Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.

Mycobacterium tuberculosis (Mtb) infects lung myeloid cells, but the specific Mtb-permissive cells and host mechanisms supporting Mtb persistence during chronic infection are incompletely characterized. We report that after the development of T cell responses, CD11clo monocyte-derived cells harbor more live Mtb than alveolar macrophages (AM), neutrophils, and CD11chi monocyte-derived cells. Transcriptomic and functional studies revealed that the lysosome pathway is underexpressed in this highly permissive subset, characterized by less lysosome content, acidification, and proteolytic activity than AM, along with less nuclear TFEB, a regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in CD11clo monocyte-derived cells but promotes recruitment of monocytes that develop into permissive lung cells, mediated by the Mtb ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome functions of macrophages in vitro and in vivo, improving control of Mtb infection. Our results suggest that Mtb exploits lysosome-poor lung cells for persistence and targeting lysosome biogenesis is a potential host-directed therapy for tuberculosis.

GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells.

GPR174 is abundantly expressed in B and T lymphocytes and has a role in restraining T cell responses, but the function of GPR174 in B cells is less clear. Here we report that upon in vitro culture B cells undergo a spontaneous GPR174-dependent activation process that is associated with marked changes in gene expression, including up-regulation of Cd86, Nr4a1, Ccr7, and phosphodiesterases. B cells lacking Gαs show a block in induction of the GPR174-dependent program. Spontaneous up-regulation of CD86 in cultured B cells is dependent on protein kinase A. Both GPR174- and Gαs-deficient B cells show enhanced survival in culture. In vivo, GPR174 contributes to NUR77 expression in follicular B cells and is needed for establishing a marginal zone compartment of normal size. Treatment of mice with lysophosphatidylserine (lysoPS), a GPR174 ligand, is sufficient to promote CD86 up-regulation by follicular B cells. These findings demonstrate that GPR174 can signal via Gαs to modulate B cell gene expression and show this can occur in vivo in response to lysoPS. Additionally, the findings illuminate a pathway that might be targeted to improve systems for the in vitro study of B cell responses.

Myeloid mineralocorticoid receptors contribute to skeletal muscle repair in muscular dystrophy and acute muscle injury.

Suppressing mineralocorticoid receptor (MR) activity with MR antagonists is therapeutic for chronic skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. Although mechanisms underlying clinical MR antagonist efficacy for DMD cardiomyopathy and other cardiac diseases are defined, mechanisms in skeletal muscles are not fully elucidated. Myofiber MR knockout improves skeletal muscle force and a subset of dystrophic pathology. However, MR signaling in myeloid cells is known to be a major contributor to cardiac efficacy. To define contributions of myeloid MR in skeletal muscle function and disease, we performed parallel assessments of muscle pathology, cytokine levels, and myeloid cell populations resulting from myeloid MR genetic knockout in muscular dystrophy and acute muscle injury. Myeloid MR knockout led to lower levels of C-C motif chemokine receptor 2 (CCR2)-expressing macrophages, resulting in sustained myofiber damage after acute injury of normal muscle. In acute injury, myeloid MR knockout also led to increased local muscle levels of the enzyme that produces the endogenous MR agonist aldosterone, further supporting important contributions of MR signaling in normal muscle repair. In muscular dystrophy, myeloid MR knockout altered cytokine levels differentially between quadriceps and diaphragm muscles, which contain different myeloid populations. Myeloid MR knockout led to higher levels of fibrosis in dystrophic diaphragm. These results support important contributions of myeloid MR signaling to skeletal muscle repair in acute and chronic injuries and highlight the useful information gained from cell-specific genetic knockouts to delineate mechanisms of pharmacological efficacy.

Early Inflammation in Muscular Dystrophy Differs between Limb and Respiratory Muscles and Increases with Dystrophic Severity.

Duchenne muscular dystrophy (DMD) is a genetic, degenerative, striated muscle disease exacerbated by chronic inflammation. Mdx mice in the genotypic DMD model poorly represent immune-mediated pathology observed in patients. Improved understanding of innate immunity in dystrophic muscles is required to develop specific anti-inflammatory treatments. Here, inflammation in mdx mice and the more fibrotic utrn+/-;mdx Het model was comprehensively investigated. Unbiased analysis showed that mdx and Het mice contain increased levels of numerous chemokines and cytokines, with further increased in Het mice. Chemokine and chemokine receptor gene expression levels were dramatically increased in 4-week-old dystrophic quadriceps muscles, and to a lesser extent in diaphragm during the early injury phase, and had a small but consistent increase at 8 and 20 weeks. An optimized direct immune cell isolation method prevented loss of up to 90% of macrophages with density-dependent centrifugation previously used for mdx flow cytometry. Het quadriceps contain higher proportions of neutrophils and infiltrating monocytes than mdx, and higher percentages of F4/80Hi, but lower percentages of F4/80Lo cells and patrolling monocytes compared with Het diaphragms. These differences may restrict regenerative potential of dystrophic diaphragms, increasing pathologic severity. Fibrotic and inflammatory gene expression levels are higher in myeloid cells isolated from Het compared with mdx quadriceps, supporting Het mice may represent an improved model for testing therapeutic manipulation of inflammation in DMD.

NSW Cannabis Medicines Advisory Service preliminary survey results: enquirer perceptions and patient outcomes.

BACKGROUND: In 2018, an innovative, State government-funded cannabis medicines drug information service was established for health professionals in New South Wales (NSW). The NSW Cannabis Medicines Advisory Service (CMAS) provides expert clinical guidance and support to medical practitioners considering prescribing a cannabis medicine to their patient(s). AIMS: This research examines quality assurance and patient outcomes related to enquirers' experience with NSW CMAS. METHODS: Data collection involved an online, anonymous survey with two components. Following a health professional enquiry, quality assurance data were collected about the enquirers' experience with NSW CMAS. The second survey focussed on patient outcomes and provides real-world observational data about cannabis medicines safety and effectiveness across a wide range of indications. RESULTS: Data collection occurred between January 2020 and June 2021. Preliminary analyses were based on 68 quality assurance and 50 patient outcomes survey responses. General practitioners represented the highest proportion of survey responses (n = 33; 49%). The most common enquiry involved 'patient-specific advice' (n = 50; 74%). Patient-specific information provided by the service was mainly used for prescribing decision support (n = 45; 90%). CONCLUSIONS: Preliminary findings highlight the impact of an innovative cannabis medicines drug information service in supporting health professional clinical practice in an area of rapid knowledge translation. Quality assurance data indicate that the service is perceived well by the majority of enquirers. Patient outcomes data across a wide range of indications suggest some effectiveness and a reasonable safety profile for prescribed cannabis medicines for most patients.

Hierarchical Learning of Statistical Regularities over Multiple Timescales of Sound Sequence Processing: A Dynamic Causal Modeling Study.

Our understanding of the sensory environment is contextualized on the basis of prior experience. Measurement of auditory ERPs provides insight into automatic processes that contextualize the relevance of sound as a function of how sequences change over time. However, task-independent exposure to sound has revealed that strong first impressions exert a lasting impact on how the relevance of sound is contextualized. Dynamic causal modeling was applied to auditory ERPs collected during presentation of alternating pattern sequences. A local regularity (a rare p = .125 vs. common p = .875 sound) alternated to create a longer timescale regularity (sound probabilities alternated regularly creating a predictable block length), and the longer timescale regularity changed halfway through the sequence (the regular block length became shorter or longer). Predictions should be revised for local patterns when blocks alternated and for longer patterning when the block length changed. Dynamic causal modeling revealed an overall higher precision for the error signal to the rare sound in the first block type, consistent with the first impression. The connectivity changes in response to errors within the underlying neural network were also different for the two blocks with significantly more revision of predictions in the arrangement that violated the first impression. Furthermore, the effects of block length change suggested errors within the first block type exerted more influence on the updating of longer timescale predictions. These observations support the hypothesis that automatic sequential learning creates a high-precision context (first impression) that impacts learning rates and updates to those learning rates when predictions arising from that context are violated. The results further evidence automatic pattern learning over multiple timescales simultaneously, even during task-independent passive exposure to sound.

