The unseen impact - a deep dive into neurocognitive impairment among patients with intracranial meningiomas: a comprehensive systematic review of the literature.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life.

Culturally Informed Neuropsychological Evaluations in Pediatric Epilepsy: Evidence-Based Practice Considerations.

OBJECTIVE: Epilepsy is one of the most common reasons for referral for a pediatric neuropsychological evaluation due its high prevalence in childhood and our well-established clinical role in tertiary care settings. Emerging evidence indicates that racial and ethnic minority populations experience increased epilepsy burden compared with White peers. Although there has been heightened recognition in our specialty regarding the dire need for culturally and linguistically responsive evaluations, the scientific evidence to support effective neuropsychological service delivery for bi/multilingual and bi/multicultural youth with epilepsy is comparatively scant and of poor quality. As a result, significant patient and clinical challenges exist, particularly in high stakes presurgical pediatric epilepsy evaluations of bi/multilingual and bi/multicultural children. METHOD: Given that Spanish is the most common language spoken in the United States after English, this paper will focus on Spanish and English measures, but will provide evidence-based practice considerations that can inform practices with other non-English speaking communities. Cultural and linguistic factors that affect clinical decision-making regarding test selection, test interpretation, and feedback with families are highlighted. RESULTS: We offer a review of neuropsychological profiles associated with pediatric epilepsy as well as a flexible, multimodal approach for the assessment of linguistically and culturally diverse children with epilepsy based on empirical evidence and the clinical experiences of pediatric neuropsychologists from diverse backgrounds who work with children with epilepsy. CONCLUSION: Limitations to this approach are discussed, including the lack of available measures and resources for culturally and linguistically diverse pediatric populations. A case illustration highlights a culturally informed assessment approach.

The Evolving Need for Neuropsychology in Neurosurgical Settings: Challenges Facing Transformative Care.

Clinical neuropsychology has been a valuable asset to neurologic surgery, contributing to lateralization and localization of pathologic brain tissue, identification of eloquent cortex, and evaluation of postoperative neuropsychological functioning. Moreover, neuropsychologists provide empirically driven interventions aimed at supporting preparation and/or recovery of neurosurgery patients. Nonetheless, several challenges may limit the reliability, validity, and generalizability of the assessment data obtained and reduce the usefulness of other neuropsychological services provided. Specifically, linguistic, cultural, educational, and other biases associated with demographic characteristics can lead to a narrowed view of an individual's life experiences, which must be confronted to fulfill the mission of ensuring that all patients have access to care that is appropriate to their needs. Instead of perceiving these challenges as insurmountable barriers, such issues can be viewed as opportunities to catalyze change and foster innovation for the future of neuropsychological care in neurosurgical settings. In addition to reviewing the possible mechanisms of these obstacles, the current article offers tangible solutions at both a macro level (e.g., discipline-wide transformations) and micro level (e.g., individualized patient-centric approaches). Outlined are practical techniques to potentially improve consensus and standardization of methods, advance and globalize research, expand representativeness of measures and practices to serve diverse individuals, and increase treatment adherence through engagement of patients and their families.

Foundations of Neuropsychology: Collaborative Care in Neurosurgery.

The disciplines of neuropsychology and neurosurgery have a history of partnership that has improved prognoses for patients with neurologic diagnoses that once had poor outcomes. This article outlines the evolution of this relationship and describes the current role that clinical neuropsychology has within a department of neurological surgery across the preoperative, intraoperative, and postoperative stages of treatment. Understanding the foundations of collaboration between neuropsychology and neurosurgery contextualizes present challenges and future innovations for advancing excellence along the continuum of care for all neurosurgical patients.

Innovations in Neuropsychology: Future Applications in Neurosurgical Patient Care.

Over the last century, collaboration between clinical neuropsychologists and neurosurgeons has advanced the state of the science in both disciplines. These advances have provided the field of neuropsychology with many opportunities for innovation in the care of patients prior to, during, and following neurosurgical intervention. Beyond giving a general overview of how present-day advances in technology are being applied in the practice of neuropsychology within a neurological surgery department, this article outlines new developments that are currently unfolding. Improvements in remote platform, computer interface, "real-time" analytics, mobile devices, and immersive virtual reality have the capacity to increase the customization, precision, and accessibility of neuropsychological services. In doing so, such innovations have the potential to improve outcomes and ameliorate health care disparities.

