Electroluminescence of atoms in a graphene nanogap.

Here, we report light emission from single atoms bridging a graphene nanogap that emit bright visible light based on fluorescence of ionized atoms. Oxygen atoms in the gap shows a peak emission wavelength of 569 nm with a full width at half maximum (FWHM) of 208 nm. The energy states produced by these ionized oxygen atoms bridging carbon atoms in the gap also produce a large negative differential resistance (NDR) in the transport across the gap with the highest peak-to-valley current ratio (PVR = 45) and highest peak current density (~90 kA/cm2) ever reported in a solid-state tunneling device. While tunneling transport has been previously observed in graphene nanogaps, the bridging of ionized oxygen observed here shows a low excess current, leading to the observed PVR. On the basis of the highly reproducible light emission and NDR from these structures, we demonstrate a 65,536-pixel light-emitting nanogap array.

Improving the Optical Quality of MoSe2 and WS2 Monolayers with Complete h-BN Encapsulation by High-Temperature Annealing.

We improved the optical quality and stability of an exfoliated monolayer (ML) MoSe2 and chemical vapor deposition (CVD)-grown WS2 MLs by encapsulating and sealing them with both top and bottom few-layer h-BN, as tested by subsequent high-temperature annealing up to 873 K and photoluminescence (PL) measurements. These transition-metal dichalcogenide (TMD) MLs remained stable up to this maximum temperature, as seen visually. After the heating/cooling cycle, the integrated photoluminescence (PL) intensity at 300 K in the MoSe2 ML was ∼4 times larger than that before heating and that from exciton and trion PL in the analogous WS2 ML sample was ∼14 times and ∼2.5 times larger at 77 K and the exciton peak was ∼9.5 times larger at 300 K. This is attributed to the reduction of impurities, the lateral expulsion of contamination leading to clean and atomically flat surfaces, and the sealing provided by the h-BN layers that prevents the diffusion of molecules such as trace O2 and H2O to the TMD ML. Stability and optical performance are much improved compared to that in earlier work using top h-BN only, in which the WS2 ML PL intensity decreased even for an optimal gas environment. This complete encapsulation is particularly promising for CVD-grown TMD MLs because they have relatively more charge and other impurities than do exfoliated MLs. These results open a new route for improving the optical properties of TMD MLs and their performance and applications both at room and higher temperatures.

Stabilization of Chemical-Vapor-Deposition-Grown WS2 Monolayers at Elevated Temperature with Hexagonal Boron Nitride Encapsulation.

Chemical vapor deposition (CVD)-grown flakes of high-quality monolayers of WS2 can be stabilized at elevated temperatures by encapsulation with several layer hexagonal boron nitride (h-BN), but to different degrees in the presence of ambient air, flowing N2, and flowing forming gas (95% N2, 5% H2). The best passivation of WS2 at elevated temperature occurs for h-BN-covered samples with flowing N2 (after heating to 873 K), as judged by optical microscopy and photoluminescence (PL) intensity after a heating/cooling cycle. Stability is worse for uncovered samples, but best with flowing forming gas. PL from trions, in addition to that from excitons, is seen for covered WS2 only for forming gas, during cooling below ∼323 K; the trion has an estimated binding energy of ∼28 meV. It might occur because of doping level changes caused by charge defect generation by H2 molecules diffusing between the h-BN and the SiO2/Si substrate. The decomposition of uncovered WS2 flakes in air suggests a dissociation and chemisorption energy barrier of O2 on the WS2 surface of ∼1.6 eV. Fitting the high-temperature PL intensities in air gives a binding energy of a free exciton of ∼229 meV.

MYSTAT: A compact potentiostat/galvanostat for general electrochemistry measurements.

An open-source potentiostat/galvanostat instrument design is introduced that provides the ability to take accurate measurements over a current range of ±200 mA and a potential range of ±12 V. The improved capability of the instrument compared to the previously published design upon which it is based makes it suitable for performing a wider range of electrochemical measurements including the ability to use larger working electrodes, study of high current density processes, study of electrochemistry in nonaqueous solutions and use in high voltage processes such as electrophoretic deposition. The instrument can be controlled from any computer capable of running the Python programming language, including a low-cost Raspberry Pi. Unlike many commercial potentiostat designs, the instrument is completely open-source, giving researchers the ability to modify the hardware and software as needed for custom measurement techniques. The low cost makes the instrument attractive for research and teaching laboratories in which multiple electrochemical measurements need to be carried out in parallel.

