On the correspondence between data revision and trend-cycle decomposition

This paper places the data revision model of Jacobs and van Norden (2011) within a class of trend-cycle decompositions relating directly to the Beveridge-Nelson decomposition. In both these approaches identifying restrictions on the covariance matrix under simple and realistic conditions may produce a smoothed estimate of the underlying series which is more volatile than the observed series

Ibuprofen Ameliorates Fatigue- And Depressive-Like Behavior in Tumor-Bearing Mice

Aims: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. Main methods: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10 mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. Key findings: Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. Significance: Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF

Tumor Growth Increases Neuroinflammation, Fatigue and Depressive-like Behavior Prior to Alterations in Muscle Function

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth

Fluoxetine Prevents the Development of Depressive-like Behavior in a Mouse Model of Cancer Related Fatigue

Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue- and depressive-like behaviors. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRIs such as fluoxetine

Central activation of alpha7 nicotinic signaling attenuates lps-induced neuroinflammation and sickness behavior in adult but not in aged animals

We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are im-plicated in the “Cholinergic anti-inflammatory pathway”, we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroven-tricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice.This work was supported by the Spanish Ministry of Science, innovation and Universities Ref. SAF2015-63935-R and Ref. RTI2018-095793-B-I00 and General Council for Research and Innovation of the Community of Madrid and European Structural Funds Ref. B2017/BMD–3827–NRF24ADCM to M.G.L. Aging studies were supported by an NIA grant (R01-AG-033028) to J.P.G

The effect of peri‐operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non‐cardiac surgical patients: a randomised, double‐blind placebo‐controlled trial

Delirium occurs commonly following major non-cardiac and cardiac surgery and is associated with: postoperative mortality; postoperative neurocognitive dysfunction; increased length of hospital stay; and major postoperative complications and morbidity. The aim of this study was to investigate the effect of peri-operative administration of dexmedetomidine on the incidence of postoperative delirium in non-cardiac and cardiac surgical patients. In this randomised, double-blind placebo-controlled trial we included 63 patients aged >= 60 years undergoing major open abdominal surgery or coronary artery bypass graft surgery with cardiopulmonary bypass. The primary outcome was the incidence of postoperative delirium, as screened for with the Confusion Assessment Method. Delirium assessment was performed twice daily until postoperative day 5, at the time of discharge from hospital or until postoperative day 14. We found that dexmedetomidine was associated with a reduced incidence of postoperative delirium within the first 5 postoperative days, 43.8% vs. 17.9%, p = 0.038. Severity of delirium, screened with the Intensive Care Delirium Screening Checklist, was comparable in both groups, with a mean maximum score of 1.54 vs. 1.68, p = 0.767. No patients in the dexmedetomidine group died while five (15.6%) patients in the placebo group died, p = 0.029. For patients aged >= 60 years undergoing major cardiac or non-cardiac surgery, we conclude that the peri-operative administration of dexmedetomidine is associated with a lower incidence of postoperative delirium

A new bond fluctuation method for a polymer undergoing gel electrophoresis

We present a new computational methodology for the investigation of gel electrophoresis of polyelectrolytes. We have developed the method initially to incorporate sliding motion of tight parts of a polymer pulled by an electric field into the bond fluctuation method (BFM). Such motion due to tensile force over distances much larger than the persistent length is realized by non-local movement of a slack monomer at an either end of the tight part. The latter movement is introduced stochastically. This new BFM overcomes the well-known difficulty in the conventional BFM that polymers are trapped by gel fibers in relatively large fields. At the same time it also reproduces properly equilibrium properties of a polymer in a vanishing filed limit. The new BFM thus turns out an efficient computational method to study gel electrophoresis in a wide range of the electric field strength.Comment: 15 pages, 11 figure

Broadband Meter-Wavelength Observations of Ionospheric Scintillation

Intensity scintillations of cosmic radio sources are used to study astrophysical plasmas like the ionosphere, the solar wind, and the interstellar medium. Normally these observations are relatively narrow band. With Low Frequency Array (LOFAR) technology at the Kilpisj\"arvi Atmospheric Imaging Receiver Array (KAIRA) station in northern Finland we have observed scintillations over a 3 octave bandwidth. ``Parabolic arcs'', which were discovered in interstellar scintillations of pulsars, can provide precise estimates of the distance and velocity of the scattering plasma. Here we report the first observations of such arcs in the ionosphere and the first broad-band observations of arcs anywhere, raising hopes that study of the phenomenon may similarly improve the analysis of ionospheric scintillations. These observations were made of the strong natural radio source Cygnus-A and covered the entire 30-250\,MHz band of KAIRA. Well-defined parabolic arcs were seen early in the observations, before transit, and disappeared after transit although scintillations continued to be obvious during the entire observation. We show that this can be attributed to the structure of Cygnus-A. Initial results from modeling these scintillation arcs are consistent with simultaneous ionospheric soundings taken with other instruments, and indicate that scattering is most likely to be associated more with the topside ionosphere than the F-region peak altitude. Further modeling and possible extension to interferometric observations, using international LOFAR stations, are discussed.Comment: 11 pages, 17 figure

How companies embed non-quantifiable product qualities through their product development process

Many consumer products have reached a high level of technical product quality. Rapid adoption of new technologies and access to a global market means that markets are getting saturated. This means that technical differentiation is often not enough to sell a product and products compete more and more on intangible product qualities - these are meant to delight, bring pleasure, be easy to use and to create an experience. These qualities are often difficult to measure in the product using scientific descriptions and numerical measures. This research studies these Non-Quantifiable Product Qualities and the thesis presents research into how companies embed these Non-Quantifiable Product Qualities into their products in an attempt to satisfy their customers. The aim of this research was to gain insight into how large manufacturing companies embed product qualities that are difficult to quantify, by studying their product development process. This was done in two stages, firstly an exploratory study into five case organisations, secondly an in-depth study into three of the original five companies. Fifty interviews with designers, engineers and marketers formed the main source of data, supplemented with observations and document analysis. In the exploratory stage nine initial themes emerged out of data analysis, which then informed the data collection in the descriptive stage. The final output is seven confirmed themes, with 43 major findings and three conceptual models, that describe how companies embed Non-Quantifiable Product Qualities through their product development process. The research has found that the researched companies have some common strategies for embedding Non-Quantifiable Product Qualities. One example is that they will typically seek to translate an emotional response in the customer into measurable product qualities that will evoke such response. It is also common to seek out customer reaction to products during development to ensure successful embedding of Non-Quantifiable Product Qualities.EThOS - Electronic Theses Online ServiceGBUnited Kingdo