The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma.

Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM.

Efficient Photoelectrochemical Hydrogen Generation Using Eco-Friendly "Giant" InP/ZnSe Core/Shell Quantum Dots.

InP quantum dots (QDs) are promising building blocks for use in solar technologies because of their low intrinsic toxicity, narrow bandgap, large absorption coefficient, and low-cost solution synthesis. However, the high surface trap density of InP QDs reduces their energy conversion efficiency and degrades their long-term stability. Encapsulating InP QDs into a wider bandgap shell is desirable to eliminate surface traps and improve optoelectronic properties. Here, we report the synthesis of "giant" InP/ZnSe core/shell QDs with tunable ZnSe shell thickness to investigate the effect of the shell thickness on the optoelectronic properties and the photoelectrochemical (PEC) performance for hydrogen generation. The optical results demonstrate that ZnSe shell growth (0.9-2.8 nm) facilitates the delocalization of electrons and holes into the shell region. The ZnSe shell simultaneously acts as a passivation layer to protect the surface of InP QDs and as a spatial tunneling barrier to extract photoexcited electrons and holes. Thus, engineering the ZnSe shell thickness is crucial for the photoexcited electrons and hole transfer dynamics to tune the optoelectronic properties of "giant" InP/ZnSe core/shell QDs. We obtained an outstanding photocurrent density of 6.2 mA cm-1 for an optimal ZnSe shell thickness of 1.6 nm, which is 288% higher than the values achieved from bare InP QD-based PEC cells. Understanding the effect of shell thickness on surface passivation and carrier dynamics offers fundamental insights into the suitable design and realization of eco-friendly InP-based "giant" core/shell QDs toward improving device performance.

Nocturnal Respiratory Rate Dynamics Enable Early Recognition of Impending Hospitalizations.

The days and weeks preceding hospitalization are poorly understood because they transpire before patients are seen in conventional clinical care settings. Home health sensors offer opportunities to learn signatures of impending hospitalizations and facilitate early interventions, however the relevant biomarkers are unknown. Nocturnal respiratory rate (NRR) is an activity-independent biomarker that can be measured by adherence-independent sensors in the home bed. Here, we report automated longitudinal monitoring of NRR dynamics in a cohort of high-risk recently hospitalized patients using non-contact mechanical sensors under patients' home beds. Since the distribution of nocturnal respiratory rates in populations is not well defined, we first quantified it in 2,000 overnight sleep studies from the NHLBI Sleep Heart Health Study. This revealed that interpatient variability was significantly greater than intrapatient variability (NRR variances of 11.7 brpm2 and 5.2 brpm2 respectively, n=1,844,110 epochs), which motivated the use of patient-specific references when monitoring longitudinally. We then performed adherence-independent longitudinal monitoring in the home beds of 34 high-risk patients and collected raw waveforms (sampled at 80 Hz) and derived quantitative NRR statistics and dynamics across 3,403 patient-nights (n= 4,326,167 epochs). We observed 23 hospitalizations for diverse causes (a 30-day hospitalization rate of 20%). Hospitalized patients had significantly greater NRR deviations from baseline compared to those who were not hospitalized (NRR variances of 3.78 brpm2 and 0.84 brpm2 respectively, n= 2,920 nights). These deviations were concentrated prior to the clinical event, suggesting that NRR can identify impending hospitalizations. We analyzed alarm threshold tradeoffs and demonstrated that nominal values would detect 11 of the 23 clinical events while only alarming 2 times in non-hospitalized patients. Taken together, our data demonstrate that NRR dynamics change days to weeks in advance of hospitalizations, with longer prodromes associating with volume overload and heart failure, and shorter prodromes associating with acute infections (pneumonia, septic shock, and covid-19), inflammation (diverticulitis), and GI bleeding. In summary, adherence-independent longitudinal NRR monitoring has potential to facilitate early recognition and management of pre-symptomatic disease.

