Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases

Estimating the distribution of the incubation periods of human avian influenza A(H7N9) virus infections

A novel avian influenza virus, influenza A(H7N9), emerged in China in early 2013 and caused severe disease in humans, with infections occurring most frequently after recent exposure to live poultry. The distribution of A(H7N9) incubation periods is of interest to epidemiologists and public health officials, but estimation of the distribution is complicated by interval censoring of exposures. Imputation of the midpoint of intervals was used in some early studies, resulting in estimated mean incubation times of approximately 5 days. In this study, we estimated the incubation period distribution of human influenza A(H7N9) infections using exposure data available for 229 patients with laboratory-confirmed A(H7N9) infection from mainland China. A nonparametric model (Turnbull) and several parametric models accounting for the interval censoring in some exposures were fitted to the data. For the best-fitting parametric model (Weibull), the mean incubation period was 3.4 days (95% confidence interval: 3.0, 3.7) and the variance was 2.9 days; results were very similar for the nonparametric Turnbull estimate. Under the Weibull model, the 95th percentile of the incubation period distribution was 6.5 days (95% confidence interval: 5.9, 7.1). The midpoint approximation for interval-censored exposures led to overestimation of the mean incubation period. Public health observation of potentially exposed persons for 7 days after exposure would be appropriate.postprin

Estimating the distribution of the incubation periods of human avian influenza A(H7N9) virus infections

A novel avian influenza virus, influenza A(H7N9), emerged in China in early 2013 and caused severe disease in humans, with infections occurring most frequently after recent exposure to live poultry. The distribution of A(H7N9) incubation periods is of interest to epidemiologists and public health officials, but estimation of the distribution is complicated by interval censoring of exposures. Imputation of the midpoint of intervals was used in some early studies, resulting in estimated mean incubation times of approximately 5 days. In this study, we estimated the incubation period distribution of human influenza A(H7N9) infections using exposure data available for 229 patients with laboratory-confirmed A(H7N9) infection from mainland China. A nonparametric model (Turnbull) and several parametric models accounting for the interval censoring in some exposures were fitted to the data. For the best-fitting parametric model (Weibull), the mean incubation period was 3.4 days (95% confidence interval: 3.0, 3.7) and the variance was 2.9 days; results were very similar for the nonparametric Turnbull estimate. Under the Weibull model, the 95th percentile of the incubation period distribution was 6.5 days (95% confidence interval: 5.9, 7.1). The midpoint approximation for interval-censored exposures led to overestimation of the mean incubation period. Public health observation of potentially exposed persons for 7 days after exposure would be appropriate.postprin

Extraction of SSVEPs-Based Inherent Fuzzy Entropy Using a Wearable Headband EEG in Migraine Patients

© 1993-2012 IEEE. Inherent fuzzy entropy is an objective measurement of electroencephalography (EEG) complexity reflecting the robustness of brain systems. In this study, we present a novel application of multiscale relative inherent fuzzy entropy using repetitive steady-state visual evoked potentials (SSVEPs) to investigate EEG complexity change between two migraine phases, i.e., interictal (baseline) and preictal (before migraine attacks) phases. We used a wearable headband EEG device with O1, Oz, O2, and Fpz electrodes to collect EEG signals from 80 participants [40 migraine patients and 40 healthy controls (HCs)] under the following two conditions: During resting state and SSVEPs with five 15-Hz photic stimuli. We found a significant enhancement in occipital EEG entropy with increasing stimulus times in both HCs and patients in the interictal phase, but a reverse trend in patients in the preictal phase. In the 1st SSVEP, occipital EEG entropy of the HCs was significantly lower than that of patents in the preictal phase (FDR-adjusted p < 0.05). Regarding the transitional variance of EEG entropy between the 1st and 5th SSVEPs, patients in the preictal phase exhibited significantly lower values than patients in the interictal phase (FDR-adjusted p < 0.05). Furthermore, in the classification model, the AdaBoost ensemble learning showed an accuracy of 81 pm 6%and area under the curve of 0.87 for classifying interictal and preictal phases. In contrast, there were no differences in EEG entropy among groups or sessions by using other competing entropy models, including approximate entropy, sample entropy, and fuzzy entropy on the same dataset. In conclusion, inherent fuzzy entropy offers novel applications in visual stimulus environments and may have the potential to provide a preictal alert to migraine patients

Ge/Si interdiffusion in the GeSi dots and wetting layers

The Ge/Si interdiffusion in GeSi dots grown on Si (001) substrate by gas-source molecular beam epitaxy is investigated. Transmission electron microscopy images show that, after annealing, the aspect ratio of the height to base diameter increases. Raman spectra show that the Si-Ge mode redshifts and the intensity of the local Si-Si mode increases with the increase of annealing temperature, which suggests the Ge/Si interdiffusion during annealing. The photoluminescence peaks from the dots and the wetting layers show blueshift due to the atomic intermixing during annealing. The interdiffusion thermal activation energies of GeSi dots and the wetting layers are 2.16 and 2.28 eV, respectively. The interdiffusion coefficient of the dots is about 40 times higher than that of wetting layers and the reasons were discussed. (C) 2001 American Institute of Physics