Comparative toxicity of five dispersants to coral larvae.

Oil spill responders require information on the absolute and relative toxicities of chemical dispersants to relevant receptor species to assess their use in spill response. However, little toxicity data are available for tropical marine species including reef-building corals. In this study, we experimentally assessed the sub-lethal toxicity of five dispersants to larvae of the coral Acropora millepora over three short exposure periods (2, 6 and 24 h) reflecting real-world spill response scenario durations. Inhibition of larval settlement increased rapidly between 2 and 6 h, and was highest at 24 h: EC50 Corexit EC9500A = 4.0 mg l-1; Ardrox 6120 = 4.0 mg l-1; Slickgone LTSW = 2.6 mg L-1; Slickgone NS = 11.1 mg L-1 and Finasol OSR52 = 3.4 mg L-1. Coral larvae were more sensitive to dispersants than most other coral life stages and marine taxa, but the toxic thresholds (EC10s) exceeded most realistic environmental dispersant concentrations. Estimating toxic threshold values for effects of dispersants on coral should benefit the decision-making of oil spill responders by contributing to the development of species sensitivity distributions (SSDs) for dispersant toxicity, and by informing net environmental benefit assessment (NEBA) for dispersant use.

Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome.

BACKGROUND: The low-FODMAP diet is a frequently used treatment for irritable bowel syndrome (IBS). Most research has focused on short-term FODMAP restriction; however, guidelines recommend that high-FODMAP foods are reintroduced to individual tolerance. This study aimed to assess the long-term effectiveness of the low-FODMAP diet following FODMAP reintroduction in IBS patients. METHODS: Patients with IBS were prospectively recruited to a questionnaire study following completion of dietitian-led low-FODMAP education. At baseline and following FODMAP restriction (short term) only, gastrointestinal symptoms were measured as part of routine clinical care. Following FODMAP reintroduction, (long term), symptoms, dietary intake, acceptability, food-related quality of life (QOL), and healthcare utilization were assessed. Data were reported for patients who continued long-term FODMAP restriction (adapted FODMAP) and/or returned to a habitual diet (habitual). KEY RESULTS: Of 103 patients, satisfactory relief of symptoms was reported in 12% at baseline, 61% at short-term follow-up, and 57% at long-term follow-up. At long-term follow-up, 84 (82%) patients continued an 'adapted FODMAP' diet (total FODMAP intake mean 20.6, SD 14.9 g/d) compared with 19 (18%) of patients following a 'habitual' diet (29.4, SD 22.9 g/d, P=.039). Nutritional adequacy was not compromised for either group. The 'adapted FODMAP' group reported the diet cost significantly more than the 'habitual' group (P<.001) and affected social eating (P<.01) but there was no effect on food-related QOL. Healthcare utilization was similar between both groups. CONCLUSION AND INFERENCES: Low-FODMAP education is effective for long-term IBS management, enables a nutritionally adequate diet, and is broadly acceptable to patients.

Passivating 1T'-MoTe2 multilayers at elevated temperatures by encapsulation.

Several-layer 1T'-MoTe2 decomposes very little during heating up to ∼550 °C under flowing argon when encapsulated by multilayer hBN, as monitored by Raman scattering and optical microscopy, but largely decomposes at much lower temperatures in incompletely covered and uncovered regions. In covered regions there are small amounts of tellurium product above ∼250 °C.

Utilisation of anti-TNF levels in a UK tertiary IBD centre.

