Mixed shift rotations, sleep, burnout and well-being in professions similar to radiographers: A systematic review.

INTRODUCTION: Delivering 24 h healthcare requires rotational shift work from doctors and the medical imaging team, while contributing to safe and timely care of patients. Additional service pressure and staff shortfall leads to workload pressures, adjusted shift patterns and risk of burnout. Evidence should be sought to the effects of this work on staff. METHODS: This systematic review followed PRISMA reporting guidelines, using a convergent mixed methods approach according to Guidance from Joanna Briggs International. Quantitative trends and results were qualified in order to thematically analyse in conjunction with qualitative data and discussed together in context. Following initial searching, returned articles were screened by title and abstract. A team of 3 reviewers undertook blinded critical appraisal of those suitable, with quality assurance from a 4th team member. Papers passing a threshold of 75% on JBI appraisal tools were accepted for synthesis. Data extraction of appropriate articles retrieved was undertaken in parallel. RESULTS: Following screening and critical appraisal, 13 studies were returned focusing exclusively on Non Consultant Doctors. No studies investigated diagnostic radiographers. 85% (n = 11) reported negative association between shift work and the three themes of sleep/fatigue, burnout and wellbeing: including after the introduction of shift pattern control or adjusted shift patterns. The remainder showed no change, or any improvement nullified by countermeasures to maintain service delivery. CONCLUSION: Current working practices and shift plans in the target population showed detrimental effects on the participants - this can be suggested that Diagnostic Radiographers may suffer fatigue, burnout and poor mental health from stretched shift working patterns. IMPLICATIONS FOR PRACTICE: Further study into the effects of shift work on Diagnostic Radiographers and other allied health professionals is indicated - relating to the above themes in the context of errors and patient safety. Additional research into Non Consultant Doctors, shift work effects and the context of wider service delivery required; with suitable interventions and education to maximise understanding of legal working practices, monitoring and self-management of symptoms.

Immune interactions and heterogeneity in transmission drives the pathogen-mediated invasion of grey squirrels in the UK.

Mathematical models highlighted the importance of pathogen-mediated invasion, with the replacement of red squirrels by squirrelpox virus (SQPV) carrying grey squirrels in the UK, a well-known example. In this study, we combine new epidemiological models, with a range of infection characteristics, with recent longitudinal field and experimental studies on the SQPV dynamics in red and grey squirrel populations to better infer the mechanistic basis of the disease interaction. A key finding is that a model with either partial immunity or waning immunity and reinfection, where individuals become seropositive on the second exposure to infection, that up to now has been shown in experimental data only, can capture the key aspects of the field study observations. By fitting to SQPV epidemic observations in isolated red squirrel populations, we can infer that SQPV transmission between red squirrels is significantly (4×) higher than the transmission between grey squirrels and as a result our model shows that disease-mediated replacement of red squirrels by greys is considerably more rapid than replacement in the absence of SQPV. Our findings recover the key results of the previous model studies, which highlights the value of simple strategic models that are appropriate when there are limited data, but also emphasise the likely complexity of immune interactions in wildlife disease and how models can help infer disease processes from field data.

Host lifespan and the evolution of resistance to multiple parasites.

Hosts are typically challenged by multiple parasites, but to date theory on the evolution of resistance has mainly focused on single infections. We develop a series of models that examine the impact of multiple parasites on the evolution of resistance under the assumption that parasites coexist at the host population scale as a consequence of superinfection. In this way, we are able to explicitly examine the impact of ecological dynamics on the evolutionary outcome. We use our models to address a key question of how host lifespan affects investment in resistance to multiple parasites. We show that investment in costly resistance depends on the specificity of the immune response and on whether or not the focal parasite leads to more acute infection than the co-circulating parasite. A key finding is that investment in resistance always increases as the immune response becomes more general independently of whether it is the focal or the co-circulating parasite that exploits the host most aggressively. Long-lived hosts always invest more than short-lived hosts in both general resistance and resistance that is specific to relatively acute focal parasites. However, for specific resistance to parasites that are less acute than co-circulating parasites it is the short-lived hosts that are predicted to invest most. We show that these results apply whatever the mode of defence, that is whether it is through avoidance or through increased recovery, with or without acquired immunity, or through acquired immunity itself. As a whole, our results emphasize the importance of considering multiple parasites in determining optimal immune investment in eco-evolutionary systems.

Deformed wing virus is a recent global epidemic in honeybees driven by Varroa mites.

Deformed wing virus (DWV) and its vector, the mite Varroa destructor, are a major threat to the world's honeybees. Although the impact of Varroa on colony-level DWV epidemiology is evident, we have little understanding of wider DWV epidemiology and the role that Varroa has played in its global spread. A phylogeographic analysis shows that DWV is globally distributed in honeybees, having recently spread from a common source, the European honeybee Apis mellifera. DWV exhibits epidemic growth and transmission that is predominantly mediated by European and North American honeybee populations and driven by trade and movement of honeybee colonies. DWV is now an important reemerging pathogen of honeybees, which are undergoing a worldwide manmade epidemic fueled by the direct transmission route that the Varroa mite provides.

The epidemiological feedbacks critical to the evolution of host immunity.

We examine in detail how epidemiological feedbacks combine with costs and benefits to determine the evolution of resistance by systematically analysing continuously stable strategies (CSS) for different host-parasite frameworks. The mode of resistance (innate versus acquired), the nature of the host (i.e. life-history and immunological memory) and the nature of the disease (effects on fertility or mortality) all impact on the feedbacks that are critical to the evolution of resistance. By identifying relationships between CSS investment and the underlying epidemiological feedback for each mode of resistance in each framework, we distil complex feedbacks into simple combinations of selection pressures. When the parasite does not affect fertility, CSS investment reflects only the benefit of resistance and we explain why this is markedly different for innate and acquired resistance. If infection has no effect on host fertility, CSS investment in acquired immunity increases with the square of disease prevalence. While in contrast for evolving innate resistance, CSS investment is greatest at intermediate prevalence. When disease impacts fertility, only a fraction of the host population reproduce, and this introduces new ecological feedbacks to both the cost of resistance and the damage from infection. The multiple feedbacks in this case lead to the alternative result that the higher the abundance of infecteds, the higher the investment in innate resistance. A key insight is that maximal investment occurs at intermediate lifespans in a range of different host-parasite interactions, but for disparate reasons which can only be understood by a detailed analysis of the feedbacks. We discuss the extension of our approach to structured host populations and parasite community dynamics.

Spatial heterogeneity lowers rather than increases host-parasite specialization.

Abiotic environmental heterogeneity can promote the evolution of diverse resource specialists, which in turn may increase the degree of host-parasite specialization. We coevolved Pseudomonas fluorescens and lytic phage ϕ2 in spatially structured populations, each consisting of two interconnected subpopulations evolving in the same or different nutrient media (homogeneous and heterogeneous environments, respectively). Counter to the normal expectation, host-parasite specialization was significantly lower in heterogeneous compared with homogeneous environments. This result could not be explained by dispersal homogenizing populations, as this would have resulted in the heterogeneous treatments having levels of specialization equal to or greater than that of the homogeneous environments. We argue that selection for costly generalists is greatest when the coevolving species are exposed to diverse environmental conditions and that this can provide an explanation for our results. A simple coevolutionary model of this process suggests that this can be a general mechanism by which environmental heterogeneity can reduce rather than increase host-parasite specialization.

Optimal immune defence in the light of variation in lifespan.

There is good evidence for costs to both the uses of immune defences and their development and maintenance. The optimal defence will be a balance of these costs with the risk of infection and the virulence of the disease. It is therefore clear that the life-history characteristics of both host and parasite will impact the optimal level of defence, and that this may in part explain the variation in immune defence against different pathogens and parasites. For instance, it has traditionally been suggested that long-lived hosts should invest in immune memory. Ecological evolutionary theory can be used to examine in detail how different host characteristics will affect the optimal immune response that evolves. Here, we review theoretical studies on the impact of host lifespan on various immune defence characteristics including acquired immunity and highlight the importance of population-level epidemiological feedbacks on the outcome. In particular, we discuss when longer-lived hosts may invest less in acquired immunity and develop new theory to highlight the importance of the mechanism of host population regulation to the outcome. We finish by discussing where more theory is needed and how comparative and experimental studies may test the theory.

Population structure of the mosquito Aedes aegypti (Stegomyia aegypti) in Pakistan.

Eleven microsatellite markers were used to determine the genetic population structure and spread of Aedes aegypti (Stegomyia aegypti) (Diptera: Culicidae) in Pakistan using mosquitoes collected from 13 different cities. There is a single genetic cluster of Ae. aegypti in Pakistan with a pattern of isolation by distance within the population. The low level of isolation by distance suggests the long-range passive dispersal of this mosquito, which may be facilitated by the tyre trade in Pakistan. A decrease in genetic diversity from south to north suggests a recent spread of this mosquito from Karachi. A strong negative correlation between genetic distance and the quality of road connections shows that populations in cities connected by better road networks are less differentiated, which suggests the human-aided passive dispersal of Ae. aegypti in Pakistan. Dispersal on a large spatial scale may facilitate the strategy of introducing transgenic Ae. aegypti or intracellular bacteria such as Wolbachia to control the spread of dengue disease in Pakistan, but it also emphasizes the need for simple measures to control container breeding sites.

Seasonality selects for more acutely virulent parasites when virulence is density dependent.

Host condition is often likely to influence parasite virulence. Furthermore, condition may often be correlated with host density, and therefore, it is important to understand the role of density-dependent virulence (DDV). We examine the consequences of DDV to the evolution of parasites in both seasonal and non-seasonal environments. In particular, we consider seasonality in host birth rate that results in a fluctuating host density and therefore a variable virulence. We show that parasites are selected for lower exploitation, and therefore lower transmission and virulence as the strength of DDV increases without seasonality. This is an important insight from our models; DDV has the opposite effect on the evolution of parasites to that of higher baseline mortality. Our key result is that although seasonality does not affect the evolution of virulence in classical models, with DDV parasites in seasonal environments are predicted to evolve to be more acute. This suggests that in more seasonal environments wildlife disease is likely to be more rather than less virulent if DDV is widespread.

A review of dengue as an emerging disease in Pakistan.

The presence of dengue virus has been detected using neutralization and haemagglutination inhibition antibodies in local populations in Pakistan since the 1960s. However, the first epidemic was not reported until 1994. This was followed by some cases in 1995, but the disease was confined to the port city of Karachi. Since 2006, dengue epidemics have occurred every year and the range has extended to most cities in Pakistan. Dengue now affects thousands of people and has caused hundreds of deaths. It has become a major health problem in Pakistan, and it is likely to become an even greater health problem in the coming years. This review gives an insight into the dengue situation from the early 1960s to the most recent epidemics in Pakistan, and also describes the primary vector of this disease (Aedes aegypti) in Pakistan. As such, it provides the first comprehensive review of the emergence of this important public health problem.

Low cost antiviral activity of Plodia interpunctella haemolymph in vivo demonstrated by dose dependent infection.

Given the ubiquity of infectious disease it is important to understand the way in which hosts defend themselves and any costs that they may pay for this defence. Despite this, we know relatively little about insect immune responses to viruses when compared to their well-characterized responses to other pathogens. In particular it is unclear whether there is significant haemocoelic response to viral infection. Here we directly examine this question by examining whether there is a dose-dependency in infection risk when a DNA virus is injected directly into the haemocoel. Infection from direct injection into the haemocoel showed a clear dose dependency that is indicative of an active intrahaemocoelic immune response to DNA viruses in insects. In contrast to the natural oral infection route, we found no measurable sublethal effects in the survivors from direct injection. This suggests that the immune responses in the haemocoel are less costly than those that occur earlier.

The evolution of host-parasite range.

