Pandemic Effect on Healthcare Use and Death in Adults with Epilepsy: A Population Study.

OBJECTIVES: We conducted a population-based study using Ontario health administrative data to describe trends in healthcare utilization and mortality in adults with epilepsy during the first pandemic year (March 2020-March 2021) compared to historical data (2016-2019). We also investigated if changes in outpatient visits and diagnostic testing during the first pandemic year were associated with increased risk for hospitalizations, emergency department (ED) visits, or death. METHODS: Projected monthly visit rates (per 100,000 people) for outpatient visits, electroencephalography, magnetic resonance, computed tomography, all-cause ED visits, hospitalizations, and mortality were calculated based on historical data by fitting monthly time series autoregressive integrated moving-average models. Two-way interactions were calculated using Quasi-Poisson models. RESULTS: In adults with epilepsy during the first quarter of the pandemic, we demonstrated a reduction in all-cause outpatient visits, diagnostic testing, ED visits and hospitalizations, and a temporary increase in mortality (observed rates of 355.8 vs projected 308.8, 95% CI: 276.3-345.1). By the end of the year, outpatient visits increased (85,535.4 vs 76,620.6, 95% CI: 71,546.9-82,059.4), and most of the diagnostic test rates returned to the projected. The increase in the rate of all-cause mortality during the pandemic, compared to pre-pandemic, was greater during months with the lower frequency of diagnostic tests than months with higher frequency (interaction p-values <.0001). CONCLUSION: We described the impact of the pandemic on healthcare utilization and mortality in adults with epilepsy during the first year. We demonstrated that access to relevant diagnostic testing is likely important for this population while planning restrictions on non-urgent health services.

Nonresonant Transmission Line Probe for Sensitive Interferometric Electron Spin Resonance Detection.

Electron spin resonance (ESR) spectroscopy measures paramagnetic free radicals, or electron spins, in a variety of biological, chemical, and physical systems. Detection of diverse paramagnetic species is important in applications ranging from quantum computation to biomedical research. Countless efforts have been made to improve the sensitivity of ESR detection. However, the improvement comes at the cost of experimental accessibility. Thus, most ESR spectrometers are limited to specific sample geometries and compositions. Here, we present a nonresonant transmission line ESR probe (microstrip geometry) that effectively couples high frequency microwave magnetic field into a wide range of sample geometries and compositions. The nonresonant transmission line probe maintains detection sensitivity while increasing availability to a wider range of applications. The high frequency magnetic field homogeneity is greatly increased by positioning the sample between the microstrip signal line and the ground plane. Sample interfacing occurs via a universal sample holder which is compatible with both solid and liquid samples. The unavoidable loss in sensitivity due to the nonresonant nature of the transmission line probe (low Q) is recuperated by using a highly sensitive microwave interferometer-based detection circuit. The combination of our sensitive interferometer and nonresonant transmission line provides similar sensitivity to a commercially available ESR spectrometer equipped with a high-Q resonator. The nonresonant probe allows for transmission, reflection, or dual-mode detection (transmission and reflection), where the dual-mode results in a √2 signal enhancement.

Survival after abdominal aortic aneurysm repair is affected by socioeconomic status.

OBJECTIVE: The association between socioeconomic status (SES) and outcome after abdominal aortic aneurysm (AAA) repair is largely unknown. This study aimed to determine the influence of SES on postoperative survival after AAA repair. METHODS: Patients undergoing surgical treatment of AAA at a tertiary referral center between January 1993 and July 2013 were retrospectively collected. Thirty-day postoperative mortality and long-term mortality were documented through medical record review and the Michigan Social Security Death Index. SES was quantified using the neighborhood deprivation index (NDI), which is a standardized and reproducible index used in research that summarizes eight domains of socioeconomic deprivation and is based on census tracts derived from patients' individual addresses. The association between SES and survival was studied by univariable and multivariable Cox regression analysis. RESULTS: A total of 767 patients were included. The mean age was 73 years; 80% were male, 77% were white, and 20% were African American. There was no difference in SES of patients who underwent open vs endovascular repair of AAA (P = .489). The average NDI was -0.18 (minimum, -1.47; maximum, 2.35). After adjusting for the variables that were significant on univariable analysis (age, medical comorbidities, length of stay, and year of surgery), the association between NDI and long-term mortality was significant (P = .021; hazard ratio, 1.21 [1.05-1.37]). CONCLUSIONS: Long-term mortality after AAA repair is associated with SES. Further studies are required to assess which risk factors (behavioral, psychosocial) are responsible for this decreased long-term survival in low SES patients after AAA repair.

Ferroelectricity in Polar Polymer-based FETs: A Hysteresis Analysis.

There is an increasing number of reports on polar polymer-based Ferroelectric Field Effect Transistors (FeFETs), where the hysteresis of the drain current - gate voltage (Id-Vg) curve is investigated as the result of the ferroelectric polarization effect. However, separating ferroelectric effect from many of the factors (such as charge injection/trapping and the presence of mobile ions in the polymer) that confound interpretation is still confusing and controversial. This work presents a methodology to reliably identify the confounding factors which obscure the polarization effect in FeFETs. Careful observation of the Id-Vg curves, as well as monitoring the Id-Vg hysteresis and flat band voltage shift as a function of temperature and sweep frequency identifies the dominant mechanism. This methodology is demonstrated using 15-nm thick high glass transition temperature polar polymer-based FeFETs. In these devices, room temperature hysteresis is largely a consequence of charge trapping and mobile ions, while ferroelectric polarization is observed at elevated temperatures. This methodology can be used to unambiguously prove the effect of ferroelectric polarization in FeFETs.

Analysis and Control of RRAM Overshoot Current.

To combat the large variability problem in RRAM, current compliance elements are commonly used to limit the in-rush current during the forming operation. Regardless of the compliance element (1R-1R or 1T-1R), some degree of current overshoot is unavoidable. The peak value of the overshoot current is often used as a predictive metric of the filament characteristics and is linked to the parasitic capacitance of the test structure. The reported detrimental effects of higher parasitic capacitance seem to support this concept. However, this understanding is inconsistent with the recent successes of compliance-free ultra-short pulse forming which guarantees a maximum peak overshoot current. We use detailed circuit analysis and experimental measurements of 1R-1R and 1T-1R structures to show that the peak overshoot is independent of the parasitic capacitance while the overshoot duration is strongly dependent on the parasitic capacitance. Forming control can be achieved, in ultra-short pulse forming, since the overshoot duration is always less than the applied pulse duration. The demonstrated success of ultra-short pulse forming becomes easier to reconcile after identifying the importance of overshoot duration.

Wafer-Level Electrically Detected Magnetic Resonance: Magnetic Resonance in a Probing Station.

We report on a novel semiconductor reliability technique that incorporates an electrically detected magnetic resonance (EDMR) spectrometer within a conventional semiconductor wafer probing station. EDMR is an ultrasensitive electron paramagnetic resonance technique with the capability to provide detailed physical and chemical information about reliability limiting defects in semiconductor devices. EDMR measurements have generally required a complex apparatus, not typically found in solid-state electronics laboratories. The union of a semiconductor probing station with EDMR allows powerful analytical measurements to be performed within individual devices at the wafer level. Our novel approach replaces the standard magnetic resonance microwave cavity or resonator with a small non- resonant near field microwave probe. Using this new approach we have demonstrated bipolar amplification effect and spin dependent charge pumping in various SiC based MOSFET structures. Although our studies have been limited to SiC based devices, the approach will be widely applicable to other types of MOSFETs, bipolar junction transistors, and various memory devices. The replacement of the resonance cavity with the very small non- resonant microwave probe greatly simplifies the EDMR detection scheme and allows for the incorporation of this powerful tool with a wafer probing station. We believe this scheme offers great promise for widespread utilization of EDMR in semiconductor reliability laboratories.

Impact of RRAM Read Fluctuations on the Program-Verify Approach.

The stochastic nature of the conductive filaments in oxide-based resistive memory (RRAM) represents a sizeable impediment to commercialization. As such, program-verify methodologies are highly alluring. However, it was recently shown that program-verify methods are unworkable due to strong resistance state relaxation after SET/RESET programming. In this paper, we demonstrate that resistance state relaxation is not the main culprit. Instead, it is fluctuation-induced false-reading (triggering) that defeats the program-verify method, producing a large distribution tail immediately after programming. The fluctuation impact on the verify mechanism has serious implications on the overall write/erase speed of RRAM.

Thermoelectric plastics: from design to synthesis, processing and structure-property relationships.

Thermoelectric plastics are a class of polymer-based materials that combine the ability to directly convert heat to electricity, and vice versa, with ease of processing. Potential applications include waste heat recovery, spot cooling and miniature power sources for autonomous electronics. Recent progress has led to surging interest in organic thermoelectrics. This tutorial review discusses the current trends in the field with regard to the four main building blocks of thermoelectric plastics: (1) organic semiconductors and in particular conjugated polymers, (2) dopants and counterions, (3) insulating polymers, and (4) conductive fillers. The design and synthesis of conjugated polymers that promise to show good thermoelectric properties are explored, followed by an overview of relevant structure-property relationships. Doping of conjugated polymers is discussed and its interplay with processing as well as structure formation is elucidated. The use of insulating polymers as binders or matrices is proposed, which permit the adjustment of the rheological and mechanical properties of a thermoelectric plastic. Then, nanocomposites of conductive fillers such as carbon nanotubes, graphene and inorganic nanowires in a polymer matrix are introduced. A case study examines poly(3,4-ethylenedioxythiophene) (PEDOT) based materials, which up to now have shown the most promising thermoelectric performance. Finally, a discussion of the advantages provided by bulk architectures e.g. for wearable applications highlights the unique advantages that thermoelectric plastics promise to offer.

Identification, library synthesis and anti-vibriosis activity of 2-benzyl-4-chlorophenol from cultures of the marine bacterium Shewanella halifaxensis.

Summer Gut Syndrome (SGS) is caused by various Vibrio bacterial species and can have negative effects on aquaculture farms worldwide. In New Zealand, SGS is caused by Vibrio harveyii infecting King Salmon (Oncorhynchus tshawytscha). To find leads for the prevention of SGS, we screened the inhibitory effects of 16 strains of Shewanella upon V. harveyii growth in competitive solid phase cultures. The detailed investigation of Shewanella halifaxensis IRL548 revealed 2-benzyl-4-chlorophenol (1), a known, commercially available antibacterial agent, as the major bioactive component. Synthesis of a small library of congeners to confirm the natural product identity and to provide a structure-activity relationship for the observed activity was also completed. Compound 1 exhibits moderate activity against two pathogenic microorganisms.

Rapid and Accurate C-V Measurements.

We report a new technique for the rapid measurement of full capacitance-voltage (C-V) characteristic curves. The displacement current from a 100 MHz applied sine-wave, which swings from accumulation to strong inversion, is digitized directly using an oscilloscope from the metal-oxide-semiconductor (MOS) capacitor under test. A C-V curve can be constructed directly from this data but is severely distorted due to non-ideal behavior of real measurement systems. The key advance of this work is to extract the system response function using the same measurement set-up and a known MOS capacitor. The system response correction to the measured C-V curve of the unknown MOS capacitor can then be done by simple deconvolution. No de-skewing and/or leakage current correction is necessary, making it a very simple and quick measurement. Excellent agreement between the new fast C-V method and C-V measured conventionally by an LCR meter is achieved. The total time required for measurement and analysis is approximately 2 seconds, which is limited by our equipment.

Electron spin resonance scanning probe spectroscopy for ultrasensitive biochemical studies.

