A Prospective Surveillance Study of Candidaemia : Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients

Funding This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. GR was also supported by a research fellowship grant from Gilead Sciences. The collection of the isolates was funded by a Gilead Fellowship to GR. Acknowledgments We are grateful to microbiology colleagues throughout Scotland for submitting isolates. Antimicrobial sensitivity testing was performed by the Mycology Reference Laboratory, Public Health England, Bristol.Peer reviewedPublisher PD

Unscented Kalman Filter for Brain-Machine Interfaces

Brain machine interfaces (BMIs) are devices that convert neural signals into commands to directly control artificial actuators, such as limb prostheses. Previous real-time methods applied to decoding behavioral commands from the activity of populations of neurons have generally relied upon linear models of neural tuning and were limited in the way they used the abundant statistical information contained in the movement profiles of motor tasks. Here, we propose an n-th order unscented Kalman filter which implements two key features: (1) use of a non-linear (quadratic) model of neural tuning which describes neural activity significantly better than commonly-used linear tuning models, and (2) augmentation of the movement state variables with a history of n-1 recent states, which improves prediction of the desired command even before incorporating neural activity information and allows the tuning model to capture relationships between neural activity and movement at multiple time offsets simultaneously. This new filter was tested in BMI experiments in which rhesus monkeys used their cortical activity, recorded through chronically implanted multielectrode arrays, to directly control computer cursors. The 10th order unscented Kalman filter outperformed the standard Kalman filter and the Wiener filter in both off-line reconstruction of movement trajectories and real-time, closed-loop BMI operation

A–C Estrogens as Potent and Selective Estrogen Receptor-Beta Agonists (SERBAs) to Enhance Memory Consolidation under Low-Estrogen Conditions

Estrogen receptor-beta (ERβ) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERβ agonists (SERBAs) with in vivo efficacy that are A–C estrogens, lacking the B and D estrogen rings. The most potent and selective A–C estrogen is selective for activating ER relative to seven other nuclear hormone receptors, with a surprising 750-fold selectivity for the β over α isoform and with EC50s of 20–30 nM in cell-based and direct binding assays. Comparison of potency in different assays suggests that the ER isoform selectivity is related to the compound’s ability to drive the productive conformational change needed to activate transcription. The compound also shows in vivo efficacy after microinfusion into the dorsal hippocampus and after intraperitoneal injection (0.5 mg/kg) or oral gavage (0.5 mg/kg). This simple yet novel A–C estrogen is selective, brain penetrant, and facilitates memory consolidation

Psychosocial factors associated with the mental health of Indigenous children living in high income countries: a systematic review

Indigenous children living in high income countries such as Australia, New Zealand, Canada and the United States of America (USA) are disproportionately affected by mental health problems when compared to their non-Indigenous counterparts. Childhood mental health disorders such as anxiety, depression and externalising behaviours are associated with a range of negative outcomes that are overrepresented in Indigenous communities, including high rates of suicidal ideation and completed suicide. The long-term sequelae of poor childhood mental health is believed to significantly contribute to the many health and social 'gaps' between Indigenous and non-Indigenous populations that occur throughout the lifespan. This systematic review of published evidence aimed to identify modifiable psychosocial risk and protective factors common to Indigenous children living in developed countries. These factors are associated with mental health outcomes typically reflected in school-aged children. The results may inform policy and aid the design of initiatives to improve the mental health of Indigenous children, as well as identifying areas for further research.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Species-specific responses of planktivorous fish to the introduction of a new piscivore: implications for prey fitness

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75539/1/j.1365-2427.2007.01810.x.pd

Stellar Content from high resolution galactic spectra via Maximum A Posteriori

This paper describes STECMAP (STEllar Content via Maximum A Posteriori), a flexible, non-parametric inversion method for the interpretation of the integrated light spectra of galaxies, based on synthetic spectra of single stellar populations (SSPs). We focus on the recovery of a galaxy's star formation history and stellar age-metallicity relation. We use the high resolution SSPs produced by PEGASE-HR to quantify the informational content of the wavelength range 4000 - 6800 Angstroms. A detailed investigation of the properties of the corresponding simplified linear problem is performed using singular value decomposition. It turns out to be a powerful tool for explaining and predicting the behaviour of the inversion. We provide means of quantifying the fundamental limitations of the problem considering the intrinsic properties of the SSPs in the spectral range of interest, as well as the noise in these models and in the data. We performed a systematic simulation campaign and found that, when the time elapsed between two bursts of star formation is larger than 0.8 dex, the properties of each episode can be constrained with a precision of 0.04 dex in age and 0.02 dex in metallicity from high quality data (R=10 000, signal-to-noise ratio SNR=100 per pixel), not taking model errors into account. The described methods and error estimates will be useful in the design and in the analysis of extragalactic spectroscopic surveys.Comment: 31 pages, 23 figures, accepted for publication in MNRA

Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S Primuline

A screen for hepatitis C virus (HCV) NS3 helicase inhibitors revealed that the commercial dye thioflavine S was the most potent inhibitor of NS3-catalyzed DNA and RNA unwinding in the 827-compound National Cancer Institute Mechanistic Set. Thioflavine S and the related dye primuline were separated here into their pure components, all of which were oligomers of substituted benzothiazoles. The most potent compound (P4), a benzothiazole tetramer, inhibited unwinding >50% at 2±1 μM, inhibited the subgenomic HCV replicon at 10 μM, and was not toxic at 100 μM. Because P4 also interacted with DNA, more specific analogs were synthesized from the abundant dimeric component of primuline. Some of the 29 analogs prepared retained ability to inhibit HCV helicase but did not appear to interact with DNA. The most potent of these specific helicase inhibitors (compound 17) was active against the replicon and inhibited the helicase more than 50% at 2.6±1 μM

Patient and caregiver perspectives on blood pressure in children with chronic kidney disease

Background: More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care. / Methods: Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology—Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8–21 years) and caregivers (of children ages 0–21 years) pertaining to blood pressure. / Results: Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects). / Conclusions: For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD

Spintronic transport and Kondo effect in quantum dots

We investigate the spin-dependent transport properties of quantum-dot based structures where Kondo correlations dominate the electronic dynamics. The coupling to ferromagnetic leads with parallel magnetizations is known to give rise to nontrivial effects in the local density of states of a single quantum dot. We show that this influence strongly depends on whether charge fluctuations are present or absent in the dot. This result is confirmed with numerical renormalization group calculations and perturbation theory in the on-site interaction. In the Fermi-liquid fixed point, we determine the correlations of the electric current at zero temperature (shot noise) and demonstrate that the Fano factor is suppressed below the Poissonian limit for the symmetric point of the Anderson Hamiltonian even for nonzero lead magnetizations. We discuss possible avenues of future research in this field: coupling to the low energy excitations of the ferromagnets (magnons), extension to double quantum dot systems with interdot antiferromagnetic interaction and effect of spin-polarized currents on higher symmetry Kondo states such as SU(4).Comment: 11 pages, 5 figures. Proceedings of the 3rd Intl. Conf. on Physics and Applications of Spin-Related Phenomena in Semiconductors, Santa Barbara, 200