SAFE-clustering: Single-cell Aggregated (from Ensemble) clustering for single-cell RNA-seq data.

MOTIVATION: Accurately clustering cell types from a mass of heterogeneous cells is a crucial first step for the analysis of single-cell RNA-seq (scRNA-Seq) data. Although several methods have been recently developed, they utilize different characteristics of data and yield varying results in terms of both the number of clusters and actual cluster assignments. RESULTS: Here, we present SAFE-clustering, single-cell aggregated (From Ensemble) clustering, a flexible, accurate and robust method for clustering scRNA-Seq data. SAFE-clustering takes as input, results from multiple clustering methods, to build one consensus solution. SAFE-clustering currently embeds four state-of-the-art methods, SC3, CIDR, Seurat and t-SNE + k-means; and ensembles solutions from these four methods using three hypergraph-based partitioning algorithms. Extensive assessment across 12 datasets with the number of clusters ranging from 3 to 14, and the number of single cells ranging from 49 to 32, 695 showcases the advantages of SAFE-clustering in terms of both cluster number (18.2-58.1% reduction in absolute deviation to the truth) and cluster assignment (on average 36.0% improvement, and up to 18.5% over the best of the four methods, measured by adjusted rand index). Moreover, SAFE-clustering is computationally efficient to accommodate large datasets, taking <10 min to process 28 733 cells. AVAILABILITY AND IMPLEMENTATION: SAFEclustering, including source codes and tutorial, is freely available at https://github.com/yycunc/SAFEclustering. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The long-term effects of the Houston Child Advocates, Inc., program on children and family outcomes.

The objective of the study is to investigate the longitudinal effects of the Houston Child Advocates, Inc., program on children's outcomes. The treatment group consisted of children in the court system that were assigned Child Advocates volunteers, and the comparison children were chosen randomly from a similar population of children. The treatment group had significantly higher scores on the protective factor and family functioning measures and received more social services than those in the comparison group. Children in the treatment group also had significantly fewer placement changes and did better academically and behaviorally in school than children in the comparison group.

Preserved color imagery in an achromatopsic.

The loss of color vision secondary to central nervous system disease (achromatopsia) is thought to preclude visual imagery of colors. We report a patient with achromatopsia, secondary to bilateral temporo-occipital infarcts inclusive of the lingual and fusiform gyri, with preserved color imagery. Our findings, in conjunction with previous cases in the literature, are consistent with a single neural network for color processing in which a disconnection of internal activation from stored color representations produces impaired color imagery with preserved color perception, whereas a disconnection of visual input to these representations produces achromatopsia with preserved color imagery.

Repetition and the arcuate fasciculus.

According to the traditional model of language organization, repetition deficits arise following damage to the arcuate fasciculus of the dominant hemisphere (conduction aphasia). Conduction aphasia may result from lesions that spare the arcuate fasciculus. However, these patients have atypical language organization. We describe a man with normal language architecture who underwent a resection of the anterior portion of his arcuate fasciculus and retained his ability to repeat words and sentences. We propose that the arcuate fasciculus is not necessary for speech repetition by the lexical route.

A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofin) in mild Alzheimer's disease patients.

A phase 1, randomized, double-blind, placebo-controlled, dose escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics) was conducted in mild Alzheimer's disease (AD) patients to evaluate multiple-dose safety, tolerability, and pharmacokinetics. Possible short-term effects of AIT-082 on cognition and memory were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease and other neurological disorders. Pre-clinical studies indicate that AIT-082 has memory enhancing properties, stimulates neuritogenesis and the production of neurotrophic factors. Patients received an oral dose of AIT-082 or placebo daily for one week. Thirty-six AD patients were divided into three dose cohorts; each dose cohort consisted of twelve patients with 8 patients randomized to AIT-082 and 4 to placebo. The 3 doses of AIT-082 evaluated in this study were 100 mg/day, 500 mg/day, and 2,000 mg/day. There were no serious adverse events at any dose and the drug was well tolerated without significant side effects. AIT-082 was orally and rapidly absorbed, resulting in peak serum concentrations within 2 hours with an elimination half-life of approximately 20 hours. Higher doses resulted in corresponding increases in peak concentrations and areas under the curve (AUC). There was an approximate 2-fold accumulation in AIT-082 with daily dosing (as reflected by the AUC) at steady state. There were no significant differences by treatment arm on the clinical or neuropsychological evaluations. AIT-082 was rapidly absorbed by the oral route with a half-life suitable for dosing once or twice daily. No problems with tolerability or safety were found. AIT-082 appears suitable for testing in larger clinical trials for the treatment of AD and other neurologic disorders.

Discriminating between simulated malingering and closed head injury on the Wechsler Memory Scale-Revised.

We tested the hypothesis that malingering is distinguished by poorer performance on recognition relative to recall tasks by evaluating the ability of discriminant functions to distinguish between 89 subjects simulating malingering and 44 subjects with a history of closed head injury (CHI) on the Wechsler Memory Scale - Revised (WMS-R). Functions with good accuracy in discriminating between simulated malingerers and controls in prior studies did not have adequate specificity when applied to the CHI group. A newly derived discriminant function achieved overall classification accuracy of 79% for the malingering versus CHI groups on cross-validation, with 79% sensitivity (true positives for malingering) and 80% specificity (true negatives for closed head injured). A complex performance pattern on seven WMS-R subtests distinguished malingering subjects from those with CHI, but did not support the recognition versus recall hypothesis. The malingering pattern involved: (a) power performance on two relatively (but inconspicuously) easy tasks dependent on immediate recall (Visual Reproduction I and Visual Memory Span); (b) better performance on two relatively (but inconspicuously) easy tasks dependent on immediate recall (Visual Paired Associates I and Digit Span); (c) poorer performance on two relatively difficult delayed tasks (Logical Memory II and Visual Paired Associates II); and (d) better performance on another difficult task involving delayed recall (Visual Reproduction II).

