A lucky covariance estimator based on cumulative coherence.

The performance of adaptive acoustic localization methodologies depends on the quality of the covariance matrix being inverted. This paper demonstrates a technique to improve covariance estimation using the principles of lucky signal processing and the cumulative coherence. Lucky processing, popularized in astro-photography, is a technique that increases signal quality by selectively keeping only a small fraction from a pool of potential snapshots. Cumulative coherence, a measure of how well a set of vectors is described by its subsets, provides the measure of "data quality" that enables the lucky processing. This approach was applied to covariance estimation on an acoustic array by taking a fixed duration sample of data and creating a dense set of snapshots with higher than usual overlap. From these densely sampled snapshots, the "luckiest" ones were found using cumulative coherence, and the covariance was averaged as normal. Using data from the SWellEX-96 experiment, this new estimator was compared with standard practice. It was found that the lucky covariance estimate was successful at adaptive matched field processing and produced a less ambiguous processor output than the conventional estimator. The lucky covariance estimate had a higher estimated signal-to-noise ratio, especially when the source was at longer ranges from the array.

"I guess you can interpret it in a number of ways like kind of a milder or the mildest form of dementia?": Multi-stakeholder perceptions of cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) has a high prevalence and is a risk factor for dementia. Furthering understanding of MCI has been identified as a public health priority. This research aimed to explore views about the causes of cognitive impairment and identify associations between cognitive impairment, dementia, and normative ageing. METHOD: Semi-structured qualitative interviews were conducted with 22 participants with different stakeholder perspectives on the area of MCI in England, and analysed thematically. RESULTS: Our analysis focuses on two main themes: 1) causes of cognitive impairment, and 2) ageing, dementia, and dying. Most participants viewed cognitive impairment as a transitional state between normative ageing and dementia. Participants expressed their fear of cognitive impairment and dementia, and made clear links between cognitive impairment and dying. Participants also showed an awareness of the links between lifestyle factors and cognitive health. However, linkage between lifestyle and cognition was discussed only when explicitly asked, suggesting that this was not especially salient for participants when considering the causes and risk factors for cognitive impairment. CONCLUSION: The results of this study highlight key areas for future public health initiatives, such as a focus on the multitude of benefits offered by adopting a healthy diet and physical exercise in reducing risk of cognitive impairment.

Overcoming snapshot-deficient measurements with knowledge-aided approaches.

The use of knowledge-aided covariance is considered for processing underwater acoustic array data in snapshot-deficient scenarios. The knowledge-aided formalism is a technique that combines array data with a known covariance to produce an invertible estimate. For underwater acoustics, simulations of ambient noise provide the a priori covariance allowing degraded signals to be processed adaptively in situations where the sample covariance matrix is rank-deficient. The method is demonstrated for matched field processing using the 21 element array event S5 from the SWellEx-96 experiment. With five snapshots, the knowledge-aided approach significantly reduces localization ambiguity compared to the adaptive white noise gain constraint processor.

Detection on a distributed network using information geometry.

A passive detection scheme based on information geometry is tested on underwater acoustic field data acquired through multiple sensors from the Distributed Network Consensus experiment. These detectors use a signal discovery method wherein a target is detected when the statistics of that signal are sufficiently different from those in a broadband background. The signal excess is viewed here as the non-Euclidean distance between two probability distributions interpreted as points in a Riemannian manifold. The SNR is artificially lowered to create a low SNR scenario and it is shown that in spite of this, the geometric detectors perform quite well.

Facilitators and barriers to adaptive implementation of the Meeting Centers Support Program (MCSP) in three European countries; the process evaluation within the MEETINGDEM study.

