LLIN Evaluation in Uganda Project (LLINEUP)-effects of a vector control trial on Plasmodium infection prevalence and genotypic markers of insecticide resistance in Anopheles vectors from 48 districts of Uganda.

Pyrethroid bednets treated with the synergist piperonyl butoxide (PBO) offer the possibility of improved vector control in mosquito populations with metabolic resistance. In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus PBO (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, we conducted cross-sectional household entomological surveys at baseline and then every 6 months for two years, which we use here to investigate longitudinal changes in mosquito infection rate and genetic markers of resistance. Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected (PCR-positive) with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s., but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Distribution of LLINs in Uganda was previously found to be associated with reductions in parasite prevalence and vector density, but here we show that the proportion of infective mosquitoes remained stable across both PBO and non-PBO LLINs, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395 .

Comparison of different trapping methods to collect malaria vectors indoors and outdoors in western Kenya.

BACKGROUND: Vector surveillance is among the World Health Organization global vector control response (2017-2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors. METHODS: Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R. RESULTS: Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P < 0.001) then UV-LT (mean = 3.70; RR = 3.97, P < 0.001) and CDC-LT (mean = 1.74; RR = 1.89, P = 0.03) compared to HLC. UV-LT and CDC-LT indoors captured averagely 0.18 An. arabiensis RR = 5.75, P = 0.028 and RR = 5.87, P = 0.028 respectively. Outdoors, UV-LT collected significantly higher Anopheles mosquitoes compared to HLC (An. funestus: RR = 5.18, P < 0.001; An. arabiensis: RR = 15.64, P = 0.009; An. coustani: RR = 11.65, P < 0.001). Anopheles funestus hourly biting indoors in UV-LT and CDC-LT indicated different peaks compared to HLC. CONCLUSIONS: Anopheles funestus remains the predominant mosquito species. More mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs. The varied trends observed at different times of the night suggest that these methods collect mosquitoes with diverse activities and care must be taken when interpreting the results.

Development of an implantable trapezium carpal bone replacement for measuring in vivo loads at the base of the thumb.

Understanding the loads that occur across musculoskeletal joints is critical to advancing our understanding of joint function and pathology, implant design and testing, as well as model verification. Substantial work in these areas has occurred in the hip and knee but has not yet been undertaken in smaller joints, such as those in the wrist. The thumb carpometacarpal (CMC) joint is a uniquely human articulation that is also a common site of osteoarthritis with unknown etiology. We present two potential designs for an instrumented trapezium implant and compare approaches to load calibration. Two instrumented trapezia designs were prototyped using strain gauge technology: Tube and Diaphragm. The Tube design is a well-established structure for sensing loads while the Diaphragm is novel. Each design was affixed to a 6-DOF load cell that was used as the reference. Loads were applied manually, and two calibration methods, supervised neural network (DEEP) and matrix algebra (MAT), were implemented. Bland-Altman 95% confidence interval for the limits of agreement (95% CI LOA) was used to assess accuracy. Overall, the DEEP calibration decreased 95% CI LOA compared with the MAT approach for both designs. The Diaphragm design outperformed the Tube design in measuring the primary load vector (joint compression). Importantly, the Diaphragm design permits the hermetic encapsulation of all electronics, which is not possible with the Tube design, given the small size of the trapezium. Substantial work remains before this device can be approved for implantation, but this work lays the foundation for further device development that will be required.

Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele specific expression.

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in cis, by regulatory sequences on the same chromosome, and by trans acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in cis-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb resistant and susceptible Anopheles gambiae strains to identify cis-regulated genes that might be responsible for the resistant phenotype using RNAseq, and cis-regulatory module sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele specific expression in hybrids of insecticide susceptible and resistant strains, suggesting cis regulation is an important mechanism of gene expression regulation in Anopheles gambiae. The genes showing allele specific expression included a higher proportion of Anopheles specific genes on average younger than genes those with balanced allelic expression.

Late morning biting behaviour of Anopheles funestus is a risk factor for transmission in schools in Siaya, western Kenya.

BACKGROUND: Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. With changing vector behaviour towards early morning biting, it is important to determine whether there is an additional risk of transmission in schools. This study sought to understand whether late morning biting by Anopheles funestus, previously documented in households in western Kenya, was replicated in schools. METHODS: From the 4th to the 6th of August 2023, human landing collections were conducted hourly in four schools in Alego Usonga sub-County, Siaya County. The collections were conducted in and outside five classrooms in each school and ran for 17 h, starting at 18:00 until 11:00 h the next morning. RESULTS: Anopheles funestus was the predominant species collected, forming 93.2% (N = 727) of the entire collection, with peak landing between 06:00 and 07:00 h and continuing until 11:00 h. More than half of the collected An. funestus were either fed or gravid, potentially indicative of multiple bloodmeals within each gonotrophic cycle, and had a sporozoite rate of 2.05%. CONCLUSION: School children spend up to 10 h of their daytime in schools, reporting between 06:00 and 07:00 h and staying in school until as late as 17:00 h, meaning that they receive potentially infectious mosquito bites during the morning hours in these settings. There is a need to consider vector control approaches targeting schools and other peridomestic spaces in the morning hours when An. funestus is active.

LLIN Evaluation in Uganda Project (LLINEUP) - Plasmodium infection prevalence and genotypic markers of insecticide resistance in Anopheles vectors from 48 districts of Uganda.

Background: In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus the synergist piperonyl butoxide (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, cross-sectional entomological surveys were carried out at baseline and then every 6 months for two years. In each survey, ten households per HSD were randomly selected for indoor household entomological collections. Results: Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s, but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Conclusions: Distribution of LLINs in Uganda was associated with reductions in parasite prevalence and vector density, but the proportion of infective mosquitoes remained stable, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration:: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395.

A comparison of the attractiveness of flowering plant blossoms versus attractive targeted sugar baits (ATSBs) in western Kenya.

Attractive Targeted Sugar Baits (ATSB) have been demonstrated to result in significant reductions in malaria vector numbers in areas of scarce vegetation cover such as in Mali and Israel, but it is not clear whether such an effect can be replicated in environments where mosquitoes have a wide range of options for sugar resources. The current study evaluated the attractiveness of the predominant flowering plants of Asembo Siaya County, western Kenya in comparison to an ATSB developed by Westham Co. Sixteen of the most common flowering plants in the study area were selected and evaluated for relative attractiveness to malaria vectors in semi-field structures. Six of the most attractive flowers were compared to determine the most attractive to local Anopheles mosquitoes. The most attractive plant was then compared to different versions of ATSB. In total, 56,600 Anopheles mosquitoes were released in the semi-field structures. From these, 5150 mosquitoes (2621 males and 2529 females) of An. arabiensis, An. funestus and An. gambiae were recaptured on the attractancy traps. Mangifera indica was the most attractive sugar source for all three species while Hyptis suaveolens and Tephrosia vogelii were the least attractive plants to the mosquitoes. Overall, ATSB version 1.2 was significantly more attractive compared to both ATSB version 1.1 and Mangifera indica. Mosquitoes were differentially attracted to various natural plants in western Kenya and ATSB. The observation that ATSB v1.2 was more attractive to local Anopheles mosquitoes than the most attractive natural sugar source indicates that this product may be able to compete with natural sugar sources in western Kenya and suggests this product may have the potential to impact mosquito populations in the field.

Septic Mycobacterium Avium Intracellulare Extensor Tenosynovitis of the Wrist.

Mycobacterium avium intracellulare (MAI) infections of the hand, wrist, and upper extremity are rare, but potentially devastating atypical mycobacterial infections that can affect tendon, bone, and other soft tissues of the musculoskeletal system. We present an immunocompromised patient presenting with acute swelling and pain in the dorsum of the hand and wrist that underwent a wrist extensor tenosynovectomy with intraoperative cultures revealing infection with MAI. The patient developed severe progression of the infection with osteomyelitis of the distal forearm and carpal bones, multiple subsequent extensor tendon ruptures, and dorsal skin necrosis. The infection was eradicated with a combination of surgical treatment and antibiotic therapy. The case is discussed in context of the prior scant literature of infectious tenosynovitis of the hand, wrist, and upper extremity caused by MAI. This case report and literature review outline recommendations for diagnosis and effective treatment of MAI.

Natural sugar feeding rates of Anopheles mosquitoes collected by different methods in western Kenya.

Attractive targeted sugar baits (ATSBs) are a potential vector control tool that exploits the sugar-feeding behaviour of mosquitoes. We evaluated the sugar-feeding behaviour of Anopheles mosquitoes as part of baseline studies for cluster randomised controlled trials of ATSBs. Mosquitoes were collected indoors and outdoors from two villages in western Kenya using prokopack aspirations, malaise tent traps and ultraviolet (UV) light traps. Individual mosquitoes were subjected to the cold anthrone test to assess the presence of sugar. Overall, 15.7% of collected mosquitoes had fed on natural sugar sources. By species and sex, the proportion sugar-fed was 41.3% and 27.7% in male and female Anopheles funestus, 27.2% and 12.8% in male and female An. arabiensis, and 9.7% and 8.3% in male and female An. coustani, respectively. Sugar-feeding was higher in unfed than blood-fed mosquitoes and higher in male than gravid mosquitoes. Anopheles mosquitoes obtained sugar meals from natural sources during all physiological stages, whether they rest indoors or outdoors. These findings offer a potential avenue to exploit for the control of mosquitoes, particularly with the advent of ATSBs, which have been shown to reduce mosquito densities in other regions.

Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for antimalarial intervention deployment.

Studies of insecticide resistance provide insights into the capacity of populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs). Resistance in the major malaria vectors has increased in concert with the expansion of LLIN distributions. Identifying genetic mechanisms underlying high-level resistance is crucial for the development and deployment of resistance-breaking tools. Using the Anopheles gambiae 1000 genomes (Ag1000g) data we identified a very recent selective sweep in mosquitoes from Uganda which localized to a cluster of cytochrome P450 genes. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in Cyp6p4 (I236M), an upstream insertion of a partial Zanzibar-like transposable element (TE) and a duplication of the Cyp6aa1 gene. The mutations appear to have originated recently in An. gambiae from the Kenya-Uganda border, with stepwise replacement of the double-mutant (Zanzibar-like TE and Cyp6p4-236 M) with the triple-mutant haplotype (including Cyp6aa1 duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple-mutant haplotype is strongly associated with increased expression of genes able to metabolize pyrethroids and is strongly predictive of resistance to pyrethroids most notably deltamethrin. Importantly, there was increased mortality in mosquitoes carrying the triple-mutation when exposed to nets cotreated with the synergist piperonyl butoxide (PBO). Frequencies of the triple-mutant haplotype remain spatially variable within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO-pyrethroid cotreated LLINs across African countries.

Reviewing the WHO Tube Bioassay Methodology: Accurate Method Reporting and Numbers of Mosquitoes Are Key to Producing Robust Results.

Accurately monitoring insecticide resistance in target mosquito populations is important for combating malaria and other vector-borne diseases, and robust methods are key. The "WHO susceptibility bioassay" has been available from the World Health Organization for 60+ years: mosquitoes of known physiological status are exposed to a discriminating concentration of insecticide. Several changes to the test procedures have been made historically, which may seem minor but could impact bioassay results. The published test procedures and literature for this method were reviewed for methodological details. Areas where there was room for interpretation in the test procedures or where the test procedures were not being followed were assessed experimentally for their impact on bioassay results: covering or uncovering of the tube end during exposure; the number of mosquitoes per test unit; and mosquito age. Many publications do not cite the most recent test procedures; methodological details are reported which contradict the test procedures referenced, or methodological details are not fully reported. As a result, the precise methodology is unclear. Experimental testing showed that using fewer than the recommended 15-30 mosquitoes per test unit significantly reduced mortality, covering the exposure tube had no significant effect, and using mosquitoes older than 2-5 days old increased mortality, particularly in the resistant strain. Recommendations are made for improved reporting of experimental parameters.

The human-baited host decoy trap (HDT) is an efficient sampling device for exophagic Anopheles arabiensis within irrigated lands in southern Malawi.

Irrigation schemes provide an ideal habitat for Anopheles mosquitoes particularly during the dry season. Reliable estimates of outdoor host-seeking behaviour are needed to assess the impact of vector control options and this is particularly the case for Anopheles arabiensis which displays a wide range of behaviours that circumvent traditional indoor-insecticide based control. In this study we compared the sampling efficiency of the host decoy trap (HDT) with the human landing catch (HLC) and Suna trap in a repeated Latin square design in two villages (Lengwe and Mwanza) on an irrigated sugar estate in southern Malawi. Over the course of 18 trapping nights, we caught 379 female Anopheles, the majority of which were identified as An. arabiensis. Across both villages, there was no detectable difference in Anopheles catch between the HDT compared with the HLC (RR = 0.85, P = 0.508). The overall sensitivity of the HLC was greater than the Suna trap regardless of mosquito density (Lengwe, α = 2.75, 95% credible interval: 2.03-3.73; Mwanza, α = 3.38, 95% credible interval: 1.50-9.30) whereas the sensitivity of the HDT was only greater than the Suna trap when mosquito numbers were high (Lengwe, α = 2.63, 95% credible interval: 2.00-3.85).We conclude that the HDT is an effective sampling device for outdoor host seeking An. arabiensis in southern Malawi. The presence of An. arabiensis in irrigated lands during the dry season poses a challenge for ongoing indoor vector control efforts.

Impacts of Diabetes, Aging, and Hearing Loss on Speech-on-Speech Masking and Spatial Release in a Large Veteran Cohort.

PURPOSE: Type 2 diabetes mellitus (DM2) is associated with impaired hearing. However, the evidence is less clear if DM2 can lead to difficulty understanding speech in complex acoustic environments, independently of age and hearing loss effects. The purpose of this study was to estimate the magnitude of DM2-related effects on speech understanding in the presence of competing speech after adjusting for age and hearing. METHOD: A cross-sectional study design was used to investigate the relationship between DM2 and speech understanding in 190 Veterans (M age = 47 years, range: 25-76). Participants were classified as having no diabetes (n = 74), prediabetes (n = 19), or DM2 that was well controlled (n = 24) or poorly controlled (n = 73). A test of spatial release from masking (SRM) was presented in a virtual acoustical simulation over insert earphones with multiple talkers using sentences from the coordinate response measure corpus to determine the target-to-masker ratio (TMR) required for 50% correct identification of target speech. A linear mixed model of the TMR results was used to estimate SRM and separate effects of diabetes group, age, and low-frequency pure-tone average (PTA-low) and high-frequency pure-tone average. A separate model estimated the effects of DM2 on PTA-low. RESULTS: After adjusting for hearing and age, diabetes-related effects remained among those whose DM2 was well controlled, showing an SRM loss of approximately 0.5 dB. Results also showed effects of hearing loss and age, consistent with the literature on people without DM2. Low-frequency hearing loss was greater among those with DM2. CONCLUSIONS: In a large cohort of Veterans, low-frequency hearing loss and older age negatively impact speech understanding. Compared with nondiabetics, individuals with controlled DM2 have additional auditory deficits beyond those associated with hearing loss or aging. These results provide a potential explanation for why individuals who have diabetes and/or are older often report difficulty understanding speech in real-world listening environments. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.16746475.

Health Care Providers' Negative Implicit Attitudes and Stereotypes of American Indians.

Research suggests that implicit biases held by health care providers may play a role in perpetuating health disparities. However, minimal work has examined the presence of providers' negative implicit attitudes and stereotypes of American Indians. The current work examined implicit attitudes and stereotypes toward American Indians among 111 health care providers using the Implicit Association Test. Results revealed evidence of negative implicit attitudes toward American Indians. In addition, results showed that providers implicitly stereotype American Indians as noncompliant. This effect was moderated by self-reports of cultural competency and implicit bias training experience such that those reporting cultural competency or implicit bias training reported lower implicit stereotyping than those reporting no cultural competency or implicit bias training. Moreover, medical students reported lower implicit stereotyping than medical residents and practicing physicians. Implications of providers' implicit biases on treatment of American Indian patients and implicit bias reduction research are discussed.

