Seq-Scope Protocol: Repurposing Illumina Sequencing Flow Cells for High-Resolution Spatial Transcriptomics.

Spatial transcriptomics (ST) technologies represent a significant advance in gene expression studies, aiming to profile the entire transcriptome from a single histological slide. These techniques are designed to overcome the constraints faced by traditional methods such as immunostaining and RNA in situ hybridization, which are capable of analyzing only a few target genes simultaneously. However, the application of ST in histopathological analysis is also limited by several factors, including low resolution, a limited range of genes, scalability issues, high cost, and the need for sophisticated equipment and complex methodologies. Seq-Scope-a recently developed novel technology-repurposes the Illumina sequencing platform for high-resolution, high-content spatial transcriptome analysis, thereby overcoming these limitations. Here we provide a detailed step-by-step protocol to implement Seq-Scope with an Illumina NovaSeq 6000 sequencing flow cell that allows for the profiling of multiple tissue sections in an area of 7 mm × 7 mm or larger. In addition to detailing how to prepare a frozen tissue section for both histological imaging and sequencing library preparation, we provide comprehensive instructions and a streamlined computational pipeline to integrate histological and transcriptomic data for high-resolution spatial analysis. This includes the use of conventional software tools for single cell and spatial analysis, as well as our recently developed segmentation-free method for analyzing spatial data at submicrometer resolution. Given its adaptability across various biological tissues, Seq-Scope establishes itself as an invaluable tool for researchers in molecular biology and histology.

Hearing Loss, Hearing Aid Use, and Risk of Dementia in Older Adults.

Importance: Hearing loss has been suggested as a risk factor for dementia, but there is still a need for high-quality research to better understand the association between these 2 conditions and the underlying causal mechanisms and treatment benefits using larger cohorts and detailed data. Objective: To investigate the association between hearing loss and incident dementia, as well as how hearing aid use contributes to this association. Design, Setting, and Participants: This population-based cohort study was conducted in Southern Denmark between January 2003 and December 2017 and included all residents 50 years and older. We excluded all persons with dementia before baseline as well as those who did not live in the region 5 years before baseline, with incomplete address history, or who had missing covariate information. Exposures: Individual hearing status based on the Hearing Examinations in Southern Denmark database, which contains data on all pure-tone audiometry examinations performed at public hearing rehabilitation clinics in Southern Denmark. Main Outcomes and Measures: Incident cases of dementia and Alzheimer disease as identified from national registries. Results: The study population comprised 573 088 persons (298 006 women [52%]; mean [SD] age, 60.8 [11.3] years) with 23 023 cases of dementia and mean (SD) follow-up of 8.6 (4.3) years. Having a hearing loss was associated with an increased risk of dementia, with an adjusted hazard ratio (HR) of 1.07 (95% CI, 1.04-1.11) compared with having no hearing loss. Severe hearing loss in the better and worse ear was associated with a higher dementia risk, with an HR of 1.20 (95% CI, 1.09-1.32) and 1.13 (95% CI, 1.06-1.20), respectively, compared with having no hearing loss in the corresponding ear. Compared with people without hearing loss, the risk of dementia was higher among people with hearing loss who were not using hearing aids than those who had hearing loss and were using hearing aids, with HRs of 1.20 (95% CI, 1.13-1.27) and 1.06 (95% CI, 1.01-1.10), respectively. Conclusions and Relevance: The results of this cohort study suggest that hearing loss was associated with increased dementia risk, especially among people not using hearing aids, suggesting that hearing aids might prevent or delay the onset and progression of dementia. The risk estimates were lower than in previous studies, highlighting the need for more high-quality longitudinal studies.

AMTASTM and user-operated smartphone research application audiometry-An evaluation study.

