Correspondence - Further reflections of the role of artificial intelligence in acute medicine.

We read with great interest the article "Artificial Intelligence: its Future and Impact on Acute Medicine". Regarding the historical perspective on artificial intelligence (AI) origins, we believe the role of John von Neumann (1903-1957) also deserves emphasis.

Extending the resolution limits of nanoshape imprint lithography using molecular dynamics of polymer crosslinking.

Emerging nanoscale applications in energy, electronics, optics, and medicine can exhibit enhanced performance by incorporating nanoshaped structures (nanoshape structures here are defined as shapes enabled by sharp corners with radius of curvature < 5 nm). Nanoshaped fabrication at high-throughput is well beyond the capabilities of advanced optical lithography. Although the highest-resolution e-beams and large-area e-beams have a resolution limit of 5 and 18 nm half-pitch lines or 20 nm half-pitch holes, respectively, their low throughput necessitates finding other fabrication techniques. By using nanoimprint lithography followed by metal-assisted chemical etching, diamond-like nanoshapes with ~3 nm radius corners and 100 nm half-pitch over large areas have been previously demonstrated to improve the nanowire capacitor performance (by ~90%). In future dynamic random-access memory (DRAM) nodes (with DRAM being an exemplar CMOS application), the implementation of nanowire capacitors scaled to <15 nm half-pitch is required. To scale nanoshape imprint lithography down to these half-pitch values, the previously established atomistic simulation framework indicates that the current imprint resist materials are unable to retain the nanoshape structures needed for DRAM capacitors. In this study, the previous simulation framework is extended to study improved shape retention by varying the resist formulations and by introducing novel bridge structures in nanoshape imprinting. This simulation study has demonstrated viable approaches to sub-10 nm nanoshaped imprinting with good shape retention, which are matched by experimental data.

Is Twice-weekly Maintenance Hemodialysis Justified?

BACKGROUND: The benefits of twice-weekly dialysis at initiation are significant with respect to access longevity, preservation of residual renal function, economic factors, and patient quality of life. It is widely practiced in developing countries due to resource and financial constraints. We present a 3-year follow-up of patients on twice-weekly dialysis and their outcomes. MATERIAL AND METHODS: This was a 3-year observational follow-up study of patients initiated on twice-weekly hemodialysis. Adequacy and basic cost-effective hematological and biochemical parameters were studied monthly. In case of complications, the patient was shifted to thrice-weekly hemodialysis. RESULTS: 88 incident hemodialysis patients were followed up. Total sessions of hemodialysis (HD) studied were 16,406. The mean hemoglobin level was 9.53 g/dl with hyperphosphatemia in 74.88% patients. The mean residual renal function (RRF) at initiation was 5.71 +/- 3.70 ml/min. The mean interdialytic weight gain was 1.91 +/- 1.26 kg with a mean ultrafiltration of 2600 ± 410 ml. The spKt/V and eKt/V were adequate in 68.54% and 48.34% patients; however, the standard Kt/V of 2 was achieved in only 10.51% patients. Emergency HD was done in 41 sessions (0.24%). There were 24 deaths (27.27%) during this period with the mean time to mortality being 503.12 +/- 296.62 days. CONCLUSION: Initiation at twice-weekly schedules for patients on maintenance hemodialysis is a viable option with increments in case of requirement, more so in patients with good urine output and residual renal function. The biochemical and hematological parameters were stable and within KDOQI guidelines and do not worsen with time.

Ruthenium-Assisted Chemical Etching of Silicon: Enabling CMOS-Compatible 3D Semiconductor Device Nanofabrication.

The semiconductor industry's transition to three-dimensional (3D) logic and memory devices has revealed the limitations of plasma etching in reliable creation of vertical high aspect ratio (HAR) nanostructures. Metal-assisted chemical etch (MacEtch) can create ultra-HAR, taper-free nanostructures in silicon, but the catalyst used for reliable MacEtch-gold-is not CMOS (complementary metal-oxide-semiconductor)-compatible and therefore cannot be used in the semiconductor industry. Here, for the first time, we report a ruthenium MacEtch process that is comparable in quality to gold MacEtch. We introduce new process variables-catalyst plasma pretreatment and surface area-to achieve this result. Ruthenium is particularly desirable as it is not only CMOS-compatible but has also been introduced in semiconductor fabrication as an interconnect material. The results presented here remove a significant barrier to adoption of MacEtch for scalable fabrication of 3D semiconductor devices, sensors, and biodevices that can benefit from production in CMOS foundries.

