Design of near allpass strictly stable minimal phase real valued rational IIR filters

In this brief, a near-allpass strictly stable minimal-phase real-valued rational infinite-impulse response filter is designed so that the maximum absolute phase error is minimized subject to a specification on the maximum absolute allpass error. This problem is actually a minimax nonsmooth optimization problem subject to both linear and quadratic functional inequality constraints. To solve this problem, the nonsmooth cost function is first approximated by a smooth function, and then our previous proposed method is employed for solving the problem. Computer numerical simulation result shows that the designed filter satisfies all functional inequality constraints and achieves a small maximum absolute phase error

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

Genetic variants, phenotypic spectrum and breast cancer risk associated with germline mutations in PALB2: identifying female PALB2 mutation carriers at time of diagnosis

© 2013 Dr. Zhi Ling (Joyce) TeoPALB2 is a breast cancer susceptibility gene which encodes a protein that is fundamental to the maintenance of genome stability via the homologous recombination DNA repair pathway. Mutations in PALB2 are rare, varying from 0.1% to 1.5% depending upon the population, but there are substantial breast cancer risks associated with at least some of the mutations in PALB2. Risk-reducing clinical screening strategies and prophylactic treatments are currently available for women who are at high risk of breast cancer. There are also potential therapies that target DNA repair dysfunction which have been shown to be effective in PALB2-deficient cells. Therefore, it is of high importance that female carriers of high-risk PALB2 mutations are identified so that these clinical benefits can be made available to them. Due to the rarity of PALB2 mutations, using current clinical screening platforms, it would be optimal to enrich for women most likely to be mutation carriers prior to genetic testing. The main objectives of the research described in this thesis were to determine the prevalence and penetrance associated with PALB2 mutations in the Australian population and to identify tumour morphological features associated with PALB2 mutation status that could facilitate the identification of female carriers of pathogenic germline mutations of PALB2 at the time of breast cancer diagnosis. A nonsense mutation, PALB2 c.3113G>A, was identified through mutation screening of the coding regions of PALB2 in 0.3% of women that were recruited via population-based sampling of young women with breast cancer without selection for their family history of the disease. Modified segregation analysis was used to estimate that this germline mutation was associated with 91% cumulative risk of breast cancer to the age of 70 years (95% confidence interval = 44-100). Further mutation screening was performed to assess the prevalence of PALB2 mutations in high-risk breast and/or ovarian cancer families attending Familial Cancer Clinics in Australasia. Four PALB2 mutations, including PALB2 c.3113G>A, were found to contribute to breast cancer risk in approximately 1.5% of these families. Tumour morphologies of 28 invasive breast cancers arising in women who carry a germline loss-of-function PALB2 mutation were compared to breast tumours of a population-based sample of 828 non-carriers. Minimal sclerosis was identified as a key morphological feature that not only distinguishes carriers of PALB2 mutations from non-carriers of high-risk mutations in BRCA1, BRCA2, ATM, TP53 and PALB2 (p < 0.001) but also distinguishes PALB2 mutation carriers from BRCA1 (p = 0.05) and BRCA2 (p = 0.04) mutation carriers. In addition to the main objectives of this research, we have used massively parallel sequencing to interrogate the exonic sequences of four individuals of a multiple-case family that segregates PALB2 c.3113G>A to identify other genetic risk factors that may be segregating through this family. We have identified a genetic variant, XAF1 c.343G>T, that has the potential of being involved in breast cancer predisposition or in breast cancer progression. This study brings together several lines of evidence to indicate that genetic information about PALB2 is relevant to breast cancer clinical genetics services. It has identified a PALB2 germline mutation that is associated with high breast cancer risk. This supports the reports of recent population-based studies of breast cancer that at least some PALB2 mutations are associated with breast cancer risks comparable to that of the average pathogenic mutation in BRCA2: 45% (95% confidence interval = 31%-56%). It has also identified a tumour morphological feature, predictive of PALB2 mutation status, which could be used to facilitate the identification of carriers of PALB2 mutations at the time of diagnosis, irrespective of family history. The important information generated by this study could expedite PALB2 mutation testing and translation of genetic information about PALB2 mutation status into clinical practice in Australia

Comparative study of chairman's statements between Singapore and UK companies

This study is a replication of the Clatworthy and Jones (2003) study in the Singapore context to examine the presence of impression management in the chairman’s statements of annual reports. Content analysis was performed on selected chairman’s statements of Singapore listed companies

Relevance of tumor-infiltrating lymphocytes in breast cancer

While breast cancer has not been considered a cancer amenable to immunotherapeutic approaches, recent studies have demonstrated evidence of significant immune cell infiltration via tumor-infiltrating lymphocytes in a subset of patient tumors. In this review we present the current evidence highlighting the clinical relevance and utility of tumor-infiltrating lymphocytes in breast cancer. Retrospective and prospective studies have shown that the presence of tumor-infiltrating lymphocytes is a prognostic marker for higher responses to neoadjuvant chemotherapy and better survival, particularly in triple negative and HER2-positive early breast cancer. Further work is required to determine the immune subsets important in this response and to discover ways of encouraging immune infiltrate in tumor-infiltrating lymphocytes-negative patients

Ethnic differences in the incidence of pterygium in a multi-ethnic Asian population: the Singapore Epidemiology of Eye Diseases Study

10.1038/s41598-020-79920-9Scientific Reports11150