Evidence that the 36kb plasmid of Brachyspira hyodysenteriae contributes to virulence

Swine dysentery (SD) results from infection of the porcine large intestine with the anaerobic intestinal spirochaete Brachyspira hyodysenteriae. Recently the genome of virulent Australian B. hyodysenteriae strain WA1 was sequenced, and a 36. kilobase (kb) circular plasmid was identified. The plasmid contained 31 genes including six rfb genes that were predicted to be involved with rhamnose biosynthesis, and others associated with glycosylation. In the current study a set of PCRs was developed to amplify portions of nine of the plasmid genes. When used with DNA extracted from virulent strain B204, PCR products were generated, but no products were generated with DNA from avirulent strain A1. Analysis of the DNA using pulsed field gel electrophoresis (PFGE) identified a plasmid band in strains WA1 and B204, but not in strain A1. These results demonstrate that strain A1 does not contain the plasmid, and suggests that lack of the plasmid may explain why this strain is avirulent. To determine how commonly strains lacking plasmids occur, DNA was extracted from 264 Australian field isolates of B. hyodysenteriae and subjected to PCRs for three of the plasmid genes. Only one isolate (WA400) that lacked the plasmid was identified, and this absence was confirmed by PFGE analysis of DNA from the isolate and further PCR testing. To assess its virulence, 24 pigs were experimentally challenged with cultures of WA400, and 12 control pigs were challenged with virulent strain WA1 under the same conditions. Significantly fewer (P= 0.03) of the pigs challenged with WA400 became colonised and developed SD (13/24; 54%) compared to the pigs infected with WA1 (11/12; 92%). Gross lesions in the pigs colonised with WA400 tended to be less extensive than those in pigs colonised with WA1, although there were no obvious differences at the microscopic level. The results support the likelihood that plasmid-encoded genes of B. hyodysenteriae are involved in colonisation and/or disease expression

Investigating the effect of photodynamic therapy on nerves using tissue engineered culture models

Introduction: Photodynamic therapy (PDT) shows potential as an effective treatment for prostate cancer. Clinical observations indicate that this approach causes fewer nerve damage related side-effects than conventional treatments. The aim here is to investigate the effect of PDT on nerve tissue using engineered 3-dimensional cell culture models. Initial experiments focussed on establishing photosensitiser localisation in neurones and Schwann cells, then developing a model for simulating nerve PDT in culture

HLAs: Key regulators of T-cell-mediated drug hypersensitivity

Adverse drug reactions (ADR) can be broadly categorised as either on-target or off-target. On-target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose-dependent. On-target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast, off-target ADRs, including immune-mediated ADRs (IM-ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non-pharmacological interactions mediated through an adaptive immune response. IM-ADRs can be classified according to the primary immune cell involved and include B-cell-mediated (Gell-Coombs type I-III reactions) and T-cell-mediated (Gell-Coombs type IV or delayed hypersensitivity) reactions. IM-ADRs mediated by T cells are associated with phenotypically distinct clinical diagnoses and can vary from a mild delayed rash to a life-threatening cutaneous, systemic or organ disease, such as Stephen Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and drug-induced liver disease. T-cell-mediated ADRs are strongly linked to the carriage of particular HLA risk alleles which are in the case of abacavir hypersensitivity and HLA-B*57:01 has led to translation into the clinic as a routine screening test. In this review, we will discuss the immunogenetics and pathogenesis of IM-ADRs and how HLA associations inform both pre-drug screening strategies and mechanistic understanding

Redundancy Strategies for a High Splitting Optically Amplified Passive Optical Network

Copyright IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE.High splitting, optically amplified, passive optical networks (SuperPONs) are investigated in terms of redundancy provision and protection mechanisms. Options for redundancy, including the important special case of dual homing, are detailed, and it is determined as to which of these options (duplication of the feeder and first distribution section, and N+1 protection of the optical amplifiers in the amplified splitter) would be required to be provided to all attached users to facilitate appropriate availability of the basic telephony service. The distributed amplified splitter dual homing solution is found to outperform the single amplified splitter solution in terms of its survivability. The protection mechanisms necessary to automatically switch to the redundant provision are discussed and it is seen that with the aid of suitable regular precautionary procedures protection switching can generally be provided rapidly (<50 ms). Finally, an availability, and cost versus availability, study confirms the aforementioned redundancy assessment for fiber-to-the-home (FTTH) implementations, but shows fiber-to-the-curb (FTTC) as needing additional redundancyPeer reviewe

Preferences for HIV testing services among men who have sex with men in the UK: A discrete choice experiment.

