Native and Non-Native Speaker Judgements on the Quality of Synthesized Speech

The difference between native speakers' and non-native speak- ers' naturalness judgements of synthetic speech is investigated. Similar/difference judgements are analysed via a multidimen- sional scaling analysis and compared to Mean opinion scores. It is shown that although the two groups generally behave in a similar manner the variance of non-native speaker judgements is generally higher. While both groups of subject can clearly distinguish natural speech from the best synthetic examples, the groups' responses to different artefacts present in the synthetic speech can vary

Further exploration of the possibilities and pitfalls of multidimensional scaling as a tool for the evaluation of the quality of synthesized speech

Multidimensional scaling (MDS) has been suggested as a useful tool for the evaluation of the quality of synthesized speech. However, it has not yet been extensively tested for its applica- tion in this specific area of evaluation. In a series of experiments based on data from the Blizzard Challenge 2008 the relations between Weighted Euclidean Distance Scaling and Simple Euclidean Distance Scaling is investigated to understand how aggregating data affects the MDS configuration. These results are compared to those collected as mean opinion scores (MOS). The ranks correspond, and MOS can be predicted from an object's space in the MDS generated stimulus space. The big advantage of MDS over MOS is its diagnostic value; dimensions along which stimuli vary are not correlated, as is the case in modular evaluation using MOS. Finally, it will be attempted to generalize from the MDS representations of the thoroughly tested subset to the aggregated data of the larger-scale Blizzard Challenge

Transgender adults, gender-affirming hormone therapy and blood pressure: a systematic review

Objectives: Gender-affirming hormone therapy (GHT) is utilized by people who are transgender to align their secondary sex characteristics with their sex identity. Data relating to cardiovascular outcomes in this population are limited. We aimed to review the impact of GHT on the blood pressure (BP) of transgender individuals. Methods: We searched PubMed/MEDLINE, SCOPUS and Cochrane Library databases for articles published relating to the BP of transgender adults commencing GHT. Methodological quality was assessed via the ‘Quality Assessment Tool for Before–After (Pre–Post) Studies with No Control Group’. Results: Six hundred articles were screened, of which 14 studies were included in this systematic review encompassing 1309 individuals (∼50% transgender men and women) treated with GHT between 1989 and 2019. These articles were all pre–post observational studies without control groups. Mean ages ranged between 23.0–36.7 years (transgender men) and 25.2–34.8 years (transgender women). Interventions were diverse and included oral, transdermal and injectable hormonal preparations with 4 months to 5 years follow-up. Most studies in transgender men did not demonstrate a change in BP, whereas transgender women on GHT demonstrated an increase in SBP but not DBP. These studies were heterogenous with significant methodological limitations and only two were determined to have a good quality rating. Conclusion: There is currently insufficient data to advise the impact of GHT on BP in transgender individuals. Better quality research is essential to elucidate whether exogenous sex hormones modulate BP in transgender people and whether this putative alteration infers poorer cardiovascular outcomes

Asymmetries in the perception of synthesized speech

It was previously observed [1] that the order of presentation of paired stimuli influenced the number of different responses in same-different tasks in speech synthesis evaluation. This paper investigates this phenomenon within the context of cognitive psychology and demonstrates that, as the cognitive psychology literature suggests, there is an effect relating to the prototypicality of the stimulus. Index Terms: speech synthesis, evaluation, perception, Blizzard Challeng

De Novo Occurrence of a Variant in ARL3 and Apparent Autosomal Dominant Transmission of Retinitis Pigmentosa.

