Electron probe microanalysis of ion exchange of selected elements between dentine and adhesive restorative materials

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: There have been numerous attempts to demonstrate the phenomenon of ion exchange between auto cure glass ionomer cements (GICs) and dentine. The purpose of this study was to employ an electron probe microanalysis (EPMA) technique to examine the interchange of elements between non-demineralized dentine and two types of restorative material, auto cure GICs and a resin composite. Methods: Restorations of auto cure GICs (Riva Fast, Fuji IX Fast, Ketac Molar Quick and Fuji VII) and a bonded composite resin were placed in each of 10 recently extracted human third molar teeth. After two weeks the restorations were sectioned and prepared for EPMA. Percentage weights of calcium, phosphorus aluminum, strontium and fluoride were calculated in the restorations 200μm from the restorative interface and 200μm into the dentine at 5μm intervals. Results: There was evidence of calcium and phosphorus in all five auto cure GICs to a depth of 50μm. Aluminum and strontium ions were also present in dentine except subjacent to Ketac Molar restorations. There was evidence of element transfer into composite resin and resin-bonded dentine. Conclusions: The findings of this paper support the concept of ion exchange as a bonding mechanism between auto cure GIC and dentine. Element penetration into tooth structure and GIC exceeded beyond the “ion exchange layer” observed in scanning electron microscopy studies. Penetration of calcium and phosphorus into composite resin from dentine likely occurred as a result of the self-etching process dissolving calcium and phosphorus and incorporating these elements into the hybrid layer. The presence of Al and Sr ions in dentine were likely to be associated with resin tags extending into the dentine.GM Knight, JM McIntyre, GG Craig and Mulyan

Screening for Alcoholism Among Medical Inpatients: How Important Is Corroboration of Patient Self-Report?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65580/1/j.1530-0277.1998.tb03925.x.pd

A Repeated Measures Experiment of Green Exercise to Improve Self-Esteem in UK School Children

Exercising in natural, green environments creates greater improvements in adult's self-esteem than exercise undertaken in urban or indoor settings. No comparable data are available for children. The aim of this study was to determine whether so called 'green exercise' affected changes in self-esteem; enjoyment and perceived exertion in children differently to urban exercise. We assessed cardiorespiratory fitness (20 m shuttle-run) and self-reported physical activity (PAQ-A) in 11 and 12 year olds (n = 75). Each pupil completed two 1.5 mile timed runs, one in an urban and another in a rural environment. Trials were completed one week apart during scheduled physical education lessons allocated using a repeated measures design. Self-esteem was measured before and after each trial, ratings of perceived exertion (RPE) and enjoyment were assessed after completing each trial. We found a significant main effect (F (1,74), = 12.2, p<0.001), for the increase in self-esteem following exercise but there was no condition by exercise interaction (F (1,74), = 0.13, p = 0.72). There were no significant differences in perceived exertion or enjoyment between conditions. There was a negative correlation (r = -0.26, p = 0.04) between habitual physical activity and RPE during the control condition, which was not evident in the green exercise condition (r = -0.07, p = 0.55). Contrary to previous studies in adults, green exercise did not produce significantly greater increases in self-esteem than the urban exercise condition. Green exercise was enjoyed more equally by children with differing levels of habitual physical activity and has the potential to engage less active children in exercise. © 2013 Reed et al

Two-electron spin correlations in precision placed donors in silicon

Substitutional donor atoms in silicon are promising qubits for quantum computation with extremely long relaxation and dephasing times demonstrated. One of the critical challenges of scaling these systems is determining inter-donor distances to achieve controllable wavefunction overlap while at the same time performing high fidelity spin readout on each qubit. Here we achieve such a device by means of scanning tunnelling microscopy lithography. We measure anti-correlated spin states between two donor-based spin qubits in silicon separated by 16 ± 1 nm. By utilising an asymmetric system with two phosphorus donors at one qubit site and one on the other (2P−1P), we demonstrate that the exchange interaction can be turned on and off via electrical control of two in-plane phosphorus doped detuning gates. We determine the tunnel coupling between the 2P−1P system to be 200 MHz and provide a roadmap for the observation of two-electron coherent exchange oscillations

Real-time selective sequencing using nanopore technology

The Oxford Nanopore Technologies MinION sequencer enables the selection of specific DNA molecules for sequencing by reversing the driving voltage across individual nanopores. To directly select molecules for sequencing, we used dynamic time warping to match reads to reference sequences. We demonstrate our open-source Read Until software in real-time selective sequencing of regions within small genomes, individual amplicon enrichment and normalization of an amplicon set

A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma

Lomeguatrib, an O6-methylguanine-DNA methyltransferase inactivator, was evaluated in an extended dosing regimen with temozolomide, designed according to pharmacodynamic data from previous studies. Patients with unresectable stage 3 or 4 cutaneous or unknown primary melanoma metastases were treated with lomeguatrib 40 mg, b.i.d. for 10 or 14 days and temozolomide 75–100 mg m−2 on days 1–5. Drugs were administered orally with cycles repeated every 28 days, for up to six cycles. A total of 32 patients were recruited to the study. Lomeguatrib for 10 days with temozolomide 75 mg m−2 was established as the optimal extended lomeguatrib dosing schedule, with haematological toxicity being dose limiting. There were two partial responses to treatment giving an overall response rate of 6.25%. Extending lomeguatrib administration beyond that of temozolomide requires a reduced dose of the latter agent. Only limited clinical activity was seen, suggesting no advantage for this regimen over conventional temozolomide administration in the treatment of melanoma

Online Health Check for Reducing Alcohol Intake among Employees:A Feasibility Study in Six Workplaces across England

BACKGROUND: Most hazardous and harmful drinkers are of working age and do not seek help with their drinking. Occupational health services are uniquely placed to universally screen employees across the range of socioeconomic and ethnic groups. The aim was to explore the feasibility and acceptability of offering electronic screening and brief intervention for alcohol misuse in the context of a health check in six different workplace settings.  METHODS AND FINDINGS: Employees were recruited from six workplaces across England, including three local authorities, one university, one hospital and one petro-chemical company. A total of 1,254 (8%) employees completed the health check and received personalised feedback on their alcohol intake, alongside feedback on smoking, fruit and vegetable consumption and physical activity. Most participants were female (65%) and of 'White British' ethnicity (94%), with a mean age of 43 years (SD 11). Participants were mostly in Intermediate occupations (58%), followed by Higher managerial / professional (39%) and Routine and manual occupations (2%). A quarter of participants (25%) were drinking at hazardous levels (33% male, 21% female), which decreased with age. Sixty-four percent (n=797) of participants completed online follow-up at three months. Most participants were supportive of workplaces offering employees an online health check (95%), their preferred format was online (91%) and many were confident of the confidentiality of their responses (60%). Whilst the feedback reminded most participants of things they already knew (75%), some were reportedly motivated to change their behaviour (13%).  CONCLUSIONS: Online health screening and personalised feedback appears feasible and acceptable, but challenges include low participation rates, potentially attracting 'worried well' employees rather than those at greatest health risk, and less acceptance of the approach among older employees and those from ethnic minority backgrounds and routine or manual occupations

A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer

To evaluate the tumour response to lomeguatrib and temozolomide (TMZ) administered for 5 consecutive days every 4 weeks in patients with metastatic colorectal carcinoma. Patients with stage IV metastatic colorectal carcinoma received lomeguatrib (40 mg) and TMZ (50–200 mg m−2) orally for 5 consecutive days every 4 weeks. Response was determined every two cycles. Pharmacokinetics of lomeguatrib and TMZ as well as their pharmacodynamic effects in peripheral blood mononuclear cells (PBMC) were determined. Nineteen patients received 49 cycles of treatments. Despite consistent depletion of O6-methylguanine-DNA methyltransferase in PBMC, none of the patients responded to treatment. Three patients had stable disease, one for the duration of the study, and no fall in carcinoembryonic antigen was observed in any patient. Median time to progression was 50 days. The commonest adverse effects were gastrointestinal and haematological and these were comparable to those of TMZ when given alone. This combination of lomeguatrib and TMZ is not efficacious in metastatic colorectal cancer. If further studies are to be performed, emerging data suggest that higher daily doses of lomeguatrib and a dosing period beyond that of TMZ should be evaluated

Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination

<p>Abstract</p> <p>Background</p> <p>Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation.</p> <p>Methods</p> <p>All patients had been enrolled in a WT1 peptide phase II vaccination trial (NCT00153582) and ultimately progressed despite induction of a WT1 specific T cell response. Blood and bone marrow samples prior to vaccination and during progression were analyzed for mRNA expression level of WT1. Base exchanges within the epitope sequence or flanking regions (10 amino acids N- and C-terminal of the epitope) were assessed with melting point analysis and sequencing. HLA class I expression and WT1 protein expression was analyzed by flow cytometry.</p> <p>Results</p> <p>Only in one patient, downregulation of WT1 mRNA by 1 log and loss of WT1 detection on protein level at time of disease progression was observed. No mutation leading to a base exchange within the epitope sequence or epitope flanking sequences could be detected in any patient. Further, no loss of HLA class I expression on leukemic blasts was observed.</p> <p>Conclusion</p> <p>Defects in antigen presentation caused by loss or mutation of WT1 or downregulation of HLA molecules are not the major basis for escape from the immune response induced by WT1 peptide vaccination.</p