Multifunctional elastomeric composites based on 3D graphene porous materials.

3D graphene porous materials (3GPM), which have low density, large porosity, excellent compressibility, high conductivity, hold huge promise for a wide range of applications. Nevertheless, most 3GPM have brittle and weak network structures, which limits their widespread use. Therefore, the preparation of a robust and elastic graphene porous network is critical for the functionalization of 3GPM. Herein, the recent research of 3GPM with excellent mechanical properties are summarized and the focus is on the effect factors that affect the mechanical properties of 3GPM. Moreover, the applications of elastic 3GPM in various fields, such as adsorption, energy storage, solar steam generation, sensors, flexible electronics, and electromagnetic wave shielding are comprehensively reviewed. At last, the new challenges and perspective for fabrication and functionalization of robust and elastic 3GPM are outlined. It is expected that the perspective will inspire more new ideas in preparation and functionalization of 3GPM.

Gradient Graphene Spiral Sponges for Efficient Solar Evaporation and Zero Liquid Discharge Desalination with Directional Salt Crystallization.

Solar desalination is a promising strategy to utilize solar energy to purify saline water. However, the accumulation of salt on the solar evaporator surface severely reduces light absorption and evaporation performance. Herein, a simple and eco-friendly method to fabricate a 3D gradient graphene spiral sponge (GGS sponge) is presented that enables high-rate solar evaporation and zero liquid discharge (ZLD) desalination of high-salinity brine. The spiral structure of the GGS sponge enhances energy recovery, while the gradient network structures facilitate radial brine transport and directional salt crystallization, which cooperate to endow the sponge with superior solar evaporation (6.5 kg m-2 h-1 for 20 wt.% brine), efficient salt collection (1.5 kg m-2 h-1 for 20 wt.% brine), ZLD desalination, and long-term durability (continuous 144 h in 20 wt.% brine). Moreover, the GGS sponge shows an ultrahigh freshwater production rate of 3.1 kg m-2 h-1 during the outdoor desalination tests. A continuous desalination-irrigation system based on the GGS sponge for crop growth, which has the potential for self-sustainable agriculture in remote areas is demonstrated. This work introduces a novel evaporator design and also provides insight into the structural principles for designing next-generation solar desalination devices that are salt-tolerant and highly efficient.

PDI-Based Organic Small Molecule Regulated by Inter/Intramolecular Interactions for Efficient Solar Vapor Generation.

Organic small molecules with processing feasibility, structural diversity, and fine-tuned properties have the potential applications in solar vapor generation. However, the common defects of narrow solar absorption, low photothermal conversion efficiency, and photobleaching result in limited materials available and unsatisfactory evaporation performance. Herein, the perylene diimide (PDI) derivatives are exploited as stable sunlight absorbers for solar vapor generation. Particularly, the N,N'-bis(3,4,5-trimethoxyphenyl)-3,4,9,10-perylenetetracarboxylic diimide (PDI-DTMA) is well-designed with donor-acceptor-donor configuration based on plane rigid PDI core. The efficient photothermal conversion is enabled through strong intermolecular π-π stacking and intramolecular charge transfer, as revealed by experimental demonstration and theoretical calculation. The PDI-DTMA with a narrow band gap of 1.17 eV exhibits expanded absorption spectrum and enhanced nonradiative transition capability. The 3D hybrid hydrogels (PPHs) combining PDI-DTMA and polyvinyl alcohol are constructed. With the synergistic effect of solar-to-heat conversion, thermal localization management, water activation, and unobstructed water transmission of PPHs, the high water evaporation rates can reach 3.61-10.07 kg m-2 h-1 under one sun. The hydrogels also possess great potential in seawater desalination and sewage treatment. Overall, this work provides valuable insights into the design of photothermal organic small molecules and demonstrates their potentials in solar water evaporation.

Superelastic 3D Assembled Clay/Graphene Aerogels for Continuous Solar Desalination and Oil/Organic Solvent Absorption.

Superelastic, arbitrary-shaped, and 3D assembled clay/graphene aerogels (CGAs) are fabricated using commercial foam as sacrificial skeleton. The CGAs possess superelasticity under compressive strain of 95% and compressive stress of 0.09-0.23 MPa. The use of clay as skeletal support significantly reduces the use of graphene by 50%. The hydrophobic CGAs show high solvent absorption capacity of 186-519 times its own weight. Moreover, both the compression and combustion methods can be adopted for reusing the CGAs. In particular, it is demonstrated a design of 3D assembled hydrophilic CGA equipped with salt collection system for continuous solar desalination. Due to energy recovery and brine transport management promoted by this design, the 3D assembled CGA system exhibits an extremely high evaporation rate of 4.11 kg m-2  h-1 and excellent salt-resistant property without salt precipitation even in 20 wt% brine for continuous 36 h illumination (1 kW m-2 ), which is the best reported result from the solar desalination devices. More importantly, salts can be collected conveniently by squeezing and drying the solution out of the salt collection system. The work provides new insights into the design of 3D assembled CGAs and advances their applications in continuous solar desalination and efficient oil/organic solvent adsorption.

Recent Advances in Simple Preparation of 3D Graphene Aerogels Based on 2D Graphene Materials.

Recently, 3D graphene aerogels (3GAs) with high electrical conductivity, excellent mechanical properties, and fast mass and electron transport have attracted increasing attention and shown wide applications (such as flexible electronics devices, sensors, absorbents, catalysis, energy storage devices, solar steam generation devices, and so on). The drying process becomes an important factor limiting the large-scale preparation of 3GAs. Therefore, how to simplify the preparation process plays an important role in the large-scale application of 3GAs. In this study, we summarize the recent progresses of 3GAs by different drying methods and focus on the effect of robust graphene network on the simple preparation of 3GAs. Besides, the design and synthesis strategies of 3GAs with robust graphene network structures have been systematically discussed. Finally, the emerging challenges and prospective for developing simple preparation and functionalization of 3GAs were outlined. It is expected that our study will lay a foundation for large-scale preparation and application of 3GAs and inspire more new ideas in this field.

Safety and immunogenicity of a multidose vial formulation of 13-valent pneumococcal conjugate vaccine administered with routine pediatric vaccines in healthy infants in India: A phase 4, randomized, open-label study.

PURPOSE: This phase 4, randomized, open-label, multicenter study in healthy Indian infants and toddlers evaluated the safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated in a multidose vial (MDV) or single prefilled syringe (PFS). METHODS: Healthy Indian infants (6 weeks of age) were randomized 1:1 to receive either PCV13-MDV or PCV13-PFS concomitant with routine pediatric vaccines. Subjects received a single dose of either PCV13-MDV or PCV13-PFS as a 4-dose schedule (infant series: 1 dose at 6, 10, and 14 weeks of age; toddler dose: 12 months of age). Safety was assessed, including local reactions, systemic events, and adverse events (AEs). Immunogenicity 1 month after both the infant series and toddler dose was measured by concentrations of serotype-specific immunoglobulin G (IgG) antibodies and opsonophagocytic activity titers. RESULTS: Rates and severities of local reactions and systemic events up to 7 days after each dose of either PCV13-MDV or PCV13-PFS were generally similar, with the majority being of mild or moderate severity. PCV13-MDV had a safety profile comparable with PCV13-PFS; both groups experienced a similar frequency of AEs. PCV13-MDV elicited immune responses comparable with those induced by PCV13-PFS. Clear boosting of immune responses after the PCV13-MDV toddler dose was observed; ≥96% of subjects showed serotype-specific IgG concentrations at or above the defined thresholds 1 month after the PCV13-MDV toddler dose. CONCLUSIONS: PCV13-MDV was safe, well tolerated, and immunogenic in healthy Indian infants and toddlers when coadministered with routine pediatric vaccinations. Safety and immunogenicity of PCV13-MDV was comparable with PCV13-PFS. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03548337.

A self-reinforcing strategy enables the intimate interface for anisotropic alginate composite hydrogels.

Natural-derived hydrogels are expected as promising structural biomaterials, but the soft character severely limits their applications. Here, a facile yet effective strategy was developed to fabricate super-strong and tough alginate composite hydrogels via a self-reinforcing method. The strategy was based on the incorporation of alginate materials with distinctive anisotropic features (fibers, fabrics and aerogels) into the precursor solution of congeneric hydrogels, followed by the in situ ionic-crosslinking. Interestingly, triggered by the concentration difference, the cations-Ca2+ in reinforcing phase could diffuse into the interface and simultaneously chelate with alginate chains of both reinforcing phase and hydrogel matrix, acting as self-generating interfacial binders. Contributed by the intimate interface, the load was effectively transferred into the rigid reinforcing phase, and the hydrogels integrated them into a mechanical network. This research offers a new path to design the interface of polysaccharide composites without extra coupling agents.

Graphene aerogels that withstand extreme compressive stress and strain.

Graphene aerogels combining elastic, lightweight, and robust mechanical properties have been explored for a wide variety of applications. However, graphene aerogels are generally subject to brittle mechanical properties and the irreversible damage of network structures during extreme compressions. Thus, the challenge of finding ways to enhance the strength and resilience of graphene aerogels remains. Herein, superelastic and ultralight aerogels are fabricated through a thermal-treatment of 3D ordered graphene aerogels. The treatments at 400-1000 °C eliminate most of the oxygen-containing functional groups and enhance the π-π stacking interactions between graphene sheets, forming a well-ordered structure of graphene sheets in cell walls. The aerogels can withstand a loading of 100 000 N (109 times their own weight) for 60 min and retain their substantial elastic resilience. This loading corresponds to an ultimate compressive stress of approximately 1000 MPa and a strain of 99.8%, and this ultimate stress is 1-2 orders of magnitude higher than the values for other (carbon-based, polymer-based, inorganic-based, and metal-based) porous materials. The superelastic properties can be attributed to the graphite-like ordered structure of cell walls. The successful fabrication of such superelastic materials opens a new avenue to explore their potential applications in pressure sensors, mechanical shock absorbers, soft robots, and deformable electronic devices.

Solvent-induced crystallization behaviors of PLLA ultrathin films investigated by RAIR spectroscopy and AFM measurements.

The crystallization of poly(L-lactide acid) (PLLA) ultrathin films induced by different solvents was investigated using reflection-absorption infrared (RAIR) spectroscopy and atomic force microscopy (AFM). Irregular PLLA dendrite lamellae grew in the flat-on orientation with dichloromethane solvent before being redissolved after longer induction times owing to the strong interaction between the PLLA segments and solvent molecules. Faster formation of PLLA spherulites was induced with acetone than with dichloromethane, and these remained unchanged with increasing induction time because of the polarity difference between the PLLA segments and acetone molecules. PLLA ultrathin films could not be induced to crystallize using chloroform because of the very strong interactions between the chloroform (CHCl3) molecules and PLLA amorphous chains, which caused the CHCl3 solvent molecules to rapidly permeate the PLLA random coils and dissolve the amorphous chains. These phenomena are attributed to solvent-specific competition between solvent-induced crystallization and dissolution effects in PLLA ultrathin films, which ultimately leads to the higher degree of crystallinity obtained with acetone than with dichloromethane.

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.

BACKGROUND: We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection. METHODS: Patients with well-differentiated or dedifferentiated liposarcoma were enrolled at four centres in France. Patients received up to three 28-day neoadjuvant treatment cycles of RG7112 1440 mg/m(2) per day for 10 days. If a patient progressed at any point after the first cycle, the lesion was resected or, if unresectable, an end-of-study biopsy was done. The primary endpoint was to assess markers of RG7112-dependent MDM2 inhibition and P53 pathway activation (P53, P21, MDM2, Ki-67, macrophage inhibitory cytokine-1 [MIC-1], and apoptosis). All analyses were per protocol. This trial is registered with EudraCT, number 2009-015522-10. RESULTS: Between June 3, and Dec 14, 2010, 20 patients were enrolled and completed pretreatment and day 8 biopsies. 18 of 20 patients had TP53 wild-type tumours and two carried missense TP53 mutations. 14 of 17 assessed patients had MDM2 gene amplification. Compared with baseline, P53 and P21 concentrations, assessed by immunohistochemistry, had increased by a median of 4·86 times (IQR 4·38-7·97; p=0·0001) and 3·48 times (2·05-4·09; p=0·0001), respectively, at day 8 (give or take 2 days). At the same timepoint, relative MDM2 mRNA expression had increased by a median of 3·03 times (1·23-4·93; p=0·003) that at baseline. The median change from baseline for Ki-67-positive tumour cells was -5·05% (IQR -12·55 to 0·05; p=0·01). Drug exposure correlated with blood concentrations of MIC-1 (p<0·0001) and haematological toxicity. One patient had a confirmed partial response and 14 had stable disease. All patients experienced at least one adverse event, mostly nausea (14 patients), vomiting (11 patients), asthenia (nine patients), diarrhoea (nine patients), and thrombocytopenia (eight patients). There were 12 serious adverse events in eight patients, the most common of which were neutropenia (six patients) and thrombocytopenia (three patients). DISCUSSION: MDM2 inhibition activates the P53 pathway and decreases cell proliferation in MDM2-amplified liposarcoma. This study suggests that it is feasible to undertake neoadjuvant biopsy-driven biomarker studies in liposarcoma. FUNDING: F Hoffmann-La Roche.

Lamellar orientation and crystallization dynamics of poly (L-lactic acid) thin films investigated by in-situ reflection absorption infrared spectroscopy.

In situ reflection-absorption infrared (RAIR) spectroscopy was used to investigate the molecular orientation and crystallization dynamics of PLLA thin films crystallized at various temperatures. The results show that the annealing temperature has significant effect on the lamellar orientation of PLLA thin films, which is confirmed by atomic force microscopy (AFM) data. It is found that edge-on lamellar crystals of PLLA thin films are mainly formed by cold crystallization at low temperatures (70-90 °C), whereas the flat-on crystals occur when the crystallization temperature reaches to 100 °C. Of particular note, our in situ RAIR data collected during the whole isothermal crystallization process suggests that the orientation of PLLA chain takes place in the early stage of the crystallization process. Moreover, the analysis on the crystallization dynamics of PLLA thin film indicates that the crystal growth dimensional and nucleation modes are also strongly affected by the crystallization temperature.

Bayesian optimal design for phase II screening trials.

Most phase II screening designs available in the literature consider one treatment at a time. Each study is considered in isolation. We propose a more systematic decision-making approach to the phase II screening process. The sequential design allows for more efficiency and greater learning about treatments. The approach incorporates a Bayesian hierarchical model that allows combining information across several related studies in a formal way and improves estimation in small data sets by borrowing strength from other treatments. The design incorporates a utility function that includes sampling costs and possible future payoff. Computer simulations show that this method has high probability of discarding treatments with low success rates and moving treatments with high success rates to phase III trial.

Cost effectiveness of adjuvant interferon in node-positive melanoma.

PURPOSE: To assess the benefits of adjuvant high-dose interferon alfa (HDI) treatment for patients with high-risk melanoma. METHODS: We designed a decision-analytic probabilistic Markov model to simulate the natural history of patients with stage IIIA, IIIB, and IIIC melanoma and evaluate the outcomes with and without HDI treatment. Outcomes were in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probability estimates and costs were derived from primary patient level data, while the efficacy of HDI and associated utilities were determined from published reports. The base-case analysis was a cohort of 50-year-old patients. RESULTS: HDI increased the median life expectancy in patients with stage III melanoma from 3.75 years in the observation cohort to 4.42 years in the HDI cohort. The difference in QALYs ranged from 0.31 years for stage IIIA patients to 0.60 years for stage IIIC patients treated with HDI. HDI was cost effective in patients with stage IIIB and IIIC melanoma, with ICERs of $95,304 and $76,068 per QALY gained, respectively. Using a threshold of $100,000 per QALY gained, HDI was cost effective for all stage III patients younger than 52 years. HDI was not cost effective for patients with stage IIIA disease and for subsets of patients older than 63 years with stage IIIB disease. CONCLUSION: Our model demonstrates that the probability of HDI being cost effective varies substantially by melanoma substage. HDI showed the greatest benefit in terms of QALYs and was most cost effective in patients younger than 60 years with stage IIIC disease.

Ethnic differences among patients with cutaneous melanoma.

BACKGROUND: Melanoma incidence continues to increase in whites, but little is known about melanoma in minority populations. Surveillance, Epidemiology, and End Results (SEER) data were used to examine the incidence, manifestations, and survival in patients with melanoma with respect to race/ethnicity. METHODS: A SEER search (1992-2002) for primary invasive cutaneous melanoma cases identified 48 143 whites, 932 Hispanics, 394 Asian/Pacific islanders, 251 African Americans, and 52 American Indians. Multivariate analyses were performed to evaluate the relationship between race/ethnicity and clinicopathologic factors; associations between race/ethnicity and survival were examined using the Cox proportional hazards model. RESULTS: Based on our cohort of patients, the average annual age-adjusted melanoma incidence per 100 000 persons was 18.4 for whites compared with 2.3, 0.8, 1.6, and 1.0 for Hispanics, African Americans, American Indians, and Asians, respectively. Lower extremity and acral lentiginous melanomas were more common among minorities. Overall 5-year survival was 72.2% to 81.1% for minorities compared with 89.6% for whites. A 1.96- to 3.01-fold greater risk of disease-specific mortality persisted in minorities compared with whites after adjusting for age, sex, and region. In addition, Hispanics (odds ratio [OR], 3.6), African Americans (OR, 4.2), American Indians (OR, 3.4), and Asians (OR, 2.4) were more likely to present with stage IV melanoma than were whites. African Americans had a 1.48-fold higher rate of risk-adjusted, stage-specific mortality compared with whites. CONCLUSIONS: Melanoma is a public health concern for all ethnic populations. Differences in disease stage at presentation contributes to disparities in survival. Understanding melanoma in minority populations may lead to early detection and ultimately save lives.

Population-based assessment of surgical treatment trends for patients with melanoma in the era of sentinel lymph node biopsy.

PURPOSE: The surgical staging of melanoma dramatically changed with the introduction of sentinel lymph node (SLN) biopsy. In this study, Surveillance, Epidemiology, and End Results (SEER) data were examined to determine how surgical treatment is being carried out and whether SLN biopsy is being performed in melanoma patients in conformance with National Comprehensive Cancer Network (NCCN) guidelines. PATIENTS AND METHODS: The SEER database (1998 to 2001) was searched for all patients with invasive melanoma. NCCN guidelines were used to define optimal stage-specific surgical treatment. Treatment trends in patients with stages I to III disease were summarized, and multivariate analyses were performed to identify factors associated with nonadherence with treatment guidelines. RESULTS: A total of 21,867 melanoma patients were identified; 18,499 of these patients met the inclusion criteria. The number of patients diagnosed with stage III melanoma increased by 55.7% over the study period, and this corresponded to a 53% increase in the number of SLN biopsies performed annually. The odds ratios for nonadherence were 2.32, 2.27, and 1.54 for stages IB, II, and III disease, respectively, compared with stage IA melanoma. Multivariate analyses revealed that age more than 65 years, marital status, minority populations, and primary tumor location were associated with nonadherence with guidelines. Treatment patterns among tumor registries also varied significantly. CONCLUSION: Stage migration is evident in the SEER registries in consort with increasing use of SLN biopsy. Although treatment trends are improving, SLN biopsy continues to be underused, particularly in the elderly and minority populations, in patients with truncal and head/neck melanomas, and also in some geographic regions of the United States.

Visual outcomes of silicone oil versus gas tamponade for macular hole surgery.

PURPOSE: To determine the effectiveness of silicone oil versus gas tamponade to treat macular holes. METHODS: A retrospective review of patients who underwent macular hole repair with either silicone oil or gas tamponade. RESULTS: Data collected from 66 eyes from a retina only practice (Retina and Vitreous of Texas) were reviewed to assess visual outcomes of surgery with silicone oil versus 14% C3F8 gas tamponade. 21 eyes were non-randomized to silicone oil tamponade and 45 eyes underwent gas tamponade. The average overall follow-up time was 11.8 months. Stage 2 holes constituted 9% of the holes; stage 3 and 4 made up 75%; recurrent holes were 11%; and 5% were traumatic holes. Of the macular holes not treated previously, 81.3% (13 of 16) were sealed successfully with silicone oil tamponade while 83.7% (36 of 43) of the gas-treated eyes were sealed. The overall primary closure rate was 83.1% (49 of 59). The pre-operative decimal visual acuity was 0.104 (20/192) for the silicone oil group and 0.193 (20/104) for the gas-treated group. The post-operative decimal visual acuity at 1 year was 0.208 (20/96) for the silicone oil group and 0.453 (20/44) for the gas-treated group. The reopening rate for the silicone oil group was 14% (3 of 21) and 9% (4 of 45) for the gas-treated group. The need for cataract surgery post macular hole repair was 36% (4 of 11 phakic patients) for the silicone oil group and 61% (17 of 28 phakic patients) for the gas-treated group. CONCLUSIONS: With short-term follow-up silicone oil tamponade and gas tamponade are both successful in anatomic closure of macular holes. In eyes with macular holes surgically repaired with gas tamponade significant improvements in visual acuity are seen more frequently than eyes treated with silicone oil tamponade. Toxicity of silicone oil to the retinal pigment epithelium and/or photoreceptors may play a role in these results.