Author Correction: Bayesian reassessment of the epigenetic architecture of complex traits

The original version of this Article contains an error in Fig. 3 in which panel B was inadvertently duplicated from panel A. This has been corrected in both the PDF and HTML versions of the Article

Using a virtual environment to assess cognition in the elderly

YesEarly diagnosis of Alzheimer’s disease (AD) is essential if treatments are to be administered at an earlier point in time before neurons degenerate to a stage beyond repair. In order for early detection to occur tools used to detect the disorder must be sensitive to the earliest of cognitive impairments. Virtual reality (VR) technology offers opportunities to provide products which attempt to mimic daily life situations, as much as is possible, within the computational environment. This may be useful for the detection of cognitive difficulties. We develop a virtual simulation designed to assess visuospatial memory in order to investigate cognitive function in a group of healthy elderly participants and those with a mild cognitive impairment. Participants were required to guide themselves along a virtual path to reach a virtual destination which they were required to remember. The preliminary results indicate that this virtual simulation has the potential to be used for detection of early AD since significant correlations of scores on the virtual environment with existing neuropsychological tests were found. Furthermore, the test discriminated between healthy elderly participants and those with a mild cognitive impairment (MCI)

Gender, school and academic year differences among Spanish university students at high-risk for developing an eating disorder: An epidemiologic study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the magnitude of the university population at high-risk of developing an eating disorder and the prevalence of unhealthy eating attitudes and behaviours amongst groups at risk; gender, school or academic year differences were also explored.</p> <p>Methods</p> <p>A cross-sectional study based on self-report was used to screen university students at high-risk for an eating disorder. The sample size was of 2551 university students enrolled in 13 schools between the ages of 18 and 26 years. The instruments included: a social-demographic questionnaire, the Eating Disorders Inventory (EDI), the Body Shape Questionnaire (BSQ), the Symptom Check List 90-R (SCL-90-R), and the Self-Esteem Scale (RSE). The sample design is a non-proportional stratified sample by academic year and school. The prevalence rate was estimated controlling academic year and school. Logistic regression analysis was used to investigate adjusted associations between gender, school and academic year.</p> <p>Results</p> <p>Female students presented unhealthy weight-control behaviours as dieting, laxatives use or self-induced vomiting to lose weight than males. A total of 6% of the females had a BMI of 17.5 or less or 2.5% had amenorrhea for 3 or more months. In contrast, a higher proportion of males (11.6%) reported binge eating behaviour. The prevalence rate of students at high-risk for an eating disorder was 14.9% (11.6–18) for males and 20.8% (18.7–22.8) for females, according to an overall cut-off point on the EDI questionnaire. Prevalence rates presented statistically significant differences by gender (p < 0.001) but not by school or academic year.</p> <p>Conclusion</p> <p>The prevalence of eating disorder risk in university students is high and is associated with unhealthy weight-control practices, similar results have been found in previous studies using cut-off points in questionnaires. These results may be taken into account to encourage early detection and a greater awareness for seeking treatment in order to improve the diagnosis, among students on university campuses.</p

A Data-Driven Clustering Method for Discovering Profiles in the Dynamics of Major Depressive Disorder Using a Smartphone-Based Ecological Momentary Assessment of Mood