Attention modulates adaptive motor learning in the ‘broken escalator’ paradigm

The physical stumble caused by stepping onto a stationary (broken) escalator represents a locomotor aftereffect (LAE) that attests to a process of adaptive motor learning. Whether such learning is primarily explicit (requiring attention resources) or implicit (independent of attention) is unknown. To address this question, we diverted attention in the adaptation (MOVING) and aftereffect (AFTER) phases of the LAE by loading these phases with a secondary cognitive task (sequential naming of a vegetable, fruit and a colour). Thirty-six healthy adults were randomly assigned to 3 equally sized groups. They performed 5 trials stepping onto a stationary sled (BEFORE), 5 with the sled moving (MOVING) and 5 with the sled stationary again (AFTER). A 'Dual-Task-MOVING (DTM)' group performed the dual-task in the MOVING phase and the 'Dual-Task-AFTEREFFECT (DTAE)' group in the AFTER phase. The 'control' group performed no dual task. We recorded trunk displacement, gait velocity and gastrocnemius muscle EMG of the left (leading) leg. The DTM, but not the DTAE group, had larger trunk displacement during the MOVING phase, and a smaller trunk displacement aftereffect compared with controls. Gait velocity was unaffected by the secondary cognitive task in either group. Thus, adaptive locomotor learning involves explicit learning, whereas the expression of the aftereffect is automatic (implicit). During rehabilitation, patients should be actively encouraged to maintain maximal attention when learning new or challenging locomotor tasks

KeV Warm Dark Matter and Composite Neutrinos

Elementary keV sterile Dirac neutrinos can be a natural ingredient of the composite neutrino scenario. For a certain class of composite neutrino theories, these sterile neutrinos naturally have the appropriate mixing angles to be resonantly produced warm dark matter (WDM). Alternatively, we show these sterile neutrinos can be WDM produced by an entropy-diluted thermal freeze-out, with the necessary entropy production arising not from an out-of-equilibrium decay, but rather from the confinement of the composite neutrino sector, provided there is sufficient supercooling.Comment: 12 pages, 2 figures, published versio

Lewis X antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involvement of the endothelial scavenger receptor C-Type lectin

Lewis x (Lex, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Lex in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Lex-dependent PMN interaction with HUVEC. Although both anti-Lex mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Lex-trisaccharide, interacts with specific glycoproteins of Mr␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.Fil: Elola, Maria Teresa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capurro, Mariana Isabel. University of Toronto; CanadáFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; ArgentinaFil: Coombs, Peter J.. Imperial College London; Reino UnidoFil: Taylor, Maureen E.. Imperial College London; Reino UnidoFil: Drickamer, Kurt. Imperial College London; Reino UnidoFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentin

Attenuation of Heparan Sulfate Proteoglycan Binding Enhances In Vivo Transduction of Human Primary Hepatocytes with AAV2

Use of the prototypical adeno-associated virus type 2 (AAV2) capsid delivered unexpectedly modest efficacy in an early liver-targeted gene therapy trial for hemophilia B. This result is consistent with subsequent data generated in chimeric mouse-human livers showing that the AAV2 capsid transduces primary human hepatocytes in vivo with low efficiency. In contrast, novel variants generated by directed evolution in the same model, such as AAV-NP59, transduce primary human hepatocytes with high efficiency. While these empirical data have immense translational implications, the mechanisms underpinning this enhanced AAV capsid transduction performance in primary human hepatocytes are yet to be fully elucidated. Remarkably, AAV-NP59 differs from the prototypical AAV2 capsid by only 11 aa and can serve as a tool to study the correlation between capsid sequence/structure and vector function. Using two orthogonal vectorological approaches, we have determined that just 2 of the 11 changes present in AAV-NP59 (T503A and N596D) account for the enhanced transduction performance of this capsid variant in primary human hepatocytes in vivo, an effect that we have associated with attenuation of heparan sulfate proteoglycan (HSPG) binding affinity. In support of this hypothesis, we have identified, using directed evolution, two additional single amino acid substitution AAV2 variants, N496D and N582S, which are highly functional in vivo. Both substitution mutations reduce AAV2's affinity for HSPG. Finally, we have modulated the ability of AAV8, a highly murine-hepatotropic serotype, to interact with HSPG. The results support our hypothesis that enhanced HSPG binding can negatively affect the in vivo function of otherwise strongly hepatotropic variants and that modulation of the interaction with HSPG is critical to ensure maximum efficiency in vivo. The insights gained through this study can have powerful implications for studies into AAV biology and capsid development for preclinical and clinical applications targeting liver and other organs

Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China

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