Identification of the pan-allergen tropomyosin from the common bed bug (Cimex lectularius).

Tropomyosin is a muscle contraction protein documented across all animal life. Despite its ubiquity, its unique structure in invertebrates leads to allergic responses in humans that vertebrate tropomyosin does not. High degrees of homology can explain cross-reactivity between tropomyosin derived from distantly-related arthropod species and establishes tropomyosin as a panallergen. Given this cross-reactivity and that they are commonly found in high numbers indoors, research on the potential of the common bed bug (Cimex lectularius L.) to contribute tropomyosin to the indoor environment is needed. Therefore, we investigated tropomyosin homology between bed bugs and known tropomyosin allergens from other taxa, tropomyosin in bed bug bodies, feces, and exuviae (cast skins), tropomyosin persistence over time, and impacts of common bed bug treatment strategies on detectable tropomyosin. Tropomyosin was detected in mechanically fractured bed bug cadavers and was detectable in bed bugs cadavers aged for 18 months. Additionally, a survey of pest management professionals showed dead bed bugs are not cleaned up following treatment. As such, dead bed bugs could act as tropomyosin reservoirs following bed bug treatment and exposure to tropomyosin from bed bugs could sensitize individuals and lead to increased responses to other arthropod tropomyosin.

Determining the factors associated with a prolonged length of stay for adolescent idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion in a single-payer health care system: are these factors different than those in the United States?

INTRODUCTION: Rapid recovery pathways (RRP) for adolescent idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion (PSIF) have been shown to be successful in reducing hospital length of stay (LOS). Although the majority of patients are discharged within 3 days, some patients require longer hospital admission. Previous studies in the United States have identified predictors of prolonged LOS for this patient population. The goal of this project was to determine if these predictors are the same for Canadian scoliosis patients and to identify those features which are different under this single-payer system. METHODS: A RRP for scoliosis surgery was implemented in March 2015 at a single, tertiary referral children's hospital in Canada. Previously identified features, along with numerous other patient factors, were collected. Spearman correlations were used to determine the factors most associated with hospital LOS and those factors were used in a multivariable regression model. RESULTS: A total of 161 patients were included in the analysis. Of the previously identified patient factors, only receiving a peri-operative transfusion was found to be significant (ρ = 0.24; p = 0.002). None of the other pre-identified variables were found to be significantly correlated with LOS. Variables not previously examined that were found to be significantly correlated with hospital LOS included ASA status (ρ = 0.19, p = 0.046), fusion involving both the thoracic and lumbar spine (ρ = 0.18, p = 0.025), and receiving celecoxib on post-operative day 1 (ρ = - 0.16; p = 0.038). The features that had the greatest association with LOS through multivariable regression was receiving a blood transfusion (B = 0.48; 95%CI 0.096-0.89; p = 0.017). CONCLUSIONS: In this study, we found that many of the features found to be significantly correlated with prolonged hospital LOS in the United States are not transferable to the Canadian healthcare system. This is important for the Canadian, and other surgeons in a single-payer system, in order to identify pre-operative or immediate post-operative factors that may extend patient LOS following PSIF and plan resources accordingly. LEVEL OF EVIDENCE: III; therapeutic.

Behavioral responses of field-collected German cockroaches to pyrethroids and pyrethroid-formulated insecticides.

