Heterogeneous length of stay of hosts’ movements and spatial epidemic spread

Infectious diseases outbreaks are often characterized by a spatial component induced by hosts’ distribution, mobility, and interactions. Spatial models that incorporate hosts’ movements are being used to describe these processes, to investigate the conditions for propagation, and to predict the spatial spread. Several assumptions are being considered to model hosts’ movements, ranging from permanent movements to daily commuting, where the time spent at destination is either infinite or assumes a homogeneous fixed value, respectively. Prompted by empirical evidence, here we introduce a general metapopulation approach to model the disease dynamics in a spatially structured population where the mobility process is characterized by a heterogeneous length of stay. We show that large fluctuations of the length of stay, as observed in reality, can have a significant impact on the threshold conditions for the global epidemic invasion, thus altering model predictions based on simple assumptions, and displaying important public health implications

Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data

Genome Dynamics of Short Oligonucleotides: The Example of Bacterial DNA Uptake Enhancing Sequences

Among the many bacteria naturally competent for transformation by DNA uptake—a phenomenon with significant clinical and financial implications— Pasteurellaceae and Neisseriaceae species preferentially take up DNA containing specific short sequences. The genomic overrepresentation of these DNA uptake enhancing sequences (DUES) causes preferential uptake of conspecific DNA, but the function(s) behind this overrepresentation and its evolution are still a matter for discovery. Here I analyze DUES genome dynamics and evolution and test the validity of the results to other selectively constrained oligonucleotides. I use statistical methods and computer simulations to examine DUESs accumulation in Haemophilus influenzae and Neisseria gonorrhoeae genomes. I analyze DUESs sequence and nucleotide frequencies, as well as those of all their mismatched forms, and prove the dependence of DUESs genomic overrepresentation on their preferential uptake by quantifying and correlating both characteristics. I then argue that mutation, uptake bias, and weak selection against DUESs in less constrained parts of the genome combined are sufficient enough to cause DUESs accumulation in susceptible parts of the genome with no need for other DUES function. The distribution of overrepresentation values across sequences with different mismatch loads compared to the DUES suggests a gradual yet not linear molecular drive of DNA sequences depending on their similarity to the DUES. Other genomically overrepresented sequences, both pro- and eukaryotic, show similar distribution of frequencies suggesting that the molecular drive reported above applies to other frequent oligonucleotides. Rare oligonucleotides, however, seem to be gradually drawn to genomic underrepresentation, thus, suggesting a molecular drag. To my knowledge this work provides the first clear evidence of the gradual evolution of selectively constrained oligonucleotides, including repeated, palindromic and protein/transcription factor-binding DNAs

No se fían

It is a standard practice to test for the signature of homologous recombination in studies examining the genetic diversity of bacterial populations. Although it has emerged that homologous recombination rates can vary widely between species, comparing the results from different studies is made difficult by the diversity of estimation methods used. Here, Multi Locus Sequence Typing (MLST) datasets from a wide variety of bacteria and archaea are analyzed using the ClonalFrame method. This enables a direct comparison between species and allows for a first exploration of the question whether phylogeny or ecology is the primary determinant of homologous recombination rate

Maternofetal consequences of <it>Coxiella burnetii</it> infection in pregnancy: a case series of two outbreaks

<p>Abstract</p> <p>Background</p> <p>A high complication rate of Q fever in pregnancy is described on the basis of a limited number of cases. All pregnant women with proven Q fever regardless of clinical symptoms should therefore receive long-term cotrimoxazole therapy. But cotrimoxazole as a folic acid antagonist may cause harm to the fetus. We therefore investigated the Q fever outbreaks, Soest in 2003 and Jena in 2005, to determine the maternofetal consequences of <it>Coxiella burnetii</it> infection contracted during pregnancy.</p> <p>Methods</p> <p>Different outbreak investigation strategies were employed at the two sides. Antibody screening was performed with an indirect immunofluorescence test. Medical history and clinical data were obtained and serological follow up performed at delivery. Available placental tissue, amniotic fluid and colostrum/milk were further investigated by polymerase chain reaction and by culture.</p> <p>Results</p> <p>11 pregnant women from Soest (screening rate: 49%) and 82 pregnant women from Jena (screening rate: 27%) participated in the outbreak investigation. 11 pregnant women with an acute <it>C. burnetii</it> infection were diagnosed. Three women had symptomatic disease.</p> <p>Three women, who were infected in the first trimester, were put on long-term therapy. The remaining women received cotrimoxazole to a lesser extent (n=3), were treated with macrolides for three weeks (n=1) or after delivery (n=1), were given no treatment at all (n=2) or received antibiotics ineffective for Q fever (n=1). One woman and her foetus died of an underlying disease not related to Q fever. One woman delivered prematurely (35^th week) and one child was born with syndactyly. We found no obvious association between <it>C. burnetii</it> infection and negative pregnancy outcome.</p> <p>Conclusions</p> <p>Our data do not support the general recommendation of long-term cotrimoxazole treatment for Q fever infection in pregnancy. Pregnant women with symptomatic <it>C. burnetii</it> infections and with chronic Q fever should be treated. The risk-benefit ratio of treatment in these patients, however, remains uncertain. If cotrimoxazole is administered, folinic acid has to be added.</p

The relationship between employees' objective internal and external pay standing and their job performance: A within-person analysis

Purpose: Researchers have paid little attention to the relationship between employees’ objective internal and external pay standing and their job performance. Moreover, few studies have considered that employees’ objective pay standing is dynamic; that is, it changes over time. In this study, we analyze the relationship between changes in employees’ objective internal and external pay standing and their job performance. Design/Methodology/Approach: We test the hypotheses using data for players in the National Basketball Association over a period of 12 seasons (n = 4830). Findings. Decreases in employees’ objective internal and external pay standing are negatively related to their task performance. Furthermore, decreases in employees’ objective internal pay standing, but not in their external pay standing, are negatively related to their contextual performance. Implications. Analyzing the relationship between changes in employees’ objective internal and external pay standing and their job performance adds to our understanding of the individual-level consequences of pay dispersion. Originality/Value. This is one of the first studies to analyze the relationship between employees’ objective internal and external pay standing and their job performance. Moreover, this is one of the first studies that considers that employees’ objective internal and external pay standing changes, for example, because the external and internal labor markets change. The study contributes to research on employee compensation and salary, and to research on pay disparities