The Effects of Increased Visual Information on Cognitive Workload in a Helicopter Simulator.

OBJECTIVE: To test the effects of enhanced display information ("symbology") on cognitive workload in a simulated helicopter environment, using the detection response task (DRT). BACKGROUND: Workload in highly demanding environments can be influenced by the amount of information given to the operator and consequently it is important to limit potential overload. METHODS: Participants (highly trained military pilots) completed simulated helicopter flights, which varied in visual conditions and the amount of information given. During these flights, participants also completed a DRT as a measure of cognitive workload. RESULTS: With more visual information available, pilots' landing accuracy was improved across environmental conditions. The DRT is sensitive to changes in cognitive workload, with workload differences shown between environmental conditions. Increasing symbology appeared to have a minor effect on workload, with an interaction effect of symbology and environmental condition showing that symbology appeared to moderate workload. CONCLUSION: The DRT is a useful workload measure in simulated helicopter settings. The level of symbology-moderated pilot workload. The increased level of symbology appeared to assist pilots' flight behavior and landing ability. Results indicate that increased symbology has benefits in more difficult scenarios. APPLICATIONS: The DRT is an easily implemented and effective measure of cognitive workload in a variety of settings. In the current experiment, the DRT captures the increased workload induced by varying the environmental conditions, and provides evidence for the use of increased symbology to assist pilots.

A Broader Application of the Detection Response Task to Cognitive Tasks and Online Environments.

OBJECTIVE: The present research applied a well-established measure of cognitive workload in driving literature to an in-lab paradigm. We then extended this by comparing the in-lab version of the task to an online version. BACKGROUND: The accurate and objective measurement of cognitive workload is important in many aspects of psychological research. The detection response task (DRT) is a well-validated method for measuring cognitive workload that has been used extensively in applied tasks, for example, to investigate the effects of phone usage or passenger conversation on driving, but has been used sparingly outside of this field. METHOD: The study investigated whether the DRT could be used to measure cognitive workload in tasks more commonly used in experimental cognitive psychology and whether this application could be extended to online environments. We had participants perform a multiple object tracking (MOT) task while simultaneously performing a DRT. We manipulated the cognitive load of the MOT task by changing the number of dots to be tracked. RESULTS: Measurements from the DRT were sensitive to changes in the cognitive load, establishing the efficacy of the DRT for experimental cognitive tasks in lab-based situations. This sensitivity continued when applied to an online environment (our code for the online DRT implementation is freely available at https://osf.io/dc39s/), though to a reduced extent compared to the in-lab situation. CONCLUSION: The MOT task provides an effective manipulation of cognitive workload. The DRT is sensitive to changes in workload across a range of settings and is suitable to use outside of driving scenarios, as well as via online delivery. APPLICATION: Methodology shows how the DRT could be used to measure sources of cognitive workload in a range of human factors contexts.

Selective Inhibition of Coxiella burnetii Replication by the Steroid Hormone Progesterone.

Coxiella burnetii is a zoonotic bacterial obligate intracellular parasite and the cause of query (Q) fever. During natural infection of female animals, C. burnetii shows tropism for the placenta and is associated with late-term abortion, at which time the pathogen titer in placental tissue can exceed one billion bacteria per gram. During later stages of pregnancy, placental trophoblasts serve as the major source of progesterone, a steroid hormone known to affect the replication of some pathogens. During infection of placenta-derived JEG-3 cells, C. burnetii showed sensitivity to progesterone but not the immediate precursor pregnenolone or estrogen, another major mammalian steroid hormone. Using host cell-free culture, progesterone was determined to have a direct inhibitory effect on C. burnetii replication. Synergy between the inhibitory effect of progesterone and the efflux pump inhibitors verapamil and 1-(1-naphthylmethyl)-piperazine is consistent with a role for efflux pumps in preventing progesterone-mediated inhibition of C. burnetii activity. The sensitivity of C. burnetii to progesterone, but not structurally related molecules, is consistent with the ability of progesterone to influence pathogen replication in progesterone-producing tissues.

Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection.

Coxiella burnetii is the causative agent of Q fever, a zoonotic disease that threatens both human and animal health. Due to the paucity of experimental animal models, little is known about how host factors interface with bacterial components and affect pathogenesis. Here, we used Drosophila melanogaster, in conjunction with the biosafety level 2 (BSL2) Nine Mile phase II (NMII) clone 4 strain of C. burnetii, as a model to investigate host and bacterial components implicated in infection. We demonstrate that adult Drosophila flies are susceptible to C. burnetii NMII infection and that this bacterial strain, which activates the immune deficiency (IMD) pathway, is able to replicate and cause mortality in the animals. We show that in the absence of Eiger, the only known tumor necrosis factor (TNF) superfamily homolog in Drosophila, Coxiella-infected flies exhibit reduced mortality from infection. We also demonstrate that the Coxiella type 4 secretion system (T4SS) is critical for the formation of the Coxiella-containing vacuole and establishment of infection in Drosophila Altogether, our data reveal that the Drosophila TNF homolog Eiger and the Coxiella T4SS are implicated in the pathogenesis of C. burnetii in flies. The Drosophila/NMII model mimics relevant aspects of the infection in mammals, such as a critical role of host TNF and the bacterial T4SS in pathogenesis. Our work also demonstrates the usefulness of this BSL2 model to investigate both host and Coxiella components implicated in infection.

Cell-type specific effects of mineralocorticoid receptor gene expression suggest intercellular communication regulating fibrosis in skeletal muscle disease.

Introduction: Duchenne muscular dystrophy (DMD) is a fatal striated muscle degenerative disease. DMD is caused by loss of dystrophin protein, which results in sarcolemmal instability and cycles of myofiber degeneration and regeneration. Pathology is exacerbated by overactivation of infiltrating immune cells and fibroblasts, which leads to chronic inflammation and fibrosis. Mineralocorticoid receptors (MR), a type of nuclear steroid hormone receptors, are potential therapeutic targets for DMD. MR antagonists show clinical efficacy on DMD cardiomyopathy and preclinical efficacy on skeletal muscle in DMD models. Methods: We have previously generated myofiber and myeloid MR knockout mouse models to dissect cell-specific functions of MR within dystrophic muscles. Here, we compared skeletal muscle gene expression from both knockouts to further define cell-type specific signaling downstream from MR. Results: Myeloid MR knockout increased proinflammatory and profibrotic signaling, including numerous myofibroblast signature genes. Tenascin C was the most highly upregulated fibrotic gene in myeloid MR-knockout skeletal muscle and is a component of fibrosis in dystrophic skeletal muscle. Surprisingly, lysyl oxidase (Lox), canonically a collagen crosslinker, was increased in both MR knockouts, but did not localize to fibrotic regions of skeletal muscle. Lox localized within myofibers, including only a region of quadriceps muscles. Lysyl oxidase like 1 (Loxl1), another Lox family member, was increased only in myeloid MR knockout muscle and localized specifically to fibrotic regions. Discussion: This study suggests that MR signaling in the dystrophic muscle microenvironment involves communication between contributing cell types and modulates inflammatory and fibrotic pathways in muscle disease.

Computational Modeling of Oddball Sequence Processing Exposes Common and Differential Auditory Network Changes in First-Episode Schizophrenia-Spectrum Disorders and Schizophrenia.

BACKGROUND AND HYPOTHESIS: Differences in sound relevance filtering in schizophrenia are proposed to represent a key index of biological changes in brain function in the illness. This study featured a computational modeling approach to test the hypothesis that processing differences might already be evident in first-episode, becoming more pronounced in the established illness. STUDY DESIGN: Auditory event-related potentials to a typical oddball sequence (rare pitch deviations amongst regular sounds) were recorded from 90 persons with schizophrenia-spectrum disorders (40 first-episode schizophrenia-spectrum, 50 established illness) and age-matched healthy controls. The data were analyzed using dynamic causal modeling to identify the changes in effective connectivity that best explained group differences. STUDY RESULTS: Group differences were linked to intrinsic (within brain region) connectivity changes. In activity-dependent measures these were restricted to the left auditory cortex in first-episode schizophrenia-spectrum but were more widespread in the established illness. Modeling suggested that both established illness and first-episode schizophrenia-spectrum groups expressed significantly lower inhibition of inhibitory interneuron activity and altered gain on superficial pyramidal cells with the data indicative of differences in both putative N-methyl-d-aspartate glutamate receptor activity-dependent plasticity and classic neuromodulation. CONCLUSIONS: The study provides further support for the notion that examining the ability to alter responsiveness to structured sound sequences in schizophrenia and first-episode schizophrenia-spectrum could be informative to uncovering the nature and progression of changes in brain function during the illness. Furthermore, modeling suggested that limited differences present at first-episode schizophrenia-spectrum may become more expansive with illness progression.

An extension of the shifted Wald model of human response times: Capturing the time dynamic properties of human cognition : Trial-varying Wald model.

Despite the ubiquitous nature of evidence accumulation models in cognitive and experimental psychology, there has been a comparatively limited uptake of such techniques in the applied literature. While quantifying latent cognitive processing properties has significant potential for applied domains such as adaptive work systems, accumulator models often fall short in practical applications. Two primary reasons for these shortcomings are the complexities and time needed for the application of cognitive models, and the failure of current models to capture systematic trial-to-trial variability in parameters. In this manuscript, we develop a novel, trial-varying extension of the shifted Wald model to address these concerns. By leveraging conjugate properties of the Wald distribution, we derive computationally efficient solutions for threshold and drift parameters which can be updated instantaneously with new data. The resulting model allows the quantification of systematic variation in latent cognitive parameters across trials and we demonstrate the utility of such analyses through simulations and an exemplar application to an existing data set. The analytic nature of our solutions opens the door for real-world applications, significantly extending the reach of computational models of behavioral responses.

FluTracking: Weekly online community-based surveillance of influenza-like illness in Australia, 2019 Annual Report.

Abstract: FluTracking provided evidence for an early, long, but moderate influenza season in the Australian community compared to prior years. Influenza-like illness (ILI) activity in 2019 peaked earlier (week ending 16 June) than any season on record in FluTracking data. ILI attack rates were above average early in the 2019 season (peak of 2.2%), and the duration of peak activity was longer than most prior years. However, ILI attack rates were lower than the five-year average in the latter half of the season. FluTracking participants reported higher vaccination coverage in 2019 (73.3%) compared with 2018 (65.7%), with the most notable increase in children aged less than five years (69.3% in 2019, compared to 55.6% in 2018). The total 2019 count of laboratory notifications (312,945) was higher than prior years (2007 onwards), and the peak weekly count of 18,429 notifications in 2019 was also higher than all prior years, except 2017. FluTracking makes a comparison to another surveillance system each year. The peak weekly percentage of calls to HealthDirect that were influenza-related was higher in 2019 (12.8%) than for 2014-2018 (range of 8.2-11.4% for peak week of activity each year). FluTracking participants reported a 2.5 times increase in influenza testing from 2018 to 2019 and a 1.5 times increase from 2017. Although 2019 was of higher activity and severity than 2018, Flutracking data indicates that 2019 was a lower activity and severity season than 2017, and notifications and influenza-related calls were heightened by increased community concern and testing.

Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.

