Temporal dynamics of the early immune response following Mycobacterium bovis infection of cattle.

Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection in cattle is characterized by a cell-mediated immune response (CMI) that precedes humoral responses, however the timing and trajectories of CMI and antibody responses determined by newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release assays (IGRA) and an eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA and IDEXX M. bovis antibody tests to assess immune trajectories following experimental M. bovis infection of cattle. The results show CMI responses developed as early as two-weeks post-infection, with all infected cattle testing positive three weeks post-infection. Interestingly, 6 of 8 infected animals were serologically positive with the Enferplex TB assay as early as 4 weeks post-infection. As expected, application of the tuberculin skin test enhanced subsequent serological reactivity. Infrequent M. bovis faecal shedding was observed but was uncorrelated with observed immune trajectories. Together, the results show that early antibody responses to M. bovis infection are detectable in some individuals and highlight an urgent need to identify biomarkers that better predict infection outcomes, particularly for application in low-and-middle income countries where test-and-slaughter based control methods are largely unfeasible.

Enferplex bovine TB antibody test and bovine TB diagnosis: letter to the editor.

Bovine tuberculosis is usually diagnosed using tuberculin skin and interferon gamma tests. However, it is clear these tests miss infected animals due to poor sensitivity. The Enferplex Bovine TB antibody test has been validated by the World Organisation for Animal Health as fit for purpose in diagnosing bovine TB. A recent paper by Madden and colleagues (Veterinary Research Communications published online 17 August 2023) presented data on the future risk of Enferplex test antibody positive animals developing bovine TB. We argue in this communication that this does not make sense. Also, the study design did not include measuring antibodies at the point of censure of the animals and hence the survival analysis performed was meaningless. Most significantly, the study misses the point that skin and interferon gamma tests fail to detect a significant proportion of infected animals identified by the Enferplex test.

Frightened of giants: fear responses to elephants approach that of predators.

Animals are faced with a variety of dangers or threats, which are increasing in frequency with ongoing environmental change. While our understanding of fearfulness of such dangers is growing in the context of predation and parasitism risk, the extent to which non-trophic, interspecific dangers elicit fear in animals remains less appreciated. We provide an experimental test for fear responses of savannah ungulates to a dominant and aggressive megaherbivore, the African bush elephant (Loxodonta africana), and contrast responses to an apex predator known to elicit fear in this system. Using an automated behavioural response system, we contrast vigilance and run responses of ungulates to elephant, leopard (Panthera pardus), and control (red-chested cuckoo Cuculus solitarius) vocalizations. Overall, we find that ungulates responded to elephant calls, both in terms of an increase in run and vigilance responses relative to controls. The magnitude of most behavioural responses (four of six considered) to elephant vocalizations were not significantly different than responses to leopards. These results suggest that megaherbivores can elicit strong non-trophic fear responses by ungulates and call to broaden frameworks on fear to consider dominant species, such as megaherbivores, as key modifiers of fear-induced interactions.

Evaluation of Antibody Tests for Mycobacterium bovis Infection in Pigs and Deer.

This study addressed the need in Great Britain for supplementary blood tests for deer and pig herds under movement restrictions due to confirmed Mycobacterium bovis infection-to enhance the overall sensitivity and reliability of tuberculosis (TB) testing and contribute to an exit strategy for these herds. We evaluated four antibody tests (lateral flow DPP VetTB Assay for Cervids, M. bovis IDEXX ELISA, Enferplex Cervid and Porcine antibody tests and an in-house comparative PPD ELISA) using serum samples from defined cohorts of TB-infected and TB-free deer and pigs. TB-infected deer included two separate cohorts; farmed deer that had received a tuberculin skin test less than 30 days prior, and park deer that had received no prior skin test. In this way, we were able to assess the effect of the skin test anamnestic boost upon antibody test sensitivity. We tested a total of 402 TB-free pigs and 416 TB-free deer, 77 infected farmed deer and 105 infected park deer, and 29 infected pigs (including 2 wild boar). For deer, we found an equivalent high performance of all four tests: specificity range 98.8-99.5% and sensitivity range 76.6-85.7% for skin test-boosted infected deer, and 51.4-58.1% for non-boosted infected deer. These data suggest an overall approximate 25% increase in test sensitivity for infected deer following a skin test boost. For pigs, the tests again had equivalent high specificity of 99-99.5% and a sensitivity range of 62.1-86.2%, with substantial agreement for three of the four tests. Retrospective application of the ELISA tests to individual culled park deer and wild boar that showed no obvious evidence of TB at larder inspection identified a significant seropositivity within wild boar suggestive of low-level M. bovis infection that would otherwise not have been detected. Overall this investigation provided a robust evaluation of four antibody tests, which is essential to generate confidence in test performance before a wider deployment within TB control measures can be considered.

Diagnostic accuracy of the Enferplex Bovine Tuberculosis antibody test in cattle sera.

Bovine tuberculosis is a contagious bacterial disease of worldwide economic, zoonotic and welfare importance caused mainly by Mycobacterium bovis infection. Current regulatory diagnostic methods lack sensitivity and require improvement. We have developed a multiplex serological test for bovine tuberculosis and here we provide an estimate of the diagnostic accuracy of the test in cattle. Positive and negative reference serum samples were obtained from animals from Europe and the United States of America. The diagnostic specificity estimate was 98.4% and 99.7% using high sensitivity and high specificity settings of the test respectively. Tuberculin boosting did not affect the overall specificity estimate. The diagnostic sensitivity in samples from Mycobacterium bovis culture positive animals following tuberculin boosting was 93.9%.The relative sensitivity following boosting in tuberculin test positive, lesion positive animals and interferon gamma test positive, lesion positive animals was 97.2% and 96.9% respectively. In tuberculin test negative, lesion positive animals and in interferon gamma test negative, lesion positive animals, the relative sensitivity following tuberculin boosting was 88.2% and 83.6% respectively. The results show that the test has high diagnostic sensitivity and specificity and can detect infected animals that are missed by tuberculin and interferon gamma testing.

Rhythmic and interval-based temporal orienting in autism.

Individuals with autism spectrum disorder (ASD) may show secondary sensory and cognitive characteristics, including differences in auditory processing, attention, and, according to a prominent hypothesis, the formulation and utilization of predictions. We explored the overlap of audition, attention, and prediction with an online auditory "temporal orienting" task in which participants utilized predictive timing cues (both rhythmic and interval-based) to improve their detection of faint sounds. We compared an autistic (n = 78) with a nonautistic (n = 83) group, controlling for nonverbal IQ, and used signal detection measures and reaction times to evaluate the effect of valid temporally predictive cues. We hypothesized that temporal orienting would be compromised in autism, but this was not supported by the data: the boost in performance induced by predictability was practically identical for the two groups, except for the small subset of the ASD group with co-occurring attention deficit hyperactivity disorder, who received less benefit from interval-based cueing. However, we found that the presence of a rhythm induced a significantly stronger bias toward reporting target detections in the ASD group at large, suggesting weakened response inhibition during rhythmic entrainment.

Autistic Adults Show Intact Learning on a Visuospatial Serial Reaction Time Task.

Some theories have proposed that autistic individuals have difficulty learning predictive relationships. We tested this hypothesis using a serial reaction time task in which participants learned to predict the locations of a repeating sequence of target locations. We conducted a large-sample online study with 61 autistic and 71 neurotypical adults. The autistic group had slower overall reaction times, but demonstrated sequence-specific learning equivalent to the neurotypical group, consistent with other findings of typical procedural memory in autism. The neurotypical group, however, made significantly more prediction-related errors early in the experiment when the stimuli changed from repeated sequences to random locations, suggesting certain limited behavioural differences in the learning or utilization of predictive relationships for autistic adults.

Altered engagement of the speech motor network is associated with reduced phonological working memory in autism.

Nonword repetition, a common clinical measure of phonological working memory, involves component processes of speech perception, working memory, and speech production. Autistic children often show behavioral challenges in nonword repetition, as do many individuals with communication disorders. It is unknown which subprocesses of phonological working memory are vulnerable in autistic individuals, and whether the same brain processes underlie the transdiagnostic difficulty with nonword repetition. We used functional magnetic resonance imaging (fMRI) to investigate the brain bases for nonword repetition challenges in autism. We compared activation during nonword repetition in functional brain networks subserving speech perception, working memory, and speech production between neurotypical and autistic children. Autistic children performed worse than neurotypical children on nonword repetition and had reduced activation in response to increasing phonological working memory load in the supplementary motor area. Multivoxel pattern analysis within the speech production network classified shorter vs longer nonword-repetition trials less accurately for autistic than neurotypical children. These speech production motor-specific differences were not observed in a group of children with reading disability who had similarly reduced nonword repetition behavior. These findings suggest that atypical function in speech production brain regions may contribute to nonword repetition difficulties in autism.

Inflated scaled scores on the digital WISC-V coding subtest in a Canadian sample.

This study examined performance differences in the traditional paper-and-pencil and new digital versions of the Coding subtest from the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V) using a cross-sectional sample. A total of 212 school-aged children between 6 and 14 years old were included in the sample, with 116 completing the paper version and 96 completing the digital version administered on a tablet in 2017-2018. One-way ANOVA revealed a significant difference with large effect size between mean scaled scores, with the digital version resulting in higher scaled scores than the paper version, F (1, 210) = 67.57, p < 0.001, d = 1.14, ηp2 = 0.24. That is, normed digital scores appear inflated as compared to paper scores. No difference in raw scores was observed when controlling for age, F (1, 209) = 0.54, p > 0.05. Post-hoc analyses were performed to account for potential confounds in demographic differences and to maximize group equivalence, with the same pattern of results. Findings have important implications for clinical interpretation of Coding scores when administering the digital version of the task. Clinicians, including psychologists and neuropsychologists, should be aware of the limitations of the new digital version of this subtest, including differences in standardized performance and task requirements. Future studies using random assignment and/or repeated-measures design are needed to replicate these findings.

Prediction in Autism Spectrum Disorder: A Systematic Review of Empirical Evidence.

According to a recent influential proposal, several phenotypic features of autism spectrum disorder (ASD) may be accounted for by differences in predictive skills between individuals with ASD and neurotypical individuals. In this systematic review, we describe results from 47 studies that have empirically tested this hypothesis. We assess the results based on two observable aspects of prediction: learning a pairing between an antecedent and a consequence and responding to an antecedent in a predictive manner. Taken together, these studies suggest distinct differences in both predictive learning and predictive response. Studies documenting differences in learning predictive pairings indicate challenges in detecting such relationships especially when predictive features of an antecedent have low salience or consistency, and studies showing differences in habituation and perceptual adaptation suggest low-level predictive processing differences in ASD. These challenges may account for the observed differences in the influence of predictive priors, in spontaneous predictive movement or gaze, and in social prediction. An important goal for future research will be to better define and constrain the broad domain-general hypothesis by testing multiple types of prediction within the same individuals. Additional promising avenues include studying prediction within naturalistic contexts and assessing the effect of prediction-based intervention on supporting functional outcomes for individuals with ASD. LAY SUMMARY: Researchers have suggested that many features of autism spectrum disorder (ASD) may be explained by differences in the prediction skills of people with ASD. We review results from 47 studies. These studies suggest that ASD may be associated with differences in the learning of predictive pairings (e.g., learning cause and effect) and in low-level predictive processing in the brain (e.g., processing repeated sounds). These findings lay the groundwork for research that can improve our understanding of ASD and inform interventions. Autism Res 2021, 14: 604-630. © 2021 International Society for Autism Research and Wiley Periodicals LLC.

Executive Functioning Rating Scale as a Screening Tool for ADHD: Independent Validation of the BDEFS-CA.

Objective: This study provides independent examination of the validity of the Barkley Deficits of Executive Functioning Scale-Children and Adolescents (BDEFS-CA) in a sample of children diagnosed with ADHD (n = 50) and typically developing controls (n = 50). Method: Parents of participants completed the BDEFS-CA and the Conners 3 rating scales. Validity of BDEFS-CA was examined using a confirmatory factor analysis, correlational analyses with Conners 3 ratings, and receiver operating characteristic (ROC) curve analysis of diagnostic accuracy. Results: Findings support the construct, concurrent, and discriminant validity of the BDEFS-CA in a mixed sample. Conclusion: Findings provide independent examination of the validity of the BDEFS-CA as a measure of executive dysfunction and a screening tool for ADHD.

