Properties Of Simultaneous Discrete Occasion Setters

This series of experiments used 80 to 120 day old water-deprived rats (Rattus norvegicus) to investigate whether simultaneously presented discrete occasion setters shared two properties of serially presented discrete occasion setters. Results of Experiment 1 revealed that all groups showed a strong reinstatement effect. In the second experiment a target stimulus was first trained as a predictor of shock and then paired with a simultaneously presented occasion setter to inhibit responding to the target stimulus. The occasion setter was then paired with a shock. Due to a limitation of the procedures, results from Experiment 2 were inconclusive. The third experiment tested whether simultaneously presented occasion setters would only transfer to other targets that underwent occasion setting training. Results from Experiment 3 revealed strong contextual control over behavior that overshadowed the ability of the features to modulate responding to the targets. A fourth experiment addressed limitations from Experiment 3. Results from Experiment 4 revealed that simultaneous discrete occasion setters were unable to transfer to another target stimulus. Overall results from this experiment indicate that simultaneously presented cues do not act as occasion setters

Genetic screening for gynecological cancer: where are we heading?

The landscape of cancer genetics in gynecological oncology is rapidly changing. The traditional family history-based approach has limitations and misses >50% mutation carriers. This is now being replaced by population-based approaches. The need for changing the clinical paradigm from family history-based to population-based BRCA1/BRCA2 testing in Ashkenazi Jews is supported by data that demonstrate population-based BRCA1/BRCA2 testing does not cause psychological harm and is cost effective. This article covers various genetic testing strategies for gynecological cancers, including population-based approaches, panel and direct-to-consumer testing as well as the need for innovative approaches to genetic counseling. Advances in genetic testing technology and computational analytics have facilitated an integrated systems medicine approach, providing increasing potential for population-based genetic testing, risk stratification, and cancer prevention. Genomic information along-with biological/computational tools will be used to deliver predictive, preventive, personalized and participatory (P4) and precision medicine in the future

Attack Rates Assessment of the 2009 Pandemic H1N1 Influenza A in Children and Their Contacts: A Systematic Review and Meta-Analysis

Background: The recent H1N1 influenza A pandemic was marked by multiple reports of illness and hospitalization in children, suggesting that children may have played a major role in the propagation of the virus. A comprehensive detailed analysis of the attack rates among children as compared with their contacts in various settings is of great importance for understanding their unique role in influenza pandemics. Methodology/Principal Findings: We searched MEDLINE (PubMed) and Embase for published studies reporting outbreak investigations with direct measurements of attack rates of the 2009 pandemic H1N1 influenza A among children, and quantified how these compare with those of their contacts. We identified 50 articles suitable for review, which reported school, household, travel and social events. The selected reports and our meta-analysis indicated that children had significantly higher attack rates as compared to adults, and that this phenomenon was observed for both virologically confirmed and clinical cases, in various settings and locations around the world. The review also provided insight into some characteristics of transmission between children and their contacts in the various settings. Conclusion/Significance: The consistently higher attack rates of the 2009 pandemic H1N1 influenza A among children, as compared to adults, as well as the magnitude of the difference is important for understanding the contribution of children to disease burden, for implementation of mitigation strategies directed towards children, as well as more precise mathematical modeling and simulation of future influenza pandemics

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

Mitochondrial DNA replication proceeds via a 'bootlace' mechanism involving the incorporation of processed transcripts

Peer reviewe

Over what area did the oil and gas spread during the 2010 Deepwater Horizon oil spill?

Author Posting. © The Oceanography Society, 2016. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 29, no. 3 (2016): 96–107, doi:10.5670/oceanog.2016.74.The 2010 Deepwater Horizon (DWH) oil spill in the Gulf of Mexico resulted in the collection of a vast amount of situ and remotely sensed data that can be used to determine the spatiotemporal extent of the oil spill and test advances in oil spill models, verifying their utility for future operational use. This article summarizes observations of hydrocarbon dispersion collected at the surface and at depth and our current understanding of the factors that affect the dispersion, as well as our improved ability to model and predict oil and gas transport. As a direct result of studying the area where oil and gas spread during the DWH oil spill, our forecasting capabilities have been greatly enhanced. State-of-the-art oil spill models now include the ability to simulate the rise of a buoyant plume of oil from sources at the seabed to the surface. A number of efforts have focused on improving our understanding of the influences of the near-surface oceanic layer and the atmospheric boundary layer on oil spill dispersion, including the effects of waves. In the future, oil spill modeling routines will likely be included in Earth system modeling environments, which will link physical models (hydrodynamic, surface wave, and atmospheric) with marine sediment and biogeochemical components.This research was made possible by a grant from BP/The Gulf of Mexico Research Initiative to the CARTHE and Deep-C Consortia, and by contract M12PC00003 from the Bureau of Ocean Energy Management (BOEM)

Bisimulation as path type for guarded recursive types

In type theory, coinductive types are used to represent processes, and are thus crucial for the formal verification of non-terminating reactive programs in proof assistants based on type theory, such as Coq and Agda. Currently, programming and reasoning about coinductive types is difficult for two reasons: The need for recursive definitions to be productive, and the lack of coincidence of the built-in identity types and the important notion of bisimilarity. Guarded recursion in the sense of Nakano has recently been suggested as a possible approach to dealing with the problem of productivity, allowing this to be encoded in types. Indeed, coinductive types can be encoded using a combination of guarded recursion and universal quantification over clocks. This paper studies the notion of bisimilarity for guarded recursive types in Ticked Cubical Type Theory, an extension of Cubical Type Theory with guarded recursion. We prove that, for any functor, an abstract, category theoretic notion of bisimilarity for the final guarded coalgebra is equivalent (in the sense of homotopy type theory) to path equality (the primitive notion of equality in cubical type theory). As a worked example we study a guarded notion of labelled transition systems, and show that, as a special case of the general theorem, path equality coincides with an adaptation of the usual notion of bisimulation for processes. In particular, this implies that guarded recursion can be used to give simple equational reasoning proofs of bisimilarity. This work should be seen as a step towards obtaining bisimilarity as path equality for coinductive types using the encodings mentioned above

Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load: A pilot study

The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer\u27s disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65-90 y, were categorised into NAL+ (n = 35) and NAL- (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEϵ4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL- participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/- as outcome were carried out. After age and APOEϵ4 adjustment, kynurenine and AA were individually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOEϵ4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesi