Automatic Detection of Cortical Arousals in Sleep and their Contribution to Daytime Sleepiness

Cortical arousals are transient events of disturbed sleep that occur spontaneously or in response to stimuli such as apneic events. The gold standard for arousal detection in human polysomnographic recordings (PSGs) is manual annotation by expert human scorers, a method with significant interscorer variability. In this study, we developed an automated method, the Multimodal Arousal Detector (MAD), to detect arousals using deep learning methods. The MAD was trained on 2,889 PSGs to detect both cortical arousals and wakefulness in 1 second intervals. Furthermore, the relationship between MAD-predicted labels on PSGs and next day mean sleep latency (MSL) on a multiple sleep latency test (MSLT), a reflection of daytime sleepiness, was analyzed in 1447 MSLT instances in 873 subjects. In a dataset of 1,026 PSGs, the MAD achieved a F1 score of 0.76 for arousal detection, while wakefulness was predicted with an accuracy of 0.95. In 60 PSGs scored by multiple human expert technicians, the MAD significantly outperformed the average human scorer for arousal detection with a difference in F1 score of 0.09. After controlling for other known covariates, a doubling of the arousal index was associated with an average decrease in MSL of 40 seconds ($\beta$ = -0.67, p = 0.0075). The MAD outperformed the average human expert and the MAD-predicted arousals were shown to be significant predictors of MSL, which demonstrate clinical validity the MAD.Comment: 40 pages, 13 figures, 9 table

Exactly solvable potentials of Calogero type for q-deformed Coxeter groups

We establish that by parameterizing the configuration space of a one-dimensional quantum system by polynomial invariants of q-deformed Coxeter groups it is possible to construct exactly solvable models of Calogero type. We adopt the previously introduced notion of solvability which consists of relating the Hamiltonian to finite dimensional representation spaces of a Lie algebra. We present explicitly the $G_2^q$-case for which we construct the potentials by means of suitable gauge transformations.Comment: 22 pages Late

Full frequency voltage noise spectral density of a single electron transistor

We calculate the full frequency spectral density of voltage fluctuations in a Single Electron Transistor (SET), used as an electrometer biased above the Coulomb threshold so that the current through the SET is carried by sequential tunnel events. We consider both a normal state SET and a superconducting SET. The whole spectrum from low frequency telegraph noise to quantum noise at frequencies comparable to the SET charging energy $(E_{C}/\hbar)$, and high frequency Nyquist noise is described. We take the energy exchange between the SET and the measured system into account using a real-time diagrammatic Keldysh technique. The voltage fluctuations determine the back-action of the SET onto the measured system and we specifically discuss the case of superconducting charge qubit read-out and measuring the so-called Coulomb staircase of a single Cooper pair box.Comment: 14 pages, 18 figures, submitted to PR

An Evolutionarily Conserved Arginine Is Essential for Tre1 G Protein-Coupled Receptor Function During Germ Cell Migration in Drosophila melanogaster

BACKGROUND: G protein-coupled receptors (GPCRs) play central roles in mediating cellular responses to environmental signals leading to changes in cell physiology and behaviors, including cell migration. Numerous clinical pathologies including metastasis, an invasive form of cell migration, have been linked to abnormal GPCR signaling. While the structures of some GPCRs have been defined, the in vivo roles of conserved amino acid residues and their relationships to receptor function are not fully understood. Trapped in endoderm 1 (Tre1) is an orphan receptor of the rhodopsin class that is necessary for primordial germ cell migration in Drosophila melanogaster embryos. In this study, we employ molecular genetic approaches to identify residues in Tre1 that are critical to its functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the previously reported scattershot mutation is an allele of tre1. The scattershot allele results in an in-frame deletion of 8 amino acids at the junction of the third transmembrane domain and the second intracellular loop of Tre1 that dramatically impairs the function of this GPCR in germ cell migration. To further refine the molecular basis for this phenotype, we assayed the effects of single amino acid substitutions in transgenic animals and determined that the arginine within the evolutionarily conserved E/N/DRY motif is critical for receptor function in mediating germ cell migration within an intact developing embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR signaling in native contexts will inform future studies into the basic biology of this large and clinically important family of receptors

3066 consecutive Gamma Nails. 12 years experience at a single centre

<p>Abstract</p> <p>Background</p> <p>Fixation of trochanteric hip fractures using the Gamma Nail has been performed since 1988 and is today well established and wide-spread. However, a number of reports have raised serious concerns about the implant's complication rate. The main focus has been the increased risk of a subsequent femoral shaft fracture and some authors have argued against its use despite other obvious advantages, when this implant is employed.</p> <p>Through access to a uniquely large patient data base available, which is available for analysis of trochanteric fractures; we have been able to evaluate the performance of the Gamma Nail over a twelve year period.</p> <p>Methods</p> <p>3066 consecutive patients were treated for trochanteric fractures using Gamma Nails between 1990 and 2002 at the Centre de Traumatologie et de l'Orthopedie (CTO), Strasbourg, France. These patients were retrospectively analysed. Information on epidemiological data, intra- and postoperative complications and patients' outcome was retrieved from patient notes. All available radiographs were assessed by a single reviewer (AJB).</p> <p>Results</p> <p>The results showed a low complication rate with the use of the Gamma Nail. There were 137 (4.5%) intraoperative fracture-related complications. Moreover 189 (6.2%) complications were detected postoperatively and during follow-up. Cut-out of the lag screw from the femoral head was the most frequent mechanical complication (57 patients, 1.85%), whereas a postoperative femoral shaft fracture occurred in 19 patients (0.6%). Other complications, such as infection, delayed healing/non-union, avascular femoral head necrosis and distal locking problems occurred in 113 patients (3.7%).</p> <p>Conclusions</p> <p>The use of the Gamma Nail in trochanteric hip fractures is a safe method with a low complication rate. In particular, a low rate of femoral shaft fractures was reported. The low complication rate reported in this series can probably be explained by strict adherence to a proper surgical technique.</p

The role of natural science collections in the biomonitoring of environmental contaminants in apex predators in support of the EU's zero pollution ambition

The chemical industry is the leading sector in the EU in terms of added value. However, contaminants pose a major threat and significant costs to the environment and human health. While EU legislation and international conventions aim to reduce this threat, regulators struggle to assess and manage chemical risks, given the vast number of substances involved and the lack of data on exposure and hazards. The European Green Deal sets a 'zero pollution ambition for a toxic free environment' by 2050 and the EU Chemicals Strategy calls for increased monitoring of chemicals in the environment. Monitoring of contaminants in biota can, inter alia: provide regulators with early warning of bioaccumulation problems with chemicals of emerging concern; trigger risk assessment of persistent, bioaccumulative and toxic substances; enable risk assessment of chemical mixtures in biota; enable risk assessment of mixtures; and enable assessment of the effectiveness of risk management measures and of chemicals regulations overall. A number of these purposes are to be addressed under the recently launched European Partnership for Risk Assessment of Chemicals (PARC). Apex predators are of particular value to biomonitoring. Securing sufficient data at European scale implies large-scale, long-term monitoring and a steady supply of large numbers of fresh apex predator tissue samples from across Europe. Natural science collections are very well-placed to supply these. Pan-European monitoring requires effective coordination among field organisations, collections and analytical laboratories for the flow of required specimens, processing and storage of specimens and tissue samples, contaminant analyses delivering pan-European data sets, and provision of specimen and population contextual data. Collections are well-placed to coordinate this. The COST Action European Raptor Biomonitoring Facility provides a well-developed model showing how this can work, integrating a European Raptor Biomonitoring Scheme, Specimen Bank and Sampling Programme. Simultaneously, the EU-funded LIFE APEX has demonstrated a range of regulatory applications using cutting-edge analytical techniques. PARC plans to make best use of such sampling and biomonitoring programmes. Collections are poised to play a critical role in supporting PARC objectives and thereby contribute to delivery of the EU's zero-pollution ambition.Non peer reviewe

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

Contains fulltext : 69534.pdf (publisher's version ) (Open Access)BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150

The World Federation of ADHD International Consensus Statement:208 Evidence-based conclusions about the disorder

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.</p

Second Language Processing Shows Increased Native-Like Neural Responses after Months of No Exposure

Although learning a second language (L2) as an adult is notoriously difficult, research has shown that adults can indeed attain native language-like brain processing and high proficiency levels. However, it is important to then retain what has been attained, even in the absence of continued exposure to the L2—particularly since periods of minimal or no L2 exposure are common. This event-related potential (ERP) study of an artificial language tested performance and neural processing following a substantial period of no exposure. Adults learned to speak and comprehend the artificial language to high proficiency with either explicit, classroom-like, or implicit, immersion-like training, and then underwent several months of no exposure to the language. Surprisingly, proficiency did not decrease during this delay. Instead, it remained unchanged, and there was an increase in native-like neural processing of syntax, as evidenced by several ERP changes—including earlier, more reliable, and more left-lateralized anterior negativities, and more robust P600s, in response to word-order violations. Moreover, both the explicitly and implicitly trained groups showed increased native-like ERP patterns over the delay, indicating that such changes can hold independently of L2 training type. The results demonstrate that substantial periods with no L2 exposure are not necessarily detrimental. Rather, benefits may ensue from such periods of time even when there is no L2 exposure. Interestingly, both before and after the delay the implicitly trained group showed more native-like processing than the explicitly trained group, indicating that type of training also affects the attainment of native-like processing in the brain. Overall, the findings may be largely explained by a combination of forgetting and consolidation in declarative and procedural memory, on which L2 grammar learning appears to depend. The study has a range of implications, and suggests a research program with potentially important consequences for second language acquisition and related fields