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Uncovering drivers of community assembly is a key aspect of learning how biological communities function. Drivers of community similarity can be especially useful in this task as they affect assemblage-level changes that lead to differences in species diversity between habitats. Concepts of β-diversity originally developed for use in free-living communities have been widely applied to parasite communities to gain insight into how infection risk changes with local conditions by comparing parasite communities across abiotic and biotic gradients. Factors shaping β-diversity in communities of immature parasites, such as larvae, are largely unknown. This is a key knowledge gap as larvae are frequently the infective life-stage and understanding variation in these larval communities is thus key for disease prevention. Our goal was to uncover links between β-diversity of parasite communities at different life stages; therefore, we used gastrointestinal nematodes infecting African buffalo in Kruger National Park, South Africa to investigate within-host and extra-host drivers of adult and larval parasite community similarity. We employed a cross-sectional approach using PERMANOVA that examined each worm community at a single time point to assess independent drivers of β-diversity in larvae and adults as well as a longitudinal approach with path analysis where adult and larval communities from the same host were compared to better link drivers of β-diversity between these two life stages. Using the cross-sectional approach, we generally found that intrinsic, within-host traits had significant effects on β-diversity of adult nematode communities, while extrinsic, extra-host variables had significant effects on β-diversity of larval nematode communities. However, the longitudinal approach provided evidence that intrinsic, within-host factors affected the larval community indirectly via the adult community. Our results provide key data for the comparison of community-level processes where adult and immature stages inhabit vastly different habitats (i.e. within-host vs. abiotic environment). In the context of parasitism, this helps elucidate host infection risk via larval stages and the drivers that shape persistence of adult parasite assemblages, both of which are useful for predicting and preventing infectious disease.

Transitional zones, such as edge habitat, are key landscapes for investigating biodiversity. "Soft edges" are permeable corridors that hosts can cross, while "hard edges" are impermeable borders that hosts cannot pass. Although pathogen transmission in the context of edges is vital to species conservation, drivers of host-parasite relationships in ecological edges remain poorly understood. Thus, we defined a framework for testing hypotheses of host-parasite interactions in hard and soft edges by (1) characterizing hard and soft edges from both the host and parasite perspectives, (2) predicting the types of parasites that would be successful in each type of edge, and (3) applying our framework to species invasion fronts as an example of host-parasite relationships in a soft edge. Generally, we posited that parasites in soft edges are more likely to be negatively affected by habitat fragmentation than their hosts because they occupy higher trophic levels but parasite transmission would benefit from increased host connectivity. Parasites along hard edges, however, are at higher risk of local extinction due to host population perturbations with limited opportunity for parasite recolonization. We then used these characteristics to predict functional traits that would lead to parasite success along soft and hard edges. Finally, we applied our framework to invasive species fronts to highlight predictions regarding host connectivity and parasite traits in soft edges. We anticipate that our work will promote a more complete discussion of habitat connectivity using a common framework and stimulate empirical research into host-parasite relationships within ecological edges and transitional zones.

We investigated the performance trade-offs of fleas (Siphonaptera) while adapting to a novel host using two host generalists (Xenopsylla conformis and Xenopsylla ramesis) and one host specialist (Parapulex chephrenis) maintained on their principal hosts (Meriones crassus for Xenopsylla and Acomys cahirinus for P. chephrenis). We asked whether, over generations, (i) a host generalist may become a specialist by evolving the ability to exploit a novel host and losing the ability to exploit an original host and (ii) a host specialist can become a generalist by evolving the ability to exploit a novel host without losing the ability to exploit an original host. We established an experimental line of each species on a novel host (Acomys russatus for Xenopsylla and M. crassus for P. chephrenis) and maintained this line on this host during 23 generations. We compared reproductive performance of progenitors of each line and their descendants when they exploited either original or novel host in terms of egg number and size, hatching success, offspring production, and offspring size. We found changes in performance over generations in female offspring size only. Xenopsylla conformis demonstrated a tendency to become a host specialist (increased performance on the novel host with a concomitant decreased performance on the original host), whereas P. chephrenis demonstrated a tendency to become a host generalist (increased performance on the novel host without a concomitant decreased performance on the original host). We conclude that the probability of generalist to specialist transition, and vice versa, is context-dependent and varies between species.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

We studied the success of fleas, Synosternus cleopatrae and Xenopsylla ramesis, in switching to a novel host by establishing experimental lines maintained on different hosts for 18 generations. Fleas fed on principal (P-line) or novel hosts, either sympatric with (S-line) or allopatric to (A-line) a flea and its principal host, then we assessed their reproductive performance via the number and size of eggs. We compared reproductive performance between hosts within a line and between lines within a host asking: (a) whether fleas adapt to a novel host species after multiple generations; (b) if yes, whether the pattern of adaptation differs between novel host species sympatric with or allopatric to a flea and its principal host; and (c) adaptation to a novel host is accompanied with a loss of success in exploitation of an original host. Fleas from the S- and A-lines increased their egg production on a novel host (except X. ramesis from the S-line). S. cleopatrae from the S-line but not the A-line increased egg size on a novel host, whereas X. ramesis from the A-line but not the S-line produced larger eggs from a novel host. We found no indication of a loss of reproductive performance on the original host while adapting to a novel host. We conclude that fleas are able to switch rapidly to a new host with the pattern of a switch to either sympatric or an allopatric host depending on the identities of both flea and host species.

Frailty is a distinctive health state in which the ability of older people to cope with acute stressors is compromised by an increased vulnerability brought by age-associated declines in physiological reserve and function across multiple organ systems. Although closely associated with age, multimorbidity, and disability, frailty is a discrete syndrome that is associated with poorer outcomes across a range of medical conditions. However, its role in cerebrovascular disease and stroke has received limited attention. The estimated rise in the prevalence of frailty associated with changing demographics over the coming decades makes it an important issue for stroke practitioners, cerebrovascular research, clinical service provision, and stroke survivors alike. This review will consider the concept and models of frailty, how frailty is common in cerebrovascular disease, the impact of frailty on stroke risk factors, acute treatments, and rehabilitation, and considerations for future applications in both cerebrovascular clinical and research settings.

ObjectiveThe efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response.MethodsA cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry.ResultsThirty-five participants completed, on average, 85 hours (IQR=70–100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen’s d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes.ConclusionsIndividuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay.Trial registration numberNCT02540889.

Drylands comprise over 41% of all terrestrial surface area and are home to approximately 35.5% of the world's population; however, both free-living and parasitic fauna of these regions remain relatively understudied. Yet, the very conditions that make these regions challenging to study – extreme environmental conditions and low population density for various organisms – also make them potentially untapped natural laboratories for examining eco-evolutionary relationships between hosts and parasites. Adaptations and ecological patterns illustrated by desert parasite communities can serve as exemplars within the extremes regarding the evolution of virulence, breadth of host spectra, and lifecycle strategies. This review provides relevant examples for each of these three topics using parasites from dryland regions in order to encourage future empirical tests of hypotheses regarding parasite ecology and evolution within dryland ecosystems and stimulate wider investigation into the parasitofauna of arid regions in general. As global climate changes and anthropogenic disturbance increases, desertification is a growing problem which has been labeled as a threat to global health. Thus, deserts not only provide useful natural laboratories in which to study parasite transmission but understanding parasite transmission within these habitats becomes increasingly important as larger, likely highly resource insecure, populations are projected to live on the margins of desert regions in the future., Graphical abstract Image 1, Highlights • Drylands comprise over 41% of Earth's surface but their parasites are understudied. • Desert parasite communities are exemplars within the extremes of parasite ecology. • Can test hypotheses of virulence evolution, host spectra, and lifecycle strategies. • Drylands can provide increasingly important insight into parasite transmission. • Larger human populations are projected to live in arid regions as climate changes.

Objectives This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-NaF]) could predict restenosis following PTA. Background Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty. Methods In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18F-FDG and 18F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months. Results Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (18F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p, Central Illustration

To model the colonization of a novel host by fleas,Synosternus cleopatraeandXenopsylla ramesis, we established experimental lines maintained for 15 generations on a principal or a novel host (either co-occurring with a flea or not). We compared the blood meal size and the energy expended for digestion by fleas from the 15thgeneration of each line on these hosts between hosts within a line and between lines within a host asking (a) whether fleas adapt to a novel host (increased blood consumption/decreased energy expended for digestion); (b) if yes, whether this adaptation leads to the loss of ability to exploit an original host, and (c) whether the success of adaptation to a novel host depends on its ecological co-occurrence with a flea. The blood consumption and digestion energetics of fleas fed on the principal host differed from those on other hosts. The effect of the principal host on feeding performance differed between fleas, withS. cleopatraeconsuming less blood and expending more energy for digestion on the principal than on any other host, whereas the opposite was true forX. ramesis. No changes in feeding performance on a novel host over generations were found. We propose several explanations for the lack of adaptation to a novel host over time. We explain the poor performance ofS. cleopatraeon its principal hostviaits immune response mounting pattern. We argue that the principal host of a parasite is not necessarily the host on which the parasite demonstrates the best performance.

ObjectivesTimely thrombolysis of ischaemic stroke improves functional recovery, yet its delivery nationally is challenging due to shortages in the stroke specialist workforce and large geographical areas. One solution is remote stroke specialist input to regional centres via telemedicine. This study evaluates the usage and key metrics of performance of the East of England Stroke Telemedicine Partnership—the largest telestroke service in the UK—in providing hyperacute stroke care.DesignProspective observational study.SettingThe East of England Stroke Telemedicine Partnership provides a horizontal ‘hubless’ model of out-of-hours hyperacute stroke care to a population of 6.2 million across a 7500 square mile semirural region.ParticipantsAll (2709) telestroke consultations between 1 January 2014 and 31 December 2019.Main outcome measuresThrombolysis decision, pre-thrombolysis and post-thrombolysis stroke severity (National Institutes of Health Stroke Scale, NIHSS), haemorrhagic complications, and hyperacute pathway timings.ResultsOver the period, 1149 (42.4%) individuals were thrombolysed. Thrombolysis rates increased from 147/379 (38.8%) in 2014 to 225/490 (45.9%) in 2019. Median (IQR) pre-thrombolysis NIHSS was 10 (6–17), reducing to 6 (2–14) 24-hour post-thrombolysis (pConclusionsThe results from this large hyperacute telestroke cohort indicate two important points for clinical practice. First, telemedicine via a hubless horizontal model provides a clinically effective and safe method for delivering hyperacute stroke thrombolysis. Second, improved door-to-needle times were offset by a concerning rise in prehospital timings. These findings indicate that although telemedicine may benefit in-hospital hyperacute stroke care, improvements across the whole stroke pathway are essential.

