The conventional gait model - success and limitations

The Conventional Gait Model (CGM) is a generic name for a family of closely related and very widely used biomechanical models for gait analysis. After describing its history, the core attributes of the model are described followed by evaluation of its strengths and weaknesses. An analysis of the current and future requirements for practical biomechanical models for clinical and other gait analysis purposes which have been rigorously calibrated suggests that the CGM is better suited for this purpose than any other currently available model. Modifications are required, however, and a number are proposed

Controlling epidemic spread by social distancing: Do it well or not at all

BACKGROUND: Existing epidemiological models have largely tended to neglect the impact of individual behaviour on the dynamics of diseases. However, awareness of the presence of illness can cause people to change their behaviour by, for example, staying at home and avoiding social contacts. Such changes can be used to control epidemics but they exact an economic cost. Our aim is to study the costs and benefits of using individual-based social distancing undertaken by healthy individuals as a form of control.METHODS: Our model is a standard SIR model superimposed on a spatial network, without and with addition of small-world interactions. Disease spread is controlled by allowing susceptible individuals to temporarily reduce their social contacts in response to the presence of infection within their local neighbourhood. We ascribe an economic cost to the loss of social contacts, and weigh this against the economic benefit gained by reducing the impact of the epidemic. We study the sensitivity of the results to two key parameters, the individuals' attitude to risk and the size of the awareness neighbourhood.RESULTS: Depending on the characteristics of the epidemic and on the relative economic importance of making contacts versus avoiding infection, the optimal control is one of two extremes: either to adopt a highly cautious control, thereby suppressing the epidemic quickly by drastically reducing contacts as soon as disease is detected; or else to forego control and allow the epidemic to run its course. The worst outcome arises when control is attempted, but not cautiously enough to cause the epidemic to be suppressed. The next main result comes from comparing the size of the neighbourhood of which individuals are aware to that of the neighbourhood within which transmission can occur. The control works best when these sizes match and is particularly ineffective when the awareness neighbourhood is smaller than the infection neighbourhood. The results are robust with respect to inclusion of long-range, small-world links which destroy the spatial structure, regardless of whether individuals can or cannot control them. However, addition of many non-local links eventually makes control ineffective.CONCLUSIONS: These results have implications for the design of control strategies using social distancing: a control that is too weak or based upon inaccurate knowledge, may give a worse outcome than doing nothing

Identifying the Age Cohort Responsible for Transmission in a Natural Outbreak of Bordetella bronchiseptica

Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica – a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans – within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter), or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings – as opposed to, for example, breeder or maternal cohorts – as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control

Models of epidemics: when contact repetition and clustering should be included

Background The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. Methods We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. Results The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. Conclusion We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.ISSN:1742-468

Is Promiscuity Associated with Enhanced Selection on MHC-DQα in Mice (genus Peromyscus)?

Reproductive behavior may play an important role in shaping selection on Major Histocompatibility Complex (MHC) genes. For example, the number of sexual partners that an individual has may affect exposure to sexually transmitted pathogens, with more partners leading to greater exposure and, hence, potentially greater selection for variation at MHC loci. To explore this hypothesis, we examined the strength of selection on exon 2 of the MHC-DQα locus in two species of Peromyscus. While the California mouse (P. californicus) is characterized by lifetime social and genetic monogamy, the deer mouse (P. maniculatus) is socially and genetically promiscuous; consistent with these differences in mating behavior, the diversity of bacteria present within the reproductive tracts of females is significantly greater for P. maniculatus. To test the prediction that more reproductive partners and exposure to a greater range of sexually transmitted pathogens are associated with enhanced diversifying selection on genes responsible for immune function, we compared patterns and levels of diversity at the Class II MHC-DQα locus in sympatric populations of P. maniculatus and P. californicus. Using likelihood based analyses, we show that selection is enhanced in the promiscuous P. maniculatus. This study is the first to compare the strength of selection in wild sympatric rodents with known differences in pathogen milieu

