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In complex tissues containing cells that are difficult to dissociate, single-nucleus RNA-sequencing (snRNA-seq) has become the preferred experimental technology over single-cell RNA-sequencing (scRNA-seq) to measure gene expression. To accurately model these data in downstream analyses, previous work has shown that droplet-based scRNA-seq data are not zero-inflated, but whether droplet-based snRNA-seq data follow the same probability distributions has not been systematically evaluated. Using pseudonegative control data from nuclei in mouse cortex sequenced with the 10x Genomics Chromium system and mouse kidney sequenced with the DropSeq system, we found that droplet-based snRNA-seq data follow a negative binomial distribution, suggesting that parametric statistical models applied to scRNA-seq are transferable to snRNA-seq. Furthermore, we found that the quantification choices in adapting quantification mapping strategies from scRNA-seq to snRNA-seq can play a significant role in downstream analyses and biological interpretation. In particular, reference transcriptomes that do not include intronic regions result in significantly smaller library sizes and incongruous cell type classifications. We also confirmed the presence of a gene length bias in snRNA-seq data, which we show is present in both exonic and intronic reads, and investigate potential causes for the bias. [ABSTRACT FROM AUTHOR]

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature—the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer. Editor's summary: Alu elements can be differentially associated with cancerous cells, but their biomarker potential is often overlooked because of technical challenges stemming from their repetitive nature. Douville et al. developed a machine learning approach to profile Alu elements in individuals with or without cancer. The method was designed for high specificity in classifying cancer and was validated in multiple independent cohorts, with solid cancers particularly marked by a reduction in AluS subfamily elements. This study suggests that Alu elements may hold valuable information to increase the likelihood of early cancer detection. —Catherine Charneski [ABSTRACT FROM AUTHOR]

An attempt was made to couple the water quality model of Danshuei River to the three-dimensional unstructured-grid hydrodynamic model [Eulerian--Lagrangian circulation model (ELCIRC)]. The Eulerian--Lagrangian scheme for the solution of the transport equations of salt in ELCIRC was demonstrated to be not mass conservative. The scheme was replaced with a finite-volume/finite-difference upwind scheme to ensure mass conservation both locally and globally. The same scheme was also used for the scalar transport equation in the water quality model. The representation of mass flux in the scalar transport equation is carefully formulated to be consistent with that of volume flux used in the continuity equations of ELCIRC. It was demonstrated that the newly revised scheme (1) conserved mass locally and globally; (2) conserved mass for both conservative and nonconservative substances subjected to biogeochemical transformation; and (3) preserved the integrity of the wetting-and-drying scheme. Further, the baroclinic simulation using the newly revised scheme showed a better result in terms of salt intrusion and salinity distribution in the Danshuei River estuary. DOI: 10.1061/(ASCE)0733-9429(2008) 134:8 (1166) CE Database subject headings: Mass transport; Numerical models; Advection; Water quality.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jenvman.2005.02.005 Byline: Wen-Cheng Liu (a), Shin-Yi Liu (b), Ming-Hsi Hsu (b), Albert Y. Kuo (c) Abstract: The Hsintien Stream is one of the major branches of the Danshuei River system, which runs through the metropolitan capital city of Taipei, Taiwan and receives a large amount of wastewater. The dissolved oxygen concentration is generally low in the tidal portion of the Hsintien Stream. Hypoxia/anoxia occurs often, particularly during the low-flow period when the Feitsui Reservoir, Chingtan Dam and Chihtan Dam impound the freshwater for municipal water supply. Fish kills happen from time to time. This paper describes the application of a numerical hydrodynamic and water quality model to the Danshuei River system, with special attention to the tidal portion of the Hsintien Stream. The model is recalibrated with the prototype conditions of the year 2000. The hydrodynamic portion of the model is recalibrated with measured surface elevation and velocity at various stations in the river system. The water quality portion of the model is recalibrated with respect to the field data provided by Taiwan EPA. The input data of point and nonpoint sources are also estimated. The model simulates the concentrations of various forms of nutrients, CBOD and dissolved oxygen. A series of sensitivity runs was conducted to investigate the effects of point source loadings and river flow on the DO level in the river. It is demonstrated that the augmentation of river flow has as much effect on raising DO level as the reduction of point source loadings. The completion of the Taipei sewer project is expected to reduce the point source loadings by at least 75%. Under these reduced loadings, if the daily instream flow is maintained above the monthly Q.sub.75 flow throughout the year, the minimum DO concentration in the river would not fall below 1mg/L, which is the suffocation level for most fish species in the Hsintien Stream. (Q.sub.75 is the flow which is equaled or exceeded 75% of the days in the month.) The Feitsui Reservoir, Chingtan Dam and Chihtan Dam may impound water during the high flow periods and release freshwater to maintain the flow at the Q.sub.75 value in the Hsintien Stream during the drought periods. Author Affiliation: (a) Department of Civil and Disaster Prevention Engineering, National United University, Miao-Li 360, Taiwan, ROC (b) Department of Bioenvironmental Systems Engineering and Hydrotech Research Institute, National Taiwan University, Taipei 10617, Taiwan, ROC (c) National Center for Ocean Research, National Taiwan University, Taipei 10617, Taiwan, ROC Article History: Received 4 April 2004; Accepted 15 February 2005