Application of Antibiotic-Impregnated Polymethyl-Methacrylate Bone Cement for the Treatment of Infected Cranioplasties: Initial Experience.

BACKGROUND: Management of infected cranioplasty implants remains a surgical challenge. Surgical debridement, removal of the infected implant, and prolonged antibiotic therapy are part of the acute management. In addition, cranioplasty removal poses the risk of dural tear. Reconstruction of the cranial defect is usually delayed for several months to years, increasing the difficulty due to soft tissue contraction and scarring. OBJECTIVE: The aim of the study was to propose an alternative to delayed reconstruction in the face of infection with a dual purpose: treat the infection with a material which delivers antibiotic to the area (polymethyl-methacrylate antibiotic) and which functions as a temporary or permanent cranioplasty. METHODS: We reviewed the records of 3 consecutive patients who underwent single-stage polymethyl-methacrylate antibiotic salvage cranioplasty. RESULTS: All patients underwent debridement of infected tissue. Titanium mesh was placed over the bony defect. Polymethyl methacrylate impregnated with vancomycin and tobramycin was then spread over the plate and defect before closure. Patients also received extended treatment with systemic antimicrobials. Early outcomes have been encouraging for both cosmesis and treatment of infection. CONCLUSIONS: Benefits of this treatment strategy include immediate reconstruction rather than staged procedures and delivery of high concentrations of antibiotics directly to the affected area in addition to systemic antibiotics.

Self-Assembly of CsPbBr3 Nanocubes into 2D Nanosheets.

All-inorganic metal halide perovskites have attracted considerable attention due to their high application potentials in optoelectronics, photonics, and energy conversion. Herein, two-dimensional (2D) CsPbBr3 nanosheets with a thickness of about 3 nm have been synthesized through a simple chemical process based on a hot-injection technique. The lateral dimension of CsPbBr3 nanosheets ranges from 11 to 110 nm, which can be tuned by adjusting the ratio of short ligands (octanoic acid and octylamine) over long ligands (oleic acid and oleylamine). The nanosheets result from the self-assembly of CsPbBr3 nanocubes with an edge length of about 3 nm, which possess the same crystal orientation. In addition, an amorphous region of about 1 nm in width is found between adjacent nanocubes. To investigate both the structure and the growth mechanism of these nanosheets, microstructural characterizations at the atomic scale are conducted, combined with X-ray diffraction analysis, 1H nuclear magnetic resonance (1H NMR) measurement, and density functional theory (DFT) calculation, aiming to determine the configuration of different ligands adsorbed onto CsPbBr3. Our results suggest that the adjacent nanocubes are mainly connected together by short ligands and inclined long ligands. On the basis of the DFT calculation results, a relationship is derived for the volume ratio of short ligands over long ligands and the lateral dimensions of CsPbBr3 nanosheets. Moreover, a physicochemical mechanism is proposed to explain the 2D growth of CsPbBr3 nanosheets. Such a finding provides new insights regarding the well-ordered self-arrangement of CsPbBr3 nanomaterials, as well as new routes to synthesize 2D CsPbX3 (X = Cl and I) nanosheets of suitable dimensions for specific and large-scale applications.

Traumatic ischemic injury in a top of the basilar distribution: a case report.

BACKGROUND: Top of the basilar syndrome is a rare, heterogeneous disorder that has previously only been described in the setting of acute ischemic stroke in predominantly elderly patients. We present the first reported case of traumatic brain injury (TBI) causing ischemia in a top of the basilar distribution. CASE PRESENTATION: A 19-year-old woman suffered an acute subdural hematoma and sustained hypoxemia after being struck by a motor vehicle. Neurosurgical evacuation of the hematoma was undertaken. Magnetic resonance imaging revealed ischemic injury in the midbrain and diencephalic structures fitting a top of the basilar distribution. No associated vascular injury was identified. The patient was eventually discharged in a state of persistent unresponsive wakefulness. CONCLUSIONS: Ischemia in a top of the basilar distribution may occur in the setting of TBI. A high degree of clinical suspicion is required to identify this disorder. Further study of the complex inflammatory microenvironment and associated tissue perfusion dynamics in TBI are needed in order to elucidate the mechanisms underlying ischemic injury patterns, develop management paradigms and predict prognosis.

Low-Cost, Air-Processed Quantum Dot Solar Cells via Diffusion-Controlled Synthesis.

Despite significant advances in the development of high-efficiency and stable quantum dot (QD) solar cells (QDSCs), recent synthetic and fabrication routes still require improvements to render QDSCs commercially feasible. Here, we describe a low-cost, industrially viable fabrication method of QDSCs under an ambient atmosphere (humid air and room temperature) using stable, high-quality, and small-sized PbS QDs prepared with low-cost, greener precursors [i.e., thioacetamide (TAA)] compared to the widely used bis(trimethylsilyl)sulfide [(TMS)2S], at low temperatures without requiring any stringent conditions. The low reaction temperature, medium reactivity of TAA, and diffusion-controlled particle growth adopted in this approach provide an opportunity to synthesize ultrasmall (emission peak ∼700 nm) to larger PbS QDs (emission peak ∼1050 nm). This also enables well-controlled large-scale (multigram) synthesis with a rough estimated production cost of PbS of 8.11 $ per gram (based on materials cost), which is the lowest among the available PbS QDs produced using wet chemistry routes. QDSCs fabricated using 3.25 nm PbS QDs (bandgap 1.29 eV) under ambient conditions yield a high circuit current density (Jsc) of 32.4 mA/cm2 (one of the highest values of Jsc ever reported) with a power conversion efficiency of 7.8% under 1 sun simulated sunlight at AM 1.5 G (100 mW/cm2). These devices exhibit better photovoltaic performance compared to devices fabricated with more traditional PbS QDs synthesized with (TMS)2S under an ambient atmosphere, confirming the quality of PbS QDs produced with our method. The diffusion-controlled TAA-based synthetic route developed herein is found to be very promising for synthesizing size-tunable PbS QDs for photovoltaic and other optoelectronic applications.

Postmortem Analysis in a Clinical Trial of AAV2-NGF Gene Therapy for Alzheimer's Disease Identifies a Need for Improved Vector Delivery.

Nerve growth factor (NGF) gene therapy rescues and stimulates cholinergic neurons, which degenerate in Alzheimer's disease (AD). In a recent clinical trial for AD, intraparenchymal adeno-associated virus serotype 2 (AAV2)-NGF delivery was safe but did not improve cognition. Before concluding that NGF gene therapy is ineffective, it must be shown that AAV2-NGF successfully engaged the target cholinergic neurons of the basal forebrain. In this study, patients with clinically diagnosed early- to middle-stage AD received a total dose of 2 × 1011 vector genomes of AAV2-NGF by stereotactic injection of the nucleus basalis of Meynert. After a mean survival of 4.0 years, AAV2-NGF targeting, spread, and expression were assessed by immunolabeling of NGF and the low-affinity NGF receptor p75 at 15 delivery sites in 3 autopsied patients. NGF gene expression persisted for at least 7 years at sites of AAV2-NGF injection. However, the mean distance of AAV2-NGF spread was only 0.96 ± 0.34 mm. NGF did not directly reach cholinergic neurons at any of the 15 injection sites due to limited spread and inaccurate stereotactic targeting. Because AAV2-NGF did not directly engage the target cholinergic neurons, we cannot conclude that growth factor gene therapy is ineffective for AD. Upcoming clinical trials for AD will utilize real-time magnetic resonance imaging guidance and convection-enhanced delivery to improve the targeting and spread of growth factor gene delivery.

Recovery of electro-mechanical properties inside self-healing composites through microencapsulation of carbon nanotubes.