Auditory Processing of Speech and Tones in Children With Tuberous Sclerosis Complex.

Individuals with Tuberous Sclerosis Complex (TSC) have atypical white matter integrity and neural connectivity in the brain, including language pathways. To explore functional activity associated with auditory and language processing in individuals with TSC, we used electroencephalography (EEG) to examine basic auditory correlates of detection (P1, N2, N4) and discrimination (mismatch negativity, MMN) of speech and non-speech stimuli for children with TSC and age- and sex-matched typically developing (TD) children. Children with TSC (TSC group) and without TSC (typically developing, TD group) participated in an auditory MMN paradigm containing two blocks of vowels (/a/and/u/) and two blocks of tones (800 Hz and 400 Hz). Continuous EEG data were collected. Multivariate pattern analysis (MVPA) was used to explore functional specificity of neural auditory processing. Speech-specific P1, N2, and N4 waveform components of the auditory evoked potential (AEP) were compared, and the mismatch response was calculated for both speech and tones. MVPA showed that the TD group, but not the TSC group, demonstrated above-chance pairwise decoding between speech and tones. The AEP component analysis suggested that while the TD group had an increased P1 amplitude in response to vowels compared to tones, the TSC group did not show this enhanced response to vowels. Additionally, the TD group had a greater N2 amplitude in response to vowels, but not tones, compared to the TSC group. The TSC group also demonstrated a longer N4 latency to vowels compared to tones, which was not seen in the TD group. No group differences were observed in the MMN response. In this study we identified features of the auditory response to speech sounds, but not acoustically matched tones, which differentiate children with TSC from TD children.

Providing visual directives via a smart watch to a student with Autism Spectrum Disorder: an intervention note.

Smart watches are discreet and wearable tools that may be repurposed to improve directive-following for individuals with autism spectrum disorder (ASD). Specifically, a mentor can transmit just-in-time (JIT) visual supports (e.g., video clips, photographs, text) that depict an upcoming directive to a learner's smart watch to prompt the learner as needed from a distance. Using a single-case multiple probe design across settings, this investigation evaluated the effectiveness of providing text-based prompts on an Apple Watch 1 to a child with ASD within a school setting. A mentor transmitted 2-step written directives via text message to the participant's Apple Watch. The participant was instructed to attend to, read, and follow directives received on the watch. Results demonstrated that the intervention improved directive-following as well as increased the instructor's distance from the learner. It is proposed that JIT supports sent to a learner's smart watch may reduce the obtrusiveness of traditional prompting while also maintaining the naturalness of ongoing social or academic interactions. Clinical limitations and implications are discussed.

Reduced graphomotor procedural learning in children and adolescents with ADHD.

PURPOSE: The present study sought to determine if children and adolescents with ADHD demonstrate reduced procedural learning of a graphomotor program. METHOD: Thirty-two children and adolescents between age 9 and 15 with (n = 16) and without ADHD (n = 16) participated in the study. Each group of participants practiced a novel grapheme on a digitizing tablet 30 times. Participants with ADHD were off stimulant medication or were medication naïve. RESULTS: Control participants demonstrated significant improvement in graphomotor fluency from the beginning to the end of practice, T = 2, z = -2.534, p = .009, whereas participants with ADHD did not, T = 4, z = -1.810, p = .074. CONCLUSIONS: Consistent with findings in adults with ADHD, results indicate that graphomotor procedural learning in children and adolescents with ADHD is attenuated. Findings have implications for future research that may inform remediation of handwriting difficulties, academic accommodations, and using digitizing technology for neuropsychological assessment.

Evaluation of a multiplex immunoassay for bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk against two indirect ELISAs using latent class analysis.

Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV) are responsible for respiratory disease and diarrhea in cattle worldwide. The Norwegian control program against these infections is based on herd-level diagnosis using a new multiplex immunoassay. The objective of this study was to estimate sensitivity and specificity across different cut-off values for the MVD-Enferplex BCV/BRSV multiplex, by comparing them to a commercially available ELISA, the SVANOVIR® BCV-Ab and SVANOVIR® BRSV-Ab, respectively. We analyzed bulk tank milk samples from 360 herds in a low- and 360 herds in a high-prevalence area. As none of the tests were considered perfect, estimation of test characteristics was performed using Bayesian latent class models. At the manufacturers' recommended cut-off values, the median sensitivity for the BRSV multiplex and the BRSV ELISA was 94.4 [89.8-98.7 95% Posterior Credibility Interval (PCI)] and 99.8 [98.7-100 95% PCI], respectively. The median specificity for the BRSV multiplex was 90.6 [85.5-94.4 95% PCI], but only 57.4 [50.5-64.4 95% PCI] for the BRSV ELISA. However, increasing the cut-off of the BRSV ELISA increased specificity without compromising sensitivity. For the BCV multiplex we found that by using only one of the three antigens included in the test, the specificity increased, without concurrent loss in sensitivity. At the recommended cut-off this resulted in a sensitivity of 99.9 [99.3-100 95% PCI] and specificity of 93.7 [88.8-97.8 95% PCI] for the multiplex and a sensitivity of 99.5 [98.1-100 95% PCI] and a specificity of 99.6 [97.6-100 95% PCI] for the BCV ELISA.

Short-term test-retest reliability of the ImPACT in healthy young athletes.

The present study examined the short-term test-retest reliability of the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) variables with healthy 11- to 14-year-old athletes. 53 young athletes (Mage = 12.4 years, 9 female) were administered the ImPACT on two separate occasions two weeks apart. Participants were instructed to complete the Post-Concussion Symptom Scale (PCSS) and the baseline computerized neurocognitive test during both the baseline and retest phases. Intraclass correlation (ICC), standard error of measurement (SEM), and reliable change index (RCI) were used as reliability metrics. PCSS Total Symptoms and Visual-Motor Speed were the only scores to reach clinical reliability standards (i.e., R > 0.7). None of the scores exceeded RCI cut-offs. Results indicate that the composite scores of the ImPACT are differentially reliable in a preadolescent sample across a two-week retest period, with only motor processing speed and self-reported symptoms exceeding clinical reliability standards. The findings support the view that neurocognitive testing should not be the sole determining factor in concussion assessment. This study highlights the importance of continuing research with younger athletes to assess the reliability of neurocognitive measures in concussion management programs. Future research should focus on a larger, heterogeneous sample, including children with learning disabilities and ADHD.

Evidenced-Based Cognitive Rehabilitation for Persons With Multiple Sclerosis: An Updated Review of the Literature From 2007 to 2016.

OBJECTIVE: To update the clinical recommendations for cognitive rehabilitation of people with multiple sclerosis (MS), based on a systematic review of the literature from 2007 through 2016. DATA SOURCES: Searches of MEDLINE, PsycINFO, and CINAHL were conducted with a combination of the following terms: attention, awareness, cognition, cognitive, communication, executive, executive function, language, learning, memory, perception, problem solving, reasoning, rehabilitation, remediation, training, processing speed, and working memory. One hundred twenty-nine articles were identified and underwent initial screening. STUDY SELECTION: Fifty-nine articles were selected for inclusion after initial screening. Nineteen studies were excluded after further detailed review. Forty studies were fully reviewed and evaluated. DATA EXTRACTION: Articles were assigned to 1 of 6 categories: attention, learning and memory, processing speed and working memory, executive functioning, metacognition, or nonspecified/combined cognitive domains. Articles were abstracted and levels of evidence were decided using specific criteria. DATA SYNTHESIS: The current review yielded 6 class I studies, 10 class II studies, and 24 class III studies. One intervention in the area of verbal learning and memory received support for a practice standard, 2 computer programs received support as practice guidelines (in the area of attention and multicognitive domains), and several studies provided support for 5 practice options in the domains of attention and learning and memory. CONCLUSIONS: Substantial progress has been made since our previous review regarding the identification of effective treatments for cognitive impairments in persons with MS. However, much work remains to be done to optimize rehabilitation potential by applying the most methodologically rigorous research designs to provide class I evidence in support of a given treatment strategy.