Development of an automated detection algorithm for patient motion blur in digital mammograms

The purpose is to develop and validate an automated method for detecting image unsharpness caused by patient motion blur in digital mammograms. The goal is that such a tool would facilitate immediate re-taking of blurred images, which has the potential to reduce the number of recalled examinations, and to ensure that sharp, high-quality mammograms are presented for reading. To meet this goal, an automated method was developed based on interpretation of the normalized image Wiener Spectrum. A preliminary algorithm was developed using 25 cases acquired using a single vendor system, read by two expert readers identifying the presence of blur, location, and severity. A predictive blur severity score was established using multivariate modeling, which had an adjusted coefficient of determination, R2 =0.63±0.02, for linear regression against the average reader-scored blur severity. A heatmap of the relative blur magnitude showed good correspondence with reader sketches of blur location, with a Spearman rank correlation of 0.70 between the algorithmestimated area fraction with blur and the maximum of the blur area fraction categories of the two readers. Given these promising results, the algorithm-estimated blur severity score and heatmap are proposed to be used to aid observer interpretation. The use of this automated blur analysis approach, ideally with feedback during an exam, could lead to a reduction in repeat appointments for technical reasons, saving time, cost, potential anxiety, and improving image quality for accurate diagnosis.</p

ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 115, doi:10.1038/s41598-017-00091-1.Mutations in Fused in Sarcoma/Translocated in Liposarcoma (FUS) cause familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive axonal degeneration mainly affecting motor neurons. Evidence from transgenic mouse models suggests mutant forms of FUS exert an unknown gain-of-toxic function in motor neurons, but mechanisms underlying this effect remain unknown. Towards this end, we studied the effect of wild type FUS (FUS WT) and three ALS-linked variants (G230C, R521G and R495X) on fast axonal transport (FAT), a cellular process critical for appropriate maintenance of axonal connectivity. All ALS-FUS variants impaired anterograde and retrograde FAT in squid axoplasm, whereas FUS WT had no effect. Misfolding of mutant FUS is implicated in this process, as the molecular chaperone Hsp110 mitigated these toxic effects. Interestingly, mutant FUS-induced impairment of FAT in squid axoplasm and of axonal outgrowth in mammalian primary motor neurons involved aberrant activation of the p38 MAPK pathway, as also reported for ALS-linked forms of Cu, Zn superoxide dismutase (SOD1). Accordingly, increased levels of active p38 MAPK were detected in post-mortem human ALS-FUS brain tissues. These data provide evidence for a novel gain-of-toxic function for ALS-linked FUS involving p38 MAPK activation.We are grateful for funding from NIH/NINDS (R01 NS078145, R01 NS090352, and R21 NS091860 to D.A.B., R01 NS066942A and R21 NS096642 to G.M., R01NS023868 and R01NS041170 to S.T.B.), the ALS Therapy Alliance/CVS Pharmacy (to D.A.B. and G.M.) and the ALS Association (to C.F. and J.M.)

Birds and berries : the costs and benefits of birds in agricultural ecosystems

There is a long history of studying bird interactions with agriculture. The field of economic ornithology, which looked at the positive and negative aspects of birds in agricultural, was popular at the end of the 19th century. However, the field quickly fell into disrepair. Today, we once again recognize that birds can provide both services and disservices to agriculture. The balance of services and disservices that birds can provide depends on many factors, such as the species found in the crop, the crop in question, and other factors such as surrounding landcover. Many of these factors are currently being disentangled in this rapidly evolving area of research. To understand how birds interact with crops, we first need to know more about the species that use different crops. In Chapter 1 I characterized the different species that use sweet cherry orchards, blueberry fields, 'Honeycrisp' apple orchards, and vineyards in three major fruit growing regions during the early 2010s. I also determined the abundance of fruit-consuming birds found in each crop and investigated which fruit-eating species could be considered important fruit consumers based on their frequency of detection and fruit consuming habits. I also examined if the heterogeneity of the surrounding landcover influenced the abundance of birds found in the various fruit fields/orchards. I found that the abundance of fruit-eating birds varied by both region and crop, as did which species were designated as important fruit consumers. However, abundance was not influenced by the heterogeneity of the surrounding landcover, counter to our predictions. Certain species of birds are known to be beneficial in agricultural areas. Birds of prey are of particular interest, as they can deter vertebrate pests. In Chapter 2, I investigated the effectiveness of installing nest boxes in attracting American Kestrels to blueberry growing operations in Western Michigan. I then compared the results with a similar study where nest boxes were used to attract kestrels to sweet cherry orchards in Northern Michigan. By installing nest boxes and performing survey transects, I found that boxes did increase the overall presence of kestrel in blueberry fields, although the effect was much weaker than in the sweet cherry study. Nest box occupancy was much lower in the blueberry system when compared to the sweet cherry study region, but reproductive success measures, such as mean clutch size, were similar. While birds of prey have been documented consuming and deterring fruit-eating birds, they may consumer/deter other species of birds as well. In Chapter 3 I investigated the effect of American kestrel presence on bird abundances in blueberry fields in Western Michigan. I found that active American kestrel boxes did not deter fruit-eating birds from blueberry fields. However, active boxes did deter non-fruit-eating birds, although this trend only held when the box was active. This finding introduces the possibility that kestrels might deter beneficial insectivorous birds, which could be detrimental to the blueberry fields. Through my work, I have found that the effect that birds will have on a particular agricultural system will be highly context dependent. The mixture of bird species present, the crop type, region, and many other factors will influence how birds fit into an agroecosystem. Introducing predators to control for pests could induce a trophic cascade with positive or negative outcomes. Predicting the nature of the outcome will require intensive studies of the crop in question, with knowledge of the bird and arthropod community in the region.Thesis (Ph. D.)--Michigan State University. Integrative Biology, 2022Includes bibliographical reference

Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda

This paper was one of four papers commissioned to review the role of social sciences in NTD control by TDR, the Special Programme for Research and Training on Tropical Diseases, which is executed by WHO and co-sponsored by UNICEF, UNDP, the World Bank and WHO.This article has been made available through the Brunel Open Access Publishing Fund.Background: Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods: Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results: The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. Conclusion: While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities.This article is available through the Brunel Open Access Publishing Fund

Storytelling and poetry in the time of Coronavirus

The coronavirus crisis occurs at a time when many clinicians have already experienced burnout. One in three Irish doctors were suffering from burnout in the 2019 National Study of Wellbeing of Hospital Doctors in Ireland; rates are also high in Irish Psychiatry. We present a perspective on the use of narrative in medicine and recognise that storytelling, and the patient history are very much at the heart of medicine. Clinician storytelling, such as Schwartz Rounds and Balint group work, has very much come to the fore in Irish Psychiatry and in training. Projects such as MindReading have explored overlaps between clinicians, humanities experts and experts by experience. We give an overview of some approaches from the movement around narrative in medicine to bolster this. We explore why clinicians write as ways to support identification, catharsis and a way to process experiences. Clinicians and patients may also use literature and poetry to promote coping. The historical context and practical strategies are highlighted, particularly with reference to poetry use during the current crisis

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Promising Practices of Dairy, Horse, and Livestock Evaluation Career Development Event Coaches: A Mixed-Methods Study

The present study describes promising practices of successful dairy, horse, and livestock judging coaches. Expert coaches were interviewed regarding previous experience, coaching philosophy, coaching objectives, coaching style, and advice. Twenty-seven promising practices and eight themes were identified from the interviews. A questionnaire was sent to the accessible population of coaches to determine practice usage and relationship to youth performance. Influential and motivating practices were found to be most used by coaches. Youth performance was related to use of competitive and expectancy related promising practices. Findings suggest use of promising practices would facilitate greater coaching success in competition and youth development