OBJECTIVE: To ascertain how anti-tumour necrosis factor (TNF) drug and anti-drug antibody levels testing is used in a 'real-world' setting to optimise inflammatory bowel disease (IBD) treatment. DESIGN: Retrospective cohort study of prospectively collected patient data. SETTING: Tertiary IBD centre in London, UK. PATIENTS: All patients at Guy's and St Thomas' Hospitals on anti-TNF who had levels measured between the start of testing in 2012 and October 2014. INTERVENTIONS: Anti-TNF drug and anti-drug antibody levels as part of routine monitoring. MAIN OUTCOME MEASURES: Indication for measuring levels and changes in management made as a result of the levels. RESULTS: 330 infliximab levels were carried out in 199 patients and 143 adalimumab levels were carried out in 103 patients. Levels were primarily done in those with evidence of loss of response; 37% of infliximab levels and 52% of adalimumab levels. Levels resulted in a change in management in 26% of patients in infliximab group and 25% of patients in adalimumab group; however, this was greater in those with loss of response, 62% and 61% respectively. Anti-drug antibodies were detected in 7% of patients. CONCLUSIONS: Our early experience has demonstrated that measuring anti-TNF drug and anti-drug antibody levels can be useful in the optimisation of IBD management. In an increasing number of patients, particularly those with evidence of loss of response, it allows early decisions to be made regarding changing therapy. It also offers the potential for significant cost-saving by preventing pointless dose escalation in the context of therapeutic levels or when high-level anti-drug antibodies are present.

Infliximab and adalimumab drug levels in Crohn's disease: contrasting associations with disease activity and influencing factors.

BACKGROUND: Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab. AIMS: To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels. METHODS: We performed a cross-sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey-Bradshaw index, C-reactive protein and faecal calprotectin. 6-tioguanine nucleotide (TGN) concentrations were measured in patients treated with thiopurines. RESULTS: A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (P=.081) and biochemical remission (P=.003) and faecal calprotectin normalisation (P<.0001) with corresponding thresholds identified on ROC analysis of 1.5, 3.4 and 5.7 µg/mL. Adalimumab levels were similar between active disease and remission regardless of the endpoint assessed. Modelling identified that higher infliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels. CONCLUSIONS: Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels.

Great Expectations: How Role Expectations and Role Experiences Relate to Perceptions of Group Cohesion.

Many athletes experience a discrepancy between the roles they expect to fulfill and the roles they eventually occupy. Drawing from met expectations theory, we applied response surface methodology to examine how role expectations, in relation to role experiences, influence perceptions of group cohesion among Canadian Interuniversity Sport athletes (N = 153). On the basis of data from two time points, as athletes approached and exceeded their role contribution expectations, they reported higher perceptions of task cohesion. Furthermore, as athletes approached and exceeded their social involvement expectations, they reported higher perceptions of social cohesion. These response surface patterns-pertaining to task and social cohesion-were driven by the positive influence of role experiences. On the basis of the interplay between athletes' role experiences and their perception of the group environment, efforts to improve team dynamics may benefit from focusing on improving the quality of role experiences, in conjunction with developing realistic role expectations.

Forming Nanoparticle Monolayers at Liquid-Air Interfaces by Using Miscible Liquids.

One standard way of forming monolayers (MLs) of nanoparticles (NPs) is to drop-cast a NP dispersion made using one solvent onto a second, immiscible solvent; after this upper solvent evaporates, the NP ML can be transferred to a solid substrate by liftoff. We show that this previously universal use of only immiscible solvent pairs can be relaxed and close-packed, hexagonally ordered NP monolayers can self-assemble at liquid-air interfaces when some miscible solvent pairs are used instead. We demonstrate this by drop-casting an iron oxide NP dispersion in toluene on a dimethyl sulfoxide (DMSO) liquid substrate. The NPs are energetically stable at the DMSO surface and remain there even with solvent mixing. Excess NPs coagulate and precipitate in the DMSO, and this limits NPs at the surface to approximately 1 ML. The ML domains at the surface nucleate independently, which is in contrast to ML growth at the receding edge of the drying drop, as is common in immiscible solvent pair systems and seen here for the toluene/diethylene glycol immiscible solvent pair system. This new use of miscible solvent pairs can enable the formation of MLs for a wider range of NPs.

Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.

BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109 /L) and faecal calprotectin (HR 2.95 for >50 µg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU. CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.

Clinical effectiveness and economic costs of group versus one-to-one education for short-chain fermentable carbohydrate restriction (low FODMAP diet) in the management of irritable bowel syndrome.