We report the successful microencapsulation of multi-walled carbon nanotubes suspended in a 5-ethylidene-2-norbornene (5E2N) self-healing monomer, into poly melamine urea formaldehyde shells through in situ polymerization. The average size of the microcapsules, their size-distribution, shell wall structural integrity and thickness are  characterized by optical and scanning electron microscopy. The presence of carbon nanotubes (CNTs) inside the core liquid content, as well as their release after breaking is confirmed by microscopy and spectroscopy analyses. A small amount of CNTs inside the microcapsules is found to have no significant impact on the thermal stability of the system, as determined by thermogravimetric analysis and differential scanning calorimetry. Both the mechanical and the electrical properties of CNT-based self-healing materials can be restored  up to 80% when CNT/5E2N microcapsules are incorporated into polymer composites, thus making them highly suitable for applications in aerospace.

Epitaxial growth and defect repair of heterostructured CuInSexS2-x/CdSeS/CdS quantum dots.

Heterostructured quantum dots (hetero-QDs) have outstanding optical properties and chemical/photostability, which make them promising building blocks for use in various optoelectronic devices. Here, CuInSexS2-x/CdSeS/CdS hetero-QDs were synthesized through a facile two-step method. Their particle size, three-dimensional (3D) shapes and the epitaxial relationship between the CuInSexS2-x/CdSeS core and CdS shell were investigated by high-resolution transmission electron microscopy (HRTEM). Our investigation proves that the as-synthesized hetero-QDs have a regular tetrahedron 3D shape with four {111} crystal facets. The epitaxial relationship between the CuInSexS2-x/CdSeS core and CdS shell is determined to be [110]core//[110]shell, {112}core//{111}shell. In situ HRTEM observations show that the screw dislocation inside the hetero-QDs can be efficiently repaired using e-beam irradiation. These results may help in designing hetero-QDs with high-quality interfaces and identifying the strategies for synthesizing defect-free hetero-QDs.

Reliability of reported peri-ictal behavior to identify psychogenic nonepileptic seizures.

PURPOSE: Differentiating psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES) can be difficult, even when expert clinicians have video recordings of seizures. Moreover, witnesses who are not trained observers may provide descriptions that differ from the expert clinicians', which often raises concern about whether the patient has both ES and PNES. As such, quantitative, evidence-based tools to help differentiate ES from PNES based on patients' and witnesses' descriptions of seizures may assist in the early, accurate diagnosis of patients. METHODS: Based on patient- and observer-reported data from 1372 patients with diagnoses documented by video-elect roencephalography (vEEG), we used logistic regression (LR) to compare specific peri-ictal behaviors and seizure triggers in five mutually exclusive groups: ES, PNES, physiologic non-epileptic seizure-like events, mixed PNES plus ES, and inconclusive monitoring. To differentiate PNES-only from ES-only, we retrospectively trained multivariate LR and a forest of decision trees (DF) to predict the documented diagnoses of 246 prospective patients. RESULTS: The areas under the receiver operating characteristic curve (AUCs) of the DF and LR were 75% and 74%, respectively (empiric 95% CI of chance 37-62%). The overall accuracy was not significantly higher than the naïve assumption that all patients have ES (accuracy DF 71%, LR 70%, naïve 68%, p > 0.05). CONCLUSIONS: Quantitative analysis of patient- and observer-reported peri-ictal behaviors objectively changed the likelihood that a patient's seizures were psychogenic, but these reports were not reliable enough to be diagnostic in isolation. Instead, our scores may identify patients with "probable" PNES that, in the right clinical context, may warrant further diagnostic assessment.

Correlation Structure in Micro-ECoG Recordings is Described by Spatially Coherent Components.

