Development and evaluation of an open source software tool for deidentification of pathology reports

BACKGROUND: Electronic medical records, including pathology reports, are often used for research purposes. Currently, there are few programs freely available to remove identifiers while leaving the remainder of the pathology report text intact. Our goal was to produce an open source, Health Insurance Portability and Accountability Act (HIPAA) compliant, deidentification tool tailored for pathology reports. We designed a three-step process for removing potential identifiers. The first step is to look for identifiers known to be associated with the patient, such as name, medical record number, pathology accession number, etc. Next, a series of pattern matches look for predictable patterns likely to represent identifying data; such as dates, accession numbers and addresses as well as patient, institution and physician names. Finally, individual words are compared with a database of proper names and geographic locations. Pathology reports from three institutions were used to design and test the algorithms. The software was improved iteratively on training sets until it exhibited good performance. 1800 new pathology reports were then processed. Each report was reviewed manually before and after deidentification to catalog all identifiers and note those that were not removed. RESULTS: 1254 (69.7 %) of 1800 pathology reports contained identifiers in the body of the report. 3439 (98.3%) of 3499 unique identifiers in the test set were removed. Only 19 HIPAA-specified identifiers (mainly consult accession numbers and misspelled names) were missed. Of 41 non-HIPAA identifiers missed, the majority were partial institutional addresses and ages. Outside consultation case reports typically contain numerous identifiers and were the most challenging to deidentify comprehensively. There was variation in performance among reports from the three institutions, highlighting the need for site-specific customization, which is easily accomplished with our tool. CONCLUSION: We have demonstrated that it is possible to create an open-source deidentification program which performs well on free-text pathology reports

Microdissection: A method developed to investigate mechanisms involved in transmissible spongiform encephalopathy pathogenesis

BACKGROUND: The transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting both human and animals. The neuroanatomical changes which occur in the central nervous system (CNS) of TSE infected animals include vacuolation, gliosis, neuronal loss and the deposition of a disease specific protein, PrP(Sc). Experimental murine models of scrapie, a TSE of sheep, have revealed that pathology may be confined to specific brain areas with targeting of particular neuronal subsets depending on route of injection and scrapie isolate. To assess the biochemical changes which are taking place in these targeted areas it was necessary to develop a reliable sampling procedure (microdissection) which could be used for a variety of tests such as western blotting and magnetic resonance spectroscopy. METHODS: The method described is for the microdissection of murine brains. To assess the usefulness of this dissection technique for producing similar sample types for analysis by various down-stream biochemical techniques, the areas dissected were analysed for PrP(Sc )by western blotting and compared to immunocytochemical (ICC) techniques. RESULTS: Results show that the method generates samples yielding a consistent protein content which can be analysed for PrP(Sc). The areas in which PrP(Sc )is found by western blotting compares well with localisation visualised by immunocytochemistry. CONCLUSION: The microdisssection method described can be used to generate samples suitable for a range of biochemical techniques. Using these samples a range of assays can be carried out which will help to elucidate the molecular and cellular mechanisms underlying TSE pathogenesis. The method would also be useful for any study requiring the investigation of discrete areas within the murine brain

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record

Medvedev and Melott (2007) have suggested that periodicity in fossil biodiversity may be induced by cosmic rays which vary as the Solar System oscillates normal to the galactic disk. We re-examine the evidence for a 62 million year (Myr) periodicity in biodiversity throughout the Phanerozoic history of animal life reported by Rohde & Mueller (2005), as well as related questions of periodicity in origination and extinction. We find that the signal is robust against variations in methods of analysis, and is based on fluctuations in the Paleozoic and a substantial part of the Mesozoic. Examination of origination and extinction is somewhat ambiguous, with results depending upon procedure. Origination and extinction intensity as defined by RM may be affected by an artifact at 27 Myr in the duration of stratigraphic intervals. Nevertheless, when a procedure free of this artifact is implemented, the 27 Myr periodicity appears in origination, suggesting that the artifact may ultimately be based on a signal in the data. A 62 Myr feature appears in extinction, when this same procedure is used. We conclude that evidence for a periodicity at 62 Myr is robust, and evidence for periodicity at approximately 27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio

Focusing and Compression of Ultrashort Pulses through Scattering Media

Light scattering in inhomogeneous media induces wavefront distortions which pose an inherent limitation in many optical applications. Examples range from microscopy and nanosurgery to astronomy. In recent years, ongoing efforts have made the correction of spatial distortions possible by wavefront shaping techniques. However, when ultrashort pulses are employed scattering induces temporal distortions which hinder their use in nonlinear processes such as in multiphoton microscopy and quantum control experiments. Here we show that correction of both spatial and temporal distortions can be attained by manipulating only the spatial degrees of freedom of the incident wavefront. Moreover, by optimizing a nonlinear signal the refocused pulse can be shorter than the input pulse. We demonstrate focusing of 100fs pulses through a 1mm thick brain tissue, and 1000-fold enhancement of a localized two-photon fluorescence signal. Our results open up new possibilities for optical manipulation and nonlinear imaging in scattering media

Cancer cells exploit an orphan RNA to drive metastatic progression.

Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies

Longer fixation duration while viewing face images

The spatio-temporal properties of saccadic eye movements can be influenced by the cognitive demand and the characteristics of the observed scene. Probably due to its crucial role in social communication, it is argued that face perception may involve different cognitive processes compared with non-face object or scene perception. In this study, we investigated whether and how face and natural scene images can influence the patterns of visuomotor activity. We recorded monkeys’ saccadic eye movements as they freely viewed monkey face and natural scene images. The face and natural scene images attracted similar number of fixations, but viewing of faces was accompanied by longer fixations compared with natural scenes. These longer fixations were dependent on the context of facial features. The duration of fixations directed at facial contours decreased when the face images were scrambled, and increased at the later stage of normal face viewing. The results suggest that face and natural scene images can generate different patterns of visuomotor activity. The extra fixation duration on faces may be correlated with the detailed analysis of facial features

Development of high-throughput methods to screen disease caused by Rhizoctonia solani AG 2-1 in oilseed rape

Background: Rhizoctonia solani (Kühn) is a soil-borne, necrotrophic fungus causing damping off, root rot and stem canker in many cultivated plants worldwide. Oilseed rape (OSR, Brassica napus) is the primary host for anastomosis group (AG) 2-1 of R. solani causing pre- and post-emergence damping-off resulting in death of seedlings and impaired crop establishment. Presently, there are no known resistant OSR genotypes and the main methods for disease control are fungicide seed treatments and cultural practices. The identification of sources of resistance for crop breeding is essential for sustainable management of the disease. However, a high-throughput, reliable screening method for resistance traits is required. The aim of this work was to develop a low cost, rapid screening method for disease phenotyping and identification of resistance traits. Results: Four growth systems were developed and tested: (1) nutrient media plates, (2) compost trays, (3) light expanded clay aggregate (LECA) trays, and (4) a hydroponic pouch and wick system. Seedlings were inoculated with virulent AG 2-1 to cause damping-off disease and grown for a period of 4–10 days. Visual disease assessments were carried out or disease was estimated through image analysis using ImageJ. Conclusion: Inoculation of LECA was the most suitable method for phenotyping disease caused by R. solani AG 2-1 as it enabled the detection of differences in disease severity among OSR genotypes within a short time period whilst allowing measurements to be conducted on whole plants. This system is expected to facilitate identification of resistant germplasm