A Compact Representation of Histopathology Images using Digital Stain Separation & Frequency-Based Encoded Local Projections

In recent years, histopathology images have been increasingly used as a diagnostic tool in the medical field. The process of accurately diagnosing a biopsy sample requires significant expertise in the field, and as such can be time-consuming and is prone to uncertainty and error. With the advent of digital pathology, using image recognition systems to highlight problem areas or locate similar images can aid pathologists in making quick and accurate diagnoses. In this paper, we specifically consider the encoded local projections (ELP) algorithm, which has previously shown some success as a tool for classification and recognition of histopathology images. We build on the success of the ELP algorithm as a means for image classification and recognition by proposing a modified algorithm which captures the local frequency information of the image. The proposed algorithm estimates local frequencies by quantifying the changes in multiple projections in local windows of greyscale images. By doing so we remove the need to store the full projections, thus significantly reducing the histogram size, and decreasing computation time for image retrieval and classification tasks. Furthermore, we investigate the effectiveness of applying our method to histopathology images which have been digitally separated into their hematoxylin and eosin stain components. The proposed algorithm is tested on the publicly available invasive ductal carcinoma (IDC) data set. The histograms are used to train an SVM to classify the data. The experiments showed that the proposed method outperforms the original ELP algorithm in image retrieval tasks. On classification tasks, the results are found to be comparable to state-of-the-art deep learning methods and better than many handcrafted features from the literature.Comment: Accepted for publication in the International Conference on Image Analysis and Recognition (ICIAR 2019

Emergent synergistic lysosomal toxicity of chemical mixtures in molluscan blood cells (hemocytes)

The problem of effective assessment of risk posed by complex mixtures of toxic chemicals in the environment is a major challenge for government regulators and industry. The biological effect of the individual contaminants, where these are known, can be measured; but the problem lies in relating toxicity to the multiple constituents of contaminant cocktails. The objective of this study was to test the hypothesis that diverse contaminant mixtures may cause a greater toxicity than the sum of their individual parts, due to synergistic interactions between contaminants with different intracellular targets. Lysosomal membrane stability in hemocytes from marine mussels was used for in vitro toxicity tests; and was coupled with analysis using the isobole method and a linear additive statistical model. The findings from both methods have shown significant emergent synergistic interactions between environmentally relevant chemicals (i.e., polycyclic aromatic hydrocarbons, pesticides, biocides and a surfactant) when exposed to isolated hemocytes as a mixture of 3 & 7 constituents. The results support the complexity-based hypothesis that emergent toxicity occurs with increasing contaminant diversity, and raises questions about the validity of estimating toxicity of contaminant mixtures based on the additive toxicity of single components. Further experimentation is required to investigate the potential for interactive effects in mixtures with more constituents (e.g., 50 –100) at more environmentally realistic concentrations in order to test other regions of the model, namely, very low concentrations and high diversity. Estimated toxicant diversity coupled with tests for lysosomal damage may provide a potential tool for determining the toxicity of estuarine sediments, dredge spoil or contaminated soil

Oxidative stress, lysosomal damage and dysfunctional autophagy in molluscan hepatopancreas (digestive gland) induced by chemical contaminants

Autophagy is a highly conserved evolutionary survival or defence process that enables cells and organisms to survive periods of environmental stress by breaking down cellular organelles and macromolecules in autolysosomes to provide a supply of nutrients for cell maintenance. However, autophagy is also a part of normal cellular physiology that facilitates the turnover of cellular constituents under normal conditions: it can be readily augmented by mild environmental stress; but becomes dysfunctional with severe oxidative stress leading to cellular pathology. The molluscan hepatopancreas or digestive gland provides a versatile and environmentally relevant model to investigate lysosomal autophagy and stress-induced dysfunctional autophagy. This latter process has been implicated in many animal and human disease conditions, including degenerative and neurodegenerative diseases, as well as obesity related conditions. Many environmental pollutants have also been found to induce dysfunctional autophagy in molluscan hepatopancreatic digestive cells, and in this study, the marine blue mussel Mytilus galloprovincialis was exposed for 7 days to: 0.1 μM, 1 μM and 10 μM concentrations of fluoranthene and phenanthrene (PAHs); chlorpyrifos and malathion (organophosphorus compounds); atrazine (triazine herbicide); copper (transition metal) and dodecylbenzene sulphonic acid (LAS, surfactant). The marine snail or periwinkle, Littorina littorea, was also exposed to phenanthrene, chlorpyrifos and copper. Indices of oxidative stress, cell injury and dysfunctional autophagy were measured (i.e., lysosomal membrane stability, protein carbonyls, lipofuscin, and lysosomal accumulation of lipid or lipidosis). Evidence of oxidative stress, based on the elevation of lipofuscin and protein carbonyls, was found for all compounds tested; with chlorpyrifos being the most toxic to both species. Dysfunctional autophagy was induced by all of the compounds tested in both species, except for atrazine in mussels. This failure of normal autophagy was consistently associated with oxidative stress. Autophagic dysfunction is an important emerging feature in the aetiology of many disease conditions in animals and humans; and an explanatory conceptual mechanistic model has been developed for dysregulation of autophagy in response to oxidative stress

The active living gender's gap challenge: 2013-2017 Eurobarometers physical inactivity data show constant higher prevalence in women with no progress towards global reduction goals

BACKGROUND: The World Health Organization (WHO) considers physical inactivity (PIA) as a critical noncommunicable factor for disease and mortality, affecting more women than men. In 2013, the WHO set a 10% reduction of the PIA prevalence, with the goal to be reached by 2025. Changes in the 2013-2017 period of physical inactivity prevalence in the 28 European Union (EU) countries were evaluated to track the progress in achieving WHO 2025 target. METHODS: In 2013 and 2017 EU Special Eurobarometers, the physical activity levels reported by the International Physical Activity Questionnaire of 53,607 adults were analyzed. Data were considered as a whole sample and country-by-country. A χ2 test was used to analyze the physical inactivity prevalence (%) between countries, analyzing women and men together and separately. Additionally, PIA prevalence was analyzed between years (2013-2017) for the overall EU sample and within-country using a Z-Score for two population proportions. RESULTS: The PIA prevalence increased between 2013 and 2017 for the overall EU sample (p <  0.001), and for women (p = 0.04) and men (p < 0.001) separately. Data showed a higher PIA prevalence in women versus men during both years (p <  0.001). When separately considering changes in PIA by gender, only Belgium's women and Luxembourg's men showed a reduction in PIA prevalence. Increases in PIA prevalence over time were observed in women from Austria, Croatia, Germany, Lithuania, Malta, Portugal, Romania, and Slovakia and in men from Bulgaria, Croatia, Czechia, Germany, Italy, Lithuania, Portugal, Romania, Slovakia, and Spain. CONCLUSIONS: PIA prevalence showed an overall increase across the EU and for both women and men between 2013 and 2017, with higher rates of PIA reported for women versus men during both years. PIA prevalence was reduced in only Belgium's women and Luxembourg's men. Our data indicate a limited gender-sensible approach while tacking PIA prevalence with no progress reaching global voluntary reductions of PIA for 2025

Social marketing and healthy eating : Findings from young people in Greece

This document is the Accepted Manuscript version. The final publication is available at Springer via http://dx.doi.org/10.1007/s12208-013-0112-xGreece has high rates of obesity and non-communicable diseases owing to poor dietary choices. This research provides lessons for social marketing to tackle the severe nutrition-related problems in this country by obtaining insight into the eating behaviour of young adults aged 18–23. Also, the main behavioural theories used to inform the research are critically discussed. The research was conducted in Athens. Nine focus groups with young adults from eight educational institutions were conducted and fifty-nine participants’ views towards eating habits, healthy eating and the factors that affect their food choices were explored. The study found that the participants adopted unhealthier nutritional habits after enrolment. Motivations for healthy eating were good health, appearance and psychological consequences, while barriers included lack of time, fast-food availability and taste, peer pressure, lack of knowledge and lack of family support. Participants reported lack of supportive environments when deciding on food choices. Based on the findings, recommendations about the development of the basic 4Ps of the marketing mix, as well as of a fifth P, for Policy are proposedPeer reviewe

From open radical hysterectomy to robot-assisted laparoscopic radical hysterectomy for early stage cervical cancer: aspects of a single institution learning curve

We analysed the introduction of the robot-assisted laparoscopic radical hysterectomy in patients with early-stage cervical cancer with respect to patient benefits and surgeon-related aspects of a surgical learning curve. A retrospective review of the first 14 robot-assisted laparoscopic radical hysterectomies and the last 14 open radical hysterectomies in a similar clinical setting with the same surgical team was conducted. Patients were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and open radical hysterectomy (RH) before August 2006 and were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and robot-assisted laparoscopic radical hysterectomy (RALRH) after August 2006. Overall, blood loss in the open cases was significantly more compared with the robot cases. Median hospital stay after RALRH was 5 days less than after RH. The median theatre time in the learning period for the robot procedure was reduced from 9 h to less that 4 h and compared well to the 3 h and 45 min for an open procedure. Three complications occurred in the open group and one in the robot group. RALRH is feasible and of benefit to the patient with early stage cervical cancer by a reduction of blood loss and reduced hospital stay. Introduction of this new technique requires a learning curve of less than 15 cases that will reduce the operating time to a level comparable to open surgery

