Deep learning quantification of percent steatosis in donor liver biopsy frozen sections

BACKGROUND: Pathologist evaluation of donor liver biopsies provides information for accepting or discarding potential donor livers. Due to the urgent nature of the decision process, this is regularly performed using frozen sectioning at the time of biopsy. The percent steatosis in a donor liver biopsy correlates with transplant outcome, however there is significant inter- and intra-observer variability in quantifying steatosis, compounded by frozen section artifact. We hypothesized that a deep learning model could identify and quantify steatosis in donor liver biopsies. METHODS: We developed a deep learning convolutional neural network that generates a steatosis probability map from an input whole slide image (WSI) of a hematoxylin and eosin-stained frozen section, and subsequently calculates the percent steatosis. Ninety-six WSI of frozen donor liver sections from our transplant pathology service were annotated for steatosis and used to train (n = 30 WSI) and test (n = 66 WSI) the deep learning model. FINDINGS: The model had good correlation and agreement with the annotation in both the training set (r of 0.88, intraclass correlation coefficient [ICC] of 0.88) and novel input test sets (r = 0.85 and ICC=0.85). These measurements were superior to the estimates of the on-service pathologist at the time of initial evaluation (r = 0.52 and ICC=0.52 for the training set, and r = 0.74 and ICC=0.72 for the test set). INTERPRETATION: Use of this deep learning algorithm could be incorporated into routine pathology workflows for fast, accurate, and reproducible donor liver evaluation. FUNDING: Mid-America Transplant Society

Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure.

BACKGROUND: The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group A and DC8, associated with severe malaria, may have a growth advantage in immunologically naïve individuals. However, this idea has not been tested in longitudinal studies. METHODS: Here we assessed expression of the var genes encoding PfEMP1, in parasites sampled from volunteers with varying prior exposure to malaria, following experimental infection by sporozoites (PfSPZ). Using qPCR, we tested for associations between the expression of various var subgroups in surviving parasite populations from each volunteer and 1) the levels of participants' antibodies to infected erythrocytes before challenge infection and 2) the apparent in vivo parasite multiplication rate. RESULTS: We show that 1) expression of var genes encoding for group A and DC8-like PfEMP1 were associated with low levels of antibodies to infected erythrocytes (αIE) before challenge, and 2) expression of a DC8-like CIDRα1.1 domain was associated with higher apparent parasite multiplication rate in a manner that was independent of levels of prior antibodies to infected erythrocytes. CONCLUSIONS: This study provides insight into the role of antibodies to infected erythrocytes surface antigens in the development of naturally acquired immunity and may help explain why specific PfEMP1 variants may be associated with severe malaria. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR201211000433272 . Date of registration: 10th October 2012

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Bioassay studies support the potential for latrogenic transmission of variant Creutzfeldt Jakob disease through dental procedures

Background: Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient? Methods: BSE-301V was used as a clinically relevant model for vCJD. VM-mice were challenged by injection of infected brain homogenate into the small intestine (Q1) or by five minute contact between a deliberately-contaminated dental file and the gingival margin (Q2). Ten tissues were collected from groups of challenged mice at three or four weekly intervals, respectively. Each tissue was pooled, homogenised and bioassayed in indicator mice. Findings: Challenge via the small intestine gave a transmission rate of 100% (mean incubation 157±17 days). Infectivity was found in both dental pulp and the gingival margin within 3 weeks of challenge and was observed in all tissues tested within the oral cavity before the appearance of clinical symptoms. Following exposure to deliberately contaminated dental files, 97% of mice developed clinical disease (mean incubation 234±33 days). Interpretation: Infectivity was higher than expected, in a wider range of oral tissues, than was allowed for in previous risk assessments. Disease was transmitted following transient exposure of the gingiva to a contaminated dental file. These observations provide evidence that dental procedures could be a route of cross-infection for vCJD and support the enforcement of single-use for certain dental instruments

“Beyond words”: a researcher’s guide to using photo elicitation in psychology

The use of photo elicitation is limited within the field of psychology despite its theoretical and practical potential. It offers significant benefits as a qualitative method that could present a new and interesting way of exploring previously understood topics within the discipline. Within our discussions, we present a Step-by-Step guide in which we outline the key practical stages, as well as ethical assurances involved in photo elicitation research, using our ongoing research as an illustrative example. It is intended that this could be used as a model of good practice for developing research paradigms beyond those typically used within the psychology discipline

A Two-Gene Balance Regulates Salmonella Typhimurium Tolerance in the Nematode Caenorhabditis elegans

Lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. However, using the nematode Caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme LYS-7 renders animals susceptible to killing by the fatal fungal human pathogen Cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria Salmonella Typhimurium. This trade-off in immunological susceptibility in C. elegans is further mediated by the reciprocal activity of lys-7 and the tyrosine kinase abl-1. Together this implies a greater complexity in C. elegans innate immune function than previously thought

The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design

Abstract: Adaptive designs (ADs) allow pre-planned changes to an ongoing trial without compromising the validity of conclusions and it is essential to distinguish pre-planned from unplanned changes that may also occur. The reporting of ADs in randomised trials is inconsistent and needs improving. Incompletely reported AD randomised trials are difficult to reproduce and are hard to interpret and synthesise. This consequently hampers their ability to inform practice as well as future research and contributes to research waste. Better transparency and adequate reporting will enable the potential benefits of ADs to be realised. This extension to the Consolidated Standards Of Reporting Trials (CONSORT) 2010 statement was developed to enhance the reporting of randomised AD clinical trials. We developed an Adaptive designs CONSORT Extension (ACE) guideline through a two-stage Delphi process with input from multidisciplinary key stakeholders in clinical trials research in the public and private sectors from 21 countries, followed by a consensus meeting. Members of the CONSORT Group were involved during the development process. The paper presents the ACE checklists for AD randomised trial reports and abstracts, as well as an explanation with examples to aid the application of the guideline. The ACE checklist comprises seven new items, nine modified items, six unchanged items for which additional explanatory text clarifies further considerations for ADs, and 20 unchanged items not requiring further explanatory text. The ACE abstract checklist has one new item, one modified item, one unchanged item with additional explanatory text for ADs, and 15 unchanged items not requiring further explanatory text. The intention is to enhance transparency and improve reporting of AD randomised trials to improve the interpretability of their results and reproducibility of their methods, results and inference. We also hope indirectly to facilitate the much-needed knowledge transfer of innovative trial designs to maximise their potential benefits. In order to encourage its wide dissemination this article is freely accessible on the BMJ and Trials journal websites.“To maximise the benefit to society, you need to not just do research but do it well” Douglas G Altma

A Systematic Review of Re-Identification Attacks on Health Data

Privacy legislation in most jurisdictions allows the disclosure of health data for secondary purposes without patient consent if it is de-identified. Some recent articles in the medical, legal, and computer science literature have argued that de-identification methods do not provide sufficient protection because they are easy to reverse. Should this be the case, it would have significant and important implications on how health information is disclosed, including: (a) potentially limiting its availability for secondary purposes such as research, and (b) resulting in more identifiable health information being disclosed. Our objectives in this systematic review were to: (a) characterize known re-identification attacks on health data and contrast that to re-identification attacks on other kinds of data, (b) compute the overall proportion of records that have been correctly re-identified in these attacks, and (c) assess whether these demonstrate weaknesses in current de-identification methods.Searches were conducted in IEEE Xplore, ACM Digital Library, and PubMed. After screening, fourteen eligible articles representing distinct attacks were identified. On average, approximately a quarter of the records were re-identified across all studies (0.26 with 95% CI 0.046-0.478) and 0.34 for attacks on health data (95% CI 0-0.744). There was considerable uncertainty around the proportions as evidenced by the wide confidence intervals, and the mean proportion of records re-identified was sensitive to unpublished studies. Two of fourteen attacks were performed with data that was de-identified using existing standards. Only one of these attacks was on health data, which resulted in a success rate of 0.00013.The current evidence shows a high re-identification rate but is dominated by small-scale studies on data that was not de-identified according to existing standards. This evidence is insufficient to draw conclusions about the efficacy of de-identification methods

The Feasibility, Appropriateness, Meaningfulness, and Effectiveness of Parenting and Family Support Programs Delivered in the Criminal Justice System: A Systematic Review

Children whose parents are involved in the criminal justice system (CJS) are at increased risk of developing social, emotional, and behavioural difficulties and are more likely than their peers to become involved in the CJS themselves. Parenting behaviour and parent-child relationships have the potential to affect children’s outcomes with positive parenting practices having the potential to moderate some of the negative outcomes associated with parental involvement in the CJS. However, many parents in the CJS may lack appropriate role models to support the development of positive parenting beliefs and practices. Parenting programs offer an opportunity for parents to enhance their parenting knowledge and behaviours and improve relationships with children. Quantitative and qualitative evidence pertaining to the implementation and effectiveness of parenting programs delivered in the CJS was included. Five databases were searched and a total of 1145 articles were identified of which 29 met the review inclusion criteria. Overall, programs were found to significantly improve parenting attitudes; however, evidence of wider effects is limited. Additionally, the findings indicate that parenting programs can be meaningful for parents. Despite this, a number of challenges for implementation were found including the transient nature of the prison population and a lack of parent-child contact. Based on these findings, recommendations for the future development and delivery of programs are discussed

Southeastern Association of Law Libraries Annual Meeting

The 2009 SEAALL Annual Meeting was held in Athens Georgia, April 16-18, 2009