THE CHANGING RURAL POLICY CONTEXT: DISCUSSION

This paper discusses a paper presented by Steven Smith at the 1995 annual meeting of the Northeastern Agricultural and Resource Economics Association. Smith presented key issues that have changed the context for rural development policy in the United States. We propose that the induced innovation model of economic development can be used to identify a variety of ways that LGU's can contribute to developing and delivering appropriate rural economic development programs. These ways include assisting rural communities in identifying comparative advantage, identifying and/or providing relevant resource persons, delivering appropriate educational programs and conducting research on important issues. The success of LGU's in these areas will depend on their willingness to undertake these activities and their ability to recognize and adapt to current to future economic and social realities affecting rural America.Community/Rural/Urban Development,

Ultrafast and memory-efficient alignment of short DNA sequences to the human genome

Bowtie: a new ultrafast memory-efficient tool for the alignment of short DNA sequence reads to large genomes

TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions

TopHat is a popular spliced aligner for RNA-sequence (RNA-seq) experiments. In this paper, we describe TopHat2, which incorporates many significant enhancements to TopHat. TopHat2 can align reads of various lengths produced by the latest sequencing technologies, while allowing for variable-length indels with respect to the reference genome. In addition to de novo spliced alignment, TopHat2 can align reads across fusion breaks, which can occur after genomic translocations. TopHat2 combines the ability to identify novel splice sites with direct mapping to known transcripts, producing sensitive and accurate alignments, even for highly repetitive genomes or in the presence of pseudogenes. TopHat2 is available at http://ccb.jhu.edu/software/tophat

Noninvasive Monitoring of Elevated Intramuscular Pressure in a Model Compartment Syndrome via Quantitative Fascial Motion

Compartment syndromes, conditions of elevated intramuscular pressure (IMP) resulting from trauma or chronic overuse, frequently require invasive IMP monitoring for accurate diagnosis. Our objective was to test a noninvasive ultrasound technique For estimating IMP based on fascial displacement waveforms from arterial blood pressure pulses. IMP was increased in the legs of 23 healthy adult subjects LIP to 80 mmHg Using two blood pressure cuffs covering the region from the knee to the ankle. Receiver operator characteristic curves and recursive partitioning were used to determine the sensitivity and specificity of diagnosing elevated IMP using fascial displacement, For one curve. in which several ultrasonic measurement parameters were used along with subject body mass index and blood pressure, the sensitivity and specificity for diagnosing normal IMP (below 30 mmHg) from elevated IMP (30 mm Hg and up) was 0.61 and 0.94, respectively. Recursive partitioning, in which IMP was divided into three ranges (normal \u3c30 \u3emmHg, midrange of 30-40 mmHg, and elevated \u3e= 50 mmHg), resulted in improved diagnostic sensitivity (0.77) with almost no change in specificity (0.93). (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:489-494 200

Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks

Recent advances in high-throughput cDNA sequencing (RNA-seq) can reveal new genes and splice variants and quantify expression genome-wide in a single assay. The volume and complexity of data from RNA-seq experiments necessitate scalable, fast and mathematically principled analysis software. TopHat and Cufflinks are free, open-source software tools for gene discovery and comprehensive expression analysis of high-throughput mRNA sequencing (RNA-seq) data. Together, they allow biologists to identify new genes and new splice variants of known ones, as well as compare gene and transcript expression under two or more conditions. This protocol describes in detail how to use TopHat and Cufflinks to perform such analyses. It also covers several accessory tools and utilities that aid in managing data, including CummeRbund, a tool for visualizing RNA-seq analysis results. Although the procedure assumes basic informatics skills, these tools assume little to no background with RNA-seq analysis and are meant for novices and experts alike. The protocol begins with raw sequencing reads and produces a transcriptome assembly, lists of differentially expressed and regulated genes and transcripts, and publication-quality visualizations of analysis results. The protocol's execution time depends on the volume of transcriptome sequencing data and available computing resources but takes less than 1 d of computer time for typical experiments and ~1 h of hands-on time

A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients.

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients\u27 disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients\u27 responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients\u27 and 73 normal donors\u27 plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors\u27 plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII

Investigating potential future changes in surface water flooding hazard and impact

Surface water flooding (SWF) is a recurrent hazard that affects lives and livelihoods. Climate change is projected to change the frequency of extreme rainfall events that can lead to SWF. Increasingly, data from Regional Climate Models (RCMs) are being used to investigate the potential water‐related impacts of climate change; such assessments often focus on broad‐scale fluvial flooding and the use of coarse resolution (>12 km) RCMs. However, high‐resolution (<4 km) convection‐permitting RCMs are now becoming available that allow impact assessments of more localised SWF to be made. At the same time, there has been an increasing demand for more robust and timely real‐time forecast and alert information on SWF. In the UK, a real‐time SWF Hazard Impact Model framework has been developed. The system uses 1‐km gridded surface runoff estimates from a hydrological model to simulate the SWF hazard. These are linked to detailed inundation model outputs through an Impact Library to assess impacts on property, people, transport, and infrastructure for four severity levels. Here, a set of high‐resolution (1.5 km and 12 km) RCM data has been used as input to a grid‐based hydrological model over southern Britain to simulate Current (1996–2009) and Future (~2100s; RCP8.5) surface runoff. Counts of threshold‐exceedance for surface runoff and precipitation (at 1‐, 3‐ and 6‐hr durations) are analysed. Results show that the percentage increases in surface runoff extremes, are less than those of precipitation extremes. The higher‐resolution RCM simulates the largest percentage increases, which occur in winter, and the winter exceedance counts are greater than summer exceedance counts. For property impacts, the largest percentage increases are also in winter; however, it is the 12‐km RCM output that leads to the largest percentage increase in impacts. The added‐value of high‐resolution climate model data for hydrological modelling is from capturing the more intense convective storms in surface runoff estimates

TopHat: discovering splice junctions with RNA-Seq

Motivation: A new protocol for sequencing the messenger RNA in a cell, known as RNA-Seq, generates millions of short sequence fragments in a single run. These fragments, or ‘reads’, can be used to measure levels of gene expression and to identify novel splice variants of genes. However, current software for aligning RNA-Seq data to a genome relies on known splice junctions and cannot identify novel ones. TopHat is an efficient read-mapping algorithm designed to align reads from an RNA-Seq experiment to a reference genome without relying on known splice sites

Developing an impact library for forecasting surface water flood risk

During surface water flooding events, emergency responders require detailed information on the risks posed in order to provide an appropriate and effective response. Few early warning systems quantitatively estimate the risk and impacts of surface water flooding. Improvements in computational processing capability, availability of new datasets and developments in forecasting models means that the forecasting information currently being supplied by the Flood Forecasting Centre can be improved upon through the application of a timely, impact‐based model. This article presents a novel approach to collating receptor datasets into a pre‐calculated Impact Library for use in a Hazard Impact Model (HIM) that will operate using real‐time probabilistic rainfall and surface runoff forecasts for England and Wales. The HIM provides an approach suitable for modelling flood impacts. Initial results are presented for a case study covering the 2012 floods in the North East of England. Information generated by the HIM provides additional benefits beyond current methods. Features include operator access to 1 km 15 min spatial–temporal data, analysis of individual impact criteria and modular refinement of the Impact Library to suit different situations. The HIM has been developed in partnership via the Natural Hazards Partnership