Chemically specifi C multiscale modeling of clay-polymer nanocomposites reveals intercalation dynamics, tactoid self-assembly and emergent materials properties

A quantitative description is presented of the dynamical process of polymer intercalation into clay tactoids and the ensuing aggregation of polymerentangled tactoids into larger structures, obtaining various characteristics of these nanocomposites, including clay-layer spacings, out-of-plane clay-sheet bending energies, X-ray diffractograms, and materials properties. This model of clay-polymer interactions is based on a three-level approach, which uses quantum mechanical and atomistic descriptions to derive a coarse-grained yet chemically specifi c representation that can resolve processes on hitherto inaccessible length and time scales. The approach is applied to study collections of clay mineral tactoids interacting with two synthetic polymers, poly(ethylene glycol) and poly(vinyl alcohol). The controlled behavior of layered materials in a polymer matrix is centrally important for many engineering and manufacturing applications. This approach opens up a route to computing the properties of complex soft materials based on knowledge of their chemical composition, molecular structure, and processing conditions.This work was funded in part by the EU FP7 MAPPER project (grant number RI-261507) and the Qatar National Research Fund (grant number 09–260–1–048). Supercomputing time was provided by PRACE on JUGENE (project PRA044), the Hartree Centre (Daresbury Laboratory) on BlueJoule and BlueWonder via the CGCLAY project, and on HECToR and ARCHER, the UK national supercomputing facility at the University of Edinburgh, via EPSRC through grants EP/F00521/1, EP/E045111/1, EP/I017763/1 and the UK Consortium on Mesoscopic Engineering Sciences (EP/L00030X/1). The authors are grateful to Professor Julian Evans for stimulating discussions during the course of this project. Data-storage and management services were provided by EUDAT (grant number 283304)

Serological and virological characterization of clinically diagnosed cases of measles in suburban Khartoum

Measles continues to be a major childhood disease in terms of global morbidity and mortality. In the main areas of its endemicity the only available means of diagnosis are based on clinical criteria: the presence of a maculopapular rash and fever accompanied by cough, coryza, and/or conjunctivitis. We have studied 38 clinically diagnosed cases of measles in Khartoum, Sudan, by means of serology, reverse transcriptase PCR (RT-PCR) on throat swabs and virus isolation from lymphocytes. On the basis of serology, 28 patients were diagnosed as having an acute measles virus (MV) infection, while in 10 cases the clinical symptoms proved to have other causes. It was shown that in cases with low serum immunoglobulin M (IgM) levels, an additional measurement of IgG or virus-neutralizing antibodies was necessary to discriminate between patients with an acute MV infection sampled during an early stage of the disease and patients who had experienced an MV infection in the more distant past. The serological laboratory diagnosis was validated by an MV-specific RT-PCR: for all confirmed measles cases tested a fragment of the correct size which hybridized with a third MV-specific primer could be amplified, while all serologically negative cases were also RT-PCR negative. MV could be isolated from 17 out of 23 of the serologically confirmed cases, demonstrating that virus isolation is less reliable as a diagnostic tool than serology or RT-PCR. This study stresses the urgent need for a rapid diagnostic field test for measles

Negative Transfer of Training: Simulator Study Into the Effects of Overruled Pilot Decision Making

This report was originally published by the Netherlands Organization for Applied Scientific Research (TNO), Human Performance; Soesterberg, The Netherlands as TNO 2023 R10152In this simulator study, we investigated the potential negative transfer of training that may result from situations where a correct decision made by the trainee is being overruled by the instructor to save training time. We hypothesized that discarding a correct decision in a training situation can introduce confusion when the trainee encounters a similar situation in operational practice. The experiment was performed in a fixed-base simulator of a twin-engine business jet. Two groups of 19 commercial pilots participated in a training session consisting of four training scenarios, immediately followed by a test session with four other test scenarios. Whereas in the \u201ccontrol\u201d group the training scenarios were presented as briefed, the pilots in the experimental, or \u201coverruled\u201d group included some events (e.g., an enhanced ground proximity warning (EGPWS)) which required a response. However, the instructor directed the pilots to refrain from the response. It was expected that pilots in the overruled group were more likely to show delayed response or even ignore alarms in the test scenarios. The objective results showed no significant effect of the training manipulation on the performance of the pilots in the test scenarios involving the same type of events as the overruled group had encountered during the training. However, according to the subjective results, 32% of the participating pilots stated that they had been confused during the test, and that the training influenced their decision making. Within the limits of this study, these findings are an indication of negative transfer of training

Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood

BACKGROUND: The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. METHODS: 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested with ELISA for dengue IgG and IgM. 74 serum pairs were tested again in another laboratory with similar methods, after a mean of 252 days. RESULTS: Cases were classified as no dengue (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue. Significant differences between the two laboratories' results were found leading to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper results correlated poorly to serum values, being more variable and lower with a mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37) for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage of frozen serum and dried filter papers, sealed in nylon bags in an air-conditioned room, had no significant effect on the ELISA results. CONCLUSION: Dengue virus IgG antibodies in serum and filter papers was not affected by duration of storage, but was subject to inter-laboratory variability. Dengue virus IgM antibodies measured in serum reconstituted from blood spots on filter papers were lower than in serum, in particular in the acute phase of disease. Therefore this method limits its value for diagnostic confirmation of individual patients with dengue virus infections. However the detection of dengue virus IgG antibodies eluted from filter paper can be used for sero-prevalence cross sectional studies

Synthesis, crystal structure, and DFT study of two new dinuclear copper(I) complexes bearing Ar-BIAN ligands functionalized with NO2 groups

Two new bis(aryl-imino)-acenaphthene, Ar-BIAN (Ar = 2,4,6-trimethylphenyl = mes) ligands, bearing the NO2 group in the naphthalene moiety of the iminoacenaphthene at para- (5-NO2) and meta- (4-NO2) position, of formulations 1,2-bis(mes-imino)-5-nitroacenaphthene, 1, and 1,2-bis(mes-imino)-4-nitroacenaphthene, 2, were synthesized. Their respective dinuclear iodide bridged copper(I) complexes [Cu2(μ-I)2(mes-BIAN-5-NO2)2], 3 and [Cu2(μ-I)2(mes-BIAN-4-NO2)2], 4, were obtained in good yields by treatment with an equimolar amount of CuI. All compounds were characterized by elemental analysis, single-crystal X-ray diffraction, 1H-NMR, 13C-NMR, FTIR, UV/Vis spectroscopy. DFT calculations helped to understand the different molecular structure observed in the crystals of 3 and 4 and the determining role of packing forces. TDDFT revealed that the absorption bands in the visible were essentially MLCT (Metal to Ligand Charge Transfer), with some n→π* character (intra ligand). The shift to the red compared to the spectrum of the Cu(I) complex analogue without the NO2 group, [Cu2(μ-I)2](mes-BIAN)2], 6, could be explained by the stabilization of the ligand unoccupied π* orbitals in the presence of NO2.info:eu-repo/semantics/publishedVersio

Health-related quality of life after prophylactic cranial irradiation for stage III non-small cell lung cancer patients:Results from the NVALT-11/DLCRG-02 phase III study

BACKGROUND AND PURPOSE: The NVALT-11/DLCRG-02 phase III trial (clinicaltrials.gov identifier: NCT01282437) showed that, after standard curative intent treatment, prophylactic cranial irradiation (PCI) decreased the incidence of symptomatic brain metastases (BM) in stage III non-small cell lung cancer (NSCLC) patients compared to observation. In this study we assessed the impact of PCI on health-related quality of life (HRQoL). In addition, an exploratory analysis was performed to assess the impact of neurocognitive symptoms and symptomatic BM on HRQoL. MATERIALS AND METHODS: Stage III NSCLC patients were randomized between PCI and observation. HRQoL was measured using the EuroQol 5D (EQ-5D-3L), EORTC QLQ-C30 and QLQ-BN20 instruments at completion of standard curative intent treatment and 4 weeks, 3, 6, 12, 24 and 36 months thereafter. Generalized linear mixed effects (GLM) models were used to assess the impact of PCI compared to observation over time on three HRQoL metrics: the EORTC QLQ-C30 global health status and the EQ-5D-3L utility and visual analogue scale (EQ VAS) scores. RESULTS: In total, 86 and 88 patients were included in the PCI and observation arm, with a median follow-up of 48.5 months (95% CI 39-54 months). Baseline mean HRQoL scores were comparable between the PCI and observation arm for the three HRQoL metrics. In the GLM models, none of the HRQoL metrics were clinically relevant or statistically significantly different between the PCI and the observation arm (p-values ranged between 0.641 and 0.914). CONCLUSION: No statistically significant nor a clinically relevant impact of PCI on HRQoL was observed

Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19):an investigator-initiated, randomised, open-label, phase 2 trial

Background Almost all patients with malignant mesothelioma eventually have disease progression after first-line therapy. Previous studies have investigated maintenance therapy, but none has shown a great effect. We aimed to assess the efficacy and safety of switch-maintenance gemcitabine in patients with malignant mesothelioma without disease progression after first-line chemotherapy. Methods We did a randomised, open-label, phase 2 trial in 18 hospitals in the Netherlands (NVALT19). We recruited patients aged older than 18 years with unresectable malignant mesothelioma with no evidence of disease progression after at least four cycles of first-line chemotherapy (with platinum and pemetrexed), who had a WHO performance status of 0-2, adequate organ function, and measurable or evaluable disease. Exclusion criteria were active uncontrolled infection or severe cardiac dysfunction, serious disabling conditions, symptomatic CNS metastases, radiotherapy within 2 weeks before enrolment, and concomitant use of any other drugs under investigation. Patients were randomly assigned (1:1), using the minimisation method, to maintenance intravenous gemcitabine (1250 mg/m(2) on days 1 and 8, in cycles of 21 days) plus supportive care, or to best supportive care alone, until disease progression, unacceptable toxicity, serious intercurrent illness, patient request for discontinuation, or need for any other anticancer agent, except for palliative radiotherapy. A CT scan of the thorax or abdomen (or both) and pulmonary function tests were done at baseline and repeated every 6 weeks. The primary outcome was progression-free survival in the intention-to-treat population. Safety was analysed in all participants who received one or more doses of the study drug or had at least one visit for supportive care. Recruitment is now closed; treatment and follow-up are ongoing. This study is registered with the Netherlands Trial Registry, NTR4132/NL3847. Findings Between March 20, 2014, and Feb 27, 2019, 130 patients were enrolled and randomly assigned to gemcitabine plus supportive care (65 patients [50%]) or supportive care alone (65 patients [50%]). No patients were lost to follow-up; median follow-up was 36.5 months (95% CI 34.2 to not reached), and one patient in the supportive care group withdrew consent. Progression-free survival was significantly longer in the gemcitabine group (median 6.2 months [95% CI 4.6-8.7]) than in the supportive care group (3.2 months [2.8-4.1]; hazard ratio [HR] 0.48 [95% CI 0.33-0.71]; p=0.0002). The benefit was confirmed by masked independent central review (HR 0.49 [0.33-0.72]; p=0.0002). Grade 3-4 adverse events occurred in 33 ( 52%) of 64 patients in the gemcitabine group and in ten (16%) of 62 patients in the supportive care group. The most frequent adverse events were anaemia, neutropenia, fatigue or asthenia, pain, and infection in the gemcitabine group, and pain, infection, and cough or dyspnoea in the supportive care group. One patient (2%) in the gemcitabine group died, due to a treatment-related infection. Interpretation Switch-maintenance gemcitabine, after first-line chemotherapy, significantly prolonged progression-free survival compared with best supportive care alone, among patients with malignant mesothelioma. This study confirms the activity of gemcitabine in treating malignant mesothelioma

Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial

BACKGROUND: Advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. Sorafenib, a multikinase inhibitor of VEGFR-2/-3, PDGFR-beta, B-Raf, and C-Raf, has shown to be active in preclinical models of cholangiocarcinoma. METHODS: We conducted a phase II trial of single-agent sorafenib in patients with advanced biliary tract carcinoma. Sorafenib was administered at a dose of 400 mg twice a day. The primary end point was the disease control rate at 12 weeks. RESULTS: A total of 46 patients were treated. In all, 26 (56%) had received chemotherapy earlier, and 36 patients completed at least 45 days of treatment. In intention-to-treat analysis, the objective response was 2% and the disease control rate at 12 weeks was 32.6%. Progression-free survival (PFS) was 2.3 months (range: 0-12 months), and the median overall survival was 4.4 months (range: 0-22 months). Performance status was significantly related to PFS: median PFS values for ECOG 0 and 1 were 5.7 and 2.1 months, respectively (P=0.0002). The most common toxicities were skin rash (35%) and fatigue (33%), requiring a dose reduction in 22% of patients. CONCLUSIONS: Sorafenib as a single agent has a low activity in cholangiocarcinoma. Patients having a good performance status have a better PFS. The toxicity profile is manageable