Enabling Ultrahigh-Aspect-Ratio Silicon Nanowires Using Precise Experiments for Detecting the Onset of Collapse.

Top-down patterning along with metal-assisted chemical etching (MACE) can enable the fabrication of highly controlled wafer-scale silicon nanowires (Si-NWs). Maximizing the NW aspect ratio, while avoiding collapse, can enable many important applications. A precise experimental technique has been developed here to study the onset of Si-NW collapse. This experimental approach has resulted in unexpectedly tall Si-NWs for oversized wires separated by sub-50-nm gaps. As compared to known theory, a factor of 4.5 increase in maximum aspect ratio was achieved for uncollapsed nanowires with 200-nm pitch and 25-nm spacing. This discrepancy between known theory and experimental results was eliminated when the gold-resist caps (which are a feature of our MACE process) on top of these nanowires were removed. This led us to incorporate electrostatic repulsion into known theoretical formulations, which matched the experimental results. In summary, this work provides new experimental and theoretical insights into nanowire collapse behavior.

Hyperspectral imaging for high-throughput, spatially resolved spectroscopic scatterometry of silicon nanopillar arrays.

Modern high-throughput nanopatterning techniques, such as nanoimprint lithography, make it possible to fabricate arrays of nanostructures (features with dimensions of 10's to 100's of nm) over large area substrates (cm2 to m2 scale) such as Si wafers, glass sheets, and flexible roll-to-roll webs. The ability to make such large-area nanostructure arrays (LNAs) has created an extensive design space, enabling a wide array of applications including optical devices, such as wire-grid polarizers, transparent conductors, color filters, and anti-reflection surfaces, and building blocks for electronic components, such as ultracapacitors, sensors, and memory storage architectures. However, existing metrology methods will have trouble scaling alongside fabrication methods. Scanning electron microscopy (SEM) and atomic force microscopy (AFM), for instance, have micron scale fields of view (FOV) that preclude comprehensive characterization of LNAs, which may be manufactured at m2 per minute rates. Scatterometry approaches have larger FOVs (typically 100's of µm to a few mm), but traditional scatterometry systems measure samples one point at a time, which also makes them too slow for large-scale LNA manufacturing. In this work, we demonstrate parallelization of the traditional spectroscopic scatterometry approach using hyperspectral imaging, increasing the throughput of the technique by a factor of 106-107. We demonstrate this approach by using hyperspectral imaging and inverse modeling of reflectance spectra to derive 3-dimensional geometric data for Si nanopillar array structures over both mm and cm-scale with µm-scale spatial resolution. This work suggests that geometric measurements for a variety of LNAs can be performed with the potential for high speed over large areas which may be critical for future LNA manufacturing.

Structural coloration with hourglass-shaped vertical silicon nanopillar arrays.

We demonstrate that arrays of hourglass-shaped nanopillars patterned into crystalline silicon substrates exhibit vibrant, highly controllable reflective structural coloration. Unlike structures with uniform sidewall profiles, the hourglass profile defines two separate regions on the pillar: a head and a body. The head acts as a suspended Mie resonator and is responsible for resonant reflectance, while the body acts to suppress broadband reflections from the surface. The combination of these effects gives rise to vibrant colors. The size of the nanopillars can be tuned to provide a variety of additive colors, including the RGB primaries. Experimental results are shown for nanopillar arrays fabricated using nanoimprint lithography and plasma etching. A finite difference time domain (FDTD) model is validated against these results and is used to elucidate the electromagnetic response of the nanopillars. Furthermore, a COMSOL model is used to investigate the angle dependence of the reflectance. In view of display applications, a genetic algorithm is used to optimize the nanopillar geometries for RGB color reflective pixels, showing that nearly all of the sRGB color space and most of the Adobe RGB color space can be covered with this technique.

Enhanced Photoresponse in Metasurface-Integrated Organic Photodetectors.

In this work, we experimentally demonstrate metasurface-enhanced photoresponse in organic photodetectors. We have designed and integrated a metasurface with broadband functionality into an organic photodetector, with the goal of significantly increasing the absorption of light and generated photocurrent from 560 up to 690 nm. We discuss how the metasurface can be integrated with the fabrication of an organic photodiode. Our results show large gains in responsivity from 1.5× to 2× between 560 and 690 nm.

Molecular dynamics modeling framework for overcoming nanoshape retention limits of imprint lithography.

Complex nanoshaped structures (nanoshape structures here are defined as shapes enabled by sharp corners with radius of curvature <5 nm) have been shown to enable emerging nanoscale applications in energy, electronics, optics, and medicine. This nanoshaped fabrication at high throughput is well beyond the capabilities of advanced optical lithography. While the highest-resolution e-beam processes (Gaussian beam tools with non-chemically amplified resists) can achieve <5 nm resolution, this is only available at very low throughputs. Large-area e-beam processes, needed for photomasks and imprint templates, are limited to ~18 nm half-pitch lines and spaces and ~20 nm half-pitch hole patterns. Using nanoimprint lithography, we have previously demonstrated the ability to fabricate precise diamond-like nanoshapes with ~3 nm radius corners over large areas. An exemplary shaped silicon nanowire ultracapacitor device was fabricated with these nanoshaped structures, wherein the half-pitch was 100 nm. The device significantly exceeded standard nanowire capacitor performance (by 90%) due to relative increase in surface area per unit projected area, enabled by the nanoshape. Going beyond the previous work, in this paper we explore the scaling of these nanoshaped structures to 10 nm half-pitch and below. At these scales a new "shape retention" resolution limit is observed due to polymer relaxation in imprint resists, which cannot be predicted with a linear elastic continuum model. An all-atom molecular dynamics model of the nanoshape structure was developed here to study this shape retention phenomenon and accurately predict the polymer relaxation. The atomistic framework is an essential modeling and design tool to extend the capability of imprint lithography to sub-10 nm nanoshapes. This framework has been used here to propose process refinements that maximize shape retention, and design template assist features (design for nanoshape retention) to achieve targeted nanoshapes.

Nanoimprint lithography steppers for volume fabrication of leading-edge semiconductor integrated circuits.

This article discusses the transition of a form of nanoimprint lithography technology, known as Jet and Flash Imprint Lithography (J-FIL), from research to a commercial fabrication infrastructure for leading-edge semiconductor integrated circuits (ICs). Leading-edge semiconductor lithography has some of the most aggressive technology requirements, and has been a key driver in the 50-year history of semiconductor scaling. Introducing a new, disruptive capability into this arena is therefore a case study in a "high-risk-high-reward" opportunity. This article first discusses relevant literature in nanopatterning including advanced lithography options that have been explored by the IC fabrication industry, novel research ideas being explored, and literature in nanoimprint lithography. The article then focuses on the J-FIL process, and the interdisciplinary nature of risk, involving nanoscale precision systems, mechanics, materials, material delivery systems, contamination control, and process engineering. Next, the article discusses the strategic decisions that were made in the early phases of the project including: (i) choosing a step and repeat process approach; (ii) identifying the first target IC market for J-FIL; (iii) defining the product scope and the appropriate collaborations to share the risk-reward landscape; and (iv) properly leveraging existing infrastructure, including minimizing disruption to the widely accepted practices in photolithography. Finally, the paper discusses the commercial J-FIL stepper system and associated infrastructure, and the resulting advances in the key lithographic process metrics such as critical dimension control, overlay, throughput, process defects, and electrical yield over the past 5 years. This article concludes with the current state of the art in J-FIL technology for IC fabrication, including description of the high volume manufacturing stepper tools created for advanced memory manufacturing.

Unique size and shape-dependent uptake behaviors of non-spherical nanoparticles by endothelial cells due to a shearing flow.

The size and shape of nanoparticle (NP) drug carriers can potentially be manipulated to increase the drug delivery efficacy because of their effects on particle margination and interactions with various cells in vivo. It is found in this work that the presence of a physiologically relevant shearing flow rate results in very different size and shape-dependent uptake behavior of negatively charged, non-spherical polyethylene glycol (PEG) hydrogel NPs by endothelial cells (ECs) cultured in a microchannel compared to uptake of either identical NPs in static culture or spherical particles in a shear flow. In particular, larger rod- and disk-shaped PEG NPs show more uptake than smaller ones, opposite to the size effect observed for spherical particles in a flow. Moreover, the trend observed in this dynamic uptake experiment also differs from that reported for uptake of similar PEG NPs by ECs in a static culture, where the smaller disks were found to be uptaken the most. These differences suggest that the increasing rotational and tumbling motions of larger-size non-spherical NPs in the flow play a dominant role in NP margination and cell interaction, compared to Brownian motion, gravity, and cell membrane deformation energy. These findings suggest that the coupling between NP geometry and shear flow is an important factor that needs to be accounted for in the design of the size and shape of nanocarriers.

Competing effects of social balance and influence.