BackgroundRetinitis pigmentosa is a phenotype with diverse genetic causes. Due to this genetic heterogeneity, genome-wide identification and analysis of protein-altering DNA variants by exome sequencing is a powerful tool for novel variant and disease gene discovery. In this study, exome sequencing analysis was used to search for potentially causal DNA variants in a two-generation pedigree with apparent dominant retinitis pigmentosa.MethodsVariant identification and analysis of three affected members (mother and two affected offspring) was performed via exome sequencing. Parental samples of the index case were used to establish inheritance. Follow-up testing of 94 additional retinitis pigmentosa pedigrees was performed via retrospective analysis or Sanger sequencing.Results and conclusionsA total of 136 high quality coding variants in 123 genes were identified which are consistent with autosomal dominant disease. Of these, one of the strongest genetic and functional candidates is a c.269A>G (p.Tyr90Cys) variant in ARL3. Follow-up testing established that this variant occurred de novo in the index case. No additional putative causal variants in ARL3 were identified in the follow-up cohort, suggesting that if ARL3 variants can cause adRP it is an extremely rare phenomenon

Emergence of hereditary hyperplastic gingivitis in Newfoundland and Labrador, Canada: an exploration into the molecular aetiology at both the gene and genome levels

Hereditary hyperplastic gingivitis (HHG) is a benign fibrous enlargement of the gingival tissue to dental encapsulation in ranched silver foxes (Vulpes vulpes). It is an autosonal recessive condition displaying male sex-biased penetrance HHG demonstrates a pleiotropic association with superior fur quality. In 2004, after the introduction of a Finnish fox line, HHG emerged in Newfoundland and Labrador, Canada. While the underlying HHG aetiology is unknown, an analogous condition called hereditary gingival fibromatosis (HGF) occurs in humans, providing a platform for investigation into the molecular mechanisms of HHG. A mutation in the son of sevenless homolog 1 gene causes one form of HGF. Candidate gene sequencing of this and related genes including epidermal growth factor receptor (EGFR), growth factor receptor bound protein 2, and mitogen-activated protein kinase kinase 6 did not uncover any putative coding sequence or splice-site mutations. HHG was also examined at the genomic level, integrating knowledge of the chromosomal loci associated with the analogous human condition, HGF. This exploration was divided into the known genetic causes of isolated HGF and HGF-associated sundromes characterized by both gingival and hair overgrowth. Global gene expression differences between affected adn unaffected foxes pinpoint SOS2 and RASA1 as candidate gene for HHG; overall, the genomic expression patterns strongly indicate the involvement of the mitogen-activated protein kinase (MAPK) signalling pathway. Specifically, the error could occur prior to the Rat sarcoma protein in this pathway. Future exploration of the pathway could elucidate the genetic basis of HHG and more broadly the molecular aetiology of gingival overgrowth in humans and canines. Additional information regarding the HHG phenotype was revealed, including the potential involvement of androgens in disease severity. The steroid-5-alpha-reductase, alpha polypeptide 2 gene was found to be up-regulated in the HHG-affected foxes, and the link between androgens and gingival sensitivity in dogs might help explain the perceived sex biased penetrance originally noted in HHG. Overall the molecular mechanisms underpinning the HHG phenotype and future work revolve around the MAPK signalling pathway including influences that other gene products like androgens have on it

Young Adult Mental Health Beyond the COVID-19 Era: Can Enlightened Policy Promote Long-Term Change?

The status of mental health for adolescents and young adults has aptly been termed a "crisis" across research, clinical, and policy quarters. Arguably, the status quo provision of mental health services for adolescents and young adults is neither acceptable nor salvageable in its current form. Instead, only a wholesale policy transformation of mental health sciences can address crises of this scope. Pandemic-related impacts on mental health, particularly among young adults, have clearly exposed the need for the mental healthcare field to develop a set of transformative priorities to achieve long overdue, systemic changes: (1) frequent mental health tracking, (2) increased access to mental health care, (3) working with and within communities, (4) collaboration across disciplines and stakeholders, (5) prevention-focused emphasis, (6) use of dimensional descriptions over categorical pronouncements, and (7) addressing systemic inequities. The pandemic required changes in mental healthcare that can and should be the beginning of long-needed reform, calling upon all mental health care disciplines to embrace innovation and relinquish outdated traditions

