Cattle remain immunocompetent during the acute phase of foot-and-mouth disease virus infection

Infection of cattle with foot-and-mouth disease virus (FMDV) results in the development of long-term protective antibody responses. In contrast, inactivated antigen vaccines fail to induce long-term protective immunity. Differences between susceptible species have also been observed during infection with FMDV, with cattle often developing persistent infections whilst pigs develop more severe symptoms and excrete higher levels of virus. This study examined the early immune response to FMDV in naïve cattle after in-contact challenge. Cattle exposed to FMDV were found to be viraemic and produced neutralising antibody, consistent with previous reports. In contrast to previous studies in pigs these cattle did not develop leucopenia, and the proliferative responses of peripheral blood mononuclear cells to either mitogen or third party antigen were not suppressed. Low levels of type 1 interferon and IL-10 were detected in the circulation. Taken together, these results suggest that there was no generalised immunosuppression during the acute phase of FMDV infection in cattle

Understanding foot-and-mouth disease virus transmission biology: identification of the indicators of infectiousness

The control of foot-and-mouth disease virus (FMDV) outbreaks in non-endemic countries relies on the rapid detection and removal of infected animals. In this paper we use the observed relationship between the onset of clinical signs and direct contact transmission of FMDV to identify predictors for the onset of clinical signs and identify possible approaches to preclinical screening in the field. Threshold levels for various virological and immunological variables were determined using Receiver Operating Characteristic (ROC) curve analysis and then tested using generalized linear mixed models to determine their ability to predict the onset of clinical signs. In addition, concordance statistics between qualitative real time PCR test results and virus isolation results were evaluated. For the majority of animals (71%), the onset of clinical signs occurred 3–4 days post infection. The onset of clinical signs was associated with high levels of virus in the blood, oropharyngeal fluid and nasal fluid. Virus is first detectable in the oropharyngeal fluid, but detection of virus in the blood and nasal fluid may also be good candidates for preclinical indicators. Detection of virus in the air was also significantly associated with transmission. This study is the first to identify statistically significant indicators of infectiousness for FMDV at defined time periods during disease progression in a natural host species. Identifying factors associated with infectiousness will advance our understanding of transmission mechanisms and refine intra-herd and inter-herd disease transmission models

Concurrence of Danish Dementia and Cataract: Insights from the Interactions of Dementia Associated Peptides with Eye Lens α-Crystallin

Familial Danish Dementia (FDD) is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens α-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide), by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Comparative Clinical Effectiveness of Management Strategies for Sciatica: Systematic Review and Network Meta-Analyses

Background There are numerous treatment approaches for sciatica. Previous systematic reviews have not compared all these strategies together. Purpose To compare the clinical effectiveness of different treatment strategies for sciatica simultaneously. Study design Systematic review and network meta-analysis. Methods: We searched 28 electronic databases and online trial registries, along with bibliographies of previous reviews, for comparative studies evaluating any intervention to treat sciatica in adults, with outcome data on global effect or pain intensity. Network meta-analysis methods were used to simultaneously compare all treatment strategies and allow indirect comparisons of treatments between studies. The study was funded by the UK National Institute for Health Research (NIHR) HTA programme; there are no potential conflict of interests. Results Of 122 relevant studies, 90 were randomised controlled trials (RCTs) or quasi-RCTs. Interventions were grouped into 21 treatment strategies. Internal and external validity of included studies was very low. For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, non-opioid analgesia, manipulation, and acupuncture. Traction, percutaneous discectomy and exercise therapy were significantly inferior to epidural injections or surgery. For pain reduction as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant. Biological agents were significantly better for pain reduction than bed rest, non-opioids, and opioids, or radiofrequency treatment. Opioids, education/advice alone, bed rest, and percutaneous discectomy and radiofrequency treatment were inferior to most other treatment strategies; although these findings represented large effects, they were statistically equivocal. Conclusions For the first time many different treatment strategies for sciatica have been compared in the same systematic review and meta-analysis. This approach has provided new data to assist shared decision-making. The findings support the effectiveness of non-opioid medication, epidural injections and disc surgery. They also suggest that spinal manipulation, acupuncture, and experimental treatments such as anti-inflammatory biological agents, may be considered. The findings do not support the effectiveness of opioid analgesia, bed rest, exercise therapy, education/advice (when used alone), percutaneous discectomy or traction. The issue of how best to estimate the effectiveness of treatment approaches according to their order within a sequential treatment pathway remains an important challenge

Operando spectroscopy study of the carbon dioxide electro-reduction by iron species on nitrogen-doped carbon

The carbon–carbon coupling via electrochemical reduction of carbon dioxide represents the biggest challenge for using this route as platform for chemicals synthesis. Here we show that nanostructured iron (III) oxyhydroxide on nitrogen-doped carbon enables high Faraday efficiency (97.4%) and selectivity to acetic acid (61%) at very-low potential (−0.5 V vs silver/silver chloride). Using a combination of electron microscopy, operando X-ray spectroscopy techniques and density functional theory simulations, we correlate the activity to acetic acid at this potential to the formation of nitrogen-coordinated iron (II) sites as single atoms or polyatomic species at the interface between iron oxyhydroxide and the nitrogen-doped carbon. The evolution of hydrogen is correlated to the formation of metallic iron and observed as dominant reaction path over iron oxyhydroxide on oxygen-doped carbon in the overall range of negative potential investigated, whereas over iron oxyhydroxide on nitrogen-doped carbon it becomes important only at more negative potentials