Integrated speaker-adaptive speech synthesis

Enabling speech synthesis systems to rapidly adapt to sound like a particular speaker is an essential attribute for building personalised systems. For deep-learning based approaches, this is difficult as these networks use a highly distributed representation. It is not simple to interpret the model parameters, which complicates the adaptation process. To address this problem, speaker characteristics can be encapsulated in fixed-length speaker-specific Identity Vectors (iVectors), which are appended to the input of the synthesis network. Altering the iVector changes the nature of the synthesised speech. The challenge is to derive an optimal iVector for each speaker that encodes all the speaker attributes required for the synthesis system. The standard approach involves two separate stages: estimation of the iVectors for the training data; and training the synthesis network. This paper proposes an integrated training scheme for speaker adaptive speech synthesis. For the iVector extraction, an attention based mechanism, which is a function of the context labels, is used to combine the data from the target speaker. This attention mechanism, as well as nature of the features being merged, are optimised at the same time as the synthesis network parameters. This should yield an iVector-like speaker representation that is optimal for use with the synthesis system. The system is evaluated on the Voice Bank corpus. The resulting system automatically provides a sensible attention sequence and shows improved performance from the standard approach.St. John’s College Internal Graduate Scholarship European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 655764 EPSRC grant EP/I031022/1 (Natural Speech Technology

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

The Association Between Women’s Perceptions of Professional Support and Problems Experienced on Breastfeeding Cessation: A Western Australian Study

A cross-sectional survey was used to determine the association among women’s breastfeeding problems, their perceptions of support from midwives and child health nurses, and breastfeeding cessation in the first 10 weeks postbirth in a sample of Western Australian women (N = 2669). Primiparous women (75.8%) experienced significantly more problems that multiparous women (52.6%). Although 78.8% of all women agreed or strongly agreed that staff were helpful with feeding, 53.4% confirmed that different midwives offered different feeding advice; however, receiving different advice from midwives around feeding was not associated with breastfeeding cessation. Differences in breastfeeding cessation were associated with parity. Primiparous women’s cessation was associated with experiencing any breastfeeding problems, unhelpful hospital midwives, and unhelpful information from child health nurses, whereas for multiparous women, this included 2 or more breastfeeding problems, not being able to choose when to feed, and unhelpful information from child health nurses

MRI characteristics are predictive for CDMS in monofocal, but not in multifocal patients with a clinically isolated syndrome

BACKGROUND: To diagnose multiple sclerosis (MS), evidence for dissemination in space and time is required. There is no clear definition on how symptoms and signs of a patient indicate clinical dissemination in space. To provide a uniform approach on this subject, a clinical classification system was described recently differentiating patients with mono- and multifocal clinical presentation. Here we assess the predictive value of clinically defined dissemination in space at first presentation for time to clinically definite MS (CDMS). METHODS: Four hundred and sixty-eight patients with a first episode suggestive of MS were classified as clinically mono- or multifocal by two neurologists blinded to magnetic resonance imaging (MRI) results. These patients were part of the BENEFIT study in which 292 patients were randomized to interferon beta-1b (IFNB-1b) and 176 to placebo. By using Kaplan-Meier statistics the risk for CDMS was studied in mono- and multifocal patients of the placebo group, both with and without taking into account MRI measures of potential prognostic relevance. RESULTS: Time to CDMS was similar in monofocal and multifocal patients. In monofocal patients, the risk for CDMS over 2 years was significantly higher when <or= 9 T2 lesions or at least one Gd-enhancing lesion were present at the first event or 3 or 6 months after the first event. In patients with multifocal presentation, these MRI measures had no significant added value in predicting time to CDMS. CONCLUSION: These data indicate that a carefully performed neurological assessment of symptoms and signs, combined with lesions on MRI, is important for defining the risk of conversion to CDMS. TRIAL REGISTRATION: The Benefit trial has been registered under NCT00185211 http://www.clinicaltrials.gov

Measuring benefits and patients' satisfaction when glasses are not needed after cataract and presbyopia surgery: scoring and psychometric validation of the Freedom from Glasses Value Scale (FGVS©)

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to reduce the number of items, create a scoring method and assess the psychometric properties of the Freedom from Glasses Value Scale (FGVS), which measures benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal intraocular lens (IOL) surgery.</p> <p>Methods</p> <p>The 21-item FGVS, developed simultaneously in French and Spanish, was administered by phone during an observational study to 152 French and 152 Spanish patients who had undergone cataract or presbyopia surgery at least 1 year before the study. Reduction of items and creation of the scoring method employed statistical methods (principal component analysis, multitrait analysis) and content analysis. Psychometric properties (validation of the structure, internal consistency reliability, and known-group validity) of the resulting version were assessed in the pooled population and per country.</p> <p>Results</p> <p>One item was deleted and 3 were kept but not aggregated in a dimension. The other 17 items were grouped into 2 dimensions ('global evaluation', 9 items; 'advantages', 8 items) and divided into 5 sub-dimensions, with higher scores indicating higher benefit of surgery. The structure was validated (good item convergent and discriminant validity). Internal consistency reliability was good for all dimensions and sub-dimensions (Cronbach's alphas above 0.70). The FGVS was able to discriminate between patients wearing glasses or not after surgery (higher scores for patients not wearing glasses). FGVS scores were significantly higher in Spain than France; however, the measure had similar psychometric performances in both countries.</p> <p>Conclusions</p> <p>The FGVS is a valid and reliable instrument measuring benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal IOL surgery.</p