The Sensitivity of Scalp EEG at Detecting Seizures-A Simultaneous Scalp and Stereo EEG Study.

PURPOSE: Compare the detection rate of seizures on scalp EEG with simultaneous intracranial stereo EEG (SEEG) recordings. METHODS: Twenty-seven drug-resistant epilepsy patients undergoing SEEG with simultaneous scalp EEG as part of their surgical work-up were included. A total of 172 seizures were captured. RESULTS: Of the 172 seizures detected on SEEG, 100 demonstrated scalp ictal patterns. Focal aware and subclinical seizures were less likely to be seen on scalp, with 33% of each observed when compared with focal impaired aware (97%) and focal to bilateral tonic-clonic seizures (100%) (P < 0.001). Of the 72 seizures without ictal scalp correlate, 32 demonstrated an abnormality during the SEEG seizure that was identical to an interictal abnormality. Seizures from patients with MRI lesions were statistically less likely to be seen on scalp than seizures from nonlesional patients (P = 0.0162). Stereo EEG seizures not seen on scalp were shorter in duration (49 seconds) compared with SEEG seizures seen on scalp (108.6 seconds) (P < 0.001). CONCLUSIONS: Scalp EEG is not a sensitive tool for the detection of focal aware and subclinical seizures but is highly sensitive for the detection of focal impaired aware and focal to bilateral tonic-clonic seizures. Longer duration of seizure and seizures from patients without MRI lesions were more likely to be apparent on scalp. Abnormalities seen interictally may at times represent an underlying seizure. The cognitive, affective, and behavioral long-term effects of ongoing difficult-to-detect seizures are not known.

Linearized radially polarized light for improved precision in strain measurements using micro-Raman spectroscopy.

Strain engineering in semiconductor transistor devices has become vital in the semiconductor industry due to the ever-increasing need for performance enhancement at the nanoscale. Raman spectroscopy is a non-invasive measurement technique with high sensitivity to mechanical stress that does not require any special sample preparation procedures in comparison to characterization involving transmission electron microscopy (TEM), making it suitable for inline strain measurement in the semiconductor industry. Indeed, at present, strain measurements using Raman spectroscopy are already routinely carried out in semiconductor devices as it is cost effective, fast and non-destructive. In this paper we explore the usage of linearized radially polarized light as an excitation source, which does provide significantly enhanced accuracy and precision as compared to linearly polarized light for this application. Numerical simulations are done to quantitatively evaluate the electric field intensities that contribute to this enhanced sensitivity. We benchmark the experimental results against TEM diffraction-based techniques like nano-beam diffraction and Bessel diffraction. Differences between both approaches are assigned to strain relaxation due to sample thinning required in TEM setups, demonstrating the benefit of Raman for nondestructive inline testing.

Building confidence in skin sensitisation potency assessment using new approach methodologies: report of the 3rd EPAA Partners Forum, Brussels, 28th October 2019.

Skin sensitising substances that induce contact allergy and consequently risk elicitation of allergic contact dermatitis (ACD) remain an important focus regarding the replacement of animal experimentation. Current in vivo methods, notably the local lymph node assay (LLNA) refined and reduced animal usage and led to a marked improvement in hazard identification, characterisation and risk assessment. Since validation, regulatory confidence in the LLNA approach has evolved until it became the first choice assay in most regulated sectors. Currently, hazard identification using the LLNA is being actively replaced by a toolbox of non-animal approaches. However, there remains a need to increase confidence in the use of new approach methodologies (NAMs) as replacements for LLNA sensitiser potency estimation. The EPAA Partners Forum exchanged the current state of knowledge on use of NAMs in various industry sectors and regulatory environments. They then debated current challenges in this area and noted several ongoing needs. These included a requirement for reference standards for potency, better characterisation of applicability domains/technical limitations of NAMs, development of a framework for weight of evidence assessments, and an increased confidence in the characterisation of non-sensitisers. Finally, exploration of an industry/regulator cross-sector user-forum on skin sensitisation was recommended.

