Fundamental properties of dipole transmitting antennas formed by carbon nanotubes are investigated. Since carbon nanotubes can be grown to centimeter lengths, and since they can be metallic, the ...properties of carbon nanotubes as antenna elements are of fundamental interest. In this paper, dipole carbon nanotube antennas are investigated via a classical Hallen's-type integral equation, based on a quantum mechanical conductivity. The input impedance, current profile, and efficiency are presented, and the radiation pattern is discussed, as are possible applications.
Many observers have argued that the regulatory framework in place prior to the global financial crisis was deficient because it was largely “microprudential” in nature. A microprudential approach is ...one in which regulation is partial equilibrium in its conception and aimed at preventing the costly failure of individual financial institutions. By contrast, a “macroprudential” approach recognizes the importance of general equilibrium effects, and seeks to safeguard the financial system as a whole. In the aftermath of the crisis, there seems to be agreement among both academics and policymakers that financial regulation needs to move in a macroprudential direction. In this paper, we offer a detailed vision for how a macroprudential regime might be designed. Our prescriptions follow from a specific theory of how modern financial crises unfold and why both an unregulated financial system, as well as one based on capital rules that only apply to traditional banks, is likely to be fragile. We begin by identifying the key market failures at work: why individual financial firms, acting in their own interests, deviate from what a social planner would have them do. Next, we discuss a number of concrete steps to remedy these market failures. We conclude the paper by comparing our proposals to recent regulatory reforms in the United States and to proposed global banking reforms.
The advent of genome editing has transformed the therapeutic landscape for several debilitating diseases, and the clinical outlook for gene therapeutics has never been more promising. The therapeutic ...potential of nucleic acids has been limited by a reliance on engineered viral vectors for delivery. Chemically defined polymers can remediate technological, regulatory, and clinical challenges associated with viral modes of gene delivery. Because of their scalability, versatility, and exquisite tunability, polymers are ideal biomaterial platforms for delivering nucleic acid payloads efficiently while minimizing immune response and cellular toxicity. While polymeric gene delivery has progressed significantly in the past four decades, clinical translation of polymeric vehicles faces several formidable challenges. The aim of our Account is to illustrate diverse concepts in designing polymeric vectors towards meeting therapeutic goals of in vivo and ex vivo gene therapy. Here, we highlight several classes of polymers employed in gene delivery and summarize the recent work on understanding the contributions of chemical and architectural design parameters. We touch upon characterization methods used to visualize and understand events transpiring at the interfaces between polymer, nucleic acids, and the physiological environment. We conclude that interdisciplinary approaches and methodologies motivated by fundamental questions are key to designing high-performing polymeric vehicles for gene therapy.
Low-intensity transcranial focused ultrasound stimulation (TFUS) holds great promise as a highly focal technique for transcranial stimulation even for deep brain areas. Yet, knowledge about the ...safety of this novel technique is still limited.
To systematically review safety related aspects of TFUS. The review covers the mechanisms-of-action by which TFUS may cause adverse effects and the available data on the possible occurrence of such effects in animal and human studies.
Initial screening used key term searches in PubMed and bioRxiv, and a review of the literature lists of relevant papers. We included only studies where safety assessment was performed, and this results in 33 studies, both in humans and animals.
Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also unintentionally affect long-term neural activity and behaviour. A variety of methods was used mainly in rodents to evaluate these adverse effects, including tissue staining, magnetic resonance imaging, temperature measurements and monitoring of neural activity and behaviour. In 30 studies, adverse effects were absent, even though at least one Food and Drug Administration (FDA) safety index was frequently exceeded. Two studies reported microhaemorrhages after long or relatively intense stimulation above safety limits. Another study reported BBB opening and neuronal damage in a control condition, which intentionally and substantially exceeded the safety limits.
Most studies point towards a favourable safety profile of TFUS. Further investigations are warranted to establish a solid safety framework for the therapeutic window of TFUS to reliably avoid adverse effects while ensuring neural effectiveness. The comparability across studies should be improved by a more standardized reporting of TFUS parameters.
•TFUS is an emerging non-invasive stimulation method with excellent focality•We summarize the safety-related data from the available literature.•Adverse effects were absent in 30 studies, and were reported in 3 studies.•Many studies used parameters outside safety limits for diagnostic ultrasound.•Further studies are warranted to establish the safety margin for TFUS.
•A head template for acoustic and thermal simulations of TUS is introduced.•The template was built from calibrated CT scans of normal adults (age < 50).•Acoustic and thermal simulations based on the ...template represent the group median well.•The template is useful for treatment planning and optimization in young adults.
Transcranial focused Ultrasound Stimulation (TUS) at low intensities is emerging as a novel non-invasive brain stimulation method with higher spatial resolution than established transcranial stimulation methods and the ability to selectively stimulate also deep brain areas. Accurate control of the focus position and strength of the TUS acoustic waves is important to enable a beneficial use of the high spatial resolution and to ensure safety. As the human skull causes strong attenuation and distortion of the waves, simulations of the transmitted waves are needed to accurately determine the TUS dose distribution inside the cranial cavity. The simulations require information of the skull morphology and its acoustic properties. Ideally, they are informed by computed tomography (CT) images of the individual head. However, suited individual imaging data is often not readily available. For this reason, we here introduce and validate a head template that can be used to estimate the average effects of the skull on the TUS acoustic wave in the population.
The template was created from CT images of the heads of 29 individuals of different ages (between 20–50 years), gender and ethnicity using an iterative non-linear co-registration procedure. For validation, we compared acoustic and thermal simulations based on the template to the average of the simulation results of all 29 individual datasets. Acoustic simulations were performed for a model of a focused transducer driven at 500 kHz, placed at 24 standardized positions by means of the EEG 10–10 system. Additional simulations at 250 kHz and 750 kHz at 16 of the positions were used for further confirmation. The amount of ultrasound-induced heating at 500 kHz was estimated for the same 16 transducer positions. Our results show that the template represents the median of the acoustic pressure and temperature maps from the individuals reasonably well in most cases. This underpins the usefulness of the template for the planning and optimization of TUS interventions in studies of healthy young adults. Our results further indicate that the amount of variability between the individual simulation results depends on the position. Specifically, the simulated ultrasound-induced heating inside the skull exhibited strong interindividual variability for three posterior positions close to the midline, caused by a high variability of the local skull shape and composition. This should be taken into account when interpreting simulation results based on the template.
Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT ...sessions and electrode placement) and acts as a biomarker of clinical outcome.
Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice.
The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery–Åsberg Depression Rating Scale change –1.0 SE 0.35, per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope –0.69 SE 0.38, p = .069).
The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.
Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. ...Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response.
Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites.
Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen’s d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman’s rank correlation ρ = −.44, p < .001), while total white matter volume remained unchanged (d = −0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome.
The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.
Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, has recently been detected in humans and wildlife. The current study characterizes the ...developmental toxicity of PFOA in the mouse. Timed-pregnant CD-1 mice were given 1, 3, 5, 10, 20, or 40 mg/kg PFOA by oral gavage daily from gestational day (GD) 1 to 17; controls received an equivalent volume (10 ml/kg) of water. PFOA treatment produced dose-dependent full-litter resorptions; all dams in the 40-mg/kg group resorbed their litters. Weight gain in dams that carried pregnancy to term was significantly lower in the 20-mg/kg group. At GD 18, some dams were sacrificed for maternal and fetal examinations (group A), and the rest were treated once more with PFOA and allowed to give birth (group B). Postnatal survival, growth, and development of the offspring were monitored. PFOA induced enlarged liver in group A dams at all dosages, but did not alter the number of implantations. The percent of live fetuses was lower only in the 20-mg/kg group (74 vs. 94% in controls), and fetal weight was also significantly lower in this group. However, no significant increase in malformations was noted in any treatment group. The incidence of live birth in group B mice was significantly lowered by PFOA: ca. 70% for the 10- and 20-mg/kg groups compared to 96% for controls. Postnatal survival was severely compromised at 10 or 20 mg/kg, and moderately so at 5 mg/kg. Dose-dependent growth deficits were detected in all PFOA-treated litters except the 1-mg/kg group. Significant delays in eye-opening (up to 2–3 days) were noted at 5 mg/kg and higher dosages. Accelerated sexual maturation was observed in male offspring, but not in females. These data indicate maternal and developmental toxicity of PFOA in the mouse, leading to early pregnancy loss, compromised postnatal survival, delays in general growth and development, and sex-specific alterations in pubertal maturation.
The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3−) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS ...daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive, and moribund within 30–60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dosage groups, the neonates also became moribund but survived for a longer period of time (8–12 h). Over 95% of these animals died within 24 h. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and thyroid-stimulating hormone TSH levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.
Purpose
The diffusion‐weighted SPLICE (split acquisition of fast spin‐echo signals) sequence employs split‐echo rapid acquisition with relaxation enhancement (RARE) readout to provide images almost ...free of geometric distortions. However, due to the varying T2$$ {}_2 $$‐weighting during k‐space traversal, SPLICE suffers from blurring. This work extends a method for controlling the spatial point spread function (PSF) while optimizing the signal‐to‐noise ratio (SNR) achieved by adjusting the flip angles in the refocusing pulse train of SPLICE.
Methods
An algorithm based on extended phase graph (EPG) simulations optimizes the flip angles by maximizing SNR for a flexibly chosen predefined target PSF that describes the desired k‐space density weighting and spatial resolution. An optimized flip angle scheme and a corresponding post‐processing correction filter which together achieve the target PSF was tested by healthy subject brain imaging using a clinical 1.5 T scanner.
Results
Brain images showed a clear and consistent improvement over those obtained with a standard constant flip angle scheme. SNR was increased and apparent diffusion coefficient estimates were more accurate. For a modified Hann k‐space weighting example, considerable benefits resulted from acquisition weighting by flip angle control.
Conclusion
The presented flexible method for optimizing SPLICE flip angle schemes offers improved MR image quality of geometrically accurate diffusion‐weighted images that makes the sequence a strong candidate for radiotherapy planning or stereotactic surgery.
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