Electrocorticography (ECoG) is becoming more prevalent due to improvements in fabrication and recording technology as well as its ease of implantation compared to intracortical electrophysiology, larger cortical coverage, and potential advantages for use in long term chronic implantation. Given the flexibility in the design of ECoG grids, which is only increasing, it remains an open question what geometry of the electrodes is optimal for an application. Conductive polymer, PEDOT:PSS, coated microelectrodes have an advantage that they can be made very small without losing low impedance. This makes them suitable for evaluating the required granularity of ECoG recording in humans and experimental animals. We used two-dimensional (2D) micro-ECoG grids to record intra-operatively in humans and during acute implantations in mouse with separation distance between neighboring electrodes (i.e., pitch) of 0.4 mm and 0.2/0.25 mm respectively. To assess the spatial properties of the signals, we used the average correlation between electrodes as a function of the pitch. In agreement with prior studies, we find a strong frequency dependence in the spatial scale of correlation. By applying independent component analysis (ICA), we find that the spatial pattern of correlation is largely due to contributions from multiple spatially extended, time-locked sources present at any given time. Our analysis indicates the presence of spatially structured activity down to the sub-millimeter spatial scale in ECoG despite the effects of volume conduction, justifying the use of dense micro-ECoG grids.

Optoelectronic Properties in Near-Infrared Colloidal Heterostructured Pyramidal "Giant" Core/Shell Quantum Dots.

Colloidal heterostructured quantum dots (QDs) are promising candidates for next-generation optoelectronic devices. In particular, "giant" core/shell QDs (g-QDs) can be engineered to exhibit outstanding optical properties and high chemical/photostability for the fabrication of high-performance optoelectronic devices. Here, the synthesis of heterostructured CuInSe x S2-x (CISeS)/CdSeS/CdS g-QDs with pyramidal shape by using a facile two-step method is reported. The CdSeS/CdS shell is demonstrated to have a pure zinc blend phase other than typical wurtzite phase. The as-obtained heterostructured g-QDs exhibit near-infrared photoluminescence (PL) emission (≈830 nm) and very long PL lifetime (in the microsecond range). The pyramidal g-QDs exhibit a quasi-type II band structure with spatial separation of electron-hole wave function, suggesting an efficient exciton extraction and transport, which is consistent with theoretical calculations. These heterostructured g-QDs are used as light harvesters to fabricate a photoelectrochemical cell, exhibiting a saturated photocurrent density as high as ≈5.5 mA cm-2 and good stability under 1 sun illumination (AM 1.5 G, 100 mW cm-2). These results are an important step toward using heterostructured pyramidal g-QDs for prospective applications in solar technologies.

Sub-millimeter ECoG pitch in human enables higher fidelity cognitive neural state estimation.

Electrocorticography (ECoG), electrophysiological recording from the pial surface of the brain, is a critical measurement technique for clinical neurophysiology, basic neurophysiology studies, and demonstrates great promise for the development of neural prosthetic devices for assistive applications and the treatment of neurological disorders. Recent advances in device engineering are poised to enable orders of magnitude increase in the resolution of ECoG without comprised measurement quality. This enhancement in cortical sensing enables the observation of neural dynamics from the cortical surface at the micrometer scale. While these technical capabilities may be enabling, the extent to which finer spatial scale recording enhances functionally relevant neural state inference is unclear. We examine this question by employing a high-density and low impedance 400 µm pitch microECoG (µECoG) grid to record neural activity from the human cortical surface during cognitive tasks. By applying machine learning techniques to classify task conditions from the envelope of high-frequency band (70-170Hz) neural activity collected from two study participants, we demonstrate that higher density grids can lead to more accurate binary task condition classification. When controlling for grid area and selecting task informative sub-regions of the complete grid, we observed a consistent increase in mean classification accuracy with higher grid density; in particular, 400 µm pitch grids outperforming spatially sub-sampled lower density grids up to 23%. We also introduce a modeling framework to provide intuition for how spatial properties of measurements affect the performance gap between high and low density grids. To our knowledge, this work is the first quantitative demonstration of human sub-millimeter pitch cortical surface recording yielding higher-fidelity state estimation relative to devices at the millimeter-scale, motivating the development and testing of µECoG for basic and clinical neurophysiology as well as towards the realization of high-performance neural prostheses.

Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial.

