The (in)effectiveness of anticipatory vibrotactile cues in mitigating motion sickness.

The introduction of (fully) automated vehicles has generated a re-interest in motion sickness, given that passengers suffer much more from motion sickness compared to car drivers. A suggested solution is to improve the anticipation of passive self-motion via cues that alert passengers of changes in the upcoming motion trajectory. We already know that auditory or visual cues can mitigate motion sickness. In this study, we used anticipatory vibrotactile cues that do not interfere with the (audio)visual tasks passengers may want to perform. We wanted to investigate (1) whether anticipatory vibrotactile cues mitigate motion sickness, and (2) whether the timing of the cue is of influence. We therefore exposed participants to four sessions on a linear sled with displacements unpredictable in motion onset. In three sessions, an anticipatory cue was presented 0.33, 1, or 3 s prior to the onset of forward motion. Using a new pre-registered measure, we quantified the reduction in motion sickness across multiple sickness scores in these sessions relative to a control session. Under the chosen experimental conditions, our results did not show a significant mitigation of motion sickness by the anticipatory vibrotactile cues, irrespective of their timing. Participants yet indicated that the cues were helpful. Considering that motion sickness is influenced by the unpredictability of displacements, vibrotactile cues may mitigate sickness when motions have more (unpredictable) variability than those studied here.

Self-motion perception without sensory motion.

Various studies have demonstrated a role for cognition on self-motion perception. Those studies all concerned modulations of the perception of a physical or visual motion stimulus. In our study, however, we investigated whether cognitive cues could elicit a percept of oscillatory self-motion in the absence of sensory motion. If so, we could use this percept to investigate if the resulting mismatch between estimated self-motion and a lack of corresponding sensory signals is motion sickening. To that end, we seated blindfolded participants on a swing that remained motionless during two conditions, apart from a deliberate perturbation at the start of each condition. The conditions only differed regarding instructions, a secondary task and a demonstration, which suggested either a quick halt ("Distraction") or continuing oscillations of the swing ("Focus"). Participants reported that the swing oscillated with larger peak-to-peak displacements and for a longer period of time in the Focus condition. That increase was not reflected in the reported motion sickness scores, which did not differ between the two conditions. As the reported motion was rather small, the lack of an effect on the motion sickness response can be explained by assuming a subthreshold neural conflict. Our results support the existence of internal models relevant to sensorimotor processing and the potential of cognitive (behavioral) therapies to alleviate undesirable perceptual issues to some extent. We conclude that oscillatory self-motion can be perceived in the absence of related sensory stimulation, which advocates for the acknowledgement of cognitive cues in studies on self-motion perception.

How feelings of unpleasantness develop during the progression of motion sickness symptoms.

To mitigate motion sickness in self-driving cars and virtual reality, one should be able to quantify its progression unambiguously. Self-report rating scales either focus on general feelings of unpleasantness or specific symptomatology. Although one generally feels worse as symptoms progress, there is anecdotal evidence suggesting a non-monotonic relationship between unpleasantness and symptomatology. This implies that individuals could (temporarily) feel better as symptoms progress, which could trouble an unambiguous measurement of motion sickness progression. Here we explicitly investigated the temporal development of both unpleasantness and symptomatology using subjective reports, as well as their mutual dependence using psychophysical scaling techniques. We found symptoms to manifest in a fixed order, while unpleasantness increased non-monotonically. Later manifesting symptoms were generally judged as more unpleasant, except for a reduction at the onset of nausea, which corresponded to feeling better. Although we cannot explicate the origin of this reduction, its existence is of importance to the quantification of motion sickness. Specifically, the reduction at nausea onset implies that rating how bad someone feels does not give you an answer to the question of how close someone is to the point of vomiting. We conclude that unpleasantness can unambiguously be inferred from symptomatology, but an ambiguity exists when inferring symptomatology from unpleasantness. These results speak in favor of rating symptomatology when prioritizing an unambiguous quantification of motion sickness progression.

Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity.

BACKGROUND & AIMS: The prenatal environment, including availability of critical nutrients, has a profound impact on offspring development. The present study examined the association between maternal long-chain polyunsaturated fatty acid (LC-PUFA) status during pregnancy and later child behavioral problems at the age of 5-6 years. In light of evidence of autonomic nervous system (ANS) dysregulation in some behavioral problems, study further tested if the above association is statistically mediated by cardiac ANS activity. METHODS: Data was collected as part of the Amsterdam Born Children and their Development-study and complete data were available for 1717 mothers and their offspring. Maternal LC-PUFA status was assessed during early pregnancy (mean gestation = 12.7, SD = 2.5 weeks) and quantified as levels of docosahexenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), as well as the ratio of n-6:n-3 fatty acids. Child emotional problems and peer problems (internalizing problems), as well as conduct problems and inattention/hyperactivity (externalizing problems), were assessed using the Strengths and Difficulties Questionnaire as rated by the mother and teacher at 5-6 years. Child cardiac respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), and heart rate (HR) were utilized as measures of ANS activity at 5-6 years. RESULTS: The results confirmed an association between maternal LC-PUFA status and internalizing behavioral problems as rated by the mother, as shown for DHA (ß = -0.11;p < 0.01), EPA (ß = -0.22;p < 0.05), and n-6:n-3 LC-PUFA (ß = 0.17;p < 0.01). Statistical mediation was only demonstrated for HR. No associations were observed between LC-PUFA status and externalizing behavioral problems. CONCLUSIONS: The present results are consistent with a role of maternal LC-PUFA status in internalizing behavioral problems as rated by the mother. These results were not observed when problem behavior was rated by the teacher. Analyses did not yield strong evidence supporting ANS activity as a possible mediator in this relationship.

A new consensus document on electrocardiographic interpretation in athletes: does it help to prevent sudden cardiac death in athletes?

Sudden cardiac arrest or death (SCA/SCD) in athletes has a low event rate. Pre-participation or eligibility screening is a widely accepted method of primary prevention of SCA/SCD in athletes. Most European countries and international sports governing bodies perform ECG-inclusive screening. However, implementation of a resting 12-lead ECG in pre-participation or eligibility cardiac screening is still a topic of debate. Recently, the 'International recommendations for electrocardiographic interpretation in athletes' was published in three leading international medical journals. These international ECG criteria are based on studies with detailed information on resting 12-lead ECG of Caucasian and Afro-Caribbean athletes or on consensus in case evidence was lacking. Normal, borderline and abnormal ECG findings in young athletes (age 12-35 years) are clearly described and illustrated to assist the screening physician in interpreting ECGs of athletes correctly.In this 'point of view paper' we will discuss whether these new ECG criteria actually help prevent SCA/SCD in athletes.

Current approach of skin lesions suspected of malignancy in general practice in the Netherlands: a quantitative overview.

BACKGROUND: The role of general practitioners (GPs) in skin cancer care is increasing. Previous, hospital-based studies suggest that GPs might not have the capabilities to gain responsibility concerning skin cancer care. OBJECTIVES: To evaluate the current approach of GPs towards skin lesions suspected of malignancy in the Netherlands. METHODS: In three general practices, all consultations in 2015 concerning skin lesions suspected of malignancy were identified and reviewed. Patients demographics, circumstances of consultation, evaluation of skin lesion(s), presumed diagnosis, diagnostic accuracy and policy were evaluated. RESULTS: Five hundred and eighty consultations were identified. Patient took initiative for encounter in 90%. Case-finding occurred in 2%. Diagnostic tools were used in 22%; dermoscopy was used in 8% and a diagnostic excision in 10%. The GP diagnosed a benign lesion in 69%. Therapeutic interventions were applied in 31% and a wait-and-see policy in 40%. The diagnosis after referral was a benign tumour in 39% of the cases, a malignancy in 29% and a premalignant lesion in 17%. The positive predictive value (PPV) of the presumed benign, malignant and premalignant diagnoses was 86%, 54% and 18%, respectively. CONCLUSIONS: Most lesions that are presented to the GP with a suspicion of a malignancy appear to be benign lesions. In the examined practices, the diagnosis of the GP is mainly based on clinical examination and little use is made of available diagnostic tools. The use of a diagnostic tool like a biopsy might prevent unnecessary referrals.

Towards clinical application: prompt gamma imaging of passively scattered proton fields with a knife-edge slit camera.

Prompt γ-ray imaging with a knife-edge shaped slit camera provides the possibility of verifying proton beam range in tumor therapy. Dedicated experiments regarding the characterization of the camera system have been performed previously. Now, we aim at implementing the prototype into clinical application of monitoring patient treatments. Focused on this goal of translation into clinical operation, we systematically addressed remaining challenges and questions. We developed a robust energy calibration routine and corresponding quality assurance protocols. Furthermore, with dedicated experiments, we determined the positioning precision of the system to 1.1 mm (2σ). For the first time, we demonstrated the application of the slit camera, which was intentionally developed for pencil beam scanning, to double scattered proton beams. Systematic experiments with increasing complexity were performed. It was possible to visualize proton range shifts of 2-5 mm with the camera system in phantom experiments in passive scattered fields. Moreover, prompt γ-ray profiles for single iso-energy layers were acquired by synchronizing time resolved measurements to the rotation of the range modulator wheel of the treatment system. Thus, a mapping of the acquired profiles to different anatomical regions along the beam path is feasible and additional information on the source of potential range shifts can be obtained. With the work presented here, we show that an application of the slit camera in clinical treatments is possible and of potential benefit.

Characterization of the microbunch time structure of proton pencil beams at a clinical treatment facility.

Proton therapy is an advantageous treatment modality compared to conventional radiotherapy. In contrast to photons, charged particles have a finite range and can thus spare organs at risk. Additionally, the increased ionization density in the so-called Bragg peak close to the particle range can be utilized for maximum dose deposition in the tumour volume. Unfortunately, the accuracy of the therapy can be affected by range uncertainties, which have to be covered by additional safety margins around the treatment volume. A real-time range and dose verification is therefore highly desired and would be key to exploit the major advantages of proton therapy. Prompt gamma rays, produced in nuclear reactions between projectile and target nuclei, can be used to measure the proton's range. The prompt gamma-ray timing (PGT) method aims at obtaining this information by determining the gamma-ray emission time along the proton path using a conventional time-of-flight detector setup. First tests at a clinical accelerator have shown the feasibility to observe range shifts of about 5 mm at clinically relevant doses. However, PGT spectra are smeared out by the bunch time spread. Additionally, accelerator related proton bunch drifts against the radio frequency have been detected, preventing a potential range verification. At OncoRay, first experiments using a proton bunch monitor (PBM) at a clinical pencil beam have been conducted. Elastic proton scattering at a hydrogen-containing foil could be utilized to create a coincident proton-proton signal in two identical PBMs. The selection of coincident events helped to suppress uncorrelated background. The PBM setup was used as time reference for a PGT detector to correct for potential bunch drifts. Furthermore, the corrected PGT data were used to image an inhomogeneous phantom. In a further systematic measurement campaign, the bunch time spread and the proton transmission rate were measured for several beam energies between 69 and 225 MeV as well as for variable momentum limiting slit openings. We conclude that the usage of a PBM increases the robustness of the PGT method in clinical conditions and that the obtained data will help to create reliable range verification procedures in clinical routine.

Detection of mixed-range proton pencil beams with a prompt gamma slit camera.

With increasing availability of proton and particle therapy centers for tumor treatment, the need for in vivo range verification methods comes more into the focus. Imaging of prompt gamma rays emitted during the treatment is one of the possibilities currently under investigation. A knife-edge shaped slit camera was recently proposed for this task and measurements proved the feasibility of range deviation detection in homogeneous and inhomogeneous targets. In the present paper, we concentrate on laterally inhomogeneous materials, which lead to range mixing situations when crossed by one pencil beam: different sections of the beam have different ranges. We chose exemplative cases from clinical irradiation and assembled idealized tissue equivalent targets. One-dimensional emission profiles were obtained by measuring the prompt gamma emission with the slit camera. It could be shown that the resulting range deviations can be detected by evaluation of the measured data with a previously developed range deviation detection algorithm. The retrieved value, however, strongly depends on the target composition, and is not necessarily in direct relation to the ranges of both parts of the beam. By combining the range deviation detection with an analysis of the slope of the distal edge of the measured prompt gamma profile, the origin of the detected range deviation, i.e. the mixed range of the beam, is also identified. It could be demonstrated that range mixed prompt gamma profiles exhibit less steep distal slopes than profiles from beams traversing laterally homogeneous material. For future application of the slit camera to patient irradiation with double scattered proton beams, situations similar to the range mixing cases are present and results could possibly apply.

Changes in myonuclear domain size do not precede muscle hypertrophy during prolonged resistance-type exercise training.

AIM: Muscle fibre hypertrophy is accompanied by an increase in myonuclear number, an increase in myonuclear domain size or both. It has been suggested that increases in myonuclear domain size precede myonuclear accretion and subsequent muscle fibre hypertrophy during prolonged exercise training. In this study, we assessed the changes in muscle fibre size, myonuclear and satellite cell content throughout 12 weeks of resistance-type exercise training in young men. METHODS: Twenty-two young men (23 ± 1 year) were assigned to a progressive, 12-weeks resistance-type exercise training programme (3 sessions per week). Muscle biopsies from the vastus lateralis muscle were taken before and after 2, 4, 8 and 12 weeks of exercise training. Muscle fibre size, myonuclear content, myonuclear domain size and satellite cell content were assessed by immunohistochemistry. RESULTS: Type I and type II muscle fibre size increased gradually throughout the 12 weeks of training (type I: 18 ± 5%, type II: 41 ± 6%, P < 0.01). Myonuclear content increased significantly over time in both the type I (P < 0.01) and type II (P < 0.001) muscle fibres. No changes in type I and type II myonuclear domain size were observed at any time point throughout the intervention. Satellite cell content increased significantly over time in both type I and type II muscle fibres (P < 0.001). CONCLUSION: Increases in myonuclear domain size do not appear to drive myonuclear accretion and muscle fibre hypertrophy during prolonged resistance-type exercise training in vivo in humans.

Grasping an object comfortably: orientation information is held in memory.

It has been shown that memorized information can influence real-time visuomotor control. For instance, a previously seen object (prime) influences grasping movements toward a target object. In this study, we examined how general the priming effect is: does it depend on the orientation of the target object and the similarity between the prime and the target? To do so, we examined whether priming effects occured for different orientations of the prime and the target objects and for primes that were either identical to the target object or only half of the target object. We found that for orientations of the target object that did not require an awkward grasp, the orientation of the prime could influence the initiation time and the final grip orientation. The priming effects on initiation time were only found when the whole target object was presented as prime, but not when only half of the target object was presented. The results suggest that a memory effect on real-time control is constrained by end-state comfort and by the relevance of the prime for the grasping movement, which might mean that the interactions between the ventral and dorsal pathways are task specific.

Analytical computation of prompt gamma ray emission and detection for proton range verification.

A prompt gamma (PG) slit camera prototype recently demonstrated that Bragg Peak position in a clinical proton scanned beam could be measured with 1-2 mm accuracy by comparing an expected PG detection profile to a measured one. The computation of the expected PG detection profile in the context of a clinical framework is challenging but must be solved before clinical implementation. Obviously, Monte Carlo methods (MC) can simulate the expected PG profile but at prohibitively long calculation times. We implemented a much faster method that is based on analytical processing of precomputed MC data that would allow practical evaluation of this range monitoring approach in clinical conditions. Reference PG emission profiles were generated with MC simulations (PENH) in targets consisting of either (12)C, (14)N, (16)O, (31)P or (40)Ca, with 10% of (1)H. In a given geometry, the local PG emission can then be derived by adding the contribution of each element, according to the local energy of the proton obtained by continuous slowing down approximation and the local composition. The actual incident spot size is taken into account using an optical model fitted to measurements and by super sampling the spot with several rays (up to 113). PG transport in the patient/camera geometries and the detector response are modelled by convolving the PG production profile with a transfer function. The latter is interpolated from a database of transfer functions fitted to MC data (PENELOPE) generated for a photon source in a cylindrical phantom with various radiuses and a camera placed at various positions. As a benchmark, the analytical model was compared to MC and experiments in homogeneous and heterogeneous phantoms. Comparisons with MC were also performed in a thoracic CT. For all cases, the analytical model reproduced the prediction of the position of the Bragg peak computed with MC within 1 mm for the camera in nominal configuration. When compared to measurements, the shape of the profiles was well reproduced and agreement for the estimation of the position of the Bragg peak was within 2.7 mm on average (1.4 mm standard deviation). On a non-optimized MATLAB code, computation time with the analytical model is between 0.3 to 10 s depending on the number of rays simulated per spot. The analytical model can be further used to determine which spots are the best candidates to evaluate the range in clinical conditions and eventually correct for over- and under-shoots depending on the acquired PG profiles.

Measurement of prompt gamma profiles in inhomogeneous targets with a knife-edge slit camera during proton irradiation.

Proton and ion beam therapies become increasingly relevant in radiation therapy. To fully exploit the potential of this irradiation technique and to achieve maximum target volume conformality, the verification of particle ranges is highly desirable. Many research activities focus on the measurement of the spatial distributions of prompt gamma rays emitted during irradiation. A passively collimating knife-edge slit camera is a promising option to perform such measurements. In former publications, the feasibility of accurate detection of proton range shifts in homogeneous targets could be shown with such a camera. We present slit camera measurements of prompt gamma depth profiles in inhomogeneous targets. From real treatment plans and their underlying CTs, representative beam paths are selected and assembled as one-dimensional inhomogeneous targets built from tissue equivalent materials. These phantoms have been irradiated with monoenergetic proton pencil beams. The accuracy of range deviation estimation as well as the detectability of range shifts is investigated in different scenarios. In most cases, range deviations can be detected within less than 2 mm. In close vicinity to low-density regions, range detection is challenging. In particular, a minimum beam penetration depth of 7 mm beyond a cavity is required for reliable detection of a cavity filling with the present setup. Dedicated data post-processing methods may be capable of overcoming this limitation.