First shark from the late Devonian (Frasnian) gogo formation, Western Australia sheds new light on the development of tessellated calcified cartilage

Background: Living gnathostomes (jawed vertebrates) comprise two divisions, Chondrichthyes (cartilaginous fishes, including euchondrichthyans with prismatic calcified cartilage, and extinct stem chondrichthyans) and Osteichthyes (bony fishes including tetrapods). Most of the early chondrichthyan (‘shark’) record is based upon isolated teeth, spines, and scales, with the oldest articulated sharks that exhibit major diagnostic characters of the group—prismatic calcified cartilage and pelvic claspers in males—being from the latest Devonian, c. 360 Mya. This paucity of information about early chondrichthyan anatomy is mainly due to their lack of endoskeletal bone and consequent low preservation potential. Methodology/Principal Findings: Here we present new data from the first well-preserved chondrichthyan fossil from the early Late Devonian (ca. 380–384 Mya) Gogo Formation Lägerstatte of Western Australia. The specimen is the first Devonian shark body fossil to be acid-prepared, revealing the endoskeletal elements as three-dimensional undistorted units: Meckel’s cartilages, nasal, ceratohyal, basibranchial and possible epibranchial cartilages, plus left and right scapulocoracoids, as well as teeth and scales. This unique specimen is assigned to Gogoselachus lynnbeazleyae n. gen. n. sp.Conclusions/Significance: The Meckel’s cartilages show a jaw articulation surface dominated by an expansive cotylus, and a small mandibular knob, an unusual condition for chondrichthyans. The scapulocoracoid of the new specimen shows evidence of two pectoral fin basal articulation facets, differing from the standard condition for early gnathostomes which have either one or three articulations. The tooth structure is intermediate between the ‘primitive’ ctenacanthiform and symmoriiform condition, and more derived forms with a euselachian-type base. Of special interest is the highly distinctive type of calcified cartilage forming the endoskeleton, comprising multiple layers of nonprismatic subpolygonal tesserae separated by a cellular matrix, interpreted as a transitional step toward the tessellated prismatic calcified cartilage that is recognized as the main diagnostic character of the chondrichthyans

Using national movement databases to help inform responses to swine disease outbreaks in Scotland:the impact of uncertainty around incursion time

Modelling is an important component of contingency planning and control of disease outbreaks. Dynamic network models are considered more useful than static models because they capture important dynamic patterns of farm behaviour as evidenced through animal movements. This study evaluates the usefulness of a dynamic network model of swine fever to predict pre-detection spread via movements of pigs, when there may be considerable uncertainty surrounding the time of incursion of infection. It explores the utility and limitations of animal movement data to inform such models and as such, provides some insight into the impact of improving traceability through real-time animal movement reporting and the use of electronic animal movement databases. The study concludes that the type of premises and uncertainty of the time of disease incursion will affect model accuracy and highlights the need for improvements in these areas

Heterogeneous shedding of influenza by human subjects and its implications for epidemiology and control

International audienceHeterogeneity of infectiousness is an important feature of the spread of many infections, with implications for disease dynamics and control, but its relevance to human influenza virus is still unclear. For a transmission event to occur, an infected individual needs to release infectious particles via respiratory symptoms. Key factors to take into account are virus dynamics, particle release in relation to respiratory symptoms, the amount of virus shed and, importantly, how these vary between infected individuals. A quantitative understanding of the process of influenza transmission is relevant to designing effective mitigation measures. Here we develop an influenza infection dynamics model fitted to virological, systemic and respiratory symptoms to investigate how within-host dynamics relates to infectiousness. We show that influenza virus shedding is highly heterogeneous between subjects. From analysis of data on experimental infections, we find that a small proportion (<20%) of influenza infected individuals are responsible for the production of 95% of infectious particles. Our work supports targeting mitigation measures at most infectious subjects to efficiently reduce transmission. The effectiveness of public health interventions targeted at highly infectious individuals would depend on accurate identification of these subjects and on how quickly control measures can be applied