Structural network efficiency is associated with cognitive impairment in small-vessel disease.

To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment.METHODS: A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested.RESULTS: Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed.CONCLUSIONS: Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies

Depression in small-vessel disease relates to white matter ultrastructural damage, not disability.

OBJECTIVE: To determine whether cerebral small-vessel disease (SVD) is a specific risk factor for depression, whether any association is mediated via white matter damage, and to study the role of depressive symptoms and disability on quality of life (QoL) in this patient group. METHODS: Using path analyses in cross-sectional data, we modeled the relationships among depression, disability, and QoL in patients with SVD presenting with radiologically confirmed lacunar stroke (n = 100), and replicated results in a second SVD cohort (n = 100). We then compared the same model in a non-SVD stroke cohort (n = 50) and healthy older adults (n = 203). In a further study, to determine the role of white matter damage in mediating the association with depression, a subgroup of patients with SVD (n = 101) underwent diffusion tensor imaging (DTI). RESULTS: Reduced QoL was associated with depression in patients with SVD, but this association was not mediated by disability or cognition; very similar results were found in the replication SVD cohort. In contrast, the non-SVD stroke group and the healthy older adult group showed a direct relationship between disability and depression. The DTI study showed that fractional anisotropy, a marker of white matter damage, was related to depressive symptoms in patients with SVD. CONCLUSION: These results suggest that in stroke patients without SVD, disability is an important causal factor for depression, whereas in SVD stroke, other factors specific to this stroke subtype have a causal role. White matter damage detected on DTI is one factor that mediates the association between SVD and depression

Ventral striatum activity in response to reward: differences between bipolar I and II disorders.

addresses: MRC Center for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK. [email protected]: PMCID: PMC3640293types: Journal Article; Research Support, Non-U.S. Gov'tThis is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode.Copyright © 2013 by the American Psychiatric AssociationThe official published article is available online at http://ajp.psychiatryonline.org/article.aspx?articleid=1676088Little is known about the neurobiology of bipolar II disorder. While bipolar I disorder is associated with abnormally elevated activity in response to reward in the ventral striatum, a key component of reward circuitry, no studies have compared reward circuitry function in bipolar I and bipolar II disorders. Furthermore, associations among reward circuitry activity, reward sensitivity, and striatal volume remain underexplored in bipolar and healthy individuals. The authors examined reward activity in the ventral striatum in participants with bipolar I and II disorders and healthy individuals, the relationships between ventral striatal activity and reward sensitivity across all participants, and between-group differences in striatal gray matter volume and relationships with ventral striatal activity across all participants

Downer cows: a reanalysis of an old data set.

CAUL Read and Publish Agreement.AIMS: To compare the performance of two predictive models for the survival of downer cows. METHODS: The first model had been developed in 1987 using a dataset containing missing values, while the second, new model was developed on the same dataset but using modern data imputation and analytical methods. Missing data were imputed using multiple imputation by chained equations and a logistic regression model fitted to the imputed data, with survival or not as the outcome variable. The predictive ability of the model built on the imputed data was contrasted with the original prognostic model by testing them both on a second smaller but complete data set, collected contemporaneously with the development of the original model but from a different region of New Zealand. Sensitivity, specificity, accuracy, and cut point for the two models were calculated. RESULTS: The original 1987 model had a slightly higher accuracy than that of the new one with a sensitivity of 0.85 (95% CI = 0.72-0.94) and a specificity of 0.82 (95% CI = 0.7-0.91), using a cut point for the probability of survival = 0.313. CONCLUSIONS: The original prognostic formula published by Clark et al. in 1987 performed as well as a modern model built on an imputed data set. CLINICAL RELEVANCE: The use of a prognostic test based on the Clark model should remain an important part of the clinical examination of downer cows by New Zealand veterinarians.Abbreviations: AUC: Area under the curve; AST: Aspartate transaminase activity; CK: Creatine phosphokinase activity; GAM: Generalised additive model; NSAID: Non-steroidal-anti-inflammatory drugs; PCV: Packed cell volume.Publishe

Photosynthetic activity and population dynamics of Amoebobacter purpureus in a meromictic saline lake

Abstract A dense population of the purple sulfur bacterium Amoebobacter purpureus in the chemocline of meromictic Mahoney Lake (British Columbia, Canada) underwent consistent changes in biomass over a two year study period. The integrated amount of bacteriochlorophyll reached maxima in August and declined markedly during early fall. Bacteriochlorophyll was only weakly correlated with the light intensity and water temperature in the chemocline. In the summer, bacterial photosynthesis was limited by sulfide availability. During this period the intracellular sulfur concentration of A. purpureus cells decreased. A minimum concentration was measured at the top of the bacterial layer in August, when specific photosynthetic rates of A. purpureus indicated that only 14% of the cells were photosynthetically active. With the exception of a time period between August and September, the specific growth rates calculated from CO2 fixation rates of A. purpureus were similar to growth rates calculated from actual biomass changes in the bacterial layer. Between August and September 86% of the A. purpureus biomass disappeared from the chemocline and were deposited on the littoral sediment of Mahoney Lake or degraded within the mixolimnion. This rise of cells to the lake surface was not mediated by an increase in the specific gas vesicle content which remained constant between April and November. The upwelling phenomenon was related to the low sulfur content of A. purpureus cells and a low resistance of surface water layers against vertical mixing by wind

Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change.

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS (p < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models (p = 0.002). Change in DSEG θ was also related to change in all other MRI markers (p < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs)

Impact of mental health problems on case fatality in male cancer patients

Background: Although mortality rates are elevated in psychiatric patients relative to their healthy counterparts, little is known about the impact of mental health on survival in people with cancer. / Methods and results: Among 16 498 Swedish men with cancer, survival was worse in those with a history of psychiatric hospital admissions: multiply-adjusted hazard ratio (95% confidence interval) comparing cancer mortality in men with and without psychiatric admissions: 1.59 (1.39, 1.83). / Conclusion: Survival in cancer patients is worse among those with a history of psychiatric disease. The mechanisms underlying this association should be further explored

RNA:protein ratio of the unicellular organism as a characteristic of phosphorous and nitrogen stoichiometry and of the cellular requirement of ribosomes for protein synthesis

Background Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N ratios with the growth rate of organisms indicate a surprising similarity among and within microbial species, plants, and insect herbivores. To reveal the cellular mechanisms underling this similarity, the macromolecular composition of seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed under different conditions of exponential growth. Results It was found that P:N ratios calculated from RNA and protein contents in these particular organisms were in the same range as the mean ratios reported for diverse organisms and had similar positive relationships with growth rate, consistent with the growth-rate hypothesis. The efficiency of protein synthesis in microorganisms is estimated as the number of active ribosomes required for the incorporation of one amino acid into the synthesized protein. This parameter is calculated as the SGR:PER ratio. Experimental and theoretical evidence indicated that the requirement of ribosomes for protein synthesis is proportional to the RNA:protein ratio. The constant of proportionality had the same values for all organisms, and was derived mechanistically from the characteristics of the protein-synthesis machinery of the cell (the number of nucleotides per ribosome, the average masses of nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and the fraction of active ribosomes). Impairment of the growth conditions decreased the RNA:protein ratio and increased the overall efficiency of protein synthesis in the microorganisms. Conclusion Our results suggest that the decrease in RNA:protein and estimated P:N ratios with decrease in the growth rate of the microorganism is a consequence of an increased overall efficiency of protein synthesis in the cell resulting from activation of the general stress response and increased transcription of cellular maintenance genes at the expense of growth related genes. The strong link between P:N stoichiometry, RNA:protein ratio, ribosomal requirement for protein synthesis, and growth rate of microorganisms indicated by the study could be used to characterize the N and P economy of complex ecosystems such as soils and the oceans

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary

Methodology for in situ gas sampling, transport and laboratory analysis of gases from stranded cetaceans

Gas-bubble lesions were described in cetaceans stranded in spatio-temporal concordance with naval exercises using high-powered sonars. A behaviourally induced decompression sickness-like disease was proposed as a plausible causal mechanism, although these findings remain scientifically controversial. Investigations into the constituents of the gas bubbles in suspected gas embolism cases are highly desirable. We have found that vacuum tubes, insulin syringes and an aspirometer are reliable tools for in situ gas sampling, storage and transportation without appreciable loss of gas and without compromising the accuracy of the analysis. Gas analysis is conducted by gas chromatography in the laboratory. This methodology was successfully applied to a mass stranding of sperm whales, to a beaked whale stranded in spatial and temporal association with military exercises and to a cetacean chronic gas embolism case. Results from the freshest animals confirmed that bubbles were relatively free of gases associated with putrefaction and consisted predominantly of nitrogen