Daily rhythm of cerebral blood flow velocity

BACKGROUND: CBFV (cerebral blood flow velocity) is lower in the morning than in the afternoon and evening. Two hypotheses have been proposed to explain the time of day changes in CBFV: 1) CBFV changes are due to sleep-associated processes or 2) time of day changes in CBFV are due to an endogenous circadian rhythm independent of sleep. The aim of this study was to examine CBFV over 30 hours of sustained wakefulness to determine whether CBFV exhibits fluctuations associated with time of day. METHODS: Eleven subjects underwent a modified constant routine protocol. CBFV from the middle cerebral artery was monitored by chronic recording of Transcranial Doppler (TCD) ultrasonography. Other variables included core body temperature (CBT), end-tidal carbon dioxide (EtCO2), blood pressure, and heart rate. Salivary dim light melatonin onset (DLMO) served as a measure of endogenous circadian phase position. RESULTS: A non-linear multiple regression, cosine fit analysis revealed that both the CBT and CBFV rhythm fit a 24 hour rhythm (R(2 )= 0.62 and R(2 )= 0.68, respectively). Circadian phase position of CBT occurred at 6:05 am while CBFV occurred at 12:02 pm, revealing a six hour, or 90 degree difference between these two rhythms (t = 4.9, df = 10, p < 0.01). Once aligned, the rhythm of CBFV closely tracked the rhythm of CBT as demonstrated by the substantial correlation between these two measures (r = 0.77, p < 0.01). CONCLUSION: In conclusion, time of day variations in CBFV have an approximately 24 hour rhythm under constant conditions, suggesting regulation by a circadian oscillator. The 90 degree-phase angle difference between the CBT and CBFV rhythms may help explain previous findings of lower CBFV values in the morning. The phase difference occurs at a time period during which cognitive performance decrements have been observed and when both cardiovascular and cerebrovascular events occur more frequently. The mechanisms underlying this phase angle difference require further exploration

Relative impact of key sources of systematic noise in Affymetrix and Illumina gene-expression microarray experiments

<p>Abstract</p> <p>Background</p> <p>Systematic processing noise, which includes batch effects, is very common in microarray experiments but is often ignored despite its potential to confound or compromise experimental results. Compromised results are most likely when re-analysing or integrating datasets from public repositories due to the different conditions under which each dataset is generated. To better understand the relative noise-contributions of various factors in experimental-design, we assessed several Illumina and Affymetrix datasets for technical variation between replicate hybridisations of Universal Human Reference (UHRR) and individual or pooled breast-tumour RNA.</p> <p>Results</p> <p>A varying degree of systematic noise was observed in each of the datasets, however in all cases the relative amount of variation between standard control RNA replicates was found to be greatest at earlier points in the sample-preparation workflow. For example, 40.6% of the total variation in reported expressions were attributed to replicate extractions, compared to 13.9% due to amplification/labelling and 10.8% between replicate hybridisations. Deliberate probe-wise batch-correction methods were effective in reducing the magnitude of this variation, although the level of improvement was dependent on the sources of noise included in the model. Systematic noise introduced at the chip, run, and experiment levels of a combined Illumina dataset were found to be highly dependant upon the experimental design. Both UHRR and pools of RNA, which were derived from the samples of interest, modelled technical variation well although the pools were significantly better correlated (4% average improvement) and better emulated the effects of systematic noise, over all probes, than the UHRRs. The effect of this noise was not uniform over all probes, with low GC-content probes found to be more vulnerable to batch variation than probes with a higher GC-content.</p> <p>Conclusions</p> <p>The magnitude of systematic processing noise in a microarray experiment is variable across probes and experiments, however it is generally the case that procedures earlier in the sample-preparation workflow are liable to introduce the most noise. Careful experimental design is important to protect against noise, detailed meta-data should always be provided, and diagnostic procedures should be routinely performed prior to downstream analyses for the detection of bias in microarray studies.</p

Genes implicated in multiple sclerosis pathogenesis from consilience of genotyping and expression profiles in relapse and remission

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Although the pathogenesis of MS remains unknown, it is widely regarded as an autoimmune disease mediated by T-lymphocytes directed against myelin proteins and/or other oligodendrocyte epitopes.</p> <p>Methods</p> <p>In this study we investigated the gene expression profiles of peripheral blood cells from patients with RRMS during the relapse and the remission phases utilizing gene microarray technology. Dysregulated genes encoded in regions associated with MS susceptibility from genomic screens or previous trancriptomic studies were identified. The proximal promoter region polymorphisms of two genes were tested for association with disease and expression level.</p> <p>Results</p> <p>Distinct sets of dysregulated genes during the relapse and remission phases were identified including genes involved in apoptosis and inflammation. Three of these dysregulated genes have been previously implicated with MS susceptibility in genomic screens: TGFβ1, CD58 and DBC1. TGFβ1 has one common SNP in the proximal promoter: -508 T>C (rs1800469). Genotyping two Australian trio sets (total 620 families) found a trend for over-transmission of the T allele in MS in females (p < 0.13). Upregulation of CD58 and DBC1 in remission is consistent with their putative roles in promoting regulatory T cells and reducing cell proliferation, respectively. A fourth gene, ALOX5, is consistently found over-expressed in MS. Two common genetic variants were confirmed in the ALOX5 putatve promoter: -557 T>C (rs12762303) and a 6 bp tandem repeat polymorphism (GGGCGG) between position -147 and -176; but no evidence for transmission distortion found.</p> <p>Conclusion</p> <p>The dysregulation of these genes tags their metabolic pathways for further investigation for potential therapeutic intervention.</p

Jets and energy flow in photon-proton collisions at HERA

Properties of the hadronic final state in photoproduction events with large transverse energy are studied at the electron-proton collider HERA. Distributions of the transverse energy, jets and underlying event energy are compared to \overline{p}p data and QCD calculations. The comparisons show that the \gamma p events can be consistently described by QCD models including -- in addition to the primary hard scattering process -- interactions between the two beam remnants. The differential jet cross sections d\sigma/dE_T^{jet} and d\sigma/d\eta^{jet} are measured

The Role of Behavioural Treatment in the Management of Insomnia

Insomnia is a highly prevalent complaint among the general public that can affect an individual's health, performance and quality of life. Despite its broad effects, patients' help-seeking rate is very low. One possible reason for this is the patients' lack of knowledge about treatment options for insomnia. In order to facilitate understanding and appreciation of the behavioural treatments of insomnia, this article offers an overview of clinical indications, procedures, and expected short term and long term effects of various effective behavioural treatments for insomnia. Treatments discussed include: 1. stimulus control instructions that eliminate the maladaptive association between bedtime cues and anxiety 2. sleep restriction therapy that enhances central sleep mechanisms by systematically curtailing the amount of time in bed 3. relaxation techniques that promote sleep by reducing physiological tension and cognitive arousal 4. biofeedback protocols that produce relaxation or enhance sleep regulation through the feedback of physiological measures 5. cognitive therapies that facilitate sleep onset by alleviating pre-sleep cognitive arousal 6. sleep hygiene that improves sleep by avoiding habits and activities interfering with sleep; and 7. chronotherapy and light therapy that facilitate sleep regulation based on the principles of circadian rhythmicity.Reviews-on-treatment, Insomnia, Cognitive-behavioural-therapy, Relaxation, Biofeedback, Phototherapy

k-Means has polynomial smoothed complexity

The k-means method is one of the most widely used clustering algorithms, drawing its popularity from its speed in practice. Recently, however, it was shown to have exponential worst-case running time. In order to close the gap between practical performance and theoretical analysis, the k-means method has been studied in the model of smoothed analysis. But even the smoothed analyses so far are unsatisfactory as the bounds are still super-polynomial in the number n of data points. In this paper, we settle the smoothed running time of the k-means method. We show that the smoothed number of iterations is bounded by a polynomial in n and 1/sigma, where sigma is the standard deviation of the Gaussian perturbations. This means that if an arbitrary input data set is randomly perturbed, then the k-means method will run in expected polynomial time on that input set

The Actigraph Data Analysis Software: I. A Novel Approach to Scoring and Interpreting Sleep-Wake Activity

Decades of empirical observations have established the validity of actigraphy primarily in individuals without sleep disorders. Methodological problems encountered thus far coupled with the widespread use of actigraphy signal the need for concentrated efforts to establish a consensus regarding scoring procedures. Currently available scoring methods show less reliability in clinical populations. To address these issues two validation studies were conducted: one for individuals without sleep disorders and the other for patients diagnosed with insomnia. The results of these two studies using the Actigraph Data Analysis Software as the scoring method have shown that the described system is fairly precise. It can be used for actigraphs with different features and mode of operation and is applicable to individuals with insomnia. These findings corroborate previous research showing that actigraphy is a valid instrument for assessment of sleep and wakefulness

The Actigraph Data Analysis Software: II. A Novel Approach to Scoring and Interpreting Sleep-Wake Activity

The widespread use of actigraphy has led to the recognition that a number of methodological issues have to be addressed to facilitate an increased acceptability of this relatively new method. These methodological issues include actigraph placement, reliability, and sensitivity, and the phenomenon known as the “first night effect.” Our findings have demonstrated that actigraphy is a reliable instrument for assessment of sleep and wakefulness. In addition, actigraph placement and reliability do not constitute a significant methodological problem as no differences were found in all of these studies. We have also observed no first-night effects associated with sleep-wake monitoring with actigraphy