The influence of climate and socio-ecological factors on invasive mosquito vectors in the Northeastern US: Assessing risk of local arboviral transmission

Background: Mosquito-borne diseases are a growing concern for temperate regions including the northeastern US. There the two primary mosquito vectors, Cx. pipiens and Ae. albopictus are widespread, endemic circulation of West Nile virus causes sporadic outbreaks, and imported arboviruses such as dengue, chikungunya, and Zika are on the rise. With temperate mosquito-borne disease outbreaks likely to increase in frequency, it is critical to reduce mosquito populations in the northeastern US. Community-based source reduction is heralded as the most sustainable component of integrated mosquito management. Yet mosquitoes develop rapidly, requiring weekly maintenance of mosquito habitat. This is onerous and community commitment flags. The development of predictive models to inform focused vector-control efforts is therefore of great utility. Objectives and Methods: The overarching objective of this research is to make robust predictive modeling frameworks based on empirically derived relationships of the ecology and epidemiology of mosquito-borne disease systems in the northeastern US. We aim to quantify the relationships between local environmental and meteorological conditions and mosquito vectors. In Chapters 2 and 4 we use lengthy surveillance records to develop models and use model ensembles to generate predictions based on out-of-sample data. For chapter 3 we use more spatially refined data to investigate the influence of intra-urban heterogeneities and how climatic conditions influence mosquito populations across these defined differences. Results: In Chapter 2, we model and forecast WNV infection rates among mosquito vectors using meteorological and hydrological conditions. We show that real-time climate information can predict WNV Culex infection rates prior to when human risk is greatest. In Chapter 3, we link infrastructure degradation and vegetation patterns with Ae. albopictus infestation levels as well as the interactive effect of precipitation across these environmental conditions. In Chapter 4, we identify key land use characteristics and meteorological conditions associated with annual Ae. albopictus abundance. Further we use imported chikungunya cases to delineate areas of high arboviral importation and, in combination with areas of high Ae. albopictus abundance, areas at heightened risk for arboviral transmission. Conclusions: While temperate outbreaks are often self-limiting they may be increasing in frequency and severity. Due to the multitude of invasive vectors and arboviruses, vector control techniques that work for multiple mosquito species are likely more effective and sustainable. Here we build build empirical models that accurately predict mosquito dynamics before populations peak which is critical for vector control. We recommend integrating predictive modeling into mosquito management guidelines as this could focus valuable resources to when and where mosquito-borne transmission risk is greatest. Further we find social and ecological determinants of mosquito dynamics, supporting further study that combine socio-ecological processes into model frameworks

Local environmental and meteorological conditions influencing the invasive mosquito Ae. albopictus and arbovirus transmission risk in New York City

Ae. albopictus, an invasive mosquito vector now endemic to much of the northeastern US, is a significant public health threat both as a nuisance biter and vector of disease (e.g. chikungunya virus). Here, we aim to quantify the relationships between local environmental and meteorological conditions and the abundance of Ae. albopictus mosquitoes in New York City. Using statistical modeling, we create a fine-scale spatially explicit risk map of Ae. albopictus abundance and validate the accuracy of spatiotemporal model predictions using observational data from 2016. We find that the spatial variability of annual Ae. albopictus abundance is greater than its temporal variability in New York City but that both local environmental and meteorological conditions are associated with Ae. albopictus numbers. Specifically, key land use characteristics, including open spaces, residential areas, and vacant lots, and spring and early summer meteorological conditions are associated with annual Ae. albopictus abundance. In addition, we investigate the distribution of imported chikungunya cases during 2014 and use these data to delineate areas with the highest rates of arboviral importation. We show that the spatial distribution of imported arboviral cases has been mostly discordant with mosquito production and thus, to date, has provided a check on local arboviral transmission in New York City. We do, however, find concordant areas where high Ae. albopictus abundance and chikungunya importation co-occur. Public health and vector control officials should prioritize control efforts to these areas and thus more cost effectively reduce the risk of local arboviral transmission. The methods applied here can be used to monitor and identify areas of risk for other imported vector-borne diseases

Use of temperature to improve West Nile virus forecasts

Ecological and laboratory studies have demonstrated that temperature modulates West Nile virus (WNV) transmission dynamics and spillover infection to humans. Here we explore whether inclusion of temperature forcing in a model depicting WNV transmission improves WNV forecast accuracy relative to a baseline model depicting WNV transmission without temperature forcing. Both models are optimized using a data assimilation method and two observed data streams: mosquito infection rates and reported human WNV cases. Each coupled model-inference framework is then used to generate retrospective ensemble forecasts of WNV for 110 outbreak years from among 12 geographically diverse United States counties. The temperature-forced model improves forecast accuracy for much of the outbreak season. From the end of July until the beginning of October, a timespan during which 70% of human cases are reported, the temperature-forced model generated forecasts of the total number of human cases over the next 3 weeks, total number of human cases over the season, the week with the highest percentage of infectious mosquitoes, and the peak percentage of infectious mosquitoes that on average increased absolute forecast accuracy 5%, 10%, 12%, and 6%, respectively, over the non-temperature forced baseline model. These results indicate that use of temperature forcing improves WNV forecast accuracy and provide further evidence that temperature influences rates of WNV transmission. The findings provide a foundation for implementation of a statistically rigorous system for real-time forecast of seasonal WNV outbreaks and their use as a quantitative decision support tool for public health officials and mosquito control programs