Sepsis can lead to cardiac arrhythmias, of which the most common is atrial fibrillation (AF). Sepsis is associated with up to a six-fold higher risk of developing AF, where it occurs most commonly in the first 3 days of hospital admission. In many patients, AF detected during sepsis is the first documented episode of AF, either as an unmasking of sub-clinical AF or as a newly developed arrhythmia. In the short term, sepsis that is complicated by AF leads to longer hospital stays and an increased risk of inpatient mortality. Sepsis-driven AF can also increase an individual's risk of inpatient stroke by nearly 3-fold, compared to sepsis patients without AF. In the long-term, it is estimated that up to 50% of patients have recurrent episodes of AF within 1-year of their episode of sepsis. The common perception that once the precipitating illness is treated or sinus rhythm is restored the risk of stroke is removed is incorrect. For clinicians, there is a paucity of evidence on how to reduce an individual's risk of stroke after developing AF during sepsis, including whether to start anticoagulation. This is pertinent when considering that more patients are surviving episodes of sepsis and are left with post-sepsis sequalae such as AF. This review provides a summary on the literature available surrounding sepsis-driven AF, focusing on AF recurrence and ischaemic stroke risk. Using this, pragmatic advice to clinicians on how to better detect and reduce an individual's stroke risk after developing AF during sepsis is discussed.

Funder: NIHR School for Primary Care Research; doi: http://dx.doi.org/10.13039/501100013374, Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272, Background: Levels of self-reported health do not always correlate with levels of physical disability in stroke survivors. We aimed to explore what underlies the difference between subjective self-reported health and objectively measured disability among stroke survivors. Methods: Face to face semi-structured interviews were conducted with stroke survivors recruited from a stroke clinic or rehabilitation ward in the UK. Fifteen stroke survivors purposively sampled from the clinic who had discordant self-rated health and levels of disability i.e. reported health as ‘excellent’ or ‘good’ despite significant physical disability (eight), or as ‘fair’ or ‘poor’ despite minimal disability (seven) were compared to each other, and to a control group of 13 stroke survivors with concordant self-rated health and disability levels. Interviews were conducted 4 to 6 months after stroke and data analysed using the constant comparative method informed by Albrecht and Devlieger’s concept of ‘disability paradox’. Results: Individuals with ‘excellent’ or ‘good’ self-rated health reported a sense of self-reliance and control over their bodies, focussed on their physical rehabilitation and lifestyle changes and reported few bodily and post-stroke symptoms regardless of level of disability. They also frequently described a positive affect and optimism towards recovery. Some, especially those with ‘good’ self-rated health and significant disability also found meaning from their stroke, reporting a spiritual outlook including practicing daily gratitude and acceptance of limitations. Individuals with minimal disability reporting ‘fair’ or ‘poor’ self-rated health on the other hand frequently referred to their post-stroke physical symptoms and comorbidities and indicated anxiety about future recovery. These differences in psychological outlook clustered with differences in perception of relational and social context including support offered by family and healthcare professionals. Conclusions: The disability paradox may be illuminated by patterns of individual attributes and relational dynamics observed among stroke survivors. Harnessing these wider understandings can inform new models of post-stroke care for evaluation.

Transitional zones, such as edge habitat, are key landscapes for investigating biodiversity. "Soft edges" are permeable corridors that hosts can cross, while "hard edges" are impermeable borders that hosts cannot pass. Although pathogen transmission in the context of edges is vital to species conservation, drivers of host-parasite relationships in ecological edges remain poorly understood. Thus, we defined a framework for testing hypotheses of host-parasite interactions in hard and soft edges by (1) characterizing hard and soft edges from both the host and parasite perspectives, (2) predicting the types of parasites that would be successful in each type of edge, and (3) applying our framework to species invasion fronts as an example of host-parasite relationships in a soft edge. Generally, we posited that parasites in soft edges are more likely to be negatively affected by habitat fragmentation than their hosts because they occupy higher trophic levels but parasite transmission would benefit from increased host connectivity. Parasites along hard edges, however, are at higher risk of local extinction due to host population perturbations with limited opportunity for parasite recolonization. We then used these characteristics to predict functional traits that would lead to parasite success along soft and hard edges. Finally, we applied our framework to invasive species fronts to highlight predictions regarding host connectivity and parasite traits in soft edges. We anticipate that our work will promote a more complete discussion of habitat connectivity using a common framework and stimulate empirical research into host-parasite relationships within ecological edges and transitional zones.

Both parasitism and social contact are common sources of stress that many gregarious species encounter in nature. Upon encountering such stressors, individuals secrete glucocorticoids and although short-term elevation of glucocorticoids is adaptive, long-term increases are correlated with higher mortality and deleterious reproductive effects. Here, we used an experimental host-parasite system, social rodents Acomys cahirinus and their characteristic fleas Parapulex chephrenis, in a fully-crossed design to test the effects of social contact and parasitism on stress during pregnancy. By analysing faecal glucocorticoid metabolites, we found that social hierarchy did not have a significant effect on glucocorticoid concentration. Rather, solitary females had significantly higher glucocorticoid levels than females housed in pairs. We found a significant interaction between the stressors of parasitism and social contact with solitary, uninfested females having the highest faecal glucocorticoid metabolite levels suggesting that both social contact and infestation mitigate allostatic load in pregnant rodents. Therefore, the increased risk of infestation that accompanies group-living could be outweighed by positive aspects of social contact within A. cahirinus colonies in nature.

