Boronotyrosine, a Borylated Amino Acid Mimetic with Enhanced Solubility, Tumor Boron Delivery, and Retention for the Re-emerging Boron Neutron Capture Therapy Field.

Boron neutron capture therapy (BNCT) is a re-emerging binary cellular level cancer intervention that occurs through the interaction of a cancer-specific 10boron (10B) drug and neutrons. We created a new 10B drug, 3-borono-l-tyrosine (BTS), that improves on the characteristics of the main historical BNCT drug 4-borono-l-phenylalanine (BPA). BTS has up to 4 times greater uptake in vitro than BPA and increased cellular retention. Like BPA, BTS uptake is mediated by the l-type amino acid transporter-1 (LAT1) but is less sensitive to natural amino acid competition. BTS can be formulated and bolus dosed at much higher levels than BPA, resulting in 2-3 times greater boron delivery in vivo. Fast blood clearance and greater tumor boron delivery result in superior tumor-to-blood ratios. BTS boron delivery appears to correlate with LAT1 expression. BTS is a promising boron delivery drug that has the potential to improve modern BNCT interventions.

Lineage Plasticity in SCLC Generates Non-Neuroendocrine Cells Primed for Vasculogenic Mimicry.

INTRODUCTION: Vasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In genetically engineered mouse models (GEMMs) of SCLC, NOTCH, and MYC co-operate to drive a neuroendocrine (NE) to non-NE phenotypic switch, and co-operation between NE and non-NE cells is required for metastasis. Here, we define the phenotype of VM-competent cells and molecular mechanisms underpinning SCLC VM using circulating tumor cell-derived explant (CDX) models and GEMMs. METHODS: We analyzed perfusion within VM vessels and their association with NE and non-NE phenotypes using multiplex immunohistochemistry in CDX, GEMMs, and patient biopsies. We evaluated their three-dimensional structure and defined collagen-integrin interactions. RESULTS: We found that VM vessels are present in 23/25 CDX models, 2 GEMMs, and in 20 patient biopsies of SCLC. Perfused VM vessels support tumor growth and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures. On Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin ß1-dependent process. CONCLUSIONS: We identified VM as an exemplar of functional heterogeneity and plasticity in SCLC and these findings take considerable steps toward understanding the molecular events that enable VM. These results support therapeutic co-targeting of both NE and non-NE cells to curtail SCLC progression and to improve the outcomes of patients with SCLC in the future.

A simple and cost-effective method for studying anoxia tolerance in plants.

Premise: We developed a novel, cost-effective protocol that facilitates testing anoxia tolerance in plants without access to specialized equipment. Methods and Results: Arabidopsis thaliana and barley (Hordeum vulgare) seedlings were treated in airtight 2-L Kilner jars. An anoxic atmosphere was generated using Oxoid AnaeroGen 2.5-L sachets placed on in-house, custom-built wire stands. The performed experiments confirmed a higher sensitivity to low oxygen stress previously observed in anac017 A. thaliana mutants and the positive effect of exogenous sucrose on anoxia tolerance reported by previous studies in A. thaliana. Barley seedlings displayed typical responses to anoxia treatment, including shoot growth cessation and the induction of marker genes for anaerobic metabolism and ethylene biosynthesis in root tissue. Conclusions: The results validate the novel method as an inexpensive, simple alternative for testing anoxia tolerance in plants, where access to an anaerobic workstation is not possible. The novel protocol requires minimum investment and is easily adaptable.

Poor Performer: A Distinct Entity in Cochlear Implant Users?

INTRODUCTION: Several factors are known to influence speech perception in cochlear implant (CI) users. To date, the underlying mechanisms have not yet been fully clarified. Although many CI users achieve a high level of speech perception, a small percentage of patients does not or only slightly benefit from the CI (poor performer, PP). In a previous study, PP showed significantly poorer results on nonauditory-based cognitive and linguistic tests than CI users with a very high level of speech understanding (star performer, SP). We now investigate if PP also differs from the CI user with an average performance (average performer, AP) in cognitive and linguistic performance. METHODS: Seventeen adult postlingually deafened CI users with speech perception scores in quiet of 55 (9.32) % (AP) on the German Freiburg monosyllabic speech test at 65 dB underwent neurocognitive (attention, working memory, short- and long-term memory, verbal fluency, inhibition) and linguistic testing (word retrieval, lexical decision, phonological input lexicon). The results were compared to the performance of 15 PP (speech perception score of 15 [11.80] %) and 19 SP (speech perception score of 80 [4.85] %). For statistical analysis, U-Test and discrimination analysis have been done. RESULTS: Significant differences between PP and AP were observed on linguistic tests, in Rapid Automatized Naming (RAN: p = 0.0026), lexical decision (LexDec: p = 0.026), phonological input lexicon (LEMO: p = 0.0085), and understanding of incomplete words (TRT: p = 0.0024). AP also had significantly better neurocognitive results than PP in the domains of attention (M3: p = 0.009) and working memory (OSPAN: p = 0.041; RST: p = 0.015) but not in delayed recall (delayed recall: p = 0.22), verbal fluency (verbal fluency: p = 0.084), and inhibition (Flanker: p = 0.35). In contrast, no differences were found hereby between AP and SP. Based on the TRT and the RAN, AP and PP could be separated in 100%. DISCUSSION: The results indicate that PP constitute a distinct entity of CI users that differs even in nonauditory abilities from CI users with an average speech perception, especially with regard to rapid word retrieval either due to reduced phonological abilities or limited storage. Further studies should investigate if improved word retrieval by increased phonological and semantic training results in better speech perception in these CI users.

A prospective audit on the use of prophylactic antiemetics and rates of CINV in patients receiving carboplatin AUC≥4 or combination anthracycline-cyclophosphamide.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are two of the most frequently experienced and distressing side effects of cancer treatment. Recent updates by ESMO/MASCC and ASCO on guidelines for prevention of CINV have recommended the addition of a neurokinin-1 receptor antagonist to antiemetic regimens for patients receiving carboplatin-based chemotherapy area under the curve (AUC) ≥4 mg/mL per minute, and an addition of olanzapine for those receiving combination anthracycline/cyclophosphamide chemotherapy. AIMS: To assess current use of prophylactic antiemetics and rates of CINV in patients under the care of MidCentral Regional Cancer Treatment Service (MRCTS) receiving carboplatin AUC≥4 or combination anthracycline/cyclophosphamide. METHODS: Data was prospectively collected on patients under the care of MRCTS receiving carboplatin AUC≥4 or combination anthracycline/cyclophosphamide chemotherapy, including breast cancer patients receiving 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Questionnaires were given to eligible patients to be completed daily from day two to day six of first cycle of chemotherapy only. Data on each patient's gender, age, types of chemotherapies, types of malignancies, presence of nausea or vomiting, number of dry retching or vomiting episodes and anti-emetics were recorded. RESULTS: From 15 September 2018 to 10 August 2019, a total of 44 patients receiving carboplatin-based chemotherapy AUC≥4 and 30 patients receiving combination anthracycline/cyclophosphamide were included. Twenty-two patients (50%) had either emesis or significant nausea in the overall and delayed phase when treated with carboplatin AUC≥4, and only three (7%) in the acute phase. Fourteen patients (56%) had either emesis or significant nausea in the overall phase when treated with FEC chemotherapy, mostly in the acute phase (13 patients) rather than in the delayed phase (9 patients). CONCLUSION: The rates of CINV are high with the existing antiemetic regimens used at MidCentral Regional Cancer Treatment Service. Therefore, in accordance with international guidelines, we will add a neurokinin-1 antagonist to the antiemetic regimens for patients receiving carboplatin-based chemotherapy AUC≥4, and olanzapine for those receiving combination anthracycline/cyclophosphamide chemotherapy, in an attempt to improve the rates of CINV in these groups. Repeating this audit post-implementation of above recommendations will be important to assess for any improvement.

Nonauditory Functions in Low-performing Adult Cochlear Implant Users.

INTRODUCTION: Despite substantial benefits of cochlear implantation (CI) there is a high variability in speech recognition, the reasons for which are not fully understood. Especially the group of low-performing CI users is under-researched. Because of limited perceptual quality, top-down mechanisms play an important role in decoding the speech signal transmitted by the CI. Thereby, differences in cognitive functioning and linguistic skills may explain speech outcome in these CI subjects. MATERIAL AND METHODS: Fifteen post-lingually deaf CI recipients with a maximum speech perception of 30% in the Freiburger monosyllabic test (low performer = LP) underwent visually presented neurocognitive and linguistic test batteries assessing attention, memory, inhibition, working memory, lexical access, phonological input as well as automatic naming. Nineteen high performer (HP) with a speech perception of more than 70% were included as a control. Pairwise comparison of the two extreme groups and discrimination analysis were carried out. RESULTS: Significant differences were found between LP and HP in phonological input lexicon and word retrieval (p = 0.0039∗∗). HP were faster in lexical access (p = 0.017∗) and distinguished more reliably between non-existing and existing words (p = 0.0021∗∗). Furthermore, HP outperformed LP in neurocognitive subtests, most prominently in attention (p = 0.003∗∗). LP and HP were primarily discriminated by linguistic performance and to a smaller extent by cognitive functioning (canonic r = 0.68, p = 0.0075). Poor rapid automatic naming of numbers helped to discriminate LP from HP CI users 91.7% of the time. CONCLUSION: Severe phonologically based deficits in fast automatic speech processing contribute significantly to distinguish LP from HP CI users. Cognitive functions might partially help to overcome these difficulties.

Neoadjuvant chemotherapy in non-metastatic breast cancer: a study on practice trends in a regional cancer treatment service.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is increasingly used for managing locally advanced and high risk non-metastatic breast cancer. AIMS: To describe trends in NACT use, assess compliance to best practice recommendations and determine treatment response rates in a regional cancer treatment service. METHODS: In this retrospective cross- sectional study, electronic records of patients who underwent NACT in centres covered by the MidCentral Regional Cancer Treatment Service in 2013 and 2017 were reviewed. Data pertaining to patient demographics, disease status, compliance to best practice recommendations and treatment outcomes were extracted and analysed. RESULTS: Of a total of 502 referrals for non-metastatic breast cancer, 34 underwent NACT with the estimated NACT rate rising from 3.85% (2013) to 9.92% (2017). Compliance to practice recommendations improved in all domains (pre-treatment tumour and axillary evaluation, marker placement, multidisciplinary discussion). Overall, NACT was well tolerated with only three patients experiencing treatment limiting toxicity. Response rates mirror published data (complete response: 29.4%, partial: 61.8%) with higher responses registered in HER2 positive and triple negative subtypes. Discordance between radiological and pathological response was 28%, with imaging overestimating response in five out of seven cases. Of the 11 (32%) patients who initially underwent breast conserving surgery, six required a second surgery. CONCLUSION: NACT is increasingly used in the Regional Cancer Treatment Service, with improving compliance to practice recommendations. These results are reassuring and can be used to help patients develop a realistic expectation towards NACT.

Impact of Lexical Parameters and Audibility on the Recognition of the Freiburg Monosyllabic Speech Test.

OBJECTIVE: Correct word recognition is generally determined by audibility, but lexical parameters also play a role. The focus of this study was to examine both the impact of audibility and lexical parameters on speech recognition of test words of the clinical German Freiburg monosyllabic speech test, and subsequently on the perceptual imbalance of test lists observed in the literature. DESIGN: For 160 participants with normal hearing that were divided into three groups with different simulated hearing thresholds, monaural speech recognition for the Freiburg monosyllabic speech test was obtained via headphones in quiet at different presentation levels. A software manipulated the original speech material to simulate two different hearing thresholds. All monosyllables were classified according to their frequency of occurrence in contemporary language and the number of lexical neighbors using the Cross-Linguistic Easy-Access Resource for Phonological and Orthographic Neighborhood Density database. Generalized linear mixed-effects regression models were used to evaluate the influences of audibility in terms of the Speech Intelligibility Index and lexical properties of the monosyllables in terms of word frequency (WF) and neighborhood density (ND) on the observed speech recognition per word and per test list, respectively. RESULTS: Audibility and interactions of audibility with WF and ND correctly predicted identification of the individual monosyllables. Test list recognition was predicted by test list choice, audibility, and ND, as well as by interactions of WF and test list, audibility and ND, ND and test list, and audibility per test list. CONCLUSIONS: Observed differences in speech recognition of the Freiburg monosyllabic speech test, which are well reported in the literature, depend not only on audibility but also on WF, neighborhood density, and test list choice and their interactions. The authors conclude that future creations of speech test material should take these lexical parameters into account.

The impact of liver fluke infection on steers in Ireland: A meta-analytic approach.

Post-mortem liver inspection results together with production parameters are often used to estimate the impact of liver fluke infection on farm animal populations. However, post mortem liver inspection is an imperfect method of determining the liver fluke infection status of cattle. This work estimates the difference in mean lifetime weight gain at 819 days (ΔLWG819) between steers assigned liver fluke negative (LFN) and liver fluke positive (LFP) status at post-mortem meat inspection, quantifies the potential impact of imperfect sensitivity and specificity on these results and estimates the economic impact of these differences. The study population is 32,007 steers that never moved from their birth herd in the Republic of Ireland and were slaughtered in one of two Irish meat processors in 2014. Individual animal-level data are used to generate 46 county - processor level estimates of ΔLWG819. Standard errors and confidence intervals for these estimates are derived using bootstrapping. A meta-analytic approach is then used to obtain 3 overall estimates of the effect of liver fluke status on the ΔLWG819 in all the county - processor combinations, assuming post - mortem liver inspection Se = Sp = 1, 0.99 and 0.95. A random effects model is used and 95% prediction intervals (95% PI) are calculated. Assuming Se = Sp = 1 for post - mortem liver inspection, the random effects summary estimate of ΔLWG819 (ΔLWG819(RE)) is 36 kg (95% PI: -1, 73). There is a minor change in ΔLWG819(RE) (38 kg, 95% PI: -1, 77) when Se = Sp = 0.99 is assumed but this increases to 46 kg (95% PI: -2, 94) assuming Se = Sp = 0.95. The corresponding cost in euros of these differences between the LFN and LFP steers, assuming a price per kg of €3.90, are €77.01 (95% PI: -2.57, 156.37), €80.65 (95% PI: -3.43, 164.74) and €98.67 (95% PI: -5.15, 202.27) respectively. Our results demonstrate an association between liver fluke infection and reduced weight gain. We show that the effect of liver fluke infection on weight gain in cattle is underestimated due to misclassification resulting from imperfection in post mortem meat inspection. These findings will aid researchers, farmers and veterinary practitioners to make informed decisions on the control of liver fluke on farms.

Changes in neuromuscular structure and functions of human colon during ageing are region-dependent.

OBJECTIVE: To determine if human colonic neuromuscular functions decline with increasing age. DESIGN: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35-91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35-60 years) groups. RESULTS: With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon. CONCLUSION: In ascending not descending colon, ageing impairs cholinergic function.

Genetic correlations between endo-parasite phenotypes and economically important traits in dairy and beef cattle.