Electron spin resonance (ESR) spectroscopy's affinity for detecting paramagnetic free radicals, or spins, has been increasingly employed to examine a large variety of biochemical interactions. Such paramagnetic species are broadly found in nature and can be intrinsic (defects in solid-state materials systems, electron/hole pairs, stable radicals in proteins) or, more often, purposefully introduced into the material of interest (doping/attachment of paramagnetic spin labels to biomolecules of interest). Using ESR to trace the reactionary path of paramagnetic spins or spin-active proxy molecules provides detailed information about the reaction's transient species and the label's local environment. For many biochemical systems, like those involving membrane proteins, synthesizing the necessary quantity of spin-labeled biomolecules (typically 50 pmol to 100 pmol) is quite challenging and often limits the possible biochemical reactions available for investigation. Quite simply, ESR is too insensitive. Here, we demonstrate an innovative approach that greatly enhances ESR's sensitivity (>20000× improvement) by developing a near-field, nonresonant, X-band ESR spectrometric method. Sensitivity improvement is confirmed via measurement of 140 amol of the most common nitroxide spin label in a ≈593 fL liquid cell at ambient temperature and pressure. This experimental approach eliminates many of the typical ESR sample restrictions imposed by conventional resonator-based ESR detection and renders the technique feasible for spatially resolved measurements on a wider variety of biochemical samples. Thus, our approach broadens the pool of possible biochemical and structural biology studies, as well as greatly enhances the analytical power of existing ESR applications.

Ecophysiological diversity of a novel member of the genus Alteromonas, and description of Alteromonas mediterranea sp. nov.

Nine non-pigmented, motile, Gram-negative bacteria originally designated as Alteromonas macleodii deep-sea ecotypes, were isolated from seawater samples collected from four separate locations; two deep-sea sites in the Mediterranean Sea and surface water of the Aegean Sea and English Channel. The six strains studied in vitro were found to tolerate up to 20 % NaCl. The DNA-DNA relatedness between the deep-sea ecotype strains was found to be between 75 and 89 %, whilst relatedness with the validly named Alteromonas species was found to be between 31 and 69 %. The average nucleotide identity (ANI) amongst the deep-sea ecotype strains was found to be 98-100 %; the in silico genome-to-genome distance (GGD), 85-100 %; the average amino acid identity (AAI) of all conserved protein-coding genes, 95-100 %; and the strains possessed 30-32 of the Karlin's genomic signature dissimilarity. The ANI between the deep-sea ecotype strains and A. macleodii ATCC 27126(T) and Alteromonas australica H 17(T) was found to be 80.6 and 74.6 %, respectively. A significant correlation was observed between the phenotypic data obtained in vitro and data retrieved in silico from whole genome sequences. The results of a phylogenetic study that incorporated a 16S rRNA gene sequence analysis, multilocus phylogenetic analysis (MLPA) and genomic analysis, together with the physiological, biochemical and chemotaxonomic data, clearly indicated that the group of deep-sea ecotype strains represents a distinct species within the genus Alteromonas. Based on these data, a new species, Alteromonas mediterranea, is proposed. The type strain is DE(T) ( = CIP 110805(T) = LMG 28347(T) = DSM 17117(T)).

Nano-optical conveyor belt, part I: Theory.

We propose a method for peristaltic transport of nanoparticles using the optical force field over a nanostructured surface. Nanostructures may be designed to produce strong near-field hot spots when illuminated. The hot spots function as optical traps, separately addressable by their resonant wavelengths and polarizations. By activating closely packed traps sequentially, nanoparticles may be handed off between adjacent traps in a peristaltic fashion. A linear repeating structure of three separately addressable traps forms a "nano-optical conveyor belt"; a unit cell with four separately addressable traps permits controlled peristaltic transport in the plane. Using specifically designed activation sequences allows particle sorting.

Nano-optical conveyor belt, part II: Demonstration of handoff between near-field optical traps.

