Molecular dating and viral load growth rates suggested that the eclipse phase lasted about a week in HIV-1 infected adults in East Africa and Thailand.

Most HIV-1 infected individuals do not know their infection dates. Precise infection timing is crucial information for studies that document transmission networks or drug levels at infection. To improve infection timing, we used the prospective RV217 cohort where the window when plasma viremia becomes detectable is narrow: the last negative visit occurred a median of four days before the first detectable HIV-1 viremia with an RNA test, referred below as diagnosis. We sequenced 1,280 HIV-1 genomes from 39 participants at a median of 4, 32 and 170 days post-diagnosis. HIV-1 infections were dated by using sequence-based methods and a viral load regression method. Bayesian coalescent and viral load regression estimated that infections occurred a median of 6 days prior to diagnosis (IQR: 9-3 and 11-4 days prior, respectively). Poisson-Fitter, which analyzes the distribution of hamming distances among sequences, estimated a median of 7 days prior to diagnosis (IQR: 15-4 days) based on sequences sampled 4 days post-diagnosis, but it did not yield plausible results using sequences sampled at 32 days. Fourteen participants reported a high-risk exposure event at a median of 8 days prior to diagnosis (IQR: 12 to 6 days prior). These different methods concurred that HIV-1 infection occurred about a week before detectable viremia, corresponding to 20 days (IQR: 34-15 days) before peak viral load. Together, our methods comparison helps define a framework for future dating studies in early HIV-1 infection.

Factors influencing estimates of HIV-1 infection timing using BEAST.

While large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed for env, gag, pol and near full-length genomes. There was no one best-fitting model across participants and genes, though relaxed molecular clocks (73% of best-fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis for env (IQR: 3-9 days) and gag (IQR: 5-9 days), whilst the genome placed it at a median of 10 days (IQR: 4-19). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to within-host datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content.

Activity Engagement and Everyday Technology Use Among Older Adults in an Urban Area.

OBJECTIVE: We investigated associations among activity engagement (AE), number of available and relevant everyday technologies, ability to use everyday technologies, and cognitive status among older adults in an urban area. METHOD: This cross-sectional study included 110 participants and used three assessments: the Frenchay Activities Index to measure AE, the Everyday Technology Use Questionnaire to measure the number of and ability to use available and relevant everyday technologies, and the Montreal Cognitive Assessment to measure cognitive status. Data analyses used a one-way analysis of variance and a multiple linear regression model. RESULTS: The number of available and relevant everyday technologies was significantly different (p < .001) among groups that varied in level of AE. Ability to use everyday technologies did not significantly differ among groups. Cognitive status did not explain level of AE when the number of available and relevant everyday technologies was considered. CONCLUSION: Increasing the accessibility of available and relevant everyday technologies among older adults in an urban area may increase AE.

RV144 vaccine imprinting constrained HIV-1 evolution following breakthrough infection.

The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1's high evolvability hints that HIV-1 could adapt to a future vaccine. Here, we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection. We analyzed 2,635 HIV-1 env sequences sampled up to a year post-diagnosis from 110 vaccine and placebo participants who became infected in the RV144 vaccine efficacy trial. We showed that the Env signature sites that were previously identified to distinguish vaccine and placebo participants were maintained over time. In addition, fewer sites were under diversifying selection in the vaccine group than in the placebo group. These results indicate that HIV-1 would possibly adapt to a vaccine upon its roll-out.

Everyday Technology Use and Overall Needed Assistance to Function in the Home and Community Among Urban Older Adults.

Background: Older adults manage increasing numbers of everyday technologies to participate in home and community activities. Purpose: We investigated how assessing use of everyday technologies enhanced predictions of overall needed assistance among urban older adults. Method: We used a cross-sectional design to analyze responses from 114 participants completing the Everyday Technology Use Questionnaire, the Montreal Cognitive Assessment, and a sociodemographic questionnaire. We estimated overall needed assistance based on definitions in the Assessment of Motor and Process Skills. We created logistic regression models and receiver operator characteristic curves to analyze variables predicting overall needed assistance. Findings: With high specificity and sensitivity, the Everyday Technology Use Questionnaire and the Montreal Cognitive Assessment were the strongest predictors of overall needed assistance. Implications: Assessing everyday technology use enhanced predictions of overall needed assistance among urban older adults.

The perceived challenge of everyday technologies in Sweden, the United States and England: Exploring differential item functioning in the everyday technology use questionnaire.

Background: The changing technological environment is reflected in regular updates made to the everyday technology (ET) use questionnaire (ETUQ). Newly added ETs may not present comparable challenges across countries and diagnoses.Aims: To identify whether country context, or dementia diagnosis, impact ETs' challenge level.Material and methods: 315 older adults from three countries were included; Sweden (n = 73), United States (n = 114), England (n = 128), and had a confirmed diagnosis of mild dementia (n = 99) or no known cognitive impairment (n = 216). Differential Items Functioning (DIF) analysis was performed on 88 ETs included in the ETUQ by country and diagnosis. The impact of DIF was evaluated in a Differential Test Functioning (DTF) analysis.Results: Nine items (10.2%) in the ETUQ showed statistically significant DIF between countries; five of which were public space ETs and none of which were information and communication technologies (ICTs). Three ICT items, and no others, showed significant DIF by diagnosis. The items' DIF was shown to have no impact upon person measures of ability to use ET in the DTF.Conclusions and significance: The utility of the ETUQ in occupational therapy practice and research internationally is highlighted through the stability of the challenge hierarchy and lack of impact on person measures.

Neutralization Sensitivity of a Novel HIV-1 CRF01_AE Panel of Infectious Molecular Clones.

BACKGROUND: HIV-1 CRF01_AE is dominant in Thailand where RV144 vaccine trial was conducted. To study immune correlates of protection in ongoing trials, CRF01_AE-derived reagents are essential. Here, we present a panel of 14 HIV-1 infectious molecular clones (IMCs) identified from different stages of infection and characterization of their neutralization sensitivity using 2 standard assays. METHODS: One full-length IMC was constructed using a transmitted-founder virus to express Renilla luciferase (LucR) reporter gene and full-length envelopes (envs) of exogenous HIV-1. A panel of IMCs was generated, expressing envs of viruses from acute (Fiebig stages I/II and I-IV) and chronic (>Fiebig VI) infection. Neutralization assays were performed using TZM-bl or A3R5 cell lines, and sera or monoclonal antibodies (mAbs). Wilcoxon matched-paired test was used to assess neutralization differences between assays and reagents; correlation coefficients were evaluated by linear regression. RESULTS: Neutralization potency observed was significantly higher in the A3R5 assay when testing mAbs and serum pools (P < 0.0001); the stage of infection from which env was derived did not associate with IMC neutralization sensitivity. Neutralization values from A3R5 and TZM-bl assays were strongly correlated when mAbs were tested (R = 0.7, P < 0.0001), but a weaker association was seen with serum pools (R = 0.17, P = 0.03). CONCLUSIONS: This novel panel of CRF01_AE reporter IMC is useful for assessing vaccine-induced neutralizing antibodies in multiple assays, including those using primary cell targets. The significant differences in TZM-bl and A3R5 neutralization sensitivity, as well as the poor association when using polyclonal sera indicates the need for caution in choosing one specific platform.

Achieving best practice: a review of evidence linked to occupation-focused practice models.

ABSTRACT The aim of this paper is to identify and synthesize evidence concerning the most widely used contemporary occupation-focused models including Ecology of human performance; Model of human occupation; Occupational adaptation; and Person-environment-occupational performance. The paper characterizes the amount and type of evidence. Evidence found includes illustrations of how the models can be applied to understand and address a particular problem or population, basic studies that test or expand theoretical concepts, psychometric studies, studies that document therapy outcomes, and studies that examine clinical reasoning and/or practice based on the models. The four models differed widely in the amount and type of evidence available.

Vocational intervention based on the Model of Human Occupation: a review of evidence.

Work is a growing concern in disability and rehabilitation fields. Specific evidence related to occupational therapy in the area of vocational rehabilitation is somewhat limited. With increased demands for occupation-focused, evidence-based, and theory-informed practice, this review aims to use clinically relevant questions to organize and synthesize evidence regarding work-related interventions specifically related to an occupation-focused theory, the Model of Human Occupation. A total of 45 published works related to both the MOHO and vocational issues were identified and included in the review. The review demonstrates that there is a range of evidence that supports the use of the MOHO and its tools as a basis for work-based clinical interventions. Evidence supports the conclusion that MOHO-based work assessments have good psychometric properties and are useful in evaluating vocational potential and needs. MOHO-based work programs have been shown to have a positive impact in improving vocational outcomes to a range of clients.