Currently, however, there are relatively few such atomically layered solids. [ 2–5 ] Here, we report on 2D nanosheets, composed of a few Ti 3 C 2 layers and conical scrolls, produced by the room temperature exfoliation of Ti 3 AlC 2 in hydrofl uoric acid. The large elastic moduli predicted by ab initio simulation, and the possibility of varying their surface chemistries (herein they are terminated by hydroxyl and/or fl uorine groups) render these nanosheets attractive as polymer composite fi llers. Theory also predicts that their bandgap can be tuned by varying their surface terminations. The good conductivity and ductility of the treated powders suggest uses in Li-ion batteries, pseudocapacitors, and other electronic applications. Since Ti 3 AlC 2 is a member of a 60 + group of layered ternary carbides and nitrides known as the MAX phases, this discovery opens a door to the synthesis of a large number of other 2D crystals. Arguably the most studied freestanding 2D material is graphene, which was produced by mechanical exfoliation into single-layers in 2004. [ 1 ] Some other layered materials, such as hexagonal BN, [ 2 ] transition metal oxides, and hydroxides, [ 4 ] as well as clays, [ 3 ] have also been exfoliated into 2D sheets. Interestingly, exfoliated MoS 2 single layers were reported as early as in 1986. [ 5 ] Graphene is fi nding its way to applications ranging from supercapacitor electrodes [ 6 ] to reinforcement in composites. [ 7 ] Although graphene has attracted more attention than all other 2D materials combined, its simple chemistry and the weak van der Waals bonding between layers in multilayer structures limit its use. Complex, layered structures that contain more than one element may offer new properties because they

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Two‐Dimensional Nanocrystals Produced by Exfoliation of Ti 3 AlC 2

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge—conventional TACE. Recently, a drug-eluting bead (DC Bead®) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

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Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study

Delirium in the critically ill is reported in 11–80% of patients. We estimated the incidence of delirium using a validated scale in a large cohort of ICU patients and determined the associated risk factors and outcomes. Prospective study in a 16-bed medical-surgical intensive care unit (ICU). 820 consecutive patients admitted to ICU for more than 24 h. Tools used were: the Intensive Care Delirium Screening Checklist for delirium, Richmond Agitation and Sedation Scale for sedation, and Numerical Rating Scale for pain. Risk factors were evaluated with univariate and multivariate analysis, and factors influencing mortality were determined using Cox regression. Delirium occurred in 31.8% of 764 patients. Risk of delirium was independently associated with a history of hypertension (OR 1.88, 95% CI 1.3–2.6), alcoholism (2.03, 1.2–3.2), and severity of illness (1.25, 1.03–1.07 per 5-point increment in APACHE II score) but not with age or corticosteroid use. Sedatives and analgesics increased the risk of delirium when used to induce coma (OR 3.2, 95% CI 1.5–6.8), and not otherwise. Delirium was linked to longer ICU stay (11.5 ± 11.5 vs. 4.4 ± 3.9 days), longer hospital stay (18.2 ± 15.7 vs. 13.2 ± 19.4 days), higher ICU mortality (19.7% vs. 10.3%), and higher hospital mortality (26.7% vs. 21.4%). Delirium is associated with a history of hypertension and alcoholism, higher APACHE II score, and with clinical effects of sedative and analgesic drugs.

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Incidence, risk factors and consequences of ICU delirium.

The MAX phases are a group of layered ternary compounds with the general formula Mn+1AXn (M: early transition metal; A: group A element; X: C and/or N; n = 1–3), which combine some properties of metals, such as good electrical and thermal conductivity, machinability, low hardness, thermal shock resistance and damage tolerance, with those of ceramics, such as high elastic moduli, high temperature strength, and oxidation and corrosion resistance. The publication of papers on the MAX phases has shown an almost exponential increase in the past decade. The existence of further MAX phases has been reported or proposed. In addition to surveying this activity, the synthesis of MAX phases in the forms of bulk, films and powders is reviewed, together with their physical, mechanical and corrosion/oxidation properties. Recent research and development has revealed potential for the practical application of the MAX phases (particularly using the pressureless sintering and physical vapour deposition coating rout...

Progress in research and development on MAX phases: a family of layered ternary compounds

Developing injectable antibacterial and conductive shape memory hemostatic with high blood absorption and fast recovery for irregularly shaped and noncompressible hemorrhage remains a challenge. Here we report injectable antibacterial conductive cryogels based on carbon nanotube (CNT) and glycidyl methacrylate functionalized quaternized chitosan for lethal noncompressible hemorrhage hemostasis and wound healing. These cryogels present robust mechanical strength, rapid blood-triggered shape recovery and absorption speed, and high blood uptake capacity. Moreover, cryogels show better blood-clotting ability, higher blood cell and platelet adhesion and activation than gelatin sponge and gauze. Cryogel with 4 mg/mL CNT (QCSG/CNT4) shows better hemostatic capability than gauze and gelatin hemostatic sponge in mouse-liver injury model and mouse-tail amputation model, and better wound healing performance than Tegaderm™ film. Importantly, QCSG/CNT4 presents excellent hemostatic performance in rabbit liver defect lethal noncompressible hemorrhage model and even better hemostatic ability than Combat Gauze in standardized circular liver bleeding model.

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Injectable antibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemorrhage and wound healing.

DC BeadTM is a FDA cleared embolisation device for the treatment of hypervascular tumours and arteriovenous malformations. This product is currently evaluated in a number of centres in Europe as an embolic device for transarterial chemoembolisation (TACE). The beads consist of poly(vinyl alcohol) microspheres modified with sulfonic acid groups and are available at different size ranges varying from 100 to 900 μm in diameter. The beads were shown to actively sequester doxorubicin hydrochloride (dox) from solution in a time dependent upon the dose of the drug and size of the beads. Drug uptake was by an ion-exchange mechanism, and in the absence of other ions in solution, the beads could load a maximum of around 40 mg dox/mL hydrated beads, with >99% of drug being sequestered from the solution. A loading of 25 mg dox/mL beads was recommended as providing a practical therapeutic dose and optimum handling characteristics. There was a decrease in equilibrium water content of the beads with increasing dox loading, which resulted in a decrease in the average diameter of the beads and an increase in the compressive modulus. The deliverability properties, however, were not affected after drug loading. Using a variety of microscopic methods, the drug was shown to be distributed throughout the bead structure, but concentrated in the outer 20 μm surface layer, a feature related to the method of synthesis. This study characterises the properties of DC Bead loaded with dox with respect to important characteristics in embolisation and demonstrates the potential of this drug device combination for the treatment of hypervascular tumours such as hepatocellular carcinoma.

Doxorubicin eluting beads − 1: Effects of drug loading on bead characteristics and drug distribution

DC Bead is a sulfonate-modified, PVA-based microspherical embolisation agent approved for the treatment of hypervascular tumours and arterio-venous malformations. The beads have previously been shown to actively sequester oppositely charged drugs, such as doxorubicin hydrochloride (dox) by an ion-exchange mechanism. In order to characterise the release kinetics and predict the in vivo behaviour of drug eluting beads (DEB), two elution methods were utilised. The first, an application of the USP dissolution method Type II - Apparatus, enables study of the complete elution of loaded DC Bead in less than 4 h, allowing relatively rapid comparison to be made between different products and formulations. Release data obtained using this method were fitted to first order kinetics (R (2) > 0.998) and the elution constants shown to increase with the total surface area of the beads exposed to the elution medium. Diffusion coefficients were calculated adopting the Fickian diffusion model, which predicted slow elution rates under physiological conditions. The second method involved the use of a T-Apparatus where the drug experiences an element of diffusion through a static environment. This method was developed to resemble the in vivo situation in embolisation procedures more closely. Slow release of dox from DC Bead with half-lives over 1,500 h were predicted for all size ranges using a slow release model. A strong linear relationship was found between the release data from T-Apparatus and pharmacokinetic data obtained from patients treated with DC Bead loaded with dox in transarterial chemoembolisation (TACE) procedures. These data indicated a Level A in vitro-in vivo correlation (IVIVC) for the first 24 h post embolisation. Both systems developed were automated and good reproducibility was obtained for all samples, demonstrating the usefulness of these elution techniques for product development and comparative testing.

