When a vowel follows an obstruent, the fundamental frequency in the first few tens of milliseconds of the vowel is known to be influenced by the voicing characteristics of the consonant. This ...influence was re-examined in the study reported here. Stops, fricatives, and the nasal /m/ were paired with the vowels /i,a/ to form CVm syllables. Target syllables were embedded in carrier sentences, and intonation was varied to produce each syllable in either a high, low, or neutral pitch environment. In a high-pitch environment, F0 following voiceless obstruents is significantly increased relative to the baseline /m/, but following voiced obstruents it closely traces the baseline. In a low-pitch environment, F0 is very slightly increased following all obstruents, voiced and unvoiced. It is suggested that for certain pitch environments a conflict can occur between gestures corresponding to the segmental feature stiff vocal folds and intonational elements. The results are different acoustic manifestations of stiff in different pitch environments. The spreading of the vocal folds that occurs during unvoiced stops in certain contexts in English is an enhancing gesture, which aids the resolution of the gestural conflict by allowing the defining segmental gesture to be weakened without losing perceptual salience.
The technical crafts of sound in classical Hollywood cinema have, until recently, remained largely 'unsung' by histories of the studio era. Yet film sound - voice, music and sound effects - is a ...crucial aspect of film style and has been key to engaging and holding audiences since the transition to sound by Hollywood's major studios in 1929. This innovative new text restores sound technicians to Hollywood's creative history. Exploring a range of films from the early sound period (1931) through to the late studio period (1948), and drawing on a wide range of archival sources, the book reveals how Hollywood's sound designers worked and why they worked in the ways that they did. The book demonstrates how sound technicians developed conventions designed to tell stories through sound, placing them within the production cultures of studio era filmmaking, and uncovering a history of collective and collaborative creativity. In doing so, it traces the emergence of a body of highly skilled sound personnel, able to apply expert technical knowledge in the science of sound to the creation of cinematic soundscapes that are alive with mood and sensation.
By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic ...criteria for Legius syndrome (LGSS).
We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups.
We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended.
The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS.
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JIA is the most common chronic inflammatory arthritis in children and young people and an estimated one-third of individuals will have persistent active disease into adulthood. There are a number of ...key differences in the clinical manifestations, assessment and management of JIA compared with adult-onset arthritis. Transition and transfer to adult services present significant challenges for many patients, their families and health care professionals. We describe key clinical issues relevant to adult rheumatology health care teams responsible for ongoing care of these young people.
Abstract
Background
Using Newcastle 85+ Study data, we investigated transitions between frailty states from age 85 to 90 years and whether multi-morbidities and socioeconomic status (SES) modify ...transitions.
Methods
The Newcastle 85+ Study is a prospective, longitudinal cohort study of all people born in 1921 in Newcastle and North Tyneside. Data included: a multidimensional health assessment; general practice record review (GPRR) and date of death. Using the Fried phenotype (participants defined as robust, pre-frail or frail), frailty was measured at baseline, 18, 36 and 60 months.
Results
Frailty scores were available for 82% (696/845) of participants at baseline. The prevalence of frailty was higher in women (29.7%, 123/414) than men (17.7%, 50/282) at baseline and all subsequent time points. Of those robust at baseline, 44.6% (50/112) remained robust at 18 months and 28% (14/50) at age 90. Most (52%) remained in the same state across consecutive interviews; only 6% of the transitions were recovery (from pre-frail to robust or frail to pre-frail), and none were from frail to robust. Four or more diseases inferred a greater likelihood of progression from robust to pre-frail even after adjustment for SES. SES did not influence the likelihood of moving from one frailty state to another.
Conclusions
Almost half the time between age 85 and 90, on average, was spent in a pre-frail state; multi-morbidity increased the chance of progression from robust and to frail; greater clinical intervention at the onset of a first chronic illness, to prevent transition to multi-morbidity, should be encouraged.