BACKGROUND: Pyrethroids are synthetic insecticides with low mammalian toxicity and broad-spectrum activity across insects. One major challenge with pyrethroids is their perceived repellency. This perception can influence decisions made by pest control operators, especially when insecticides are used to reduce insect entry into or movement within structures. One major indoor pest that has been repeatedly shown to be repelled by some pyrethroids is the German cockroach, Blattella germanica. However, most experiments evaluating pyrethroid repellency in the German cockroach have used end-point assays, which do not provide information on the movement that led to the final position. Therefore, we evaluated the kinetic behavioral response of field-collected German cockroaches to five pyrethroid-based products and their active ingredients (A.I.) in open behavioral arenas using advanced video tracking software. In addition, in an effort to compare our free-moving experiments with end-point assays, we evaluated sheltering behavior using two-choice harborage arrestment assays where German cockroaches were provided a choice between pyrethroid-treated and untreated shelters. RESULTS: All pyrethroid-formulated products and their respective A.I.'s failed to affect field-collected German cockroach movement behavior in free-moving assays, while positive controls (DEET, corn mint oil) resulted in reduced time spent by German cockroaches in treated areas. However, despite their willingness to move over pyrethroids-treated surfaces, field-collected German cockroaches displayed a reduced propensity to arrest on pyrethroids treated tents. CONCLUSION: While most pyrethroids/pyrethroid-formulated products affected German cockroach arrestment, pyrethroids and pyrethroid-formulated products failed to change German cockroach movement behavior in free-moving assays. These results indicate the pyrethroids tested act as contact irritants rather than true-spatial repellents on field-collected German cockroaches. This distinction is critical to refining pest management strategies involving pyrethroids. © 2023 Society of Chemical Industry.

Histamine excretion in common indoor and hematophagous arthropods.

Histamine is a biogenic amine that regulates multiple physiological functions in diverse organisms, specifically playing a central role in the mammalian immune response. The common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), excretes histamine in large amounts in its feces as a component of its aggregation pheromone, which contaminates homes. The potential health risks associated with the presence of indoor histamine are unclear, but to predict future exposure risks, it is critical that we understand if other arthropods excrete histamine in any discernible phylogenetic pattern. In the present study, we evaluated histamine excretion by various arthropods; specifically those commonly found in large numbers indoors, other hematophagous species, and other species in the order Hemiptera. To evaluate arthropods for histamine excretion, rearing containers for each arthropod were swabbed and/or the harborage substrates were collected. Samples were then analyzed for the presence of histamine using gas chromatography-mass spectrometry. For those arthropods where histamine was present above the method detection limit, total histamine excretion was quantified over a period of 2 wk. Our results indicate that histamine excretion is limited to hematophagous hemipterans (bed bugs, bat bugs, tropical bed bugs, and kissing bugs), suggesting that indoor histamine contamination in the United States can be primarily linked to bed bugs.

Spatial distribution of histamine in bed bug-infested homes.

Histamine is a component of the bed bug aggregation pheromone. It was recently identified as an environmental contaminant in homes with active bed bug infestations, posing a potential health risk to humans via skin contact or inhalation. It remains unclear how histamine is distributed in homes and if histamine can become airborne. In the present study, histamine levels in household dust were quantified from multiple locations within bed bug infested and uninfested apartments. Bed bug population levels were quantified using both traps and visual counts. The amount of histamine detected varied significantly with respect to sampling location, with the highest concentration of histamine quantified from bedding material. Infestation severity did not have a significant effect on histamine quantified at any location. Our results indicate that the bedroom should be the primary focus of histamine mitigation efforts, although histamine can be found throughout the home. Histamine quantified from homes without active bed bug infestations suggests that histamine from previous infestations can persist following pest eradication. These findings highlight the importance of histamine as a potential insect allergen and will be important for the development of targeted mitigation strategies of bed bug histamine.

Histamine Excretion by the Common Bed Bug (Hemiptera: Cimicidae).

The common bed bug (Cimex lectularius L.) is a hematophagous pest species that lives in close proximity to humans. Following a blood meal, bed bugs deposit fecal material indoors. The feces contain a variety of compounds, including histamine, which serves as a component of their aggregation pheromone. Histamine is a pivotal mammalian immune modulator, and recently it was shown to be present in high concentrations in household dust from homes infested with bed bugs. To better understand the dynamics of histamine excretion, we analyzed bed bug fecal material from different life stages and populations, along with fecal material collected at different post-feeding times and from bed bugs fed on different diets. Our analysis showed significant variation in histamine excretion among life stages, with mated females excreting the most histamine and first instar nymphs excreting the least histamine. However, when histamine excretion was normalized for blood consumption, males were found to excrete more histamine than the other life stages. There was no difference in histamine excretion among laboratory and recently home-collected bed bug populations. Further, we found histamine excretion continued for at least 14 d post-feeding, with the highest amount of histamine excreted 3-4 d after a bloodmeal. Overall, this work demonstrates that bed bugs excrete histamine across all feeding life stages, populations, and at various times after feeding, and that histamine excretion is directly related to blood feeding. These results will be used to better understand the health risks associated with histamine excretion and potential mitigation strategies of environmental histamine.

Multiple Mechanisms Confer Fipronil Resistance in the German Cockroach: Enhanced Detoxification and Rdl Mutation.

Populations of Blattella germanica (L.) (German cockroach) have been documented worldwide to be resistant to a wide variety of insecticides with multiple modes of action. The phenylpyrazole insecticide fipronil has been used extensively to control German cockroach populations, exclusively in baits, yet the highest reported fipronil resistance is 38-fold in a single population. We evaluated five populations of German cockroaches, collected in 2018-2019 in apartments in North Carolina and assayed in 2019, to determine the status of fipronil resistance in the state. Resistance ratios in field-collected strains ranged from 22.4 to 37.2, indicating little change in fipronil resistance over the past 20 yr. In contrast, resistance to pyrethroids continues to escalate. We also assessed the roles of detoxification enzymes in fipronil resistance with four synergists previously shown to diminish metabolic resistance to various insecticides in German cockroaches-piperonyl butoxide, S,S,S-tributyl phosphorotrithioate, diethyl maleate, and triphenyl phosphate. These enzymes appear to play a variable role in fipronil resistance. We also sequenced a fragment of the Rdl (resistant to dieldrin) gene that encodes a subunit of the GABA receptor. Our findings showed that all field-collected strains are homozygous for a mutation that substitutes serine for an alanine (A302S) in Rdl, and confers low resistance to fipronil. Understanding why cockroaches rapidly evolve high levels of resistance to some insecticides and not others, despite intensive selection pressure, will contribute to more efficacious pest management.

Human skin triglycerides prevent bed bug (Cimex lectularius L.) arrestment.

Bed bugs (Cimex lectularius) have proliferated globally and have become one of the most challenging pests to control indoors. They are nocturnal and use multiple sensory cues to detect and orient towards their human hosts. After feeding, usually on a sleeping human, they return to a shelter on or around the sleeping surface, but not directly on the host. We hypothesized that although human skin odors attract hungry bed bugs, human skin compounds may also prevent arrestment on hosts. We used arrestment assays to test human skin swabs, extracts from human skin swabs, and pure compounds identified from human skin swabs. When given a choice, bed bugs preferred to arrest on substrates not previously conditioned by humans. These responses were consistent among laboratory-reared and apartment-collected bed bugs. The compounds responsible for this behavior were found to be extractable in hexane, and bed bugs responded to such extracts in a dose-dependent manner. Bioassay-guided fractionation paired with thin-layer chromatography, GC-MS, and LC-MS analyses suggested that triglycerides (TAGs), common compounds found on human skin, were preventing arrestment on shelters. Bed bugs universally avoided sheltering in TAG-treated shelters, which was independent of the number of carbons or the number of double bonds in the TAG. These results provide strong evidence that the complex of human skin compounds serve as multifunctional semiochemicals for bed bugs, with some odorants attracting host-seeking stages, and others (TAGs and possibly other compounds) preventing bed bug arrestment. Host chemistry, environmental conditions and the physiological state of bed bugs likely influence the dual nature behavioral responses of bed bugs to human skin compounds.

Acetabular Morphology and Spinopelvic Characteristics: What Predominantly Determines Functional Acetabular Version?

BACKGROUND: In addition to the relative size of the acetabular rim and how the pelvis is positioned in space, the plane in which the acetabular version is calculated also affects its measurement. PURPOSE: To determine the relative contribution of pelvic and acetabular characteristics on morphological version (measured relative to the anterior pelvic plane angle [APPA]) and functional version (measured relative to the horizontal table). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Included were 50 acetabular dysplasia patients and 109 asymptomatic controls. Using image analysis software, morphological parameters of the pelvis and acetabulum were determined from 2-dimensional computed topography: pelvic incidence, pelvic tilt angle, sacral slope, APPA, morphological and functional acetabular versions, and subtended angles (measure of acetabular rim prominence relative to the femoral head center) around the acetabular clockface in 30° increments. Correlation and multivariable regression analyses were performed with morphological and functional version as dependent variables and spinopelvic and acetabular parameters as independent variables. RESULTS: Morphological version was moderately associated with differences between anterior and posterior subtended angles (R = 0.68 [P < .001] and R = 0.57 [P < .001] for differences at 165° and 15° and 135° and 45°, respectively). Functional version was moderately associated with pelvic tilt angle (R = 0.56; P <.001) and the difference in subtended angles between anterior and posterior rims (R = 0.61 [P < .001] and R = 0.50 [P < .001] for differences at 165° and 15° and 135° and 45°, respectively). Multivariate analysis revealed a good model for predicting morphological version (R 2 = 0.44; P < .01) and functional version (R 2 = 0.58; P < .01). Subtended angle difference between 165° and 15° (B = 0.36 [95% CI, 0.24-0.49]; P < .001) was most strongly related to morphological version, and pelvic tilt angle (B = 0.57 [95% CI, 0.46-0.68]; P < .001) was most strongly related to functional version. CONCLUSION: Functional acetabular version was influenced most strongly by pelvic tilt angle rather than the relative prominence of the acetabular rims. Before determining surgical management for version abnormalities, it would be prudent to assess pelvic mobility and characteristics in different functional positions. In patients with minimal pelvic tilt change dynamically, corrective osteotomy would be the treatment of choice to improve functional version.

Resistance to Fipronil in the Common Bed Bug (Hemiptera: Cimicidae).

Cimex lectularius L. populations have been documented worldwide to be resistant to pyrethroids and neonicotinoids, insecticides that have been widely used to control bed bugs. There is an urgent need to discover new active ingredients with different modes of action to control bed bug populations. Fipronil, a phenylpyrazole that targets the GABA receptor, has been shown to be highly effective on bed bugs. However, because fipronil shares the same target site with dieldrin, we investigated the potential of fipronil resistance in bed bugs. Resistance ratios in eight North American populations and one European population ranged from 1.4- to >985-fold, with highly resistant populations on both continents. We evaluated metabolic resistance mechanisms mediated by cytochrome P450s, esterases, carboxylesterases, and glutathione S-transferases using synergists and a combination of synergists. All four detoxification enzyme classes play significant but variable roles in bed bug resistance to fipronil. Suppression of P450s and esterases with synergists eliminated resistance to fipronil in highly resistant bed bugs. Target-site insensitivity was evaluated by sequencing a fragment of the Rdl gene to detect the A302S mutation, known to confer resistance to dieldrin and fipronil in other species. All nine populations were homozygous for the wild-type genotype (susceptible phenotype). Highly resistant populations were also highly resistant to deltamethrin, suggesting that metabolic enzymes that are responsible for pyrethroid detoxification might also metabolize fipronil. It is imperative to understand the origins of fipronil resistance in the development or adoption of new active ingredients and implementation of integrated pest management programs.

Using a national surgical database to predict complications following posterior lumbar surgery and comparing the area under the curve and F1-score for the assessment of prognostic capability.