BACKGROUND: Restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is an effective dietary treatment for irritable bowel syndrome (IBS). Patient dietary education is essential but labour intensive. Group FODMAP education may alleviate this somewhat but has not previously been investigated. The present study aimed to investigate the clinical effectiveness of low FODMAP group education in patients with IBS and to explore the cost of a group pathway. METHODS: Patients with IBS (n = 364) were assessed for their suitability to attend dietitian-led group education or traditional one-to-one education in a novel group pathway. Clinical effectiveness (global symptom question, symptom prevalence, stool output) were compared at baseline and follow-up using the chi-squared test. The costs of the novel group pathway were assessed using a decision model. RESULTS: The global symptom question indicated more patients were satisfied with their symptoms following dietary advice, in both group education [baseline 48/263 (18%) versus follow-up 142/263 (54%), P < 0.001] and one-to-one education [baseline 5/101 (5%) versus follow-up 61/101 (60%), P < 0.001], with no difference between group and one-to-one education at follow-up (P = 0.271). Overall, there was a significant decrease in symptom severity from baseline to follow-up (P < 0.001 for both groups) but no difference in symptom response between group and one-to-one education. The cost for the group education pathway for all 364 patients was £31 713.36. CONCLUSIONS: The present study shows that dietitian-led FODMAP group education is clinically effective and the costs associated with a FODMAP group pathway are worthy of further consideration for routine clinical care.

Electronic transport in nanoparticle monolayers sandwiched between graphene electrodes.

Graphene/CdSe nanoparticle monolayer/graphene sandwich structures were fabricated to explore the interactions between these layered materials. Electrical transport across these heterostructures suggests that transport is limited by tunneling through the nanoparticle (NP) ligands but not the NP core itself. Photoconductivity suggests ligands may affect the exciton separation efficiency.

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients.

BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

Reassessment of Crohn's disease treated with at least 12†months of anti-TNF therapy: how likely is treatment withdrawal?

OBJECTIVE: To assess methods of disease reassessment and rates of treatment withdrawal in patients with Crohn's disease (CD) treated with biologics and to report retrospective risk stratification for treatment withdrawal as suggested by the STORI trial in the context of this cohort. DESIGN: A retrospective observational cohort study of all patients with CD treated with antitumour necrosis factor (anti-TNF) therapy for >12 months in 2011. SETTING: Tertiary care. PATIENTS: Patients with CD treated with anti-TNF therapy. MAIN OUTCOME MEASURES: Method and outcome of reassessment and whether patient was withdrawn from therapy; also, whether patients met low-risk criteria for withdrawal as identified by the STORI trial, and outcome of those meeting low-risk criteria. RESULTS: 73 patients (infliximab n=48, adalimumab n=25) underwent disease reassessment. Nine patients were deemed to have achieved remission and were withdrawn from treatment: 6 (67%) maintained remission at 12 months, three patients relapsed and were successfully retreated. 52 patients had sufficient data available for STORI criteria to be applied retrospectively. 37% (19/52) fulfilled low-risk criteria for withdrawal-of these, 26% (5/19) were withdrawn from anti-TNF therapy and three had sustained clinical remission at 1 year. Reasons for non-withdrawal included ongoing endoscopic activity (n=8), radiological activity (n=2) and clinical concern due to previous disease behaviour (n=4). CONCLUSIONS: Relatively few patients were deemed in sufficient depth of remission to warrant a trial of withdrawal of anti-TNF therapy. Many patients were not withdrawn, despite meeting STORI low-risk criteria, due to ongoing disease activity highlighting the limitations of applying such criteria in a 'real world' setting.

Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease.

BACKGROUND: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.

Thermoelectric performance of PbSe quantum dot films.

The thermoelectric (TE) performance of films of colloidal lead selenide (PbSe) quantum dots (QDs) with metal-chalcogenide complex ligands is seen to change with QD size and temperature. Films of smaller QDs have higher Seebeck coefficient magnitudes, indicating stronger quantum confinement, and lower electrical and thermal conductivities. The thermoelectric figure of merit ZT is ∼0.5 at room temperature and increases with temperature to 1.0-1.37 at ∼400 K, where it is larger for smaller QD films. This is better than previous results for solution-prepared QD TE materials at these elevated temperatures.