Doxorubicin eluting beads - 2: methods for evaluating drug elution and in-vitro:in-vivo correlation

Mesoporous carbide-derived carbon with porosity tuned for efficient adsorption of cytokines

The textural and adsorption characteristics of a series of activated carbons (ACs), porous poly(vinyl alcohol) (PVA) gels, and PVA/AC composites were studied using scanning electron microscopy, mercury porosimetry, adsorption of nitrogen (at 77.4 K), cationic methylene blue (MB), anionic methyl orange (MO), and Congo red (CR) from the aqueous solutions. Dye-PVA-AC-water interactions were modeled using the semiempirical quantum chemical method PM6. The percentage of dye removed (C(rem)) by the ACs was close to 100% at an equilibrium concentration (C(eq)) of less than 0.1 mM but decreased with increasing dye concentration. This decrease was stronger at C(eq) of less than 1 mM, and C(rem) was less than 50% at a C(eq) of 10-20 mM. For PVA and the PVA/AC composite containing C-7, the C(rem) values were minimal (<75%). The free energy distribution functions (f(ΔG)) for dye adsorption include one to three peaks in the -ΔG range of 1-60 kJ/mol, depending on the dye concentration range used and the spatial, charge symmetry of the hydrated dye ions and the structural characteristics of the adsorbents. The f(ΔG) shape is most complex for MO with the most asymmetrical geometry and charge distribution and adsorbed at concentrations over a large C(eq) range. For symmetrical CR ions, adsorbed over a narrow C(eq) range, the f(ΔG) plot includes mainly one narrow peak. MB has a minimal molecular size at a planar geometry (especially important for effective adsorption in slit-shaped pores) which explains its greater adsorptive capacity over that of MO or CR. Dye adsorption was greatest for ACs with the largest surface area but as molecular size increases adsorption depends to a greater extent on the pore size distribution in addition to total and nanopore surface areas and pore volume.

Adsorption of anionic and cationic dyes by activated carbons, PVA hydrogels, and PVA/AC composite.

The porous structure and the state of the water are two main factors which define the vast applications of hydrogels in the life science arena. The structural characterisation and water state in hydrogels produced by the cryogelation of poly(hydroxyethyl methacrylate) and gelatine were undertaken using different techniques. Images obtained using confocal laser scanning and multiphoton microscopies were analysed using ImageJ/Fiji software to estimate the total porosity, specific surface area and pore size and wall thickness distribution functions of each of the hydrogels. The hydration properties and structural characteristics of the nanopore component of the polymer and protein hydrogels were analysed using DSC, 1H NMR spectroscopy and cryoporometry and modelled using the PM6 quantum chemical method. The hydrogels produced by cryogelation were shown to have a large macropore volume, high pore interconnectivity and small specific surface area. The main portion of water was shown to be attributable to bulk water located within macropores. The relative amounts of bound water in the hydrogels were demonstrated to be small (<10 wt% of bulk water) making macroporous hydrogels an attractive system for biological applications. An understanding of the parameters studied here is important for the future engineering of cryogels for biological applications.

Gary Phillips

Papers

Doxorubicin eluting beads − 1: Effects of drug loading on bead characteristics and drug distribution

Doxorubicin eluting beads - 2: methods for evaluating drug elution and in-vitro:in-vivo correlation

Mesoporous carbide-derived carbon with porosity tuned for efficient adsorption of cytokines

Adsorption of anionic and cationic dyes by activated carbons, PVA hydrogels, and PVA/AC composite.

Porous structure and water state in cross-linked polymer and protein cryo-hydrogels