Wideband CDMA I: Guest editorial

published_or_final_versio

Probabilistic Clustering of Time-Evolving Distance Data

We present a novel probabilistic clustering model for objects that are represented via pairwise distances and observed at different time points. The proposed method utilizes the information given by adjacent time points to find the underlying cluster structure and obtain a smooth cluster evolution. This approach allows the number of objects and clusters to differ at every time point, and no identification on the identities of the objects is needed. Further, the model does not require the number of clusters being specified in advance -- they are instead determined automatically using a Dirichlet process prior. We validate our model on synthetic data showing that the proposed method is more accurate than state-of-the-art clustering methods. Finally, we use our dynamic clustering model to analyze and illustrate the evolution of brain cancer patients over time

Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid beta (Aβ1-40) administration in mice

Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In the present study, we used ghrelin knockout (KO) and their wild-type littermates to test whether or not endogenous ghrelin is protective in a mouse model of AD, in which human amyloid β peptide 1-40 (Aβ1-40 ) was injected into the lateral ventricles i.c.v. Recognition memory, using the novel object recognition task, was significantly impaired in ghrelin KO mice and after i.c.v. Aβ1-40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Spatial orientation, as assessed by the Y-maze task, was also significantly impaired in ghrelin KO mice and after i.c.v. Aβ1-40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Ghrelin KO mice had deficits in olfactory discrimination; however, neither i.c.v. Aβ1-40 treatment, nor acyl ghrelin injections affected olfactory discrimination. We used stereology to show that ghrelin KO and Aβ1-40 increased the total number of glial fibrillary acidic protein expressing astrocytes and ionised calcium-binding adapter expressing microglial in the rostral hippocampus. Finally, Aβ1-40 blocked long-term potentiation induced by high-frequency stimulation and this effect could be acutely blocked with co-administration of acyl ghrelin. Collectively, our studies demonstrate that ghrelin deletion affects memory performance and also that acyl ghrelin treatment may delay the onset of early events of AD. This supports the idea that acyl ghrelin treatment may be therapeutically beneficial with respect to restricting disease progression in AD

Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin

Autoantibodies targeting TLR and SMAD pathways define new subgroups in systemic lupus erythematosus

T.J.V. was awarded funding to from the George Koukis Foundation and an Arthritis Research UK Special Strategic Award. The study received support from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and the Biomedical Research Centre based at Guy’s & St. Thomas’ National Health Service (NHS) Foundation Trust, in partnership with King’s College London. The TwinsUK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013)

Nonidentifiability of the Source of Intrinsic Noise in Gene Expression from Single-Burst Data

Over the last few years, experimental data on the fluctuations in gene activity between individual cells and within the same cell over time have confirmed that gene expression is a “noisy” process. This variation is in part due to the small number of molecules taking part in some of the key reactions that are involved in gene expression. One of the consequences of this is that protein production often occurs in bursts, each due to a single promoter or transcription factor binding event. Recently, the distribution of the number of proteins produced in such bursts has been experimentally measured, offering a unique opportunity to study the relative importance of different sources of noise in gene expression. Here, we provide a derivation of the theoretical probability distribution of these bursts for a wide variety of different models of gene expression. We show that there is a good fit between our theoretical distribution and that obtained from two different published experimental datasets. We then prove that, irrespective of the details of the model, the burst size distribution is always geometric and hence determined by a single parameter. Many different combinations of the biochemical rates for the constituent reactions of both transcription and translation will therefore lead to the same experimentally observed burst size distribution. It is thus impossible to identify different sources of fluctuations purely from protein burst size data or to use such data to estimate all of the model parameters. We explore methods of inferring these values when additional types of experimental data are available

Sensitivity of Chaos Measures in Detecting Stress in the Focusing Control Mechanism of the Short-Sighted Eye

yesWhen fixating on a stationary object, the power of the eye’s lens fluctuates. Studies have suggested that changes in these so-called microfluctuations in accommodation may be a factor in the onset and progression of short-sightedness. Like many physiological signals, the fluctuations in the power of the lens exhibit chaotic behaviour. A breakdown or reduction in chaos in physiological systems indicates stress to the system or pathology. The purpose of this study was to determine whether the chaos in fluctuations of the power of the lens changes with refractive error, i.e. how short-sighted a subject is, and/or accommodative demand, i.e. the effective distance of the object that is being viewed. Six emmetropes (EMMs, non-short-sighted), six early-onset myopes (EOMs, onset of short-sightedness before the age of 15), and six late-onset myopes (LOMs, onset of short-sightedness after the age of 15) took part in the study. Accommodative microfluctuations were measured at 22 Hz using an SRW-5000 autorefractor at accommodative demands of 1 D (dioptres), 2 D, and 3 D. Chaos theory analysis was used to determine the embedding lag, embedding dimension, limit of predictability, and Lyapunov exponent. Topological transitivity was also tested for. For comparison, the power spectrum and standard deviation were calculated for each time record. The EMMs had a statistically significant higher Lyapunov exponent than the LOMs ( 0.64±0.330.64±0.33 vs. 0.39±0.20 D/s0.39±0.20 D/s ) and a lower embedding dimension than the LOMs ( 3.28±0.463.28±0.46 vs. 3.67±0.493.67±0.49 ). There was insufficient evidence (non-significant p value) of a difference between EOMs and EMMs or EOMs and LOMs. The majority of time records were topologically transitive. There was insufficient evidence of accommodative demand having an effect. Power spectrum analysis and assessment of the standard deviation of the fluctuations failed to discern differences based on refractive error. Chaos differences in accommodation microfluctuations indicate that the control system for LOMs is under stress in comparison to EMMs. Chaos theory analysis is a more sensitive marker of changes in accommodation microfluctuations than traditional analysis methods

