Father's care uniquely influences male neurodevelopment.

Mammalian infants depend on parental care for survival, with numerous consequences for their behavioral development. We investigated the epigenetic and neurodevelopmental mechanisms mediating the impact of early biparental care on development of alloparenting behavior, or caring for offspring that are not one's own. We find that receiving high parental care early in life leads to slower epigenetic aging of both sexes and widespread male-specific differential expression of genes related to synaptic transmission and autism in the nucleus accumbens. Examination of parental care composition indicates that high-care fathers promote a male-specific increase in excitatory synapses and increases in pup retrieval behavior as juveniles. Interestingly, females raised by high-care fathers have the opposite behavioral response and display fewer pup retrievals. These results support the concept that neurodevelopmental trajectories are programmed by different features of early-life parental care and reveal that male neurodevelopmental processes are uniquely sensitive to care by fathers.

Evidence for Semiochemical Divergence Between Sibling Bark Beetle Species: Dendroctonus brevicomis and Dendroctonus barberi.

We investigated geographic variation in the semiochemistry of major disturbance agents of western North American pine forests, Dendroctonus brevicomis Le Conte and Dendroctonus barberi Hopkins (Coleoptera: Curculionidae: Scolytinae), species separated by the Great Basin in the USA that until recently were synonymous. At 15 sites in the western USA and northern Mexico, beetle populations were examined to determine (1) pheromone production by solitary, mining females, (2) male electroantennogram amplitudes in response to known semiochemicals for the genus, or (3) relative attractiveness of two female-produced pheromone components (endo- and exo-brevicomin) and two host odors (alpha-pinene and myrcene) to beetles in the field. Compared to female beetles collected east of the Great Basin (D. barberi), western females (D. brevicomis) produced a consistently higher proportion of, and male antenna were correspondingly more sensitive to, the exo- than the endo-isomer of brevicomin. With the exception of one sampling location (where no preference was observed), beetles west of the Great Basin were more attracted to exo- than endo- brevicomin trap lures, whereas eastern beetles displayed the reverse preference. In contrast, there was not a consistent difference between these populations regarding relative attraction or olfactory response to myrcene or alpha-pinene, although some geographic variability was evident. These data show that the semiochemical systems of D. brevicomis and D. barberi have diverged and corroborate genetic and morphological evidence that they are distinct, allopatric species.

Quantitative Measurement of the Improvement Derived From a 10-Mo Progressive Exercise Program to Improve Balance and Function in Women at Increased Risk for Fragility Fractures.

INTRODUCTION/BACKGROUND: Osteoporosis is a common disorder and is associated with an increased risk of bone fracture. Falls are a proximate cause of a high proportion of medical costs and mortality. Improving balance can reduce the risk of falls and improve health outcomes, especially for the at-risk population of people with osteoporosis and osteopenia. The FrameWorksTM exercise program is a formal, standardized, informational and interventional 10-month exercise program. The purpose of this study was to quantitatively assess the improvement in standing balance, functional reach, and overall confidence in balance after participating in the 10-month program. METHODOLOGY: This study is a prospectively designed study with a pre and post study measurement of balance metrics. Sixty-two female participants, 45 years of age or older and at increased risk for fragility fractures, completed the 10-month program as well the pre and post program testing. Confidence was measured with the Activities-specific Balance Confidence Scale, a self-reported survey. Balance was measured digitally by means of testing with a NeuroCom® Basic Balance Master® system. Measurements were made of the Limits of Stability (LOS) Test and Modified Clinical Test of Sensory Interaction on Balance (mCTSIB). Balance was clinically assessed with the Functional Reach Test (FRT). RESULTS: Participation in the 10 months FrameWorksTM program resulted in improvement in quantitative measures of balance (Composite Sway Velocity, -12%, p < 0.001; End point excursion, 17.1%, p < 0.000001). A clinical measure of balance, the Functional Reach Test, improved, (2.9 cm, p < 0.0001). Participation also resulted in improvement in balance confidence (9.4 %, p < 0.00001). A height increase was observed (0.6 cm, p < 0.000001). CONCLUSIONS: The 10-month FrameWorksTM program improves balance and confidence in women at risk for fragility fractures. By improving balance and confidence, people are less likely to fall and therefore sustain fewer fractures and associated injuries.

Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial.

RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups. CONCLUSIONS: Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

Accelerated epigenetic age is associated with whole-brain functional connectivity and impaired cognitive performance in older adults.

While chronological age is a strong predictor for health-related risk factors, it is an incomplete metric that fails to fully characterize the unique aging process of individuals with different genetic makeup, neurodevelopment, and environmental experiences. Recent advances in epigenomic array technologies have made it possible to generate DNA methylation-based biomarkers of biological aging, which may be useful in predicting a myriad of cognitive abilities and functional brain network organization across older individuals. It is currently unclear which cognitive domains are negatively correlated with epigenetic age above and beyond chronological age, and it is unknown if functional brain organization is an important mechanism for explaining these associations. In this study, individuals with accelerated epigenetic age (i.e. AgeAccelGrim) performed worse on tasks that spanned a wide variety of cognitive faculties including both fluid and crystallized intelligence (N = 103, average age = 68.98 years, 73 females, 30 males). Additionally, fMRI connectome-based predictive models suggested a mediating mechanism of functional connectivity on epigenetic age acceleration-cognition associations primarily in medial temporal lobe and limbic structures. This research highlights the important role of epigenetic aging processes on the development and maintenance of healthy cognitive capacities and function of the aging brain.

Susceptibility of Walnut and Hickory Species to Geosmithia morbida.

Thousand cankers disease (TCD) of walnut is a result of feeding in the phloem by the walnut twig beetle (WTB), Pityophthorus juglandis, and subsequent canker formation caused by Geosmithia morbida around galleries. TCD has caused extensive morbidity and mortality to Juglans nigra in the western United States and, in 2010, was discovered in the eastern United States, where the tree is a highly valuable timber resource. WTB and G. morbida also have been found in J. regia orchards throughout major production areas in California, and the numbers of damaged trees are increasing. We tested the susceptibility of walnut and hickory species to G. morbida in greenhouse and field studies. Carya illinoinensis, C. aquatica, and C. ovata were immune. All walnut species tested, including J. ailantifolia, J. californica, J. cinerea, J. hindsii, J. major, J. mandshurica, J. microcarpa, J. nigra, and J. regia, developed cankers following inoculation with G. morbida. J. nigra was the most susceptible, whereas J. major, a native host of the WTB and, presumably, G. morbida, had smaller and more superficial cankers. Canker formation differed among maternal half-sibling families of J. nigra and J. cinerea, indicating genetic variability in resistance to G. morbida. Our inoculation studies with G. morbida have corroborated many of the field observations on susceptibility of walnut and hickory species to TCD, although the ability of the WTB to successfully attack and breed in walnut is also an important component in TCD resistance.

Sanitation options for managing oak wood infested with the invasive goldspotted oak borer (Coleoptera: Buprestidae) in southern California.

Movement of invasive wood-boring insects in wood products presents a threat to forest health and a management challenge for public and private land managers. The goldspotted oak borer, Agrilus auroguttatus Schaeffer (Coleoptera: Buprestidae), is a new pest in San Diego and Riverside Cos., CA, believed to have been introduced on firewood. This beetle has caused elevated levels of oak mortality since 2002. From 2009-2011, we tested several sanitation methods, applicable to large and small land parcels, to reduce or prevent goldspotted oak borer emergence from infested oak wood. In most experiments, emergence of goldspotted oak borer adults from the positive controls demonstrated that the beetle could complete development in firewood-sized pieces of cut oak wood. In 2009, adult emergence from sun-exposed oak wood began and peaked 2- to 4-wks earlier at a low elevation site than at a high elevation site (late May to late June). However, there were no significant effects of elevation or host species on the emergence response of goldspotted oak borer by solarization treatment in this study. Solarization of infested wood with thick (6 mil) and thin (1 mil) plastic tarpaulins (tarps) did not significantly reduce emergence of adults despite recordings of greater mean and maximum daily temperatures in both tarped treatments and greater relative humidity in the thick-tarped treatment (all compared with nontarped controls). Grinding wood with a 3"-minus screen (< or = 7.6 cm) significantly reduced goldspotted oak borer emergence compared with control treatments, and this was the best method for reducing adult emergence among those tested. In a separate grinding study, no adults emerged when wood was ground to 9"-minus (22.9 cm), 2"-minus (5.1 cm), or 1"-minus (2.5 cm) screen sizes, but a low level of adult emergence from the positive controls limited any inferences from this experiment. Debarking cut wood pieces eliminated goldspotted oak borer emergence from the wood fraction, but adults emerged from the shaved bark and phloem.

