Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

OBJECTIVE: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT). METHOD: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40). RESULTS: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals. CONCLUSIONS: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Novel ENT live telehealth and live video-otoscopy clinics in remote Australia: outcomes and comparisons to traditional clinic models.

BACKGROUND: Coronavirus disease 2019 challenged the delivery of healthcare in Australia, disproportionately impacting vulnerable patients, including Aboriginal and/or Torres Strait Islander peoples and those living in remote regions. The otolaryngology service provided to remote Western Australia adapted to these barriers by altering clinical consultations to a digital model. METHODS: A review was undertaken of patients in regional Western Australia. Demographics and clinical outcomes from 20 live telehealth clinics were retrospectively reviewed and compared to 16 face-to-face clinics. RESULTS: The demographics of patients reviewed in both live telehealth and face-to-face clinics were similar, except for a larger proportion of Aboriginal and/or Torres Strait Islander patients utilising telehealth. The outcomes of patients reviewed through each model of care were comparable. Live video-otoscopy provided diagnostic quality images in 92 per cent of cases. CONCLUSION: The findings of our review suggest that, despite its limitations, a large proportion of ENT patients may be safely assessed through a live telehealth model.

The impact of respiratory infections and probiotic use on the nasal microbiota of frail residents in long-term care homes.

Background: Residents in long-term care homes, who tend to be of advanced age and frail, are at increased risk of respiratory infections. The respiratory microbiota is known to change with age, but whether these changes contribute to the risk of infection is not known. Our goal was to determine how the nasal microbiota of frail older adults changes during symptoms of influenza-like illness (ILI) and how this may be impacted by enrolment in a placebo-controlled trial testing the feasibility of administering a Lactobacillus rhamnosus GG probiotic to prevent respiratory infection (2014-2017). Methods: The microbiome of the nasal (mid-turbinate) of 150 residents of long-term care homes was interrogated using 16S rRNA gene sequencing. Results: We identified a diverse and individualised microbiota which could be separated into nine distinct clusters based on Bray-Curtis distances. Samples collected during symptoms of ILI differed statistically from those collected pre- and post-cold and influenza season, and we observed decreased temporal stability (as measured by movement between clusters) in individuals who experienced ILI compared to those who did not. Conclusions: The use of probiotics decreased ILI-induced changes to the microbiota; however, it is not clear whether this decrease is sufficient to prevent respiratory illness.

Staphylococcal Periscope proteins Aap, SasG, and Pls project noncanonical legume-like lectin adhesin domains from the bacterial surface.

Staphylococcus aureus and Staphylococcus epidermidis are frequently associated with medical device infections that involve establishment of a bacterial biofilm on the device surface. Staphylococcal surface proteins Aap, SasG, and Pls are members of the Periscope Protein class and have been implicated in biofilm formation and host colonization; they comprise a repetitive region ("B region") and an N-terminal host colonization domain within the "A region," predicted to be a lectin domain. Repetitive E-G5 domains (as found in Aap, SasG, and Pls) form elongated "stalks" that would vary in length with repeat number, resulting in projection of the N-terminal A domain variable distances from the bacterial cell surface. Here, we present the structures of the lectin domains within A regions of SasG, Aap, and Pls and a structure of the Aap lectin domain attached to contiguous E-G5 repeats, suggesting the lectin domains will sit at the tip of the variable length rod. We demonstrate that these isolated domains (Aap, SasG) are sufficient to bind to human host desquamated nasal epithelial cells. Previously, proteolytic cleavage or a deletion within the A domain had been reported to induce biofilm formation; the structures suggest a potential link between these observations. Intriguingly, while the Aap, SasG, and Pls lectin domains bind a metal ion, they lack the nonproline cis peptide bond thought to be key for carbohydrate binding by the lectin fold. This suggestion of noncanonical ligand binding should be a key consideration when investigating the host cell interactions of these bacterial surface proteins.

Construct identification in the neuropsychological battery: What are we measuring?

