Risk factors and topographies for self-injurious behaviour in a sample of adults with intellectual developmental disorders.

BACKGROUND: Self-injurious behaviour (SIB) is a prevalent form of challenging behaviour in people with intellectual developmental disorders (IDD). Existing research has yielded conflicting findings concerning the major risk factors involved, and in addition, SIB shows multiple topographies and presentations. Although presence of autism spectrum disorders (ASD) and severity of intellectual disability (ID) are known risk factors for SIB, there are no studies comparing SIB topographies by severity degrees of ID and ASD. The purpose of the present paper has been to identify risk factors and topographies for SIB in a representative, stratified and randomised sample of adults with IDD. METHOD: This study was conducted on the basis of data collected by the POMONA-ESP project, in a sample of 833 adults with IDD. Data concerning demographic and health information, ASD symptoms, psychopathology and ID, have been analysed to determine the presence of risk factors for SIB among participants and to explore the occurrence and topographies of SIB across different severity levels of ID and ASD symptoms. RESULTS: Self-injurious behaviour prevalence in the sample was 16.2%. Younger age, oral pain, greater severity of ID, presence of dual diagnosis, psychiatric medication intake and higher scores on Childhood Autism Rating Scale were risk factors for SIB among participants, whereas number of areas with functioning limitations, place of residence, diagnosis of epilepsy and sex were not. SIB was more frequent in participants with ASD symptoms regardless of its severity level, and they displayed a higher number of different topographies of SIB. People with profound ID without co-morbid ASD symptoms showed similar results concerning SIB prevalence and topographies. CONCLUSIONS: Knowledge on risk factors and topographies of SIB might play a vital role in the development of prevention strategies and management of SIB in people with IDD. The mere presence of ASD symptoms, regardless of its severity level, can be a crucial factor to be taken into account in assessing SIB. Accordingly, the presence of SIB in people with ID, especially when presented with a varied number of topographies, might provide guidance on ASD differential diagnosis.

Anak Krakatau triggers volcanic freezer in the upper troposphere.

Volcanic activity occurring in tropical moist atmospheres can promote deep convection and trigger volcanic thunderstorms. These phenomena, however, are rarely observed to last continuously for more than a day and so insights into the dynamics, microphysics and electrification processes are limited. Here we present a multidisciplinary study on an extreme case, where volcanically-triggered deep convection lasted for six days. We show that this unprecedented event was caused and sustained by phreatomagmatic activity at Anak Krakatau volcano, Indonesia during 22-28 December 2018. Our modelling suggests an ice mass flow rate of ~5 × 106 kg/s for the initial explosive eruption associated with a flank collapse. Following the flank collapse, a deep convective cloud column formed over the volcano and acted as a 'volcanic freezer' containing ~3 × 109 kg of ice on average with maxima reaching ~1010 kg. Our satellite analyses reveal that the convective anvil cloud, reaching 16-18 km above sea level, was ice-rich and ash-poor. Cloud-top temperatures hovered around -80 °C and ice particles produced in the anvil were notably small (effective radii ~20 µm). Our analyses indicate that vigorous updrafts (>50 m/s) and prodigious ice production explain the impressive number of lightning flashes (~100,000) recorded near the volcano from 22 to 28 December 2018. Our results, together with the unique dataset we have compiled, show that lightning flash rates were strongly correlated (R = 0.77) with satellite-derived plume heights for this event.

Author Correction: Anak Krakatau triggers volcanic freezer in the upper troposphere.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A microfluidic platform for functional testing of cancer drugs on intact tumor slices.

Present approaches to assess cancer treatments are often inaccurate, costly, and/or cumbersome. Functional testing platforms that use live tumor cells are a promising tool both for drug development and for identifying the optimal therapy for a given patient, i.e. precision oncology. However, current methods that utilize patient-derived cells from dissociated tissue typically lack the microenvironment of the tumor tissue and/or cannot inform on a timescale rapid enough to guide decisions for patient-specific therapy. We have developed a microfluidic platform that allows for multiplexed drug testing of intact tumor slices cultured on a porous membrane. The device is digitally-manufactured in a biocompatible thermoplastic by laser-cutting and solvent bonding. Here we describe the fabrication process in detail, we characterize the fluidic performance of the device, and demonstrate on-device drug-response testing with tumor slices from xenografts and from a patient colorectal tumor.