The goals of this study were to quantify delays in diagnosing HIV infection in patients presenting for medical care prior to the identification of their HIV infection, and to determine characteristics of visits preceding the identification of HIV infection. This was a retrospective cohort study of consecutive newly diagnosed HIV infected patients in a large urban setting. Patients were predominantly minorities and identified from all inpatient and outpatient HIV tests performed between December 29, 1998 and December 27, 1999. Data were collected from all emergency department and clinic visits for each patient included in this study for a 3-year period preceding the first diagnosis of HIV infection. Two hundred seventy-eight patients tested positive for HIV during the study period. Of these, 76 (27%) met inclusion criteria. Twenty-three patients made a total of 53 health care visits preceding the diagnosis of their HIV infection. The median delay in diagnosis of HIV infection was 2 days (interquartile range [IQR], 1-22 days; range, 0-1093 days) for all subjects, although 19 (25%; 95% confidence interval [CI]: 16%-36%) patients had a delay in diagnosis of 30 days or more. Among those patients who had made prior health care visits, the median delay in diagnosis was 112 days (IQR, 33-690 days; range, 2-1093 days). No specific risk factor, historical clue, physical examination finding, or laboratory finding reliably identified patients with HIV infection. Documentation in the medical record of specific risk factors and clinical characteristics suggestive of HIV infection was poor. This study documented missed opportunities and delays in diagnosis of patients with unrecognized HIV infection. Clinicians must maintain a high index of suspicion for HIV infection in all patients.

A vertical (laterally integrated) two-dimensional numerical model was applied to study the salt water intrusion in the Tanshui River estuarine system, Taiwan. The river system has experienced dramatic changes in the past half century because of human intervention. The construction of two reservoirs and water diversion in the upper reaches of the fiver system significantly reduces the freshwater inflow. The land subsidence within the Taipei basin and the enlargement of the river constriction at Kuan-Du have lowered the river bed. Both changes have contributed farther to the intrusion of tidal flow and salt water in the upstream direction. The model was reverified with the earliest available hydrographic data measured in 1977. The overall performance of the model is in reasonable agreement with the field data. The model was then used to investigate the change in salt water intrusion as a result of reservoir construction and bathymetric changes in the river system. The model simulation study reveals that significant salinity increases have resulted from the combined changes. It has been speculated by ecological researchers that the long-term increase in salinity might be the driving force altering the aquatic ecosystem structure in the lower reach of the estuary and the Kuan-Du mangrove swamp, particularly the enlargement of the mangrove area and the disappearance of freshwater marshes. However, concrete proof has not been available since no prototype salinity data were available prior to the reservoir construction. This case study offers the first quantitative estimate of the salinity changes due to human interference in this natural system. CE Database subject headings: Salt water intrusion; Taiwan; River systems; Numerical models; Reservoirs; Bathymetry.

The net, long-term transport of materials in estuaries is governed primarily by the residual (or tidally averaged) circulation in the system. Knowledge of the residual circulation is essential for predicting the transport of algal patches, debris, and pollutants of concern in an estuary. A real-time, two-dimensional, laterally averaged hydrodynamic model is used to analyze residual current and salinity distributions in the Tanshui River estuary. The model results were filtered to arrive at the subtidal, or residual quantities. The characteristic two-layered estuarine circulation prevails for most of the time at Kuan-Du station near the river mouth. Though the circulation strengthens with increasing river discharge at low flow, its strength decreases at moderate river discharge and the two-layered circulation ceases at moderately high flow. This implies a weak trapping capacity in the estuary. At the upriver stations where salinity is lower, strength of circulation generally decreases with increasing river discharge. The response of residual velocity to the spring-neap cycle indicates stronger residual circulation during neap tide than spring tide.