Early maternal separation impacts cognitive flexibility at the age of first independence in mice.

Early life adversity is associated with increased risk for mental and physical health problems, including substance abuse. Changes in neural development caused by early life insults could cause or complicate these conditions. Maternal separation (MS) is a model of early adversity for rodents. Clear effects of MS have been shown on behavioral flexibility in rats, but studies of effects of MS on cognition in mice have been mixed. We hypothesized that previous studies focused on adult mice may have overlooked a developmental transition point when juvenile mice exhibit greater flexibility in reversal learning. Here, using a 4-choice reversal learning task we find that early MS leads to decreased flexibility in post-weaning juvenile mice, but no significant effects in adults. In a further study of voluntary ethanol consumption, we found that adult mice that had experienced MS showed greater cumulative 20% ethanol consumption in an intermittent access paradigm compared to controls. Our data confirm that the MS paradigm can reduce cognitive flexibility in mice and may enhance risk for substance abuse. We discuss possible interpretations of these data as stress-related impairment or adaptive earlier maturation in response to an adverse environment

The Electrochemistry of Hydrogen Peroxide on Uranium Dioxide and the Modelling of Used Nuclear Fuel Corrosion under Permanent Disposal Conditions

This thesis reports a series of investigations examining the corrosion process of used nuclear fuel under permanent disposal conditions. The motivation of the project is that the safety assessment of deep geological disposal of spent nuclear fuel requires a fundamental understanding of the processes controlling fuel corrosion which could lead to the release of radionuclides to the geosphere from a failed container. One primary objective of this project was to develop a computational model in order to simulate fuel corrosion under the disposal conditions. A series of simulations based on COMSOL were designed and developed to determine the influence of redox conditions, with the emphasis on α-radiolysis and steel vessel corrosion products, on the corrosion rate of spent fuel. A second objective of this project was to develop a more detailed understanding of the H2O2 decomposition process and its influence on UO2 (nuclear fuel) corrosion. The radiolytically produced H2O2 is the primary driving force for nuclear fuel corrosion under disposal conditions. The influence of several variables (potential, pH, carbonate/bicarbonate, and fission products) on the reactivity of H2O2 has been evaluated. Their influence on the surface composition and electrical conductivity of UO2 was found to significantly affect the surface redox reaction rates and alter the overall fuel corrosion rate. The analytical techniques include electrochemical measurements (CV, CSV, ECORR, LPR, EIS) and surface/solution analyses (SEM, XPS, ICP-AES)

Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

Background: Few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: The postcodes of the 2424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: Higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: Features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies

Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

Background: Few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: The postcodes of the 2424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: Higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: Features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies

Improving ART Pregnancy Rate with Two Kinds of Media and Two Types of Incubators

Culture media and incubators have played a key role in embryo quality. Here, we observed individual patient’s embryos to have different response for media and incubators. Patient’s 1850 zygotes were divided into two groups randomly and were cultured in Global and in P1 medium. The cleavage rate and embryo quality were recorded. The result showed that the cleavage, top quality embryos on Day 2 and Day 3 were not statistically different between media. However, 45% patient’s embryos grew very well in both Global and P1. 22% patient’s embryos grew well only in Global but poor quality in P1, while 21% grew well in the Global but poorly in the P1. Only 12% patient embryos did not grow well in both. The pregnant rate was only 40% in P1 or 42.5% in Global (P>0.05). However, when two media were used simultaneously, the pregnant rate increased to 70.1%. Also, two incubators showed significant higher pregnant rate than in single incubator (73.2% vs. 60%, P<0.05). In conclusion, the favorable response of individual patient’s embryos to media and incubators suggests that using two media and two incubators for embryo culture could significantly improve embryo quality and pregnant rates

Breast density classification with deep convolutional neural networks

Breast density classification is an essential part of breast cancer screening. Although a lot of prior work considered this problem as a task for learning algorithms, to our knowledge, all of them used small and not clinically realistic data both for training and evaluation of their models. In this work, we explore the limits of this task with a data set coming from over 200,000 breast cancer screening exams. We use this data to train and evaluate a strong convolutional neural network classifier. In a reader study, we find that our model can perform this task comparably to a human expert

Role of myosin light chain kinase in intestinal epithelial barrier defects in a rat model of bowel obstruction

<p>Abstract</p> <p>Background</p> <p>Bowel obstruction is a common cause of abdominal emergency, since the patients are at increased risk of septicemia resulting in high mortality rate. While the compartmentalized changes in enteric microfloral population and augmentation of bacterial translocation (BT) have already been reported using experimental obstruction models, alterations in epithelial permeability of the obstructed guts has not been studied in detail. Myosin light chain kinase (MLCK) is actively involved in the contraction of epithelial perijunctional actinomyosin ring and thereby increases paracellular permeability. In the current study we attempt to investigate the role of MLCK in epithelial barrier defects using a rat model of simple mechanical obstruction.</p> <p>Methods</p> <p>Wistar rats received intraperitoneal injection of ML-7 (a MLCK inhibitor) or vehicle at 24, 12 and 1 hrs before and 12 hrs after intestinal obstruction (IO). The distal small intestine was obstructed with a single ligature placed 10 cm proximal to the ileocecal junction in IO rats for 24 hrs. Sham-operated rats served as controls.</p> <p>Results</p> <p>Mucosal injury, such as villous blunting and increased crypt/villus ratio, was observed in the distal small intestine of IO rats. Despite massive enterocyte shedding, intestinal villi were covered with a contiguous epithelial layer without cell apoptosis. Increased transmural macromolecular flux was noticed in the distal small intestine and the proximal colon after IO. The bacterial colony forming units in the spleen and liver of IO rats were significantly higher than those of sham controls. Addition of ML-7 ameliorated the IO-triggered epithelial MLC phosphorylation, mucosal injury and macromolecular flux, but not the level of BT.</p> <p>Conclusions</p> <p>The results suggest that IO-induced premature enterocytic sloughing and enhanced paracellular antigenic flux were mediated by epithelial MLCK activation. In addition, enteric bacteria may undergo transcytotic routes other than paracellular paths to cross the epithelium.</p