A proposed framework for the development and qualitative evaluation of West Nile virus models and their application to local public health decision-making

West Nile virus(WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m–km, days–weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

The Self-Exhibition of Reason: Hegel on Intuition and Logical Content

My dissertation offers an innovative reading of Hegel’s mature philosophy that presents the first systematic study of the role of perception and perceptual themes across all three volumes (logic, nature, and spirit) of Hegel’s mature Encyclopedia project. I argue that Hegel’s Encyclopedic texts offer a robust and nuanced account of the conceptuality of perceptual content that has been largely overlooked or misunderstood by previous interpreters. On my reading, Hegel rejects the empirical realism of Immanuel Kant, according to which view our phenomenal experience of objects yields knowledge of their reality. He also rejects a “conceptual realist” picture according to which our knowledge of reality inheres merely in knowledge of the reality of a universal or some set of universals. Instead, I propose that Hegel endorses a “rational realism” according to which sensory knowledge of concrete singulars is achieved by means of conceptual thought. On a first look the potential coherence of such a view appears dubious: it seems to either fundamentally conflate the cognitive acts of thinking and perceiving, or else to reduce perceiving to thinking in a way that yields an infelicitous solipsism. In this context, the goal of the first two chapters of my project is to motivate the idea that Hegel’s rational realism avoids these pitfalls by giving an exegesis of the philosophical considerations that lead him to his view. Towards this end, I offer readings of Hegel’s respective engagements with two of his primary historical interlocutors, Kant and Schelling, on the topic of the proper role of perception in a philosophical account of cognition. In Chapter 1, I examine Hegel’s critique of Kant’s theoretical philosophy. One of the central innovations of the Critique of Pure Reason is Kant’s proposal that space and time serve as a priori “forms of intuition” that condition all of the deliverances of sense perception. Although Hegel is strongly influenced by Kant’s transcendental idealism, his own philosophy lacks an analogue to these Kantian forms of intuition. I argue that Hegel’s rejection of Kant’s forms of intuition forms the backbone of his self-professed post-Kantianism. I demonstrate that Hegel finds resources in Kant’s own system, specifically in the Critique of Aesthetic Judgment, that allow him to offer an alternative account of the formal character of perception. In Chapter 2, I expand on this account by breaking down Hegel’s critique of Friedrich Schelling’s theory of intellectual intuition. This chapter fills a pressing gap in the literature. I argue that Hegel and Schelling share a commitment to offering an account of perception that is centered on the way in which the concrete individual objects of sense perception can demonstrate the physical existence of universals. Both thinkers propose that works of fine art are paradigmatic sense objects of this kind. Contra Schelling, however, Hegel believes that logic itself should also perform this function. In Chapters 3 and 4, I turn to Hegel’s positive account of the way in which the forms belonging to logic demonstrate the way in which universals appear to the senses in particular objects. Against recent interpretations that have sought to understand Hegel’s logic as offering only a “theory of explanation” (Kreines, Pippin) I show that Hegel’s logic also offers a “theory of exhibition”: that is, a theory of the way in which sensible particulars exhibit the existence of universals. I claim that Hegel achieves this by emphasizing the logical primacy of the function of the copula in the activities of judgment and inference. On Hegel’s view as I articulate it, perception is conceptual, and this conceptuality consists in the way in which our reasoning about sense objects exhibits the necessary existence of universal terms. Chapter 5 takes this reading from the abstract context of the Logic into the concrete realms of nature and spirit, the topics of the other two volumes of Hegel’s tripartite Encyclopedia project. I discuss the fate of Kant’s forms of intuition, space and time, as the opening moments of Hegel’s Philosophy of Nature. I also discuss the role of sense-affection in the Philosophy of Spirit

Overview of entomologic data showing the number of traps collecting <i>Ae</i>. <i>albopictus</i> (traps positive), the total mosquitoes caught in gravid and light traps, and the abundance (calculated as the number caught per trap location divided by the 23 weeks of surveillance) for gravid, light, and both trap types together.

<p>Overview of entomologic data showing the number of traps collecting <i>Ae</i>. <i>albopictus</i> (traps positive), the total mosquitoes caught in gravid and light traps, and the abundance (calculated as the number caught per trap location divided by the 23 weeks of surveillance) for gravid, light, and both trap types together.</p