OBJECTIVE: To evaluate two user-operated audiometry methods, the AMTASTM PC-based audiometry and a low-cost smartphone audiometry research application (R-App). DESIGN: A repeated-measures within-subject study design was used to compare both user-operated methods to traditional manual audiometry and to evaluate test-retest reliability of each method. STUDY SAMPLE: 58 subjects were recruited in the study of which 83 ears had normal hearing thresholds and 33 ears had hearing loss (pure-tone average > 25 dB HL). Average age of participants was 44.8 years, with an age range of 11-85. RESULTS: Standard deviation of absolute differences ranged between 3.9-6.9 dB on AMTASTM and 4.5-6.8 dB on the R-App. The highest variability was found at the 8000 Hz frequency (R-App and AMTASTM test) and 3000 Hz frequency (AMTASTM retest). Evaluation of test-retest reliability of AMTASTM and R-App showed SD of absolute differences ranging between 3.5-5.8 dB and 3.1-5.0 dB, respectively. The mean threshold difference between test and retest was within ±1.5 dB on AMTASTM and ±1 dB on the R-App. CONCLUSION: Accuracy of AMTASTM and the R-App was within acceptable limits for audiometry and comparable to traditional manual audiometry on all tested frequencies (250-8000 Hz). Evaluation of test-retest reliability showed acceptable variation on both AMTASTM and R-App. Both user-operated methods could be reliably performed in a quiet non-soundproofed environment.

Eye-Tracking on Touch Screen - Evaluating User Interaction.

This paper suggests a setup for using remote eye-tracking on a touchscreen tablet to evaluate user interaction for older adults interacting with a user-driven hearing test. By using video recordings to support the eye-tracking data, it was possible to evaluate quantitative usability metrics that could be compared to other research findings. The video recordings revealed useful information to distinguish between reasons for gaps in data and missing data and to inform future similar studies of human-computer interaction on a touch screen. Using only portable equipment allows researchers to move to the location of the user and investigate the user interaction of devices in real-world scenarios.

Comparison of hearing aid fitting effectiveness with audiograms from either user-operated or traditional audiometry in a clinical setting: a study protocol for a blinded non-inferiority randomised controlled trial.

INTRODUCTION: There is a worldwide need to enhance the capacity of audiometry testing. The objective of this study is to compare the User-operated Audiometry (UAud) system with traditional audiometry in a clinical setting, by investigating if hearing aid effectiveness based on UAud is non-inferior to hearing aid effectiveness based on traditional audiometry, and whether thresholds obtained with the user-operated version of the Audible Contrast Threshold (ACT) test correlates to traditional measures of speech intelligibility. METHODS AND ANALYSIS: The design will be a blinded non-inferiority randomised controlled trial. 250 adults referred for hearing aid treatment will be enrolled in the study. Study participants will be tested using both traditional audiometry as well as the UAud system and they will answer the questionnaire Speech, Spatial and Qualities of Hearing Scale (SSQ12) at baseline. Participants will be randomly divided to receive hearing aids fitted based on either UAud or traditional audiometry. Three months after participants have started using their hearing aids, they will undergo a hearing in noise test with hearing aids to measure their speech-in-noise performance and answer the following questionnaires: SSQ12, the Abbreviated Profile of Hearing Aid Benefit and the International Outcome Inventory for Hearing Aids. The primary outcome is a comparison of the change in SSQ12 scores from baseline to follow-up between the two groups. Participants will undergo the user-operated ACT test of spectro-temporal modulation sensitivity as part of the UAud system. The ACT results will be compared with measures of speech intelligibility from the traditional audiometry session and follow-up measurements. ETHICS AND DISSEMINATION: The project was evaluated by the Research Ethics Committee of Southern Denmark and judged not to need approval. The findings will be submitted to an international peer-reviewed journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05043207.

Ambient Noise in Candidate Rooms for User-Operated Audiometry.

Hearing loss is a widespread problem while treatment is not always accessible, mainly because of the limited availability of hearing care professionals and clinics. In this work, part of the User-Operated Audiometry project, we investigate the acoustic environment of inexpensive non-sound-treated rooms that could be used for unsupervised audiometric testing. Measurements of 10 min of ambient noise were taken from 20 non-sound-treated rooms in libraries and private and public clinics, nine of which were measured twice. Ambient noise was compared against two traditional audiometric sound-treated rooms and Maximum Permissible Ambient noise levels by ISO 8231-1, while factoring for the attenuation by the DD450 circumaural headphones provided. In most non-sound-treated rooms, MPAs were violated only by transient sounds, while the floor-noise level was below MPAs. Non-sound-treated rooms' ambient noise levels presented with much larger fluctuations compared to sound-treated rooms. Almost all violations occurred at low to mid-low frequencies. Our results suggest that large-scale implementation of user-operated audiometry outside traditional audiometric rooms is possible, at least under some realizable conditions. Circumaural headphones' attenuation is probably a necessary condition for all cases. Depending on the room, an online system making decisions based on ambient noise might also be included in combination with active attenuation.

Transportation Noise and Risk of Tinnitus: A Nationwide Cohort Study from Denmark.

BACKGROUND: There is a growing body of evidence linking residential exposure to transportation noise with several nonauditory health outcomes. However, auditory outcomes, such as tinnitus, are virtually unexplored. OBJECTIVES: We aimed to investigate the association between residential transportation noise and risk of incident tinnitus. METHODS: We conducted a nationwide cohort study including all residents in Denmark age ≥30y, of whom 40,692 were diagnosed with tinnitus. We modeled road traffic and railway noise at the most (Ldenmax) and least (Ldenmin) exposed façades of all Danish addresses from 1990 until 2017. For all participants, we calculated 1-, 5-, and 10-y time-weighted mean noise exposure and retrieved detailed information on individual- and area-level socioeconomic covariates. We conducted analyses using Cox proportional hazards models. RESULTS: We found positive associations between exposure to road traffic noise and risk of tinnitus, with hazard ratios of 1.06 [95% confidence interval (CI): 1.04, 1.08] and 1.02 (95% CI: 1.01, 1.03) per 10-dB increase in 10-y Ldenmin and Ldenmax, respectively. Highest risk estimates were found for women, people without a hearing loss, people with high education and income, and people who had never been in a blue-collar job. The association with road Ldenmin followed a positive, monotonic exposure-response relationship. We found no association between railway noise and tinnitus. DISCUSSION: To our knowledge, this is the first study to show that residential exposure to road traffic noise may increase risk of tinnitus, suggesting noise may negatively affect the auditory system. If confirmed, this finding adds to the growing evidence of road traffic noise as a harmful pollutant with a substantial health burden. https://doi.org/10.1289/EHP11248.

Risk of cardiovascular diseases following residential exposure to airborne polychlorinated biphenyls: A register-based cohort study.

BACKGROUND: Indoor air in buildings constructed with materials containing polychlorinated biphenyls (PCBs) may be contaminated with especially lower-chlorinated PCBs. So far, the cardiovascular consequences of living with such contamination are unknown. OBJECTIVES: To determine the risk of cardiovascular disease (CVD) following residential exposure to predominantly lower-chlorinated PCBs in indoor air. METHODS: The Health Effects of PCBs in Indoor Air (HESPAIR) cohort is register-based with 51 921 residents of two residential areas near Copenhagen: Farum Midtpunkt and Brøndby Strand Parkerne. Here, indoor air was contaminated with PCB in one third of the apartments due to construction with materials containing PCB. Individual PCB exposure was estimated based on register-based information on relocation dates and indoor air PCB measurements in subsets of the apartments. Information on CVD was retrieved from the Danish National Patient Register for the follow-up period of 1977-2018. We estimated adjusted hazard ratios using Cox regression with time-varying exposure. RESULTS: Cumulative residential exposure to airborne PCB was not associated with a higher overall risk for CVD (HR for highly exposed (≥3300 ng/m3 PCB × year): 1.02, 95% CI 0.94-1.10). This was also the case for most of the specific cardiovascular diseases, apart from acute myocardial infarction where a higher risk was observed for residents exposed to ≥3300 ng/m3 PCB × year compared to the reference group (HR 1.17, 95% CI 1.00-1.35). However, no exposure-response relationship was apparent and additional adjustment for education attenuated the risk estimate. DISCUSSION: In this, to our knowledge, first study ever to examine the risk of CVD following residential exposure to PCBs in indoor air, we observed limited support for cardiovascular effects of living in PCB-contaminated indoor air. Considering the prevalence of exposure to airborne PCBs and lack of literature on their potential health effects, these findings need to be corroborated in other studies.

User-operated audiometry - an evaluation of expert vs. non-expert headphone placement.

