined the effects of inhomogeneity, mixing ferromagnetic and antiferromagnetic coupling, which induces an unexpected bifurcation diagram with a "bubbling" behavior, as also happens for dilution.

The second will be first: competition on directed networks.

Multiple sinks competition is investigated for a walker diffusing on directed complex networks. The asymmetry of the imposed spatial support makes the system non transitive. As a consequence, it is always possible to identify a suitable location for the second absorbing sink that screens at most the flux of agents directed against the first trap, whose position has been preliminarily assigned. The degree of mutual competition between pairs of nodes is analytically quantified through apt indicators that build on the topological characteristics of the hosting graph. Moreover, the positioning of the second trap can be chosen so as to minimize, at the same time, the probability of being in turn shaded by a thirdly added trap. Supervised placing of absorbing traps on a asymmetric disordered and complex graph is hence possible, as follows a robust optimization protocol. This latter is here discussed and successfully tested against synthetic data.

Histologic chorioamnionitis and severity of illness in very low birth weight newborns.

OBJECTIVE: Estimating the risk of in-hospital mortality in the neonatal intensive care unit provides important information for health care providers, and several neonatal illness severity scores have been developed. Histologic chorioamnionitis (HCA) is a known cause of neonatal morbidity and mortality. To date, the relationship between HCA and neonatal illness severity scores has not been rigorously tested. In this study, the relationships among HCA, initial illness severity, and neonatal outcomes were analyzed in very low birth weight (VLBW) newborns admitted to the neonatal intensive care unit. DESIGN: Prospective. SETTING: Neonatal intensive care unit. PATIENTS: A total of 116 VLBW inborn infants (gestational age, 28.1 +/- 2.82 wks; birth weight, 1009 +/- 312 g) were categorized as HCA-positive (n = 67) and HCA-negative (n = 49). INTERVENTIONS: Placental histology was performed to identify HCA. Illness severity evaluation included several different neonatal illness severity scores-Clinical Risk Index for Babies (CRIB), CRIB-II, Score for Neonatal Acute Physiology-II (SNAP-II), and Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II)-as well as the recording of severe morbidity and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: HCA-positive VLBW newborns showed significantly lower gestational age (p < .0001) and birth weight (p = .0010), together with higher CRIB, CRIB-II, SNAP-II, and SNAPPE-II scores at admission to the NICU (p 5 (odds ratio [OR], 21.37; 95% confidence interval [CI], 6.24-73.21); CRIB-II > 10 (OR, 56.17; 95% CI, 6.75-467.2); SNAP-II > 22 (OR, 43.05; 95% CI, 11.9-155.7), and SNAPPE-II > 42 (OR, 48.95; 95% CI, 10.18-235.4) (all p values <.0001). CONCLUSIONS: Our findings indicate that HCA is a major predictor of morbidity and mortality in VLBW newborns.

Phase transitions of extended-range probabilistic cellular automata with two absorbing states.

We study phase transitions in a long-range one-dimensional cellular automaton with two symmetric absorbing states. It includes and extends several other models, like the Ising and Domany-Kinzel ones. It is characterized by competing ferromagnetic linear and antiferromagnetic nonlinear couplings. Despite its simplicity, this model exhibits an extremely rich phase diagram. We present numerical results and mean-field approximations.

Bifurcations in models of a society of reasonable contrarians and conformists.

We study models of a society composed of a mixture of conformist and reasonable contrarian agents that at any instant hold one of two opinions. Conformists tend to agree with the average opinion of their neighbors and reasonable contrarians tend to disagree, but revert to a conformist behavior in the presence of an overwhelming majority, in line with psychological experiments. The model is studied in the mean-field approximation and on small-world and scale-free networks. In the mean-field approximation, a large fraction of conformists triggers a polarization of the opinions, a pitchfork bifurcation, while a majority of reasonable contrarians leads to coherent oscillations, with an alternation of period-doubling and pitchfork bifurcations up to chaos. Similar scenarios are obtained by changing the fraction of long-range rewiring and the parameter of scale-free networks related to the average connectivity.

Pathogenic mechanism, prophylaxis, and therapy of symptomatic acidosis induced by acetazolamide.

BACKGROUND: Acetazolamide, a noncompetitive carbonic anhydrase inhibitor, can produce symptomatic acidosis and bone marrow suppression by a mechanism that is still unknown. This presentation occurs in the elderly, patients with renal or liver failure, people with diabetes, and newborns. The objective of this study was to understand the pathogenic mechanism of these adverse effects and to propose a possible prophylaxis and therapy. METHODS: Four human clinical cases were studied, and one animal experiment was performed. Four preterm newborns with posthemorrhagic ventricular dilation developed severe metabolic acidosis after treatment with acetazolamide. The acidosis suddenly disappeared after a packed red blood cell transfusion. Metabolic studies were performed in one patient and in newborn guinea pigs treated with 200 mg/kg acetazolamide. RESULTS: Acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low beta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. The acquired enzymatic injury resulting from the inhibition of mitochondrial carbonic anhydrase V that provides bicarbonate to pyruvate carboxylase can produce tricarboxylic acid cycle damage. We demonstrate that the dramatic disappearance of metabolic acidosis and normalizing metabolism after blood transfusion were due to the citrate contained in the packed red blood cell bag. This hypothesis was confirmed by animal experimentation. We argue that the metabolic disorder and bone marrow suppression may be related. CONCLUSION: We demonstrate how acetazolamide can lead to symptomatic metabolic acidosis and probably to bone marrow suppression. We suggest citrate as a possible prophylaxis and treatment for these adverse reactions.