On detectable and meaningful speech-intelligibility benefits

The most important parameter that affects the ability to hear and understand speech in the presence of background noise is the signal-to-noise ratio (SNR). Despite decades of research in speech intelligibility, it is not currently known how much improvement in SNR is needed to provide a meaningful benefit to someone. We propose that the underlying psychophysical basis to a meaningful benefit should be the just noticeable difference (JND) for SNR. The SNR JND was measured in a series of experiments using both adaptive and fixed-level procedures across participants of varying hearing ability. The results showed an average SNR JND of approximately 3 dB for sentences in same-spectrum noise. The role of the stimulus and link to intelligibility was examined by measuring speech-intelligibility psychometric functions and comparing the intelligibility JND estimated from those functions with measured SNR JNDs. Several experiments were then conducted to establish a just meaningful difference (JMD) for SNR. SNR changes that could induce intervention-seeking behaviour for an individual were measured with subjective scaling and report, using the same stimuli as the SNR JND experiment as pre- and post-benefit examples. The results across different rating and willingness-to-change tasks showed that the mean ratings increased near linearly with a change in SNR, but a change of at least 6 dB was necessary to reliably motivate participants to seek intervention. The magnitude of the JNDs and JMDs for speech-intelligibility benefits measured here suggest a gap between what is achievable and what is meaningful

The Physical Attributes Most Required in Professional Ballet: A Delphi Study

Background It is commonly accepted that dancers are undoubtedly athletes, with ballet perhaps the most demanding dance form. No previous study has sought to define the physical attributes most desired for classical ballet by professional companies and vocational schools. These are likely to include both aesthetic features and attributes that reduce the risk of injury as well as enhance performance. Method An initial survey question using the modified Delphi technique was sent using Opinio Survey Software to a selected international expert panel. This was drawn both from those involved in selection of elite professional ballet dancers, and the international medical professionals involved in the care of dancers. The first questionnaire was open-ended to scope for all the physical attributes most favoured by the professional experts. Results There were 148 responses from the panel of international experts. In total 34 physical attributes were suggested. The 2 most recommended physical criteria for selection into the profession were overall flexibility and overall strength. These results are discussed in the context of the published literature on the mechanics, anatomy and physiology of ballet. Conclusion Flexibility and strength are the 2 features most sought after in elite ballet dancers

The effect of a randomized 12-week soy drink intervention on everyday mood in postmenopausal women

Objective: Dietary soy may improve menopausal symptoms, and subsequently mediate mood. This novel study examines various doses of dietary soy drink on everyday mood stability and variability in postmenopausal women. Methods: Community-dwelling women (n = 101), within 7 years postmenopause, consumed daily either a low (10 mg, n = 35), medium (35 mg, n = 37), or high (60 mg, n = 29) dose of isoflavones, for 12 weeks. Menopausal symptoms and repeated measures of everyday mood (positive [PA] and negative [NA] affect) (assessed at four time points per day for 4 consecutive days, using The Positive and Negative Affect Schedule) were completed at baseline and follow-up. Results: The dietary soy intervention had no effect on everyday mood stability (for PA [F{2,70} = 0.95, P = 0.390] and NA [F{2,70} = 0.72, P = 0.489]) or variability (for PA [F{2,70} = 0.21, P = 0.807] and for NA [F{2,70} = 0.15, P = 0.864]), or on menopausal symptoms (for vasomotor [F{2,89} = 2.83, P = 0.064], psychological [F{2,88} = 0.63, P = 0.535], somatic [F{2,89} = 0.32, P = 0.729], and total menopausal symptoms [F{2,86} = 0.79, P = 0.458]). There were between-group differences with the medium dose reporting higher PA (low, mean 24.2, SD 6; and medium, mean 29.7, SD 6) and the low dose reporting higher NA (P = 0. 048) (low, mean 11.6, SD 2; and high, mean 10.6, SD 1) in mood scores. Psychological (baseline M = 18 and follow-up M = 16.5) and vasomotor (baseline M = 4.2 and follow-up M = 3.6) scores declined from baseline to follow-up for the overall sample. Conclusions: Soy isoflavones had no effect on mood at any of the doses tested. Future research should focus on the menopause transition from peri to postmenopause as there may be a window of vulnerability, with fluctuating hormones and increased symptoms which may affect mood

Guidance in social and ethical issues related to clinical, diagnostic care and novel therapies for hereditary neuromuscular rare diseases: "translating" the translational.

Drug trials in children engage with many ethical issues, from drug-related safety concerns to communication with patients and parents, and recruitment and informed consent procedures. This paper addresses the field of neuromuscular disorders where the possibility of genetic, mutation-specific treatments, has added new complexity. Not only must trial design address issues of equity of access, but researchers must also think through the implications of adopting a personalised medicine approach, which requires a precise molecular diagnosis, in addition to other implications of developing orphan drugs. It is against this background of change and complexity that the Project Ethics Council (PEC) was established within the TREAT-NMD EU Network of Excellence. The PEC is a high level advisory group that draws upon the expertise of its interdisciplinary membership which includes clinicians, lawyers, scientists, parents, representatives of patient organisations, social scientists and ethicists. In this paper we describe the establishment and terms of reference of the PEC, give an indication of the range and depth of its work and provide some analysis of the kinds of complex questions encountered. The paper describes how the PEC has responded to substantive ethical issues raised within the TREAT-NMD consortium and how it has provided a wider resource for any concerned parent, patient, or clinician to ask a question of ethical concern. Issues raised range from science related ethical issues, issues related to hereditary neuromuscular diseases and the new therapeutic approaches and questions concerning patients rights in the context of patient registries and bio-banks. We conclude by recommending the PEC as a model for similar research contexts in rare diseases

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

INTRODUCTION: Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates. METHODS: In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method. RESULTS: Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI. CONCLUSIONS: These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels

Background risk of breast cancer and the association between physical activity and mammographic density

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Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014