Sebastián D'HErs

Ticks are vectors of many human and animal zoonotic disease-causing agents causing significant global health and economic strain. Repellents and acaricides are integral to the human capacity for personal protection from tick bites. Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide. Research has also noted repellent effects against some tick species. In this study, our aim was to investigate the effect of synthetic, high-purity (+)-nootkatone on adult Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum ticks in an in vitro, vertical filter paper bioassay. (+)-nootkatone showed compelling tick repellency, but median effective concentrations (EC₅₀) significantly differed among species. Ixodes scapularis were repelled at very low concentrations (EC₅₀ = 0.87 ± 0.05 µg/cm²). Higher concentrations were required to repel D. variabilis (EC₅₀ = 252 ± 12 µg/cm²) and A. americanum (EC₅₀ = 2313 ± 179 µg/cm²). Significant post-exposure mortality, assessed 24 h after repellency trials, was also observed in I. scapularis but was absent entirely in D. variabilis and A. americanum. These tests demonstrate that nootkatone has a promising dual-action personal protection capacity against adult I. scapularis ticks, warranting further investigation in more natural environments and in the presence of host cues.

A systematic study of the post‐cure cycle of soy‐based polyurethane thermosets was conducted as a function of crosslinker content, post‐cure temperature and time. An improvement of 207% of the flexural strength, up to 175 MPa, was measured by increasing the crosslinking content to 60 wt% and by using a post‐cure cycle temperature of 110°C. Similarly, the flexural modulus also increased by 199%, up to 3.2 GPa, while maintaining a flexural strain to failure of 6.60%. In situ studies of the post‐cure cycle using dynamical mechanical analysis revealed the interplay between the two interpenetrating polymer networks as a function of crosslinker content. At a crosslinker content below 40 wt%, two rubbery to glass transition temperatures (T_g) were found at 60 and 200°C, respectively. At 60 wt%, only one T_g at temperatures close to the degradation temperature was identified (250°C). Scanning electron microscope micrographs of the fracture surface revealed the formation of stress induced cracks which were mitigated through the use of a temperature stepped post‐cure cycle. The formation of soft segments with high degradation temperatures (485°C) were revealed by thermogravimetric analysis, which can be attributed to the presence of additional covalent bonds such as allophanate and carbodiimide that were also identified through Fourier transform infrared analysis. The results revealed in this work are key for the development of biobased polyurethanes applied for the polymer composite industry. In this regard, this study represented the first analysis of the post‐cure cycle of a soy‐based polyurethane thermoset.

U.S. military troops are exposed to mosquito-borne pathogens when deployed to endemic regions. Personal protective measures such as permethrin-treated uniforms and dermal repellents are the cornerstones of mosquito-borne disease prevention for the U.S. military. These measures have limitations and additional personal protection tools, such as spatial repellent devices to decrease the risk of vector-borne pathogen transmission, are required. Novel spatial repellent controlled-release devices formulated with metofluthrin were evaluated in an outdoor setting in the northern Amazon of Peru to evaluate performance under field conditions. The metofluthrin emitting devices lowered the number of mosquitoes captured in protected human landing collections (HLC) compared to blank devices, although there were effect differences between Anopheles spp. and species in other mosquito genera. A computational-experimental model was developed to correlate HLC and active ingredient (AI) concentrations as a function of time and space. Results show a strong correlation between the released AI and the decrease in HLC. This model represents the first effort to obtain a predictive analytical tool on device performance using HLC as the entomological endpoint.

Repellents serve an important role in bite protection. Tick repellents largely rely on biomechanisms that induce responses with direct contact, but synthetic pyrethroids used as spatial repellents against insects have received recent attention for potential use in tick protection systems. An in vitro vertical climb assay was designed to assess spatial repellency against Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis adult, female ticks. Climbing behavior was assessed with and without the presence of two spatial repellents, transfluthrin and metofluthrin. Repellency parameters were defined to simulate the natural questing behavior of ambushing ticks, including measures of detachment, pseudo-questing duration, climbing deterrence, and activity. Significant effects were observed within each parameter. D. variabilis showed the greatest general susceptibility to each repellent, followed by A. americanum, and I. scapularis. The most important and integrative measure of repellency was climbing deterrence–a measure of the spatial repellent’s ability to disrupt a tick’s natural propensity to climb. Transfluthrin deterred 75% of D. variabilis, 67% of A. americanum, and 50% of I. scapularis. Metofluthrin was slightly more effective, deterring 81% of D. variabilis, 73% of A. americanum, and 72% of I. scapularis. The present study poses a novel paradigm for repellency and reports a preliminary assessment of spatial repellent effect on tick behavior. Further research will assess spatial repellency in a more natural setting, scale exposure conditions, and incorporate host cues.