Parasitic diseases have economic consequences in cattle production systems. Although breeding for parasite resistance can complement current control practices to reduce the prevalence globally, there is little knowledge of the implications of such a strategy on other performance traits. Records on individual animal antibody responses to Fasciola hepatica, Ostertagia ostertagi, and Neospora caninum were available from cows in 68 dairy herds (study herds); national abattoir data on F. hepatica-damaged livers were also available from dairy and beef cattle. After data edits, 9,271 dairy cows remained in the study herd dataset, whereas 19,542 dairy cows and 68,048 young dairy and beef animals had a record for the presence or absence of F. hepatica-damaged liver in the national dataset. Milk, reproductive, and carcass phenotypes were also available for a proportion of these animals as well as their contemporaries. Linear mixed models were used to estimate variance components of antibody responses to the three parasites; covariance components were estimated between the parasite phenotypes and economically important traits. Heritability of antibody responses to the different parasites, when treated as a continuous trait, ranged from 0.07 (O. ostertagi) to 0.13 (F. hepatica), whereas the coefficient of genetic variation ranged from 4% (O. ostertagi) to 20% (F. hepatica). The antibody response to N. caninum was genetically correlated with the antibody response to both F. hepatica (-0.29) and O. ostertagi (-0.67); a moderately positive genetic correlation existed between the antibody response to F. hepatica and O. ostertagi (0.66). Genetic correlations between the parasite phenotypes and the milk production traits were all close to zero (-0.14 to 0.10), as were the genetic correlations between F. hepatica-damaged livers and the carcass traits of carcass weight, conformation, and fat score evaluated in cows and young animals (0.00 to 0.16). The genetic correlation between F. hepatica-damaged livers in cows and milk somatic cell score was 0.32 (SE = 0.20). Antibody responses to F. hepatica and O. ostertagi had favorable genetic correlations with fertility traits, but conversely, antibody response to N. caninum and F. hepatica-damaged livers were unfavorably genetically correlated with fertility. This study provides the necessary information to undertake national multitrait genetic evaluations for parasite phenotypes.

A protocol to identify and minimise selection and information bias in abattoir surveys estimating prevalence, using Fasciola hepatica as an example.

Abattoir surveys and findings from post-mortem meat inspection are commonly used to estimate infection or disease prevalence in farm animal populations. However, the function of an abattoir is to slaughter animals for human consumption, and the collection of information on animal health for research purposes is a secondary objective. This can result in methodological shortcomings leading to biased prevalence estimates. Selection bias can occur when the study population as obtained from the abattoir is not an accurate representation of the target population. Virtually all of the tests used in abattoir surveys to detect infections or diseases that impact animal health are imperfect, leading to errors in identifying the outcome of interest and consequently, information bias. Examination of abattoir surveys estimating prevalence in the literature reveals shortcomings in the methods used in these studies. While the STROBE-Vet statement provides clear guidance on the reporting of observational research, we have not found any guidelines in the literature advising researchers on how to conduct abattoir surveys. This paper presents a protocol in two flowcharts to help researchers (regardless of their background in epidemiology) to first identify, and, where possible, minimise biases in abattoir surveys estimating prevalence. Flowchart 1 examines the identification of the target population and the appropriate study population while Flowchart 2 guides the researcher in identifying, and, where possible, correcting potential sources of outcome misclassification. Examples of simple sensitivity analyses are also presented which approximate the likely uncertainty in prevalence estimates due to systematic errors. Finally, the researcher is directed to outline any limitations of the study in the discussion section of the paper. This protocol makes it easier to conduct an abattoir survey using sound methods, identifying and, where possible, minimizing biases.

The Contribution of Cognitive Factors to Individual Differences in Understanding Noise-Vocoded Speech in Young and Older Adults.

Noise-vocoded speech is commonly used to simulate the sensation after cochlear implantation as it consists of spectrally degraded speech. High individual variability exists in learning to understand both noise-vocoded speech and speech perceived through a cochlear implant (CI). This variability is partly ascribed to differing cognitive abilities like working memory, verbal skills or attention. Although clinically highly relevant, up to now, no consensus has been achieved about which cognitive factors exactly predict the intelligibility of speech in noise-vocoded situations in healthy subjects or in patients after cochlear implantation. We aimed to establish a test battery that can be used to predict speech understanding in patients prior to receiving a CI. Young and old healthy listeners completed a noise-vocoded speech test in addition to cognitive tests tapping on verbal memory, working memory, lexicon and retrieval skills as well as cognitive flexibility and attention. Partial-least-squares analysis revealed that six variables were important to significantly predict vocoded-speech performance. These were the ability to perceive visually degraded speech tested by the Text Reception Threshold, vocabulary size assessed with the Multiple Choice Word Test, working memory gauged with the Operation Span Test, verbal learning and recall of the Verbal Learning and Retention Test and task switching abilities tested by the Comprehensive Trail-Making Test. Thus, these cognitive abilities explain individual differences in noise-vocoded speech understanding and should be considered when aiming to predict hearing-aid outcome.

Processing Mechanisms in Hearing-Impaired Listeners: Evidence from Reaction Times and Sentence Interpretation.

OBJECTIVE: The authors aimed to determine whether hearing impairment affects sentence comprehension beyond phoneme or word recognition (i.e., on the sentence level), and to distinguish grammatically induced processing difficulties in structurally complex sentences from perceptual difficulties associated with listening to degraded speech. Effects of hearing impairment or speech in noise were expected to reflect hearer-specific speech recognition difficulties. Any additional processing time caused by the sustained perceptual challenges across the sentence may either be independent of or interact with top-down processing mechanisms associated with grammatical sentence structure. DESIGN: Forty-nine participants listened to canonical subject-initial or noncanonical object-initial sentences that were presented either in quiet or in noise. Twenty-four participants had mild-to-moderate hearing impairment and received hearing-loss-specific amplification. Twenty-five participants were age-matched peers with normal hearing status. Reaction times were measured on-line at syntactically critical processing points as well as two control points to capture differences in processing mechanisms. An off-line comprehension task served as an additional indicator of sentence (mis)interpretation, and enforced syntactic processing. RESULTS: The authors found general effects of hearing impairment and speech in noise that negatively affected perceptual processing, and an effect of word order, where complex grammar locally caused processing difficulties for the noncanonical sentence structure. Listeners with hearing impairment were hardly affected by noise at the beginning of the sentence, but were affected markedly toward the end of the sentence, indicating a sustained perceptual effect of speech recognition. Comprehension of sentences with noncanonical word order was negatively affected by degraded signals even after sentence presentation. CONCLUSION: Hearing impairment adds perceptual processing load during sentence processing, but affects grammatical processing beyond the word level to the same degree as in normal hearing, with minor differences in processing mechanisms. The data contribute to our understanding of individual differences in speech perception and language understanding. The authors interpret their results within the ease of language understanding model.

Age-Related Differences in Lexical Access Relate to Speech Recognition in Noise.

Vocabulary size has been suggested as a useful measure of "verbal abilities" that correlates with speech recognition scores. Knowing more words is linked to better speech recognition. How vocabulary knowledge translates to general speech recognition mechanisms, how these mechanisms relate to offline speech recognition scores, and how they may be modulated by acoustical distortion or age, is less clear. Age-related differences in linguistic measures may predict age-related differences in speech recognition in noise performance. We hypothesized that speech recognition performance can be predicted by the efficiency of lexical access, which refers to the speed with which a given word can be searched and accessed relative to the size of the mental lexicon. We tested speech recognition in a clinical German sentence-in-noise test at two signal-to-noise ratios (SNRs), in 22 younger (18-35 years) and 22 older (60-78 years) listeners with normal hearing. We also assessed receptive vocabulary, lexical access time, verbal working memory, and hearing thresholds as measures of individual differences. Age group, SNR level, vocabulary size, and lexical access time were significant predictors of individual speech recognition scores, but working memory and hearing threshold were not. Interestingly, longer accessing times were correlated with better speech recognition scores. Hierarchical regression models for each subset of age group and SNR showed very similar patterns: the combination of vocabulary size and lexical access time contributed most to speech recognition performance; only for the younger group at the better SNR (yielding about 85% correct speech recognition) did vocabulary size alone predict performance. Our data suggest that successful speech recognition in noise is mainly modulated by the efficiency of lexical access. This suggests that older adults' poorer performance in the speech recognition task may have arisen from reduced efficiency in lexical access; with an average vocabulary size similar to that of younger adults, they were still slower in lexical access.

ERP responses to processing prosodic phrasing of sentences in amplitude modulated noise.