Multiplexed drug testing of tumor slices using a microfluidic platform.

Current methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly assess the response of patient cancer tissue to drugs or small molecules offer a promising way to improve drug testing, and have the potential to identify the best therapy for individual patients. We developed a digitally manufactured microfluidic platform for multiplexed drug testing of intact cancer slice cultures, and demonstrate the use of this platform to evaluate drug responses in slice cultures from human glioma xenografts and patient tumor biopsies. This approach retains much of the tissue microenvironment and can provide results rapidly enough, within days of surgery, to guide the choice of effective initial therapies. Our results establish a useful preclinical platform for cancer drug testing and development with the potential to improve cancer personalized medicine.

Potential ash impact from Antarctic volcanoes: Insights from Deception Island's most recent eruption.

Ash emitted during explosive volcanic eruptions may disperse over vast areas of the globe posing a threat to human health and infrastructures and causing significant disruption to air traffic. In Antarctica, at least five volcanoes have reported historic activity. However, no attention has been paid to the potential socio-economic and environmental consequences of an ash-forming eruption occurring at high southern latitudes. This work shows how ash from Antarctic volcanoes may pose a higher threat than previously believed. As a case study, we evaluate the potential impacts of ash for a given eruption scenario from Deception Island, one of the most active volcanoes in Antarctica. Numerical simulations using the novel MMB-MONARCH-ASH model demonstrate that volcanic ash emitted from Antarctic volcanoes could potentially encircle the globe, leading to significant consequences for global aviation safety. Results obtained recall the need for performing proper hazard assessment on Antarctic volcanoes, and are crucial for understanding the patterns of ash distribution at high southern latitudes with strong implications for tephrostratigraphy, which is pivotal to synchronize palaeoclimatic records.

Continuous-flow multi-pulse electroporation at low DC voltages by microfluidic flipping of the voltage space topology.

Concerns over biosafety, cost, and carrying capacity of viral vectors have accelerated research into physical techniques for gene delivery such as electroporation and mechanoporation. Advances in microfabrication have made it possible to create high electric fields over microscales, resulting in more efficient DNA delivery and higher cell viability. Continuous-flow microfluidic methods are typically more suitable for cellular therapies where a large number of cells need to be transfected under sterile conditions. However, the existing continuous-flow designs used to generate multiple pulses either require expensive peripherals such as high-voltage (>400 V) sources or function generators, or result in reduced cell viability due to the proximity of the cells to the electrodes. In this paper, we report a continuous-flow microfluidic device whose channel geometry reduces instrumentation demands and minimizes cellular toxicity. Our design can generate multiple pulses of high DC electric field strength using significantly lower voltages (15-60 V) than previous designs. The cells flow along a serpentine channel that repeatedly flips the cells between a cathode and an anode at high throughput. The cells must flow through a constriction each time they pass from an anode to a cathode, exposing them to high electric field strength for short durations of time (the "pulse-width"). A conductive biocompatible poly-aniline hydrogel network formed in situ is used to apply the DC voltage without bringing the metal electrodes close to the cells, further sheltering cells from the already low voltage electrodes. The device was used to electroporate multiple cell lines using electric field strengths between 700 and 800 V/cm with transfection efficiencies superior than previous flow-through designs.

Cellular micropatterns on biocompatible materials.

We present a method to produce micropatterns of cells on tissue culture substrates. A network of deep elastomeric microchannels defining the desired pattern is sealed onto the surface of interest, and a protein template is created by injecting sub-milliliter quantities of protein solution into the microchannels. Protein adsorbs only on the areas that were exposed to the microflow. After the channels are flushed and the elastomer is removed, cells attach only on the protein template. Micropatterns of collagen or fibronectin were used to selectively adhere cells on various biomedical polymers and on heterogeneous or microtextured substrates. Since the bare substrate areas remain apt for seeding other, more adhesive cell types such as fibroblasts, we were able to create micropatterned co-cultures. Our method allows for inexpensive patterning of a rich assortment of biomolecules, cells, and surfaces under physiological conditions.

Stable chemical bonding of porous membranes and poly(dimethylsiloxane) devices for long-term cell culture.