We tested whether and how the maternal environment (i.e. host species exploited by a mother), rearing conditions (i.e. host species exploited by her offspring) or both (i.e. matches and mismatches in host species exploited by a mother and her offspring) affect reproductive performance in the offspring. We experimentally manipulated maternal and rearing environments in two generalist fleas (Xenopsylla conformis and Xenopsylla ramesis) implementing a factorial cross-rearing design. Mothers exploited either the principal host (PH) or auxiliary hosts that were either closely (CAH) or distantly related (DAH) to the PH. After six generations of infesting a given host species, we cross-reared fleas within and between host species. These fleas reproduced and we measured their reproductive performance both quantitatively (i.e. egg number) and qualitatively (i.e. egg size, development time, body size of the next generation). We found that identity of the host a flea was reared on (=actual host) had the strongest effect on its performance. Individuals reared on the PH performed considerably better than those reared on either auxiliary host. Moreover, fleas reared on a CAH performed better than those reared on a DAH. Actual host identity also had a stronger effect on reproductive performance in X. ramesis than in X. conformis. Nevertheless, there was no difference in performance between match and mismatch maternal and actual host identities. We conclude that rearing environment has the strongest effect on fitness in generalist parasites. Moreover, phylogenetic distance between an auxiliary host and the PH determines the level of suitability of the former.

Parasites can cause a broad range of sublethal fitness effects across a wide variety of host taxa. However, a host's efforts to compensate for possible parasite-induced fitness effects are less well-known. Parental effects may beneficially alter the offspring phenotype if parental environments sufficiently predict the offspring environment. Parasitism is a common stressor across generations; therefore, parental infestation could reliably predict the likelihood of infestation for offspring. However, little is known about relationships between parasitism and transgenerational phenotypic plasticity. Thus, we investigated how maternal and grandmaternal infestation with fleas (Xenopsylla ramesis) affected offspring quality and quantity in a desert rodent (Meriones crassus). We used a fully-crossed design with control and infested treatments to examine litter size, pup body mass at birth, and pup mass gain before weaning for combinations of maternal and grandmaternal infestation status. No effect of treatment on litter size or pup body mass at birth was found. However, maternal and grandmaternal infestation status significantly affected pre-weaning body mass gain, a proxy for the rate of maturation, in male pups. Pups gained significantly more weight before weaning if maternal and grandmaternal infestation statuses matched, regardless of the treatment. Thus, pups whose mothers and grandmothers experienced similar risks of parasitism, either both non-parasitized or both infested, would reach sexual maturity more quickly than those pups whose mothers' infestation status did not match that of their grandmothers. These results support the contention that parents can receive external cues such as the risk of parasitism, that prompt them to alter offspring provisioning. Therefore, parasites could be a mediator of environmentally-induced maternal effects and could affect host reproductive fitness across multiple generations.

We tested whether biogeographic patterns characteristic of species diversity and composition may also apply to community assembly by investigating geographic variation in the pattern (PSA) (aggregation versus segregation) and strength of species associations (SSA) in flea and mite communities harbored by small mammalian hosts in Western Siberia. We asked whether (a) there is a relationship between latitude and PSA or SSA and (b) similarities in PSA or SSA follow a distance decay pattern or if they are better explained by variation in environmental factors (altitude, amount of vegetation, precipitation, and air temperature). We used a sign of a co-occurrence metric (the C-score) as an indicator of PSA and its absolute standardized value as a measure of SSA. We analyzed data using logistic and linear models, generalized dissimilarity modeling (GDM), and a logistic version of the multiple regression on distance matrices (MRM). The majority of the C-scores of the observed presence/absence matrices indicated a tendency to species aggregation rather than segregation. No effect of latitude on PSA or SSA was found. The dissimilarity in PSA was affected by environmental dissimilarity in mite compound communities only. A relatively large proportion of the deviance of spatial variation in SSA was explained by the GDMs in infracommunities, but not component communities, and in only three (of seven) and two (of eight) host species of fleas and mites, respectively. The best predictors of dissimilarity in SSA in fleas differed between host species, whereas the same factor (precipitation) was the best predictor of dissimilarity in SSA in mites. We conclude that PSA and SSA in parasite communities rarely conform to biogeographic rules. However, when a biogeographic pattern is detected, its manifestation differs among hosts and between ectoparasite taxa.

We studied patterns of phylogenetic and compositional diversity of fleas parasitic on small mammals and asked whether these patterns are affected by environmental variation or evolutionary/historical processes. We considered environmental variation via both off‐host (air temperature, precipitation, the amount of green vegetation, latitude) and host‐associated (phylogenetic and species composition) environments. The indicators of evolutionary/historical processes were phylogenetic and compositional uniqueness estimated via phylogenetic or compositional, respectively, β‐diversity of either fleas or hosts. We found that phylogenetic uniqueness of flea assemblages was the main predictor of their phylogenetic diversity in all realms. In addition, host phylogenetic diversity and uniqueness played also some role in the Palearctic, whereas the effect of the off‐host environment was either extremely weak or absent. Compositional diversity of fleas was consistently affected by compositional diversity of hosts in all realms except the Neotropics. The effect of the off‐host environment on compositional flea diversity was substantial in all realms except the Palearctic. No effect of latitude on either metric of flea diversity was found. We conclude that phylogenetic diversity of fleas is driven mainly by evolutionary/historical processes, whereas drivers of their compositional diversity are associated with current ecological conditions.

Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk.

BACKGROUNDChronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied.METHODSWe conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death).RESULTSFrom August 2015 through November 2019, a total of 748 patients were included in the trial after randomization — 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, −6.4 percentage points [95% confidence interval, −11.4 to −1.4] in favor of the placebo group; P=0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group.CONCLUSIONSAmong adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810. opens in new tab.)

