Auditory Biases in Cognitive Assessment: Insights from a Hearing-Loss Simulation for the Screening of Dementia due to Alzheimer's Disease

Cognitive-screening tests are used to detect pathological changes in mental abilities. Many use orally presented instructions and test items. Hence, hearing loss (HL), whose prevalence increases with age, may bias cognitive-test performance in the target population for the screening of dementia due to Alzheimer's disease. To study the effect of the auditory test format, an impairment-simulation approach was used in normal-hearing listeners to compare performance on the Hopkins Verbal Learning Test, a memory task employed in dementia screening and research, when test items were unprocessed and processed to simulate age-related HL. Immediate verbal recall declined with simulated HL, suggesting that auditory factors are confounding variables in cognitive assessment and result in the underestimation of cognitive functioning

On the (un)importance of working memory in speech-in-noise processing for listeners with normal hearing thresholds

With the advent of cognitive hearing science, increased attention has been given to individual differences in cognitive functioning and their explanatory power in accounting for inter-listener variability in the processing of speech in noise (SiN). The psychological construct that has received much interest in recent years is working memory. Empirical evidence indeed confirms the association between WM capacity (WMC) and SiN identification in older hearing-impaired listeners. However, some theoretical models propose that variations in WMC are an important predictor for variations in speech processing abilities in adverse perceptual conditions for all listeners, and this notion has become widely accepted within the field. To assess whether WMC also plays a role when listeners without hearing loss process speech in adverse listening conditions, we surveyed published and unpublished studies in which the Reading-Span test (a widely used measure of WMC) was administered in conjunction with a measure of SiN identification, using sentence material routinely used in audiological and hearing research. A meta-analysis revealed that, for young listeners with audiometrically normal hearing, individual variations in WMC are estimated to account for, on average, less than 2% of the variance in SiN identification scores. This result cautions against the (intuitively appealing) assumption that individual variations in WMC are predictive of SiN identification independently of the age and hearing status of the listener

Monogamy? In this economy? Stigma and resilience in consensual non-monogamous relationships.

Monogamous marriage, sometimes called "the bedrock of society," still carries an apparent "halo" of moral superiority as a relationship structure. In contrast, consensual non-monogamous (CNM) configurations are stigmatized. Research indicates a connection between stigma, stress, and negative health outcomes, despite CNM comparing favorably with monogamy. The present study uses interviews to explore minority stress and resilience among individuals in CNM relationships. Participants experienced structural stigma as erasure, and interpersonal stigma as erasure and educational/emotional work. They also describe complex enmeshment between their relationship minority status and other aspects of their sexual and gender identities. Strategic disclosure and concealment were important management tools. Furthermore, managing individual (internalized) stigma was described as unlearning mononormative bias and surrounding oneself with supportive peers/allies. The strongest motivator for perseverance was the steadfast conviction that the advantages of CNM outweighed the challenges

Von Joghurtbechern und Bügeleisen

Was heute noch wie ein Märchen klingt, kann morgen Wirklichkeit sein. Hier ist ein Märchen von übermorgen: Es gibt keine Nationalstaaten mehr. Es gibt nur noch die Menschheit und ihre Kolonien im Weltraum. Man siedelt auf fernen Sternen. Der Meeresboden ist als Wohnraum erschlossen. Mit heute noch unvorstellbaren Geschwindigkeiten durcheilen Raumschiffe unser Milchstraßensystem. Eines dieser Raumschiffe ist die Orion, winziger Teil eines gigantischen Sicherheitssystems, das die Erde und ihre ..

