Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of Quality Adjusted Life Years in people with common mental health problems

Multi-criteria Resource Allocation in Modal Hard Real-Time Systems

In this paper, a novel resource allocation approach dedicated to hard real-time systems with distinctive operational modes is proposed. The aim of this approach is to reduce the energy dissipation of the computing cores by either powering them off or switching them into energy-saving states while still guaranteeing to meet all timing constraints. The approach is illustrated with two industrial applications, an engine control management and an engine control unit. Moreover, the amount of data to be migrated during the mode change is minimised. Since the number of processing cores and their energy dissipation are often negatively correlated with the amount of data to be migrated during the mode change, there is some trade-off between these values, which is also analysed in this paper

Comparison of visual and refractive results of Toric Implantable Collamer Lens with bioptics for myopic astigmatism

PURPOSE: To compare visual and refractive results of Toric Implantable Collamer Lens (TICL) and bioptics (ICL plus excimer corneal surgery) to treat myopic astigmatism. METHODS: Eighty-one eyes underwent TICL implantation and 83 eyes were treated with bioptics (corneal ablation was performed between 1.5 and 6 months after ICL implantation). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, adverse events, safety, and efficacy were evaluated 12 months postoperatively. RESULTS: At 12 months postoperatively, the mean spherical equivalent was -0.15 ± 0.36 diopters (D) in the TICL group and -0.08 ± 0.26 D in the bioptics group (p = 0.099). Sixty-six (81.5 %) and 78 (94.0 %) eyes were within ±0.50 D for TICL and bioptics groups, respectively. The mean Snellen UDVA was not statistically different between both procedures (p = 0.909); 53 (65.4 %) and 54 (65.1 %) eyes achieved at least 20/25 or better in TICL and bioptics groups, respectively. No eye had lost more than two lines of CDVA, and 32.1 % of eyes (26/81) in the TICL group and 57.8 % of eyes (48/83) in the bioptics group had better postoperative UDVA than preoperative CDVA (p < 0.001). Safety was not statistically different between groups (p = 0.464) while efficacy was significantly higher in the bioptics group (p = 0.000). Two eyes with a TICL were treated to correct TICL decentration. CONCLUSIONS: Bioptics showed slightly better outcomes in some clinical measures such as uncorrected visual acuity, efficacy, and refractive predictability. TICL implantation shows reliable results similar to bioptics. A single procedure with TICL implantation might be preferred, eliminating the inherent risks of laser treatments and the risks of a second surgical procedure.The authors have no proprietary interests in any of the materials mentioned in this article. This research was supported in part by a Universitat de Valencia Research Grant to Robert Montes-Mico (#SAF2009-13342 and #SAF2008-01114-E#) and Fundacao para a Ciencia e Tecnologia of Portugal through a Grant to Paulo Fernandes (#FCT-SFRH-BD-34303-2007#)

Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations

Towards a Practical Cluster Analysis over Encrypted Data

Cluster analysis is one of the most significant unsupervised machine learning tasks, and it is utilized in various fields associated with privacy issues including bioinformatics, finance and image processing. In this paper, we propose a practical solution for privacy-preserving cluster analysis based on homomorphic encryption~(HE). Our work is the first HE solution for the mean-shift clustering algorithm. To reduce the super-linear complexity of the original mean-shift algorithm, we adopt a novel random sampling method called dust sampling which perfectly fits in HE and achieves the linear complexity. We also substitute non-polynomial kernels by a new polynomial kernel so that it can be efficiently computed in HE. The HE implementation of our modified mean-shift clustering algorithm based on the approximate HE scheme HEAAN shows prominent performance in terms of speed and accuracy. It takes about $30$ minutes with $99\%$ accuracy over several public datasets with hundreds of data, and even for the dataset with $262,144$ data it takes only $82$ minutes applying SIMD operations in HEAAN. Our results outperform the previously best known result (SAC 2018) over $400$ times

Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Effective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment.</p> <p>Methods/Design</p> <p>The present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied.</p> <p>Discussion</p> <p>The study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00970437">NCT00970437</a>).</p

Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme

Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics

Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using real and simulated molecular marker data. Our study also compared the performance of traditional hierarchical clustering with model-based clustering (STRUCTURE). We showed that the cophenetic correlation coefficient is directly related to subgroup differentiation and can thus be used as an indicator of the presence of genetically distinct subgroups in germplasm collections. Whereas UPGMA performed well in preserving distances between accessions, Ward excelled in recovering groups. Our results also showed a close similarity between clusters obtained by Ward and by STRUCTURE. Traditional cluster analysis can provide an easy and effective way of determining structure in germplasm collections using molecular marker data, and, the output can be used for sampling core collections or for association studies