OBJECTIVE: Major obstacles to data harmonization in neuropsychology include lack of consensus about what constructs and tests are most important and invariant across healthy and clinical populations. This study addressed these challenges using data from the National Neuropsychology Network (NNN). METHOD: Data were obtained from 5,000 NNN participants and Pearson standardization samples. Analyses included variables from four instruments: Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV); Wechsler Memory Scale, 4th Edition (WMS-IV); California Verbal Learning Test, 3rd Edition (CVLT3); and Delis-Kaplan Executive Function System (D-KEFS). We used confirmatory factor analysis to evaluate models suggested by prior work and examined fit statistics and measurement invariance across samples. We examined relations of factor scores to demographic and clinical characteristics. RESULTS: For each instrument, we identified four first-order and one second-order factor. Optimal models in patients generally paralleled the best-fitting models in the standardization samples, including task-specific factors. Analysis of the NNN data prompted specification of a Recognition-Familiarity factor on the WMS-IV and an Inhibition-Switching factor on the D-KEFS. Analyses showed strong to strict factorial invariance across samples with expected differences in factor means and variances. The Recognition-Familiarity factor correlated with age more strongly in NNN than in the standardization sample. CONCLUSIONS: Factor models derived from healthy groups generally fit well in patients. NNN data helped identify novel Recognition-Familiarity and Inhibition-Switching factors that were also invariant across samples and may be clinically useful. The findings support efforts to identify evidence-based and optimally efficient measurements of neuropsychological constructs that are valid across groups. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Efficient O-demethylation of lignin monoaromatics using the peroxygenase activity of cytochrome P450 enzymes.

A crucial reaction in harnessing renewable carbon from lignin is O-demethylation. We demonstrate the selective O-demethylation of syringol and guaiacol using different cytochrome P450 enzymes. These can efficiently use hydrogen peroxide which, when compared to nicotinamide cofactor-dependent monooxygenases and synthetic methods, allows for cheap and clean O-demethylation of lignin-derived aromatics.

The long and the short of Periscope Proteins.

Bacteria sense, interact with, and modify their environmental niche by deploying a molecular ensemble at the cell surface. The changeability of this exposed interface, combined with extreme changes in the functional repertoire associated with lifestyle switches from planktonic to adherent and biofilm states necessitate dynamic variability. Dynamic surface changes include chemical modifications to the cell wall; export of diverse extracellular biofilm components; and modulation of expression of cell surface proteins for adhesion, co-aggregation and virulence. Local enrichment for highly repetitive proteins with high tandem repeat identity has been an enigmatic phenomenon observed in diverse bacterial species. Preliminary observations over decades of research suggested these repeat regions were hypervariable, as highly related strains appeared to express homologues with diverse molecular mass. Long-read sequencing data have been interrogated to reveal variation in repeat number; in combination with structural, biophysical and molecular dynamics approaches, the Periscope Protein class has been defined for cell surface attached proteins that dynamically expand and contract tandem repeat tracts at the population level. Here, I review the diverse high-stability protein folds and coherent interdomain linkages culminating in the formation of highly anisotropic linear repeat arrays, so-called rod-like protein 'stalks', supporting roles in bacterial adhesion, biofilm formation, cell surface spatial competition, and immune system modulation. An understanding of the functional impacts of dynamic changes in repeat arrays and broader characterisation of the unusual protein folds underpinning this variability will help with the design of immunisation strategies, and contribute to synthetic biology approaches including protein engineering and microbial consortia construction.

The Effectiveness of a Specialized Primary Care Medical Home for Patients with Serious Mental Illness.

BACKGROUND: There are unmet primary care needs among people with serious mental illness that might be improved with integrated care and medical care management. Many healthcare organizations have attempted to address this problem, but few interventions have been rigorously studied and found to be effective. OBJECTIVE: Study the implementation and effectiveness of a novel, specialized primary care medical home designed to improve the healthcare of patients with serious mental illness. DESIGN, SETTING, AND PARTICIPANTS: Clustered controlled trial for a median of 401 days. One Veterans Health Administration medical center was assigned to intervention and two were assigned to usual care (control). Thirty-nine clinicians and managers were included in the study, as well as 331 patients who met eligibility criteria. INTERVENTION: A specialized medical home with systematic patient engagement, proactive nurse panel management, a collaborative care psychiatrist, and a primary care physician providing care that included psychiatric treatment. MAIN MEASURES: Quality of care, chronic illness care and care experience, symptoms, and quality of life. KEY RESULTS: Sixty-five intervention patients (40%) moved all psychiatric care to the primary care team. No adverse events were attributable to the intervention. Compared with control, intervention patients had greater improvement over time in appropriate screening for body mass index, lipids, and glucose (χ2 = 6.9, 14.3, and 3.9; P's < .05); greater improvement in all domains of chronic illness care (activation, decision support, goal-setting, counseling, coordination) and care experience (doctor-patient interaction, shared decision-making, care coordination, access; F for each 10-24, P's < .05); and greater improvement in mental health-related quality of life (F = 3.9, P = .05) and psychotic symptoms (F = 3.9, P = .05). CONCLUSION: A primary care medical home for serious mental illness can be feasible to implement, safe, and more effective than usual care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01668355.

Rationale and Design of the National Neuropsychology Network.

OBJECTIVE: The National Neuropsychology Network (NNN) is a multicenter clinical research initiative funded by the National Institute of Mental Health (NIMH; R01 MH118514) to facilitate neuropsychology's transition to contemporary psychometric assessment methods with resultant improvement in test validation and assessment efficiency. METHOD: The NNN includes four clinical research sites (Emory University; Medical College of Wisconsin; University of California, Los Angeles (UCLA); University of Florida) and Pearson Clinical Assessment. Pearson Q-interactive (Q-i) is used for data capture for Pearson published tests; web-based data capture tools programmed by UCLA, which serves as the Coordinating Center, are employed for remaining measures. RESULTS: NNN is acquiring item-level data from 500-10,000 patients across 47 widely used Neuropsychology (NP) tests and sharing these data via the NIMH Data Archive. Modern psychometric methods (e.g., item response theory) will specify the constructs measured by different tests and determine their positive/negative predictive power regarding diagnostic outcomes and relationships to other clinical, historical, and demographic factors. The Structured History Protocol for NP (SHiP-NP) helps standardize acquisition of relevant history and self-report data. CONCLUSIONS: NNN is a proof-of-principle collaboration: by addressing logistical challenges, NNN aims to engage other clinics to create a national and ultimately an international network. The mature NNN will provide mechanisms for data aggregation enabling shared analysis and collaborative research. NNN promises ultimately to enable robust diagnostic inferences about neuropsychological test patterns and to promote the validation of novel adaptive assessment strategies that will be more efficient, more precise, and more sensitive to clinical contexts and individual/cultural differences.

Model Systems to Study the Chronic, Polymicrobial Infections in Cystic Fibrosis: Current Approaches and Exploring Future Directions.

A recent workshop titled "Developing Models to Study Polymicrobial Infections," sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 35+ investigators over two virtual sessions. Here, we present the findings of this workshop, summarize some of the challenges involved with developing such models, and suggest three frameworks to tackle this complex problem. The frameworks proposed here, we believe, could be generally useful in developing new model systems for other infectious diseases. Developing and validating new approaches to study the complex polymicrobial communities in the CF airway could open windows to new therapeutics to treat these recalcitrant infections, as well as uncovering organizing principles applicable to chronic polymicrobial infections more generally.

Gene-gene relationships in an Escherichia coli accessory genome are linked to function and mobility.

The pangenome contains all genes encoded by a species, with the core genome present in all strains and the accessory genome in only a subset. Coincident gene relationships are expected within the accessory genome, where the presence or absence of one gene is influenced by the presence or absence of another. Here, we analysed the accessory genome of an Escherichia coli pangenome consisting of 400 genomes from 20 sequence types to identify genes that display significant co-occurrence or avoidance patterns with one another. We present a complex network of genes that are either found together or that avoid one another more often than would be expected by chance, and show that these relationships vary by lineage. We demonstrate that genes co-occur by function, and that several highly connected gene relationships are linked to mobile genetic elements. We find that genes are more likely to co-occur with, rather than avoid, another gene in the accessory genome. This work furthers our understanding of the dynamic nature of prokaryote pangenomes and implicates both function and mobility as drivers of gene relationships.

Integrating Mental Health in Safety-net Primary Care: A Five-year Observational Study on Visits in a County Health System.

BACKGROUND: Beginning in 2010, Los Angeles County Departments of Health Services and Mental Health collaborated to increase access to effective mental health care. The Mental Health Integration Program (MHIP) embedded behavioral health specialists in primary care clinics to deliver brief, problem-focused treatments, and psychiatric consultation support for primary care-prescribed psychotropic medications. OBJECTIVE: The aim was to compare primary care visits associated with psychiatric diagnoses before and after MHIP implementation. METHODS: This retrospective cohort study (2009-2014) examined 62,945 patients from 8 safety-net clinics that implemented MHIP in a staggered manner in Los Angeles. Patients' primary care visits (n=695,354) were either associated or not with a previously identified or "new" (defined as having no diagnosis within the prior year) psychiatric diagnosis. Multilevel regression models used MHIP implementation to predict odds of visits being associated with psychiatric diagnoses, controlling for time, clinic, and patient characteristics. RESULTS: 9.4% of visits were associated with psychiatric diagnoses (6.4% depression, 3.1% anxiety, <1% alcohol, and substance use disorders). Odds of visits being associated with psychiatric diagnoses were 9% higher [95% confidence interval (CI)=1.05-1.13; P<0.0001], and 10% higher for diagnoses that were new (CI=1.04-1.16; P=0.002), after MHIP implementation than before. This appeared to be fueled by increased visits for depression post-MHIP (odds ratio=1.11; CI=1.06-1.15; P<0.0001). CONCLUSIONS: MHIP implementation was associated with more psychiatric diagnoses coded in safety-net primary care visits. Scaling up this effort will require greater attention to the notable differences across patient populations and languages, as well as the markedly low coding of alcohol and substance use services in primary care.

Periscope Proteins are variable-length regulators of bacterial cell surface interactions.

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal "Periscope Proteins" as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this "rule," suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system.

Evidence for Selection in the Abundant Accessory Gene Content of a Prokaryote Pangenome.

A pangenome is the complete set of genes (core and accessory) present in a phylogenetic clade. We hypothesize that a pangenome's accessory gene content is structured and maintained by selection. To test this hypothesis, we interrogated the genomes of 40 Pseudomonas species for statistically significant coincident (i.e., co-occurring/avoiding) gene patterns. We found that 86.7% of common accessory genes are involved in ≥1 coincident relationship. Further, genes that co-occur and/or avoid each other-but are not vertically inherited-are more likely to share functional categories, are more likely to be simultaneously transcribed, and are more likely to produce interacting proteins, than would be expected by chance. These results are not due to coincident genes being adjacent to one another on the chromosome. Together, these findings suggest that the accessory genome is structured into sets of genes that function together within a given strain. Given the similarity of the Pseudomonas pangenome with open pangenomes of other prokaryotic species, we speculate that these results are generalizable.

A Multisite Randomized Controlled Trial Comparing the Effects of Intervention Intensity and Intervention Style on Outcomes for Young Children With Autism.

OBJECTIVE: This randomized, multisite, intent-to-treat study tested the effects of 2 levels of treatment intensity (number of hours) and 2 treatment styles on the progress of young children with autism spectrum disorder (ASD). We predicted that initial severity of developmental delay or autism symptoms would moderate the effects of intensity and style on progress in 4 domains: autism symptom severity, expressive communication, receptive language, and nonverbal ability. METHOD: A total of 87 children with ASD, mean age 23.4 months, were assigned to 1 of 2 intervention styles (naturalistic developmental/behavioral or discrete trial teaching), each delivered for either 15 or 25 hours per week of 1:1 intervention for 12 months by trained research staff. All caregivers received coaching twice monthly. Children were assessed at 4 timepoints. Examiners and coders were naive to treatment assignment. RESULTS: Neither style nor intensity had main effects on the 4 outcome variables. In terms of moderating the effects of initial severity of developmental delay and of autism symptom severity, neither moderated the effects of treatment style on progress in any of the 4 domains. In terms of treatment intensity, initial severity moderated effect of treatment intensity on only 1 domain, namely, change in autism symptom severity; in a secondary analysis, this effect was found in only 1 site. CONCLUSION: Neither treatment style nor intensity had overall effects on child outcomes in the 4 domains examined. Initial severity did not predict better response to 1 intervention style than to another. We found very limited evidence that initial severity predicted better response to 25 vs 15 hours per week of intervention in the domains studied. CLINICAL TRIAL REGISTRATION INFORMATION: Intervention Effects of Intensity and Delivery Style for Toddlers With Autism: https://clinicaltrials.gov/; NCT02272192.

Horizontal Gene Transfer as a Source of Conflict and Cooperation in Prokaryotes.

Horizontal gene transfer (HGT) is one of the most important processes in prokaryote evolution. The sharing of DNA can spread neutral or beneficial genes, as well as genetic parasites across populations and communities, creating a large proportion of the variability acted on by natural selection. Here, we highlight the role of HGT in enhancing the opportunities for conflict and cooperation within and between prokaryote genomes. We discuss how horizontally acquired genes can cooperate or conflict both with each other and with a recipient genome, resulting in signature patterns of gene co-occurrence, avoidance, and dependence. We then describe how interactions involving horizontally transferred genes may influence cooperation and conflict at higher levels (populations, communities, and symbioses). Finally, we consider the benefits and drawbacks of HGT for prokaryotes and its fundamental role in understanding conflict and cooperation from the gene-gene to the microbiome level.

