Management of insomnia in sleep disordered breathing

Both obstructive sleep apnoea (OSA) and chronic insomnia disorder are highly prevalent in the general population. Whilst both disorders may occur together by mere coincidence, it appears that they share clinical features and that they may aggravate each other as a result of reciprocally adverse pathogenetic mechanisms. Comorbidity between chronic insomnia disorder and OSA is a clinically relevant condition that may confront practitioners with serious diagnostic and therapeutic challenges. Current data, while still scarce, advocate an integrated and multidisciplinary approach that seems superior over the isolated treatment of each sleep disorder alone

Analyzing the contributions of a government-commissioned research project: a case study

Background: It often remains unclear to investigators how their research contributes to the work of the commissioner. We initiated the 'Risk Model' case study to gain insight into how a Dutch National Institute for Public Health and the Environment (RIVM) project and its knowledge products contribute to the commissioner's work, the commissioner being the Health Care Inspectorate. We aimed to identify the alignment efforts that influenced the research project contributions. Based on the literature, we expected interaction between investigators and key users to be the most determining factor for the contributions of a research project.Methods: In this qualitative case study, we analyzed the alignment efforts and contributions in the Risk Model project by means of document analysis and interviews according to the evaluation method Contribution Mapping. Furthermore, a map of the research process was drafted and a feedback session was organized. After the feedback session with stakeholders discussing the findings, we completed the case study report.Results: Both organizations had divergent views on the ownership of the research product and the relationship between RIVM and the Inspectorate, which resulted in different expectations. The RIVM considered the use of the risk models to be problematic, but the inspectors had a positive opinion about its contributions. Investigators, inspectors, and managers were not aware of these remarkably different perceptions. In this research project, we identified six relevant categories of both horizontal alignment efforts (between investigators and key users) as well as vertical alignment efforts (within own organization) that influenced the contributions to the Inspectorate's work.Conclusions: Relevant alignment efforts influencing the contributions of the project became manifest at three levels: the first level directly relates to the project, the second to the organizational environment, and the third to the formal and historical relationship between the organizations. Both external and internal alignments influence the contributions of a research project. Based on the findings, we recommend that research institutes invest in a reflective attitude towards the social aspects of research projects at all levels of the organization and develop alignment strategies to enhance the contributions of research. © 2014 Hegger et al.; licensee BioMed Central Ltd

Traffic-related pollution and asthma prevalence in children. Quantification of associations with nitrogen dioxide.

Ambient nitrogen dioxide is a widely available measure of traffic-related air pollution and is inconsistently associated with the prevalence of asthma symptoms in children. The use of this relationship to evaluate the health impact of policies affecting traffic management and traffic emissions is limited by the lack of a concentration-response function based on systematic review and meta-analysis of relevant studies. Using systematic methods, we identified papers containing quantitative estimates for nitrogen dioxide and the 12 month period prevalence of asthma symptoms in children in which the exposure contrast was within-community and dominated by traffic pollution. One estimate was selected from each study according to an a priori algorithm. Odds ratios were standardised to 10 μg/m(3) and summary estimates were obtained using random- and fixed-effects estimates. Eighteen studies were identified. Concentrations of nitrogen dioxide were estimated for the home address (12) and/or school (8) using a range of methods; land use regression (6), study monitors (6), dispersion modelling (4) and interpolation (2). Fourteen studies showed positive associations but only two associations were statistically significant at the 5 % level. There was moderate heterogeneity (I(2) = 32.8 %) and the random-effects estimate for the odds ratio was 1.06 (95 % CI 1.00 to 1.11). There was no evidence of small study bias. Individual studies tended to have only weak positive associations between nitrogen dioxide and asthma prevalence but the summary estimate bordered on statistical significance at the 5 % level. Although small, the potential impact on asthma prevalence could be considerable because of the high level of baseline prevalence in many cities. Whether the association is causal or indicates the effects of a correlated pollutant or other confounders, the estimate obtained by the meta-analysis would be appropriate for estimating impacts of traffic pollution on asthma prevalence

Arm hand skilled performance in cerebral palsy: activity preferences and their movement components

Background: Assessment of arm-hand use is very important in children with cerebral palsy (CP) who encounter arm-hand problems. To determine validity and reliability of new instruments to assess actual performance, a set of standardized test situations including activities of daily living (ADL) is required. This study gives information with which such a set for upper extremity skill research may be fine-tuned, relative to a specific research question. Aim of this study is to a) identify upper extremity related ADL children with CP want to improve on, b) determine the 10 most preferred goals of children with CP, and c) identify movement components of all goals identified. Method: The Canadian Occupational Performance Measure was used to identify upper extremity-related ADL preferences (goals) of 53 children with CP encountering arm-hand problems (mean age 9 +/- 4.5 year). Goals were ranked based on importance attributed to each goal and the number of times a goal was mentioned, resulting in a gross list with goals. Additionally, two studies were performed, i.e. study A to determine the 10 most preferred goals for 3 age groups (2.5-5 years; 6-11 years, 12-19 years), based on the total preference score, and study B to identify movement components, like reaching and grasping, of all goals identified for both the leading and the assisting arm-hand. Results: Seventy-two goals were identified. The 10 most preferred goals differed with age, changing from dressing and leisure-related goals in the youngest children to goals regarding personal care and eating for children aged 6-11 years. The oldest children preferred goals regarding eating, personal care and computer use. The movement components 'positioning', 'reach', 'grasp', and 'hold' were present in most tasks. 'Manipulating' was more important for the leading arm-hand, whereas 'fixating' was more important for the assisting arm-hand. Conclusion: This study gave insight into the preferences regarding ADL children with CP would like to improve on, and the movement components characterizing these activities. This information can be used to create a set of standardized test situations, which can be used to assess the validity and reliability of new measurement instruments to gauge actual arm-hand skilled performance

Parameter selection for peak alignment in chromatographic sample profiling: objective quality indicators and use of control samples

In chromatographic profiling applications, peak alignment is often essential as most chromatographic systems exhibit small peak shifts over time. When using currently available alignment algorithms, there are several parameters that determine the outcome of the alignment process. Selecting the optimum set of parameters, however, is not straightforward, and the quality of an alignment result is at least partly determined by subjective decisions. Here, we demonstrate a new strategy to objectively determine the quality of an alignment result. This strategy makes use of a set of control samples that are analysed both spiked and non-spiked. With this set, not only the system and the method can be checked but also the quality of the peak alignment can be evaluated. The developed strategy was tested on a representative metabolomics data set using three software packages, namely Markerlynx™, MZmine and MetAlign. The results indicate that the method was able to assess and define the quality of an alignment process without any subjective interference of the analyst, making the method a valuable contribution to the data handling process of chromatography-based metabolomics data

On the Perturbative Stability of Quantum Field Theories in de Sitter Space

We use a field theoretic generalization of the Wigner-Weisskopf method to study the stability of the Bunch-Davies vacuum state for a massless, conformally coupled interacting test field in de Sitter space. We find that in $\lambda \phi^4$ theory the vacuum does {\em not} decay, while in non-conformally invariant models, the vacuum decays as a consequence of a vacuum wave function renormalization that depends \emph{singularly} on (conformal) time and is proportional to the spatial volume. In a particular regularization scheme the vacuum wave function renormalization is the same as in Minkowski spacetime, but in terms of the \emph{physical volume}, which leads to an interpretation of the decay. A simple example of the impact of vacuum decay upon a non-gaussian correlation is discussed. Single particle excitations also decay into two particle states, leading to particle production that hastens the exiting of modes from the de Sitter horizon resulting in the production of \emph{entangled superhorizon pairs} with a population consistent with unitary evolution. We find a non-perturbative, self-consistent "screening" mechanism that shuts off vacuum decay asymptotically, leading to a stationary vacuum state in a manner not unlike the approach to a fixed point in the space of states.Comment: 36 pages, 4 figures. Version to appear in JHEP, more explanation

Discrimination of grade 2 and 3 cervical intraepithelial neoplasia by means of analysis of water soluble proteins recovered from cervical biopsies

<p>Abstract</p> <p>Background</p> <p>Cervical intraepithelial neoplasia (CIN) grades 2 and 3 are usually grouped and treated in the same way as "high grade", in spite of their different risk to cancer progression and spontaneous regression rates. CIN2-3 is usually diagnosed in formaldehyde-fixed paraffin embedded (FFPE) punch biopsies. This procedure virtually eliminates the availability of water-soluble proteins which could have diagnostic and prognostic value.</p> <p>Aim</p> <p>To investigate whether a water-soluble protein-saving biopsy processing method followed by a proteomic analysis of supernatant samples using LC-MS/MS (LTQ Orbitrap) can be used to distinguish between CIN2 and CIN3.</p> <p>Methods</p> <p>Fresh cervical punch biopsies from 20 women were incubated in RPMI1640 medium for 24 hours at 4°C for protein extraction and subsequently subjected to standard FFPE processing. P16 and Ki67-supported histologic consensus review CIN grade (CIN2, n = 10, CIN3, n = 10) was assessed by independent gynecological pathologists. The biopsy supernatants were depleted of 7 high abundance proteins prior to uni-dimensional LC-MS/MS analysis for protein identifications.</p> <p>Results</p> <p>The age of the patients ranged from 25-40 years (median 29.7), and mean protein concentration was 0.81 mg/ml (range 0.55 - 1.14). After application of multistep identification criteria, 114 proteins were identified, including proteins like vimentin, actin, transthyretin, apolipoprotein A-1, Heat Shock protein beta 1, vitamin D binding protein and different cytokeratins. The identified proteins are annotated to metabolic processes (36%), signal transduction (27%), cell cycle processes (15%) and trafficking/transport (9%). Using binary logistic regression, Cytokeratin 2 was found to have the strongest independent discriminatory power resulting in 90% overall correct classification.</p> <p>Conclusions</p> <p>114 proteins were identified in supernatants from fresh cervical biopsies and many differed between CIN2 and 3. Cytokeratin 2 is the strongest discriminator with 90% overall correct classifications.</p

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

Chronic non-specific abdominal complaints in general practice: a prospective study on management, patient health status and course of complaints

BACKGROUND: While in general practice chronic non-specific abdominal complaints are common, there is insufficient data on the clinical course and the management of these complaints. Aim of this study was to present a primary care based profile of these chronic complaints including health care involvement, health status and clinical course. METHODS: Thirty general practitioners (GPs) and patients from their practices participated in a prospective follow-up study. All patients and GPs were asked to complete questionnaires at baseline and at 6, 12 and 18 months of follow-up. The GPs provided information on diagnostic and therapeutic management and on referral concerning 619 patients with chronic non-specific abdominal complaints, while 291 patients provided information about health status and clinical course of the complaints. RESULTS: When asked after 18 months of follow-up, 51,7% of the patients reported an equal or worsened severity of complaints. General health perception was impaired and patients had high scores on SCL-anxiety and SCL-depression scales. Diagnostic tests other than physical examination and laboratory tests were not frequently used. Medication was the most frequent type of treatment. The persistence of chronic non-specific abdominal complaints was quite stable. CONCLUSION: Once non-specific chronic abdominal complaints have become labelled as chronic by the attending physician, little improvement can be expected. The impact on patients' physiological and psychological well-being is large. GPs use a variety of diagnostic and therapeutic strategies. Research into the evidence base of currently applied management strategies is recommended

Akathisia and Newer Second‐Generation Antipsychotic Drugs: A Review of Current Evidence

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155998/1/phar2404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155998/2/phar2404.pd