Neuron-immune mechanisms contribute to pain in early stages of arthritis

Background: Rheumatoid arthritis (RA) patients frequently show weak correlations between the magnitude of pain and inflammation suggesting that mechanisms other than overt peripheral inflammation contribute to pain in RA. We assessed changes in microglial reactivity and spinal excitability and their contribution to pain-like behaviour in the early stages of collagen-induced arthritis (CIA) model. Methods: Mechanically evoked hypersensitivity, spinal nociceptive withdrawal reflexes (NWRs) and hind paw swelling were evaluated in female Lewis rats before and until 13 days following collagen immunization. In the spinal dorsal horn, microgliosis was assayed using immunohistochemistry (Iba-1/p-p38) and cyto(chemo)kine levels in the cerebrospinal fluid (CSF). Intrathecal administration of microglia-targeting drugs A-438079 (P2X7 antagonist) and LHVS (cathepsin S inhibitor) were examined upon hypersensitivity, NWRs, microgliosis andcyto(chemo)kine levels in the early phase of CIA. Results: The early phase of CIA was associated with mechanical allodynia and exaggerated mechanically evoked spinal NWRs, evident before hind paw swelling, and exacerbated with the development of swelling. Concomitant with the development of hypersensitivity was the presence of reactive spinal microgliosis and an increase of IL-1β levels in CSF (just detectable in plasma). Prolonged intrathecal administration of microglial inhibitors attenuated the development of mechanical allodynia, reduced microgliosis and attenuated IL-1β increments. Acute spinal application of either microglial inhibitor significantly diminished the sensitization of the spinal NWRs. Conclusions: Mechanical hypersensitivity in the early phase of CIA is associated with central sensitization that is dependent upon microglial-mediated release of IL-1β in the spinal cord. Blockade of these spinal events may provide pain relief in RA patients

The influence of predator odours and overcrowded mouse odours on regulation of oestrous cycles in house mice (\u3ci\u3eMus musculus\u3c/i\u3e)

We investigated the influence of chemical signals derived from different sources—urine of feral cats (Felis catus) and urine from overcrowded mice (Mus musculus) on regulation of oestrous cycles in Mus musculus musculus under laboratory conditions. Cat urine and urine from mice housed in overcrowded conditions caused very similar effects. Application of urine from feral cats and from overcrowded conspecifics to the bedding of experimental animals for a period of 21 days caused a significant increase in numbers of animals with extended oestrous cycles. Application of cat urine or overcrowded mouse urine to the bedding of female mice caused an extension of oestrous cycles in 56.0% and 62.5% of tested animals, respectively. The results of the present study and other experimental data from our laboratory may indicate that predator urine and urine from overcrowded conspecifics share the same chemical information

RNA modification landscape of the human mitochondrial tRNA(LYs) regulates protein synthesis

Post-transcriptional RNA modifications play a critical role in the pathogenesis of human mitochondrial disorders, but the mechanisms by which specific modifications affect mitochondrial protein synthesis remain poorly understood. Here we used a quantitative RNA sequencing approach to investigate, at nucleotide resolution, the stoichiometry and methyl modifications of the entire mitochondrial tRNA pool, and establish the relevance to human disease. We discovered that a N-1 -methyladenosine (m(1)A) modification is missing at position 58 in the mitochondrial tRNA(LYs) of patients with the mitochondrial DNA mutation m.8344 A > G associated with MERRF (myoclonus epilepsy, ragged-red fibers). By restoring the modification on the mitochondrial tRNA(LYs), we demonstrated the importance of the m(1)A58 to translation elongation and the stability of selected nascent chains. Our data indicates regulation of post-transcriptional modifications on mitochondrial tRNAs is finely tuned for the control of mitochondrial gene expression. Collectively, our findings provide novel insight into the regulation of mitochondrial tRNAs and reveal greater complexity to the molecular pathogenesis of MERRF.Peer reviewe