Rational Design and Self-Assembly of Coiled-Coil Linked SasG Protein Fibrils.

Protein engineering is an attractive approach for the self-assembly of nanometer-scale architectures for a range of potential nanotechnologies. Using the versatile chemistry provided by protein folding and assembly, coupled with amino acid side-chain functionality, allows for the construction of precise molecular "protein origami" hierarchical patterned structures for a range of nanoapplications such as stand-alone enzymatic pathways and molecular machines. The Staphyloccocus aureus surface protein SasG is a rigid, rod-like structure shown to have high mechanical strength due to "clamp-like" intradomain features and a stabilizing interface between the G5 and E domains, making it an excellent building block for molecular self-assembly. Here we characterize a new two subunit system composed of the SasG rod protein genetically conjugated with de novo designed coiled-coils, resulting in the self-assembly of fibrils. Circular dichroism (CD) and quartz-crystal microbalance with dissipation (QCM-D) are used to show the specific, alternating binding between the two subunits. Furthermore, we use atomic force microscopy (AFM) to study the extent of subunit polymerization in a liquid environment, demonstrating self-assembly culminating in the formation of linear macromolecular fibrils.

Coinfinder: detecting significant associations and dissociations in pangenomes.

The accessory genes of prokaryote and eukaryote pangenomes accumulate by horizontal gene transfer, differential gene loss, and the effects of selection and drift. We have developed Coinfinder, a software program that assesses whether sets of homologous genes (gene families) in pangenomes associate or dissociate with each other (i.e. are 'coincident') more often than would be expected by chance. Coinfinder employs a user-supplied phylogenetic tree in order to assess the lineage-dependence (i.e. the phylogenetic distribution) of each accessory gene, allowing Coinfinder to focus on coincident gene pairs whose joint presence is not simply because they happened to appear in the same clade, but rather that they tend to appear together more often than expected across the phylogeny. Coinfinder is implemented in C++, Python3 and R and is freely available under the GNU license from https://github.com/fwhelan/coinfinder.

Culture-enriched metagenomic sequencing enables in-depth profiling of the cystic fibrosis lung microbiota.

Amplicon sequencing (for example, of the 16S rRNA gene) identifies the presence and relative abundance of microbial community members. However, metagenomic sequencing is needed to identify the genetic content and functional potential of a community. Metagenomics is challenging in samples dominated by host DNA, such as those from the skin, tissue and respiratory tract. Here, we combine advances in amplicon and metagenomic sequencing with culture-enriched molecular profiling to study the human microbiota. Using the cystic fibrosis lung as an example, we cultured an average of 82.13% of the operational taxonomic units representing 99.3% of the relative abundance identified in direct sequencing of sputum samples; importantly, culture enrichment identified 63.3% more operational taxonomic units than direct sequencing. We developed the PLate Coverage Algorithm (PLCA) to determine a representative subset of culture plates on which to conduct culture-enriched metagenomics, resulting in the recovery of greater taxonomic diversity-including of low-abundance taxa-with better metagenome-assembled genomes, longer contigs and better functional annotations when compared to culture-independent methods. The PLCA is also applied as a proof of principle to a previously published gut microbiota dataset. Culture-enriched molecular profiling can be used to better understand the role of the human microbiota in health and disease.

Mobile Phone and Smartphone Use by People With Serious Mental Illness.

OBJECTIVE: Mobile technologies, such as smartphones, can improve health services by delivering assessments and interventions that reach people in their daily lives. There is, however, disagreement regarding whether people with serious mental illness make meaningful use of mobile technology and whether interventions that rely on mobile technology should be tailored for this population. METHODS: At two clinics, 249 people with serious mental illness were interviewed regarding mobile phone use, and their cognitive functioning was assessed. RESULTS: Mobile phones were used by 86% of participants, including 60% who used a smartphone. Phones were used for messaging by 81%, Internet by 52%, e-mail by 46%, and applications by 45%. Individuals who were older, had a persistent psychotic disorder rather than bipolar disorder, received disability income, or had worse neurocognitive functioning were less likely to own a smartphone (χ2=52.7, p<0.001). CONCLUSIONS: Most patients with serious mental illness owned a mobile phone; a majority owned a smartphone. Developers should consider tailoring mobile interventions for psychosis and cognitive deficits.