Sub-cortical brain structure segmentation using F-CNN's

In this paper we propose a deep learning approach for segmenting sub-cortical structures of the human brain in Magnetic Resonance (MR) image data. We draw inspiration from a state-of-the-art Fully-Convolutional Neural Network (F-CNN) architecture for semantic segmentation of objects in natural images, and adapt it to our task. Unlike previous CNN-based methods that operate on image patches, our model is applied on a full blown 2D image, without any alignment or registration steps at testing time. We further improve segmentation results by interpreting the CNN output as potentials of a Markov Random Field (MRF), whose topology corresponds to a volumetric grid. Alpha-expansion is used to perform approximate inference imposing spatial volumetric homogeneity to the CNN priors. We compare the performance of the proposed pipeline with a similar system using Random Forest-based priors, as well as state-of-art segmentation algorithms, and show promising results on two different brain MRI datasets.Comment: ISBI 2016: International Symposium on Biomedical Imaging, Apr 2016, Prague, Czech Republi

A specific group of genes respond to cold dehydration stress in cut Alstroemeria flowers whereas ambient dehydration stress accelerates developmental senescence expression patterns

Petal development and senescence entails a normally irreversible process. It starts with petal expansion and pigment production, and ends with nutrient remobilization and ultimately cell death. In many species this is accompanied by petal abscission. Post-harvest stress is an important factor in limiting petal longevity in cut flowers and accelerates some of the processes of senescence such as petal wilting and abscission. However, some of the effects of moderate stress in young flowers are reversible with appropriate treatments. Transcriptomic studies have shown that distinct gene sets are expressed during petal development and senescence. Despite this, the overlap in gene expression between developmental and stress-induced senescence in petals has not been fully investigated in any species. Here a custom-made cDNA microarray from Alstroemeria petals was used to investigate the overlap in gene expression between developmental changes (bud to first sign of senescence) and typical post-harvest stress treatments. Young flowers were stressed by cold or ambient temperatures without water followed by a recovery and rehydration period. Stressed flowers were still at the bud stage after stress treatments. Microarray analysis showed that ambient dehydration stress accelerates many of the changes in gene expression patterns that would normally occur during developmental senescence. However, a higher proportion of gene expression changes in response to cold stress were specific to this stimulus and not senescence related. The expression of 21 transcription factors was characterized, showing that overlapping sets of regulatory genes are activated during developmental senescence and by different stresses

Modulation of nucleosome dynamics in Huntington's disease

Transcriptional dysregulation and aberrant chromatin remodeling are central features in the pathology of Huntington's disease (HD). In order to more fully characterize these pathogenic events, an assessment of histone profiles and associated gene changes were performed in transgenic N171-82Q (82Q) and R6/2 HD mice. Analyses revealed significant chromatin modification, resulting in reduced histone acetylation with concomitant increased histone methylation, consistent with findings observed in HD patients. While there are no known interventions that ameliorate or arrest HD progression, DNA/RNA-binding anthracyclines may provide significant therapeutic potential by correcting pathological nucleosome changes and realigning transcription. Two such anthracyclines, chromomycin and mithramycin, improved altered nucleosome homeostasis in HD mice, normalizing the chromatin pattern. There was a significant shift in the balance between methylation and acetylation in treated HD mice to that found in wild-type mice, resulting in greater acetylation of histone H3 at lysine 9 and promoting gene transcription. Gene expression profiling in anthracycline-treated HD mice showed molecular changes that correlate with disease correction, such that a subset of downregulated genes were upregulated with anthracycline treatment. Improved nucleosomal dynamics were concurrent with a significant improvement in the behavioral and neuropathological phenotype observed in HD mice. These data show the ability of anthracycline compounds to rebalance epigenetic histone modification and, as such, may provide the rationale for the design of human clinical trials in HD patient

Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage

To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2Q150/Q150, 18-month HdhQ92/Q92 and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trial

Determination of the UV Inactivation Constant Under 280 Nm UV LED Irradiation for SARS-CoV-2