We study a three-state (leftist, rightist, centrist) model that couples the dynamics of social balance with an external deradicalizing field. The mean-field analysis shows that there exists a critical value of the external field p_{c} such that for a weak external field (pp_{c}), there is only one (stable) fixed point, which corresponds to an all-centrist consensus state (absorbing state). In the weak-field regime, the convergence time to the absorbing state is evaluated using the quasistationary distribution and is found to be in agreement with the results obtained by numerical simulations.

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms.

Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, mammalian epithelial and immune cells preferentially internalize disc-shaped, negatively charged hydrophilic nanoparticles of high aspect ratios compared with nanorods and lower aspect-ratio nanodiscs. Endothelial cells also prefer nanodiscs, however those of intermediate aspect ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and nanorods are internalized more efficiently than their smallest counterparts. Kinetics, efficiency, and mechanisms of uptake are all shape-dependent and cell type-specific. Although macropinocytosis is used by both epithelial and endothelial cells, epithelial cells uniquely internalize these nanoparticles using the caveolae-mediated pathway. Human umbilical vein endothelial cells, on the other hand, use clathrin-mediated uptake for all shapes and show significantly higher uptake efficiency compared with epithelial cells. Using results from both upright and inverted cultures, we propose that nanoparticle internalization is a complex manifestation of three shape- and size-dependent parameters: particle surface-to-cell membrane contact area, i.e., particle-cell adhesion, strain energy for membrane deformation, and sedimentation or local particle concentration at the cell membrane. These studies provide a fundamental understanding on how nanoparticle uptake in different mammalian cells is influenced by the nanoscale geometry and is critical for designing improved nanocarriers and predicting nanomaterial toxicity.

Threshold-limited spreading in social networks with multiple initiators.

A classical model for social-influence-driven opinion change is the threshold model. Here we study cascades of opinion change driven by threshold model dynamics in the case where multiple initiators trigger the cascade, and where all nodes possess the same adoption threshold ϕ. Specifically, using empirical and stylized models of social networks, we study cascade size as a function of the initiator fraction p. We find that even for arbitrarily high value of ϕ, there exists a critical initiator fraction pc(ϕ) beyond which the cascade becomes global. Network structure, in particular clustering, plays a significant role in this scenario. Similarly to the case of single-node or single-clique initiators studied previously, we observe that community structure within the network facilitates opinion spread to a larger extent than a homogeneous random network. Finally, we study the efficacy of different initiator selection strategies on the size of the cascade and the cascade window.

A multicenter, U.S. experience of single-balloon, double-balloon, and rotational overtube-assisted enteroscopy ERCP in patients with surgically altered pancreaticobiliary anatomy (with video).

BACKGROUND: Data on overtube-assisted enteroscopy to facilitate ERCP in patients with surgically altered pancreaticobiliary anatomy, or long-limb surgical bypass, is limited. OBJECTIVE: To evaluate and compare ERCP success by using single-balloon (SBE), double-balloon (DBE), or rotational overtube enteroscopy. DESIGN: Consecutive patients identified retrospectively. SETTING: Eight U.S. referral centers. PATIENTS: Long-limb surgical bypass patients with suspected pancreaticobiliary diseases. INTERVENTION: Overtube-assisted enteroscopy ERCP. MAIN OUTCOME MEASUREMENTS: Enteroscopy success: visualizing the pancreaticobiliary-enteric anastomosis or papilla. ERCP success: completing the intended pancreaticobiliary intervention. Clinical success: greater than 50% reduction in abdominal pain or level of hepatic enzyme elevations or resolution of jaundice. RESULTS: From January 2008 through October 2009, 129 patients had 180 enteroscopy-ERCPs. Anatomy was Roux-en-Y: gastric bypass (n = 63), hepaticojejunostomy (n = 45), postgastrectomy (n = 6), Whipple procedure (n = 10), and other (n = 5). ERCP success was 81 of 129 (63%). Enteroscopy success: 92 of 129 (71%), of whom 81 of 92 (88%) achieved ERCP success. Reasons for ERCP failure (n = 48): afferent limb entered but pancreaticobiliary anastomosis and/or papilla not reached (n = 23), cannulation failure (n = 11), afferent limb angulation (n = 8), and jejunojejunostomy not identified (n = 6). Select interventions: anastomotic stricturoplasty (cautery ± dilation, n = 16), stone removal (n = 21), stent (n = 25), and direct cholangioscopy (n = 11). ERCP success rates were similar between Roux-en-Y gastric bypass and other long-limb surgical bypass and among SBE, DBE, and rotational overtube enteroscopy. Complications were 16 of 129, 12.4%. LIMITATIONS: Retrospective study. CONCLUSION: (1) ERCP is successful in nearly two-thirds of long-limb surgical bypass patients and in 88% when the papilla or pancreaticobiliary-enteric anastomosis is reached. (2) Enteroscopy success in long-limb surgical bypass is similar among SBE, DBE, and rotational overtube enteroscopy methods. (3) Referral of long-limb surgical bypass patients who require ERCP to high-volume institutions may be considered before more invasive percutaneous or surgical alternatives.