BACKGROUND: With spinal surgery rates increasing in North America, models that are able to accurately predict which patients are at greater risk of developing complications are highly warranted. However, the previously published methods which have used large, multi-centre databases to develop their prediction models have relied on the receiver operator characteristics curve with the associated area under the curve (AUC) to assess their model's performance. Recently, it has been found that a precision-recall curve with the associated F1-score could provide a more realistic analysis for these models. PURPOSE: To develop a logistic regression (LR) model for the prediction of complications following posterior lumbar spine surgery and to then assess for any difference in performance of the model when using the AUC versus the F1-score. STUDY DESIGN: Retrospective review of a prospective cohort. PATIENT SAMPLE: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) registry was used. All patients that underwent posterior lumbar spine surgery between 2005 to 2016 with appropriate data were included. OUTCOME MEASURES: Both the AUC and F1-score were utilized to assess the prognostic performance of the prediction model. METHODS: In order to develop the LR model used to predict a complication during or following spine surgery, 19 variables were selected by three orthopedic spine surgeons from the NSQIP registry. Two datasets were developed for this analysis: (1) an imbalanced dataset, which was taken directly from the NSQIP registry, and (2) a down-sampled set. The purpose of the down-sampled set was to balance the data in order to evaluate whether balancing the data had an effect on model performance. The AUC and F1-score were applied to both of these datasets. RESULTS: Within the NSQIP database, 52,787 spine surgery cases were identified of which only 10% of these cases had complications during surgery. Applying the LR model showed a large difference between the AUC (0.69) and the F1 score (0.075) on the imbalanced dataset. However, no major differences existed between the AUC and F1-score when the data was balanced and the LR model was reapplied (0.69 and 0.62, AUC and F1-score, respectively). CONCLUSIONS: The F1-score detected a drastically lower performance for the prediction of complications when using the imbalanced data, but detected a performance similar to the AUC level when balancing techniques were utilized for the dataset. This difference is due to a low precision score when many false positive classifications are present, which is not identified when using the AUC value. This lowers the utility of the AUC score, as many of the datasets used in medicine are imbalanced. Therefore, we recommend using the F1-score on large, prospective databases when the data is imbalanced with a large amount of true negative classifications.

Mating and starvation modulate feeding and host-seeking responses in female bed bugs, Cimex lectularius.

Reproductive fitness and survival are enhanced by adaptive behaviors that are modulated by internal physiological states and external social contexts. The common bed bug, Cimex lectularius, is an obligate hematophagous ectoparasite that requires host blood for growth, development, and reproduction. We investigated how mating, starvation and social interactions affect host-seeking, blood feeding, oviposition, and survival of female bed bugs. The percentage of females that fed and the amount of blood they ingested were greater in mated females (90-100%) than in unmated females (48-60%). Mating state also modulated the female's orientation towards human skin odor in an olfactometer; more mated (69%) than unmated (23%) females responded to human odors. The response rate of unmated females (60%) to skin odor increased with longer starvation period, while the opposite pattern was observed in mated females (20%). Although fecundity after a single blood meal was unaffected by long or short residence and interaction with males, females subjected to frequent copulation attempts had lower survivorship and lifespan than females housed with males for only 24 h. Taken together, these results indicate that by adaptively and coordinately expressing behaviors based on the internal physiological state, females maximize their survival and reproductive fitness.

Reproductive compatibility among populations and host-associated lineages of the common bed bug (Cimex lectularius L.).

As populations differentiate across geographic or host-association barriers, interpopulation fertility is often a measure of the extent of incipient speciation. The bed bug, Cimex lectularius L., was recently found to form two host-associated lineages within Europe: one found with humans (human-associated, HA) and the other found with bats (bat-associated, BA). No unequivocal evidence of contemporary gene flow between these lineages has been found; however, it is unclear whether this is due to an inability to produce viable "hybrid" offspring. To address this question and determine the extent of compatibility between host-associated lineages, we set up mating crosses among populations of bed bugs based on both their host association (human-HA vs. bat-BA) and geographic origin (North America vs. Europe). Within-population fecundity was significantly higher for all HA populations (>1.7 eggs/day) than for BA populations (<1 egg/day). However, all within-population crosses, regardless of host association, had >92% egg hatch rates. Contrary to previous reports, in all interlineage crosses, successful matings occurred, fertile eggs were oviposited, and the F1 "hybrid" generation was found to be reproductively viable. In addition, we evaluated interpopulation genetic variation in Wolbachia among host-associated lineages. We did not find any clear patterns related to host association, nor did we observe a homogenization of Wolbachia lineages across populations that might explain a breakdown of reproductive incompatibility. These results indicate that while the HA and BA populations of C. lectularius represent genetically differentiated host-associated lineages, possibly undergoing sympatric speciation, this is in its incipient stage as they remain reproductively compatible. Other behavioral, physiological, and/or ecological factors likely maintain host-associated differentiation.

The Role of Antennae in Heat Detection and Feeding Behavior in the Bed Bug (Hemiptera: Cimicidae).