We studied the success of fleas, Synosternus cleopatrae and Xenopsylla ramesis, in switching to a novel host by establishing experimental lines maintained on different hosts for 18 generations. Fleas fed on principal (P-line) or novel hosts, either sympatric with (S-line) or allopatric to (A-line) a flea and its principal host, then we assessed their reproductive performance via the number and size of eggs. We compared reproductive performance between hosts within a line and between lines within a host asking: (a) whether fleas adapt to a novel host species after multiple generations; (b) if yes, whether the pattern of adaptation differs between novel host species sympatric with or allopatric to a flea and its principal host; and (c) adaptation to a novel host is accompanied with a loss of success in exploitation of an original host. Fleas from the S- and A-lines increased their egg production on a novel host (except X. ramesis from the S-line). S. cleopatrae from the S-line but not the A-line increased egg size on a novel host, whereas X. ramesis from the A-line but not the S-line produced larger eggs from a novel host. We found no indication of a loss of reproductive performance on the original host while adapting to a novel host. We conclude that fleas are able to switch rapidly to a new host with the pattern of a switch to either sympatric or an allopatric host depending on the identities of both flea and host species.

Background Carotid artery atherosclerosis is an important cause of ischaemic stroke. In oncology, textural analysis (“radiomics”) of computed tomography (CT) images can predict the metastatic potential and prognosis of several types of malignant tumours. We investigated whether this quantitative approach could be applied in carotid artery disease. Purpose (1) To evaluate the feasibility of computed tomography angiography (CTA) texture analysis in differentiating symptomatic from asymptomatic patients. (2) To investigate whether CTA carotid texture analysis can identify culprit lesions in patients with stroke and transient ischaemic attack (TIA). Methods Carotid CTAs of consented research subjects were included in the study. Symptomatic patients had confirmed carotid artery-related ischaemic stroke or TIA in the 7 days before CTA imaging. Asymptomatic (ASX) patients had no prior stroke/TIA. Both TexRAD, a research texture analysis software, and PyRadiomics, a Python package for radiomics studies, were used to extract 99 first-order and higher-order texture features from regions-of-interest (ROI) drawn around the outer wall of the carotid artery. Single-slice analysis compared the carotid bifurcations of symptomatic and asymptomatic patients, and of culprit (CC) and non-culprit (NC) arteries in symptomatic patients. Multi-slice analysis was conducted using a 3D volume defined by ROIs drawn on 14 consecutive CT slices of 3mm thickness, covering 3cm of carotid artery. The Mann-Whitney U test was used for inter-subject comparisons (ASX vs CC; ASX vs NC) and the Wilcoxon signed-rank test was used for intra-subject comparisons (CC vs NC). A p value Results The dataset comprised 82 carotid arteries from 41 symptomatic patients (41 culprit; 41 non-culprit) and 50 carotid arteries from 25 asymptomatic patients. Single-slice analysis revealed greater homogeneity in asymptomatic carotids versus symptomatic culprit carotids (Uniformity: ASX 0.11 (0.05); CC 0.08 (0.05), p Conclusion Textural analysis of carotid CTAs reveal significant differences between symptomatic and asymptomatic patients and between culprit and non-culprit carotid arteries within symptomatic patients. This approach could be used to identify patients at high risk of further stroke for aggressive medical therapy and surveillance. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): EPVL is undertaking a PhD funded by the Cambridge School of Clinical Medicine and the Medical Research Council's Doctoral Training Partnership

Background Convolutional neural networks (CNNs), part of deep learning, are used widely for computer vision tasks and in some medical domains, such as mammography interpretation. The application of deep learning to carotid artery imaging is scarce. We investigated the ability of deep learning to correctly classify contrast CT images of the carotid arteries without the need for prior feature selection. Purpose (1) To assess the ability of deep learning to differentiate symptomatic patients (had prior stroke or transient ischaemic attack [TIA]) from asymptomatic patients (no prior stroke/TIA) using contrast CT scans alone. (2) To investigate whether deep learning can further discriminate between culprit and non-culprit carotid arteries in symptomatic patients. (3) To assess the interpretability of the deep learning models. Methods Carotid contrast CT scans of consented research subjects were included in the study. Symptomatic patients had confirmed carotid artery-related ischaemic stroke or TIA in the 7 days before CT imaging, and asymptomatic patients had no prior cerebrovascular events. The dataset comprised 1148 axial symptomatic slices (covering a 3cm area of each carotid artery in 41 patients; 41 culprit and 41 non-culprit carotids) and 700 asymptomatic slices (from the bilateral carotid arteries of 25 patients). The dataset was split such that 75% was used for training and 25% for testing. A 30x30 bounding box was used to create patches of the carotid arteries from these axial slices for use as input to the CNN, a modified VGG16 architecture initialised with ImageNet weights to leverage transfer learning (the application of a model trained in one domain to a different domain) implemented in Python. Data augmentation was applied to the training set and the model was trained for 100 epochs using a cyclic learning rate, the RMSProp optimizer and binary cross-entropy loss. Class activation heatmaps were generated using the GradCAM method to highlight the areas of the image that were most important to the model for making its classification decision. Results The deep learning model was 92% accurate in correctly identifying carotid arteries from symptomatic patients versus those from asymptomatic patients. Discriminating between culprit versus non-culprit carotid arteries in symptomatic patients alone was 71% accurate. The class activation heatmaps demonstrated how the model learnt to localise the carotid artery within the image patch, and to ignore the arterial lumen when making its classification decision. Conclusions Deep learning can be used to differentiate between symptomatic and asymptomatic carotid CT scans from stroke/TIA subjects without the need for prior feature engineering. The model learns to identify relevant features in the image that predict the patients' symptom state. If further validated, this approach could be used to identify high-risk patients for intensive medical therapy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): EPVL is undertaking a PhD funded by the Cambridge School of Clinical Medicine and the Medical Research Council's Doctoral Training Partnership

