Reduced responsiveness is an essential feature of chronic fatigue syndrome: A fMRI study

BACKGROUND: Although the neural mechanism of chronic fatigue syndrome has been investigated by a number of researchers, it remains poorly understood. METHODS: Using functional magnetic resonance imaging, we studied brain responsiveness in 6 male chronic fatigue syndrome patients and in 7 age-matched male healthy volunteers. Responsiveness of auditory cortices to transient, short-lived, noise reduction was measured while subjects performed a fatigue-inducing continual visual search task. RESULTS: Responsiveness of the task-dependent brain regions was decreased after the fatigue-inducing task in the normal and chronic fatigue syndrome subjects and the decrement of the responsiveness was equivalent between the 2 groups. In contrast, during the fatigue-inducing period, although responsiveness of auditory cortices remained constant in the normal subjects, it was attenuated in the chronic fatigue syndrome patients. In addition, the rate of this attenuation was positively correlated with the subjective sensation of fatigue as measured using a fatigue visual analogue scale, immediately before the magnetic resonance imaging session. CONCLUSION: Chronic fatigue syndrome may be characterised by attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing task

The Phrenic Component of Acute Schizophrenia – A Name and Its Physiological Reality

Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt®, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging)

Autonomic Modulation and Health-Related Quality of Life among Schizophrenic Patients Treated with Non-Intensive Case Management

Schizophrenia is associated with autonomic dysfunction and this may increase cardiovascular mortality. Past studies on autonomic modulation of schizophrenic patients focused on inpatients rather than individuals in a community setting, especially those receiving non-intensive case management (non-ICM). Besides, autonomic modulation and its association with health-related quality of life (HRQoL) in this population remain unexplored.A total of 25 schizophrenic patients treated by non-ICM and 40 healthy volunteers were matched by age, gender and body mass index; smokers were excluded. Between the two groups, we compared the individuals' 5 min resting assessments of heart rate variability and their HRQoL, which was measured using EuroQoL-5D (EQ-5D). Patients with schizophrenia were assessed for psychopathology using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). We examined the relationship between heart rate variability measurements, HRQoL scores, PANSS scores, and other clinical variables among the schizophrenic patients treated by non-ICM.Compared to the controls, patients with schizophrenia showed a significant impairment of autonomic modulation and a worse HRQoL. Cardiovagal dysfunction among the schizophrenic patients could be predicted independently based on lower educational level and more negative symptoms. Sympathetic predominance was directly associated with anticholinergics use and EQ-5D using a visual analogue scale (EQ-VAS).Patients with schizophrenia treated by non-ICM show a significant impairment of their autonomic function and HRQoL compared to the controls. Since the sympathovagal dysfunction is associated with more negative symptoms or higher VAS score, the treatment of the negative symptoms as well as the monitoring of HRQoL might help to manage cardiovascular risk among these individuals. In addition, EQ-VAS scores must be interpreted more cautiously in such a population

Fine Tuning in General Gauge Mediation

We study the fine-tuning problem in the context of general gauge mediation. Numerical analyses toward for relaxing fine-tuning are presented. We analyse the problem in typical three cases of the messenger scale, that is, GUT ($2\times10^{16}$ GeV), intermediate ($10^{10}$ GeV), and relatively low energy ($10^6$ GeV) scales. In each messenger scale, the parameter space reducing the degree of tuning as around 10% is found. Certain ratios among gluino mass, wino mass and soft scalar masses are favorable. It is shown that the favorable region becomes narrow as the messenger scale becomes lower, and tachyonic initial conditions of stop masses at the messenger scale are favored to relax the fine-tuning problem for the relatively low energy messenger scale. Our spectra would also be important from the viewpoint of the $\mu-B$ problem.Comment: 22 pages, 16 figures, comment adde

The NIRS Analysis Package: Noise Reduction and Statistical Inference

Near infrared spectroscopy (NIRS) is a non-invasive optical imaging technique that can be used to measure cortical hemodynamic responses to specific stimuli or tasks. While analyses of NIRS data are normally adapted from established fMRI techniques, there are nevertheless substantial differences between the two modalities. Here, we investigate the impact of NIRS-specific noise; e.g., systemic (physiological), motion-related artifacts, and serial autocorrelations, upon the validity of statistical inference within the framework of the general linear model. We present a comprehensive framework for noise reduction and statistical inference, which is custom-tailored to the noise characteristics of NIRS. These methods have been implemented in a public domain Matlab toolbox, the NIRS Analysis Package (NAP). Finally, we validate NAP using both simulated and actual data, showing marked improvement in the detection power and reliability of NIRS

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Drug-Eluting Stents in Patients with Chronic Kidney Disease: A Prospective Registry Study

BACKGROUND: Chronic kidney disease (CKD) is strongly associated with adverse outcomes after percutaneous coronary intervention (PCI). There are limited data on the effectiveness of drug-eluting stents (DES) in patients with CKD. METHODOLOGY/PRINCIPAL FINDINGS: Of 3,752 consecutive patients enrolled in the Guthrie PCI Registry between 2001 and 2006, 436 patients with CKD - defined as a creatinine clearance <60 mL/min - were included in this study. Patients who received DES were compared to those who received bare metal stents (BMS). Patients were followed for a mean duration of 3 years after the index PCI to determine the prognostic impact of stent type. Study end-points were all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and the composite of major adverse cardiovascular events (MACE), defined as death, MI or TVR. Patients receiving DES in our study, by virtue of physician selection, had more stable coronary artery disease and had lower baseline risk of thrombotic or restenotic events. Kaplan-Meier estimates of proportions of patients reaching the end-points were significantly lower for DES vs. BMS for all-cause death (p = 0.0008), TVR (p = 0.029) and MACE (p = 0.0015), but not MI (p = 0.945) or ST (p = 0.88). Multivariable analysis with propensity adjustment demonstrated that DES implantation was an independent predictor of lower rates of all-cause death (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25-0.92), TVR (HR 0.50, 95% CI 0.27-0.94) and MACE (HR 0.62, 95% CI 0.41-0.94). CONCLUSIONS: In a contemporary PCI registry, selective use of DES in patients with CKD was safe and effective in the long term, with lower risk of all-cause death, TVR and MACE and similar risk of MI and ST as compared with BMS. The mortality benefit may be a result of selection bias and residual confounding, or represent a true finding; a hypothesis that warrants clarification by randomized clinical trials

Clinical Usefulness of Multiplex PCR Lateral Flow in MRSA Detection: A Novel, Rapid Genetic Testing Method

Methicillin-resistant Staphylococcus aureus (MRSA) with exogenous cassette DNA containing the methicillin-resistant gene mecA (SCCmec) poses a problem as a drug-resistant bacterium responsible for hospital- and community-acquired infections. The frequency of MRSA detection has recently been increasing rapidly in Japan, and SCCmec has also been classified more diversely into types I–V. A rapid test is essential for early diagnosis and treatment of MRSA infections, but detection by conventional methods requires at least two days. The newly developed multiplex PCR lateral flow method allows specific amplification of femA to detect S. aureus, mecA to detect SCCmec, and kdpC to detect SCCmec type II; moreover, PCR products can be evaluated visually in about 3 h. In the present study, we developed a PCR lateral flow method for MRSA using this method and investigated its clinical usefulness in the detection of MRSA. The results showed a diagnostic concordance rate of 91.7% for MRSA and methicillin-susceptible S. aureus between bacteriological examination and PCR lateral flow, and a high level of specificity in PCR lateral flow. In addition, a higher detection rate for S. aureus using the same sample was observed for PCR lateral flow (70.2%) than for bacteriological tests (48.6%). The above results show that PCR lateral flow for MRSA detection has high sensitivity, specificity, and speed, and its clinical application as a method for early diagnosis of MRSA infections appears to be feasible