The return of the nucleus : epigenetic regulation of autophagy

Autophagy is an evolutionary conserved catabolic process activated in response to a variety of cellular stresses, for example nutrient deprivation or chemotherapy. During autophagy, cells engulf parts of their cytplasm in a double-membrane vesicle, where misfolded proteins or damaged organelles are degraded. A plethora of human diseases has been linked to autophagy, including cancer and neurodegenerative disorders. Previously, autophagy has been considered a purely cytosolic event as even enucleated cells were able to display autophagic vesicles. Here we have shown for the first time that epigenetic changes are a major component of the autophagic process and involve global changes in the level of several histone modifications and local alterations in DNA methylation. Autophagy-related epigenetic modifications are involved during all stages of autophagy and have the potential to influence the autophagic life and death decision. During the early steps of autophagy, histone modifications are involved in the transcriptional up-regulation of autophagy-related genes. However, global down-regulation of histone H4 lysine 16 acetylation (H4K16ac) occurring at later stages protects cells from an overstimulation of autophagy, which can lead to a lethal level of autophagy. Furthermore, we have uncovered a critical role for the histone H3 lysine 36 (H3K36) demethylase Rph1/KDM4A in suppressing autophagy under baseline conditions. As we and others have shown that histone modifications are part of the autophagic process, we wondered how long the autophagy induced epigenetic modifications remain. By definition, an epigenetic regulation of autophagy should involve heritable changes that alter the cellular gene expression for a prolonged period of time. We indeed found that cancer cells in which autophagy has been induced show a lower expression of autophagy-related proteins. Upon renewed stimulation these pre-treated cells show an alteration in autophagic flux compared to untreated cells. This ‘autophagic memory’ involves an early up-regulation of DNA methyl transferase 3A (DNMT3A) which induces a stable down-regulation of autophagy-related genes by DNA methylation. In the future, development of new drugs for a variety of diseases involving deregulated autophagy may benefit from a widened knowledge about the epigenetic autophagy-regulatory network

Functional analysis of the helper-component proteinase (HC-Pro) of zucchini yellow mosaic virus

