Methods for the transfer function design of multiple narrow-band bandpass sigma-delta modulators

This paper presents the design analysis of novel tunable narrow-band bandpass sigma-delta modulators, which can achieve concurrent multiple noise-shaping for multi-tone input signals. Four different design methodologies based on the noise transfer functions of comb filters, slink filters, multi-notch filters and fractional delay comb filters are applied for the design of these multiple-band sigma-delta modulators. The latter approach utilises conventional comb filters in conjunction with FIR, or allpass IIR fractional delay filters, to deliver the desired nulls for the quantisation noise transfer function. Detailed simulation results show that FIR fractional delay comb filter-based sigma-delta modulators tune accurately to most centre frequencies, but suffer from degraded resolution at frequencies close to Nyquist. However, superior accuracies are obtained from their allpass IIR fractional delay counterpart at the expense of a slight shift in noise-shaping bands at very high frequencies. The merits and drawbacks of each technique for the various sigma-delta topologies are assessed in terms of in-band signal-to-noise ratios, accuracy of tunability and coefficient complexity for ease of implementation.

Patterns of cortisol and DHEA secretion and relationships with attachment style and psychosocial variables in female adolescents: a developmental psychopathology approach

This programme of research used a developmental psychopathology approach to investigate females across the adolescent period. A two-sided story is presented; first, a study of neuroendocrine and psychosocial parameters in a group of healthy female adolescents (N = 63), followed by a parallel study of female adolescents with anorexia nervosa (AN) (N = 8). A biopsychosocial, multi-method measurement approach was taken, which utilised self-report, interview and hypothalamic-pituitary-adrenocortical (HPA) axis measures. Saliva samples for the measurement of cortisol and DHEA were collected using the best-recommended methodology: multiple samples over the day, strict reference to time of awakening, and two consecutive sampling weekdays. The research was adolescent-orientated: specifically, by using creative and ageappropriate strategies to ensure participant adherence to protocol, as well as more generally by adopting various procedures to facilitate engagement with the research process. In the healthy females mean (± SD) age 13.9 (± 2.7) years, cortisol and DHEA secretion exhibited typical adult-like diurnal patterns. Developmental markers of chronological age, menarche status and body mass index (BMI) had differential associations with cortisol and DHEA secretory activity. The pattern of the cortisol awakening response (CAR) was sensitive to whether participants had experienced first menses, but not to chronological age or BMI. Those who were post-menarche generally reached their peak point of cortisol secretion at 45 minutes post-awakening, in contrast to the pre-menarche group who were more evenly spread. Subsequent daytime cortisol levels were also higher in post-menarche females, and this effect was also noted for increasing age and BMI. Both morning and evening DHEA were positively associated with developmental markers. None of the situational or self-report psychosocial variables that were measured modulated any of the key findings regarding cortisol and DHEA secretion. The healthy group of girls were within age-appropriate norms for all the self-report measures used, however just under half of this group were insecurely attached (as assessed by interview). Only attachment style was associated with neuroendocrine parameters. In particular, those with an anxious insecure style exhibited a higher awakening sample (levels were 7.16 nmol/l, 10.40 nmol/l and 7.93 nmol/l for secure, anxious and avoidant groups, respectively) and a flatter CAR (mean increases over the awakening period were 6.38 nmol/l, 2.32 nmol/l and 8.61 nmol/l for secure, anxious and avoidant groups, respectively). The afore-mentioned pattern is similar to that consistently associated with psychological disorder in adults, and so this may be a pre-clinical vulnerability factor for subsequent mental health problems. A group of females with AN, mean (± SD) age 15.1 (± 1.6) years, were recruited from a specialist residential clinic and compared to the above group of healthy control (HC) female adolescents. A general picture of cortisol and DHEA hypersecretion was revealed in those with AN. The mean (± SD) change exhibited in cortisol levels over the 30 minute post-awakening period was 7.05 nmol/l (± 5.99) and 8.33 nmol/l (± 6.41) for HC and AN groups, respectively. The mean (± SD) evening cortisol level for the HC girls was 1.95 nmol/l (± 2.11), in comparison to 6.42 nmol/l (± 11.10) for the AN group. Mean (± SD) morning DHEA concentrations were 1.47 nmol/l (± 0.85) and 2.25 nmol/l (± 0.88) for HC and AN groups, respectively. The HC group’s mean (± SD) concentration of 12 hour DHEA was 0.55 nmol/l (± 0.46) and the AN group’s mean level was 0.89 nmol/l (± 0.90). This adrenal steroid hypersecretion evidenced by the AN group was not associated with BMI or eating disorder symptomatology. Insecure attachment characterised by fearfulness and anger was most apparent; a style which was unparalleled in the healthy group of female adolescents. The causal directions of the AN group findings remain unclear. Examining some of the participants with AN as case studies one year post-discharge from the clinic illustrated that for one participant who was recovered, in terms of returning to ordinary school life and no longer exhibiting clinical levels of eating disorder symptomatology, her CARs were no longer inconsistent over sampling days and her DHEA levels were also now generally comparable to the healthy control group. For another participant who had not recovered from her AN one year later, the profile of her CAR continued to be inconsistent over sampling days and her DHEA concentrations over the diurnal period were significantly higher in comparison to the healthy control group. In its entirety, this work’s unique contribution lies in its consideration of methodological and developmental issues specifically pertaining to adolescents. Findings also contribute to knowledge of AN and understanding of vulnerability factors, and how these may be used to develop interventions dedicated to improving adolescent health.

Increasing the variability of centre frequency locations in multiple-band sigma-delta modulators via the use of fractional delay filters

This paper presents the design analysis of novel tunable narrow-band bandpass sigma-delta modulators, that can achieve concurrent multiple noise-shaping for multi-tone input signals. This approach utilises conventional comb filters in conjunction with FIR, or allpass IIR fractional delay filters, to deliver the desired nulls for the quantisation noise transfer function. Detailed simulation results show that FIR fractional delay comb filter based sigma-delta modulators tune accurately to most centre frequencies, but suffer from degraded resolution at frequencies close to Nyquist. However, superior accuracies are obtained from their allpass IIR fractional delay counterpart at the expense of a slight shift in noise-shaping bands at very high frequencies.

Bevacizumab in NF2-related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation

Background: NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality. Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. Methods: Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. Results: Sixty-one patients (59% male), median age 25 years (range, 10–57), were reviewed. Median follow-up was 23 months (range, 3–53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. Conclusion: Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.