Enhanced photocurrent in thin-film amorphous silicon solar cells via shape controlled three-dimensional nanostructures.

In this paper, we have explored manufacturable approaches to sub-wavelength controlled three-dimensional (3D) nano-patterns with the goal of significantly enhancing the photocurrent in amorphous silicon solar cells. Here we demonstrate efficiency enhancement of about 50% over typical flat a-Si thin-film solar cells, and report an enhancement of 20% in optical absorption over Asahi textured glass by fabricating sub-wavelength nano-patterned a-Si on glass substrates. External quantum efficiency showed superior results for the 3D nano-patterned thin-film solar cells due to enhancement of broadband optical absorption. The results further indicate that this enhanced light trapping is achieved with minimal parasitic absorption losses in the deposited transparent conductive oxide for the nano-patterned substrate thin-film amorphous silicon solar cell configuration. Optical simulations are in good agreement with experimental results, and also show a significant enhancement in optical absorption, quantum efficiency and photocurrent.

Use of prednisolone to aid propagation of Toxoplasma gondii in mice.

AIM: To determine the usefulness of prednisolone in increasing the number of Toxoplasma (T.) gondii tachyzoites and bradyzoites in mice. MATERIALS AND METHODS: The mice were water-fasted prior to being immunosuppressed with oral inoculation of prednisolone. Tachyzoites of 7T gondii RH strain were inoculated into mice and the number of the parasites in the intraperitoneal fluids was then determined at 96 hs post-infection. In addition, tachyzoites of T. gondii ME49 strains were orally introduced into mice and the number of brain cysts formed was observed by microscopic observation at 45 days post-infection. RESULTS: T. gondii propagation was found to be significantly improved by introduction of the prednisolone (p = 0.0004); and the number of parasite showed positive correlation with the increment in dosage of prednisolone (r = 0.9051). CONCLUSIONS: The use of prednisolone greatly improved the number of parasite formed in mice: both tachyzoite and cyst forms.

Accelerating consensus on coevolving networks: the effect of committed individuals.

Social networks are not static but, rather, constantly evolve in time. One of the elements thought to drive the evolution of social network structure is homophily-the need for individuals to connect with others who are similar to them. In this paper, we study how the spread of a new opinion, idea, or behavior on such a homophily-driven social network is affected by the changing network structure. In particular, using simulations, we study a variant of the Axelrod model on a network with a homophily-driven rewiring rule imposed. First, we find that the presence of rewiring within the network, in general, impedes the reaching of consensus in opinion, as the time to reach consensus diverges exponentially with network size N. We then investigate whether the introduction of committed individuals who are rigid in their opinion on a particular issue can speed up the convergence to consensus on that issue. We demonstrate that as committed agents are added, beyond a critical value of the committed fraction, the consensus time growth becomes logarithmic in network size N. Furthermore, we show that slight changes in the interaction rule can produce strikingly different results in the scaling behavior of consensus time, T(c). However, the benefit gained by introducing committed agents is qualitatively preserved across all the interaction rules we consider.

Scalable imprinting of shape-specific polymeric nanocarriers using a release layer of switchable water solubility.

There is increasing interest in fabricating shape-specific polymeric nano- and microparticles for efficient delivery of drugs and imaging agents. The size and shape of these particles could significantly influence their transport properties and play an important role in in vivo biodistribution, targeting, and cellular uptake. Nanoimprint lithography methods, such as jet-and-flash imprint lithography (J-FIL), provide versatile top-down processes to fabricate shape-specific, biocompatible nanoscale hydrogels that can deliver therapeutic and diagnostic molecules in response to disease-specific cues. However, the key challenges in top-down fabrication of such nanocarriers are scalable imprinting with biological and biocompatible materials, ease of particle-surface modification using both aqueous and organic chemistry as well as simple yet biocompatible harvesting. Here we report that a biopolymer-based sacrificial release layer in combination with improved nanocarrier-material formulation can address these challenges. The sacrificial layer improves scalability and ease of imprint-surface modification due to its switchable solubility through simple ion exchange between monovalent and divalent cations. This process enables large-scale bionanoimprinting and efficient, one-step harvesting of hydrogel nanoparticles in both water- and organic-based imprint solutions.