Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Weight of evidence evaluation for chemical-induced immunotoxicity for PFOA and PFOS: findings from an independent panel of experts.

Immunotoxicity is the critical endpoint used by some regulatory agencies to establish toxicity values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, the hypothesis that exposure to certain per- and polyfluoroalkyl substances (PFAS) causes immune dysregulation is subject to much debate. An independent, international expert panel was engaged utilizing methods to reduce bias and "groupthink". The panel concluded there is moderate evidence that PFOS and PFOA are immunotoxic, based primarily on evidence from animal data. However, species concordance and human relevance cannot be well established due to data limitations. The panel recommended additional testing that includes longer-term exposures, evaluates both genders, includes other species of animals, tests lower dose levels, assesses more complete measures of immune responses, and elucidates the mechanism of action. Panel members agreed that the Faroe Islands cohort data should not be used as the primary basis for deriving PFAS risk assessment values. The panel agreed that vaccine antibody titer is not useful as a stand-alone metric for risk assessment. Instead, PFOA and PFOS toxicity values should rely on multiple high-quality studies, which are currently not available for immune suppression. The panel concluded that the available PFAS immune epidemiology studies suffer from weaknesses in study design that preclude their use, whereas available animal toxicity studies provide comprehensive dataset to derive points of departure (PODs) for non-immune endpoints. The panel recommends accounting for potential PFAS immunotoxicity by applying a database uncertainty factor to POD values derived from animal studies for other more robustly supported critical effects.

Evaluation of a workplace suicide prevention program in the Australian manufacturing industry: protocol for a cluster-randomised trial of MATES in manufacturing.

Males are at higher risk of death by suicide than females in Australia, and among men, blue-collar males are at higher risk compared to other working males. In response, MATES in Construction developed a workplace suicide prevention program for the construction sector in 2007 that has been widely implemented in Australia. In the current project, this program is being adapted and trialled in the manufacturing sector. The common aims of MATES programs are to improve suicide prevention literacy, help-seeking intentions, and helping behaviours. The program will be evaluated using a cluster randomised-controlled trial design with waitlist controls across up to 12 manufacturing worksites in Australia. We hypothesise that after 8 months of the MATES in Manufacturing program, there will be significantly greater improvements in help-seeking intentions (primary outcome) compared to waitlist controls. The project is led by Deakin University in collaboration with the University of Melbourne, and in partnership with MATES in Construction and a joint labour-management Steering Group.Trial registration: The trial was registered retrospectively with the Australian New Zealand Clinical Trials Registry on 25 January 2022 (ACTRN12622000122752).Protocol version: 2.0, November 2022.

The effect of PARO robotic seals for hospitalized patients with dementia: A feasibility study.

Robotic seals have been studied in long-term care settings; though, no studies of patients with dementia in the acute care setting have been reported. The purpose of this study was to evaluate the feasibility of PARO interventions for hospitalized patients with dementia, determine physiological effects and describe social-affective interactions. Using a prospective descriptive design with pre-post PARO intervention physiological measurements, we studied 55 participants who received up to five 15-min PARO interventions. The PARO was favorably accepted for 212 (95%) of the 223 PARO interventions. Differences in pre- and post-physiological measures for mean arterial pressure, pulse, respiration, oxygenation, stress, and pain levels were evaluated using Wilcoxon Signed Rank test with statistically significant pre and post differences (p=<0.05); however, the differences were not clinically significant. Participants (95%) demonstrated beneficial PARO interactions with the most frequent interactions being speaking and petting. The PARO shows promise for enhancing social and affective responses for hospitalized patients with dementia.

[Cognitive and legal aspects in older people]. / Aspectos cognitivos y legales en personas mayores: "Sano Juicio".

In Chile, 7.1% of people aged over 60 years have some type of cognitive disorder. The frequency of the latter increases to 13% in people between 75-79 years and 36.2% in people over 85 years. The concept of mild cognitive impairment (MCI) and dementia have evolved over time. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term minor and major neurocognitive disorder, replacing the DCL and dementia respectively. Major cognitive disorder impairs functional performance while minor disorders does not. There is an arbitrary discrimination against the elderly. A form of discrimination is the request made by some notaries of a medical certification of the cognitive function for older people willing to carry out a legal procedure. This request has the sole effect of pre-establishing evidence in favor of the notary and not protecting the testator or the vulnerable person. Assessing the ability of older people to care for themselves and their possessions has important implications for them and their families, since there is a serious risk of prejudice when someone is declared as disabled. Thus, considering the epidemiology of cognitive disorders in our country we propose a series of legal and medical discussion points aimed to protect autonomy and to protect individuals and their possessions when they have difficulties to control their decisions.

Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND: PF-04965842 is an oral Janus kinase 1 inhibitor being investigated for the treatment of plaque psoriasis. OBJECTIVES: To evaluate the efficacy, safety and tolerability of PF-04965842 in patients with moderate-to-severe plaque psoriasis. METHODS: Patients in this phase II, placebo-controlled study (NCT02201524) were randomized to receive placebo, 200 mg once daily (OD), 400 mg OD or 200 mg twice daily (TD) PF-04965842 for 4 weeks. The primary endpoint was change from baseline in Psoriasis Area Severity Index (PASI) at week 4. Study enrolment was discontinued on 25 June 2015 due to changes in the sponsor's development priorities. RESULTS: Fifty-nine patients were randomized and received at least one dose of PF-04965842 or placebo. The estimated treatment effect (active -placebo PASI change from baseline) and 90% confidence interval at week 4 was -5·1 (-9·2 to -1·0), -5·6 (-9·6 to -1·6) and -10·0 (-14·2 to -5·8) for the 200 mg OD, 400 mg OD and 200 mg TD groups, respectively. At week 4, the proportion of patients achieving PASI 75 was 17% for the placebo and 200 mg OD groups, 50% for the 400 mg OD group and 60% for the 200 mg TD group. There were more abnormal laboratory test results of clinical interest (low neutrophil, reticulocyte and platelet counts) in the 200 mg TD group compared with the OD treatment groups. No serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively, were reported. CONCLUSIONS: These results suggest that treatment with PF-04965842 improves symptoms and is well tolerated in patients with moderate-to-severe psoriasis.

Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus.

This study's objective was to assess the effects of PD-0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony-stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD-0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre- and post-treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14(+) CD16(+) monocytes, urinary N-terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater-than-dose-proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14(+) CD16(+) cells, uNTX, ALT, AST and CK levels at most time-points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between-group differences were seen in CLASI. Patients receiving PD-0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD-0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end-points.

Impact of muffle furnace preparation on the results of crystalline silica analysis.

A prior report demonstrated an unacceptably low level of accuracy in silica analytical testing, with a general negative bias (i.e., underreporting) although other inaccuracies included false-positive results when analyzing blank filters. The possible bias may have been due to the loss of sample during shipping and or sample preparation. We report on a follow-up study that was designed to mimic the original study, but in which sources of variability were evaluated. We found no effect on silica recoveries due to shipping and confirmed the prior study results that the muffle furnace ashing process led to low overall recoveries (49-104%), depending on the adherence to the recommended preparation method. Plasma ashing recoveries ranged from 89 to 108%. Our results suggest that muffle-furnace ashing using a crucible should be restricted. More broadly, however, muffle-furnace ashing is only one source of analytical error that contributes to the relatively poor overall performance revealed by Cox et al. Whatever the case, OSHA should ensure that its proposed requirements to improve laboratory performance will actually lead to the discovery and correction of all major sources of error by participating laboratories. This is particularly important in light of OSHA's proposed reduction in the PEL and action level proposed by OSHA.

Distribution of vertebral fractures varies among patients according to hip fracture type.

UNLABELLED: This study explored the distribution of vertebral fractures in hip fracture patients. Unlike patients with intertrochanteric fractures, those with subcapital fractures were less likely to have vertebral fractures in the T4-T10 region of the spine. The dissimilar distribution of vertebral fractures among patients with intertrochanteric and subcapital fractures may indicate different underlying etiologies. INTRODUCTION: There are two main types of hip fractures: intertrochanteric and subcapital. Both types can have associated vertebral fractures. In this study, we explored the distribution of vertebral fractures in the two hip fracture populations. METHODS: This was a retrospective analysis of a convenience sample of 120 patients: 40 with subcapital fractures and vertebral fractures, 40 with intertrochanteric fractures and vertebral fractures, and 40 with vertebral fractures only. Based on Genant's semiquantitative assessment method of radiographic images, the distribution and severity of each patient's vertebral fractures were explored [1]. RESULTS: Patients with subcapital fractures had significantly fewer total vertebral fractures (93 vs. 144, p = 0.005; 93 vs. 127, p = 0.019), vertebral fractures from T4 to T10 (41 vs. 81, p = 0.005; 41 vs. 64, p = 0.042), and vertebral fractures at the T7-T8 peak (11 vs. 31, p = 0.002; 11 vs. 30, p = 0.003) than patients with intertrochanteric fractures and those with vertebral fractures alone, respectively, and they were more likely to have only one vertebral fracture (15 vs. 3, p < 0.001; 15 vs. 2, p < 0.001). The number of vertebral fractures from T11 to L4 and at the T12-L1 peak did not differ among the groups. The numbers of fractures at each vertebral level was significantly correlated only between those with intertrochanteric fractures and those with vertebral fractures alone (r = 0.65, p = 0.009). CONCLUSION: The distribution of vertebral fractures among patients with subcapital fractures differed from the other fracture groups, which may indicate that subcapital fractures and some lumbar fractures have a different underlying etiology than intertrochanteric fractures and thoracic (T4-T10) fractures.

Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report.

Rhinitis is an umbrella term that encompasses many different subtypes, several of which still elude complete characterization. The concept of phenotyping, being the definition of disease subtypes on the basis of clinical presentation, has been well established in the last decade. Classification of rhinitis entities on the basis of phenotypes has facilitated their characterization and has helped practicing clinicians to efficiently approach rhinitis patients. Recently, the concept of endotypes, that is, the definition of disease subtypes on the basis of underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic, overlapping, and may evolve into one another, thus rendering clear-cut definitions difficult. Nevertheless, a phenotype-/endotype-based classification approach could lead toward the application of stratified and personalized medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes and endotypes are described, and rhinitis diagnosis and management approaches focusing on those phenotypes/endotypes are presented and discussed. We emphasize the concept of control-based management, which transcends all rhinitis subtypes.

How reliable are crystalline silica dust concentration measurements?

To determine how reliably commercial laboratories measure crystalline silica concentrations corresponding to OSHA's proposed limits, 105 filters were prepared with known masses of 20, 40, and 80 µg of respirable quartz corresponding to airborne silica concentrations of 25, 50, and 100 µg/m(3) and were submitted, in a blind test, to qualified commercial laboratories over a nine month period. Under these test conditions, the reported results indicated a lack of accuracy and precision needed to reliably inform regulatory compliance decisions. This was true even for filters containing only silica, without an interfering matrix. For 36 filters loaded with 20 or more micrograms of silica, the laboratories reported non-detected levels of silica. Inter-laboratory variability in this performance test program was so high that the reported results could not be used to reliably discriminate among filters prepared to reflect 8-h exposures to respirable quartz concentrations of 25, 50 and 100 µg/m(3). Moreover, even in intra-laboratory performance, there was so much variability in the reported results that 2-fold variations in exposure concentrations could not be reliably distinguished. Part of the variability and underreporting may result from the sample preparation process. The results of this study suggest that current laboratory methods and practices cannot necessarily be depended on, with high confidence, to support proposed regulatory standards with reliable data.

Association of caesarean delivery with child adiposity from age 6 weeks to 15 years.

OBJECTIVES: o assess associations of caesarean section with body mass from birth through adolescence. DESIGN: ongitudinal birth cohort study, following subjects up to 15 years of age. SETTING AND PARTICIPANTS: Children born in 1991-1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219). PRIMARY OUTCOME: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI: 85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years. RESULTS: Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak. CONCLUSION: Cesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.

Infant antibiotic exposures and early-life body mass.

OBJECTIVES: To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life. DESIGN: Longitudinal birth cohort study. SUBJECTS: A total of 11 532 children born at 2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992. MEASUREMENTS: Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years). RESULTS: Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass. CONCLUSIONS: Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.

Alterations to the subchondral bone architecture during osteoarthritis: bone adaptation vs endochondral bone formation.

OBJECTIVE: Osteoarthritis (OA) is characterized by loss of cartilage and alterations in subchondral bone architecture. Changes in cartilage and bone tissue occur simultaneously and are spatially correlated, indicating that they are probably related. We investigated two hypotheses regarding this relationship. According to the first hypothesis, both wear and tear changes in cartilage, and remodeling changes in bone are a result of abnormal loading conditions. According to the second hypothesis, loss of cartilage and changes in bone architecture result from endochondral ossification. DESIGN: With an established bone adaptation model, we simulated adaptation to high load and endochondral ossification, and investigated whether alterations in bone architecture between these conditions were different. In addition, we analyzed bone structure differences between human bone samples with increasing degrees of OA, and compared these data to the simulation results. RESULTS: The simulation of endochondral ossification led to a more refined structure, with a higher number of trabeculae in agreement with the finding of a higher trabecular number in osteochondral plugs with severe OA. Furthermore, endochondral ossification could explain the presence of a "double subchondral plate" which we found in some human bone samples. However, endochondral ossification could not explain the increase in bone volume fraction that we observed, whereas adaptation to high loading could. CONCLUSION: Based on the simulation and experimental data, we postulate that both endochondral ossification and adaptation to high load may contribute to OA bone structural changes, while both wear and tear and the replacement of mineralized cartilage with bone tissue may contribute cartilage thinning.