Systematic review of tonsil surgery quality registers and introduction of the Nordic Tonsil Surgery Register Collaboration

Surgical quality registers provide tools to measure and improve the outcome of surgery. International register collaboration creates an opportunity to assess and critically evaluate national practices, and increases the size of available datasets. Even though millions of yearly tonsillectomies and tonsillotomies are performed worldwide, clinical practices are variable and inconsistency of evidence regarding the best clinical practice exists. The need for quality improvement actions is evident. We aimed to systematically investigate the existing tonsil surgery quality registers found in the literature, and to provide a thorough presentation of the planned Nordic Tonsil Surgery Register Collaboration. A systematic literature search of MEDLINE and EMBASE databases (from January 1990 to December 2016) was conducted to identify registers, databases, quality improvement programs or comprehensive audit programs addressing tonsil surgery. We identified two active registers and three completed audit programs focusing on tonsil surgery quality registration. Recorded variables were fairly similar, but considerable variation in coverage, number of operations included and length of time period for inclusion was discovered. Considering tonsillectomies and tonsillotomies being among the most commonly performed surgical procedures in otorhinolaryngology, it is surprising that only two active registers could be identified. We present a Nordic Tonsil Surgery Register Collaboration-an international tonsil surgery quality register project aiming to provide accurate benchmarks and enhance the quality of tonsil surgery in Denmark, Finland, Norway and Sweden.Peer reviewe

Immunomodulation by Different Types of N-Oxides in the Hemocytes of the Marine Bivalve Mytilus galloprovincialis

The potential toxicity of engineered nanoparticles (NPs) for humans and the environment represents an emerging issue. Since the aquatic environment represents the ultimate sink for NP deposition, the development of suitable assays is needed to evaluate the potential impact of NPs on aquatic biota. The immune system is a sensitive target for NPs, and conservation of innate immunity represents an useful basis for studying common biological responses to NPs. Suspension-feeding invertebrates, such as bivalves, are particularly at risk to NP exposure, since they have extremely developed systems for uptake of nano and microscale particles integral to intracellular digestion and cellular immunity. Evaluation of the effects of NPs on functional parameters of bivalve immunocytes, the hemocytes, may help understanding the major toxic mechanisms and modes of actions that could be relevant for different NP types in aquatic organisms.In this work, a battery of assays was applied to the hemocytes of the marine bivalve Mytilus galloprovincialis to compare the in vitro effects of different n-oxides (n-TiO2, n-SiO2, n-ZnO, n-CeO2) chosen on the basis of their commercial and environmental relevance. Physico-chemical characterization of both primary particles and NP suspensions in artificial sea water-ASW was performed. Hemocyte lysosomal and mitochondrial parameters, oxyradical and nitric oxide production, phagocytic activity, as well as NP uptake, were evaluated. The results show that different n-oxides rapidly elicited differential responses hemocytes in relation to their chemical properties, concentration, behavior in sea water, and interactions with subcellular compartments. These represent the most extensive data so far available on the effects of NPs in the cells of aquatic organisms. The results indicate that Mytilus hemocytes can be utilized as a suitable model for screening the potential effects of NPs in the cells of aquatic invertebrates, and may provide a basis for future experimental work for designing environmentally safer nanomaterials

Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue

Background: DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have been limited to the investigation of specific target regions. Analyses spanning the entire mitochondrial genome have been limited, potentially due to the amount of input DNA required. Further, mitochondrial genetic studies have been previously confounded by nuclear-mitochondrial pseudogenes. Methylated DNA Immunoprecipitation Sequencing is a technique widely used to profile DNA methylation across the nuclear genome; however, reads mapped to mitochondrial DNA are often discarded. Here, we have developed an approach to control for nuclear-mitochondrial pseudogenes within Methylated DNA Immunoprecipitation Sequencing data. We highlight the utility of this approach in identifying differences in mitochondrial DNA methylation across regions of the human brain and pre-mortem blood. Results: We were able to correlate mitochondrial DNA methylation patterns between the cortex, cerebellum and blood. We identified 74 nominally significant differentially methylated regions (p < 0.05) in the mitochondrial genome, between anatomically separate cortical regions and the cerebellum in matched samples (N = 3 matched donors). Further analysis identified eight significant differentially methylated regions between the total cortex and cerebellum after correcting for multiple testing. Using unsupervised hierarchical clustering analysis of the mitochondrial DNA methylome, we were able to identify tissue-specific patterns of mitochondrial DNA methylation between blood, cerebellum and cortex. Conclusions: Our study represents a comprehensive analysis of the mitochondrial methylome using pre-existing Methylated DNA Immunoprecipitation Sequencing data to identify brain region-specific patterns of mitochondrial DNA methylation

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty