Observational study on the neonatal outcome during the COVID-19 pandemic in Germany.

AIM: We aimed to determine stillbirth, preterm birth, perinatal complications, and the developmental outcome of children born preterm during the COVID-19 pandemic in Germany. METHODS: National data from the perinatal survey of preterm and term infants born in 2017-2020 between 22 March and 31 December were evaluated. Neurodevelopment of preterm infants at 2 years corrected age was tested with the Parent Report of Children's Abilities-Revised questionnaire and by clinical testing with Bayley scales, either before or during the COVID-19 pandemic. Statistical significance was calculated using a Pearson's chi-square-independence test and a linear regression model. RESULTS: In 2020, there was an increase of stillbirths of 0.02% (p = 0.01) and a decrease in preterm births by 0.38% (p < 0.001). No changes were found in a representative subgroup of infants with regard to neurodevelopmental scores (mental developmental index and psychomotor developmental index) or in parent survey data (non-verbal cognition scale and language development scale). CONCLUSION: Increasing rates of stillbirths and decreasing preterm births in Germany were observed. Existing networks might stabilise neurodevelopment of preterm infants during the COVID-19 pandemic.

Task requirements affect the neural correlates of consciousness.

In the search for the neural correlates of consciousness, it is often assumed that there is a stable set within the relevant sensory modality. Within the visual modality, the debate has centred upon whether frontal or occipital activations are the best predictors of perceptual awareness. Although not accepted by all as definitive evidence, no-report and decoding studies have indicated that occipital activity is the most consistently correlated with perceptual awareness whereas frontal activity might be closely related to aspects of cognition typically related to reports. However, perception is rarely just passive perception of something, but more or less always perception for something. That is, the task at hand for the perceiver may influence what is being perceived. This suggests an alternative view: that consciousness is not one specific 'function' that can be localized consistently to one area or event-related component and that the specific attributes of the neural correlates of consciousness depend on the task at hand. To investigate whether and how tasks may influence the neural correlates of consciousness, we here contrasted two tasks, a perceptual task and a conceptual task, using identical stimuli in both tasks. Using magnetoencephalography, we found that the perceptual task recruited more occipital resources than the conceptual task. Furthermore, we found that between the two conditions, the amount of frontal resources recruited differed between different gradations of perceptual awareness partly in an unexpected manner. These findings support a view of task affecting the neural correlates of consciousness.

Gas permeation rates of ultrathin graphite sealed SiO2 cavities.

Despite the proven impermeability of graphene toward most standard gases, graphene/graphite sealed SiO2 cavities always exhibit a nonzero leak rate, and the physical leakage mechanism is still unclear. By measuring leak rates of different gases for the same cavities sealed by ultrathin graphite under identical conditions, we find that the leak rates generally depend on the kinetic diameter of the gas molecules, which implies that the leakage is caused by a molecular sieving mechanism. By comparing different samples, we find that the leak rate of any gas in a particular sample is well predicted by the leak rate of N2 in that sample. In addition, we observe enhanced leak rates of water-soluble molecules. We infer that the leakage path (i.e., the graphene/graphite-SiO2 interface) favors hydrophilic species.

The cerebellar clock: Predicting and timing somatosensory touch.

The cerebellum is involved in predicting the sensory feedback resulting from movements and sensations, but little is known about the precise timing of these predictions due to the scarcity of time-sensitive cerebellar neuroimaging studies. We here, using magnetoencephalography, investigated the hypothesis that one function of the cerebellum is to predict with millisecond precision when rhythmic stimuli are expected to impinge on sensory receptors. This revealed that omissions following regular trains of stimulation showed higher cerebellar power in the beta band (14-30 Hz) than those following irregular trains of stimulation, within milliseconds of when the omitted stimulus should have appeared. We also found evidence of cerebellar theta band (4-7 Hz) activity encoding the rhythm of new sequences of stimulation. Our results also strongly suggest that the putamen and the thalamus mirror the cerebellum in showing higher beta band power when omissions followed regular trains of stimulation compared to when they followed irregular trains of stimulation. We interpret this as the cerebellum functioning as a clock that precisely encodes and predicts upcoming stimulation, perhaps in tandem with the putamen and thalamus. Relative to less predictable stimuli, perfectly predictable stimuli induce greater cerebellar power. This implies that the cerebellum entrains to rhythmic stimuli for the purpose of detecting any deviations from that rhythm.

Can EEG and MEG detect signals from the human cerebellum?

The cerebellum plays a key role in the regulation of motor learning, coordination and timing, and has been implicated in sensory and cognitive processes as well. However, our current knowledge of its electrophysiological mechanisms comes primarily from direct recordings in animals, as investigations into cerebellar function in humans have instead predominantly relied on lesion, haemodynamic and metabolic imaging studies. While the latter provide fundamental insights into the contribution of the cerebellum to various cerebellar-cortical pathways mediating behaviour, they remain limited in terms of temporal and spectral resolution. In principle, this shortcoming could be overcome by monitoring the cerebellum's electrophysiological signals. Non-invasive assessment of cerebellar electrophysiology in humans, however, is hampered by the limited spatial resolution of electroencephalography (EEG) and magnetoencephalography (MEG) in subcortical structures, i.e., deep sources. Furthermore, it has been argued that the anatomical configuration of the cerebellum leads to signal cancellation in MEG and EEG. Yet, claims that MEG and EEG are unable to detect cerebellar activity have been challenged by an increasing number of studies over the last decade. Here we address this controversy and survey reports in which electrophysiological signals were successfully recorded from the human cerebellum. We argue that the detection of cerebellum activity non-invasively with MEG and EEG is indeed possible and can be enhanced with appropriate methods, in particular using connectivity analysis in source space. We provide illustrative examples of cerebellar activity detected with MEG and EEG. Furthermore, we propose practical guidelines to optimize the detection of cerebellar activity with MEG and EEG. Finally, we discuss MEG and EEG signal contamination that may lead to localizing spurious sources in the cerebellum and suggest ways of handling such artefacts. This review is to be read as a perspective review that highlights that it is indeed possible to measure cerebellum with MEG and EEG and encourages MEG and EEG researchers to do so. Its added value beyond highlighting and encouraging is that it offers useful advice for researchers aspiring to investigate the cerebellum with MEG and EEG.

Attentional modulation of the auditory steady-state response across the cortex.

Selective auditory attention allows us to focus on relevant sounds within noisy or complex auditory environments, and is essential for the processing of speech and music. The auditory steady-state response (ASSR) has been proposed as a neural measure for tracking selective auditory attention, even within continuous and complex soundscapes. However, the current literature is inconsistent on how the ASSR is influenced by selective attention, with findings based primarily on attention being directed to either ear rather than to sound content. In this experiment, a mixture of melody streams was presented to both ears identically (diotically) as we examined if selective auditory attention to sound content influences the ASSR. Using magnetoencephalography (MEG), we assessed the stream-specific ASSRs from three frequency-tagged melody streams when attention was directed between each melody stream, based on their respective pitch and timing. Our main results showed that selective attention enhances the ASSR power of an attended melody stream by 14% at a general sensor level. This ability to readily capture attentional changes in a stimuli-precise manner makes the ASSR a useful tool for studying selective auditory attention, especially in complex auditory environments. As a secondary aim, we explored the distribution of cortical ASSR sources and their respective attentional modulation using a distributed source model of the ASSR activity. Notably, we uncovered the existence of ASSR attentional modulation outside the temporal cortices. Across-subject averages of the attentional enhancement over the cortical surface suggest that frontal regions show up to ~80% enhancement, while temporal and parietal cortices were enhanced by 20-25%. Importantly, this work advocates a novel 'beyond the temporal cortex' perspective on ASSR modulation and also serves as a template for future studies to precisely pin-point which cortical sites are more susceptible to ASSR attentional modulation.

On-scalp MEG SQUIDs are sensitive to early somatosensory activity unseen by conventional MEG.

Magnetoencephalography (MEG) has a unique capacity to resolve the spatio-temporal development of brain activity from non-invasive measurements. Conventional MEG, however, relies on sensors that sample from a distance (20-40 â€‹mm) to the head due to thermal insulation requirements (the MEG sensors function at 4 â€‹K in a helmet). A gain in signal strength and spatial resolution may be achieved if sensors are moved closer to the head. Here, we report a study comparing measurements from a seven-channel on-scalp SQUID MEG system to those from a conventional (in-helmet) SQUID MEG system. We compared the spatio-temporal resolution between on-scalp and conventional MEG by comparing the discrimination accuracy for neural activity patterns resulting from stimulating five different phalanges of the right hand. Because of proximity and sensor density differences between on-scalp and conventional MEG, we hypothesized that on-scalp MEG would allow for a more high-resolved assessment of these activity patterns, and therefore also a better classification performance in discriminating between neural activations from the different phalanges. We observed that on-scalp MEG provided better classification performance during an early post-stimulus period (10-20 â€‹ms). This corresponded to the electroencephalographic (EEG) component P16/N16 and was an unexpected observation as this component is usually not observed in conventional MEG. This finding shows that on-scalp MEG enables a richer registration of the cortical signal, indicating a sensitivity to what are potentially sources in the thalamo-cortical radiation. We had originally expected that on-scalp MEG would provide better classification accuracy based on activity in proximity to the P60m component compared to conventional MEG. This component indeed allowed for the best classification performance for both MEG systems (60-75%, chance 50%). However, we did not find that on-scalp MEG allowed for better classification than conventional MEG at this latency. We suggest that this absence of differences is due to the limited sensor coverage in the recording, in combination with our strategy for positioning the on-scalp MEG sensors. We show how the current sensor coverage may have limited our chances to register the necessary between-phalange source field dissimilarities for fair hypothesis testing, an approach we otherwise believe to be useful for future benchmarking measurements.

On-scalp MEG sensor localization using magnetic dipole-like coils: A method for highly accurate co-registration.

Source modelling in magnetoencephalography (MEG) requires precise co-registration of the sensor array and the anatomical structure of the measured individual's head. In conventional MEG, the positions and orientations of the sensors relative to each other are fixed and known beforehand, requiring only localization of the head relative to the sensor array. Since the sensors in on-scalp MEG are positioned on the scalp, locations of the individual sensors depend on the subject's head shape and size. The positions and orientations of on-scalp sensors must therefore be measured at every recording. This can be achieved by inverting conventional head localization, localizing the sensors relative to the head - rather than the other way around. In this study we present a practical method for localizing sensors using magnetic dipole-like coils attached to the subject's head. We implement and evaluate the method in a set of on-scalp MEG recordings using a 7-channel on-scalp MEG system based on high critical temperature superconducting quantum interference devices (high-Tc SQUIDs). The method allows individually localizing the sensor positions, orientations, and responsivities with high accuracy using only a short averaging time (≤ 2 â€‹mm, < 3° and < 3%, respectively, with 1-s averaging), enabling continuous sensor localization. Calibrating and jointly localizing the sensor array can further improve the accuracy of position and orientation (< 1 â€‹mm and < 1°, respectively, with 1-s coil recordings). We demonstrate source localization of on-scalp recorded somatosensory evoked activity based on co-registration with our method. Equivalent current dipole fits of the evoked responses corresponded well (within 4.2 â€‹mm) with those based on a commercial, whole-head MEG system.

Somatosensory responses to nothing: An MEG study of expectations during omission of tactile stimulations.

The brain builds up expectations to future events based on the patterns of past events. This function has been studied extensively in the auditory and visual domains using various oddball paradigms, but only little exploration of this phenomenon has been done in the somatosensory domain. In this study, we explore how expectations of somatosensory stimulations are established and expressed in neural activity as measured with magnetoencephalography. Using tactile stimulations to the index finger, we compared conditions with actual stimulation to conditions with omitted stimulations, both of which were either expected or unexpected. Our results show that when a stimulation is expected but omitted, a time-locked response occurs ∼135 ms subsequent to the expected stimulation. This somatosensory response to "nothing" was source localized to the secondary somatosensory cortex and to the insula. This provides novel evidence of the capability of the brain of millisecond time-keeping of somatosensory patterns across intervals of 3000 ms. Our results also show that when stimuli are repeated and expectations are established, there is associated activity in the theta and beta bands. These theta and beta band expressions of expectation were localized to the primary somatosensory area, inferior parietal cortex and cerebellum. Furthermore, there was gamma band activity in the right insula for the first stimulation after an omission, which indicates the detection of a new stimulation event after an expected pattern has been broken. Finally, our results show that cerebellum play a crucial role in predicting upcoming stimulation and in predicting when stimulation may begin again.

Refinement of eDNA as an early monitoring tool at the landscape-level: study design considerations.