Alport syndrome (AS) is a predominantly X-linked hereditary nephritis associated with high-tone, sensorineural deafness and characteristic eye signs. Clinical diagnostic criteria were defined in ...1988. Most cases result from mutations in the X-linked collagen gene COL4A5, with mutations in the autosomal genes COL4A3 and COL4A4 on chromosome 2 accounting for the rest. Mutation analysis of COL4A5 with a combination of sequencing and multiplex ligation-dependent probe amplification has been available for several years. The objective of this study was to determine the utility of clinical diagnostic criteria in identifying patients likely to have a COL4A5 mutation.
Clinical information was available on 206 patients whose DNA was received for testing between 1994 and June 2008; predictive tests for a known familial mutation, samples from duplicate family members, and incompletely screened samples were excluded. One hundred and twenty-eight patients (62.1%) had a pathogenic COL4A5 mutation.
The mutation detection rate in families fulfilling zero, one, two, three, or four diagnostic criteria was 0%, 18%, 64%, 89%, and 81%, respectively. Sixty-seven percent of patients with COL4A5 mutations meeting only two diagnostic criteria had not had a complete clinical assessment. In two thirds of families meeting four diagnostic criteria without an identified COL4A5 mutation, autosomal inheritance was confirmed or suspected.
The authors recommend COL4A5 analysis in any patient meeting at least two clinical diagnostic criteria. COL4A3 and COL4A4 analysis should be considered if a COL4A5 mutation is not detected and primarily if autosomal inheritance is suspected.
Introduction
Patient decision aids (PtDA) complement shared decision‐making with healthcare professionals and improve decision quality. However, PtDA often lack theoretical underpinning. We are ...codesigning a PtDA to help people with increased genetic cancer risks manage choices. The aim of an innovative workshop described here was to engage with the people who will use the PtDA regarding the theoretical underpinning and logic model outlining our hypothesis of how the PtDA would lead to more informed decision‐making.
Methods
Short presentations about psychological and behavioural theories by an expert were interspersed with facilitated, small‐group discussions led by patients. Patients were asked what is important to them when they make health decisions, what theoretical constructs are most meaningful and how this should be applied to codesign of a PtDA. An artist created a visual summary. Notes from patient discussions and the artwork were analysed using reflexive thematic analysis.
Results
The overarching theme was: It's personal. Contextual factors important for decision‐making were varied and changed over time. There was no one ‘best fit’ theory to target support needs in a PtDA, suggesting an inductive, flexible framework approach to programme theory would be most effective. The PtDA logic model was revised based on patient feedback.
Conclusion
Meaningful codesign of PtDA including discussions about the theoretical mechanisms through which they support decision‐making has the potential to lead to improved patient care through understanding the intricately personal nature of health decisions, and tailoring content and format for holistic care.
Patient Contribution
Patients with lived experience were involved in codesign and coproduction of this workshop and analysis as partners and coauthors. Patient discussions were the primary data source. Facilitators provided a semi‐structured guide, but they did not influence the patient discussions or provide clinical advice. The premise of this workshop was to prioritise the importance of patient lived experience: to listen, learn, then reflect together to understand and propose ideas to improve patient care through codesign of a PtDA.
Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70-100% lifetime risk of developing ...cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin's mechanism of anticancer activity in this context is unclear.
Metformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged ≥ 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI.
Alongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis.
ISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.
The aim of the research reported in this paper is to formulate a set of acoustic parameters of the voicing source that reflect individual differences in the voice qualities of female speakers. ...Theoretical analysis and observations of experimental data suggest that a more open glottal configuration results in a glottal volume-velocity waveform with relatively greater low-frequency and weaker high-frequency components, compared to a waveform produced with a more adducted glottal configuration. The more open glottal configuration also leads to a greater source of aspiration noise and larger bandwidths of the natural frequencies of the vocal tract, particularly the first formant. These different attributes of the glottal waveform can be measured directly from the speech spectrum or waveform. A set of acoustic parameters that are likely to indicate glottal characteristics is described. These parameters are measured in the speech of a group of female speakers, and the glottal configurations of the speakers are hypothesized. This research contributes to the description of normal variations of voicing characteristics across speakers and to a continuing effort to improve the analysis and synthesis of female speech. It may also have applications in clinical settings.
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