Importance: Nerve growth factor (NGF) is an endogenous neurotrophic factor that prevents the death and augments the functional state of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease (AD). Objective: To determine whether stereotactically guided intracerebral injections of adeno-associated viral vector (serotype 2)-nerve growth factor (AAV2-NGF) are well tolerated and exhibit preliminary evidence of impact on cognitive decline in mild to moderate AD-associated dementia. Design, Setting, and Participants: In a multicenter phase 2 trial, 49 participants with mild to moderate AD were randomly assigned in a 1:1 ratio to receive stereotactically guided intracerebral injections of AAV2-NGF or sham surgery. Participants were enrolled between November 2009 and December 2012. Analyses began in February 2015. The study was conducted at 10 US academic medical centers. Eligibility required a diagnosis of mild to moderate dementia due to AD and individuals aged 55 to 80 years. A total of 39 participants did not pass screening; the most common reason was Mini-Mental State Examination scores below cutoff. Analyses were intention-to-treat. Interventions: Stereotactically guided intracerebral injections of AAV2-NGF into the nucleus basalis of Meynert of each hemisphere or sham surgery. Main Outcomes and Measures: Change from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale at month 24. Results: Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white, and the mean (SD) age was 68 (6.4) years. AAV2-NGF was safe and well-tolerated through 24 months. No significant difference was noted between the treatment group and placebo on the primary outcome measure, the Alzheimer's Disease Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11 [4.65], P = .17). Conclusions and Relevance: This multicenter randomized clinical trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery studies in patients with AD. AAV2-NGF delivery was well-tolerated but did not affect clinical outcomes or selected AD biomarkers. Pathological confirmation of accurate gene targeting is needed. Trial Registration: clinicaltrials.gov Identifier NCT00876863.

An objective score to identify psychogenic seizures based on age of onset and history.

OBJECTIVE: Psychogenic nonepileptic seizure (PNES) is a common diagnosis after evaluation of medication resistant or atypical seizures with video-electroencephalographic monitoring (VEM), but usually follows a long delay after the development of seizures, during which patients are treated for epilepsy. Therefore, more readily available diagnostic tools are needed for earlier identification of patients at risk for PNES. A tool based on patient-reported psychosocial history would be especially beneficial because it could be implemented in the outpatient clinic. METHODS: Based on the data from 1375 patients with VEM-confirmed diagnoses, we used logistic regression to compare the frequency of specific patient-reported historical events, demographic information, age of onset, and delay from first seizure until VEM in five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of this information to differentiate PNES only from ES only, we used multivariate piecewise-linear logistic regression trained using retrospective data from chart review and validated based on data from 246 prospective standardized interviews. RESULTS: The prospective area under the curve of our weighted multivariate piecewise-linear by-sex score was 73%, with the threshold that maximized overall retrospective accuracy resulting in a prospective sensitivity of 74% (95% CI: 70-79%) and prospective specificity of 71% (95% CI: 64-82%). The linear model and piecewise linear without an interaction term for sex had very similar performance statistics. In the multivariate piecewise-linear sex-split predictive model, the significant factors positively associated with ES were history of febrile seizures, current employment or active student status, history of traumatic brain injury (TBI), and longer delay from first seizure until VEM. The significant factors associated with PNES were female sex, older age of onset, mild TBI, and significant stressful events with sexual abuse, in particular, increasing the likelihood of PNES. Delays longer than 20years, age of onset after 31years for men, and age of onset after 40years for women had no additional effect on the likelihood of PNES. DISCUSSION: Our promising results suggest that an objective score has the potential to serve as an early outpatient screening tool to identify patients with greater likelihood of PNES when considered in combination with other factors. In addition, our analysis suggests that sexual abuse, more than other psychological stressors including physical abuse, is more associated with PNES. There was a trend of increasing frequency of PNES for women during childbearing years and plateauing outside those years that was not observed in men.

Identifying psychogenic seizures through comorbidities and medication history.

OBJECTIVE: Low-cost evidence-based tools are needed to facilitate the early identification of patients with possible psychogenic nonepileptic seizures (PNES). Prior to accurate diagnosis, patients with PNES do not receive interventions that address the cause of their seizures and therefore incur high medical costs and disability due to an uncontrolled seizure disorder. Both seizures and comorbidities may contribute to this high cost. METHODS: Based on data from 1,365 adult patients with video-electroencephalography-confirmed diagnoses from a single center, we used logistic and Poisson regression to compare the total number of comorbidities, number of medications, and presence of specific comorbidities in five mutually exclusive groups of diagnoses: epileptic seizures (ES) only, PNES only, mixed PNES and ES, physiologic nonepileptic seizurelike events, and inconclusive monitoring. To determine the diagnostic utility of comorbid diagnoses and medication history to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and age, trained using a retrospective database and validated using a prospective database. RESULTS: Our model differentiated PNES only from ES only with a prospective accuracy of 78% (95% confidence interval =72-84%) and area under the curve of 79%. With a few exceptions, the number of comorbidities and medications was more predictive than a specific comorbidity. Comorbidities associated with PNES were asthma, chronic pain, and migraines (p < 0.01). Comorbidities associated with ES were diabetes mellitus and nonmetastatic neoplasm (p < 0.01). The population-level analysis suggested that patients with mixed PNES and ES may be a population distinct from patients with either condition alone. SIGNIFICANCE: An accurate patient-reported medical history and medication history can be useful when screening for possible PNES. Our prospectively validated and objective score may assist in the interpretation of the medication and medical history in the context of the seizure description and history.

Diagnostic implications of review-of-systems questionnaires to differentiate epileptic seizures from psychogenic seizures.

OBJECTIVE: Early and accurate diagnosis of patients with psychogenic nonepileptic seizures (PNES) leads to appropriate treatment and improves long-term seizure prognosis. However, this is complicated by the need to record seizures to make a definitive diagnosis. Suspicion for PNES can be raised through knowledge that patients with PNES have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (RoSQs) than patients with epileptic seizures. If the responses on the RoSQ can differentiate PNES from other seizure types, then these forms could be an early screening tool. METHODS: Our dataset included all patients admitted from January 2006 to June 2016 for video-electroencephalography at UCLA. RoSQs prior to May 2015 were acquired through retrospective chart review (n=405), whereas RoSQs from subsequent patients were acquired prospectively (n=190). Controlling for sex and number of comorbidities, we used binomial regression to compare the total number of symptoms and the frequency of specific symptoms between five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of RoSQs to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and the number of medical comorbidities. RESULTS: On average, patients with PNES or mixed PNES and ES reported more than twice as many symptoms than patients with isolated ES or PSLE (p<0.001). The prospective accuracy to differentiate PNES from ES was not significantly higher than naïve assumption that all patients had ES (76% vs 70%, p>0.1). DISCUSSION: This analysis of RoSQs confirms that patients with PNES with and without comorbid ES report more symptoms on a population level than patients with epilepsy or PSLE. While these differences help describe the population of patients with PNES, the consistency of RoSQ responses was neither accurate nor specific enough to be used solely as an early screening tool for PNES. Our results suggest that the RoSQ may help differentiate PNES from ES only when, based on other information, the pre-test probability of PNES is at least 50%.

Effect of nanocavities on Ge nanoclustering and out-diffusion in SiO2.

Germanium nanocrystals (Ge-ncs) were synthesized by implantation of Ge+ ions into the fused silica, followed by a thermal annealing at 1000 °C. High-resolution transmission electron microscopy was employed to characterize both the morphology of the formed Ge-ncs and the evolution of their depth-distribution as a function of annealing durations. The formation of nanocavities in the vicinity of nanocrystal/SiO2 interface is evidenced, as well as their influence on the release of the compressive stress exerted on Ge-ncs by surrounding SiO2. Some Ge-ncs are found inside nanocavities, and can move into the implanted layer through a nanocavity-assisted diffusion mechanism. This finding sheds light on a new process that can explain the non-uniformity of the Ge-nanocrystal spatial distribution.