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Supersaturation mediated large area growth of hexagonal boron nitride (h-BN) for graphene electronics.

Networks and systems which exhibit brain-like behavior can analyze information from intrinsically noisy and unstructured data with very low power consumption. Such characteristics arise due to the critical nature and complex interconnectivity of the brain and its neuronal network. We demonstrate that a system comprising of multilayer hexagonal Boron Nitride (hBN) films contacted with Silver (Ag), that can uniquely host two different self-assembled networks, which are self-organized at criticality (SOC). This system shows bipolar resistive switching between high resistance (HRS) and low resistance states (LRS). In the HRS, Ag clusters (nodes) intercalate in the van der Waals gaps of hBN forming a network of tunnel junctions, whereas the LRS contains a network of Ag filaments. The temporal avalanche dynamics in both these states exhibit power-law scaling, long-range temporal correlation, and SOC. These networks can be tuned from one to another with voltage as a control parameter. For the first time, different neuron-like networks are realized in a single CMOS compatible, 2D materials platform.

Diesel contamination of soil due to oil spills, disposal of refinery waste, oil exploration constitutes a major environmental problem. This paper reports the remediation of diesel contaminated clay soil using Zn/Fe

Despite being widely investigated for their memristive behavior, ferroelectrics are barely studied as channel materials in field-effect transistor (FET) configurations. In this work, we use multilayer α-In2Se3 to realize a ferroelectric channel semiconductor FET, i.e., FeS-FET, whose gate-triggered and polarization-induced resistive switching is then exploited to mimic an artificial synapse. The FeS-FET exhibits key signatures of a synapse such as excitatory and inhibitory postsynaptic current, potentiation/depression, and paired pulsed facilitation. Multiple stable conductance states obtained by tuning the device are then used as synaptic weights to demonstrate pattern recognition by invoking a hidden layer perceptron model. Detailed artificial neural network (ANN) simulations are performed on binary scale MNIST data digits, invoking 784 input (28 × 28 pixels) and 10 output neurons which are used in the training of 42 000 MNIST data digits. By updating the synaptic weights with conductance weight values on 18 000 digits, we achieved a successful recognition rate of 93% on the testing data. Introduction of 0.10 variance of noise pixels results in an accuracy of more than 70% showing the strong fault-tolerant nature of the conductance states. These synaptic functionalities, learning rules, and device to system-level simulation results based on α-In2Se3 could facilitate the development of more complex neuromorphic hardware systems based on FeS-FETs.

A 2D/0D heteronanostructure (HNS) employing WSe2 as 2D nanosheets and Fe3O4 as 0D nanoparticles has been facilely synthesized at room temperature using a simple wet chemical route. The process invo...

Despite being widely investigated for their memristive behavior, ferroelectrics are barely studied as channel materials in field-effect transistor (FET) configurations. In this work, we use multilayer α-In

F- and Cl-doped (10 at%) TiO2 powders were prepared by a sol-gel route and calcined at different temperatures and for different times. X-ray diffraction, thermogravimetric- and differential-thermal analysis showed that doping suppressed both the amorphous to anatase transformation and the anatase to rutile transformation and refines the particle size. F was found to be more effective than Cl. Preliminary hemolysis and cytotoxicity testing demonstrated that F- and Cl-doped anatase powders were more hemolytic and toxic than the undoped anatase powder; however, the doped rutile powders were less hemolytic and toxic than the undoped rutile powder. The lattice strain (calculated from Rietveld analysis) was less for the doped rutile powders, which could explain their enhanced biocompatibility. X-ray photoelectron spectroscopy revealed the presence of Ti3+ in F-doped anatase powder. Ti3+ ions create reactive oxygen species and made the doped anatase sample less biocompatible. X-ray photoelectron spectroscopy revealed that when these doped samples were calcined at 400 °C or higher temperature, the doping ions disappeared from the material. Absence of the dopants may generate a significant defect per unit volume in anatase and influence the anatase to rutile nucleation density and particle size. Presumably, these higher-energy defects present in the doped powders acted as new nucleation sites, and higher temperature and/or a longer transformation time provided the ions with greater mobility to rearrange themselves. With a longer conversion time for the doped powders, the new rutile phase had less strain and greater thermodynamic stability.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To critically appraise the safety data of immunotherapy by identifying rates of toxicities focusing on neurologic adverse events. To compare the survival outcomes of immunotherapy including progression free survival, overall survival, and clinical response rate. To appraise evidence‐based treatments for intracranial metastatic melanoma.

Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet. Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS). Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%). At baseline, 88% of patients had a performance status (PS) of 0-1 and 20% had brain metastases. Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma. Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%). At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively. The 2-year OS was significantly lower for patients with poorer PS (Pandlt;0.0001), low albumin concentrations (Pandlt;0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (Pandlt;0.0001) at baseline. These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.

499 Background: Regorafenib was the first treatment to demonstrate a survival benefit in patients with HCC after progression on sorafenib. The RESORCE trial found that regorafenib improved overall survival with acceptable toxicity, in patients with disease progression on sorafenib who tolerated ≥400mg sorafenib daily and had Child-Pugh A liver function. Methods: We performed a multicentre, retrospective, observational study of patients with HCC receiving regorafenib in the UK, following its availability in April 2018. Results: Data on a total of 104 patients were included from April 2018–August 2019, and 80.8% were male. Age was collected in 85 patients, with a median of 68 years (range 22–86). 23.5% had NAFLD, 21.2% had ALD, 12.9% had HBV, and 3.5% had HCV. Prior management included sorafenib (100%), TACE (30.8%), resection (12.9%). Duration of sorafenib treatment was evaluable in 99/104 patients, and reported a median of 8.7 months (range 1.8–76.6). Duration of regorafenib treatment was evaluable in 92/104 patients, and reported a median of 3.9 months (range 0.0–15.7). Following treatment with regorafenib, 6 patients (5.8%) achieved partial response, 37 (35.6%) achieved stable disease and 45 (43.3%) had progressive disease as the best response. 15 (14.4%) were not assessed and 1 (1.1%) had mixed response. Survival data is immature with 62/101 (61.4%) patients alive at the time of census with median survival currently 6.5 months. Fatigue was the most frequent AE, with 69/88 patients (85.2%) for all grades. 12/88 patients (14.8%) had Grade 3 fatigue. Other significant AEs include hand-foot syndrome (6/85 patients [7.3%] had Grade 3) and diarrhoea (4/83 patients [4.9%] had Grade 3). Conclusions: The population in our real-world experience of regorafenib for HCC had a similar duration of prior sorafenib to those in the RESORCE trial. However, there was different balance of aetiologies with a lower proportion of patients with HBV and HCV. The rate of partial response is similar to the RESORCE trial with fewer patients achieving stable disease. The incidence of fatigue was higher, but the incidence of hand-foot syndrome and diarrhoea were lower. Further expansion and follow-up of this population is warranted.

This trial tested a dendritic cell (DC) therapeutic cancer vaccine in which antigen is loaded using a novel non-viral transfection method enabling the uptake of plasmid DNA condensed with a cationic peptide. Proof of principle required the demonstration of diverse T lymphocyte responses following vaccination, including multiple reactivities restricted through both major histocompatibility complex (MHC) class I and II. Patients with advanced melanoma were offered four cycles of vaccination with autologous DC expressing melan A and gp100. Disease response was measured using Response Evaluation Criteria in Solid Tumours. Circulating MHC class I- and II-restricted responses were measured against peptide and whole antigen targets using interferon-γ ELIspot and enzyme-linked immunosorbent assay assays, respectively. Responses were analyzed across the trial population and presented descriptively for some individuals. Twenty-five patients received at least one cycle. Vaccination was well tolerated. Three patients had reduction in disease volume. Across the trial population, vaccination resulted in an expansion of effector responses to both antigens, to the human leukocyte antigen A2-restricted modified epitope, melan A ELAGIGILTV, and to a panel of MHC class I- and II-restricted epitopes. Vaccination with mature DC non-virally transfected with DNA encoding antigen had biological effect causing tumour regression and inducing diverse T lymphocyte responses.

Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short-duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment.

BACKGROUND: The natural history of Epstein-Barr virus (EBV) infection is poorly defined. We report the prevalence and subsequent incidence of EBV infection in a cohort of sexually active young women and explore the social and sexual determinants of incident infections.METHODS: The study population was drawn from a cohort of young women, who were recruited for a longitudinal study of risk factors for early cervical neoplasia. A case-control analysis, nested within the cohort of 45 women for whom the first EBV sample tested was EBV-negative and who had further follow-up, was undertaken. EBV serostatus was determined in serum with a synthetic peptide-based enzyme-linked immunosorbent assay; EBV DNA was measured in cervical smears with the use of quantitative polymerase chain reaction.RESULTS: Of 1023 women 15-19 years of age included in this analysis, 978 (95.6%) tested positive for antibodies to EBV in their first serum sample. Of 45 women who tested negative, 22 subsequently acquired an asymptomatic EBV infection; the median time to seroconversion was 25 months (range, 1-60 months), and the median age at seroconversion was 18 years (range, 16-21 years). The risk of seroconversion increased with increasing number of sexual partners [compared with 1 partner, odds ratio (OR) was 1.28 for 2 partners and 2.23 for 3 or more; chiTREND 5.02; df 1; P < 0.05] and was greatest when a new sexual partner had been acquired in the 2 years before seroconversion (OR 4.78; chi 4.62; df 1; P < 0.05). EBV DNA was detected in 9 of 14 women who seroconverted and who also provided cervical samples.CONCLUSIONS: In susceptible young women, the acquisition of EBV infection is associated with their sexual behavior.

Dendritic cells (DC) are positioned between adaptive and innate immune systems: integrating microbial, tissue damage and inflammatory signals and activating antigen-specific effectors. In extensive in vitro, in vivo and clinical experiments there is a clear signal that use of ex vivo manipulated DC vaccines (DCV) targeting tumour-associated antigens can overcome tolerance and induce immune responses and tumor regression. None the less, DCV have yet to prove an effective cancer treatment modality and most trials have been small and uncontrolled. Antigen can be loaded as exogenous cells, debris, protein or peptides and by endogenous production through genetic modification. Introduction of nucleic acid encoding antigen by RNA electroporation or viral transduction can result in presentation of diverse epitopes restricted through both MHC Class I and II to cytotoxic and helper T cells respectively. DC integrate signals resulting in their maturation: switching from antigen acquisition to enhanced processing and presentation, increasing and polarisating cytokine release, up-regulating cell-surface costimulatory and adhesive molecules and acquisition of a migratory phenotype. Conventionally, DCV have been matured using a cytokine cocktail with prostaglandin (PG) E2, whereas greater exploitation of signaling pathways evolved to detect microbial signatures, tissue damage and signaling from immune effectors can enhance their immunogenicity. The potential of DCV as cancer therapeutics is likely to be realized through a renewed understanding of DC biology resulting in re-engineering of next generation products. These should be better characterized, standardized and tested in more informative trials, designed to rationally select the better DCV preparations for further investigation. Such DCV will need testing in combination with other approaches such as cytokine therapy and chemotherapy.

e16046Background: More than 95% of patients diagnosed with advanced seminoma are cured with chemotherapy - either 3 cycles of bleomycin (B), etoposide (E) and cisplatin (P) or 4 cycles of E-P. Radiotherapy can also be used for low-volume (Stage IIA-B) metastatic disease but may be associated with a higher risk of secondary malignancy. There is increasing emphasis on minimising late treatment toxicity in chemo-curable cancers. The optimal regimen to achieve long-term survival with minimal toxicity in advanced seminoma remains uncertain, in particular the value of bleomycin. Methods: Patients with advanced (Stage IIA and above) pure seminoma treated with etoposide 120mg/m2 days 1,2 and 3 and cisplatin 50mg/m2 day 1 and 2 (EP120) every 3 weeks for 3 cycles between the years 2000 and 2015 were retrospectively identified. Demographics, stage, clinical response, time of relapse, subsequent treatments and overall survival were recorded. Results: 117 patients were identified with a median age of 41years, and 15% ...