We have investigated the bonding stability of various silane treatments for the integration of track-etched membranes with poly(dimethylsiloxane) (PDMS) microfluidic devices. We compare various treatments using trialkoxysilanes or dipodal silanes to determine the effect of the organofunctional group, cross-link density, reaction solvent, and catalyst on the bond stability. We find that devices made using existing silane methods delaminated after one day when immersed in cell culture medium at 37 °C. In contrast, the dipodal silane, bis[3-(trimethoxysilyl)propyl]amine, is shown to yield stable and functional integration of membranes with PDMS that is suitable for long-term cell culture. To demonstrate application of the technique, we fabricated an open-surface device in which cells cultured on a track-etched membrane can be stimulated at their basal side via embedded microfluidic channels. C2C12 mouse myoblasts were differentiated into myotubes over the course of two weeks on these devices to demonstrate biocompatibility. Finally, devices were imaged during the basal-side delivery of a fluorescent stain to validate the membrane operation and long-term stability of the bonding technique.

Microengineering of cellular interactions.

Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation--and adaptation--of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.

Microfabricated elastomeric stencils for micropatterning cell cultures.

Here we present an inexpensive method to fabricate microscopic cellular cultures, which does not require any surface modification of the substrate prior to cell seeding. The method utilizes a reusable elastomeric stencil (i.e., a membrane containing thru holes) which seals spontaneously against the surface. The stencil is applied to the cell-culture substrate before seeding. During seeding, the stencil prevents the substrate from being exposed to the cell suspension except on the hole areas. After cells are allowed to attach and the stencil is peeled off, cellular islands with a shape similar to the holes remain on the cell-culture substrate. This solvent-free method can be combined with a wide range of substrates (including biocompatible polymers, homogeneous or nonplanar surfaces, microelectronic chips, and gels), biomolecules, and virtually any adherent cell type.

Molding of deep polydimethylsiloxane microstructures for microfluidics and biological applications.

Here we demonstrate the microfabrication of deep (> 25 microns) polymeric microstructures created by replica-molding polydimethylsiloxane (PDMS) from microfabricated Si substrates. The use of PDMS structures in microfluidics and biological applications is discussed. We investigated the feasibility of two methods for the microfabrication of the Si molds: deep plasma etch of silicon-on-insulator (SOI) wafers and photolithographic patterning of a spin-coated photoplastic layer. Although the SOI wafers can be patterned at higher resolution, we found that the inexpensive photoplastic yields similar replication fidelity. The latter is mostly limited by the mechanical stability of the replicated PDMS structures. As an example, we demonstrate the selective delivery of different cell suspensions to specific locations of a tissue culture substrate resulting in micropatterns of attached cells.

Numerical model of fluid flow and oxygen transport in a radial-flow microchannel containing hepatocytes.

The incorporation of monolayers of cultured hepatocytes into an extracorporeal perfusion system has become a promising approach for the development of a temporary bioartificial liver (BAL) support system. In this paper we present a numerical investigation of the oxygen tension, shear stress, and pressure drop in a bioreactor for a BAL composed of plasma-perfused chambers containing monolayers of porcine hepatocytes. The chambers consist of microfabricated parallel disks with center-to-edge radial flow. The oxygen uptake rate (OUR), measured in vitro for porcine hepatocytes, was curve-fitted using Michaelis-Menten kinetics for simulation of the oxygen concentration profile. The effect of different parameters that may influence the oxygen transport inside the chambers, such as the plasma flow rate, the chamber height, the initial oxygen tension in the perfused plasma, the OUR, and K(m) was investigated. We found that both the plasma flow rate and the initial oxygen tension may have an important effect upon oxygen transport. Increasing the flow rate and/or the inlet oxygen tension resulted in improved oxygen transport to cells in the radial-flow microchannels, and allowed significantly greater diameter reactor without oxygen limitation to the hepatocytes. In the range investigated in this paper (10 microns < H < 100 microns), and for a constant plasma flow rate, the chamber height, H, had a negligible effect on the oxygen transport to hepatocytes. On the contrary, it strongly affected the mechanical stress on the cells that is also crucial for the successful design of the BAL reactors. A twofold decrease in chamber height from 50 to 25 microns produced approximately a fivefold increase in maximal shear stress at the inlet of the reactor from 2 to 10 dyn/cm2. Further decrease in chamber height resulted in shear stress values that are physiologically unrealistic. Therefore, the channel height needs to be carefully chosen in a BAL design to avoid deleterious hydrodynamic effects on hepatocytes.