The common bed bug (Cimex lectularius L.) is an obligate hematophagous ectoparasite that has significant impacts on human health and well-being. All life stages of bed bugs (except eggs) feed solely on blood, which is required to molt and reproduce. Bed bugs use multiple cues to locate their hosts, including heat, CO2, and body odors. Of these cues, detection of heat appears limited to a short distance of <3 cm. However, it remains unclear if bed bugs can detect radiant heat, what structure(s) are responsible for heat detection, and if heat detection via the antennae is required for feeding. In this study, bed bug response to radiant heat was evaluated using the two-choice T-maze assay with the heat source either in contact with the surface (i.e., conduction) or not in contact (i.e., radiation) in nonantennectomized bed bugs. Further, we systematically ablated the bed bug's antennal segments (distal tip, first segment, and all four segments) and assessed their responses to heat and feeding in a unique two-choice T-maze assay and individual feeding assays, respectively. Our two-choice assays with contact to or no contact with the surface indicated that bed bugs cannot detect radiant heat. Later, we found that the distal tip of the terminal antennal segment is responsible for orientation toward a heat source. However, >50% of the bed bugs fed even when the entire antenna was removed, suggesting redundancy in sensory cues that drive feeding. These results will be used to better understand the role heat plays in bed bug host attraction and design of traps.

Bed bugs shape the indoor microbial community composition of infested homes.

Indoor pests, and the allergens they produce, adversely affect human health. Surprisingly, however, their effects on indoor microbial communities have not been assessed. Bed bug (Cimex lectularius) infestations pose severe challenges in elderly and low-income housing. They void large amounts of liquid feces into the home environment, which might alter the indoor microbial community composition. In this study, using bed bug-infested and uninfested homes, we showed a strong impact of bed bug infestations on the indoor microbial diversity. Floor dust samples were collected from uninfested and bed bug-infested homes and their microbiomes were analyzed before and after heat interventions that eliminated bed bugs. The microbial communities of bed bug-infested homes were radically different from those of uninfested homes, and the bed bug endosymbiont Wolbachia was the major driver of this difference. After bed bugs were eliminated, the microbial community gradually shifted toward the community composition of uninfested homes, strongly implicating bed bugs in shaping the dust-associated environmental microbiome. Further studies are needed to understand the viability of these microbial communities and the potential risks that bed bug-associated microbes and their metabolites pose to human health.

Is it feasible to implement a rapid recovery pathway for adolescent idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion in a single-payer universal health care system?

PURPOSE: The purpose of this project was to determine if it is feasible to implement a rapid recovery pathway (RRP) for the surgical treatment of adolescent idiopathic scoliosis (AIS) within a single-payer universal healthcare system while simultaneously decreasing length of stay (LOS) without increasing post-operative complications. METHODS: A retrospective analysis was completed for all patients who underwent posterior spinal fusion for AIS at a tertiary children's hospital in Canada between March 2010 and February 2019, with date of implementation of the RRP being March 1st, 2015. Patient demographic information was collected along with a variety of outcome variables including: LOS, wound complication, infection, 30-day return to the OR, 30-day emergency department visit, and 30-day hospital readmission. An interrupted time series analysis was utilized to determine if any benefits were associated with the implementation of the RRP. RESULTS: A total of 244 patients were identified, with 113 patients in the conventional pathway and 131 in the RRP. No significant differences in demographic features or post-operative complications were found between the two cohorts (p > 0.05). Using a robust linear time series model, LOS was found to be significantly shorter in the RRP group, with the average LOS being 5.2 [95% IQR 4.3-6.1] days in the conventional group and 3.4 [95% IQR 3.3-3.5] days in the RRP group (p < 0.05). CONCLUSION: This study shows that it is possible to implement a RRP for the surgical treatment of AIS within a single-payer universal healthcare system. Use of the pathway can effectively reduce hospital LOS without increasing the risk of developing a post-operative complication. This has the upside potential to reduce healthcare and family costs. LEVEL OF EVIDENCE: Therapeutic III.