Mycobacterium tuberculosis (Mtb) persists in lung myeloid cells during chronic infection. However, the mechanisms allowing Mtb to evade elimination are not fully understood. Here, we determined that in chronic phase, CD11clo monocyte-derived lung cells termed MNC1 (mononuclear cell subset 1), harbor more live Mtb than alveolar macrophages (AM), neutrophils, and less permissive CD11chi MNC2. Transcriptomic and functional studies of sorted cells revealed that the lysosome biogenesis pathway is underexpressed in MNC1, which have less lysosome content, acidification, and proteolytic activity than AM, and less nuclear TFEB, a master regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in MNC1. Instead, Mtb recruits MNC1 and MNC2 to the lungs for its spread from AM to these cells via its ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome function of primary macrophages and MNC1 and MNC2 in vivo, improving control of Mtb infection. Our results indicate that Mtb exploits lysosome-poor monocyte-derived cells for in vivo persistence, suggesting a potential target for host-directed tuberculosis therapy.

Mineralocorticoid Receptor Signaling in the Inflammatory Skeletal Muscle Microenvironments of Muscular Dystrophy and Acute Injury.

Duchenne muscular dystrophy (DMD) is a striated muscle degenerative disease due to loss of functional dystrophin protein. Loss of dystrophin results in susceptibility of muscle membranes to damage, leading to muscle degeneration and continuous inflammation and fibrosis that further exacerbate pathology. Long-term glucocorticoid receptor (GR) agonist treatment, the current standard-of-care for DMD, modestly improves prognosis but has serious side effects. The mineralocorticoid receptor (MR), a ligand-activated transcription factor present in many cell types, has been implicated as a therapeutic target for DMD. MR antagonists (MRAs) have fewer side effects than GR agonists and are used clinically for heart failure. MRA efficacy has recently been demonstrated for DMD cardiomyopathy and in preclinical studies, MRAs also alleviate dystrophic skeletal muscle pathology. MRAs lead to improvements in muscle force and membrane stability and reductions in degeneration, inflammation, and fibrosis in dystrophic muscles. Myofiber-specific MR knockout leads to most of these improvements, supporting an MR-dependent mechanism of action, but MRAs additionally stabilize myofiber membranes in an MR-independent manner. Immune cell MR signaling in dystrophic and acutely injured normal muscle contributes to wound healing, and myeloid-specific MR knockout is detrimental. More research is needed to fully elucidate MR signaling in striated muscle microenvironments. Direct comparisons of genomic and non-genomic effects of glucocorticoids and MRAs on skeletal muscles and heart will contribute to optimal temporal use of these drugs, since they compete for binding conserved receptors. Despite the advent of genetic medicines, therapies targeting inflammation and fibrosis will be necessary to achieve optimal patient outcomes.

Mineralocorticoid receptor antagonists and glucocorticoids differentially affect skeletal muscle inflammation and pathology in muscular dystrophy.

Mineralocorticoid receptor antagonists (MRAs) slow cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) and improve skeletal muscle pathology and function in dystrophic mice. However, glucocorticoids, known antiinflammatory drugs, remain a standard of care for DMD, despite substantial side effects. Exact mechanisms underlying mineralocorticoid receptor (MR) signaling contribution to dystrophy are unknown. Whether MRAs affect inflammation in dystrophic muscles and how they compare with glucocorticoids is unclear. The MRA spironolactone and glucocorticoid prednisolone were each administered for 1 week to dystrophic mdx mice during peak skeletal muscle necrosis to compare effects on inflammation. Both drugs reduced cytokine levels in mdx quadriceps, but prednisolone elevated diaphragm cytokines. Spironolactone did not alter myeloid populations in mdx quadriceps or diaphragms, but prednisolone increased F4/80hi macrophages. Both spironolactone and prednisolone reduced inflammatory gene expression in myeloid cells sorted from mdx quadriceps, while prednisolone additionally perturbed cell cycle genes. Spironolactone also repressed myeloid expression of the gene encoding fibronectin, while prednisolone increased its expression. Overall, spironolactone exhibits antiinflammatory properties without altering leukocyte distribution within skeletal muscles, while prednisolone suppresses quadriceps cytokines but increases diaphragm cytokines and pathology. Antiinflammatory properties of MRAs and different limb and respiratory muscle responses to glucocorticoids should be considered when optimizing treatments for patients with DMD.

Using Past and Present Indicators of Human Workload to Explain Variance in Human Performance.

