Continuous Time Structural Equation Modeling with R Package ctsem

We introduce ctsem, an R package for continuous time structural equation modeling of panel (N > 1) and time series (N = 1) data, using full information maximum likelihood. Most dynamic models (e.g., cross-lagged panel models) in the social and behavioural sciences are discrete time models. An assumption of discrete time models is that time intervals between measurements are equal, and that all subjects were assessed at the same intervals. Violations of this assumption are often ignored due to the difficulty of accounting for varying time intervals, therefore parameter estimates can be biased and the time course of effects becomes ambiguous. By using stochastic differential equations to estimate an underlying continuous process, continuous time models allow for any pattern of measurement occasions. By interfacing to OpenMx, ctsem combines the flexible specification of structural equation models with the enhanced data gathering opportunities and improved estimation of continuous time models. ctsem can estimate relationships over time for multiple latent processes, measured by multiple noisy indicators with varying time intervals between observations. Within and between effects are estimated simultaneously by modeling both observed covariates and unobserved heterogeneity. Exogenous shocks with different shapes, group differences, higher order diffusion effects and oscillating processes can all be simply modeled. We first introduce and define continuous time models, then show how to specify and estimate a range of continuous time models using ctsem

A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

BACKGROUND: Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. RESULTS: Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G \u3e T; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. CONCLUSIONS: Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy

Effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions: A scoping review

Background In the field of orthotics, the use of three-dimensional (3D) technology as an alternative to the conventional production process of orthoses is growing. Purpose This scoping review aimed to systematically map and summarize studies assessing the effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions, and to identify knowledge gaps. Methods The Cochrane Library, PubMed, EMBASE, CINAHL, Web of Science, IEEE, and PEDro were searched for studies of any type of 3D-printed orthoses for traumatic and chronic hand conditions. Any outcome related to the effectiveness of 3D-printed orthoses was considered. Two reviewers selected eligible studies, charted data on study characteristics by impairment type, and critically appraised the studies, except for case reports/series. Results Seventeen studies were included: Four randomized controlled trials, four uncontrolled trials, four case series and five case reports. Only three studies had a sample size >20. Impairments described were forearm fractures (n = 5), spasticity (n = 5), muscle weakness (n = 4), joint contractures (n = 2) and pain (n = 1). Four poor to fair quality studies on forearm fractures supported the effectiveness of 3D-printed orthoses on hand function, functionality, and satisfaction. One good quality study on spasticity demonstrated the effectiveness of 3D-printed orthoses on hand function. One poor quality pain study reported limited positive effects on satisfaction. Studies on muscle weakness and joint contractures showed no benefits. Conclusion Current literature addressing the effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions consists primarily of small and poor methodological quality studies. There is a need for well-designed controlled trials including patient-related outcomes, production time and cost analyses

Care provided by general practitioners to patients with psychotic disorders: a cohort study

Background: Patients suffering from psychotic disorders have an increased risk of comorbid somatic diseases such as cardiovascular disorders and diabetes mellitus. Doctor-related factors, such as unfamiliarity with these patients, as well as patient-related factors, such as cognitive disturbance and negative symptoms, contribute to suboptimal health care for these patients. General practitioners (GPs) could play a key role in diagnosing and treating this somatic comorbidity as in the Netherlands, almost all residents are registered at a general practice. This study aims to find out whether there are any differences between the levels of health care provided by GPs to patients with psychotic disorders, compared to other types of patients. Methods: A cohort of patients with an ICPC code of psychosis and two matched control groups, one consisting of patients with other mental problems and the other one of patients without any mental problems, were followed over a period of 5 years. Results: Patients with psychotic disorders (N = 734) contacted the GP practice more often than patients in the control groups. These patients, both adults (p = 0.051) and the elderly (p < 0.005), received more home visits from their GPs. In the adult group (16 to 65 years old inclusive), the number of consultations was significantly higher among both psychosis patients and the group of patients with other mental problems (p < 0.0005). The number of telephone consultations was significantly higher in both age categories, adult group (p < 0.0005), and > 65 years old (p = 0.007). With regard to chronic illnesses, elderly psychosis patients had fewer contacts related to cardiovascular diseases or chronic lung diseases. Conclusion: Patients with psychotic disorders contact the GP practice more frequently than other types of patients. Adult psychosis patients with diabetes mellitus, cardiovascular diseases or chronic lung diseases receive the same amount of health care for these diseases as other primary care patients. The finding that older patients with psychotic disorders are diagnosed with cardiovascular diseases and obstructive lung diseases less frequently than other types of elderly patients requires further study

Psychological interventions for adults with bipolar disorder: a systematic review and meta-analysis