In dieser Arbeit wurde der Einfluss einer Punktmutation der ZYMV HC-ProFINK auf die RNA Silencing Suppressor-Aktivität und die miRNA-Akkumulation in N. benthamiana-Pflanzen untersucht. Dabei konnte eine RNA Silencing Suppressor-Aktivität der HC-ProFINK nachgewiesen werden. Sowohl die HC-ProFRNK als auch die HC-ProFINK zeigten in vivo keinen Einfluss auf die Änderung der miRNA-Mengen in N. benthamiana-Pflanzen. Untersuchungen der in vitro sRNA-Bindung mit rekombinanten HC-Pro-Proteinen aus Pflanzen führte zu einer Bindung von 21 bp siRNAs und miRNAs durch die HC-ProFRNK, wobei kein Einfluss zwischen der Anzahl und Lage der Basenfehlpaarungen der miRNAs und der Bindungskapazität identifiziert werden konnte. Diese Bindung ist vermutlich abhängig von der Sequenz der miRNAs. Die Mutation von HC-ProFRNK zu HC-ProFINK bewirkte dagegen den Verlust der Bindung von kleinen RNA-Molekülen. Die HC-Pro Proteine konnten rekombinant mit einem N-terminalen Fusionsprotein exprimiert und gereinigt werden. Die funktionelle Analyse des MBP-HA-HC-ProFRNK-Proteins wies eine längenspezifische Bindung von 21 bp siRNAs auf. Die Analyse der in vitro Bindung von unterschiedlichen miRNAs aus A. thaliana und Mensch durch das rekombinante HC-ProFRNK-Protein aus Bakterien zeigte keinen Zusammenhang zwischen der Anzahl und Lage der Basenfehlpaarungen in den miRNAs und der Bindekapazität. Die Mutation im MBP-HA-HC-ProFINK-Protein führte zum Verlust der sRNA-Bindung. Diese Ergebnisse bestätigten die Beobachtungen der Gelshift-Analysen mit den rekombinanten HC-Pro-Proteinen aus Pflanzen. Durch die Fraktionierung eines A. thaliana-Proteinextrakts konnte ein nicht näher beschriebenes Protein unbekannter Funktion, welches eine Cupin-Domäne (QP) besitzt, identifiziert werden. Dies hat einen Einfluss auf die in vitro Bindung von sRNA-Molekülen durch die HC-Pro. Eine funktionelle Analyse des Trx-QP-His-Proteins mit Hilfe von Gelshift-Analysen nach der Expression in Bakterien und Reinigung zeigte einen konzentrationsabhängigen verstärkenden Effekt der siRNA Bindung durch das rekombinante MBP-HA-HC-Pro-Protein. Die Zugabe eines fraktionierten N. benthamiana-Proteinextrakts zur in vitro Bindungsreaktion führte ebenfalls zu einer verstärkten siRNA-Bindung durch die HC-Pro; Proteinextrakte von N. tabacum und der ZYMV Wirtspflanze Zucchini zeigten jedoch keinen Effekt. Die ZYMV HC-Pro besitzt eine von der TEV HC-Pro abweichende proteolytisch aktive Domäne. Durch eine rekombinante Expression des MBP-HA-HC-Pro-GFP-Fusionsproteins in Bakterien und Deletionsanalysen konnten zwei kritische Aminosäuren im C-terminalen Bereich der HC-Pro identifiziert werden. Eine Deletion der AS Asn-353 oder Glu-356 führte zum vollständigen Verlust der autoproteolytischen Aktivität des Proteins. Ein Austausch der AS Gly-456 innerhalb der Schnittstelle sowie eine N-terminale Deletion von 93 AS der HC-Pro hatten dagegen keinen Einfluss auf die autoproteolytische Aktivität. Mit Hilfe einer N-terminalen Sequenzierung des C-terminalen Spaltproduktes des MBP HC Pro mut C7-GFP, welches vermutlich in Folge einer Spaltung durch bakterielle Proteasen entsteht, sollten durch Deletionsmutanten die kritischen Aminosäuren für die Spaltung untersucht werden. Eine Deletion der konservierten AS Thr-146 von ZYMV HC-Pro sowie der flankierenden AS Val-145 bzw. Gln-147 hatte jedoch keinen Einfluss auf die Spaltung der HC-Pro. Dies deutet darauf hin, dass die Schnittstelle der Protease von deren Erkennungssequenz abweicht. Die in dieser Arbeit erzielten Ergebnisse zeigen, dass die ZYMV HC-Pro neben der sRNA-Bindung einen weiteren Mechanismus besitzt, um die Funktion als RSS auszuüben. Weitere Analysen sind nötig, um die Interaktion mit pflanzlichen Komponenten zu identifizieren und den Einfluss auf den RNA Silencing-Mechanismus aufzuklären.An amino acid change in the highly conserved FRNK-box of the ZYMV HC-Pro, where the arginine at position 180 was replaced by isoleucine, caused attenuation of the symptoms after virus infection of the host plants. To further characterize the effect of the point mutation on the RNA silencing suppressor activity, the HC-ProFINK protein was transiently expressed in N. benthamiana 16c plants using the Agrobacterium-mediated infiltration method, whereas the silencing suppressor construct was co-infiltrated with a GFP inverted repeat construct to induce silencing. It was demonstrated that the mutant shows silencing suppressor activity, comparable to the HC-Pro wild type. In vivo studies analyzing the change of miRNA levels in infiltrated N. benthamiana plants, where either the HC-ProFRNK or the HC-ProFINK proteins were transiently expressed showed no significant changes in the miRNA levels compared to the control plants. To gain insight into the binding activities of small RNAs, recombinant HC-Pro proteins from plants were used for in vitro binding studies using artificial siRNA and miRNA duplexes. A strong binding of 21 bp siRNAs could be observed for HC-ProFRNK, although different miRNA heteroduplex structures from plants and human were analyzed for the influence of structure and length on binding capacity. This analysis showed a clear difference in the binding behaviour of the tested miRNAs by HC-Pro, but no correlation between the amount and position of the mismatches and the binding strength. Surprisingly, the mutant HC-ProFINK completely lost the ability to bind small RNA molecules in vitro, indicating the importance of the FRNK-box in RNA binding. To obtain a high amount of purified and functional ZYMV HC-Pro protein, it was expressed as a recombinant protein in E. coli. Therefore, the HC-Pro was expressed together with a maltose binding protein (MBP) at the N-termini to produce high amounts of the protein in a soluble form, and to enable a simple purification. The functional analysis of the MBP-HA-HC-ProFRNK protein by in vitro studies using artificial siRNAs, resulted in a size-specific binding of 21 bp siRNAs. Moreover, the analysis of the in vitro binding of different miRNAs from A. thaliana and human using the recombinant HC-ProFRNK protein from bacteria provides no correlation between the number and position of mismatches of the miRNA heteroduplex and the binding capacity. In contrast, the mutation of the MBP-HA-HC-ProFINK protein apparently resulted in a loss of binding of sRNA molecules. These results confirmed the observations of the gel shift analysis achieved with the recombinant HC-Pro proteins from plants. Analyzing the effect of host proteins affecting the in vitro binding capacity of the HC-Pro should identify this factor and give detailed information about the function and mechanism supporting RNA binding of HC-Pro. A fractionation of an A. thaliana total protein extract and functional analysis of the fractions identified a protein with unknown function, containing a cupin domain (QP), which plays a role in the in vitro binding of sRNA molecules by the HC-Pro. This putative host factor was cloned and recombinant expressed in E. coli to further characterize and prove the effect on small RNA binding. The functional analysis by using gel-shift assays revealed that the Trx-QP-His protein was affecting the siRNA binding by the recombinant MBP-HA-HC-Pro protein in a concentration-dependent manner. Additionally, a fractionated N. benthamiana protein extract showed the same effect on siRNA binding by the HC-Pro. Moreover, protein extracts from N. tabacum and the host plant of ZYMV Zucchini showed no effect. The multifunctional HC-Pro from potyviruses contains an autoproteolytic function to process the polyprotein together with the P1 and NIa-proteinase into mature proteins. HC-Pro catalyzes the autoproteolytic cleavage on its own C-termini at the Gly-Gly dipeptid in the polyprotein at the transition to the P3 protein. The TEV HC-Pro has been identified as a cysteine proteinase with the amino acids Cys-345 and His-418 in the catalytic active domain. In order to identify the proteolytic active domain of ZYMV HC-Pro, recombinant MBP:HA-HC-Pro:GFP fusion proteins from E. coli and different mutants containing either deletions or point mutations at the C-termini of the HC-Pro protein were analyzed. We show that a point mutation at the transition between HC-Pro and GFP, as well point mutations of the conserved catalytic amino acids of TEV HC-Pro in the ZYMV HC-Pro protein had no effect on the processing of the GFP. A catalytic active domain was localized in the stretch of amino acids 350-358. The deletions of Asn-353 or Glu-356 cause a drastic reduction of the proteolytic activity of ZYMV HC-Pro