OBJECTIVE: User-operated audiometry faces multiple barriers. One of these is the concern of audiologists that patients (non-experts) placing headphones by themselves results in invalid hearing thresholds due to greater placement variability. DESIGN: Comparative study. Participants took the AMTAS pure-tone air-conduction audiometry under two different conditions, expert and non-expert circumaural headphone placement for five frequencies within the range 250-8000 Hz. Questionnaires were also used to gain insight into the usability of the user-operated audiometry system - as well as the participants' perceived handling of the audiometry headphones. STUDY SAMPLE: Thirty participants (mean age 67.5 years). RESULTS: No statistically significant mean differences in hearing thresholds between the expert and non-expert conditions were found. The mean system usability scale score was 84.5. Handling the headphones was also rated as being easy (30%) or very easy (60%) by most non-experts. CONCLUSION: The conclusion of the study is that non-experts can be trusted to properly equip a pair of circumaural audiometry headphones for the correct conduction of pure-tone audiometry with only a few digital instructions.

User-Operated Audiometry Project (UAud) - Introducing an Automated User-Operated System for Audiometric Testing Into Everyday Clinic Practice.

Hearing loss is the third leading cause of years lived with disability. It is estimated that 430 million people worldwide are affected, and the number of cases is expected to increase in the future. There is therefore increased pressure on hearing health systems around the world to improve efficiency and reduce costs to ensure increased access to quality hearing health care. Here, we describe the User-Operated Audiometry project, the goal of which is to introduce an automated system for user-operated audiometric testing into everyday clinic practice as a means to relieve part of this pressure. The alternative to the existing referral route is presented in which examination is executed via the user-operated system. This route is conceptualized as an interaction between the patient, the system, and the hearing care professional (HCP). Technological requirements of the system and challenges that are related to the interaction between patients, the user-operated system, and the HCPs within the specific medical setting are discussed. Lastly, a strategy for the development and implementation of user-operated audiometry is presented, which includes initial investigations, a validation study, and implementation in a real-life clinical situation.

Residential exposure to transportation noise in Denmark and incidence of dementia: national cohort study.

OBJECTIVE: To investigate the association between long term residential exposure to road traffic and railway noise and risk of incident dementia. DESIGN: Nationwide prospective register based cohort study. SETTING: Denmark. PARTICIPANTS: 1 938 994 adults aged ≥60 years living in Denmark between 1 January 2004 and 31 December 2017. MAIN OUTCOME MEASURES: Incident cases of all cause dementia and dementia subtypes (Alzheimer's disease, vascular dementia, and Parkinson's disease related dementia), identified from national hospital and prescription registries. RESULTS: The study population included 103 500 participants with incident dementia, and of those, 31 219 received a diagnosis of Alzheimer's disease, 8664 of vascular dementia, and 2192 of Parkinson's disease related dementia. Using Cox regression models, 10 year mean exposure to road traffic and railway noise at the most (Ldenmax) and least (Ldenmin) exposed façades of buildings were associated with a higher risk of all cause dementia. These associations showed a general pattern of higher hazard ratios with higher noise exposure, but with a levelling off or even small declines in risk at higher noise levels. In subtype analyses, both road traffic noise and railway noise were associated with a higher risk of Alzheimer's disease, with hazard ratios of 1.16 (95% confidence interval 1.11 to 1.22) for road Ldenmax ≥65 dB compared with <45 dB, 1.27 (1.22 to 1.34) for road Ldenmin ≥55 dB compared with <40 dB, 1.16 (1.10 to 1.23) for railway Ldenmax ≥60 dB compared with <40 dB, and 1.24 (1.17 to 1.30) for railway Ldenmin ≥50 dB compared with <40 dB. Road traffic, but not railway, noise was associated with an increased risk of vascular dementia. Results indicated associations between road traffic Ldenmin and Parkinson's disease related dementia. CONCLUSIONS: This nationwide cohort study found transportation noise to be associated with a higher risk of all cause dementia and dementia subtypes, especially Alzheimer's disease.

Maternal exposure to airborne polychlorinated biphenyls (PCBs) and risk of adverse birth outcomes.

Human health effects of airborne lower-chlorinated polychlorinated biphenyls (LC-PCBs) are largely unexplored. Since PCBs may cross the placenta, maternal exposure could potentially have negative consequences for fetal development. We aimed to determine if exposure to airborne PCB during pregnancy was associated with adverse birth outcomes. In this cohort study, exposed women had lived in PCB contaminated apartments at least one year during the 3.6 years before conception or the entire first trimester of pregnancy. The women and their children were followed for birth outcomes in Danish health registers. Logistic regression was performed to estimate odds ratios (OR) for changes in secondary sex ratio, preterm birth, major congenital malformations, cryptorchidism, and being born small for gestational age. We performed linear regression to estimate difference in birth weight among children of exposed and unexposed mothers. All models were adjusted for maternal age, educational level, ethnicity, and calendar time. We identified 885 exposed pregnancies and 3327 unexposed pregnancies. Relative to unexposed women, exposed women had OR 0.97 (95% CI 0.82, 1.15) for secondary sex ratio, OR 1.13 (95% CI 0.76, 1.67) for preterm birth, OR 1.28 (95% CI 0.81, 2.01) for having a child with major malformations, OR 1.73 (95% CI 1.01, 2.95) for cryptorchidism and OR 1.23 (95% CI 0.88, 1.72) for giving birth to a child born small for gestational age. The difference in birth weight for children of exposed compared to unexposed women was - 32 g (95% CI-79, 14). We observed an increased risk of cryptorchidism among boys after maternal airborne LC-PCB exposure, but due to the proxy measure of exposure, inability to perform dose-response analyses, and the lack of comparable literature, larger cohort studies with direct measures of exposure are needed to investigate the safety of airborne LC-PCB exposure during pregnancy.

A non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA.

The current nucleic acid signal amplification methods for SARS-CoV-2 RNA detection heavily rely on the functions of biological enzymes which imposes stringent transportation and storage conditions, high cost and global supply shortages. Here, a non-enzymatic whole genome detection method based on a simple isothermal signal amplification approach is developed for rapid detection of SARS-CoV-2 RNA and potentially any types of nucleic acids regardless of their size. The assay, termed non-enzymatic isothermal strand displacement and amplification (NISDA), is able to quantify 10 RNA copies.µL-1. In 164 clinical oropharyngeal RNA samples, NISDA assay is 100 % specific, and it is 96.77% and 100% sensitive when setting up in the laboratory and hospital, respectively. The NISDA assay does not require RNA reverse-transcription step and is fast (<30 min), affordable, highly robust at room temperature (>1 month), isothermal (42 °C) and user-friendly, making it an excellent assay for broad-based testing.

Hearing examinations in Southern Denmark (HESD) database: a valuable tool for hearing-related epidemiological research.

OBJECTIVE: To introduce and document the recently established HESD (Hearing Examinations in Southern Denmark) database, including the necessary data preprocessing steps, and to describe the hearing loss (HL) characteristics of the study sample. DESIGN: Clinical auditory information has been collected for approximately 20 years in the state-funded clinics of the Region of Southern Denmark. We reviewed these data and conducted extensive preprocessing through data selection, integration, cleaning, transformation, and classification. HL profiling was then assessed in terms of severity, asymmetry, configuration, site of lesion, and audiogram shape. STUDY SAMPLE: The final number of complete audiograms available in the HESD database was 271,556, corresponding to detailed hearing information for 143,793 adults. RESULTS: The distribution of HL characteristics differed significantly (p < 0.001) between men and women for all categories analysed. Clear differences were observed for asymmetry and audiogram configuration. However, both men and women had higher prevalence of unilateral, moderate, and sensorineural HL. CONCLUSIONS: This work highlights the potential of the HESD database as a source of audiology-related epidemiological data. It can be used to evaluate the distribution of HL characteristics and also to investigate risk factors for HL and the associations between HL and other health outcomes.

Occupational lifting predicts hospital admission due to low back pain in a cohort of airport baggage handlers.

PURPOSE: To examine if occupational lifting assessed as cumulative years as a baggage handler is associated with first-time hospital diagnosis or treatment for low back disorders. METHODS: This study is based on the Copenhagen Airport Cohort consisting of male baggage handlers performing heavy lifting every day and a reference group of unskilled men from the greater Copenhagen area during the period 1990-2012. We followed the cohort in the National Patient Register and Civil Registration System to obtain information on diagnoses, surgery, mortality, and migration. The outcomes were first-time hospital diagnosis or surgery for (1) lumbar disc herniation or (2) low back pain (LBP). RESULTS: Baggage handlers (N = 3473) had a higher incidence rate of LBP, but not of lumbar disc herniation, compared to the reference group (N = 65,702). Baggage handlers with longer employment had a higher incidence of LBP compared to baggage handlers with shorter employment. The linear association of cumulative years as a baggage handler on LBP was significantly increased with an incidence rate ratio of 1.16 (95% CI 1.07-1.25) for a 5-year increase of employment as baggage handler. CONCLUSIONS: In this large cohort study, we found an increased incidence of LBP among baggage handlers compared to the reference group with indications of a dose-response relationship between years of employment and the outcome. For baggage handlers working on the apron, the incidence was particularly increased before introduction of technical lifting equipment, suggesting that preventive measures to reduce cumulative work load may have a positive effect.

Knee osteoarthritis among airport baggage handlers: A prospective cohort study.

BACKGROUND: Knee osteoarthritis is a common and often disabling disorder, which has been related to knee-straining work. However, exposure response relations are uncertain and there are few prospective studies. We studied prospectively if incident knee osteoarthritis is associated with cumulative exposure as an airport baggage handler, lifting on average 5000 kg/d. METHODS: The study is based on the Copenhagen Airport Cohort, a historical cohort of male baggage handlers and a reference group of unskilled men from the greater Copenhagen area, followed from 1990 to 2012. Cumulative years of employment as a baggage handler was based on information from company employment and union registers. Outcome was first hospital admission with a discharge diagnosis of knee osteoarthritis and/or knee replacement, ascertained from the Danish National Patient Register. RESULTS: The cohort contained 3442 baggage handlers and 65 511 workers in the reference group. The unadjusted incidence rate ratio (IRR) of knee osteoarthritis increased steeply with cumulative years as a baggage handler. Although the exposure-response pattern became weaker and statistically nonsignificant (P ≈ .10) when adjusting for age, the risk of knee osteoarthritis was still increased in baggage handlers at the highest exposure level. Additional analyses showed that the association between age and osteoarthritis was stronger for baggage handlers (IRR = 2.09; 95% CI: 1.68-2.60) than for referents (IRR = 1.58; 95% CI: 1.53-1.63), indicating that knee osteoarthritis occurred at a younger age among baggage handlers than in the reference group. CONCLUSIONS: The results of this prospective cohort study support that long-term heavy lifting increases the risk of knee osteoarthritis.

Eye hazard classification according to UN GHS / EU CLP and the severity of eye symptoms caused by accidental exposures to detergents and cleaning products.

The use of lower cut-off values/concentration limits for the calculation of mixture classification in UN GHS/EU CLP versus the previous regulatory scheme (EU Dangerous Preparations Directive, DPD), has resulted in an increased number of classifications in the highest eye hazard category. Herein, a semi-quantitative categorisation of severity of eye effects, following accidental human exposures to detergents, was compared to the classification category of the products. Three schemes were evaluated: EU DPD; EU CLP (based on all available data and information, including weight of evidence); and EU CLP (based entirely on the calculation method). As reported by four EU Poison Centres, the vast majority of exposures had caused minor or no symptoms. Classification was a poor predictor of effects in man subjected to accidental exposure. Note however that this is also because effects are not only driven by the intrinsic hazard (as reflected in the classification), but also by the exposure conditions and mitigation (i.e. rinsing). EU CLP classification using all available data and information was more predictive of medically relevant symptoms than the EU CLP calculation method. The latter led to a poorer differentiation between irritating products versus products potentially causing serious eye damage.

The Danish test battery for auditory processing disorder evaluated with patient and control data.

OBJECTIVE: This study evaluates the Danish test battery for auditory processing disorder (APD). The battery consists of four behavioural tests, two speech and two non-speech stimuli tests. The evaluation includes determination of: (1) new cut-off values (pass-fail criteria), (2) the sensitivity and the specificity of the entire test battery and (3) the failure rate of different test combinations. DESIGN: For each test in the battery, cut-off values were determined using the weighted Youden index. Applying the newly derived cut-off values, the distribution of failing specific test combinations was determined. STUDY SAMPLE: A group of 112 children diagnosed with APD (57 boys, 55 girls, aged 6-16 years) and a control group containing 158 children without auditory problems (75 boys, 83 girls, aged 6-16 years). RESULTS: Cut-off values for different weights of the sensitivity and the specificity have been determined. Using the criterion that at least two tests have to be failed for APD to be suspected, the sensitivity and the specificity of the entire test battery were 95.3% and 91.6%, respectively. Some test combinations were found to have higher failure rates than others. CONCLUSIONS: Due to the high sensitivity and specificity the test battery has good predictive value in APD assessment.