Systematic Review and Meta Analysis of the Relative Effect on Plaque Index among Pediatric Patients Using Powered (Electric) versus Manual Toothbrushes.

Although many randomized controlled trials (RCT) have evaluated the efficacy of powered or electric toothbrushes compared with manual or traditional toothbrushes to remove biofilm and plaque, only one systematic review has been published for pediatric patients. The primary objective of this study was to perform a systematic review and meta analysis for this population. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol, N = 321 studies were initially identified. Three independent, blinded abstract reviews were completed resulting in a total of n = 38/322 or 11.8% for the final analysis (n = 27 non-orthodontic, n = 11 orthodontic studies). Meta analysis of these outcome data have revealed a strong reduction in plaque index scores among pediatric patients using electric toothbrushes of approximately 17.2% for non-orthodontic patients and 13.9% for orthodontic patients. These results provide strong clinical evidence for recommending electric toothbrushing to pediatric patients, as well as those patients undergoing orthodontic therapy and treatment.

Functional brain connectivity during social attention predicts individual differences in social skill.

Social attention involves selectively attending to and encoding socially relevant information. We investigated the neural systems underlying the wide range of variability in both social attention ability and social experience in a neurotypical sample. Participants performed a selective social attention task, while undergoing fMRI and completed self-report measures of social functioning. Using connectome-based predictive modeling, we demonstrated that individual differences in whole-brain functional connectivity patterns during selective attention to faces predicted task performance. Individuals with more cerebellar-occipital connectivity performed better on the social attention task, suggesting more efficient social information processing. Then, we estimated latent communities of autistic and socially anxious traits using exploratory graph analysis to decompose heterogeneity in social functioning between individuals. Connectivity strength within the identified social attention network was associated with social skills, such that more temporal-parietal connectivity predicted fewer challenges with social communication and interaction. These findings demonstrate that individual differences in functional connectivity strength during a selective social attention task are related to varying levels of self-reported social skill.

An epigenetic mechanism for differential maturation of amygdala-prefrontal connectivity in childhood socio-emotional development.

Functional connectivity between the amygdala and the medial prefrontal cortex (mPFC) has been identified as a neural substrate of emotion regulation that undergoes changes throughout development, with a mature profile typically emerging at 10 years of age. Maternal bonding in childhood has been shown to buffer amygdala reactivity and to influence the trajectory of amygdala-mPFC coupling. The oxytocinergic system is critical in the development of social behavior and maternal bonding. Early-life parental care influences the methylation status of the oxytocin receptor (OXTRm) in animal models and humans, and higher OXTRm is associated with lower amygdala-PFC functional connectivity in adults. Using a neuroimaging-epigenetic approach, we investigated saliva-derived OXTRm as a biological marker of structural and functional connectivity maturation in 57 typically developing children (P < 0.05). We utilized seed-based connectivity analysis during a novel abstract movie paradigm and find that higher levels of OXTRm are associated with a more adult-like functional connectivity profile. Concurrently, more adult-like functional connectivity was associated with higher reported self-control and more diffusion streamlines between the amygdala and mPFC. OXTRm mediates the association between structural and functional connectivity with higher levels of OXTRm being associated with more streamlines. Lastly, we also find that lower OXTRm blunts the association between amygdala-mPFC connectivity and future internalizing behaviors in early adolescence. These findings implicate OXTRm as a biological marker at the interface of the social environment and amygdala-mPFC connectivity in emotional and behavioral regulation. Ultimately, identification of neurobiological markers may lead to earlier detection of children at risk for socio-emotional dysfunction.

Western Spruce Budworm Effects on Forest Resilience.

Western spruce budworm (Choristoneura freemani Razowski) is the most destructive defoliator of forests in the western US. Forests in northern New Mexico experienced high levels of WSBW-caused defoliation and subsequent mortality between the 1980s and 2010s. The effects of severe western spruce budworm outbreaks on stand dynamics in the US Southwest are still relatively unknown, but understanding the impacts is important to the management and resilience of these forests. To begin addressing this knowledge gap, we conducted a study along two gradients: an elevational gradient from mixed-conifer to spruce-fir forests and a gradient of WSBW-caused defoliation intensity. We recorded overstory and understory stand conditions (size structure, species composition, damaging agents). Western spruce budworm was the primary damaging agent of host trees in all stands andcaused host tree mortality across all size classes, particularly in spruce-fir stands. Results indicate an unsustainable level of mortality in spruce-fir stands and a transition towards non-host species in mixed-conifer stands. Low levels of regeneration coupled with high overstory mortality rates indicate a potential lack of resilience in spruce-fir stands, whereas resilience to future western spruce budworm defoliation events may have increased in mixed-conifer stands affected by these outbreaks.

Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression.

BACKGROUND: The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. RESULTS: Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3' portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. CONCLUSIONS: These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3' portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3' portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.

A Biodegradable Formulation of MCH (3-Methylcyclohex-2-en-1-one) for Protecting Pseudotsuga menziesii from Dendroctonus pseudotsugae (Coleoptera: Curculionidae) Colonization.

Douglas-fir, Pseudotsuga menziesii (Mirb.) Franco, trees and stands can be protected from Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins (DFB)-caused mortality by application of synthetic formulations of the beetle's antiaggregation pheromone, 3-methylcyclohex-2-en-1-one (MCH). A biodegradable formulation of MCH, SPLAT MCH, was developed and evaluated for protecting individual Douglas-fir trees and small stands from colonization and mortality by DFB. In an individual-tree experiment in Idaho, both MCH bubble capsules and SPLAT MCH significantly reduced the proportion of treated trees colonized and killed by DFB compared to untreated controls. SPLAT MCH was as effective as MCH bubble capsules for protecting individual trees. Both MCH bubble capsules and SPLAT MCH significantly reduced the proportion of trees colonized and killed by DFB within 0.04-ha circular plots surrounding each treated tree compared to untreated controls. In 0.41 ha stands in New Mexico, both MCH bubble capsules and SPLAT MCH significantly reduced the proportion of trees colonized and killed by DFB compared to untreated controls, again with no differences observed between MCH treatments. In a similar stand level trial in Idaho, neither MCH treatment significantly reduced the proportion of trees colonized by DFB, and only MCH bubble capsules significantly reduced levels of tree mortality compared to untreated controls, but no significant difference was observed between SPLAT MCH and MCH bubble capsules. Overall, the results indicate that SPLAT MCH is as effective as MCH bubble capsules for protecting individual trees and small stands of Douglas-fir from DFB-caused mortality.

Management of a patient with a clot-filled pulmonary arteriovenous malformation.

Transcatheter coil embolization is an established treatment for pulmonary arteriovenous malformations (PAVMs). Encountering a patient with a symptomatic PAVM partially occluded with a prominent clot is rare. Successful and safe coil embolization of such a PAVM is described in this case report.

Advances in Semiochemical Repellents to Mitigate Host Mortality From the Spruce Beetle (Coleoptera: Curculionidae).