Thermosetting polyurethanes were obtained using an aromatic isocyanate and a hydrophobic polyol formulation obtained from epoxidized soybean oil (ESO) crosslinked with glycerin. A systematic DSC analysis of the effect of catalyst type, crosslinker concentration, isocyanate index and ESO crystallization on cure kinetics was conducted. The combination of a stannic catalyst at 0.2 wt% and glycerin at 20 wt% produced a cure kinetics governed by an autocatalytic heat flow where vitrification played a key role in the formation of chemical bonds. The evolution of T_g as a function of conversion, which followed Di‐Benedetto's predictions, supported the hypothesis that vitrification was a preponderant phenomenon during cure. Dynamic Mechanical Analysis (DMA) of a post‐cured sample revealed a Tg centered at 220°C, whereas quasi‐static flexural mechanical tests shown a flexural modulus of 2.14 GPa and a flexural strength of 99.4 MPa. Rheological experiments at isothermal conditions supported the hypothesis that vitrification played a key role in the evolution of apparent viscosity. A master model using Kim‐Macosko equations was obtained for the proposed formulation. The results presented in this work will serve to further extend the use of biobased polymers applied in the polymer composite industry.

Addressing the prevalence of tick-borne disease requires robust chemical options as an integral component of Integrative Vector Management (IVM) program. Spatial repellency is a novel concept in tick bite prevention. To date, there is no standard for the evaluation of spatial repellency against ticks, despite the speculated value of volatilized chemicals in control systems. This study reports a novel vertical climb assay that was specifically created for the quantitative evaluation of spatial repellency in ticks. Controlled release devices (CRDs) were used to control the dispersion of multiple Active Ingredients (AIs) transfluthrin, metofluthrin, nootkatone, and DEET against adult females of three medically important tick species: Dermacentor variabilis, Amblyomma americanum , and Ixodes scapulari s. Results of our study indicate significant associations between AI exposure and changing in tick climbing behavior when compared controls in the absence of the AI, from several perspectives, including changes in tick movement velocity, displacement, detachment, and rate of successful vertical climbing. Metofluthrin and transfluthrin caused strong reductions in host seeking activities against D. variabilis and A. americanum , while both demonstrated slightly weaker effects against I. scapularis . Further work is planned to evaluate spatial repellency in ticks in more natural environments and assess their potential in future tick control programs.

Thermosetting polyurethanes were obtained using an aromatic isocyanate and a hydrophobic polyol formulation obtained from epoxidized soybean oil (ESO) crosslinked with glycerin. A systematic DSC analysis of the effect of catalyst type, crosslinker concentration, isocyanate index and ESO crystallization on the cure kinetics was conducted. The combination of a stannic catalyst at 0.2 wt.\% and glycerin at 20 wt.\% produced a cure kinetics governed by autocatalytic heat flow where vitrification played a key role in the formation of chemical bonds. The evolution of Tg as a function of conversion, which followed Di-Benedetto{\'}s predictions, supported the hypothesis that vitrification was a preponderant phenomenon during cure. The ESO crystallization had a melting endotherm centered at 35{\deg}C, affecting substantially the availability of reactive hydroxide groups. Dynamic Mechanical Analysis (DMA) of a post-cured sample revealed a Tg centered at 220{\deg}C, whereas quasi-static flexural mechanical tests revealed a flexural modulus of 2.14 GPa and a flexural strength of 99.4 MPa. Rheological experiments using a rheometer at isothermal conditions supported the hypothesis that vitrification played a key role in the evolution of apparent viscosity. A master model using Kim-Macosko equations was obtained for the proposed formulation.

The emergence of mosquitoes that can avoid indoor-deployed interventions, such as treated bed nets and indoor residual spraying, threatens the mainstay of malaria control in Zambia. Furthermore, the requirement for high coverage of these tools poses operational challenges. Spatial repellents are being assessed to supplement these vector control tools, but limitations exist in the residual effect of the repellent and the need for external power or heat for diffusion of the volatiles. A semi-field evaluation of a novel controlled release spatial repellent device (CRD) was conducted in Macha, Zambia. These devices emanate metofluthrin with no need for external power. Devices were deployed in huts within the semi-field system (SFS). Female Anopheles gambiae sensu stricto released within the SFS were trapped overnight by light traps and collected by aspiration the next morning inside and outside of huts to determine the extent of mosquito repellency and the impact on host-seeking and survival. Experiments studied the impact of number of devices as well as the presence of hut occupants. The study was complemented with numerical methods based on computational fluid dynamics to simulate spatial distribution of metofluthrin. Presence of CRDs was associated with significant reductions in indoor counts of mosquitoes, regardless of whether huts were occupied or not. Repellency ranged from 15 to 60% compared to huts with no devices. Reducing the number of devices from 16 to 4 had little impact on repellency. When huts were occupied, indoor mosquito host-seeking was higher in the presence of CRDs, whilst survival was significantly reduced. This study demonstrated that deployment of as few as four CRDs within a hut was associated with reduced indoor mosquito densities. As would be expected, presence of occupants within huts, resulted in greater indoor catches (both with and without devices). The increased indoor mosquito host-seeking and mortality in huts when devices were present may be explained by the excito-repellency activity of metofluthrin. These semi-field experiments provide preliminary data on the utility of CRD spatial repellents to reduce indoor densities of An. gambiae mosquitoes. Studies will further investigate the impact of CRDs on mosquito behaviour as well as epidemiological protective efficacy.