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Background: Perinatal arterial ischemic stroke (PAIS) is a focal brain injury in term neonates, identified postnatally but presumed to occur around birth. Early risk detection and targeted treatments are limited. We developed and validated a diagnostic risk prediction model from common clinical factors to predict a term neonate’s probability of PAIS. Methods: A diagnostic prediction model was developed using multivariable logistic regression. Common pregnancy, delivery, and neonatal clinical factors were collected across four registries. Variable selection was based on peer-reviewed literature. Participant inclusion criteria were term birth and no underlying predisposition to stroke. The primary outcome was discriminative accuracy of the model predicting PAIS, measured by the concordance (C-) statistic. Results: 2571 participants (527 cases, 2044 controls) were eligible for analysis. Nine variables were included in the model – maternal age, tobacco exposure, recreational drug exposure, pre-eclampsia, chorioamnionitis, maternal fever, emergency c-section, low 5-minute Apgar score, and sex – to predict the risk of PAIS in a term neonate. This model demonstrated good discrimination between cases and controls (C-statistic 0.73) and model fit (Hosmer-Lemeshow p=0.20). Conclusions: Clinical variables can be used to develop and internally validate a model of PAIS risk prediction. Identifying high-risk neonates for early screening and treatment could reduce lifelong morbidity.
Background: Perinatal arterial ischemic stroke (PAIS) is a leading cause of hemiparetic cerebral palsy. Multiple risk factors are associated with PAIS but studies are limited by small sample sizes and complex interactions. Unbiased machine learning applied to larger datasets may enable the development of robust predictive models. We aimed to use machine learning to identify risk factors predictive of PAIS and compare these to the existing literature. Methods: Common data elements of maternal, delivery, and neonatal factors were collected from three perinatal stroke registries and one control sample over a 7-year period. Inclusion criteria were MRI-confirmed PAIS, term birth, and idiopathic etiology. Random forest machine learning in combination with feature selection was used to develop a predictive model of PAIS. Results: Total of 2571 neonates were included (527 cases, 2044 controls). Risk factors uniquely identified through machine learning were infertility, miscarriage, primigravida, and meconium. When compared, factors identified through both literature-based selection and machine learning included maternal age, fetal tobacco exposure, intrapartum fever, and low 5-minute APGAR. Conclusions: Machine learning offers a novel, less biased method to identify PAIS predictors and complex pathophysiology. Our findings support known associations with concepts of placental disease and difficult fetal transition and may support early screening for PAIS.
Background: Early recognition of neonatal seizures secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications, but respond well to sodium-channel blockers. We report a unique aEEG pattern in neonatal seizures caused by SCN2A and KCNQ3 pathogenic variants, as well as adding regular EEG description. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and conventional EEG findings of 10 newborns with seizures due to pathogenic SCN2A and KCNQ3 gene variants. Results: Seizures started in the first postnatal week. Seizure semiology typically included tonic posturing with apnea and desaturation. The aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral attenuation in the EEG at onset, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. The majority of patients became seizure free upon initiation of a sodium-channel blocker. Conclusions: Neonatal seizures caused by SCN2A and KCNQ3 mutations can be recognized by a characteristic ictal aEEG pattern and clinical semiology. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium-channel blockers even before genetic test results are available.
Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.
Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined.
Methods
We harmonized data from 1489 participants (9–27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood.
Results
Three dimensions of antisociality were uncovered: ‘callous-unemotional (CU)/manipulative traits’, ‘intentional aggression/conduct’, and ‘reactivity/impulsivity/irritability’. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age.
Conclusions
Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations.
This paper aimed to: retrospectively analyse single-centre results in terms of surgical success, respiratory outcomes and adverse events after short-term follow up in obstructive sleep apnoea patients treated with upper airway stimulation; and evaluate the correlation between pre-operative drug-induced sleep endoscopy findings and surgical success.
Methods
A retrospective descriptive cohort study was conducted, including a consecutive series of obstructive sleep apnoea patients undergoing implantation of an upper airway stimulation system.
Results
Forty-four patients were included. The total median Apnoea–Hypopnea Index and oxygen desaturation index significantly decreased from 37.6 to 8.3 events per hour (p < 0.001) and from 37.1 to 15.9 events per hour (p < 0.001), respectively. The surgical success rate was 88.6 per cent, and did not significantly differ between patients with or without complete collapse at the retropalatal level (p = 0.784). The most common therapy-related adverse event reported was (temporary) stimulation-related discomfort.
Conclusion
Upper airway stimulation is an effective and safe treatment in obstructive sleep apnoea patients with continuous positive airway pressure intolerance or failure. There was no significant difference in surgical outcome between patients with tongue base collapse with or without complete anteroposterior collapse at the level of the palate.
Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated.
Methods
We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems.
Results
A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not.
Conclusions
The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.
This study evaluated the psychometric properties of the Strengths and Difficulties Questionnaire Self-Report (SDQ-S) in South African adolescents, and compared findings with data from the UK, Australia and China.
Methods.
A sample of 3451 South African adolescents in grade 8, the first year of secondary school (Mage = 13.7 years), completed the SDQ-S in Afrikaans, English or isiXhosa. Means, group differences and internal consistency were analysed using SPSS V22, and confirmatory factor analyses were conducted using MPlus V7.
Results.
In the South African sample, significant gender differences were found for four of the five sub-scale means and for total difficulties, but gender differences of alpha scores were negligible. The internal consistency for the total difficulties, prosocial behaviour and emotional symptoms sub-scales were fair. UK cut-off values for caseness (set to identify the top 10% of scores in a UK sample) led to a higher proportion of South African adolescents classified in the ‘abnormal’ range on emotional and peer difficulties and a lower proportion classified in the ‘abnormal’ range for hyperactivity. South African cut-offs were therefore generated. The cross-country comparison with UK, Australian and Chinese data showed that South African adolescent boys and girls had the highest mean scores on total difficulties as well as on the subscales of emotional symptoms and conduct problems. In contrast, South African boys and girls had the lowest mean scores for hyperactivity/inattention. The UK boys and girls had the highest mean scores for hyperactivity/inattention, while the Australian sample had the highest scores for prosocial behaviours. The Chinese boys had the highest peer problem mean scores and Chinese boys and girls had the lowest means on prosocial behaviours. Confirmatory factor analyses showed significant item loadings with loadings higher than 0.40 for the emotional and prosocial behaviour sub-scales on the five-factor model, but not for all relevant items on the other three domains.
Conclusions.
Findings support the potential usefulness of the SDQ-S in a South African setting, but suggest that the SDQ-S should not be used with UK cut-off values, and indicate the need for further validation and standardisation work in South African adolescents. We recommend that in-country cut-offs for ‘caseness’ should be used for clinical purposes in South Africa, that cross-country comparisons should be made with caution, and that further examination of naturalistic clusters and factors of the SDQ should be performed in culturally and contextually diverse settings.
The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to β-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies’ mothers, as well as a mother–infant series including meconium, fecal samples collected through the infant’s 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds’ samples a particularly elevated prevalence of mecA (>45%), six-fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant’s GIT as a noteworthy reservoir of this gene.
The need for symmetry and ordering objects related to a “just right”-feeling is a common symptom in Tourette's syndrome (TS) and resembles symmetry behavior in obsessive-compulsive disorder, but its pathophysiology is unknown. We used a symptom provocation paradigm to investigate the neural correlates of symmetry behavior in TS and hypothesized the involvement of frontal-striatal and limbic brain areas.
Methods
Pictures of asymmetrically and symmetrically arranged objects were presented in randomized blocks (4 blocks of each condition) to 14 patients with TS and 10 matched healthy controls (HC). A H215O positron emission tomography scan was acquired during each stimulus block, resulting in 8 scans per subject. After each scan, state anxiety and symmetry behavior (the urge to rearrange objects) were measured using a visual analogue scale.
