The role of recovered envelope cues in the identification of temporal-fine-structure speech for hearing-impaired listeners

Narrowband speech can be separated into fast temporal cues [temporal fine structure (TFS)], and slow amplitude modulations (envelope). Speech processed to contain only TFS leads to envelope recovery through cochlear filtering, which has been suggested to account for TFS-speech intelligibility for normal-hearing listeners. Hearing-impaired listeners have deficits with TFS-speech identification, but the contribution of recovered-envelope cues to these deficits is unknown. This was assessed for hearing-impaired listeners by measuring identification of disyllables processed to contain TFS or recovered-envelope cues. Hearing-impaired listeners performed worse than normal-hearing listeners, but TFS-speech intelligibility was accounted for by recovered-envelope cues for both groups.National Institutes of Health (U.S.) (Grant R43 DC013006)National Institutes of Health (U.S.) (Grant R01 DC00117

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The role of recovered envelope cues in the identification of temporal-fine-structure speech for hearing-impaired listeners

Narrowband speech can be separated into fast temporal cues [temporal fine structure (TFS)], and slow amplitude modulations (envelope). Speech processed to contain only TFS leads to envelope recovery through cochlear filtering, which has been suggested to account for TFS-speech intelligibility for normal-hearing listeners. Hearing-impaired listeners have deficits with TFS-speech identification, but the contribution of recovered-envelope cues to these deficits is unknown. This was assessed for hearing-impaired listeners by measuring identification of disyllables processed to contain TFS or recovered-envelope cues. Hearing-impaired listeners performed worse than normal-hearing listeners, but TFS-speech intelligibility was accounted for by recovered-envelope cues for both groups

Consonant identification in noise using Hilbert-transform temporal fine-structure speech and recovered-envelope speech for listeners with normal and impaired hearing

Consonant-identification ability was examined in normal-hearing (NH) and hearing-impaired (HI) listeners in the presence of steady-state and 10-Hz square-wave interrupted speech-shaped noise. The Hilbert transform was used to process speech stimuli (16 consonants in a-C-a syllables) to present envelope cues, temporal fine-structure (TFS) cues, or envelope cues recovered from TFS speech. The performance of the HI listeners was inferior to that of the NH listeners both in terms of lower levels of performance in the baseline condition and in the need for higher signal-to-noise ratio to yield a given level of performance. For NH listeners, scores were higher in interrupted noise than in steady-state noise for all speech types (indicating substantial masking release). For HI listeners, masking release was typically observed for TFS and recovered-envelope speech but not for unprocessed and envelope speech. For both groups of listeners, TFS and recovered-envelope speech yielded similar levels of performance and consonant confusion patterns. The masking release observed for TFS and recovered-envelope speech may be related to level effects associated with the manner in which the TFS processing interacts with the interrupted noise signal, rather than to the contributions of TFS cues per se.National Institute on Deafness and Other Communication Disorders (U.S.) (Award R01DC000117

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy : a multicountry open-label randomised controlled trial.

CAPRISA, 2016.Abstract available in PDF file

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old