ABSTRACTBackground:In the MEETINGDEM project, the Meeting Centers Support Program (MCSP) was adaptively implemented and evaluated in three European countries: Italy, Poland, and the United Kingdom. The aim of this study was to investigate overall and country-specific facilitators and barriers to the implementation of MCSP in these European countries. METHODS: A qualitative multiple case study design was used. Based on the theoretical model of adaptive implementation, a checklist was composed of potential facilitators and barriers to the implementation of MCSP. This checklist was administered among stakeholders involved in the implementation of MCSP to trace the experienced facilitators and barriers. Twenty-eight checklists were completed. RESULTS: Main similarities between countries were related to the presence of suitable staff, management, and a project manager, and the fact that the MCSP is attuned to needs and wishes of people with dementia and informal caregivers. Main differences between countries were related to: communication with potential referrers, setting up an inter-organizational collaboration network, receiving support of national organizations, having clear discharge criteria for the MCSP and continuous PR in the region. CONCLUSION: The results of this study provide insight into generic and country specific factors that can influence the implementation of MCSP in different European countries. This study informs further implementation and dissemination of MCSP in Europe and may also serve as an example for the dissemination and implementation of other effective psychosocial support interventions for people with dementia and their informal caregivers across and beyond Europe.

Comparison of the adaptive implementation and evaluation of the Meeting Centers Support Program for people with dementia and their family carers in Europe; study protocol of the MEETINGDEM project.

BACKGROUND: The MEETINGDEM study aims to implement and evaluate an innovative, inclusive, approach to supporting community dwelling people with mild to moderate dementia and their family carers, called the Meeting Centers Support Program (MCSP), in three countries in the European Union (EU): Italy, Poland and United Kingdom. Demonstrated benefits of this person-centered approach, developed in The Netherlands, include high user satisfaction, reduced behavioral and mood problems, delayed admission to residential care, lower levels of caregiving-related stress, higher carer competence, and improved collaboration between care and welfare organizations. METHODS: The project will be carried out over a 36 month period. Project partners in the three countries will utilize, and adapt, strategies and tools developed in the Netherlands. In Phase One (month 1-18) activities will focus on establishing an initiative group of relevant organizations and user representatives in each country, exploring pathways to care and potential facilitators and barriers to implementing the program, and developing country specific implementation plans and materials. In Phase Two (month 19­36) training will be provided to organizations and staff, after which the meeting centers will be established and evaluated for impact on behavior, mood and quality of life of people with dementia and carers, cost-effectiveness, changes in service use, user satisfaction and implementation process. DISCUSSION: An overall evaluation will draw together findings from the three countries to develop recommendations for successful implementation of MCSP across the EU. If the Meeting Centers approach can be widely implemented, this could lead to major improvements in dementia care across Europe and beyond. TRIAL REGISTRATION: The trial was retrospectively registered in May 2016: trial number: NTR5936 .

Not re-inventing the wheel: the adaptive implementation of the meeting centres support programme in four European countries.

OBJECTIVES: The implementation of new health services is a complex process. This study investigated the first phase of the adaptive implementation of the Dutch Meeting Centres Support Programme (MCSP) for people with dementia and their carers in three European countries (Italy, Poland, the UK) within the JPND-MEETINGDEM project. Anticipated and experienced factors influencing the implementation, and the efficacy of the implementation process, were investigated. Findings were compared with previous research in the Netherlands. METHOD: A qualitative multiple case study design was applied. Checklist on anticipated facilitators and barriers to the implementation and semi-structured interview were completed by stakeholders, respectively at the end and at the beginning of the preparation phase. RESULTS: Overall, few differences between countries were founded. Facilitators for all countries were: added value of MCSP matching needs of the target group, evidence of effectiveness of MCSP, enthusiasm of stakeholders. General barriers were: competition with existing care and welfare organizations and scarce funding. Some countries experienced improved collaborations, others had difficulties finding a socially integrated location for MCSP. The step-by-step implementation method proved efficacious. CONCLUSION: These insights into factors influencing the implementation of MCSP in three European countries and the efficacy of the step-by-step preparation may aid further implementation of MCSP in Europe.

Analysis of the mouse mutant Cloth-ears shows a role for the voltage-gated sodium channel Scn8a in peripheral neural hearing loss.

Deafness is the most common sensory disorder in humans and the aetiology of genetic deafness is complex. Mouse mutants have been crucial in identifying genes involved in hearing. However, many deafness genes remain unidentified. Using N-ethyl N-nitrosourea (ENU) mutagenesis to generate new mouse models of deafness, we identified a novel semi-dominant mouse mutant, Cloth-ears (Clth). Cloth-ears mice show reduced acoustic startle response and mild hearing loss from approximately 30 days old. Auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) analyses indicate that the peripheral neural auditory pathway is impaired in Cloth-ears mice, but that cochlear function is normal. In addition, both Clth/Clth and Clth/+ mice display paroxysmal tremor episodes with behavioural arrest. Clth/Clth mice also show a milder continuous tremor during movement and rest. Longitudinal phenotypic analysis showed that Clth/+ and Clth/Clth mice also have complex defects in behaviour, growth, neurological and motor function. Positional cloning of Cloth-ears identified a point mutation in the neuronal voltage-gated sodium channel alpha-subunit gene, Scn8a, causing an aspartic acid to valine (D981V) change six amino acids downstream of the sixth transmembrane segment of the second domain (D2S6). Complementation testing with a known Scn8a mouse mutant confirmed that this mutation is responsible for the Cloth-ears phenotype. Our findings suggest a novel role for Scn8a in peripheral neural hearing loss and paroxysmal motor dysfunction.

A preliminary study of simple voice assessment in a routine clinical setting to predict vocal cord paralysis after thyroid or parathyroid surgery.

OBJECTIVE: To determine if a simple assessment of vocal cord function performed in a routine clinical setting can predict vocal cord paralysis on laryngoscopy in patients following thyroid or parathyroid surgery. METHOD: Prospective observational cohort study of patients undergoing thyroid or parathyroid surgery. Vocal cord function was assessed in terms of an abnormality of voice or cough reported by the patient or detected by the examiner. Laryngoscopy was performed by indirect mirror examination or fibreoptic nasopharyngolaryngoscopy. Examiners included otolaryngology consultants, registrars, senior house officers and a general practitioner with a special interest in otolaryngology. The patient was often examined by a different clinician before and after surgery. RESULTS: Eighty-six patients participated in the study between August 2003 and July 2004. Eleven had a change in their voice postoperatively and one patient had difficulty coughing. Six of these patients had a vocal cord paralysis. A further five apparently asymptomatic patients had a vocal cord paralysis. The positive predictive value of voice assessment for vocal cord paralysis was 55%. CONCLUSION: In a routine clinical setting where the assessment of vocal cord function is often reported by different clinicians of varying experience at each patient attendance, the assessment of a patient's voice following thyroid or parathyroid surgery is not adequately predictive of vocal cord paralysis on indirect laryngoscopy or fibreoptic nasopharyngolaryngoscopy. Further study is required to determine reasons for this.

Descending necrotising mediastinitis: a safe treatment algorithm.

Descending necrotising mediastinitis can complicate oropharyngeal infection and has a high associated mortality. We present three cases treated in our department and propose a treatment algorithm based on our experience and literature review. The primary oropharyngeal infection was peritonsillar abscess in two cases and odontogenic abscess in one. Two patients underwent cervicotomy and later thoracotomy. The third underwent cervicotomy with transcervical mediastinal drainage and later required pericardial drainage via a subxiphoid incision. All recovered fully and were discharged within 6 weeks. To enable successful treatment, diagnosis needs to be prompt and surgical drainage adequate. Thoracic management of the chest is essential.

Soft tissue myoepithelioma: a case report.

Myoepitheliomas are tumours composed predominantly or exclusively of myoepithelial cells. They are well described, especially within the salivary gland, but their occurrence in soft tissues is less well known and this often results in diagnostic problems. We report a case involving the deep soft tissues of the lower neck behind the clavicle. Grossly, the tumour was well circumscribed with solid and cystic areas. Histology showed a richly vascularised tumour composed of bland round, ovoid or spindle-shaped cells. Various growth patterns were present including solid, nested, microcystic and trabecular arrangements. In some areas there was an alveolar pattern with tumour cells lining fibrous septae. Immunohistochemistry showed diffuse strong positivity for S100 protein, calponin, vimentin and glial fibrillary acidic protein and focal positivity for epithelial membrane antigen, 34betaE12 and AE1/AE3, in keeping with myoepithelial differentiation. Electron microscopy revealed tumour cells surrounded by basal lamina with subplasmalemmal densities and containing cytoplasmic myofilaments. This case report highlights the rare occurrence of myoepitheliomas in deep soft tissues. Pathologists should be aware of this and should consider a myoepithelioma in the differential diagnosis of a soft tissue spindle cell neoplasm.

Pharyngo-laryngo-oesophagectomy and gastric pull-up for post-cricoid and cervical oesophageal squamous cell carcinoma.

Pharyngo-laryngo-oesophagectomy and gastric pull-up (PLOGP) is a complex and relatively uncommon procedure. The aim of this study is to analyse the results of PLOGP in patients with post-cricoid and cervical oesophageal squamous cell carcinomas. This study was a retrospective review of 26 patients (11 males + 15 females, mean age 63.5 years) who underwent PLOGP from 1988 to 1997. Eighteen (69 per cent) patients were staged as T(3) and eight (31 per cent) T(4). Eighteen (69 per cent) patients had N(0), seven (27 per cent) N(1) and one (four per cent) N(2) disease. Multiple primary tumours were recorded in three (11.5 per cent) patients. Four (15 per cent) patients had pre-operative radiotherapy with poor response and two (eight per cent) required emergency tracheotomy prior to surgery. Feeding jejunostomy was performed on 19 (73 per cent) and neck lymph node dissection in eight (31 per cent) patients. The mean duration of surgery was five hours (range 3.5 to 7.5) with a mean blood loss of 840 ml (range 160 to 1800), a mean stay in ICU of 4.2 days and hospital stay ranged from nine to 84 days (mean 34). Three (11.5 per cent) patients died (pneumonia - one, congestive heart failure - one, pulmonary embolus - one) in the early post-operative period. Eight (31 per cent) patients remain alive from 30 to 136 months (mean 58 months). Two (eight per cent) patients died with no evidence of disease. Thirteen (50 per cent) patients died of their disease between two to 51 months (mean 17.3 months) post-operatively. Kaplan-Meier survival estimates for one year was 65 per cent, for three years 35 per cent and for five years 26 per cent (see Figure 1). Median survival in the whole series was 18 months. Post-operative speech was with an electrolarynx in 16 (62 per cent). One patient (four per cent) used gastric speech and one patient (four per cent) used a Blom-Singer valve effectively. Five (19 per cent) patients had no speech post-operatively. All patients maintained oral feeding. Gastric transposition constitutes a safe and reliable method of restoring the continuity of the upper digestive tract following pharyngo-laryngo-oesophagectomy.

Synovial sarcoma in the retropharyngeal space.

Synovial sarcoma is an aggressive mesenchymal tumour, rarely occurring in the head and neck. Management guidelines are by extrapolation of management of sarcomas in the extremities. We present a case involving the retropharyngeal space in a 20-year-old male. Analysis of more data on head and neck synovial sarcoma is necessary to make meaningful management recommendations.

Metastatic breast carcinoma in the parapharyngeal space.

The parapharyngeal space is a complex anatomical area, which can give rise to a variety of both primary and metastatic neoplasms. We present an unusual case of metastatic adenocarcinoma of the breast, masquerading as a deep lobe parotid neoplasm, 15 years after the primary presentation. Metastatic breast carcinoma has been previously reported at other sites in the head and neck but this is the first report of metastases in the parapharyngeal space with an oropharyngeal presentation.

A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.

As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.

Cloning and functional expression of the mouse epithelial sodium channel.

The epithelial sodium channel (ENaC) plays a major role in the transepithelial reabsorption of sodium in the renal cortical collecting duct, distal colon, and lung. ENaCs are formed by three structurally related subunits, termed alpha-, beta-, and gammaENaC. We previously isolated and sequenced cDNAs encoding a portion of mouse alpha-, beta-, and gammaENaC (alpha-, beta-, and gammamENaC). These cDNAs were used to screen an oligo-dT-primed mouse kidney cDNA library. Full-length betamENaC and partial-length alpha- and gammamENaC clones were isolated. Full-length alpha- and gammamENaC cDNAs were subsequently obtained by 5'-rapid amplification of cDNA ends (5'-RACE) PCR. Injection of mouse alpha-, beta-, and gammaENaC cRNAs into Xenopus oocytes led to expression of amiloride-sensitive (K(i) = 103 nM), Na(+)-selective currents with a single-channel conductance of 4.7 pS. Northern blots revealed that alpha-, beta-, and gammamENaC were expressed in lung and kidney. Interestingly, alphamENaC was detected in liver, although transcript sizes of 9.8 kb and 3.1 kb differed in size from the 3.2-kb message observed in other tissues. A partial cDNA clone was isolated from mouse liver by 5'-RACE PCR. Its sequence was found to be nearly identical to alphamENaC. To begin to identify regions within alphamENaC that might be important in assembly of the native heteroligomeric channel, a series of functional experiments were performed using a construct of alphamENaC encoding the predicted cytoplasmic NH(2) terminus. Coinjection of wild-type alpha-, beta-, and gammamENaC with the intracellular NH(2) terminus of alphamENaC abolished amiloride-sensitive currents in Xenopus oocytes, suggesting that the NH(2) terminus of alphamENaC is involved in subunit assembly, and when present in a 10-fold excess, plays a dominant negative role in functional ENaC expression.

Cloning of a major human retinal pigment epithelial lysosomal aspartic protease and mapping its transcriptional start sites.

PURPOSE: It has been proposed that the major proteolytic enzyme responsible for the proteolysis of photoreceptor outer segments is an aspartic protease similar or identical to cathepsin D. The aim of this study was to determine if the major retinal pigment epithelial (RPE) aspartic protease was cathepsin D, to study its distribution and investigate its transcription start sites (TSS). METHODS: An RPE cDNA library was screened at low stringency for the presence of aspartic proteases. DNA sequencing was used to analyze the identified clones. The expression of cathepsin D mRNA was analyzed by Northern blot while immunohistochemistry was used to demonstrate cathepsin D related immunoreactivity in an eye section. RNase protection assay was used to map the Cathepsin D TSS in RPE cells. RESULTS: The aspartic protease identified in the RPE cDNA library was identical to the DNA sequence of cathepsin D found in other tissues. Northern blot analysis of a wide range of cell types showed that the highest level of cathepsin D mRNA expression was found in RPE cells which was similar only to cathepsin D expression in MCF7 breast cancer cells. Immunohistochemical staining of a human retina confirmed the inherent nature of high cathepsin D expression in RPE cells. An RNase protection assay demonstrated two major cathepsin D TSS in RPE cells. One of them was identical to the TSS responsible for the constitutive expression of cathepsin D and the other, a TATA box-controlled TSS, was identical to a TSS found in MCF7 cells. Cathepsin D expression was not enhanced by the phagocytosis and digestion of rod outer segments (ROS) and ROS phagocytosis did not induce the use of other cathepsin D TSS in the RPE cells. CONCLUSION: The major aspartic protease identified in RPE cells was cathepsin D. In addition, it was demonstrated that the high level of cathepsin D expression in RPE cells is the intrinsic nature of these cells and that it is linked to a TATA box-controlled TSS. This TSS has previously been described as an estrogen regulated TSS and further studies are required to identify the RPE-specific inducer or indirect factors that may be responsible for the enhanced expression of cathepsin D in the RPE cells.

Staff and patient feedback in mental health services for older people.

OBJECTIVES: To compare the views of patients and staff on the quality of care provided on a psychogeriatric assessment ward over a five year period. To describe the quality improvements which were made as a result of their respective comments. DESIGN: Structured interviews were conducted with both patients and staff to obtain qualitative feedback and suggestions for improvement. An analysis of the percentage of positive and negative comments made by both patients and staff was used to compare the levels of satisfaction on a variety of aspects of the service provided. SETTING: Psychogeriatric inpatient assessment ward. SUBJECTS: 75 patients and 85 staff interviews were conducted. MAIN MEASURES: Structured interviews covering various aspects of service quality. RESULTS: Staff and patients picked up on different aspects of service quality as important. Quality improvements which arose from the interviews were clearly different. Generally patients were more positive about the physical environment and standards of professional care than staff, but less positive about issues of privacy, social interaction, and empowerment. CONCLUSIONS: The perspectives of patients and staff in this area are not interchangeable. Both series of interviews led to several positive changes in the quality of care. Interviews with staff seem to have been valuable in a low morale situation. A structured interview format provided patients with an opportunity to feedback openly and led to changes in service quality which would not otherwise have occurred.