Transcriptional regulation of mammalian autophagy at a glance.

Macroautophagy, hereafter referred to as autophagy, is a catabolic process that results in the lysosomal degradation of cytoplasmic contents ranging from abnormal proteins to damaged cell organelles. It is activated  under diverse conditions, including nutrient deprivation and hypoxia. During autophagy, members of the core autophagy-related (ATG) family of proteins mediate membrane rearrangements, which lead to the engulfment and degradation of cytoplasmic cargo. Recently, the nuclear regulation of autophagy, especially by transcription factors and histone modifiers, has gained increased attention. These factors are not only involved in rapid responses to autophagic stimuli, but also regulate the long-term outcome of autophagy. Now there are more than 20 transcription factors that have been shown to be linked to the autophagic process. However, their interplay and timing appear enigmatic as several have been individually shown to act as major regulators of autophagy. This Cell Science at a Glance article and the accompanying poster highlights the main cellular regulators of transcription involved in mammalian autophagy and their target genes

Untersuchungen zum kulturellen und molekularbiologischen Nachweis von Mycobacterium avium ssp. paratuberculosis (MAP) aus humanen Darmbioptaten

Mycobacterium avium ssp. paratuberculosis (MAP) ist der Erreger der Paratuberkulose der Wiederkäuer. Bereits seit Anfang des letzten Jahrhunderts wird aufgrund der pathomorphologischen Ähnlichkeiten ein ursächlicher Zusammenhang mit Morbus Crohn (MC), einer chronisch-entzündlichen Darmerkrankung des Menschen, vermutet und seitdem kontrovers diskutiert. Für Milchrinderbestände werden in einzelnen Bundesländern Seroprävalenzdaten für Paratuberkulose von bis zu ca. 80 % angegeben. Abgesehen von einer Erregerübertragung durch direkten Tierkontakt und der weiten Verbreitung des Erregers in der Umwelt, werden Lebensmittel als mögliche Vehikel diskutiert. In zahlreichen Studien wurde MAP-Desoxyribonukleinsäure im Darmgewebe von MC-Patienten und Kontrollen nachgewiesen. Nur in wenigen Untersuchungen wurde parallel die kulturelle Überprüfung der Vermehrungsfähigkeit durchgeführt. Zudem mangelt es den Polymerase-chain-reaction (PCR)-Verfahren an einer diagnostischen Qualitätssicherung mit interner Amplifikationskontrolle (IAK) und die gewählten Marker weisen Kreuzreaktionen mit anderen Mykobakterienspezies auf. In den eigenen Arbeiten wurde daher die kulturelle Anzüchtung unter Einsatz eines zuvor eigens validierten Dekontaminationsverfahrens unter Verwendung von N-Acetyl-L-Cystein-NaOH mit der PCR-Analytik kombiniert. Um die Zuverlässigkeit der Nachweisverfahren zu steigern, wurde eine nested PCR und eine kürzlich entwickelte Triplex Real Time-PCR (SCHÖNENBRÜCHER et al., 2008) inklusive einer internen Amplifikationskontrolle verwendet. So wurden erstmals die drei MAP-spezifischen Marker IS900, ISMav2 und F57 bei humanen Darmbioptaten diagnostisch kombiniert. Für die spätere Subkultivierung und Archivierung der MAP-Stämme wurden in einer vergleichenden Untersuchung preiswerte, einfach zu handhabende und produktive Selektivmedien ermittelt. Es konnten insgesamt 120 Proben von 32 Probanden berücksichtigt werden. Darunter befanden sich Bioptate von 12 MC- und acht Colitis ulcerosa (CU)-Patienten sowie 12 Kontrollprobanden, die nicht an einer chronisch-entzündlichen Darmerkrankung leiden. Darunter erwiesen sich Anreicherungskulturen von vier (33,3 %) MC- und zwei (25,0 %) CU-Patienten sowie von neun (75,0 %) Kontrollprobanden (p = 0,059) als molekularbiologisch MAP-positiv. Die Subkultivierung und Isolierung von MAP gelang aus dem Colon transversum einer Kontrollperson. Bei zwei Colitis ulcerosa-Patienten und einer Kontrollperson konnten vermehrungsfähige Mycobacterium avium ssp. avium-Stämme isoliert werden. Alle Isolate wurden mittels Sequenzanalyse der 16S-ribosomalen RNA (ribonucleic acid) und der 16S-23S „intragenic spacer region” (ITS) bestätigt und für die institutseigene Mykobakterienstammsammlung in Form von Gefrierkulturen und Lyophilisaten archiviert. Nach den Ergebnissen dieser Fall-Kontroll-Studie kann nicht auf ein ausschließliches Vorkommen von MAP bei MC-Patienten geschlossen werden, und die Gewinnung überlebensfähiger MAP gestaltet sich schwierig, möglicherweise aufgrund eines Sphäroblasten-Stadiums. Die PCR-Verfahren weisen zusätzlich auf eine weite Verbreitung von MAP bei Kontrollprobanden hin. Das angewandte Triplex PCR-Verfahren in Kombination mit einer nested PCR und der kulturellen Diagnostik liefert Ergebnisse hoher Aussagekraft über das Vorkommen von MAP in humanen Darmbioptaten. Von den für die MAP-Kultivierung untersuchten Festmedien eignete sich aufgrund der kürzesten Nachweisdauer das Herrold’s Egg Yolk-Schrägmedium (Becton Dickinson®) für einen Direktnachweis am besten. Zur Beurteilung von Einzelkolonien, beispielsweise als Kontaminationskontrolle, ist der Einsatz des Middlebrook 7H10-Agars empfehlenswert (Becton Dickinson®). Um den möglichen kausalen Zusammenhang von MAP und MC zu erhellen, sind weitere Untersuchungen mit einer größeren Probandenzahl und unter Einbeziehung einer genauen Erhebung von anamnestischen, klinischen, genetischen und psychosozialen Daten sowie der MAP-Exposition nötig.The zoonotic potential of Mycobacterium avium ssp. paratuberculosis (MAP), the causative agent of Johne’s disease in human chronic inflammatory bowel disease remains uncertain. The involvement in the pathogenesis of Crohn’s disease (CD) is discussed since the beginning of the last century. The Paratuberculosis data for milk cattle stock show over 80 % prevalence in many countries of the Federal Republic of Germany. Aside from the conceivable transmission of the bacteria to humans by the direct animal contact and the widespread in the environment, food has been considered as possible vector. Previous studies on the occurrence of MAP in gut tissues were based only on one single molecular detection system (e. g. Polymerase-chain-reaction [PCR]). In addition, these PCR-methods lacked of an internal amplification control (IAC) for diagnostic quality assurance and the used markers show cross reactions with other mycobacteria species. Furthermore the examination of the agent’s viability was not considered. For this reasons, the present investigation included the cultivation of MAP, using a previously validated decontamination protocol, and PCR-analysis. A nested PCR system as well as a recently developed real time-PCR method were used to increase the reliability of the PCR results. In total three MAP-specific genes were used. Comparative studies of culture media were done to find appropriate media for subcultures of the mycobacteria isolates In this study the three PCR markers IS900, ISMav2 and F57 were first combined with cultural detection of MAP in human biopsies. Four (33.3 %) of the CD-, two (25.0 %) of the ulcerative colitis (UC) - and nine (75.0 %) of the control patients were positive for MAP with the PCR marker (p = 0.059). MAP could be cultivated out of the colon transversum of one control person. M. avium ssp. avium has been isolated out of the biopsies of two UC-patients as well as of a control person. The cultured strains were verified by amplicon sequencing of the 16S-ribosomal RNA (ribonucleic acid) and the 16S-23S „intragenic spacer region” (ITS). The three markers were sequenced as well. All isolates were preserved by deep freezing with glycerol and by freeze drying (lyophilization). On the basis of the preliminary results it can not be concluded that MAP appeared exclusively in Crohn’s disease patients. In addition, the PCR-systems indicate a frequent occurrence of MAP in control specimens and the recovery of viable MAP has been proven to be difficult. The used triplex real-time PCR system combined with nested PCR and cultural detection of MAP presents reliable results. Because of the shortest time to detection Herrold‘s Egg Yolk Medium (Becton Dickinson®) can be recommended for isolation of MAP out of different samples (e. g. biopsy, feces). The low-priced “Paratuberkulosemedium” (Artelt-ENCLIT®) should be used for sub-cultures. Middlebrook 7H10-agar, prepared on plate, offers potential for the examination of single colonies (e. g. control of pure cultures)

