Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

<p>Abstract</p> <p>Background</p> <p>In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances.</p> <p>Methods</p> <p>We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario.</p> <p>Results</p> <p>The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing), estimated to have less than 1 in 1,000,000 (0.000001) risk of transmission.</p> <p>Conclusions</p> <p>Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.</p

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of &gt;0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes

Comparative indoor and outdoor stability measurements of polymer based solar cells

We report comparative indoor and outdoor stability testing of organic solar cells based on a blend between a donor-acceptor polyfluorene copolymer and a fullerene derivative. The outdoor testing was conducted for a period over 12,000 hours in Sheffield, England, with a Ts80 lifetime determined in excess of 10,000 hours (420 days). Indoor lifetime testing was performed on solar cells using a solar simulator under a constant irradiance of 1000 W/m(2) for more than 650 hours. We show that under the conditions explored here, device degradation under the two sets of conditions is approximately dependent on the absorbed optical energy dose

An fMRI Investigation of Preparatory Set in the Human Cerebral Cortex and Superior Colliculus for Pro- and Anti-Saccades

Previous studies have identified several cortical regions that show larger BOLD responses during preparation and execution of anti-saccades than pro-saccades. We confirmed this finding with a greater BOLD response for anti-saccades than pro-saccades during the preparation phase in the FEF, IPS and DLPFC and in the FEF and IPS in the execution phase. We then applied multi-voxel pattern analysis (MVPA) to establish whether different neural populations are involved in the two types of saccade. Pro-saccades and anti-saccades were reliably decoded during saccade execution in all three cortical regions (FEF, DLPFC and IPS) and in IPS during saccade preparation. This indicates neural specialization, for programming the desired response depending on the task rule, in these regions. In a further study tailored for imaging the superior colliculus in the midbrain a similar magnitude BOLD response was observed for pro-saccades and anti-saccades and the two saccade types could not be decoded with MVPA. This was the case both for activity related to the preparation phase and also for that elicited during the execution phase. We conclude that separate cortical neural populations are involved in the task-specific programming of a saccade while in contrast, the SC has a role in response preparation but may be less involved in high-level, task-specific aspects of the control of saccades

Acute interaction between hydrocortisone and insulin alters the plasma metabolome in humans

With the aim of identifying biomarkers of glucocorticoid action and their relationship with biomarkers of insulin action, metabolomic profiling was carried out in plasma samples from twenty healthy men who were administered either a low or medium dose insulin infusion (n = 10 each group). In addition, all subjects were given metyrapone (to inhibit adrenal cortisol secretion) +/-hydrocortisone (HC) in a randomised crossover design to produce low, medium and high glucocorticoid levels. The clearest effects of insulin were to reduce plasma levels of the branched chain amino acids (BCAs) leucine/isoleucine and their deaminated metabolites, and lowered free fatty acids and acylcarnitines. The highest dose of hydrocortisone increased plasma BCAs in both insulin groups but increased free fatty acids only in the high insulin group, however hydrocortisone did not affect the levels of acyl carnitines in either group. The clearest interaction between HC and insulin was that hydrocortisone produced an elevation in levels of BCAs and their metabolites which were lowered by insulin. The direct modulation of BCAs by glucocorticoids and insulin may provide the basis for improved in vivo monitoring of glucocorticoid and insulin action

MACSIMS : multiple alignment of complete sequences information management system

BACKGROUND: In the post-genomic era, systems-level studies are being performed that seek to explain complex biological systems by integrating diverse resources from fields such as genomics, proteomics or transcriptomics. New information management systems are now needed for the collection, validation and analysis of the vast amount of heterogeneous data available. Multiple alignments of complete sequences provide an ideal environment for the integration of this information in the context of the protein family. RESULTS: MACSIMS is a multiple alignment-based information management program that combines the advantages of both knowledge-based and ab initio sequence analysis methods. Structural and functional information is retrieved automatically from the public databases. In the multiple alignment, homologous regions are identified and the retrieved data is evaluated and propagated from known to unknown sequences with these reliable regions. In a large-scale evaluation, the specificity of the propagated sequence features is estimated to be >99%, i.e. very few false positive predictions are made. MACSIMS is then used to characterise mutations in a test set of 100 proteins that are known to be involved in human genetic diseases. The number of sequence features associated with these proteins was increased by 60%, compared to the features available in the public databases. An XML format output file allows automatic parsing of the MACSIM results, while a graphical display using the JalView program allows manual analysis. CONCLUSION: MACSIMS is a new information management system that incorporates detailed analyses of protein families at the structural, functional and evolutionary levels. MACSIMS thus provides a unique environment that facilitates knowledge extraction and the presentation of the most pertinent information to the biologist. A web server and the source code are available at

Novel Topical Microbicides Through Combinatorial Strategies

Purpose Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards epithelial cells. Here, we report on the discovery of unique surfactant formulations with improved safety and efficacy profile for epithelial applications, via a combination of high throughput screening techniques. Methods Over three-hundred formulations derived from nine surfactants were screened for antibacterial properties against E. coli in vitro. A subset of these formulations showed high antibacterial activity and was screened for cytotoxicity in vitro. Formulations showing high antibacterial activity and reduced cytotoxicity compared to their individual components were tested for efficacy against B. thailendensis, a model for melioidosis-causing B. pseudomallei. Results Lead formulations showed lower toxicity towards epidermal keratinocytes, with LC50 values up to 3.5-fold higher than their component surfactants, while maintaining antibacterial efficacy against B. thailendensis. Conclusions Our results demonstrate that such a combinatorial screening approach can be used for designing safe and potent microbicides for epithelial applications

Giant Intra-Articular Extrasynovial Osteochondroma of the Knee: A Report of Two Cases

We report two cases of a giant extrasynovial osteochondroma of the knee located in the infrapatellar fat pad region, in two females who were 58 and 71 years old respectively. Both patients had noticed the mass many years before our first clinical observation. In both patients, at physical examination a solid, firm and hard mass was palpable in the anterior part of the knee in Hoffa’s fat pad region, and the range of motion of the knee was severely restricted and painful. CT scan examination with 3D-reconstruction showed two large, calcified neoformations behind the patellar tendon, between the apex of the patella and the proximal third of the tibia. In both cases, the mass was completely resected surgically through an anterior longitudinal approach. At histological examination, the excised masses consisted of an outer layer of hyaline cartilage without significant chondrocyte atypia and an inner region of bone trabeculae formed by endochondral ossification. At follow-up, 8 and 4 years after the operation, both patients were pain-free, with complete recovery of the range of motion of the knee and without any clinical or radiographic evidence of recurrence. The authors believe that intra-articular extrasynovial osteochondroma of the knee is a primary metaplasia of Hoffa’s fat pad. Usually, the tumor develops slowly and asymptomatically over many years. The treatment of choice is a marginal resection of the mass, although a biopsy should be considered in some cases. Recurrences are extremely rare

How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics