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open Master Hearing Aid (openMHA) was developed and provided to the hearing aid research community as an open-source software platform with the aim to support sustainable and reproducible research towards improvement and new types of assistive hearing systems not limited by proprietary software. The software offers a flexible framework that allows the users to conduct hearing aid research using tools and a number of signal processing plugins provided with the software as well as the implementation of own methods. The openMHA software is independent of a specific hardware and supports Linux, macOS and Windows operating systems as well as 32-bit and 64-bit ARM-based architectures such as used in small portable integrated systems. www.openmha.org

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC.

Abstract Currently little is known about structure-function mappings in the human subcortex. Here we present a large-scale automated meta-analysis on the literature to understand the structure-function mapping in the human subcortex. The results provide converging evidence into unique large scale structure-function mappings of the human subcortex based on their functional and anatomical similarity.

Annette van Maanen,1 Anne Marie Meijer,1 Marcel G Smits,2 Frans J Oort1 1Research Institute Child Development and Education, University of Amsterdam, Amsterdam, 2Centre for Sleep-Wake Disorders and Chronobiology, Hospital Gelderse Vallei, Ede, the Netherlands Abstract: Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism) received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism) who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light. Keywords: melatonin, classical conditioning, children, delayed sleep

Background: The majority of human papillomavirus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN) present upregulation of the epidermal growth factor receptor (EGFR) and frequent alterations in the cyclin D1-cyclin dependent kinase (CDK) 4/6 (CDK 4/6)-retinoblastoma protein (pRb) pathway, resulting in cell cycle progression and tumor proliferation. This study investigated the combination of ribociclib, an orally highly selective inhibitor of CDK 4/6, and cetuximab in recurrent and/or metastatic (R/M) SCCHN.Methods: A phase I trial using a 3 + 3 design was performed to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of ribociclib with standard dose of weekly cetuximab in HPV-negative patients with R/M SCCHN. Ribociclib was administered orally (3 weeks on/1 week off) at dose level 1 of 400 mg daily and dose level 2 of 600 mg daily. The MTD of ribocilib was then further evaluated in an expansion cohort.Results: 10 patients were enrolled in the escalation trial. No DLTs were observed at dose level 1 (n = 3); at dose level 2, one patient was replaced due to rapid disease progression, and one patient out of six evaluable patients experienced a DLT (grade 4 thrombocytopenia >7 days). Ribociclib 600 mg daily was thus determined to be the MTD. Eleven additional patients were enrolled in the expansion cohort. Diarrhea (52%), rash (52%), fatigue (43%), nausea (33%), and mucositis (28%) were the most frequent grade 1–2 adverse events (AE). Neutropenia was the most frequent grade 3–4 AE (20%). Median progression-free survival (PFS) was 3.5 months (range 0.4–17.3 months) and median overall survival (OS) was 8.3 months (range 0.4–24.1 months). Among the 19 radiologically evaluable patients, two (10.5%) achieved a partial response and 11 (58%) had stable disease.Conclusions: The MTD of ribociclib is 600 mg daily when administered in combination with standard dose cetuximab for 3 weeks on and 1 week off. This combination was safe and showed efficacy. Further clinical trials should be conducted to evaluate the antitumor effects of this combination.Trial Information:ClinicalTrials.gov: NCT02429089; Eudract number 2014-005371-83.

This article describes the design and validation of deployable low-power probes and sensors to investigate the influence of the ionosphere and the Earth’s magnetic field on radio wave propagation below the plasma frequency of the ionosphere, known as Near Vertical Incidence Skywave (NVIS) propagation. The propagation of waves that are bent downward by the ionosphere is dominated by a bi-refractive mechanism called ‘magneto-ionic propagation’. The polarization of both downward waves depends on the spatial angle between the Earth’s magnetic field and the direction of propagation of the radio wave. The probes and sensors described in this article are needed to simultaneously investigate signal fading and polarization dynamics on six radio wave propagation paths. The 1-Watt probes realize a 57 dB signal-to-noise ratio. The probe polarization is controlled using direct digital synthesis and the cross-polarization is 25−35 dB. The intermodulation-free dynamic range of the sensor exceeds 100 dB. Measurement speed is 3000 samples/second. This publication covers design, practical realization and deployment issues. Research performed with these devices will be shared in subsequent publications.

Foot and mouth disease (FMD) epidemics recur in Israel almost every year. Wild even-toed ungulates are seldom affected during these epidemics. The sero-prevalence of FMD in wild ungulates during 2000 and 2005-13 was estimated using anti non-structural proteins (NSP) ELISA. Overall, 209 samples were tested, comprising sera of 120 wild boar (Sus scrofa lybicus), 64 mountain gazelles (Gazella gazella gazella), six water buffaloes (Bubalus bubalis), and 19 Persian fallow deer (Dama dama mesopotamica). None of the tested animals presented clinical signs of FMD during blood collection. Sixteen samples (7.7% (95% confidence interval (CI95%) = 4.4 - 12.1%)) were found to be sero-positive. Fifteen out of 120 samples (12.5%) from wild boar were sero-positive, compared with only one out of 89 samples (1.1%) from all other species combined (Fisher's Exact test: p=0.003). Most of the positive samples obtained from wild boar (13/15 (86.7%)) were collected during 2007 and analysis was restricted to that year and species only. The sero-prevalence of FMD in this species during 2007 was estimated at 54.2% (CI95%=32.8 - 74.5%; n=24). A significant infection cluster, comprising nine sero-positive samples collected in three different locations, was identified in the north-eastern part of Israel. These findings indicate that wild boar were affected during the 2007 FMD epidemic, even though wild boar presenting FMD typical clinical signs were not observed during that year. The actual role of wild boar in the spread of FMD virus in this epidemic, however, could not be determined. The negligible sero-prevalence of FMD found for all other surveillance years indicates that ongoing circulation of FMD among wildlife in Israel is unlikely. It is concluded that while the role of wildlife species in the dynamics of FMD in Israel is usually limited, there might be occasions in which wildlife play a part in the spread of the virus.

The notion of "mixtures" has become pervasive in behavioral and cognitive sciences, due to the success of dual-process theories of cognition. However, providing support for such dual-process theories is not trivial, as it crucially requires properties in the data that are specific to mixture of cognitive processes. In theory, one such property could be the fixed-point property of binary mixture data, applied-for instance- to response times. In that case, the fixed-point property entails that response time distributions obtained in an experiment in which the mixture proportion is manipulated would have a common density point. In the current article, we discuss the application of the fixed-point property and identify three boundary conditions under which the fixed-point property will not be interpretable. In Boundary condition 1, a finding in support of the fixed-point will be mute because of a lack of difference between conditions. Boundary condition 2 refers to the case in which the extreme conditions are so different that a mixture may display bimodality. In this case, a mixture hypothesis is clearly supported, yet the fixed-point may not be found. In Boundary condition 3 the fixed-point may also not be present, yet a mixture might still exist but is occluded due to additional changes in behavior. Finding the fixed-property provides strong support for a dual-process account, yet the boundary conditions that we identify should be considered before making inferences about underlying psychological processes.

The environmental toxin bisphenol A (BPA) is a known mammalian hormone disrupter but its effects on plants have not been well established. The effect of BPA on gene expression in Arabidopsis thaliana was determined using microarray analysis and quantitative gene PCR. Many hormone responsive genes showed changes in expression after BPA treatment. BPA disrupted flowering by a mechanism that may involve disruption of auxin signaling. The results presented here indicate that BPA is a plant hormone disrupter.

An artificial neural network (ANN) was developed to predict the depth-integrated alongshore suspended sediment transport rate using 4 input variables (water depth, wave height and period, and alongshore velocity). The ANN was trained and validated using a dataset obtained on the intertidal beach of Egmond aan Zee, the Netherlands. Root-mean-square deviation between observations and predictions was calculated to show that, for this specific dataset, the ANN (εrms=0.43) outperforms the commonly used Bailard (1981) formula (εrms=1.63), even when this formula is calibrated (εrms=0.66). Because of correlations between input variables, the predictive quality of the ANN can be improved further by considering only 3 out of the 4 available input variables (εrms=0.39). Finally, we use the partial derivatives method to "open and lighten" the generated ANNs with the purpose of showing that, although specific to the dataset in question, they are not "black-box" type models and can be used to analyze the physical processes associated with alongshore sediment transport. In this case, the alongshore component of the velocity, by itself or in combination with other input variables, has the largest explanatory power. Moreover, the behaviour of the ANN indicates that predictions can be unphysical and therefore unreliable when the input lies outside the parameter space over which the ANN has been developed. Our approach of combining the strong predictive power of ANNs with "lightening" the black box and testing its sensitivity, demonstrates that the use of an ANN approach can result in the development of generalized models of suspended sediment transport.

To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge.Retrospective cohort study between January 2007 and July 2011.Academic teaching hospital in the Netherlands.Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73 m(2) at discharge and prescribed one or more medicines of which the dose is renal function dependent.The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR

INTRODUCTION:The cholinergic anti-inflammatory pathway can downregulate inflammation via the release of acetylcholine (ACh) by the vagus nerve. This neurotransmitter binds to the α7 subunit of nicotinic acetylcholine receptors (α7nAChR), expressed on macrophages and other immune cells. We tested the pharmacological and functional profile of two novel compounds, PMP-311 and PMP-072 and investigated their role in modulating collagen-induced arthritis (CIA) in mice. METHODS:Both compounds were characterized with binding, electrophysiological, and pharmacokinetic studies. For in vivo efficacy studies in the CIA model the compounds were administered daily by oral gavage from day 20 till sacrifice at day 34. Disease progression was monitored by visual clinical scoring and measurement of paw swelling. Inflammation and joint destruction were examined by histology and radiology. RESULTS:Treatment with PMP-311 was effective in preventing disease onset, reducing clinical signs of arthritis, and reducing synovial inflammation and bone destruction. PMP-072 also showed a trend in arthritis reduction at all concentrations tested. The data showed that while both compounds bind to α7nAChR with high affinity, PMP-311 acts like a classical agonist of ion channel activity, and PMP-072 can actually act as an ion channel antagonist. Moreover, PMP-072 was clearly distinct from typical competitive antagonists, since it was able to act as a silent agonist. It synergizes with the allosteric modulator PNU-120596, and subsequently activates desensitized α7nAChR. However, PMP-072 was less efficacious than PMP-311 at both channel activation and desensitization, suggesting that both conducting and non-conducting states maybe of importance in driving an anti-inflammatory response. Finally, we found that the anti-arthritic effect can be observed despite limited penetration of the central nervous system. CONCLUSIONS:These data provide direct evidence that the α7nAChR in immune cells does not require typical ion channel activation to exert its antiinflammatory effects.

Four cowpox virus (CPXV) outbreaks occurred in unrelated alpaca herds in Eastern Germany during 2012–2017. All incidents were initially noticed due to severe, generalized, and finally lethal CPXV infections, which were confirmed by testing of tissue and serum samples. As CPXV-infection has been described in South American camelids (SACs) only three times, all four herds were investigated to gain a deeper understanding of CPXV epidemiology in alpacas. The different herds were investigated twice, and various samples (serum, swab samples, and crusts of suspicious pox lesions, feces) were taken to identify additionally infected animals. Serum was used to detect CPXV-specific antibodies by performing an indirect immunofluorescence assay (iIFA); swab samples, crusts, and feces were used for detection of CPXV-specific DNA in a real-time PCR. In total, 28 out of 107 animals could be identified as affected by CPXV, by iIFA and/or PCR. Herd seroprevalence ranged from 16.1% to 81.2%. To investigate the potential source of infection, wild small mammals were trapped around all alpaca herds. In two herds, CPXV-specific antibodies were found in the local rodent population. In the third herd, CPXV could be isolated from a common vole (Microtus arvalis) found drowned in a water bucket used to water the alpacas. Full genome sequencing and comparison with the genome of a CPXV from an alpaca from the same herd reveal 99.997% identity, providing further evidence that the common vole is a reservoir host and infection source of CPXV. Only in the remaining fourth herd, none of the trapped rodents were found to be CPXV-infected. Rodents, as ubiquitous reservoir hosts, in combination with increasingly popular alpacas, as susceptible species, suggest an enhanced risk of future zoonotic infections.

With the increasing number of active magnetic bearing applications, satisfying additional requirements is becoming increasingly more important. As for every technology, moving away from being a niche product and achieving a higher level of maturity, these requirements relate to robustness, reliability, availability, safety, security, traceability, certification, handling, flexibility, reporting, costs, and delivery times. Employing standard industrial components, such as those from flexible modular motion control drive systems, is an approach that allows these requirements to be satisfied while achieving rapid technological innovation. In this article, we discuss technical and non-technical aspects of using standard industrial components in magnetic bearing applications.

When multiple strategies can be used to solve a type of problem, the observed response time distributions are often mixtures of multiple underlying base distributions each representing one of these strategies. For the case of two possible strategies, the observed response time distributions obey the fixed-point property. That is, there exists one reaction time that has the same probability of being observed irrespective of the actual mixture proportion of each strategy. In this paper we discuss how to compute this fixed-point, and how to statistically assess the probability that indeed the observed response times are generated by two competing strategies. Accompanying this paper is a free R package that can be used to compute and test the presence or absence of the fixed-point property in response time data, allowing for easy to use tests of strategic behavior.

A recent study by van Ede et al. (2012) shows that the accuracy and reaction time in humans of tactile perceptual decisions are affected by an attentional cue via distinct cognitive and neural processes. These results are controversial as they undermine the notion that accuracy and reaction time are influenced by the same latent process that underlie the decision process. Typically, accumulation-to-bound models (like the drift diffusion model) can explain variability in both accuracy and reaction time by a change of a single parameter. To elaborate the findings of van Ede et al., we fitted the drift diffusion model to their behavioral data. Results show that both changes in accuracy and reaction time can be partly explained by an increase in the accumulation of sensory evidence (drift rate). In addition, a change in non-decision time is necessary to account for reaction time changes as well. These results provide a subtle explanation of how the underlying dynamics of the decision process might give rise to differences in both the speed and accuracy of perceptual tactile decisions. Furthermore, our analyses highlight the importance of applying a model-based approach, as the observed changes in the model parameters might be ecologically more valid, since they have an intuitive relationship with the neuronal processes underlying perceptual decision making.

BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I) and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II). All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol). Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year). All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year) b: Oligomenorrhea (5 to 9 cycles/year) c: Severe oligomenorrhea (1 to 4 cycles/year) d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status. These data are very important for the choice of endocrine therapy.

Being quick often comes at the expense of being accurate. This speed-accuracy tradeoff is a central feature of many types of decision making. It has been proposed that dopamine plays an important role in adjusting responses between fast and accurate behavior. In the current study we investigated the role of dopamine in perceptual decision making in humans, focusing on speed-accuracy tradeoff. Using a cued version of the random dot motion task, we instructed subjects to either make a fast or an accurate decision. We investigated decision making behavior in subjects who were given bromocriptine (a dopamine receptor agonist) or placebo. We analyzed the behavioral data using two accumulator models, the drift diffusion model and the linear ballistic accumulator model. On a behavioral level, there were clear differences in decision threshold between speed and accuracy focus, but decision threshold did not differ between the drug and placebo sessions. Bayesian analyses support the null hypothesis that there is no effect of bromocriptine on decision threshold. On the neural level, we replicate previous findings that the striatum and pre-supplementary motor area are active when preparing for speed, compared with accurate decisions. We do not find an effect of bromocriptine on this activation. Therefore, we conclude that bromocriptine does not alter speed-accuracy tradeoff.

Piéron's Law describes a psychophysical regularity between mean response times and stimulus intensity in signal detection tasks. In this paper we extend this notion to perceptual two-choice decision-making, and demonstrate that Piéron's Law holds as the discriminability between two competing choices is manipulated. We present a Bayesian ideal observer model that explains why a Piéron-like regularity is found when stimulus discriminability is manipulated, and discuss how this model can be extended to cover signal detection tasks.

Hacer etnografía implicaba, en el pasado, vivir con un grupo, observar su comportamiento, tomar notas de campo y, posteriormente, escribir sobre ello. Hoy en día, la etnografía ha sido puesta en cuestión epistemológicamente y el campo se encuentra en un e

Recent advancements in neuroscientific research and miniaturized ear-electroencephalography (EEG) technologies have led to the idea of employing brain signals as additional input to hearing aid algorithms. The information acquired through EEG could potentially be used to control the audio signal processing of the hearing aid or to monitor communication-related physiological factors. In previous work, we implemented a research platform to develop methods that utilize EEG in combination with a hearing device. The setup combines currently available mobile EEG hardware and the so-called Portable Hearing Laboratory (PHL), which can fully replicate a complete hearing aid. Audio and EEG data are synchronized using the Lab Streaming Layer (LSL) framework. In this study, we evaluated the setup in three scenarios focusing particularly on the alignment of audio and EEG data. In Scenario I, we measured the latency between software event markers and actual audio playback of the PHL. In Scenario II, we measured the latency between an analog input signal and the sampled data stream of the EEG system. In Scenario III, we measured the latency in the whole setup as it would be used in a real EEG experiment. The results of Scenario I showed a jitter (standard deviation of trial latencies) of below 0.1 ms. The jitter in Scenarios II and III was around 3 ms in both cases. The results suggest that the increased jitter compared to Scenario I can be attributed to the EEG system. Overall, the findings show that the measurement setup can time-accurately present acoustic stimuli while generating LSL data streams over multiple hours of playback. Further, the setup can capture the audio and EEG LSL streams with sufficient temporal accuracy to extract event-related potentials from EEG signals. We conclude that our setup is suitable for studying closed-loop EEG & audio applications for future hearing aids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dasenbrock, Blum, Maanen, Debener, Hohmann and Kayser.)

This Letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97  GeV/c bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate (≈121  kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a 1 standard deviation range of σ=0.21  rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26  mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles.

We observe a deuteron beam polarization lifetime near 1000 s in the horizontal plane of a magnetic storage ring (COSY). This long spin coherence time is maintained through a combination of beam bunching, electron cooling, sextupole field corrections, and the suppression of collective effects through beam current limits. This record lifetime is required for a storage ring search for an intrinsic electric dipole moment on the deuteron at a statistical sensitivity level approaching 10^{-29}  e cm.

A new method to determine the spin tune is described and tested. In an ideal planar magnetic ring, the spin tune-defined as the number of spin precessions per turn-is given by ν(s)=γG (γ is the Lorentz factor, G the gyromagnetic anomaly). At 970  MeV/c, the deuteron spins coherently precess at a frequency of ≈120  kHz in the Cooler Synchrotron COSY. The spin tune is deduced from the up-down asymmetry of deuteron-carbon scattering. In a time interval of 2.6 s, the spin tune was determined with a precision of the order 10^{-8}, and to 1×10^{-10} for a continuous 100 s accelerator cycle. This renders the presented method a new precision tool for accelerator physics; controlling the spin motion of particles to high precision is mandatory, in particular, for the measurement of electric dipole moments of charged particles in a storage ring.