The ongoing emergency provoked by the SARS-CoV-2 pandemic demands the development of technologies to mitigate the spread of infection, and UV irradiation is a technique that can efficiently address this issue. However, proper use of UV equipment for disinfection requires an understanding of how the effects on SARS-CoV-2 are dependent on certain parameters. In this work, we determined the UV-C inactivation constant k for SARS-CoV-2 using an LED source at lambda = 280 nm. Specifically, a Log3 reduction was measured after irradiation for 24 min with a delivered UV-C dose of 23 J m(-2). By multitarget model fitting, n = 2 and k = 0.32 +/- 0.02 m(2) J(-1) were obtained. A lag time for the inactivation effect was also observed, which was attributed to the low irradiation levels used to perform the study. The combination of k and delay time allows for reliable estimation of disinfection times in small, closed environments

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Real world performance of privacy preserving record linkage

Introduction Privacy preserving record linkage (PPRL) using encoded or hashed data has potential to enable large-scale record linkage of previously inaccessible data. With limited real-world evaluation and implementation of PPRL at scale it is challenging for linkage practitioners to judiciously balance data protection with the accuracy and usability of linked datasets. Objectives and Approach We evaluated the performance of PPRL techniques using Bloom filters for linkage of data across primary and secondary care settings. This technique limits the need to disclose personal information for linkage activities. Primary care data included 272,202 records from 16 general practices in NSW. This was linked to 42.8 million records from a 7 year series of emergency presentations, hospitalisations and death registrations. For the purpose of evaluation, personal information was encoded within the data linkage centre. The quality of PPRL linkage was assessed against the true match status based on a gold standard probabilistic linkage using full personal identifiers. Results Compared to the gold standard probabilistic linkage using full personal identifiers, the PPRL techniques produced quality metrics of precision, recall and F measure in excess of 0.90. When configured to leverage pre-existing links between emergency department, hospital and mortality data, quality metrics around 0.98-0.99 were achieved. Lower rates of linkage quality were associated with missing demographic information and some residual variation in linkage quality across practices was observed. Conclusion/Implications PPRL using Bloom filters is a promising technique for achieving high quality linkage across primary and secondary care in Australia. Further evaluation will assess scalability and quality in Australia but international collaborations are encouraged to more rapidly develop the evidence base and tactical approaches to support real world implementations

Canadian trends in the social determinants of health inequalities, a census-mortality linkage approach

Introduction Mortality inequalities by income and education levels have historically been estimated using an area-based approach in Canada. Although useful in measuring socioeconomic inequalities overtime, this method underestimates the level of inequality and only allows the examination of a single dimension at a time. Objectives and Approach To create a series of census linked datasets that allowed for the examination of health inequalities across different socioeconomic dimensions. Specifically, five census cycles (beginning with the 1991 Census) were probabilistically and deterministically linked to different health outcomes (mortality, cancer, hospitalization) to create the Canadian Census Health and Environment Cohort (CanCHEC). Each dataset was created using a similar methodological approach which allowed for the measurement of these health inequalities over time. Mortality inequalities by both income and education level (including multidimensional) for all causes and cause-specific groups were examined. Results Five census linked datasets were constructed that followed mortality for a period of up to 20 years. The 1991 CanCHEC includes 2.6 million adults, the 1996 and 2001 CanCHECs include 3.5 million adults respectively, and the 2006 and 2011 CanCHECs include 5.9 and 6.5 million people respectively. Findings revealed a stair-stepped gradient in all-cause and cause-specific mortality by educational attainment and income quintile across each time period. The lowest mortality rates were among the university educated and richest income quintile and highest mortality rates among those with less than high school graduation and the poorest income quintile. The gradient differed by cause of death groupings. Over the 25-year time period, the mortality gradient trend varied by socioeconomic dimension and cause of death. Conclusion/Implications These data show clear mortality inequalities by socioeconomic position across the different time periods. These linked datasets can help advance knowledge in understanding health inequalities in Canada as well as provide a tool for on-going surveillance of health inequalities by different socioeconomic dimensions

INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial

Background: The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. Methods: Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. Results: Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. Conclusions: Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel