Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

The Galactic Center Black Hole Laboratory

The super-massive 4 million solar mass black hole Sagittarius~A* (SgrA*) shows flare emission from the millimeter to the X-ray domain. A detailed analysis of the infrared light curves allows us to address the accretion phenomenon in a statistical way. The analysis shows that the near-infrared flare amplitudes are dominated by a single state power law, with the low states in SgrA* limited by confusion through the unresolved stellar background. There are several dusty objects in the immediate vicinity of SgrA*. The source G2/DSO is one of them. Its nature is unclear. It may be comparable to similar stellar dusty sources in the region or may consist predominantly of gas and dust. In this case a particularly enhanced accretion activity onto SgrA* may be expected in the near future. Here the interpretation of recent data and ongoing observations are discussed.Comment: 30 pages - 7 figures - accepted for publication by Springer's "Fundamental Theories of Physics" series; summarizing GC contributions of 2 conferences: 'Equations of Motion in Relativistic Gravity' at the Physikzentrum Bad Honnef, Bad Honnef, Germany, (Feb. 17-23, 2013) and the COST MP0905 'The Galactic Center Black Hole Laboratory' Granada, Spain (Nov. 19 - 22, 2013

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Effect of genotypic, meteorological and agronomic factors on the gluten index of winter durum wheat

The determination of the gluten index is a widely used method for analysing the gluten strength of bread wheat and spring durum wheat genotypes. The present work was carried out to study the effect of the genotype, meteorological factors (temperature, precipitation and number of days with Tmax ≥ 30 °C) and agronomic treatments (N fertilisation and plant protection) on the gluten index of winter durum wheat varieties and breeding lines. The results indicated that the gluten index had little dependence on the environment, being determined to the greatest extent by the genotype. Compared with varieties having weak gluten, those with a strong gluten matrix responded less sensitively to changes in environmental conditions. Among the meteorological factors, high temperature at the end of the grain-filling period caused the greatest reduction in the mean gluten index of three varieties (R 2 = 0.462), while the fertiliser was found to be a significant factor affecting the gluten strength of winter durum wheat varieties. Using selection based on the gluten index, the gluten strength of winter durum wheat lines can be improved sufficiently to make them competitive with high quality spring varieties

How to juggle priorities? An interactive tool to provide quantitative support for strategic patient-mix decisions: an ophthalmology case

An interactive tool was developed for the ophthalmology department of the Academic Medical Center to quantitatively support management with strategic patient-mix decisions. The tool enables management to alter the number of patients in various patient groups and to see the consequences in terms of key performance indicators. In our case study, we focused on the bottleneck: the operating room. First, we performed a literature review to identify all factors that influence an operating room's utilization rate. Next, we decided which factors were relevant to our study. For these relevant factors, two quantitative methods were applied to quantify the impact of an individual factor: regression analysis and computer simulation. Finally, the average duration of an operation, the number of cancellations due to overrun of previous surgeries, and the waiting time target for elective patients all turned out to have significant impact. Accordingly, for the case study, the interactive tool was shown to offer management quantitative decision support to act proactively to expected alterations in patient-mix. Hence, management can anticipate the future situation, and either alter the expected patient-mix or expand capacity to ensure that the key performance indicators will be met in the future

Decision tools in health care: focus on the problem, not the solution

BACKGROUND: Systematic reviews or randomised-controlled trials usually help to establish the effectiveness of drugs and other health technologies, but are rarely sufficient by themselves to ensure actual clinical use of the technology. The process from innovation to routine clinical use is complex. Numerous computerised decision support systems (DSS) have been developed, but many fail to be taken up into actual use. Some developers construct technologically advanced systems with little relevance to the real world. Others did not determine whether a clinical need exists. With NHS investing £5 billion in computer systems, also occurring in other countries, there is an urgent need to shift from a technology-driven approach to one that identifies and employs the most cost-effective method to manage knowledge, regardless of the technology. The generic term, 'decision tool' (DT), is therefore suggested to demonstrate that these aids, which seem different technically, are conceptually the same from a clinical viewpoint. DISCUSSION: Many computerised DSSs failed for various reasons, for example, they were not based on best available knowledge; there was insufficient emphasis on their need for high quality clinical data; their development was technology-led; or evaluation methods were misapplied. We argue that DSSs and other computer-based, paper-based and even mechanical decision aids are members of a wider family of decision tools. A DT is an active knowledge resource that uses patient data to generate case specific advice, which supports decision making about individual patients by health professionals, the patients themselves or others concerned about them. The identification of DTs as a consistent and important category of health technology should encourage the sharing of lessons between DT developers and users and reduce the frequency of decision tool projects focusing only on technology. The focus of evaluation should become more clinical, with the impact of computer-based DTs being evaluated against other computer, paper- or mechanical tools, to identify the most cost effective tool for each clinical problem. SUMMARY: We suggested the generic term 'decision tool' to demonstrate that decision-making aids, such as computerised DSSs, paper algorithms, and reminders are conceptually the same, so the methods to evaluate them should be the same

Evaluation of Brain Iron Content Based on Magnetic Resonance Imaging (MRI): Comparison among Phase Value, R2* and Magnitude Signal Intensity

Background and Purpose: Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn’t commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron. Methods: We measured both phase values and R2 * in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2 * and brain iron. Results: We found phase value correlated with R2 * in substantia nigra (r = 20.723, p,0.001) and putamen (r = 20.514, p = 0.010), while no correlations in red nucleus (r = 20.236, p = 0.268) and globus pallidus (r = 20.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = 20.593, p = 0.002), substantia nigra (r = 20.521, p = 0.009), globus pallidus (r = 20.750, p,0.001) and putamen (r = 20.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = 20.982, P,0.001). Conclusions: Our study indicates that phase value may not be used for assessing the iron content in some brain region

Identification of emulsifier potato peptides by bioinformatics: application to omega-3 delivery emulsions and release from potato industry side streams

We are grateful for the financial support from Innovation Fund Denmark (Grant nr: 7045-00021B, PROVIDE project). We also acknowledge K.M.C. amba (Brande, Denmark) and A.K.V. amba (Langholt, Denmark) for providing the potato samples used in this study.In this work, we developed a novel approach combining bioinformatics, testing of functionality and bottom-up proteomics to obtain peptide emulsifiers from potato side-streams. This is a significant advancement in the process to obtain emulsifier peptides and it is applicable to any type of protein. Our results indicated that structure at the interface is the major determining factor of the emulsifying activity of peptide emulsifiers. Fish oil-in-water emulsions with high physical stability were stabilized with peptides to be predicted to have facial amphiphilicity: (i) peptides with predominantly α-helix conformation at the interface and having 18–29 amino acids, and (ii) peptides with predominantly β-strand conformation at the interface and having 13–15 amino acids. In addition, high physically stable emulsions were obtained with peptides that were predicted to have axial hydrophobic/hydrophilic regions. Peptides containing the sequence FCLKVGV showed high in vitro antioxidant activity and led to emulsions with high oxidative stability. Peptide-level proteomics data and sequence analysis revealed the feasibility to obtain the potent emulsifier peptides found in this study (e.g. γ-1) by trypsin-based hydrolysis of different side streams in the potato industry.Innovation Fund Denmark 7045-00021