Modulation masking produced by second-order modulators

Recent studies suggest that an auditory nonlinearity converts second-order sinusoidal amplitude modulation (SAM) (i.e., modulation of SAM depth) into a first-order SAM component, which contributes to the perception of second-order SAM. However, conversion may also occur in other ways such as cochlear filtering. The present experiments explored the source of the first-order SAM component by investigating the ability to detect a 5-Hz, first-order SAM probe in the presence of a second-order SAM masker beating at the probe frequency. Detection performance was measured as a function of masker-carrier modulation frequency, phase relationship between the probe and masker modulator, and probe modulation depth. In experiment 1, the carrier was a 5-kHz sinusoid presented either alone or within a notched-noise masker in order to restrict off-frequency listening. In experiment 2, the carrier was a white noise. The data obtained in both carrier conditions are consistent with the existence of a modulation distortion component. However, the phase yielding poorest detection performance varied across experimental conditions between 0° and 180°, confirming that, in addition to nonlinear mechanisms, cochlear filtering and off-frequency listening play a role in second-order SAM perception. The estimated magnitude of the modulation distortion component ranges from 5%-12%

Evaluation of a method for determining binaural sensitivity to temporal fine structure (TFS-AF test) for older listeners with normal and impaired low-frequency hearing

The ability to process binaural temporal fine structure (TFS) information was assessed using the TFS-AF test (where AF stands for adaptive frequency) for 26 listeners aged 60 years or more with normal or elevated low-frequency audiometric thresholds. The test estimates the highest frequency at which a fixed interaural phase difference (IPD) of ϕ (varied here between 30° and 180°) can be discriminated from an IPD of 0°, with higher thresholds indicating better performance. A sensation level of 30 dB was used. All listeners were able to perform the task reliably, giving thresholds well above the lowest allowed frequency of 30 Hz. The duration of a run averaged 5 min. Repeated testing of the normal-hearing listeners showed no significant practice effects. Thresholds varied markedly across listeners, but their ranking was fairly consistent across values of ϕ. Thresholds decreased (worsened) with decreasing ϕ and were lower than for a group of young listeners tested in an earlier study. There were weak to moderate, negative correlations between TFS-AF thresholds and audiometric thresholds at low frequencies (125–1000 Hz) but not at high frequencies (4000–8000 Hz). In conclusion, the TFS-AF test yielded a graded measure of binaural TFS sensitivity for all listeners. This contrasts with the TFS-LF (low-frequency) test, which measures the smallest detectable shift in IPD for a fixed frequency. The absence of practice effects and a reasonably short administration time make the TFS-AF test a good candidate for the assessment of sensitivity to changes in binaural TFS for older listeners without or with hearing loss