Snow Control - An RCT protocol for a web-based self-help therapy to reduce cocaine consumption in problematic cocaine users

Background: Cocaine use has increased in most European countries, including Switzerland, and many states worldwide. The international literature has described treatment models that target the general population. In addition to supplying informative measures at the level of primary and secondary prevention, the literature also offers web-based self-help tools for problematic substance users, which is in line with tertiary prevention. Such programs, however, have been primarily tested on individuals with problematic alcohol and cannabis consumption, but not on cocaine-dependent individuals. Methods/Design: This paper presents the protocol of a randomised clinical trial to test the effectiveness of a web-based self-help therapy to reduce cocaine use in problematic cocaine users. The primary outcome is severity of cocaine dependence. Secondary outcome measures include cocaine craving, consumption of cocaine and other substances of abuse in the past month, and changes in depression characteristics. The therapy group will receive a 6-week self-help therapy to reduce cocaine consumption based on methods of Cognitive Behavioural Therapy, principles of Motivational Interviewing and self-control practices. The control group will be presented weekly psycho-educative information with a quiz. The predictive validity of participant characteristics on treatment retention and outcome will be explored. Discussion: To the best of our knowledge, this will be the first randomised clinical trial to test the effectiveness of online self-help therapy to reduce or abstain from cocaine use. It will also investigate predictors of outcome and retention. This trial is registered at Current Controlled Trials and is traceable as NTR-ISRCTN93702927

Reproducibility of exhaled nitric oxide in smokers and non-smokers: relevance for longitudinal studies

<p>Abstract</p> <p>Background</p> <p>Currently, there is much interest in measuring fractional exhaled nitric oxide (<b>FE_NO</b>) in populations. We evaluated the reproducibility of <b>FE_NO</b>in healthy subjects and determined the number of subjects necessary to carry out a longitudinal survey of <b>FE_NO</b>in a population containing smokers and non-smokers, based on the assessed reproducibility.</p> <p>Methods</p> <p>The reproducibility of <b>FE_NO</b>was examined in 18 healthy smokers and 21 non-smokers. <b>FE_NO</b>was assessed once at 9 AM on five consecutive days; in the last day this measurement was repeated at 2 PM. Respiratory symptoms and medical history were assessed by questionnaire. The within- and between-session repeatability of <b>FE_NO</b>and log-transformed <b>FE_NO</b>was described. The power of a longitudinal study based on a relative increase in <b>FE_NO</b>was estimated using a bilateral t-test of the log-transformed <b>FE_NO</b>using the between-session variance of the assay.</p> <p>Results</p> <p><b>FE_NO</b>measurements were highly reproducible throughout the study. <b>FE_NO</b>was significantly higher in males than females regardless of smoking status. <b>FE_NO</b>was positively associated with height (p < 0.001), gender (p < 0.034), smoking (p < 0.0001) and percent FEV₁/FVC (p < 0.001) but not with age (p = 0.987). The between-session standard deviation was roughly constant on the log scale. Assuming the between-session standard deviation is equal to its longitudinal equivalent, either 111 or 29 subjects would be necessary to achieve an 80% power in detecting a 3% or a 10% increase in <b>FE_NO</b>respectively.</p> <p>Conclusion</p> <p>The good reproducibility of <b>FE_NO</b>is not influenced by gender or smoking habits. In a well controlled, longitudinal study it should allow detecting even small increases in <b>FE_NO</b>with a reasonable population size.</p

Trends in Depression and Antidepressant Prescribing in Children and Adolescents: A Cohort Study in The Health Improvement Network (THIN)

In 2003, the Committee on Safety of Medicines (CSM) advised against treatment with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine in children, due to a possible increased risk of suicidal behaviour. This study examined the effects of this safety warning on general practitioners' depression diagnosing and prescription behaviour in children