Development of an unsupervised machine learning algorithm for the prognostication of walking ability in spinal cord injury patients.

BACKGROUND CONTEXT: Traumatic spinal cord injury can have a dramatic effect on a patient's life. The degree of neurologic recovery greatly influences a patient's treatment and expected quality of life. This has resulted in the development of machine learning algorithms (MLA) that use acute demographic and neurologic information to prognosticate recovery. The van Middendorp et al. (2011) (vM) logistic regression (LR) model has been established as a reference model for the prediction of walking recovery following spinal cord injury as it has been validated within many different countries. However, an examination of the way in which these prediction models are evaluated is warranted. The area under the receiver operators curve (AUROC) has been consistently used when evaluating model performance, but it has been shown that AUROC overemphasizes the most common event resulting in an inaccurate assessment when the data are imbalanced. Furthermore, there is evidence that the use of more advanced MLA, such as an unsupervised k-means model, may show superior performance compared to LR as they can handle a larger number of features. PURPOSE: The first objective of the study was to assess the performance of both an unsupervised MLA and LR model with complete admission neurologic information against the vM and Hicks models. Second, a comparison between the accuracy of the AUROC and the F1-score will be made to determine which method is superior for the assessment of diagnostic performance of prediction models on large-scale datasets. STUDY DESIGN: Retrospective review of a prospective cohort study. PATIENT SAMPLE: The Rick Hansen Spinal Cord Injury Registry (RHSCIR) was used in this study. All patients enrolled between 2004 and 2017 with complete neurologic examination and Functional Independence Measure outcome data at ≥1 year follow-up or who could walk at discharge were included. The prognostic variables included age (dichotomized at ≥65 years old); American Spinal Injury Association Impairment Scale (AIS) grade; and individual motor, light touch, and pinprick score from L2 to S1. OUTCOME MEASURES: The Functional Independence Measure locomotor score was used to assess independent walking ability at discharge or 1-year follow-up. METHODS: An unsupervised MLA with k=2 was chosen in order to identify a "walk" cluster and a "not walk" cluster. Model performance was assessed through the development of a receiver operating characteristic curve with associated AUROC and a precision-recall curve with associated F1-score. The study and the RHSCIR are supported by funding from Health Canada, Western Economic Diversification Canada, and the Governments of Alberta, British Columbia, Manitoba, and Ontario. These funders had no role in the study or study reporting and the authors have no conflicts of interest to report. RESULTS: No clinically relevant differences were found between with the use of an unsupervised MLA with a greater amount of initial neurologic information compared to the established standards for any AIS classification. Although demonstrated for all separate AIS classifications, most notably, the AUROC for the vM (0.78) and Hicks models (0.76) were found to be superior to that of the new LR model (0.72); however, the vM and Hicks models had more than double the amount of false negative classifications compared to the LR. The F1-scores between these three models were also found to be different but with the vM and Hicks models being lower than the LR (0.85, 0.81, and 0.89, respectively). CONCLUSIONS: No clinically relevant differences were found between the use of an unsupervised MLA with complete admission neurologic information compared to the previously validated standards; however, when comparing the performance of the AUROC and F1-score, the AUROC showed inaccurate prognostic performance when there was an imbalance toward a greater amount of false negatives. Importantly, the F1-score did not succumb to this imbalance. As AUROC has been used as the standard when evaluating performance of prediction models, consideration as to whether this is the most appropriate method is warranted. Future work should focus on comparing AUROC and F1-scores with other previously validated models.

Pervasive Resistance to Pyrethroids in German Cockroaches (Blattodea: Ectobiidae) Related to Lack of Efficacy of Total Release Foggers.