HAADF-STEM block-scanning strategy for local measurement of strain at the nanoscale.

Lattice strain measurement of nanoscale semiconductor devices is crucial for the semiconductor industry as strain substantially improves the electrical performance of transistors. High resolution scanning transmission electron microscopy (HR-STEM) imaging is an excellent tool that provides spatial resolution at the atomic scale and strain information by applying Geometric Phase Analysis or image fitting procedures. However, HR-STEM images regularly suffer from scanning distortions and sample drift during image acquisition. In this paper, we propose a new scanning strategy that drastically reduces artefacts due to drift and scanning distortion, along with extending the field of view. It consists of the acquisition of a series of independent small subimages containing an atomic resolution image of the local lattice. All subimages are then analysed individually for strain by fitting a nonlinear model to the lattice images. The method allows flexible tuning of spatial resolution and the field of view within the limits of the dynamic range of the scan engine while maintaining atomic resolution sampling within the subimages. The obtained experimental strain maps are quantitatively benchmarked against the Bessel diffraction technique. We demonstrate that the proposed scanning strategy approaches the performance of the diffraction technique while having the advantage that it does not require specialized diffraction cameras.

Chemical vapor deposition of monolayer-thin WS2 crystals from the WF6 and H2S precursors at low deposition temperature.

Monolayer-thin WS2 with (0002) texture grows by chemical vapor deposition (CVD) from gas-phase precursors WF6 and H2S at a deposition temperature of 450 °C on 300 mm Si wafers covered with an amorphous Al2O3 starting surface. We investigate the growth and nucleation mechanism during the CVD process by analyzing the morphology of the WS2 crystals. The CVD process consists of two distinct growth regimes. During (i) the initial growth regime, a fast and self-limiting reaction of the CVD precursors with the Al2O3 starting surface forms predominantly monolayer-thin WS2 crystals and AlF3 crystals that completely cover the starting surface. During (ii) the steady-state growth regime, a much slower, anisotropic reaction on the bottom, first WS2 layer proceeds with the next WS2 layer growing preferentially in the lateral dimensions. We propose that the precursor adsorption reaction rate strongly diminishes when the precursors have no more access to the Al2O3 surface as soon as the WS2 layer completely covers the Al2O3 surface and that the WS2 crystal basal planes and AlF3 crystals have a low reactivity for WF6 adsorption at 450 °C. Nonetheless, a second layer of WS2 starts to form before the first WS2 layer completely covers the starting surface, albeit the surface coverage of the second layer is low (<20%, after 25 min of CVD reaction). During the steady-state growth regime, predominantly the WS2 crystals in the second monolayer continue to grow in lateral dimensions up to ∼40 nm. These crystals reach larger lateral dimensions compared to the crystals in the bottom, first layer due to low reactivity for WF6 adsorption on the WS2 basal plane compared to Al2O3. Presumably, they grow laterally by precursor species that adsorb on and diffuse across the WS2 surface, before being incorporated at the more reactive edges of the WS2 crystals in the second layer. Such a process proceeds slowly with only up to 40% surface coverage of the second WS2 layer after 150 min of CVD reaction. The CVD reaction is mediated by the starting surface: WF6 precursor preferentially adsorbs on Al2O3, whereas adsorption is not observed on SiO2. Nevertheless, WS2 grows on SiO2 in close proximity to Al2O3 in 90 nm pitch Al2O3/SiO2 line patterns. Hence, functionalization of the starting surface (e.g., SiO2 with Al2O3) can provide opportunities to grow monolayer-thin WS2 crystals at predetermined locations by selective, lateral growth with tunable crystal size, even at low deposition temperatures.

[Health-Related Quality of Life in the Context of Early Benefit Assessment of Drugs According to § 35a of the German Social Code Book V: A Challenging Endpoint for all the Involved Stakeholders]. / Gesundheitsbezogene Lebensqualität im Rahmen der frühen Nutzenbewertung von Arzneimitteln nach § 35a SGB V: Ein Endpunkt mit vielen Herausforderungen für alle beteiligten Akteure.

Considering repeated demands to present data on health-related quality of life (HRQoL) in the context of early benefit assessment of drugs in Germany, on the one hand, and the ongoing methodical debates on this outcome, on the other, the question about its significance in the evaluation procedure has been raised. Published documents of the first 90 early benefit assessments were extracted in order to estimate the importance of HRQoL in the assessment process for each involved stakeholder, and synoptically evaluated. The main challenge is to quantify a qualitative effect variable and to estimate its value. In several early benefit assessments, HRQoL had not been elicited a priori. In many cases where some data on HRQoL are presented, no added benefit can be derived. Finally, in most of the remaining assessments, no added benefit was recognized by IQWiG or the Federal Joint Committee. Even though the incorporation of HRQoL in clinical trial protocols is increasing, the endpoint is mostly conceptualized in an explorative manner. Hence, there is heterogeneity in the identified evidence. Beyond missing statistical significance, the assessment reports refer to a range of different methodological limitations, leading the responsible stakeholders to exclude HRQoL from their assessments, e. g. a high proportion of missing patient data or difficulties in the interpretation of the measurement results are mentioned. Regarding the implemented assessment approaches, inconsistencies in the applied conceptual and methodological standards were uncovered. To increase the importance of the endpoint HRQoL in the context of the early benefit assessment of drugs, establishing reliable measurement standards by consensus seems to be necessary. Furthermore, the valuation criteria should be made more transparent and attempts must be made to harmonize them with the approval process for at least the first early assessment of a new drug.

Structural characterization of SnS crystals formed by chemical vapour deposition.

The crystal and defect structure of SnS crystals grown using chemical vapour deposition for application in electronic devices are investigated. The structural analysis shows the presence of two distinct crystal morphologies, that is thin flakes with lateral sizes up to 50 µm and nanometer scale thickness, and much thicker but smaller crystallites. Both show similar Raman response associated with SnS. The structural analysis with transmission electron microscopy shows that the flakes are single crystals of α-SnS with [010] normal to the substrate. Parallel with the surface of the flakes, lamellae with varying thickness of a new SnS phase are observed. High-resolution transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), first-principles simulations (DFT) and nanobeam diffraction (NBD) techniques are employed to characterise this phase in detail. DFT results suggest that the phase is a strain stabilised ß' one grown epitaxially on the α-SnS crystals. TEM analysis shows that the crystallites are also α-SnS with generally the [010] direction orthogonal to the substrate. Contrary to the flakes the crystallites consist of two to four grains which are tilted up to 15° relative to the substrate. The various grain boundary structures and twin relations are discussed. Under high-dose electron irradiation, the SnS structure is reduced and ß-Sn formed. It is shown that this damage only occurs for SnS in direct contact with SiO2 .

X-ray absorption in pillar shaped transmission electron microscopy specimens.

The dependence of the X-ray absorption on the position in a pillar shaped transmission electron microscopy specimen is modeled for X-ray analysis with single and multiple detector configurations and for different pillar orientations relative to the detectors. Universal curves, applicable to any pillar diameter, are derived for the relative intensities between weak and medium or strongly absorbed X-ray emission. For the configuration as used in 360° X-ray tomography, the absorption correction for weak and medium absorbed X-rays is shown to be nearly constant along the pillar diameter. Absorption effects in pillars are about a factor 3 less important than in planar specimens with thickness equal to the pillar diameter. A practical approach for the absorption correction in pillar shaped samples is proposed and its limitations discussed. The modeled absorption dependences are verified experimentally for pillars with HfO2 and SiGe stacks.

Observation and understanding of anisotropic strain relaxation in selectively grown SiGe fin structures.

The performance of heterogeneous 3D transistor structures critically depends on the composition and strain state of the buffer, channel and source/drain regions. In this paper we used an in-line high resolution x-ray diffraction (HRXRD) tool to study in detail the composition and strain in selectively grown SiGe/Ge fin structures with widths down to 20 nm. For this purpose we arranged fins of identical dimensions into larger arrays which were then analyzed using an x-ray beam several tens of micrometers in size. Asymmetric reciprocal space maps measured both parallel and perpendicular to the fins allowed us to extract the lattice parameters in all three spatial directions. Our results demonstrate an anisotropic in-plane strain state of the selectively grown SiGe buffer in case of narrower fins with significantly reduced relaxation in the direction along the fin. This observation was verified using nano-beam electron diffraction, and is explained based on the reduced probability for dislocation half-loops to evolve in trenches narrower than a few times the critical radius. Moreover, we introduce and discuss in detail a methodology for the determination of the composition in case of an anisotropic in-plane strain state which differs from the procedure commonly used for blanket layers. Our findings verify the importance of in-line HRXRD measurements for process development and monitoring as well as the fundamental study of relaxation and defect formation in confined volumes.

Cognitive estimations as a measure of executive dysfunction in childhood epilepsy.

Children and adolescents with epilepsy are known to demonstrate executive function deficits. Despite prior work that has shown that cognitive estimation tasks are sensitive to executive dysfunction in children, such tasks have not been studied in children with epilepsy. This is particularly important given the fact that executive tasks have heretofore shown poor ecological validity, and it has been speculated that estimation tasks may show stronger ecological validity than other executive tests. One hundred and thirteen clinically referred children and adolescents with epilepsy were included. The Biber Cognitive Estimations Test was sensitive to cognitive dysfunction, with about half showing impairments on this task in comparison to age-matched normative data; the most frequently impaired subscales were quantity estimation and time estimation. Moreover, the Biber Cognitive Estimation Test showed moderate correlations with not only overall intellectual functions and academic achievement but also other commonly administered tests of executive functions, including digit span, Trailmaking, and the Tower of London but not with the contingency naming test. Cognitive estimations were also modestly correlated with age of epilepsy onset but not other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive Estimation Test would show strong ecological validity was not supported, as it showed weak relations with parent-reported executive function deficits. The significance and limitations of this investigation are discussed.

Low temperature deposition of 2D WS2 layers from WF6 and H2S precursors: impact of reducing agents.

We demonstrate the impact of reducing agents for Chemical Vapor Deposition (CVD) and Atomic Layer Deposition (ALD) of WS2 from WF6 and H2S precursors. Nanocrystalline WS2 layers with a two-dimensional structure can be obtained at low deposition temperatures (300-450 °C) without using a template or anneal.

Epitaxial diamond-hexagonal silicon nano-ribbon growth on (001) silicon.

Silicon crystallizes in the diamond-cubic phase and shows only a weak emission at 1.1 eV. Diamond-hexagonal silicon however has an indirect bandgap at 1.5 eV and has therefore potential for application in opto-electronic devices. Here we discuss a method based on advanced silicon device processing to form diamond-hexagonal silicon nano-ribbons. With an appropriate temperature anneal applied to densify the oxide fillings between silicon fins, the lateral outward stress exerted on fins sandwiched between wide and narrow oxide windows can result in a phase transition from diamond-cubic to diamond-hexagonal Si at the base of these fins. The diamond-hexagonal slabs are generally 5-8 nm thick and can extend over the full width and length of the fins, i.e. have a nano-ribbon shape along the fins. Although hexagonal silicon is a metastable phase, once formed it is found being stable during subsequent high temperature treatments even during process steps up to 1050 ºC.

Motor skills development in children with inattentive versus combined subtypes of ADHD.

The relations between attention-deficit hyperactivity disorder (ADHD) and motor skills are well documented, with research indicating both early and lifelong motor deficits in children with this disorder. Despite neuroanatomical and neurodevelopmental differences, which may predict differential rates of motor impairment between ADHD subtypes, evaluation of motor skill deficits in children with different presentations are limited in scope and equivocal in findings. The present investigation evaluated early motor development history and objectively measured motor skills in children with ADHD-Inattentive subtype (ADHD-I) and ADHD-Combined subtype (ADHD-C). One hundred and one children with ADHD-I (n = 53) and ADHD-C (n = 48) were included. Variables included Full-Scale IQ (FSIQ), history of motor delays, and utilization of early intervention services, as well as objectively measured motor impairment as assessed via tasks of fine-motor coordination. No between-group differences were found for FSIQ, but differences in age emerged, with the ADHD-I group being older. No differences in early motor delays were observed, though a considerably higher percentage of children with ADHD-C demonstrated early difficulties. Surprisingly, although children and adolescents with ADHD-C reported more frequent utilization of early intervention services, those with ADHD-I exhibited greater levels of current motor impairment on objective tasks. Given the over-representation of older children in the ADHD-I group, data were reanalyzed after excluding participants older than 10 years of age. Although the between-group differences were no longer significant, more than twice the number of parents of children with ADHD-C reported early motor delays, as compared with the ADHD-I group. Overall, children with ADHD-I were more likely to exhibit current objectively measured motor impairment, possibly due to later identification, less intervention, and/or different neurodevelopmental substrates underlying this disorder subtype.

[Fever during blood transfusion. A case of coincidence instead of causality]. / Fieber während einer Bluttransfusion. Ein Fall von Koinzidenz statt Kausalität.

A boy aged 2 years and 5 months showed agitation, shivering and fever with a temperature of 38.9 °C during a red blood cell transfusion. Examination of the assumed adverse transfusion reaction gave no indications of erythrocyte incompatibility, hemolysis or IgA incompatibility. No antibodies against HLA class I antigens or HPA antigens were found in the recipient's blood. Sterility testing of the blood product showed no growth, but in the blood cultures taken from the patient immediately after the blood transfusion, Enterobacter cloacae was detected which also could be found in blood cultures and nose and throat swabs taken 3 days before. Therefore, the fever during blood transfusion was not a case of causality but of coincidence. This case underlines the recommendation to examine blood cultures from the recipient in all suspected cases of adverse transfusion reaction.

Neurologic and neurodevelopmental phenotypes in young children with early-treated combined methylmalonic acidemia and homocystinuria, cobalamin C type.

Abnormal neurodevelopment has been widely reported in combined methylmalonic aciduria (MMA) and homocystinuria, cblC type (cblC disease), but neurodevelopmental phenotypes in cblC have not previously been systematically studied. We sought to further characterize developmental neurology in children with molecularly-confirmed cblC. Thirteen children at our center with cblC, born since implementation of expanded newborn screening in New York State, undertook standard-of-care evaluations with a pediatric neurologist and pediatric ophthalmologist. At most recent follow-up (mean age 50 months, range 9-84 months), of twelve children with early-onset cblC, three (25%) had a history of clinical seizures and two (17%) meet criteria for microcephaly. A majority of children had hypotonia and nystagmus. Twelve out of thirteen (92%) underwent neurodevelopmental evaluation (mean age 41 months; range 9-76 months), each child tested with standardized parental interviews and, where possible, age- and disability-appropriate neuropsychological batteries. All patients showed evidence of developmental delay with the exception of one patient with a genotype predictive of attenuated disease and near-normal biochemical parameters. Neurodevelopmental deficits were noted most prominently in motor skills, with relative preservation of socialization and communication skills. Nine children with early-onset cblC underwent magnetic resonance imaging and spectroscopy (MRI/MRS) at mean age of 47 months (range 6-81 months); common abnormalities included callosal thinning, craniocaudally short pons, and increased T2 FLAIR signal in periventricular and periatrial white matter. Our study further characterizes variable neurodevelopmental phenotypes in treated cblC, and provides insights into the etiopathogenesis of disordered neurodevelopment frequently encountered in cblC. Plasma homocysteine and MMA, routinely measured at clinical follow-up, may be poor predictors for neurodevelopmental outcomes. Additional data from large, prospective, multi-center natural history studies are required to more accurately define the role of these metabolites and others, as well as that of other genetic and environmental factors in the etiopathogenesis of the neurologic components of this disorder.