Spatial targeting of Screening + Eave tubes (SET), a house-based malaria control intervention, in Côte d'Ivoire: A geostatistical modelling study.

New malaria control tools and tailoring interventions to local contexts are needed to reduce the malaria burden and meet global goals. The housing modification, screening plus a targeted house-based insecticide delivery system called the In2Care® Eave Tubes, has been shown to reduce clinical malaria in a large cluster randomised controlled trial. However, the widescale suitability of this approach is unknown. We aimed to predict household suitability and define the most appropriate locations for ground-truthing where Screening + Eave Tubes (SET) could be implemented across Côte d'Ivoire. We classified DHS sampled households into suitable for SET based on the walls and roof materials. We fitted a Bayesian beta-binomial logistic model using the integrated nested Laplace approximation (INLA) to predict suitability of SET and to define priority locations for ground-truthing and to calculate the potential population coverage and costs. Based on currently available data on house type and malaria infection rate, 31% of the total population and 17.5% of the population in areas of high malaria transmission live in areas suitable for SET. The estimated cost of implementing SET in suitable high malaria transmission areas would be $46m ($13m -$108m). Ground-truthing and more studies should be conducted to evaluate the efficacy and feasibility of SET in these settings. The study provides an example of implementing strategies to reflect local socio-economic and epidemiological factors, and move beyond blanket, one-size-fits-all strategies.

Health Benefits In 2020: Premiums In Employer-Sponsored Plans Grow 4 Percent; Employers Consider Responses To Pandemic.

The annual Kaiser Family Foundation Employer Health Benefits Survey is the benchmark survey of the cost and coverage of employer-sponsored health benefits in the United States. The 2020 survey was designed and largely fielded before the full extent of the coronavirus disease 2019 (COVID-19) pandemic had been felt by employers. Data collection took place from mid-January through July, with half of the interviews being completed in the first three months of the year. Most of the key metrics that we measure-including premiums and cost sharing-reflect employers' decisions made before the full impacts of the pandemic were felt. We found that in 2020 the average annual premium for single coverage rose 4 percent, to $7,470, and the average annual premium for family coverage also rose 4 percent, to $21,342. Covered workers, on average, contributed 17 percent of the cost for single coverage and 27 percent of the cost for family coverage. Fifty-six percent of firms offered health benefits to at least some of their workers, and 64 percent of workers were covered at their own firm. Many large employers reported having "very broad" provider networks, but many recognized that their largest plan had a narrower network for mental health providers.

Myeloid cell responsiveness to interferon-gamma is sufficient for initial resistance to Listeria monocytogenes.

The type II interferon (IFNγ) promotes resistance to intracellular pathogens. Most immune and somatic cells also express the IFNγ receptor (IFNGR) and respond to IFNγ. While myeloid cell have been implicated as important targets of IFNγ, it remains unknown if IFNγ signaling to myeloid cell types suffices for resistance to infection. Here, we addressed this question by generating mice in which IFNGR1 is selectively expressed by myeloid cells. These "MSGR1" (myeloid selective IFNGR1) mice express an epitope-tagged Ifngr1 transgene (fGR1) from the myeloid-specific c-fms promoter in a background lacking endogenous Ifngr1. IFNGR staining was selectively observed on myeloid cells in the MSGR1 mice and correlated with responsiveness of these cells to IFNγ. During systemic infection by the bacterium Listeria monocytogenes, activation marker staining was comparable on monocytes from MSGR1 and control B6 mice. Bacterial burdens and survival were also equivalent in MSGR1 and wildtype B6 animals at a timepoint when B6.Ifngr1 -/- mice began to succumb. These data confirm that activation of inflammatory monocytes and neutrophils is a key mechanism by which IFNγ promotes innate anti-bacterial immunity and suggest that IFNγ targeting of myeloid cells is largely sufficient to mediate protection against systemic L. monocytogenes.

Health Benefits In 2019: Premiums Inch Higher, Employers Respond To Federal Policy.

The annual Kaiser Family Foundation Employer Health Benefits Survey found that in 2019 the average annual premium for single coverage rose 4 percent to $7,188, and the average annual premium for family coverage rose 5 percent to $20,576. Covered workers contributed 18 percent of the cost for single coverage and 30 percent of the cost for family coverage, on average, with considerable variation across firms. Fifty-seven percent of firms offered health benefits to at least some of their workers. While some larger firms reported that take-up dropped because of the elimination of the individual mandate penalty, the overall share of workers covered at their own firm (61 percent) was similar to that in recent years. Large employers reported taking a variety of steps to address the opioid epidemic over the past few years. Our findings offer some context for the role of health insurance reform in the 2020 election cycle.

A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection.

The bacterial pathogen Listeria monocytogenes (Lm) capitalizes on natural killer (NK) cell production of regulatory interleukin (IL)-10 to establish severe systemic infections. Here, we identify regulators of this IL-10 secretion. We show that IL-18 signals to NK cells license their ability to produce IL-10. IL-18 acts independent of IL-12 and STAT4, which co-stimulate IFNγ secretion. Dendritic cell (DC) expression of Nlrp3 is required for IL-18 release in response to the Lm p60 virulence protein. Therefore, mice lacking Nlrp3, Il18, or Il18R fail to accumulate serum IL-10 and are highly resistant to systemic Lm infection. We further show that cells expressing or dependent on Batf3 are required for IL-18-inducing IL-10 production observed in infected mice. These findings explain how Il18 and Batf3 promote susceptibility to bacterial infection and demonstrate the ability of Lm to exploit NLRP3 for the promotion of regulatory NK cell activity.

Description, Normative Data, and Utility of the Hearing Aid Skills and Knowledge Test.

BACKGROUND: The ability to manage hearing aids is crucial for successful outcomes and for maintaining hearing aid use. It is therefore important to have a tool that can effectively identify which hearing aid management skills are lacking so that the audiologist can provide additional education and training on that skill. Such a tool can also provide useful quantitative data for researchers. PURPOSE: To collect normative data (Experiment 1) and assess inter- and intrarater reliability (Experiment 2) for a hearing aid management assessment tool known as the Hearing Aid Skills and Knowledge (HASK) test. STUDY SAMPLE: Two hundred thirty-six new hearing aid users recruited from the VA Portland Health Care System and 126 experienced hearing aid users recruited from the local Portland community participated in Experiment 1. The veteran participants were taking part in a larger hearing aid study, and the community participants were recruited at community events that took place around Portland, OR. Three clinical audiologists and two AuD students completing their fourth year externship participated in Experiment 2. DATA COLLECTION AND ANALYSIS: In Experiment 1, HASK data were collected from the new hearing aid users at 4-8 wk and 6-8 mo after the fitting of their first pair of hearing aids, and from experienced users on a single occasion. In addition, self-reported hearing aid use, benefit, and satisfaction were assessed for all participants. The audiologists/students in Experiment 2 watched and independently scored videos of six individuals completing the HASK. Intraclass correlation coefficients (ICCs) across audiologists were computed for HASK scores. Three audiologists/students rated at least one video on two occasions to provide interrater reliability data. RESULTS: Mean performance on the HASK was about 70% for knowledge and 80% for skills for both the new and experienced hearing aid users. Performance did not change among the new users between the 4-8 wk and 6-8 mo administration. The specific skills lacking were associated with advanced management abilities (cleaning and troubleshooting). Experiment 2 revealed ICCs for inter- and intrarater reliability for HASK to range from 0.76 to 0.94, showing acceptable to excellent reliability. CONCLUSIONS: The HASK is a quick and easy test with good-to-excellent inter- and intrarater reliability. It can effectively identify which hearing aid management skills are lacking so that the audiologist can provide additional education and training on those skills. Data show performance is ∼70% for knowledge and 80% for skills and this does not change with hearing aid experience. The significant positive correlations between HASK scores and hearing aid use and satisfaction highlight the notion that ability to manage hearing aids successfully is integral to good hearing aid outcome.