Optical tweezers have been widely used to manipulate biological and colloidal material, but the diffraction limit of far-field optics makes focused beams unsuitable for manipulating nanoscale objects with dimensions much smaller than the wavelength of light. While plasmonic structures have recently been successful in trapping nanoscale objects with high positioning accuracy, using such structures for manipulation over longer range has remained a significant challenge. In this work, we introduce a conveyor belt design based on a novel plasmonic structure, the resonant C-shaped engraving (CSE). We show how long-range manipulation is made possible by means of handoff between neighboring CSEs, and we present a simple technique for controlling handoff by rotating the polarization of laser illumination. We experimentally demonstrate handoff between a pair of CSEs for polystyrene spheres 200, 390, and 500 nm in diameter. We then extend this technique and demonstrate controlled particle transport down a 4.5 µm long "nano-optical conveyor belt."

A Survey of Knowledge and Perspectives of Ventricular Assist Device Therapy: Evaluating the Timing of Advanced Heart Failure Referral.

BACKGROUND: While advancements in ventricular assist device (VAD) therapy have improved survival and quality of life for select patients with advanced heart failure (HF), variations in provider knowledge and opinions may ultimately serve as barriers to therapy. METHODS AND RESULTS: A 12-item survey assessing experience, knowledge, and perspectives of VAD therapy was sent to 106 practicing cardiologists at three neighboring institutions. We received 34 responses for a total response rate of 32.1%. The majority of respondents elected to refer patients with refractory disease for VAD therapy, while only 29.4% elected to refer when standard medical therapy is withdrawn due to hypotension. CONCLUSIONS: While providers are well-informed on the fundamentals of advanced therapy, identifying patients with advanced HF who may benefit from referral remains an educational challenge. An automated referral program that identifies patients with advanced HF based on validated clinical parameters could increase appropriately timed referrals to HF specialists to further improve survival and quality of life outcomes with advanced therapy.

Paenibacillus darwinianus sp. nov., isolated from gamma-irradiated Antarctic soil.

A novel bacterium, strain Br(T), was isolated from gamma-irradiated soils of the Britannia drift, Lake Wellman Region, Antarctica. This isolate was rod-shaped, endospore forming, Gram-stain-variable, catalase-positive, oxidase-negative and strictly aerobic. Cells possessed a monotrichous flagellum. Optimal growth was observed at 18 °C, pH 7.0 in PYGV or R2A broth. The major cellular fatty acid was anteiso-C15 : 0 (63.4 %). Primary identified lipids included phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. Total phospholipid was 60 % (w/w) of the total lipid extract. MK-7 was the dominant isoprenoid quinone. The genomic DNA G+C content was 55.6 mol%. Based on 16S rRNA gene sequence similarity, strain Br(T) clusters within the genus Paenibacillus with similarity values ranging from 93.9 to 95.1 %. Phylogenetic analyses by maximum-likelihood, maximum-parsimony and neighbour-joining methods revealed that strain Br(T) clusters with Paenibacillus daejeonensis (AF290916), Paenibacillus tarimensis (EF125184) and Paenibacillus pinihumi (GQ423057), albeit with weak bootstrap support. On the basis of phenotypic, chemotaxonomic and phylogenetic characteristics, we propose that strain Br(T) represents a novel species, Paenibacillus darwinianus sp. nov. The type strain is Br(T) ( = DSM 27245(T) = ICMP 19912(T)).

Thermoflavifilum aggregans gen. nov., sp. nov., a thermophilic and slightly halophilic filamentous bacterium from the phylum Bacteroidetes.

A strictly aerobic, thermophilic, moderately acidophilic, non-spore-forming bacterium, strain P373(T), was isolated from geothermally heated soil at Waikite, New Zealand. Cells were filamentous rods, 0.2-0.4 µm in diameter and grew in chains up to 80 µm in length. On the basis of 16S rRNA gene sequence similarity, strain P373(T) was shown to belong to the family Chitinophagaceae (class Sphingobacteriia) of the phylum Bacteroidetes, with the most closely related cultivated strain, Chitinophaga pinensis UQM 2034(T), having 87.6 % sequence similarity. Cells stained Gram-negative, and were catalase- and oxidase-positive. The major fatty acids were i-15 : 0 (10.8 %), i-17 : 0 (24.5 %) and i-17 : 0 3-OH (35.2 %). Primary lipids were phosphatidylethanolamine, two unidentified aminolipids and three other unidentified polar lipids. The presence of sulfonolipids (N-acyl-capnines) was observed in the total lipid extract by mass spectrometry. The G+C content of the genomic DNA was 47.3 mol% and the primary respiratory quinone was MK-7. Strain P373(T) grew at 35-63 °C with an optimum temperature of 60 °C, and at pH 5.5-8.7 with an optimum growth pH of 7.3-7.4. NaCl tolerance was up to 5 % (w/v) with an optimum of 0.1-0.25 % (w/v). Cell colonies were non-translucent and pigmented vivid yellow-orange. Cells displayed an oxidative chemoheterotrophic metabolism. The distinct phylogenetic position and the phenotypic characteristics separate strain P373(T) from all other members of the phylum Bacteroidetes and indicate that it represents a novel species in a new genus, for which the name Thermoflavifilum aggregans gen. nov., sp. nov. is proposed. The type strain of the type species is P373(T) ( = ICMP 20041(T) = DSM 27268(T)).

Discovery of lipids from B. longum subsp. infantis using whole cell MALDI analysis.

Bifidobacteria are dominant members of the microbial community in the intestinal tract of infants, and studies have shown that glycolipids extracted from the cell surface of these bacteria elicit beneficial immune responses. Accordingly, the identification and structural characterization of glycolipids from the cell wall of bifidobacteria is the first step in correlating glycolipid structure with biological activity. Using whole cell MALDI as a screening tool, we herein present for the first time the identification and structural elucidation of the major polar lipids from Bifidobacterium longum subs. infantis. The lipids identified include an unprecedented plasmenyl cyclophosphatidic acid and a mixed acetal glycolipid, with the latter subsequently being isolated and found to suppress the innate immune response.

In vitro fermentation of prebiotic oligosaccharides by Bifidobacterium lactis HN019 and Lactobacillus spp.

The utilisation of various prebiotic oligosaccharides by probiotic strains of Bifidobacterium lactis, Lactobacillus rhamnosus and Lactobacillus acidophilus was investigated in order to determine the synbiotic potential of various prebiotic/probiotic combinations. Analysis by HPLC and high-performance anion-exchange chromatography of the cell-free medium taken during growth of the three probiotic bacteria showed differences in the consumption of the various oligosaccharides. Analysis of galactooligosaccharides showed that both L. rhamnosus and B. lactis consumed mostly mono- and di-saccharide, while L. acidophilus consumed oligosaccharides up to trisaccharide. Both B. lactis and L. acidophilus utilised fructooligosaccharides and inulin, but showed different patterns of oligosaccharide consumption. Only L. rhamnosus grew on ß-glucan oligosaccharides and preferentially consumed the trisaccharide. The results indicate the synbiotic potential of the various probiotic/prebiotic combinations, particularly L. acidophilus/galactooligosaccharides, L. acidophilus/fructooligosaccharides or inulin and L. rhamnosus/ß-glucan oligosaccharides.

Cyclic 3-alkyl pyridinium alkaloid monomers from a New Zealand Haliclona sp. marine sponge.

Bioassay and NMR approaches have been used to guide the isolation of one known and two new cyclic 3-alkyl pyridinium alkaloid (3-APA) monomers from the New Zealand marine sponge Haliclona sp. The new compounds, dehydrohaliclocyclins C (3) and F (4), are the first reported examples of cyclic 3-APA monomers with unsaturation in the alkyl chain. The known compound haliclocyclin C (2) was also isolated from a mixture with 4. The structures of compounds 2-4 were elucidated using NMR spectroscopy, mass spectrometry, and chemical degradation.