Nursing home placement after stroke indicates a poor outcome but numbers placed vary between hospitals. The aim of this study is to determine whether between-hospital variations in new nursing home placements post-stroke are reliant solely on case-mix differences or whether service heterogeneity plays a role. A prospective, multi-center cohort study of acute stroke patients admitted to eight National Health Service acute hospitals within the Anglia Stroke and Heart Clinical Network between 2009 and 2011 was conducted. We modeled the association between hospitals (as a fixed-effect) and rates of new discharges to nursing homes using multiple logistic regression, adjusting for important patient risk factors. Descriptive and graphical data analyses were undertaken to explore the role of hospital characteristics. Of 1335 stroke admissions, 135 (10%) were discharged to a nursing home but rates varied considerably from 6% to 19% between hospitals. The hospital with the highest adjusted odds ratio of nursing home discharges (OR 4.26, 95% CI 1.69 to 10.73), was the only hospital that did not provide rehabilitation beds in the stroke unit. Increasing hospital size appeared to be related to an increased odds of nursing home placement, although attenuated by the number of hospital stroke admissions. Our results highlight the potential influence of hospital characteristics on this important outcome, independently of patient-level factors.

Funder: University of Cambridge, The prolonged mechanical ventilation that is often required by patients with severe COVID-19 is expected to result in significant intensive care unit-acquired weakness (ICUAW) in many of the survivors. However, in our post-COVID-19 follow-up clinic we have found that, as well as the anticipated global weakness related to loss of muscle mass, a significant proportion of these patients also have disabling focal neurological deficits relating to multiple axonal mononeuropathies. Amongst the 69 patients with severe COVID-19 that have been discharged from the intensive care units in our hospital, we have seen 11 individuals (16%) with such a mononeuritis multiplex. In many instances, the multi-focal nature of the weakness in these patients was initially unrecognised as symptoms were wrongly assumed to relate simply to “critical illness neuromyopathy”. While mononeuropathy is well recognised as an occasional complication of intensive care, our experience suggests that such deficits are surprisingly frequent and often disabling in patients recovering from severe COVID-19.

The prolonged mechanical ventilation required by patients with severe COVID-19 is expected to result in significant Intensive Care Unit – Acquired Weakness (ICUAW) in many of the survivors. However, in our post-COVID-19 follow up clinic we have found that, as well as the anticipated global weakness related to loss of muscle mass, a significant proportion of these patients also have disabling focal neurological deficits relating to an axonal mononeuritis multiplex. Amongst the 69 patients with severe COVID-19 that have been discharged from the intensive care units in our hospital, we have seen 11 individuals (16%) with such neuropathies. In many instances, the multi-focal nature of the weakness in these patients was initially unrecognised as symptoms were wrongly assumed to simply relate to “critical illness neuropathy”. While mononeuropathy is well recognised as an occasional complication of intensive care, our experience suggests that such deficits are common and frequently disabling in patients recovering from COVID-19.

Biotic and abiotic stressors impose various fitness costs on individuals across a variety of taxa. In vertebrates, these stressors typically trigger complex neuroendocrine responses that stimulate glucocorticoid (GC) secretion from the adrenal cortex. Short-term elevation of GCs can be adaptive as it shifts energy toward physiological processes that cope with acute stressors; however, chronic increases in GC levels could have detrimental effects on fitness. Parasitism can be considered an important biotic stressor in nature and a possible cause of reproductive failure that could substantially affect an individual’s fitness. Thus, we aimed to test the effects of parasitism and maternal stress, as measured by GCs, during pregnancy and the relationship between these variables and measures of reproductive output using a rodent-flea system. Female Egyptian spiny mice (Acomys cahirinus) were randomly assigned to flea (Parapulex chephrenis) infested or uninfested treatments before and during pregnancy. The offspring of these females were flea-free. Feces were collected at five time points during the experiment to determine maternal fecal glucocorticoid metabolite (FGCM) concentrations. Overall, infested females had lower FGCM levels during gestation but higher FGCM levels post-parturition and larger mass changes than uninfested females. Additionally, models related to pup quality and quantity often included some measure of maternal investment or body condition moderating relationships between infestation and stress. This suggests that flea parasitism or high GC levels alone might not significantly impact host reproduction but rather females can experience different effects depending on their level of investment, which could be limited by body condition and/or the number of pups present in a litter.

Introduction Carotid atherosclerosis is the main cause of ischaemic stroke. Texture analysis is a radiomic approach used to quantify image heterogeneity which can predict tumour aggression in oncology. We investigated whether this method could be applied to carotid artery disease to differentiate symptomatic from asymptomatic patients and culprit from non-culprit plaques, and then whether machine learning (ML) could correctly classify plaques based on these features. Methods CT angiography (CTA) images from symptomatic patients with carotid artery-related cerebrovascular accidents (CVAs) and from asymptomatic (ASX) patients were studied. Regions-of-interest (ROIs) were drawn on 14 consecutive carotid artery CTA slices with 3mm slice thickness. PyRadiomics was used for isotropic image (1x1x1) resampling and normalisation prior to texture feature extraction from 6 different classes (Table 1). Asymptomatic carotids were compared to culprit carotids (CC), and non-culprit (NC) carotids using the Mann Whitney U test or Wilcoxon signed-rank tests as appropriate, with a p-value Results The dataset comprised 82 carotid arteries from 41 symptomatic patients (41 culprit; 41 non-culprit) and 50 carotid arteries from 25 asymptomatic patients. CC and NC carotids showed significant differences in both first- and second-order features (IH Median: CC 618 (61); NC 646 (97), p Conclusions Textural analysis combined with machine learning on carotid CT scans reveals highly significant differences between symptomatic and asymptomatic patients, and between culprit and non-culprit carotid arteries within symptomatic patients. This approach could help identify patients at high-risk of stroke for aggressive medical therapy and surveillance. Conflict of Interest None

Background Clinical frailty is an important syndrome for clinical care and research, independently predicting mortality and rates of institutionalisation in a range of medical conditions. However, there has been little research into the role of frailty in stroke. Objective This study investigates the effect of frailty on 28-day mortality following ischaemic stroke and outcomes following stroke thrombolysis. Methods Frailty was measured using the Clinical Frailty Scale (CFS) for all ischaemic stroke admissions aged ≥75 years. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). 28-day mortality and clinical outcomes were collected retrospectively. Analysis included both dichotomised measures of frailty (non-frail: CFS 1–4, frail: 5–8) and CFS as a continuous ordinal scale. Results In 433 individuals with ischaemic stroke, 28-day mortality was higher in frail versus non-frail individuals (39 (16.7%) versus 10 (5%), P Conclusion Clinical frailty is independently associated with 28-day mortality after ischaemic stroke and appears independently associated with attenuated improvement in NIHSS following stroke thrombolysis. Further research is needed to elucidate the underlying mechanisms and how frailty may be utilised in clinical decision-making.

Atherosclerosis is a systemic inflammatory disease typified by the development of lipid-rich atheroma (plaques), the rupture of which are a major cause of myocardial infarction and stroke. Anatomical evaluation of the plaque considering only the degree of luminal stenosis overlooks features associated with vulnerable plaques, such as high-risk morphological features or pathophysiology, and hence risks missing vulnerable or ruptured non-stenotic plaques. Consequently, there has been interest in identifying these markers of vulnerability using either MRI for morphology, or positron emission tomography (PET) for physiological processes involved in atherogenesis. The advent of hybrid PET/MRI scanners offers the potential to combine the strengths of PET and MRI to allow comprehensive assessment of the atherosclerotic plaque. This review will discuss the principles and technical aspects of hybrid PET/MRI assessment of atherosclerosis, and consider how combining the complementary modalities of PET and MRI has already furthered our understanding of atherogenesis, advanced drug development, and how it may hold potential for clinical application.

Background: Inflammation and microcalcification are interrelated processes contributing to atherosclerotic plaque vulnerability. Positron-emission tomography can quantify these processes in vivo. This study investigates (1) 18 F-fluorodeoxyglucose (FDG) and 18 F-sodium fluoride (NaF) uptake in culprit versus nonculprit carotid atheroma, (2) spatial distributions of uptake, and (3) how macrocalcification affects this relationship. Methods: Individuals with acute ischemic stroke with ipsilateral carotid stenosis of ≥50% underwent FDG-positron-emission tomography and NaF-positron-emission tomography. Tracer uptake was quantified using maximum tissue-to-background ratios (TBR max ) and macrocalcification quantified using Agatston scoring. Results: In 26 individuals, median most diseased segment TBR max (interquartile range) was higher in culprit than in nonculprit atheroma for both FDG (2.08 [0.52] versus 1.89 [0.40]; P P max was higher in culprit arteries for FDG (1.92 [0.41] versus 1.71 [0.31]; P P =0.10). NaF uptake was concentrated at carotid bifurcations, while FDG was distributed evenly throughout arteries. Correlations between FDG and NaF TBR max differed between bifurcations with low macrocalcification ( r s =0.38; P r s =0.59; P Conclusions: This is the first study to demonstrate increased uptake of both FDG and NaF in culprit carotid plaques, with discrete distributions of pathophysiology influencing vulnerability in vivo. These findings have implications for our understanding of the natural history of the disease and for the clinical assessment and management of carotid atherosclerosis.

Theβ-diversity of fleas parasitic on small mammals in 45 regions of the Palearctic was partitioned into species [species contributions toβ-diversity (SCBD)] and site ( = assemblage) contributions [local contributions toβ-diversity (LCBD)]. We asked what are the factors affecting SCBD and LCBD and tested whether (a) variation in ecological, morphological, life history and geographic traits of fleas can predict SCBD and (b) variation in flea and host community metrics, off-host environmental factors, host species composition of flea assemblages can predict LCBD. We used spatial variables to describe geographic distribution of flea assemblages with various LCBD values. SCBD significantly increased with an increase in abundance and a decrease in phylogenetic host specificity of a flea as well as with size and latitude of its geographic range, but was not associated with any morphological/life history trait. LCBD of flea assemblages did not depend on either flea or host species richness or environmental predictors, but was significantly affected by compositional uniqueness ( = LCBD) of regional host assemblages and variables describing their species composition. In addition, variation in LCBD was also explained by broad-to-moderate-scale spatial variables. We conclude that SCBD of fleas could be predictedviatheir ecological and geographic traits, whereas LCBD of their assemblages could be predictedviahost composition.

The distribution of body sizes of co-existing species at different scales reflects the scale-dependency of rules governing community assembly. Investigation of among-scale variation in community assembly is impeded by the methodological difficulties of establishing scale boundaries. Studying body size distribution in parasites allows us to avoid the problem of defining scale because parasite communities have clear boundaries and are represented by infracommunities (an assemblage harboured by an individual host), component communities (an assemblage harboured by a host population in a locality), and compound communities (an assemblage harboured by a host community in a locality). We studied body size distribution of fleas parasitic on small mammals in Western Siberia using null models. We asked whether body size ratios (i.e., size differences among coexisting species) in these communities demonstrate non-random segregated or aggregated patterns and whether these patterns differ between (a) host species, (b) host sexes and (c) infra-, component, and compound communities. No effect of host sex on the pattern of body size distribution was found at either scale, whereas an effect of host species was found in infracommunities only. We found a tendency of flea infracommunities toward segregation, whereas body size distributions in component and compound communities were consistently aggregated. We propose that the former could be caused by apparent competition (= negative indirect interactions among fleas due to shared natural enemy, i.e. a host), whereas we the latter could be explained by host- and environment-associated filtering (= factors restricting co-occurring species to a certain subset that share certain traits). We conclude that, counterintuitively, flea communities at the lowest hierarchical scale are mainly governed by evolutionary mechanisms, whereas communities at higher scale are assembled via ecological processes.

We tested whether geographic range position of fleas parasitic on small mammals in the Palearctic is affected by environmental niche conservatism or geographic range conservatism by measuring phylogenetic signal in range centroids and boundaries. We predicted that stronger phylogenetic signal in latitudinal than longitudinal range positions would indicate the important role of niche conservatism as a driver of the evolution of fleas' geographic ranges. Phylogenetic signals in geographic range positions were measured across 120 species, as well as within five flea lineages (subfamily/family rank) of different evolutionary ages. To investigate the temporal pattern of the geographic range position's evolution, we fitted the phylogenetic patterns in the geographic coordinates of range centroids and border extremes to four models of trait evolution. We consistently detected significant phylogenetic signals in the latitudes of the range centroids and the northern range borders. The latitudes of the southern range borders and the longitudes of the eastern/western borders demonstrated phylogenetic signals less often, whereas no signal was found for the longitudes of the range centroids. The phylogenetic signal in range position was more pronounced in younger lineages. The phylogenetic signal indices mainly suggested the evolution of range positions according to the Brownian motion model, whereas the best fit was often provided by the Orstein-Uhlenbeck model. This contradiction forced us to invoke a parsimonious explanation that the phylogenetic signal in range positions results from the interplay between the footprint of the speciation pattern and limited dispersal from the ancestral ranges.

Modern ischaemic stroke management involves intravenous thrombolysis followed by mechanical thrombectomy, which allows markedly higher rates of recanalization and penumbral salvage than thrombolysis alone. However

Host specificity is a fundamental trait of a parasite species. Recently, multiple aspects of host specificity have been recognized, but the relationships between these facets are still poorly understood. Here, we studied pairwise relationships between basic, structural, phylogenetic and geographic host specificity in three taxa of haematophagous ectoparasitic arthropods that differ in tightness of their association with the host. We asked which metrics of host specificity are correlated within each parasite taxon and whether the patterns of the association between different facets of host specificity are similar among parasite taxa. Data on bat flies were taken from published surveys across the Neotropics while data on fleas and mites parasitic on small mammals were compiled from multiple published surveys across the Palaearctic. Basic, structural, phylogenetic and geographic specificity indices were calculated for 18 bat fly species recorded on 40 host species from 15 regions, 109 flea species recorded on 120 host species from 51 regions and 34 mite species recorded on 67 host species from 28 regions. Then, we tested for the correlation between any two measures of host specificity using model II regressions. We found that structural and basic specificity, as well as structural and geographic specificity, exhibited a positive association in all three taxa. However, basic and geographic specificity, as well as basic and phylogenetic specificity, were significantly positively associated in fleas but did not correlate in bat flies or mites. In addition, we found a significant negative association between structural and phylogenetic specificity in bat flies but no association in the remaining taxa. Moreover, geographic and phylogenetic specificity were not associated in any parasite taxon. Our results suggest that different facets of host specificity were shaped differently by natural selection in different taxa.

SUMMARYWe revisited the role of dissimilarity of host assemblages in shaping dissimilarity of flea assemblages using a non-linear approach. Generalized dissimilarity models (GDMs) were applied using data from regional surveys of fleas parasitic on small mammals in four biogeographical realms. We compared (1) model fit, (2) the relative effects of host compositional and phylogenetic turnover and geographic distance on flea compositional and phylogenetic turnover, and (3) the rate of flea turnover along gradients of host turnover and geographic distance with those from earlier application of a linear approach. GDMs outperformed linear models in explaining variation in flea species turnover and host dissimilarity was the best predictor of flea dissimilarity, irrespective of scale. The shape of the relationships between flea compositional turnovers along host compositional turnover was similar in all realms, whereas turnover along geographic distance differed among realms. In contrast, the rate of flea phylogenetic turnover along gradients of host phylogenetic turnover differed among realms, whereas flea phylogenetic turnover did not depend on geographic distance in any realm. We demonstrated that a non-linear approach (a) explained spatial variation in parasite community composition better than and (b) revealed patterns that were obscured by earlier linear analyses.