Revisiting port performance measurement: A hybrid multi-stakeholder framework for the modelling of port performance indicators

This study develops a new port performance measurement model by taking the perspectives from different port stakeholders. The novelty lies in the modelling of interdependencies among port performance measures, and the combination of weights of interdependent measures with both qualitative and quantitative evaluations of the measures from multiple stakeholders for quantitative port performance measurement. It represents an effective performance measurement tool and offers a diagnostic instrument for performance evaluation and/or monitoring of ports and terminals so as to satisfy different requirements of various port stakeholders in a flexible manner. © 201

Quantifying single nucleotide variant detection sensitivity in exome sequencing

BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give “power estimates” for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5–15% of heterozygous and 1–4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the “missing heritability” of quantitative traits

Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma

published_or_final_versio

Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Half-dose verteporfin photodynamic therapy for bullous variant of central serous chorioretinopathy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Central serous chorioretinopathy is characterized by serous neurosensory detachment of the macula and it usually resolves spontaneously with good visual prognosis. In some patients, however, the serous retinal detachment might be very extensive and can result in bullous exudative retinal detachment. We evaluated the use of half-dose verteporfin photodynamic therapy for the treatment of bullous retinal detachment in idiopathic central serous chorioretinopathy.</p> <p>Case presentation</p> <p>We report the case of a 51-year-old Chinese man who presented with blurred vision in his right eye and superior visual field defect due to bullous variant of central serous chorioretinopathy. No improvement in vision and retinal detachment was noted after three months of observation and a short course of oral acetazolamide. He was then treated with half-dose verteporfin photodynamic therapy and his visual acuity improved from 20/70 to 20/25 within one month of treatment. Three months after photodynamic therapy, there was complete resolution of sub-retinal fluid and bullous retinal detachment. No recurrence of central serous chorioretinopathy was noted in three years of follow-up.</p> <p>Conclusion</p> <p>We report the beneficial effect of photodynamic therapy with half-dose verteporfin as a treatment option for bullous retinal detachment caused by central serous chorioretinopathy.</p

Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity

© 2015 Al Khamici et al. The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the catalytic cysteine residue in CLIC1, which is consistent with its structure. CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione-dependent manner. Previous electrophysiological studies have shown that the drugs IAA-94 and A9C specifically block CLIC channel activity. These same compounds inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a functional activity to the soluble form of the CLIC proteins. Our results demonstrate that the soluble form of the CLIC proteins has an enzymatic activity that is distinct from the channel activity of their integral membrane form. This CLIC enzymatic activity may be important for protecting the intracellular environment against oxidation. It is also likely that this enzymatic activity regulates the CLIC ion channel function

Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2

OBJECTIVE: Subfield-specific measurements provide superior information in the early stages of neurodegenerative diseases compared to global hippocampal measurements. The overall goal was to systematically compare the performance of five representative manual and automated T1 and T2 based subfield labeling techniques in a sub-set of the ADNI2 population. METHODS: The high resolution T2 weighted hippocampal images (T2-HighRes) and the corresponding T1 images from 106 ADNI2 subjects (41 controls, 57 MCI, 8 AD) were processed as follows. A. T1-based: 1. Freesurfer + Large-Diffeomorphic-Metric-Mapping in combination with shape analysis. 2. FreeSurfer 5.1 subfields using in-vivo atlas. B. T2-HighRes: 1. Model-based subfield segmentation using ex-vivo atlas (FreeSurfer 6.0). 2. T2-based automated multi-atlas segmentation combined with similarity-weighted voting (ASHS). 3. Manual subfield parcellation. Multiple regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. RESULTS: Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between controls and MCI (ES: 0.27 vs 0.11). T2-HighRes approaches outperformed T1 approaches for the detection of early stage atrophy (ES: 0.27 vs.0.10), amyloid positivity (ES: 0.11 vs 0.04), and cognitive associations (ES: 0.22 vs 0.19). CONCLUSIONS: T2-HighRes subfield approaches outperformed whole hippocampus and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

Parametric methods outperformed non-parametric methods in comparisons of discrete numerical variables

<p>Abstract</p> <p>Background</p> <p>The number of events per individual is a widely reported variable in medical research papers. Such variables are the most common representation of the general variable type called discrete numerical. There is currently no consensus on how to compare and present such variables, and recommendations are lacking. The objective of this paper is to present recommendations for analysis and presentation of results for discrete numerical variables.</p> <p>Methods</p> <p>Two simulation studies were used to investigate the performance of hypothesis tests and confidence interval methods for variables with outcomes {0, 1, 2}, {0, 1, 2, 3}, {0, 1, 2, 3, 4}, and {0, 1, 2, 3, 4, 5}, using the difference between the means as an effect measure.</p> <p>Results</p> <p>The Welch U test (the T test with adjustment for unequal variances) and its associated confidence interval performed well for almost all situations considered. The Brunner-Munzel test also performed well, except for small sample sizes (10 in each group). The ordinary T test, the Wilcoxon-Mann-Whitney test, the percentile bootstrap interval, and the bootstrap-<it>t </it>interval did not perform satisfactorily.</p> <p>Conclusions</p> <p>The difference between the means is an appropriate effect measure for comparing two independent discrete numerical variables that has both lower and upper bounds. To analyze this problem, we encourage more frequent use of parametric hypothesis tests and confidence intervals.</p