We tested 3-methyl-2-cyclohexen-1-one (MCH) and novel semiochemicals as potential spruce beetle (Dendroctonus rufipennis Kirby) (Coleoptera: Curculionidae, Scolytinae) repellents over multiple years in Utah and Colorado trapping bioassays. MCH is a known spruce beetle repellent and our testing revealed Acer kairomone blend (AKB) and isophorone plus sulcatone as repellents. We subsequently tested these semiochemicals for area and single tree protection to prevent spruce beetle attacks at locations in Utah, Colorado, Wyoming, New Mexico, and Alaska. Individual tree protection trials found MCH-AKB provided significant protection against spruce beetle attacks in the southern Rocky Mountains but not in Alaska. Adding sulcatone or doubling MCH-AKB pouches did not further enhance protection. A degree of protection was extended to spruce at least 10 m distant from the repellents, including in Alaska. Tree diameter was not a significant covariate among treated trees but was positively correlated with the probability of infestation for surrounding spruce. In area protection trials, spruce in control plots were 2.4 times more likely to be in a higher severity attack class compared with spruce in plots treated with MCH-AKB pouches deployed at 30 sets per hectare. Tree diameter had a significant, positive relationship to the probability of infestation. We found MCH-AKB to offer a high degree of protection against beetle attack in Engelmann spruce (Picea engelmannii Parry ex Engelm.) (Pinales: Pinaceae) (Picea engelmannii Parry ex Engelm.) (Pinales: Pinaceae), especially for single tree protection (66% of control trees were strip- or mass-attacked compared with 6% of repellent-treated trees). AKB requires registration and labeling, however, before this economical and environmentally benign semiochemical can be used operationally.

Mycobiota associated with insect galleries in walnut with thousand cankers disease reveals a potential natural enemy against Geosmithia morbida.

Thousand Cankers Disease (TCD) affects Juglans and Pterocarya species. This disease poses not only a major threat to the nut and timber industries but also to native stands of walnut trees. Galleries created by Pityophthorus juglandis (vector) are colonized by the fungus Geosmithia morbida (causal agent of necrosis). It is unknown if other fungi colonizing these galleries might act antagonistically towards G. morbida. The objectives of this study were to: (1) characterize the fungal community associated with TCD-infected trees and (2) develop a pilot study addressing their potential antagonism towards G. morbida. We collected non-Geosmithia fungi from ten TCD-infected walnut trees from California and Tennessee. Four hundred and fifty-seven isolates, representing sixty-five Operational Taxonomic Units (99 % ITS similarity) were obtained. Fungal communities were found to be highly diverse. Ophiostoma dominated the communities associated with TCD-compromised trees from California, whereas Trichoderma dominated TCD-compromised trees in Tennessee. Six Trichoderma isolates showed varying levels of antagonism against three isolates of G. morbida, suggesting potential applications for the biological control of TCD. Furthermore, results from this study contribute to the growing knowledge about the observed differential disease development between the western and eastern USA and could overall impact our understanding of TCD etiology.

Registered Replication Report: Dijksterhuis and van Knippenberg (1998).

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the "professor" category and those primed with the "hooligan" category (0.14%) and no moderation by gender.

3-Methylcyclohex-2-en-1-one for area and individual tree protection against spruce beetle (Coleoptera: Curculionidae: Scolytinae) attack in the southern Rocky Mountains.

We tested 3-methylcyclohex-2-en-1-one (MCH) and an Acer kairomone blend (AKB) as repellent semiochemicals for area and single tree protection to prevent spruce beetle (Dendroctonus rufipennis Kirby) attacks at locations in Utah and New Mexico. In the area protection study, we compared host infestation rates of MCH applications at three densities (20, 40, and 80 g MCH ha-1) against a control treatment over 0.64 ha plots centered within ~1.25 ha treatment blocks. All treatments included two baited funnel traps within the plot to assure spruce beetle pressure. Following beetle attack, plots were surveyed for new spruce beetle attacks and to quantify stand characteristics. The probability of more severe spruce beetle attacks was significantly reduced, by ~50%, in each of the MCH area treatments compared with the control treatment but there was no significant treatment difference among the MCH deployment densities. For the single tree protection study, we compared attack rates of MCH, Acer kairomone blend (AKB), and MCH plus AKB on spruce beetle-baited trees against bait-only trees. Each treatment was applied over a range of host diameters to test for host size effects. Seventy-five percent of control trees were mass-attacked, about one-third of MCH- and AKB-alone spruce was mass-attacked, and no MCH plus AKB spruce were mass-attacked. These results suggest that MCH alone is a marginal area and single tree protectant against spruce beetle but that deployment with other repellents can significantly increase treatment efficacy.