Understanding the coevolution of hosts and parasites is one of the key challenges for evolutionary biology. In particular, it is important to understand the processes that generate and maintain variation. Here, we examine a coevolutionary model of hosts and parasites where infection does not depend on absolute rates of transmission and defense but is approximately all-or-nothing, depending on the relative levels of defense and infectivity of the host and the parasite. We show that considerable diversity can be generated and maintained because of epidemiological feedbacks, with strains differing in the range of host and parasite types they can respectively infect or resist. Parasites with broad and narrow ranges therefore coexist, as do broadly and narrowly resistant hosts, but this diversity occurs without the assumption of highly specific gene interactions. In contrast to gene-for-gene models, cycling in strain types is found only under a restrictive set of circumstances. The generation of diversity in both hosts and parasites is dependent on the shape of the trade-off relationships but is more likely in long-lived hosts and chronic disease with long infectious periods. Overall, our model shows that significant diversity in infectivity and resistance range can evolve and be maintained from initially monomorphic populations.

Examining the relationship between hemolymph phenoloxidase and resistance to a DNA virus, Plodia interpunctella granulosis virus (PiGV).

We have a detailed understanding of invertebrate immune responses to bacteria and fungal pathogens, but we know less about how insects respond to virus challenge. Phenoloxidase (PO) functions as an important immune response against many parasites and pathogens and is routinely used as a measure of immune competance. We examine the role of haemolymph PO activity in Plodia interpuncetella's response to its natural granulosis virus (PiGV). Larvae were challenged with virus by both oral inoculation of occluded virus (the natural infection route) and direct intrahaemocoelic injection of budded virus. Haemolymph was collected at time points post-viral challenge using a novel method that allows the volume of haemolymph to be quanitified. The haemolmyph was collected without killing the larvae so that haemolymph samples from individuals that developed viral disease could be distinguished from samples collected from those that fought off infection. The level of haemolymph PO activity in resistant larvae did not differ from control larvae. Therefore we have no evidence that PO is involved in resistance to virus in the haemocoel whether larvae are challenged naturally by oral innoculation or directly by intraheamocoelic injection. Phenoloxidase may therefore not be a relevant metric of immunocompetence for viral infection.

Maintenance of host variation in tolerance to pathogens and parasites.

Tolerance and resistance provide hosts with two distinct defense strategies against parasitism. In resistance the hosts "fight" the parasite directly, whereas in tolerance the hosts fight the disease by ameliorating the damage that infection causes. There is increasing recognition that the two mechanisms may exhibit very different evolutionary behaviors. Although empirical work has often noted considerable variance in tolerance within hosts, theory has predicted the fixation of tolerance due to positive frequency dependence through a feedback with disease prevalence. Here we reconcile these findings through a series of dynamic game theoretical models. We emphasize that there is a crucial distinction between tolerance to the effects of disease-induced mortality and tolerance to the effect of the disease-induced reductions in fecundity. Only mortality tolerance has a positive effect on parasite fitness, whereas sterility tolerance is neutral and may therefore result in polymorphisms. The nature of the costs to defense and their relationship to trade-offs between resistance and tolerance are crucial in determining the likelihood of variation, whereas the co-evolution of the parasite will not affect diversity. Our findings stress that it is important to measure the effects of different mechanisms on characteristics that affect the epidemiology of the parasite to completely understand the evolutionary dynamics of defense.

Effects of blood and virus-infected blood on protein expression in the midgut of the dengue vector Aedes albopictus.

Although the mosquito midgut is the primary site of bloodmeal storage and the first line of defence against pathogenic infection, little is known about its proteic composition at a time when an increasing number of proteins are reported to impair viral infection. Aedes albopictus Skuse (Diptera: Culicidae) is an important vector of the dengue virus. We compared 2-dimensional protein profiles of the adult midgut in this species, taking into account bloodmeal status. The comparison of profiles from sugar-fed and blood-fed females showed that a considerable number of proteins were present in both midguts. In addition, one set of proteins was present only after sugar intake and another set only after blood intake. The comparison of profiles of blood-fed midguts and dengue virus-2 infected blood-fed midguts revealed that at least six proteins were present only in the infected midguts. These results are discussed in the context of the identification of midgut proteins involved in the dengue virus infection process.