Natural resource managers use data on the spatial range of species to guide management decisions. These data come from survey or monitoring efforts that use a wide variety of tools. Environmental DNA (eDNA) is a surveillance tool that uses genetic markers for detecting species and holds potential as a tool for large-scale monitoring programs. Two challenges of eDNA-based studies are uncertainties created by imperfect capture of eDNA in collection samples (e.g., water field samples) and imperfect detection of eDNA using molecular methods (e.g., quantitative PCR). Occurrence models can be used to address these challenges, thus we use an occurrence model to address two objectives: first, to determine how many samples were required to detect species using eDNA; second, to examine when and where to take samples. We collected water samples from three different habitat types in the Upper Mississippi River when both Bighead Carp and Silver Carp were known to be present based on telemetry detections. Each habitat type (backwater, tributary, and impoundment) was sampled during April, May, and November. Detections of eDNA for both species varied across sites and months, but were generally low, 0-19.3% of samples were positive for eDNA. Overall, we found that eDNA-based sampling holds promise to be a powerful monitoring tool for resource managers; however, limitations of eDNA-based sampling include different biological and ecological characteristics of target species such as seasonal habitat usage patterns as well as aspects of different physical environments that impact the implementation of these methods such as water temperature.

Bone mineral density from early to middle adulthood in persons with Down syndrome.

BACKGROUND: While accelerated ageing is recognised among individuals with Down syndrome (DS), the trajectory of their bone health across adulthood remains poorly understood. METHODS: This study aimed to determine the age-related loss of bone mineral density (BMD) of the lumbar spine in 128 adults with DS aged 18 to 54 years compared with 723 counterparts without DS. RESULTS: Men and women with DS had lower level of BMD than counterparts without DS across age groups. Magnitude of decrement in BMD as reflected in the z-scores was similar between younger and older men with DS. Older women with DS, on the contrary, showed greater decrement in older ages especially in their fourth decade of life. Osteopenia and osteoporosis as defined using age-specific and gender-specific T-scores affected greater number of men with DS (38% and 25%) than women (17% and 17%) aged 40-49 years. CONCLUSIONS: Findings supported adults with DS, especially men, to have early bone mineral testing.

DNA extraction from benthic Cyanobacteria: comparative assessment and optimization.

AIMS: Benthic Cyanobacteria produce toxic and odorous compounds similar to their planktonic counterparts, challenging the quality of drinking water supplies. The biofilm that benthic algae and other micro-organisms produce is a complex and protective matrix. Monitoring to determine the abundance and identification of Cyanobacteria, therefore, relies on molecular techniques, with the choice of DNA isolation technique critical. This study investigated which DNA extraction method is optimal for DNA recovery in order to guarantee the best DNA yield for PCR-based analysis of benthic Cyanobacteria. METHODS AND RESULTS: The conventional phenol-chloroform extraction method was compared with five commercial kits, with the addition of chemical and physical cell-lysis steps also trialled. The efficacy of the various methods was evaluated by measuring the quantity and quality of DNA by UV spectrophotometry and by quantitative PCR (qPCR) using Cyanobacteria-specific primers. The yield and quality of DNA retrieved with the commercial kits was significantly higher than that of DNA obtained with the phenol-chloroform protocol. CONCLUSIONS: Kits including a physical cell-lysis step, such as the MO BIO Power Soil and Biofilm kits, were the most efficient for DNA isolation from benthic Cyanobacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: These commercial kits allow greater recovery and the elimination of dangerous chemicals for DNA extraction, making them the method of choice for the isolation of DNA from benthic mats. They also facilitate the extraction of DNA from benthic Cyanobacteria, which can help to improve the characterization of Cyanobacteria in environmental studies using qPCRs or population composition analysis using next-generation sequencing.

Occipital MEG Activity in the Early Time Range (<300 ms) Predicts Graded Changes in Perceptual Consciousness.

Two electrophysiological components have been extensively investigated as candidate neural correlates of perceptual consciousness: An early, occipitally realized component occurring 130-320 ms after stimulus onset and a late, frontally realized component occurring 320-510 ms after stimulus onset. Recent studies have suggested that the late component may not be uniquely related to perceptual consciousness, but also to sensory expectations, task associations, and selective attention. We conducted a magnetoencephalographic study; using multivariate analysis, we compared classification accuracies when decoding perceptual consciousness from the 2 components using sources from occipital and frontal lobes. We found that occipital sources during the early time range were significantly more accurate in decoding perceptual consciousness than frontal sources during both the early and late time ranges. These results are the first of its kind where the predictive values of the 2 components are quantitatively compared, and they provide further evidence for the primary importance of occipital sources in realizing perceptual consciousness. The results have important consequences for current theories of perceptual consciousness, especially theories emphasizing the role of frontal sources.

Developing a multidisciplinary Young Women's Blood Disorders Program: a single-centre approach with guidance for other centres.

INTRODUCTION: Bleeding from the reproductive tract in women is a natural event, generally occurring with menstruation and childbirth. Women with an underlying bleeding disorder may experience heavy menstrual bleeding (HMB) and thereby, unacceptable blood loss. Up to 20% of US women with abnormal uterine bleeding and a normal gynaecological exam may have an underlying bleeding disorder corresponding to almost 2-3 million American women. These females face many obstacles in achieving optimum medical care for their problems. A haematologist may not evaluate these women as they are treated symptomatically. Recognition of an underlying bleeding disorder is not straightforward and many come to attention after serious bleeding events. Although mortality from HMB is uncommon, the true burden of HMB is its impact on health-related quality of life. To address these issues, women with HMB require a comprehensive approach to their care. METHODS: These reasons compelled us to institute a multidisciplinary Young Women's Blood Disorders (YWBD) Program at our institution. RESULTS: Herein, we describe the process of developing this program involving paediatric haematology, adolescent medicine and paediatric/adolescent gynaecology, and the expertise of a laboratory coagulationist, a nutritionist and nursing professionals. We also describe our experience with patient selection, the role of each specialty in the program, our approach to testing, the coordination of care and overall management of this patient population. Lastly, we propose metrics that could be followed in justifying the support of such a program. CONCLUSIONS: There is a growing need to offer comprehensive care to women with HMB and blood disorders. The YWBD program at our institution appears to be successful in delivering optimal care to young women affected with HMB.

Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis.

The mechanism by which human leukocyte antigen B27 (HLA-B27) contributes to ankylosing spondylitis (AS) remains unclear. Genetic studies demonstrate that association with and interaction between polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 influence the risk of AS. It has been hypothesised that ERAP1-mediated HLA-B27 misfolding increases endoplasmic reticulum (ER) stress, driving an interleukin (IL) 23-dependent, pro-inflammatory immune response. We tested the hypothesis that AS-risk ERAP1 variants increase ER-stress and concomitant pro-inflammatory cytokine production in HLA-B27(+) but not HLA-B27(-) AS patients or controls. Forty-nine AS cases and 22 healthy controls were grouped according to HLA-B27 status and AS-associated ERAP1 rs30187 genotypes: HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective), HLA-B27(-)ERAP1(risk) and HLA-B27(-)ERAP1(protective). Expression levels of ER-stress markers GRP78 (8 kDa glucose-regulated protein), CHOP (C/EBP-homologous protein) and inflammatory cytokines were determined in peripheral blood mononuclear cell and ileal biopsies. We found no differences in ER-stress gene expression between HLA-B27(+) and HLA-B27(-) cases or healthy controls, or between cases or controls stratified by carriage of ERAP1 risk or protective alleles in the presence or absence of HLA-B27. No differences were observed between expression of IL17A or TNF (tumour necrosis factor) in HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective) and HLA-B27(-)ERAP1(protective) cases. These data demonstrate that aberrant ERAP1 activity and HLA-B27 carriage does not alter ER-stress levels in AS, suggesting that ERAP1 and HLA-B27 may influence disease susceptibility through other mechanisms.

Making sense: Dopamine activates conscious self-monitoring through medial prefrontal cortex.

When experiences become meaningful to the self, they are linked to synchronous activity in a paralimbic network of self-awareness and dopaminergic activity. This network includes medial prefrontal and medial parietal/posterior cingulate cortices, where transcranial magnetic stimulation may transiently impair self-awareness. Conversely, we hypothesize that dopaminergic stimulation may improve self-awareness and metacognition (i.e., the ability of the brain to consciously monitor its own cognitive processes). Here, we demonstrate improved noetic (conscious) metacognition by oral administration of 100 mg dopamine in minimal self-awareness. In a separate experiment with extended self-awareness dopamine improved the retrieval accuracy of memories of self-judgment (autonoetic, i.e., explicitly self-conscious) metacognition. Concomitantly, magnetoencephalography (MEG) showed increased amplitudes of oscillations (power) preferentially in the medial prefrontal cortex. Given that electromagnetic activity in this region is instrumental in self-awareness, this explains the specific effect of dopamine on explicit self-awareness and autonoetic metacognition.