Prevalence of moderate or greater permanent childhood hearing impairment and effectiveness of targeted surveillance for babies who pass newborn hearing screening.

OBJECTIVE: To assess the utility of targeted surveillance for the identification of moderate to profound PCHI in babies who pass newborn hearing screening in England and have risk factors. DESIGN: Retrospective analysis. STUDY SAMPLE: A total of 3,957,891 children born 01/04/2012-31/03/2018 in England. RESULTS: A total of 7148 PCHI cases were identified (1.81 per 1,000 babies). 6,707 followed an immediate referral from the screen (1 per 16 referrals), 51 followed targeted surveillance referral (1 per 540 referrals) and 390 without a referral. Audiology uptake was higher following an immediate referral (96.7% overall, 77.2% within NHSP-defined timescales) than following targeted surveillance (63.8% overall, 51.1% within 52 weeks of birth). The screening was 94.5% sensitive overall, with similar sensitivities for each of the risk factors. General linearised logistic regression models identified syndrome as the risk factor with the highest odds ratio (14.08 for all babies, 22.19 for babies without immediate referral). Close family history of hearing loss was the next highest (10.93 for all babies, 12.29 for babies without immediate referral). CONCLUSION: The evidence for a targeted surveillance programme, based on risk factors, for babies in England who pass the newborn screen is not strong.

Prevalence of human papillomavirus antibodies in males and females in England.

BACKGROUND: Most studies of human papillomavirus (HPV) epidemiology have employed DNA testing, which measures current infections. Serum antibodies offer a longer-term marker of infection in individuals who seroconvert and can therefore provide additional information about the exposure of populations to HPV. METHODS: Sera from a population-based sample of males and females aged 10 to 49 years, in England, were tested for type-specific HPV antibodies using a multiplexed competitive Luminex assay and previously defined cutoffs of 20, 16, 20, and 24 mMU mL for HPV 6, 11, 16, and 18, respectively. Seropositivity and geometric mean titers of seropositives were analyzed by HPV type, gender, and age. Catalytic models were developed to explore potential effects of antibody waning over time and changing risk of infection by age-cohort. RESULTS: Seroprevalence for HPV 6, 11, 16, and 18 was 16.4%, 5.7%, 14.7%, and 6.3%, respectively, among females and 7.6%, 2.2%, 5.0%, and 2.0%, respectively, among males. Seroprevalence in females was significantly higher than males (P < 0.001 for all types) and showed a decline in older ages that was not seen in males. There was no evidence of declining antibody titers with increasing age. Model results suggest that cohort effects mediated through changes in sexual behavior better explain the observed trend in seroprevalence than waning antibodies over time. CONCLUSIONS: Preimmunization HPV seroprevalence in England shows similar trends to reports from other developed countries. We find the lower seroprevalence in older females probably reflects changes in sexual behavior over the last few decades. This study provides baseline data to monitor the impact of the immunization programme.

Molecular and crystal deformation of cellulose: uniform strain or uniform stress?

The molecular and crystal deformations of a range of lyocell cellulose fibres, produced using different drawing conditions, are reported. The fibres are spun using increasing draw ratios to both increase the molecular and crystal orientation and, consequently, mechanical stiffness. Raman spectroscopy and X-ray diffraction are used to follow molecular and crystal deformation, respectively. It is shown that these techniques are complementary, and that both must be used for semicrystalline cellulose fibres if a full picture of their micromechanics is to be obtained. By following the shift in the 1095 cm(-1) Raman band with respect to external tensile deformation of the fibres we show that we can build up a picture of the microstructure. Using theoretical predictions of the relationship between the Raman band shift rates with respect to strain and stress and the modulus of the fibres we show that the fibres have properties that suggest a hybrid series-series aggregate structure. By using X-ray diffraction we show that the crystal modulus of the fibres appears to change with increasing draw ratio. Furthermore the crystal modulus of the fibres appears to vary systematically with the crystallinity of the sample. Other relationships between the predicted fibre modulus and the experimental values and between the Raman band shift rates and modulus suggest that the assumption of a uniform stress microstructure prior to the measurement of crystal modulus may be an incorrect one. A more realistic structure is proposed for semicrystalline regenerated cellulose fibres, wherein crystals and amorphous regions are both in series and in parallel with each other.

Influence of domain orientation on the mechanical properties of regenerated cellulose fibers.

The determination of the crystal orientation of regenerated cellulose fibers produced under different drawing regimes is presented. Orientation is determined by using wide-angle X-ray diffraction from a synchrotron source and by measuring the azimuthal width of equatorial reflections. The orientation parameter theta is then determined to compare fiber samples. By using a 500 nm beam size, clear differences between the crystal orientations of the skin and the core of the fibers are reported for a range of differently processed fibers for the first time. These results are shown to have implications for the mechanical properties of regenerated cellulose fibers. By applying tensile deformation to fiber bundles it is shown that the most misoriented samples undergo rapid decreases in the orientation parameter, which is an indication of crystal reorientation. However, the more highly oriented fibers undergo little reorientation. An average shear modulus for these fibers is determined by placing the data on a master curve and fitting with a model equation. By using another model for the fibers of low orientation and the shear modulus from the master curve analysis, it is shown that the deformation of less oriented fibers is dominated by shear between crystals, whereas the more oriented filaments are likely to undergo more significant chain deformation. By using a new model for fibers of low orientation, a parameter ksigma is introduced that gives the proportion of the fiber stress that is due to crystal shear. Systematic differences between this parameter for fibers of increasing initial orientation are reported. Moreover it is shown that the fibers of initially lower average orientation are governed by uniform strain, in agreement with the new model, whereas more highly oriented fibers deform under uniform stress. Furthermore, the model that we propose for misoriented domains and the use of a new factor dictating the proportion of shear stress may have general applications in materials engineering.

Tumor necrosis factor-alpha activates the human prolactin gene promoter via nuclear factor-kappaB signaling.

Pituitary function has been shown to be regulated by an increasing number of intrapituitary factors, including cytokines. Here we show that the important cytokine TNF-alpha activates prolactin gene transcription in pituitary GH3 cells stably expressing luciferase under control of 5 kb of the human prolactin promoter. Similar regulation of the endogenous rat prolactin gene by TNF-alpha in GH3 cells was confirmed using real-time PCR. Luminescence microscopy revealed heterogeneous dynamic response patterns of promoter activity in individual cells. In GH3 cells treated with TNF-alpha, Western blot analysis showed rapid inhibitory protein kappaB (IkappaBalpha) degradation and phosphorylation of p65. Confocal microscopy of cells expressing fluorescence-labeled p65 and IkappaBalpha fusion proteins showed transient cytoplasmic-nuclear translocation and subsequent oscillations in p65 localization and confirmed IkappaBalpha degradation. This was associated with increased nuclear factor kappaB (NF-kappaB)-mediated transcription from an NF-kappaB-responsive luciferase reporter construct. Disruption of NF-kappaB signaling by expression of dominant-negative variants of IkappaB kinases or truncated IkappaBalpha abolished TNF-alpha activation of the prolactin promoter, suggesting that this effect was mediated by NF-kappaB. TNF-alpha signaling was found to interact with other endocrine signals to regulate prolactin gene expression and is likely to be a major paracrine modulator of lactotroph function.