BACKGROUND: In the UK, approximately 4,200 men who have sex with men (MSM) are living with HIV but remain undiagnosed. Maximising the number of high-risk people testing for HIV is key to ensuring prompt treatment and preventing onward infection. This study assessed how different HIV test characteristics affect the choice of testing option, including remote testing (HIV self-testing or HIV self-sampling), in the UK, a country with universal access to healthcare. METHODS AND FINDINGS: Between 3 April and 11 May 2017, a cross-sectional online-questionnaire-based discrete choice experiment (DCE) was conducted in which respondents who expressed an interest in online material used by MSM were asked to imagine that they were at risk of HIV infection and to choose between different hypothetical HIV testing options, including the option not to test. A variety of different testing options with different defining characteristics were described so that the independent preference for each characteristic could be valued. The characteristics included where each test is taken, the sampling method, how the test is obtained, whether infections other than HIV are tested for, test accuracy, the cost of the test, the infection window period, and how long it takes to receive the test result. Participants were recruited and completed the instrument online, in order to include those not currently engaged with healthcare services. The main analysis was conducted using a latent class model (LCM), with results displayed as odds ratios (ORs) and probabilities. The ORs indicate the strength of preference for one characteristic relative to another (base) characteristic. In total, 620 respondents answered the DCE questions. Most respondents reported that they were white (93%) and were either gay or bisexual (99%). The LCM showed that there were 2 classes within the respondent sample that appeared to have different preferences for the testing options. The first group, which was likely to contain 86% of respondents, had a strong preference for face-to-face tests by healthcare professionals (HCPs) compared to remote testing (OR 6.4; 95% CI 5.6, 7.4) and viewed not testing as less preferable than remote testing (OR 0.10; 95% CI 0.09, 0.11). In the second group, which was likely to include 14% of participants, not testing was viewed as less desirable than remote testing (OR 0.56; 95% CI 0.53, 0.59) as were tests by HCPs compared to remote testing (OR 0.23; 95% CI 0.15, 0.36). In both classes, free remote tests instead of each test costing £30 was the test characteristic with the largest impact on the choice of testing option. Participants in the second group were more likely to have never previously tested and to be non-white than participants in the first group. The main study limitations were that the sample was recruited solely via social media, the study advert was viewed only by people expressing an interest in online material used by MSM, and the choices in the experiment were hypothetical rather than observed in the real world. CONCLUSIONS: Our results suggest that preferences in the context we examined are broadly dichotomous. One group, containing the majority of MSM, appears comfortable testing for HIV but prefers face-to-face testing by HCPs rather than remote testing. The other group is much smaller, but contains MSM who are more likely to be at high infection risk. For these people, the availability of remote testing has the potential to significantly increase net testing rates, particularly if provided for free

Effect of dietary carbohydrate to lipid ratio on performance of Nile tilapia and enhancement of natural food in pond aquaculture

This study tested the effect of two diets differing in carbohydrate to lipid (CHO:LIP) ratio (4.7 vs. 19.5 g/g) on the contribution of natural food and the total fish production in tilapia ponds. Eight ponds, each divided into three equally sized compartments, were assigned to one of the two diets, which differed in CHO:LIP ratio but had the same digestible protein to digestible energy (DP:DE) ratio (15.5 and 15.6 g/MJ). Ponds were fed equal amounts of crude protein. Three feeding levels (no, low and high) were nested in each pond in a split plot design. Average body weight of fish at stocking was 90 g, and the duration of the experiment was 42 days. Increasing the CHO:LIP ratio had no impact on tilapia production. However, the feeding level influenced both biomass gain, specific growth rate and survival. The apparent digestibility coefficient (ADC) for fat and carbohydrate was influenced by dietary CHO:LIP ratio but ADC for energy was unaffected. Proximate analysis of fish body composition showed no effect of diet except for levels of ash. Diet had no effect on the organic matter composition of the faeces, and the contribution of natural food to fish nitrogen gain. Therefore, we postulate that changing the dietary non-protein energy source from lipid to carbohydrate does not have any impact on tilapia culture in semi-intensive ponds.</p

Hall Conductivity near the z=2 Superconductor-Insulator Transition in 2D

We analyze here the behavior of the Hall conductivity $\sigma_{xy}$ near a $z=2$ insulator-superconductor quantum critical point in a perpendicular magnetic field. We show that the form of the conductivity is sensitive to the presence of dissipation $\eta$, and depends non-monotonically on $H$ once $\eta$ is weak enough. $\sigma_{xy}$ passes through a maximum at $H \sim \eta T$ in the quantum critical regime, suggesting that the limits $H \to 0$ and $\eta \to 0$ do not commute.Comment: 4 pages, 1 .eps figure, to appear in Phys. Rev.

Quantum Disordered Regime and Spin Gap in the Cuprate Superconductors

We discuss the crossover from the quantum critical, $z\!=\!1$, to the quantum disordered regime in high-T$_c$ materials in relation to the experimental data on the nuclear relaxation, bulk susceptibility, and inelastic neutron scattering. In our scenario, the spin excitations develop a gap $\Delta\!\sim\!1/\xi$ well above T$_c$, which is supplemented by the quasiparticle gap below T$_c$. The above experiments yield consistent estimates for the value of the spin gap, which increases as the correlation length decreases.Comment: 14 pages, REVTeX v3.0, PostScript file for 3 figures is attached, UIUC-P-93-07-06

Inelastic light, neutron, and X-ray scatterings related to the heterogeneous elasticity of glasses

The effects of plasticization of poly(methyl methacrylate) glass on the boson peaks observed by Raman and neutron scattering are compared. In plasticized glass the cohesion heterogeneities are responsible for the neutron boson peak and partially for the Raman one, which is enhanced by the composition heterogeneities. Because the composition heterogeneities have a size similar to that of the cohesion ones and form quasiperiodic clusters, as observed by small angle X-ray scattering, it is inferred that the cohesion heterogeneities in a normal glass form nearly periodic arrangements too. Such structure at the nanometric scale explains the linear dispersion of the vibrational frequency versus the transfer momentum observed by inelastic X-ray scattering.Comment: 9 pages, 2 figures, to be published in J. Non-Cryst. Solids (Proceedings of the 4th IDMRCS

Nonlinear optics via double dark resonances

Double dark resonances originate from a coherent perturbation of a system displaying electromagnetically induced transparency. We experimentally show and theoretically confirm that this leads to the possibility of extremely sharp resonances prevailing even in the presence of considerable Doppler broadening. A gas of 87Rb atoms is subjected to a strong drive laser and a weak probe laser and a radio frequency field, where the magnetic coupling between the Zeeman levels leads to nonlinear generation of a comb of sidebands.Comment: 6 pages, 9 figure