Background Psychological interventions may be beneficial for bipolar disorder. Aims Efficacy evaluation of psychological interventions for adults with bipolar disorder. Methods A systematic review of randomised controlled trials.. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE-method. Results We included 55 trials with 6010 participants. Moderate quality evidence associated individual psychological interventions with reduced relapses at post-treatment and follow-up, and collaborative care with a reduction in hospitalisations. . Low quality evidence associated group interventions with fewer depression relapses at post-treatment and follow-up, and family psycho-education with reduced symptoms of depression and mania at post-treatment. Conclusions There is evidence that psychological interventions are effective for people with bipolar disorder. Limits were the very low quality of much of the evidence and therefore inconclusive. Further research should identify the most (cost)-effective interventions for each phase of this disorder

The predictive value of the 'VMS frail older patients' for adverse outcomes in geriatric inpatients

Background/Objective: The Dutch Safety Management system (VMS) screening for frail older patients is used as a predictor for adverse outcomes. We aimed to determine the predictive value of the VMS for adverse outcomes in geriatric inpatients. Design: Retrospective cohort study in geriatric inpatients. Outcomes were institutionalization, readmission and mortality (3- and 12-months). Logistic regression analysis was performed to assess the predictive value of the number of positive VMS domains, a VMS score >= 1, and individual domains for adverse outcomes. Results: We included 477 patients. Median age was 85 years (54-99) and 37% were male. Eighty-seven % scored positive on delirium risk, 57% on fall risk, 39% on malnutrition and 64% on physical impairment. One-hundredthirty-five patients (28%) were institutionalized, 78 patients (16%) were readmitted and mortality rate was 127 (27%) at 3 months and 184 (39%) at one year. The VMS was not predictive for readmission (OR 1.6; 95%-CI 0.213.7) and mortality, (OR 0.6 95%-CI 0.2-2.0 and OR 1.1; 95%-CI 0.3-3.7). For institutionalization, delirium risk (OR 2.2; 95%-CI 1.1-4.4), physical impairment (OR 1.8; 95%-CI 1.1-2.9) and a positive score on all four domains were predictive (OR 12.1 95%-CI-1.4-101.7). Malnutrition was predictive for readmission (OR 1.74; 95%-CI 1.05-2.91) and three-month mortality (OR 1.69; 95%-CI 1.11-2.57), delirium risk for one -year mortality (OR 2.0; 95%-CI 1.0-4.0) . Conclusions: Almost all geriatric inpatients scored positive on at least one domain of the VMS. The number of positive VMS domains had some predictive value for institutionalization. Individual domains were able to predict adverse outcomes

Visualization and Analysis Techniques for Three Dimensional Information Acquired by Confocal Microscopy

Confocal Scanning Laser Microscopy (CSLM) is particularly well suited for the acquisition of 3-dimensional data of microscopic objects. In the CSLM a specific volume in the object is sampled during the imaging process and the result is stored in a digital computer as a three-dimensional memory array. Optimal use of these data requires both the development of effective visual representations as well as analysis methods. In addition to the well known stereoscopic representation method a number of alternatives for various purposes are presented. When rendering in terms of solid-looking or semitransparent objects is required, an algorithm based on a simulated process of excitation and fluorescence is very suitable. Graphic techniques can be used to examine the 3-dimensional shape of surfaces. For (near-)real time applications a representation method should not require extensive previous data-processing or analysis. From the very extensive field of 3-D image analysis two examples are given

Global Ethics and Nanotechnology: A Comparison of the Nanoethics Environments of the EU and China

The following article offers a brief overview of current nanotechnology policy, regulation and ethics in Europe and The People’s Republic of China with the intent of noting (dis)similarities in approach, before focusing on the involvement of the public in science and technology policy (i.e. participatory Technology Assessment). The conclusions of this article are, that (a) in terms of nanosafety as expressed through policy and regulation, China PR and the EU have similar approaches towards, and concerns about, nanotoxicity—the official debate on benefits and risks is not markedly different in the two regions; (b) that there is a similar economic drive behind both regions’ approach to nanodevelopment, the difference being the degree of public concern admitted; and (c) participation in decision-making is fundamentally different in the two regions. Thus in China PR, the focus is on the responsibility of the scientist; in the EU, it is about government accountability to the public. The formulation of a Code of Conduct for scientists in both regions (China PR’s predicted for 2012) reveals both similarity and difference in approach to nanotechnology development. This may change, since individual responsibility alone cannot guide S&T development, and as public participation is increasingly seen globally as integral to governmental decision-making

A Bodyweight-Dependent Allometric Exponent for Scaling Clearance Across the Human Life-Span

Purpose: To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. Methods: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model. Results: Model I adequately described clearance in adults and older children, but overestimated clearance of neonates and underestimated clearance of infants. Use of two different exponents in Model II and Model III showed significantly improved performance, but yielded ambiguities on the boundaries of the two subpopulations. This discontinuity was overcome in Model IV, in which the exponent changed sigmoidally from 1.35 at a hypothetical bodyweight of 0 kg to a value of 0.56 from 10 kg onwards, thereby describing clearance of all individuals best. Conclusions: A model was developed for scaling clearance over the entire human life-span with a single continuous equation, in which the exponent of the bodyweight-based exponential equation varied with bodyweight