PIGG variant pathogenicity assessment reveals characteristic features within 19 families.

PURPOSE: Phosphatidylinositol Glycan Anchor Biosynthesis, class G (PIGG) is an ethanolamine phosphate transferase catalyzing the modification of glycosylphosphatidylinositol (GPI). GPI serves as an anchor on the cell membrane for surface proteins called GPI-anchored proteins (GPI-APs). Pathogenic variants in genes involved in the biosynthesis of GPI cause inherited GPI deficiency (IGD), which still needs to be further characterized. METHODS: We describe 22 individuals from 19 unrelated families with biallelic variants in PIGG. We analyzed GPI-AP surface levels on granulocytes and fibroblasts for three and two individuals, respectively. We demonstrated enzymatic activity defects for PIGG variants in vitro in a PIGG/PIGO double knockout system. RESULTS: Phenotypic analysis of reported individuals reveals shared PIGG deficiency-associated features. All tested GPI-APs were unchanged on granulocytes whereas CD73 level in fibroblasts was decreased. In addition to classic IGD symptoms such as hypotonia, intellectual disability/developmental delay (ID/DD), and seizures, individuals with PIGG variants of null or severely decreased activity showed cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction, a feature increasingly recognized in IGDs. Individuals with mildly decreased activity showed autism spectrum disorder. CONCLUSION: This in vitro system is a useful method to validate the pathogenicity of variants in PIGG and to study PIGG physiological functions.

Objective Assessment of Speech Intelligibility in Crowded Public Spaces.

The objective of this study was to obtain a normative database of speech intelligibility data for young normal-hearing listeners communicating in public spaces. A total of 174 listeners participated in an interactive speech intelligibility task that required four-person groups to conduct a live version of the Modified Rhyme Test in noisy public spaces. The public spaces tested included a college library, a college cafeteria, a casual dining restaurant during lunch hour, and a crowded bar during happy hour. At the start of each trial, one of the participants was randomly selected as the talker, and a tablet computer was used to prompt them to say a word aloud from the Modified Rhyme Test. Then, the other three participants were required to select this word from one of six rhyming alternatives displayed on three other tablet computers. The tablet computers were also used to record the SPL at each listener location during and after the interval where the target talker was speaking. These SPL measurements were used to estimate the signal-to-noise ratio (SNR) in each trial of the experiment. As expected, the results show that speech intelligibility decreases, response time increases, and perceived difficulty increases as the background noise level increases. There was also a systematic decrease in SNR with increasing background noise, with SNR decreasing 0.44 dB for every 1 dB increase in ambient noise level above 60 dB. Overall, the results of this study have demonstrated how low-cost tablet computer-based data collection systems can be used to collect live-talker speech intelligibility data in real-world environments. We believe these techniques could be adapted for use in future studies focused on obtaining ecologically valid assessments of the effects of age, hearing impairment, amplification, and other factors on speech intelligibility performance in real-world environments.

Assessment of auditory spatial awareness in complex listening environments.

In the real world, listeners often need to track multiple simultaneous sources in order to maintain awareness of the relevant sounds in their environments. Thus, there is reason to believe that simple single source sound localization tasks may not accurately capture the impact that a listening device such as a hearing aid might have on a listener's level of auditory awareness. In this experiment, 10 normal hearing listeners and 20 hearing impaired listeners were tested in a task that required them to identify and localize sound sources in three different listening tasks of increasing complexity: a single-source localization task, where listeners identified and localized a single sound source presented in isolation; an added source task, where listeners identified and localized a source that was added to an existing auditory scene, and a remove source task, where listeners identified and localized a source that was removed from an existing auditory scene. Hearing impaired listeners completed these tasks with and without the use of their previously fit hearing aids. As expected, the results show that performance decreased both with increasing task complexity and with the number of competing sound sources in the acoustic scene. The results also show that the added source task was as sensitive to differences in performance across listening conditions as the standard localization task, but that it correlated with a different pattern of subjective and objective performance measures across listeners. This result suggests that a measure of complex auditory situation awareness such as the one tested here may be a useful tool for evaluating differences in performance across different types of listening devices, such as hearing aids or hearing protection devices.

Is three a crowd? Clients, clinicians, and managed care.

How does therapy change when therapists work under managed care plans? To explore this question, the authors conducted in-depth, semistructured interviews with therapists. The interview texts were analyzed using a structured thematic coding system. A central theme in the interviews was a culture clash between managed care companies and these therapists. Working for managed care organizations demanded several practices that violated the therapists' standard of care and professional ethics. Also, participants reported that managed care personnel misrepresented the nature of psychotherapy to clients, thereby undermining the therapeutic work and the therapist-client relationship. If these therapists' experiences are representative, the growth of managed care has serious implications for the nature of psychotherapy, practitioners' integrity and morale, and the public image of the therapy professions.