Interference and the persistence of vertically transmitted parasites.

Given their ubiquity in nature, understanding the factors that allow the persistence of multiple enemies and in particular vertically transmitted parasites (VTPs) is of considerable importance. Here a model that allows a virulent VTP to be maintained in a system containing a host and a horizontally transmitted parasite (HTP) is analysed. The method of persistence relies on the VTP offering the host a level of protection from the HTP. The VTP is assumed to reduce the HTPs ability to transmit to the host through ecological interference. We show that VTPs are more likely to persist with HTPs that prevent host reproduction than with those that allow it. The VTP persists more easily in r-selected hosts and with highly transmittable HTPs. As the level of protection through interference increases the densities of the host also increase. We also show that VTPs when they do persist tend to stabilise the host population cycles produced by free-living HTPs. The study raised questions about persistence of diseases through interactions with others, and also the stabilising effects of VTPs on dynamical systems in a biological control context.

Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok.

Dengue virus, the causative agent of dengue fever and its more serious manifestation dengue hemorrhagic fever, is widespread throughout tropical and subtropical regions. The virus exists as four distinct serotypes, all of which have cocirculated in Bangkok for several decades with epidemic outbreaks occurring every 8-10 years. We analyze time-series data of monthly infection incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and 3 occurring at approximately the same time and an isolated epidemic of serotype 4 occurring in the intervening years. Phylogenetic analysis of virus samples collected over the same period shows that clade replacement events are linked to the epidemic cycle and indicates that there is an interserotypic immune reaction. Using an epidemic model with stochastic seasonal forcing showing 8- to 10-year epidemic oscillations, we demonstrate that moderate cross-protective immunity gives rise to persistent out-of-phase oscillations similar to those observed in the data, but that strong or weak cross-protection or cross-enhancement only produces in-phase patterns. This behavior suggests that the epidemic pattern observed in Bangkok is the result of cross-protective immunity and may be significantly altered by changes in the interserotypic immune reaction.

An indirect approach to imply trade-off shapes: population level patterns in resistance suggest a decreasingly costly resistance mechanism in a model insect system.

Trade-offs between life history and other traits play a key role in shaping the evolution of individuals. It is well established theoretically that the shapes of trade-off curves are as crucial to the evolutionary outcome as their strengths. However, measuring the shape of these relationships directly is often impractical. Here we use an indirect approach that examines the patterns seen within a population and then use theory to infer the shape of the trade-off curve. Using a bioassay we found that most individuals had either high susceptibility or relatively high resistance to a microparasite in a lepidopteran host population. According to general theory, this type of pattern in resistance would be most likely with a deceleratingly costly impact on fitness of increasing resistance. The implications and generality of the approach are discussed, along with the implications of the results to our understanding of the nature of innate resistance to parasites.

Spatiotemporal patterns of malaria incidence in northern Thailand.

We present a detailed analysis of long-term time series of malaria incidence in northern Thailand. Positive cases for Plasmodium falciparum and P. vivax have been recorded monthly from 1977-2002 at 13 provinces in the region. Time series statistical methods are used to examine the long-term trends and seasonal dynamics of malaria incidence at regional and provincial scales. Both malarial types are declining throughout the region, except in the two provinces that share a large border with Myanmar. The rate of decline in P. vivax has decreased across the region since the end of the 1980s, and this may be a signal of developing resistance or changing vector potential. Both species display a two-peak annual seasonality that may be attributed to patterns of vector occurrence, farming practice and migration of individuals across international borders. In a number of provinces, the importance of the first seasonal peak has grown in recent years, possibly owing to increases in vector densities. The medium-term fluctuations of both species exhibit a clear spatial organisation. There is some evidence of a subtle close to 4-year super annual cycle in P. falciparum, which we suggest is driven by extrinsic factors relating to the climate of the region.