Intonation phrase boundaries (IPBs) were hypothesized to be especially difficult to process in the presence of an amplitude modulated noise masker because of a potential rhythmic competition. In an event-related potential study, IPBs were presented in silence, stationary, and amplitude modulated noise. We elicited centro-parietal Closure Positive Shifts (CPS) in 23 young adults with normal hearing at IPBs in all acoustic conditions, albeit with some differences. CPS peak amplitudes were highest in stationary noise, followed by modulated noise, and lowest in silence. Both noise types elicited CPS delays, slightly more so in stationary compared to amplitude modulated noise. These data suggest that amplitude modulation is not tantamount to a rhythmic competitor for prosodic phrasing but rather supports an assumed speech perception benefit due to local release from masking. The duration of CPS time windows was, however, not only longer in noise compared to silence, but also longer for amplitude modulated compared to stationary noise. This is interpreted as support for additional processing load associated with amplitude modulation for the CPS component. Taken together, processing prosodic phrasing of sentences in amplitude modulated noise seems to involve the same issues that have been observed for the perception and processing of segmental information that are related to lexical items presented in noise: a benefit from local release from masking, even for prosodic cues, and a detrimental additional processing load that is associated with either stream segregation or signal reconstruction.

Development of a German reading span test with dual task design for application in cognitive hearing research.

OBJECTIVE: To report the development of a standardized German version of a reading span test (RST) with a dual task design. Special attention was paid to psycholinguistic control of the test items and time-sensitive scoring. We aim to establish our RST version to use for determining an individual's working memory in the framework of hearing research in German contexts. DESIGN: RST stimuli were controlled and pretested for psycholinguistic factors. The RST task was to read sentences, quickly determine their plausibility, and later recall certain words to determine a listener's individual reading span. RST results were correlated with outcomes of additional sentence-in-noise tests measured in an aided and an unaided listening condition, each at two reception thresholds. STUDY SAMPLE: Item plausibility was pre-determined by 28 native German participants. An additional 62 listeners (45-86 years, M = 69.8) with mild-to-moderate hearing loss were tested for speech intelligibility and reading span in a multicenter study. RESULTS: The reading span test significantly correlated with speech intelligibility at both speech reception thresholds in the aided listening condition. CONCLUSION: Our German RST is standardized with respect to psycholinguistic construction principles of the stimuli, and is a cognitive correlate of intelligibility in a German matrix speech-in-noise test.

Development and evaluation of a linguistically and audiologically controlled sentence intelligibility test.

To allow for a systematic variation of linguistic complexity of sentences while acoustically controlling for intelligibility of sentence fragments, a German corpus, Oldenburg linguistically and audiologically controlled sentences (OLACS), was designed, implemented, and evaluated. Sentences were controlled for plausibility with a questionnaire survey. Verification of the speech material was performed in three listening conditions (quiet, stationary, and fluctuating noise) by collecting speech reception thresholds (SRTs) and response latencies as well as individual cognitive measures for 20 young listeners with normal hearing. Consistent differences in response latencies across sentence types verified the effect of linguistic complexity on processing speed. The addition of noise decreased response latencies, giving evidence for different response strategies for measurements in noise. Linguistic complexity had a significant effect on SRT. In fluctuating noise, this effect was more pronounced, indicating that fluctuating noise correlates with stronger cognitive contributions. SRTs in quiet correlated with hearing thresholds, whereas cognitive measures explained up to 40% of the variance in SRTs in noise. In conclusion, OLACS appears to be a suitable tool for assessing the interaction between aspects of speech understanding (including cognitive processing) and speech intelligibility in German.

The effects of syntactic complexity on processing sentences in noise.

This paper discusses the influence of stationary (non-fluctuating) noise on processing and understanding of sentences, which vary in their syntactic complexity (with the factors canonicity, embedding, ambiguity). It presents data from two RT-studies with 44 participants testing processing of German sentences in silence and in noise. Results show a stronger impact of noise on the processing of structurally difficult than on syntactically simpler parts of the sentence. This may be explained by a combination of decreased acoustical information and an increased strain on cognitive resources, such as working memory or attention, which is caused by noise. The noise effect for embedded sentences is less than for non-embedded sentences, which may be explained by a benefit from prosodic information.