Pathogenic Potential to Humans of Bovine Escherichia coli O26, Scotland

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin–producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx<sub>2</sub> in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26–associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx<sub>2</sub> phage acquisition

Prevalence of permanent neonatal hearing impairment: systematic review and Bayesian meta-analysis

Objective: To investigate the variance in reported prevalence rates of permanent neonatal hearing impairment (HI) worldwide. Design: A systematic review and meta-analysis was performed on reported prevalence rates of sensorineural and permanent conductive or mixed HI worse than 40 dB in neonates, detected as a result of a screening programme or audiometric study. Study sample: For meta-analysis, 35 articles were selected, 25 from high-income countries and 10 from middle-income countries according to the world bank classification system. Results: The prevalence rate of permanent uni- and bilateral HI worse than 40 dB in neonates varied from 1 to 6 per 1000, the overall prevalence was 2.21 per 1000 [1.71, 2.8]. In NICU populations the prevalence rate was higher with a larger fraction of bilateral cases. Although not significant, prevalence rates were slightly higher in Asia compared to Europe and the number of infants lost to follow-up appeared higher in countries with lower gross national income. Conclusion: Substantial variations exist in prevalence rates of neonatal permanent HI across countries and regions. There is a strong need for more data from low-income countries to identify demographic factors that account for this variability in reported prevalence rates. Reporting these data in a uniform way is advocated

Modelling the cost-effectiveness of a newborn hearing screening programme:Usability and pitfalls

Objective: The EUSCREEN project concerns the study of European vision and hearing screening programmes. Part of the project was the development of a cost-effectiveness model to analyse such programmes. We describe the development and usability of an online tool to enable stakeholders to design, analyse or modify a newborn hearing screening (NHS) programme. Design: Data from literature, from existing NHS programmes, and observations by users were used to develop and refine the tool. Required inputs include prevalence of the hearing impairment, test sequence and its timing, attendance, sensitivity, and specificity of each screening step. Outputs include the number of cases detected and the costs of screening and diagnostics. Study sample: Eleven NHS programmes with reliable data. Results: Three analyses are presented, exploring the effect of low attendance, number of screening steps, testing in the maternity ward, or screening at a later age, on the benefits and costs of the programme. Knowledge of the epidemiology of a staged screening programme is crucial when using the tool. Conclusions: This study presents a tool intended to aid stakeholders to design a new or analyse an existing hearing screening programme in terms of benefits and costs.</p

Development and characterization of a microfluidic model of the tumour microenvironment

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live ‘window’ into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device’s potential to enable more physiological in vitro drug screening

Neutral-Current Atmospheric Neutrino Flux Measurement Using Neutrino-Proton Elastic Scattering in Super-Kamiokande

Recent results show that atmospheric $\nu_\mu$ oscillate with $\delta m^2 \simeq 3 \times 10^{-3}$ eV$^2$ and $\sin^2{2\theta_{atm}} \simeq 1$, and that conversion into $\nu_e$ is strongly disfavored. The Super-Kamiokande (SK) collaboration, using a combination of three techniques, reports that their data favor $\nu_\mu \to \nu_\tau$ over $\nu_\mu \to \nu_{sterile}$. This distinction is extremely important for both four-neutrino models and cosmology. We propose that neutrino-proton elastic scattering ($\nu + p \to \nu + p$) in water \v{C}erenkov detectors can also distinguish between active and sterile oscillations. This was not previously recognized as a useful channel since only about 2% of struck protons are above the \v{C}erenkov threshold. Nevertheless, in the present SK data there should be about 40 identifiable events. We show that these events have unique particle identification characteristics, point in the direction of the incoming neutrinos, and correspond to a narrow range of neutrino energies (1-3 GeV, oscillating near the horizon). This channel will be particularly important in Hyper-Kamiokande, with $\sim 40$ times higher rate. Our results have other important applications. First, for a similarly small fraction of atmospheric neutrino quasielastic events, the proton is relativistic. This uniquely selects $\nu_\mu$ (not $\bar{\nu}_\mu$) events, useful for understanding matter effects, and allows determination of the neutrino energy and direction, useful for the $L/E$ dependence of oscillations. Second, using accelerator neutrinos, both elastic and quasielastic events with relativistic protons can be seen in the K2K 1-kton near detector and MiniBooNE.Comment: 10 pages RevTeX, 8 figure

Probing neutrino non-standard interactions with atmospheric neutrino data

We have reconsidered the atmospheric neutrino anomaly in light of the laetst data from Super-Kamiokande contained events and from Super-Kamiokande and MACRO up-going muons. We have reanalysed the proposed solution to the atmospheric neutrino anomaly in terms of non-standard neutrino-matter interactions (NSI) as well as the standard nu_mu -> nu_tau oscillations (OSC). Our statistical analysis shows that a pure NSI mechanism is now ruled out at 99%, while the standard nu_mu -> nu_tau OSC mechanism provides a quite remarkably good description of the anomaly. We therefore study an extended mechanism of neutrino propagation which combines both oscillation and non-standard neutrino-matter interactions, in order to derive limits on flavour-changing (FC) and non-universal (NU) neutrino interactions. We obtain that the off-diagonal flavour-changing neutrino parameter epsilon and the diagonal non-universality neutrino parameter epsilon' are confined to -0.03 < epsilon < 0.02 and |epsilon'| < 0.05 at 99.73% CL. These limits are model independent and they are obtained from pure neutrino-physics processes. The stability of the neutrino oscillation solution to the atmospheric neutrino anomaly against the presence of non-standard neutrino interactions establishes the robustness of the near-maximal atmospheric mixing and massive-neutrino hypothesis. The best agreement with the data is obtained for Delta_m^2 = 2.3*10^{-3} eV^2, sin^2(2*theta) = 1, epsilon = 6.7*10^{-3} and epsilon' = 1.1*10^{-3}, although the chi^2 function is quite flat in the epsilon and epsilon' directions for epsilon, epsilon' -> 0.Comment: 26 pages, LaTeX file using REVTeX4, 1 table and 12 figures included. Added a revised analysis which takes into account the new 1489-day Super-Kamiokande and final MACRO data. The bound on NSI parameters is considerably improve

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

Unified Maxwell-Einstein and Yang-Mills-Einstein Supergravity Theories in Five Dimensions

Unified N=2 Maxwell-Einstein supergravity theories (MESGTs) are supergravity theories in which all the vector fields, including the graviphoton, transform in an irreducible representation of a simple global symmetry group of the Lagrangian. As was established long time ago, in five dimensions there exist only four unified Maxwell-Einstein supergravity theories whose target manifolds are symmetric spaces. These theories are defined by the four simple Euclidean Jordan algebras of degree three. In this paper, we show that, in addition to these four unified MESGTs with symmetric target spaces, there exist three infinite families of unified MESGTs as well as another exceptional one. These novel unified MESGTs are defined by non-compact (Minkowskian) Jordan algebras, and their target spaces are in general neither symmetric nor homogeneous. The members of one of these three infinite families can be gauged in such a way as to obtain an infinite family of unified N=2 Yang-Mills-Einstein supergravity theories, in which all vector fields transform in the adjoint representation of a simple gauge group of the type SU(N,1). The corresponding gaugings in the other two infinite families lead to Yang-Mills-Einstein supergravity theories coupled to tensor multiplets.Comment: Latex 2e, 28 pages. v2: reference added, footnote 14 enlarge