BackgroundAlthough major depressive disorder (MDD) is characterized by a pervasive negative mood, research indicates that the mood of depressed patients is rarely entirely stagnant. It is often dynamic, distinguished by highs and lows, and it is highly responsive to external and internal regulatory processes. Mood dynamics can be defined as a combination of mood variability (the magnitude of the mood changes) and emotional inertia (the speed of mood shifts). The purpose of this study is to explore various distinctive profiles in real-time monitored mood dynamics among MDD patients in routine mental healthcare. MethodsEcological momentary assessment (EMA) data were collected as part of the cross-European E-COMPARED trial, in which approximately half of the patients were randomly assigned to receive the blended Cognitive Behavioral Therapy (bCBT). In this study a subsample of the bCBT group was included (n = 287). As part of bCBT, patients were prompted to rate their current mood (on a 1-10 scale) using a smartphone-based EMA application. During the first week of treatment, the patients were prompted to rate their mood on three separate occasions during the day. Latent profile analyses were subsequently applied to identify distinct profiles based on average mood, mood variability, and emotional inertia across the monitoring period. ResultsOverall, four profiles were identified, which we labeled as: (1) "very negative and least variable mood" (n = 14) (2) "negative and moderate variable mood" (n = 204), (3) "positive and moderate variable mood" (n = 41), and (4) "negative and highest variable mood" (n = 28). The degree of emotional inertia was virtually identical across the profiles. ConclusionsThe real-time monitoring conducted in the present study provides some preliminary indications of different patterns of both average mood and mood variability among MDD patients in treatment in mental health settings. Such varying patterns were not found for emotional inertia

Feasibility of a walking virtual reality system for rehabilitation: objective and subjective parameters

[EN] Background: Even though virtual reality (VR) is increasingly used in rehabilitation, the implementation of walking navigation in VR still poses a technological challenge for current motion tracking systems. Different metaphors simulate locomotion without involving real gait kinematics, which can affect presence, orientation, spatial memory and cognition, and even performance. All these factors can dissuade their use in rehabilitation. We hypothesize that a marker-based head tracking solution would allow walking in VR with high sense of presence and without causing sickness. The objectives of this study were to determine the accuracy, the jitter, and the lag of the tracking system and its elicited sickness and presence in comparison of a CAVE system. Methods: The accuracy and the jitter around the working area at three different heights and the lag of the head tracking system were analyzed. In addition, 47 healthy subjects completed a search task that involved navigation in the walking VR system and in the CAVE system. Navigation was enabled by natural locomotion in the walking VR system and through a specific device in the CAVE system. An HMD was used as display in the walking VR system. After interacting with each system, subjects rated their sickness in a seven-point scale and their presence in the Slater-Usoh-Steed Questionnaire and a modified version of the Presence Questionnaire. Results: Better performance was registered at higher heights, where accuracy was less than 0.6 cm and the jitter was about 6 mm. The lag of the system was 120 ms. Participants reported that both systems caused similar low levels of sickness (about 2.4 over 7). However, ratings showed that the walking VR system elicited higher sense of presence than the CAVE system in both the Slater-Usoh-Steed Questionnaire (17.6 +/- 0.3 vs 14.6 +/- 0.6 over 21, respectively) and the modified Presence Questionnaire (107.4 +/- 2.0 vs 93.5 +/- 3.2 over 147, respectively). Conclusions: The marker-based solution provided accurate, robust, and fast head tracking to allow navigation in the VR system by walking without causing relevant sickness and promoting higher sense of presence than CAVE systems, thus enabling natural walking in full-scale environments, which can enhance the ecological validity of VR-based rehabilitation applications.The authors wish to thank the staff of LabHuman for their support in this project, especially José Miguel Martínez and José Roda for their assistance. This study was funded in part by Ministerio de Economia y Competitividad of Spain (Project NeuroVR, TIN2013-44741-R and Project REACT, TIN2014-61975-EXP), by Ministerio de Educacion y Ciencia of Spain (Project Consolider-C, SEJ2006-14301/PSIC), and by Universitat Politecnica de Valencia (Grant PAID-10-14).Borrego, A.; Latorre Grau, J.; Llorens Rodríguez, R.; Alcañiz Raya, ML.; Noé, E. (2016). Feasibility of a walking virtual reality system for rehabilitation: objective and subjective parameters. Journal of NeuroEngineering and Rehabilitation. 13:1-9. https://doi.org/10.1186/s12984-016-0174-1S1913Lee KM. Presence. Explicated Communication Theory. 2004;14(1):27–50.Riva G. Is presence a technology issue? Some insights from cognitive sciences. Virtual Reality. 2009;13(3):159–69.Banos RM, et al. Immersion and emotion: their impact on the sense of presence. Cyberpsychol Behav. 2004;7(6):734–41.Llorens R, et al. Tracking systems for virtual rehabilitation: objective performance vs. subjective experience. A practical scenario. Sensors (Basel). 2015;15(3):6586–606.Navarro MD, et al. Validation of a low-cost virtual reality system for training street-crossing. A comparative study in healthy, neglected and non-neglected stroke individuals. Neuropsychol Rehabil. 2013;23(4):597–618.Parsons TD. Virtual reality for enhanced ecological validity and experimental control in the clinical, affective and social neurosciences. Front Hum Neurosci. 2015;9:660.Cameirao MS, et al. Neurorehabilitation using the virtual reality based Rehabilitation Gaming System: methodology, design, psychometrics, usability and validation. J Neuroeng Rehabil. 2010;7:48.Llorens R, et al. Improvement in balance using a virtual reality-based stepping exercise: a randomized controlled trial involving individuals with chronic stroke. Clin Rehabil. 2015;29(3):261–8.Llorens R, et al. Videogame-based group therapy to improve self-awareness and social skills after traumatic brain injury. J Neuroeng Rehabil. 2015;12:37.Fong KN, et al. Usability of a virtual reality environment simulating an automated teller machine for assessing and training persons with acquired brain injury. J Neuroeng Rehabil. 2010;7:19.Levin MF, Weiss PL, Keshner EA. Emergence of virtual reality as a tool for upper limb rehabilitation: incorporation of motor control and motor learning principles. Phys Ther. 2015;95(3):415–25.Llorens R, et al. Effectiveness, usability, and cost-benefit of a virtual reality-based telerehabilitation program for balance recovery after stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2015;96(3):418–25. e2.Cruz-Neira C, et al. Scientists in wonderland: A report on visualization applications in the CAVE virtual reality environment. In: 1993. Proceedings IEEE 1993 Symposium on Research Frontiers in Virtual Reality. 1993.Juan MC, Perez D. Comparison of the levels of presence and anxiety in an acrophobic environment viewed via HMD or CAVE. Presence. 2009;18(3):232–48.Yang YR, et al. Virtual reality-based training improves community ambulation in individuals with stroke: a randomized controlled trial. Gait Posture. 2008;28(2):201–6.Cho KH, Lee WH. Virtual walking training program using a real-world video recording for patients with chronic stroke: a pilot study. Am J Phys Med Rehabil. 2013;92(5):371–84.Darter BJ, Wilken JM. Gait training with virtual reality-based real-time feedback: improving gait performance following transfemoral amputation. Phys Ther. 2011;91(9):1385–94.Yang S, et al. Improving balance skills in patients who had stroke through virtual reality treadmill training. Am J Phys Med Rehabil. 2011;90(12):969–78.Walker ML, et al. Virtual reality-enhanced partial body weight-supported treadmill training poststroke: feasibility and effectiveness in 6 subjects. Arch Phys Med Rehabil. 2010;91(1):115–22.Riley PO, et al. A kinematic and kinetic comparison of overground and treadmill walking in healthy subjects. Gait Posture. 2007;26(1):17–24.Alton F, et al. A kinematic comparison of overground and treadmill walking. Clin Biomech. 1998;13(6):434–40.Lee SJ, Hidler J. Biomechanics of overground vs. treadmill walking in healthy individuals. J Appl Physiol. 2008;104(3).Slater M. Measuring presence: a response to the witmer and Singer presence questionnaire. Presence. 1999;8(5):560–5.Viau A, et al. Reaching in reality and virtual reality: a comparison of movement kinematics in healthy subjects and in adults with hemiparesis. J Neuroeng Rehabil. 2004;1(1):11.Parsons TD, et al. The potential of function-led virtual environments for ecologically valid measures of executive function in experimental and clinical neuropsychology. Neuropsychol Rehabil. 2015;11:1–31. doi: 10.1080/09602011.2015.1109524 .Aravind G, Lamontagne A. Perceptual and locomotor factors affect obstacle avoidance in persons with visuospatial neglect. J Neuroeng Rehabil. 2014;11:38.Darekar A, Lamontagne A, Fung J. Dynamic clearance measure to evaluate locomotor and perceptuo-motor strategies used for obstacle circumvention in a virtual environment. Hum Mov Sci. 2015;40:359–71.Whittle MW. Chapter 4 - Methods of gait analysis. In: Whittle MW, editor. Gait analysis. Edinburgh: Butterworth-Heinemann; 2007. p. 137–75.Hodgson E, et al. WeaVR: a self-contained and wearable immersive virtual environment simulation system. Behav Res Methods. 2015;47(1):296–307.Akizuki H, et al. Effects of immersion in virtual reality on postural control. Neurosci Lett. 2005;379(1):23–6.Thies SB, et al. Comparison of linear accelerations from three measurement systems during "reach & grasp". Med Eng Phys. 2007;29(9):967–72.Fiala M. Designing highly reliable fiducial markers. IEEE Trans Pattern Anal Mach Intell. 2010;32(7):1317–24.Garrido-Jurado S, et al. Automatic generation and detection of highly reliable fiducial markers under occlusion. Pattern Recognition. 2014;47(6):2280–92.Kim K, et al. Effects of virtual environment platforms on emotional responses. Comput Methods Programs Biomed. 2014;113(3):882–93.Slater M, Steed A. A virtual presence counter. Presence. 2000;9(5):413–34.Witmer BG, Singer MJ. Measuring presence in virtual environments: a presence questionnaire. Presence Teleop Virt. 1998;7(3):225–40.Martín-Gutiérrez J, et al. Design and validation of an augmented book for spatial abilities development in engineering students. Comput Graph. 2010;34(1):77–91.Lopez-Mir F, et al. Design and validation of an augmented reality system for laparoscopic surgery in a real environment. Biomed Res Int. 2013;2013:758491.Abawi DF, Bienwald J, Dorner R. Accuracy in optical tracking with fiducial markers: an accuracy function for ARToolKit. In: Third IEEE and ACM International symposium on mixed and augmented reality, ISMAR 2004. 2004.Malbezin P, Piekarski W, Thomas BH. Measuring ARTootKit accuracy in long distance tracking experiments. In: The first IEEE International workshop augmented reality toolkit. 2002.Paquette C, Paquet N, Fung J. Aging affects coordination of rapid head motions with trunk and pelvis movements during standing and walking. Gait Posture. 2006;24(1):62–9.Graham JE, et al. Walking speed threshold for classifying walking independence in hospitalized older adults. Phys Ther. 2010;90(11):1591–7.Gorea A. A refresher of the original Bloch’s Law paper (bloch, july 1885). i-Perception. 2015;6:4.Moss JD, Muth ER. Characteristics of head-mounted displays and their effects on Simulator sickness. Hum Factors. 2011;53(3):308–19.Draper MH, et al. Effects of image scale and system time delay on Simulator sickness within head-coupled virtual environments. Hum Factors. 2001;43(1):129–46.Fujisaki W. Effects of delayed visual feedback on grooved pegboard test performance. Front Psychol. 2012;3:61.Keshner EA, et al. Augmenting sensory-motor conflict promotes adaptation of postural behaviors in a virtual environment. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:1379–82.Slaboda JC, Keshner EA. Reorientation to vertical modulated by combined support surface tilt and virtual visual flow in healthy elders and adults with stroke. J Neurol. 2012;259(12):2664–72.Tossavainen T. Comparison of CAVE and HMD for visual stimulation in postural control research. Stud Health Technol Inform. 2004;98:385–7.Akiduki H, et al. Visual-vestibular conflict induced by virtual reality in humans. Neurosci Lett. 2003;340(3):197–200.Duh HBL, et al. Effects of field of view on balance in an immersive environment. In: Virtual Reality, 2001. Proceedings. IEEE. 2001.Krijn M, et al. Treatment of acrophobia in virtual reality: the role of immersion and presence. Behav Res Ther. 2004;42(2):229–39.Mania K, Chalmers A. The effects of levels of immersion on memory and presence in virtual environments: a reality centered approach. Cyberpsychol Behav. 2001;4(2):247–64.Gorini A, et al. The role of immersion and narrative in mediated presence: the virtual hospital experience. Cyberpsychol Behav Soc Netw. 2011;14(3):99–105.Fromberger P, et al. Virtual viewing time: the relationship between presence and sexual interest in androphilic and gynephilic Men. PLoS One. 2015;10(5), e0127156.Slater M, et al. Visual realism enhances realistic response in an immersive virtual environment. IEEE Comput Graph Appl. 2009;29(3):76–84.Nir-Hadad SY, et al. A virtual shopping task for the assessment of executive functions: Validity for people with stroke. Neuropsychol Rehabil. 2015;11:1–26. doi: 10.1080/09602011.2015.1109523 .Vasilyeva M, Lourenco SF. Development of spatial cognition. Wiley Interdiscip Rev Cogn Sci. 2012;3(3):349–62.Banakou D, Groten R, Slater M. Illusory ownership of a virtual child body causes overestimation of object sizes and implicit attitude changes. Proc Natl Acad Sci U S A. 2013;110(31):12846–51.Yee N, Bailenson JN, Ducheneaut N. The proteus effect: implications of transformed digital self-representation on online and offline behavior. Commun Res. 2009;36(2):285–312.Baylor AL. Promoting motivation with virtual agents and avatars: role of visual presence and appearance. Philos Trans R Soc Lond B Biol Sci. 2009;364(1535):3559–65.Clemente M, et al. Assessment of the influence of navigation control and screen size on the sense of presence in virtual reality using EEG. Expert Sys App. 2014;41(4, Part 2):1584–92.Clemente M, et al. An fMRI study to analyze neural correlates of presence during virtual reality experiences. 2013. Interacting with Computers

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Method specific calibration corrects for DNA extraction method effects on relative telomere length measurements by quantitative PCR

Telomere length (TL) is increasingly being used as a biomarker in epidemiological, biomedical and ecological studies. A wide range of DNA extraction techniques have been used in telomere experiments and recent quantitative PCR (qPCR) based studies suggest that the choice of DNA extraction method may influence average relative TL (RTL) measurements. Such extraction method effects may limit the use of historically collected DNA samples extracted with different methods. However, if extraction method effects are systematic an extraction method specific (MS) calibrator might be able to correct for them, because systematic effects would influence the calibrator sample in the same way as all other samples. In the present study we tested whether leukocyte RTL in blood samples from Holstein Friesian cattle and Soay sheep measured by qPCR was influenced by DNA extraction method and whether MS calibration could account for any observed differences. We compared two silica membrane-based DNA extraction kits and a salting out method. All extraction methods were optimized to yield enough high quality DNA for TL measurement. In both species we found that silica membrane-based DNA extraction methods produced shorter RTL measurements than the non-membrane-based method when calibrated against an identical calibrator. However, these differences were not statistically detectable when a MS calibrator was used to calculate RTL. This approach produced RTL measurements that were highly correlated across extraction methods (r > 0.76) and had coefficients of variation lower than 10% across plates of identical samples extracted by different methods. Our results are consistent with previous findings that popular membrane-based DNA extraction methods may lead to shorter RTL measurements than non-membrane-based methods. However, we also demonstrate that these differences can be accounted for by using an extraction method-specific calibrator, offering researchers a simple means of accounting for differences in RTL measurements from samples extracted by different DNA extraction methods within a study

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe

Evidence for Top Quark Production in Nucleus-Nucleus Collisions

Peer reviewe