Results
During the asymmetry condition, TS patients showed increased regional cerebral blood flow (rCBF) in the anterior cingulate cortex, supplementary motor area, and inferior frontal cortex, whereas HC showed increased rCBF in the visual cortex, primary motor cortex, and dorsal prefrontal cortex. Symmetry ratings during provocation correlated positively with orbitofrontal activation in the TS group and sensorimotor activation in the HC group, and negatively with dorsal prefrontal activity in HC.
Conclusions
Results suggest that both motor and limbic circuits are involved in symmetry behavior in TS. Motor activity may relate to an urge to move or perform tics, and limbic activation may indicate that asymmetry stimuli are salient for TS patients. In contrast, symmetry provocation in HC resulted in activation of brain regions implicated in sensorimotor function and cognitive control.
Neospora caninum is an Apicomplexan protozoan that has the dog as a definitive host and cattle (among other animals) as intermediate hosts. It causes encephalopathy in dogs and abortion in cows, with significant loss in worldwide livestock. As any Apicomplexan, the parasite invades the cells using proteins contained in the phylum-specific organelles, like the micronemes, rhoptries and dense granules. The aim of this study was the characterization of a homologue (denominated NcMIC2-like1) of N. caninum thrombospondin-related anonymous protein (NcMIC2), a micronemal protein previously shown to be involved in the attachment and connection with the intracellular motor responsible for the active process of invasion. A polyclonal antiserum raised against the recombinant NcMIC2-like1 functional core (thrombospondin and integrin domains) recognized the native form of NcMIC2-like1, inhibited the in vitro invasion process and localized NcMIC2-like1 at the apical complex of the parasite by confocal immunofluorescence, indicating its micronemal localization. The new molecule, NcMIC2-like1, has features that differentiates it from NcMIC2 in a substantial way to be considered a homologue†.
Visual–perceptual abilities were assessed in 5-year-old children with the following neonatal neurological conditions: born preterm with normal ultrasound scan (NL, n=17); born preterm with ultrasound diagnosis of intraventricular haemorrhage (IVH, n=17); born preterm with ultrasound diagnosis of periventricular leukomalacia (PVL, n=12); born term with hypoxic–ischaemic encephalopathy (HIE, n=11). Visual–perceptual ability was evaluated with the L94: eight visual–perceptual tasks designed to evaluate different aspects of visual perception at the preschool level in children with multiple disabilities. Impairment was established in comparison to the performance age obtained on non-verbal intelligence subtests, instead of chronological age. Frequency of L94 impairment was highest in children with PVL, while children with IVH did not differ from the NL control group. Impairment rates were increased also in children with transient periventricular echodensities, and in children with HIE. Impairments were only moderately related to the delay of visual acuity maturation in infancy.
The electrodeposition of WO3 thin films from peroxy-tungstate solution is discussed. The emphasis is on the feasibility of this deposition technique for production of electrochromic devices. Therefore, the influence of deposition parameters (solution composition, electrodeposition potential, mass transport, etc.) on the properties of WO3 was studied. Furthermore, it was investigated whether electrodeposition of WO3 offers unique possibilities as compared to WO3 deposition by other techniques.
The prototype for applications of group theory to physics, and to mathematical physics, is the quantum theory of angular momentum [1] ; the use of such techniques is now almost universal, and familiarly (through somewhat imprecisely) known as “Racah algebra”. To categorize, group theoretically, those characteristics which underlay this applicability to physical problems, Wigner [30] isolated two significant conditions, and designated groups possessing these properties as simply reducible.
The two conditions for simple reducibility are:
(a)Every element is equivalent to its reciprocal, i.e., all classes are ambivalent.
(b) The Kronecker (or “direct“) product of any two irreducible representations of the group contains no representation more than once.
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