Lack of unique neuropathology in amyotrophic lateral sclerosis associated with p.K54E angiogenin (ANG) mutation.

AIMS: Five to 10% of cases of amyotrophic lateral sclerosis are familial, with the most common genetic causes being mutations in the C9ORF72, SOD1, TARDBP and FUS genes. Mutations in the angiogenin gene, ANG, have been identified in both familial and sporadic patients in several populations within Europe and North America. The aim of this study was to establish the incidence of ANG mutations in a large cohort of 517 patients from Northern England and establish the neuropathology associated with these cases. METHODS: The single exon ANG gene was amplified, sequenced and analysed for mutations. Pathological examination of brain, spinal cord and skeletal muscle included conventional histology and immunohistochemistry. RESULTS: Mutation screening identified a single sporadic amyotrophic lateral sclerosis case with a p.K54E mutation, which is absent from 278 neurologically normal control samples. The clinical presentation was of limb onset amyotrophic lateral sclerosis, with rapid disease progression and no evidence of cognitive impairment. Neuropathological examination established the presence of characteristic ubiquitinated and TDP-43-positive neuronal and glial inclusions, but no abnormality in the distribution of angiogenin protein. DISCUSSION: There is only one previous report describing the neuropathology in a single case with a p.K17I ANG mutation which highlighted the presence of eosinophilic neuronal intranuclear inclusions in the hippocampus. The absence of this feature in the present case indicates that patients with ANG mutations do not always have pathological changes distinguishable from those of sporadic amyotrophic lateral sclerosis.

Practical guide to skin prick tests in allergy to aeroallergens.

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

Word recognition within a linguistic context: effects of age, hearing acuity, verbal ability, and cognitive function.

OBJECTIVE: Participants in traditional studies of the effects of context on spoken word recognition have been university undergraduates. When older adults have been included, they have typically been matched with these young adults for verbal ability or years of education. Although this may be a good strategy for eliminating confounding variables, it is not clear how results of these studies may extend to the general population of young and older adults. The objective of this study was to examine the effects of adult age, hearing acuity, verbal ability, and cognitive function on the use of linguistic context in spoken word recognition. DESIGN: Fifty-three adults, aged 19 to 89 yr, heard short sentences in which the final word was masked by multitalker babble. The level of babble was progressively reduced in 2 dB steps until the sentence-final word could be correctly identified. Published norms were used to construct sets of sentences in which the same word could be heard with three levels of predictability (low, medium, and high) based on the linguistic context. In a fourth condition (no context), the words were preceded by a neutral carrier phrase. Participants received tests of verbal ability, with an emphasis on vocabulary knowledge, a brief test battery to assess cognitive function, and an assessment of hearing acuity based on pure-tone thresholds. Participants' hearing acuity ranged from normal acuity to moderate hearing loss. RESULTS: Results showed that the signal to noise ratio necessary for correct word recognition varied inversely with the probability of that word occurring in the sentence context. Hearing loss had a significant effect on word recognition for words heard in a neutral context, but the effect of hearing acuity diminished progressively with increasing contextual probability of the target word. Hierarchical multiple regressions showed that hearing acuity accounted for a significant amount of the variance at the lowest three levels of contextual probability but not at the highest probability level tested. Cognitive function contributed significantly to the obtained variance in word recognition performance at all levels of contextual probability tested. Moreover, participant age accounted for a significant amount of variance even after hearing acuity and cognitive function were taken into account. Verbal ability in the range represented by the test participants did not contribute significantly to recognition performance in any of the context conditions. CONCLUSIONS: Peripheral hearing acuity accounted for only a part of the variance in word recognition accuracy, with significant variance also contributed by individual differences in cognitive function and participant age. Results showed the ability to use linguistic context to aid spoken word recognition is sufficiently robust that a relatively wide range in verbal ability among native English speakers had no effect on recognition performance.