The differential effects of simulating malingering, closed head injury, and other CNS pathology on the Wisconsin Card Sorting Test: support for the "pattern of performance" hypothesis.

We investigated the effects of faking bad on the Wisconsin Card Sorting Test, comparing the performance of simulating malingerers (M; n = 24) to controls (C; n = 21), closed head-injured patients (CHI, n = 70), and patients with mixed CNS pathology other than CHI alone (CNS; n = 89). Stepwise discriminant functions achieved good accuracy (91-96%), sensitivity (58-100%), and specificity (92-100%) in differentiating simulating malingerers from these groups. The Categories score was a consistent significant independent discriminating variable. Categories alone could differentiate between the M and C groups. However, in discriminating between simulating malingerers and both CHI or CNS patients, more complex patterns of performance emerged, consisting of relatively poorer performance ratios on Categories compared to Perseverative Errors. This supported the Pattern of Performance theory of the effects of simulating malingering on neuropsychological tests, which holds that people simulating malingering do more poorly on obvious vs. subtle tasks compared to people with verified brain damage. Due to the difficulty of tracking one's performance on several different indices simultaneously, known patterns of performance for patients with verified brain dysfunction should be very difficult to fake, even with coaching.

Le Fort I maxillary osteotomies in cleft palate cases. Surgical changes and stability.

Surgical and postsurgical changes in maxillary position following transpalatal osteotomy at the le Fort I level in 30 patients with clefts of lip and palate were evaluated cephalometrically. By superimposing on natural reference structures, a more accurate and detailed evaluation of change in maxillary position was possible than by using conventional cephalometric analyses. The mean horizontal advancement was 9 mm, with a mean vertical change of 3 mm. While it is customary to express postsurgical relapse as a percentage of surgical change (in this case 7% mean horizontal relapse and 23% mean vertical relapse), the most remarkable finding to emerge from this study was the variability in surgical and postsurgical change which would be obscured by concentrating on descriptive statistics. Postsurgical change was related to the amount of surgical change, but the correlation coefficients are quite low, and so other factors must be responsible for a significant proportion of any relapse.

Correcting performance-rating errors in oral examinations.

Although oral examinations are widely used for making decisions regarding an individual's level of competence, they are frequently of limited reliability. A significant part of the error in oral performance ratings is due to the tendency for some evaluators to be lenient and others to be stringent in their assignment of ratings. This article describes and evaluates a simple method to identify and correct for errors of leniency and stringency. The method, which is based on a regression model recommended by Wilson (1988), extends and simplifies the procedures recommended by Cason and Cason (1984, 1985). The method provides an estimate of each individual's performance that has been corrected for errors of leniency and stringency. In addition, it produces for each rater an index of leniency or stringency and several other statistics useful in evaluating the properties of rating data. The regression method is applied to performance ratings from three separate administrations of an oral examination in a medical specialty. The results indicate modest but significant levels of leniency and stringency error; correcting for such errors would change the pass/fail decisions for about 6% of the examinees. Limitations of the procedure, as well as the need for additional research, are discussed.

The prevention of softball injuries: the experience at Yokota.

Softball injuries occur in a predictable pattern. Review of Emergency Room records at Yokota AB Hospital for three summers showed a high incidence of ankle injuries. Sliding is the cause of many of these injuries. Common sense interventions should reduce the incidence of softball injury. Use of low profile bases or the outlawing of sliding are reasonable interventions that should be considered by policy makers.

Bases for the analysis of cephalometric radiographs: intracranial reference structures or natural head position.

The inherent variability of intracranial cephalometric reference structures makes analysis based upon them potentially misleading with serious implications for orthodontic and orthognathic surgical treatment planning. These problems can be avoided by using natural head position and relating measurement to the true horizontal. The lack of suitable norms has been a barrier to this approach. This paper demonstrates that norms can be derived from existing data, enabling the clinical application of analyses related to the true horizontal.

The analysis of errors in orthodontic measurements.

The sources of error in cephalometric measurement and their analyses are discussed. The importance of distinguishing bias and random errors is emphasized, and methods of control are discussed. Randomization of record measurement is one of the most important methods of avoiding bias, but it is rarely undertaken in cephalometric studies. Random errors are particularly important in the evaluation of individual radiographs, and a measurement that has a high error in relation to its total variability will be of little value in clinical assessment. In serial studies of facial change, the error variance is always a major part of the total variance and thus results have to be interpreted with caution. In cross-sectional studies it is not possible to specify exactly the acceptable limits of random errors, because this will depend on the difference between groups that would be of interest and on the number of cases. The judicious replication of measurements can be important in the control of random errors. In many papers, adequate error evaluation and control is lacking. In these circumstances, the results are of limited value because it is not possible to tell whether an apparent effect is the result of bias in measurement or whether a real effect is being obscured by random errors. It is incumbent on authors to consider how their measurement errors should affect the interpretation of results.