Sources of variability in childhood obesity indicators and related behaviors

The purpose of this study was to describe sources of variability in obesity-related variables in 6022 children aged 9-11 years from 12 countries. The study design involved recruitment of students, nested within schools, which were nested within study sites. Height, weight and waist circumference (WC) were measured and body mass index (BMI) was calculated; sleep duration and total and in-school moderate-to-vigorous physical activity (MVPA) and sedentary time were measured by accelerometry; and diet scores were obtained by questionnaire. Variance in most variables was largely explained at the student level: BMI (91.9%), WC (93.5%), sleep (75.3%), MVPA (72.5%), sedentary time (76.9%), healthy diet score (88.3%), unhealthy diet score (66.2%), with the exception of in-school MVPA (53.8%) and in-school sedentary time (25.1%). Variance explained at the school level ranged from 3.3% for BMI to 29.8% for in-school MVPA, and variance explained at the site level ranged from 3.2% for WC to 54.2% for in-school sedentary time. In general, more variance was explained at the school and site levels for behaviors than for anthropometric traits. Given the variance in obesity-related behaviors in primary school children explained at school and site levels, interventions that target policy and environmental changes may enhance obesity intervention efforts.Peer reviewe

Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

<p>Abstract</p> <p>Background</p> <p>Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.</p> <p>Methods</p> <p>This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/²/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.</p> <p>Results</p> <p>Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (<it>DPYD</it>) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).</p> <p>Conclusion</p> <p>Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.</p

Syndromic surveillance and heat wave morbidity: a pilot study based on emergency departments in France

<p>Abstract</p> <p>Background</p> <p>The health impacts of heat waves are serious and have prompted the development of heat wave response plans. Even when they are efficient, these plans are developed to limit the health effects of heat waves. This study was designed to determine relevant indicators related to health effects of heat waves and to evaluate the ability of a syndromic surveillance system to monitor variations in the activity of emergency departments over time. The study uses data collected during the summer 2006 when a new heat wave occurred in France.</p> <p>Methods</p> <p>Data recorded from 49 emergency departments since July 2004, were transmitted daily via the Internet to the French Institute for Public Health Surveillance. Items collected on patients included diagnosis (ICD10 codes), outcome, and age. Statistical t-tests were used to compare, for several health conditions, the daily averages of patients within different age groups and periods (whether 'on alert' or 'off alert').</p> <p>Results</p> <p>A limited number of adverse health conditions occurred more frequently during hot period: dehydration, hyperthermia, malaise, hyponatremia, renal colic, and renal failure. Over all health conditions, the total number of patients per day remained equal between the 'on alert' and 'off alert' periods (4,557.7/day vs. 4,511.2/day), but the number of elderly patients increased significantly during the 'on alert' period relative to the 'off alert' period (476.7/day vs. 446.2/day p < 0.05).</p> <p>Conclusion</p> <p>Our results show the interest to monitor specific indicators during hot periods and to focus surveillance efforts on the elderly. Syndromic surveillance allowed the collection of data in real time and the subsequent optimization of the response by public health agencies. This method of surveillance should therefore be considered as an essential part of efforts to prevent the health effects of heat waves.</p

Extreme-ultraviolet fine structure and variability associated with coronal rain revealed by Solar Orbiter/EUI HRIEUV and SPICE

CONTEXT: Coronal rain is the most dramatic cooling phenomenon of the solar corona. Recent observations in the visible and UV spectrum have shown that coronal rain is a pervasive phenomenon in active regions. Its strong link with coronal heating through the thermal non-equilibrium (TNE) a-thermal instability (TI) scenario makes it an essential diagnostic tool for the heating properties. Another puzzling feature of the solar corona in addition to the heating is its filamentary structure and variability, particularly in the extreme UV (EUV). AIMS: We aim to identify observable features of the TNE-TI scenario underlying coronal rain at small and large spatial scales to understand the role it plays in the solar corona. METHODS: We used EUV datasets at an unprecedented spatial resolution of 240 km from the High Resolution Imager (HRI) in the EUV (HRIEUV) of the Extreme Ultraviolet Imager (EUI) and SPICE on board Solar Orbiter from the perihelion in March and April 2022. RESULTS: EUV absorption features produced by coronal rain are detected at scales as small as 260 km. As the rain falls, heating and compression is produced immediately downstream, leading to a small EUV brightening that accompanies the fall and produces a fireball phenomenon in the solar corona. Just prior to impact, a flash-like EUV brightening downstream of the rain, lasting a few minutes, is observed for the fastest events. For the first time, we detect the atmospheric response to the impact of the rain on the chromosphere, and it consists of upward-propagating rebound shocks and flows that partly reheat the loop. The observed widths of the rain clumps are 500a-±a-200 km. They exhibit a broad velocity distribution of 10a-a-A-150 km sa-1and peak below 50 km sa-1. Coronal strands of similar widths are observed along the same loops. They are co-spatial with cool filamentary structure seen with SPICE, which we interpret as the condensation corona transition region. Prior to the appearance of the rain, sequential loop brightenings are detected in gradually cooler lines from coronal to chromospheric temperatures. This matches the expected cooling. Despite the large rain showers, most cannot be detected in AIA 171 in quadrature, indicating that line-of-sight effects play a major role in the visibility of coronal rain. The AIA 304 and SPICE observations still reveal that only a small fraction of the rain can be captured by HRIEUV. CONCLUSIONS: Coronal rain generates EUV structure and variability over a wide range of scales, from coronal loops to the smallest resolvable scales. This establishes the major role that TNE-TI plays in the observed EUV morphology and variability of the corona

Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.

Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines