The impact of auditory hallucinations on “living well” with dementia: Findings from the IDEAL programme

This is the final version. Available from Wiley via the DOI in this record.data availability statement: IDEAL data were deposited with the UK data archive in April 2020 and will be available to access from April 2023. Details of how the data can be accessed after that date can be found here: http:// reshare.ukdataservice.ac.uk/854293/Objective: To determine whether auditory hallucinations in community-dwelling people with dementia (PwD) living in the community impacted on quality of life (QoL), subjective wellbeing and life satisfaction. Design: Cross-sectional cohort study. Settings and participants: 1251 community-dwelling PwD and caregivers were included in this study. Measures: Neuropsychiatric Inventory Questionnaire completed by caregiver interview. Mean differences between the absence and presence of auditory hallucinations were compared to scores on three validated measures of living well: QoL in Alzheimer's disease scale (QoL-AD), World Health Organization-Five Well-being Index and Satisfaction with Life Scale. Analysis of covariance determined the confounding contributions of cognition via Mini-Mental State Examination, depression via Geriatric Depression Scale-10, caregiver stress via Relative Stress Scale and whether antipsychotic drugs were prescribed. Results: Auditory hallucinations were associated with lower scores for QoL (p < 0.001, η2 = 0.01), wellbeing (p < 0.001, η2 = 0.02) and life satisfaction (p < 0.001, η2 = 0.01). After controlling for background measures, which were potential confounds, the relationship between auditory hallucinations and QoL (p = 0.04, pη2 = 0.01) and wellbeing (p < 0.000, pη2 = 0.02) remained significant but there was no significant association with life satisfaction. Conclusion: Auditory hallucinations are associated with lower QoL and wellbeing in PwD living in the community. This has implications for targeted therapies in PwD with psychotic symptoms.Economic and Social Research Council (ESRC)Alzheimer's Societ

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood

Findings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990–1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers. © 1999 Cancer Research Campaig

Comprehensive Serum Profiling for the Discovery of Epithelial Ovarian Cancer Biomarkers

FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC = 0.933) and CA-125 (AUC = 0.907) were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800). To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912). Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the detection of ovarian cancer

Evaluation of the function and quality of life of patients submitted to girdlestone's resection arthroplasty

OBJECTIVES: To evaluate function and quality of life of patients submitted to Girdlestone's arthroplasty, and to compare outcomes between unilateral Girdlestone's group with the group with contralateral total hip prosthesis. METHODS: Cross-sectional study where 9 patients were evaluated with unilateral Girdlestone's and 3 with Girdlestone's in one hip and contralateral total hip prosthesis. The evaluation consisted in filling in a generic questionnaire on quality of life SF-36 and a specific questionnaire for hip function Harris Hip Score (HHS). The comparison between groups was made by using the Student's t-test and the Fisher's test. RESULTS: The patients of the unilateral Girdlestone's group presented a higher number of SF-36 domains classified as high, although 77.8% of these showed poor results on the HHS. All patients had a leg-length discrepancy and positive Trendelenburg's test, which led to limping gait in 11 of 12 patients evaluated. Of these, only 6 underwent physiotherapy after surgery. CONCLUSION: Girdlestone's postoperative quality of life and function in a Brazilian population still requires further studies, because these outcomes are indicative of study variables' behavior and cannot be regarded as definite.OBJETIVOS: Avaliar a função e a qualidade de vida dos pacientes pós-artroplastia de Girdlestone e comparar os resultados entre os grupos Girdlestone unilateral e o grupo com prótese total de quadril contralateral. MÉTODOS: estudo transversal no qual foram avaliados 9 pacientes com Girdlestone unilateral e 3 com Girdlestone em um quadril e prótese total no quadril contralateral. A avaliação constitui-se em aplicar o questionário genérico de qualidade de vida SF-36 e um questionário funcional específico para o quadril, Harris Hip Score (HHS). A comparação dos grupos foi realizada usando-se o teste t- Student e o teste de Fisher. RESULTADOS: Os pacientes do grupo Girdlestone unilateral apresentaram maior quantidade de domínios do SF-36 classificados como elevados, embora 77,8% destes tenham obtido resultados ruins no HHS. Todos os pacientes apresentaram o teste de Trendelenburg positivo e discrepância de membros, o que levou à marcha claudicante em 11 dos 12 pacientes avaliados. Destes, apenas 6 submeteram-se a fisioterapia pós-operatória. CONCLUSÃO: A qualidade de vida e a função pós-operatória de Girdlestone, na população brasileira, ainda necessita ser mais pesquisada, pois estes resultados são indicações do comportamento das variáveis de estudo e não podem ser consideradas encerradas.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Ortopedia e TraumatologiaUNIFESP-EPM DOTUNIFESP, EPM, Depto. de Ortopedia e TraumatologiaUNIFESP, EPM DOTSciEL

Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified

Role of Caveolae in Cardiac Protection

Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality. The molecular signaling pathways involved in cardiac protection from myocardial ischemia/reperfusion injury are complex. An emerging idea in signal transduction suggests the existence of spatially organized complexes of signaling molecules in lipid-rich microdomains of the plasma membrane known as caveolae. Caveolins—proteins abundant in caveolae—provide a scaffold to organize, traffic, and regulate signaling molecules. Numerous signaling molecules involved in cardiac protection are known to exist within caveolae or interact directly with caveolins. Over the last 4 years, our laboratories have explored the hypothesis that caveolae are vitally important to cardiac protection from myocardial ischemia/reperfusion injury. We have provided evidence that (1) caveolae and the caveolin isoforms 1 and 3 are essential for cardiac protection from myocardial ischemia/reperfusion injury, (2) stimuli that produce preconditioning of cardiac myocytes, including brief periods of ischemia/reperfusion and exposure to volatile anesthetics, alter the number of membrane caveolae, and (3) cardiac myocyte-specific overexpression of caveolin-3 can produce innate cardiac protection from myocardial ischemia/reperfusion injury. The work demonstrates that caveolae and caveolins are critical elements of signaling pathways involved in cardiac protection and suggests that caveolins are unique targets for therapy in patients at risk of myocardial ischemia

Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis

One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates

OpenMS – An open-source software framework for mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry is an essential analytical technique for high-throughput analysis in proteomics and metabolomics. The development of new separation techniques, precise mass analyzers and experimental protocols is a very active field of research. This leads to more complex experimental setups yielding ever increasing amounts of data. Consequently, analysis of the data is currently often the bottleneck for experimental studies. Although software tools for many data analysis tasks are available today, they are often hard to combine with each other or not flexible enough to allow for rapid prototyping of a new analysis workflow.</p> <p>Results</p> <p>We present OpenMS, a software framework for rapid application development in mass spectrometry. OpenMS has been designed to be portable, easy-to-use and robust while offering a rich functionality ranging from basic data structures to sophisticated algorithms for data analysis. This has already been demonstrated in several studies.</p> <p>Conclusion</p> <p>OpenMS is available under the Lesser GNU Public License (LGPL) from the project website at <url>http://www.openms.de</url>.</p