Measuring distance through dense weighted networks: The case of hospital-associated pathogens

Hospital networks, formed by patients visiting multiple hospitals, affect the spread of hospital-associated infections, resulting in differences in risks for hospitals depending on their network position. These networks are increasingly used to inform strategies to prevent and control the spread of hospital-associated pathogens. However, many studies only consider patients that are received directly from the initial hospital, without considering the effect of indirect trajectories through the network. We determine the optimal way to measure the distance between hospitals within the network, by reconstructing the English hospital network based on shared patients in 2014–2015, and simulating the spread of a hospital-associated pathogen between hospitals, taking into consideration that each intermediate hospital conveys a delay in the further spread of the pathogen. While the risk of transferring a hospital-associated pathogen between directly neighbouring hospitals is a direct reflection of the number of shared patients, the distance between two hospitals far-away in the network is determined largely by the number of intermediate hospitals in the network. Because the network is dense, most long distance transmission chains in fact involve only few intermediate steps, spreading along the many weak links. The dense connectivity of hospital networks, together with a strong regional structure, causes hospital-associated pathogens to spread from the initial outbreak in a two-step process: first, the directly surrounding hospitals are affected through the strong connections, second all other hospitals receive introductions through the multitude of weaker links. Although the strong connections matter for local spread, weak links in the network can offer ideal routes for hospital-associated pathogens to travel further faster. This hold important implications for infection prevention and control efforts: if a local outbreak is not controlled in time, colonised patients will appear in other regions, irrespective of the distance to the initial outbreak, making import screening ever more difficult

Research and knowledge transfer priorities in developmental coordination disorder: Results from consultations with multiple stakeholders

Abstract : Background: Priority‐setting is a way to focus research and knowledge translation (KT) efforts for community‐based research partnerships (CBRP). Objective: To identify the developmental coordination disorder (DCD) research and KT priorities of stakeholders in Quebec, Canada, and their perceptions regarding the implementation of a CBRP. Design: An advisory committee oversaw the research process including an online survey and four community forums. Setting and participants: The survey was posted online and four community forums were organized. Participants included parents of children with DCD, adults with DCD, health professionals and school staff. Main variables: Stakeholder generated research and KT priorities, and optimal CBPR conditions. Outcome measures: Participants selected their top five priorities based on a predefined list of 16 research and 12 KT priorities determined in collaboration with the advisory committee. They also rated the importance of various CBRP conditions. Preliminary survey results were discussed during the forums. Results: Survey participants (n = 395) identified interwoven research and KT priorities where access to services was considered to be essential: supporting children at school; improving DCD identification and diagnosis; preventing secondary consequences; improving the organization of services and implementing effective services. Forum participants (n = 52) confirmed the relevance of these priorities and supported the establishment of a CBRP inclusive of all stakeholders to improve DCD services, research and KT. Discussion and conclusions: A general consensus emerged among all groups, but adults with DCD were more concerned with employment than were the other stakeholder groups. These findings are presently being used to shape an ongoing, online CBRP

Timing of positive blood samples does not differentiate pathogens causing healthcare-associated from community-acquired bloodstream infections in children in England: a linked retrospective cohort study.

Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paediatric (3 months to 5 years) bacterial blood isolates were linked to in-patient hospital data and plotted in relation to hospital admission. The majority (88·6%) of linked pathogens were isolated <2 days after hospital admission, including pathogens widely regarded as hospital acquired: Enterococcus spp. (67·2%) and Klebsiella spp. (88·9%). Neisseria meningitidis, Streptococcus pneumoniae, group A streptococcus and Salmonella spp. were unlikely to cause hospital-acquired BSI. Pathogens commonly associated with hospital-acquired BSI are being isolated <2 days after hospital admission alongside pathogens commonly associated with community-acquired BSI. We confirm that timing of blood samples alone does not differentiate between bacterial pathogens. Additional factors including clinical patient characteristics and healthcare contact should be considered to help predict the causative pathogen and guide empirical antibiotic therapy

Mapping quantitative trait loci in line cross with repeat records

<p>Abstract</p> <p>Background</p> <p>Phenotypes with repeat records from one individual or multiple individuals were often encountered in practices of mapping QTL in linecross. The current genetic mapping method for a trait with repeat records is adopted by simply replacing the phenotype by the average value of the repeat records. This simple treatment has not sufficiently utilized the information from the replication and ignored the impacts of the permanent environmental effects on the accuracy of the estimated QTL.</p> <p>Results</p> <p>We propose to map QTL by using the repeatability model to directly analyze the repeat records rather than simply analyze the mean phenotype, improving the efficiency of QTL detecting because of adequately utilizing the information from data and allowing for the permanent environmental effects. A maximum likelihood method implemented via the expectation-maximization (EM) algorithm is applied to perform the parameter estimation of the repeatability model. The superiority of the mapping method based on the repeatability model over simple analysis using the mean phenotype was demonstrated by a series of simulations.</p> <p>Conclusion</p> <p>Our results suggest that the proposed method can serve as a powerful alternative to existing methods. By mean of the repeatability model, utilizing the repeat records on individual may improve the efficiency of QTL detecting in line cross.</p

Why should we care about quantum discord?

Entanglement is a central feature of quantum theory. Mathematical properties and physical applications of pure state entanglement make it a template to study quantum correlations. However, an extension of entanglement measures to mixed states in terms of separability does not always correspond to all the operational aspects. Quantum discord measures allow an alternative way to extend the idea of quantum correlations to mixed states. In many cases these extensions are motivated by physical scenarios and quantum information protocols. In this chapter we discuss several settings involving correlated quantum systems, ranging from distributed gates to detectors testing quantum fields. In each setting we show how entanglement fails to capture the relevant features of the correlated system, and discuss the role of discord as a possible alternative.Comment: Written for "Lectures on general quantum correlations and their applications

Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

BACKGROUND: Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique. METHODOLOGY: Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP). PRINCIPAL FINDINGS: All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9-540 months). CONCLUSIONS: RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels)

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

High Resolution Spectral Domain Optical Coherence Tomography (SD-OCT) in Multiple Sclerosis: The First Follow Up Study over Two Years

“Non-invasive, faster and less expensive than MRI” and “the eye is a window to the brain” are recent slogans promoting optical coherence tomography (OCT) as a new surrogate marker in multiple sclerosis (MS). Indeed, OCT allows for the first time a non-invasive visualization of axons of the central nervous system (CNS). Reduction of retina nerve fibre layer (RNFL) thickness was suggested to correlate with disease activity and duration. However, several issues are unclear: Do a few million axons, which build up both optic nerves, really resemble billions of CNS neurons? Does global CNS damage really result in global RNFL reduction? And if so, does global RNFL reduction really exist in all MS patients, and follow a slowly but steadily ongoing pattern? How can these (hypothesized) subtle global RNFL changes be reliably measured and separated from the rather gross RNFL changes caused by optic neuritis? Before generally being accepted, this interpretation needs further critical and objective validation.We prospectively studied 37 MS patients with relapsing remitting (n = 27) and secondary progressive (n = 10) course on two occasions with a median interval of 22.4±0.5 months [range 19–27]. We used the high resolution spectral domain (SD-)OCT with the Spectralis 3.5 mm circle scan protocol with locked reference images and eye tracking mode. Patients with an attack of optic neuritis within 12 months prior to the onset of the study were excluded.Although the disease was highly active over the observation period in more than half of the included relapsing remitting MS patients (19 patients/32 relapses) and the initial RNFL pattern showed a broad range, from normal to markedly reduced thickness, no significant changes between baseline and follow-up examinations could be detected.These results show that caution is required when using OCT for monitoring disease activity and global axonal injury in MS