Cognitive workload is assumed to influence performance due to resource competition. However, there is a lack of evidence for a direct relationship between changes in workload within an individual over time and changes in that individual's performance. We collected performance data using a multiple object-tracking task in which we measured workload objectively in real-time using a modified detection response task. Using a multi-level Bayesian model controlling for task difficulty and past performance, we found strong evidence that workload both during and preceding a tracking trial was predictive of performance, such that higher workload led to poorer performance. These negative workload-performance relationships were remarkably consistent across individuals. Importantly, we demonstrate that fluctuations in workload independent from the task demands accounted for significant performance variation. The outcomes have implications for designing real-time adaptive systems to proactively mitigate human performance decrements, but also highlight the pervasive influence of cognitive workload more generally.

A show about nothing: No-signal processes in systems factorial technology.

Systems Factorial Technology (SFT) is a popular framework for that has been used to investigate processing capacity across many psychological domains over the past 25+ years. To date, it had been assumed that no processing resources are used for sources in which no signal has been presented (i.e., in a location that can contain a signal but does not on a given trial). Hence, response times are purely driven by the signal-containing location or locations. This assumption is critical to the underlying mathematics of the capacity coefficient measure of SFT. In this article, we show that stimulus locations influence response times even when they contain no signal, and that this influence has repercussions for the interpretation of processing capacity under the SFT framework, particularly in conjunctive (AND) tasks-where positive responses require detection of signals in multiple locations. We propose a modification to the AND task requiring participants to fully identify both target locations on all trials. This modification allows a new coefficient to be derived. We apply the new coefficient to novel experimental data and resolve a previously reported empirical paradox, where observed capacity was limited in an OR detection task but super capacity in an AND detection task. Hence, previously reported differences in processing capacity between OR and AND task designs are likely to have been spurious. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Impact of funding on influenza vaccine uptake in Australian children.

Objectives and importance of study: Young children are at higher risk for serious influenza outcomes but, historically, Australian children aged less than 5 years have had low seasonal influenza vaccine uptake. In 2018, most Australian jurisdictions implemented funded influenza vaccine programs targeted at improving vaccine uptake in this age group. Our aim was to determine how successful these programs were at improving self-reported seasonal influenza vaccine uptake at the community level by comparing vaccination rates in each Australian jurisdiction before and after the introduction of funded vaccines for children aged 6 months to less than 5 years, as well as other age groups. STUDY TYPE: Volunteer observational cohort study. METHODS: Flutracking is an email-based surveillance tool for influenza-like illness that collects information about symptoms and influenza vaccination. We used historical data from 2014 to 2017 to estimate baseline vaccination status before funding of childhood influenza vaccines was introduced. We compared self-reported vaccine uptake in children younger than 5 years, children aged 5-17 years and adults (18-64 years, and 65 years and older) in 2018 and 2019 by state or territory. Mixed effects logistic regressions were used to measure the association between vaccination and a number of predictors, including whether the child was eligible for free vaccines, and whether adults resided with children or not. RESULTS: We found large increases in vaccine uptake for children younger than 5 years in 2018 in all jurisdictions except Western Australia (where vaccines were already funded) and the Northern Territory (where funded vaccines were not introduced until 2019) that coincided with vaccine policy changes. Self-reported vaccination rates for young children in 2018 increased 2.7-4.2-fold in jurisdictions that funded the vaccine (compared with the previous, unfunded period). Being eligible for the funded vaccine was associated with much higher odds (odds ratio [OR] 4.75; 95% confidence interval [CI] 4.57, 4.79) of a young child being vaccinated. Older children and adults younger than 65 years were also more likely to receive the vaccine following policy changes. CONCLUSION: The seasonal influenza vaccine is an important protective measure for those at risk of serious outcomes, including young children. Flutracking data demonstrates that government-funded vaccines can lead to an almost five-fold increase in self-reported vaccine uptake of the targeted age group, as well as previously unreported flow-on effects to older children. This suggests that funded vaccines for young children may encourage caregivers to also vaccinate themselves and their older children.