Despite limited efficacy data, do-it-yourself (DIY) insecticide products often promise low-cost alternatives to professional pest control. Total release foggers (TRFs, 'bug bombs'), which are prominent DIY products, were recently shown to be ineffective at reducing German cockroach (Blattella germanica L.) infestations, in contrast to highly effective baits. However, the reason(s) for TRF failure remain unknown. Therefore, we investigated insecticide resistance of apartment-collected cockroaches from homes where TRFs failed. In topical (direct) application assays, resistance to cypermethrin (a common active ingredient in TRFs) was 202 ± 33 times that of a laboratory insecticide-susceptible population (based on LD50 ratios), while resistance to fipronil, a common bait active ingredient, was considerably lower at 14 ± 2 times that of the laboratory insecticide-susceptible population. The addition of PBO, a P450 inhibitor that synergizes pyrethroids, enhanced the efficacy of cypermethrin, but only at high doses of cypermethrin. Additionally, >96% of screened cockroaches possessed at least one copy of the L993F mutation in the voltage-gated sodium channel, known to confer resistance to pyrethroids (knockdown resistance, kdr). Because TRF treatments killed insecticide-susceptible sentinel cockroaches but failed to kill apartment-collected cockroaches, these results suggest that pyrethroid resistance is a major factor contributing to the failure of TRFs. Multiple mechanisms of resistance, including metabolic detoxification of the pyrethroids and kdr mutations that confer target-site insensitivity, suggest that TRFs would lack efficacy against German cockroaches in residential settings, where high levels of pyrethroid resistance have been documented globally.

Exposure risks and ineffectiveness of total release foggers (TRFs) used for cockroach control in residential settings.

BACKGROUND: The German cockroach, Blattella germanica, is one of the most challenging pests to eradicate from indoor environments. Professional pest control is often prohibitively expensive, prompting low-income residents to turn to over-the-counter consumer products, including total release foggers (TRFs, "bug bombs"). Despite their widespread use, little is known regarding either the associated pesticide exposure risks or the efficacy of TRFs. METHODS: Cockroach-infested homes were recruited into the study. Wipe samples were collected from various surfaces before TRFs were discharged, immediately after, and one month later to determine pesticide exposure risks in 20 homes (divided equally among four different TRF products). Simultaneously, cockroach populations were monitored in all homes to assess the efficacy of TRFs. In parallel, 10 homes were treated with gel baits (divided equally between two bait products), to compare TRFs to a more targeted, low-risk, do-it-yourself intervention strategy. RESULTS: TRFs failed to reduce cockroach populations, whereas similarly priced gel baits caused significant declines in the cockroach populations. Use of TRFs resulted in significant pesticide deposits throughout the kitchen. Across all products, pesticides, and horizontal kitchen surfaces, pesticide residues following TRF discharge were 603-times (SEM ±184) higher than baseline, with a median increase of 85 times. CONCLUSIONS: The high risks of pesticide exposure associated with TRFs combined with their ineffectiveness in controlling German cockroach infestations call into question their utility in the marketplace, especially because similarly priced and much safer bait products are highly effective in the indoor environment.

Bed Bug (Hemiptera: Cimicidae) Attraction to Human Odors: Validation of a Two-Choice Olfactometer.

Bed bugs (Cimex lectularius L.) (Hemiptera: Cimicidae) are obligate hematophagous ectoparasites, and, therefore, must locate suitable hosts to ensure survival and reproduction. Their largely nocturnal activity suggests that chemosensory and thermosensory cues would play critical roles in host location. Yet, the importance of olfaction in host attraction of bed bugs remains unclear. We developed and validated a Y-tube, two-choice olfactometer and tested its suitability for investigating attraction to human odors (from skin swabs). Olfactometer orientation significantly affected the percentage of bed bugs that were activated by human odors, with significantly more bed bugs responding when the olfactometer was oriented vertically (bug introduced at bottom of the olfactometer) compared with all other orientations. Starved (7-10 d) adult males, mated females, and nymphs responded (47-77% moved up the olfactometer and made a choice) when human odors were present in the olfactometer, while starved, unmated females did not respond. Skin swabs from all five human participants elicited high response rates (65-82%), and bed bugs from four different populations responded to skin swabs (40-82% response rate). However, in all assays including those resulting in relatively low response rates, bed bugs exhibited >90% preference for human odors over blank controls. These results provide strong evidence that bed bugs can respond and orient towards human odors, independently of all other host cues. Furthermore, the validated olfactometer should enable rapid and efficient evaluations of bed bug behavioral responses to semiochemicals.