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The aim of this study was to evaluate and correlate objectively the microspectroscopically derived biochemical components of sound, infected and affected carious dentine with their microhardness and autofluorescence (AF) characteristics. Over 3 million high-resolution Raman spectra from 8 extracted human carious teeth were recorded using Raman spectrometer with parallel spectrum acquisition. Green AF signals across each carious lesion from all samples were acquired with a similar spatial resolution using confocal fluorescence microscopy. The Knoop microhardness (KHN) from a total of 233 co-localized areas was recorded from the same samples and allocated subjectively into the three zones. Cluster analysis of the Raman data, performed using in-house software, produced five independent spectral components representing mineral content, protein content, porphyrin fluorescence (PF), putative infected dentine signal (IDS) and affected dentine signal (ADS). The distributions of the 5 Raman components and the AF signal were matched across all samples and their average values were calculated for each corresponding KHN area. The infected dentine was defined significantly by the KHN, AF and by the relative contribution of the mineral, PF and IDS clusters. Protein cluster was not statistically related to the KHN or AF. A delineation between affected and sound dentine was observed using the KHN, AF, PF and ADS parameters. This study concludes that micro-Raman spectroscopy can provide a non-invasive and objective evaluation of different carious dentine zones. Being able to detect and assess clinically the caries-affected dentine during minimally invasive operative caries management is important to control the risk of unnecessary tissue removal.

This in vitro, split–tooth study aimed to evaluate the efficiency (time taken) and effectiveness (quantity of dentine removed) of four techniques of carious dentine excavation (bur, air–abrasion, sono–abrasion and Carisolv™ gel) compared to conventional hand excavation. Eighty freshly extracted human molars were assigned to four experimental groups (n = 20), sectioned longitudinally through occlusal lesions and pre–excavation colour photomicrographs obtained. Using the natural autofluorescence of carious dentine (detected using confocal laser scanning microscopy) as an objective and reproducible guide, carious dentine removal was assessed in each half of the split tooth sample, comparing hand excavation to the test method. The time taken to reach a cavity floor that was hard to a dental probe was noted and final colour photomicrographs were taken. From the results, it was concluded that bur excavation was quickest but overprepared cavities relative to the autofluorescent signature, whereas Carisolv excavation was slowest but removed adequate quantities of tissue. Sono–abrasion tended to underprepare whereas air–abrasion was more comparable to hand excavation in both the time and amounts of dentine removed. Conventional hand excavation appeared to offer the best combination of efficiency and effectiveness for carious dentine excavation within the parameters used in this study.

Clinical air abrasion is known to remove dental hard tissues effectively. The aim of this study was to quantify and compare the efficiency of alumina air abrasion in the removal of sound and carious dentine. Twelve non-cavitated carious lesions in freshly extracted molars were bisected mesiodistally. The Knoop hardness number (KHN) was measured on the cut sample surface at 250-µm intervals along a line running axially through the centre of the lesion, from the enamel-dentine junction to the pulp including both sound and carious tissue. The cut surface was then abraded over the same path using alumina particles (27 µm). Powder flow rates, pressure, distance and the angle of the nozzle to the tooth were kept constant throughout the experiment. Non-contact surface profilometry and surface analysis software were used to calculate the rate of dentine removal at the site of each KHN measurement. The results showed that dentine Knoop hardness can be used as a predictor of the rate of dentine removal, with a Somers’ D value of 0.826. Carious dentine with a low KHN was removed less efficiently than the hard sound dentine with a higher KHN. Thus, dentists should be aware that air abrasion systems using alumina particles remove healthy dentine more efficiently than carious dentine, with the associated implications for clinical caries excavation and cavity preparation.

The long term scaling prospects for solid-state quantum computing architectures relies heavily on the ability to simply and reliably measure and control the coherent electron interaction strength, known as the tunnel coupling, tc. Here, we describe a method to extract the tc between two quantum dots (QDs) utilising their different tunnel rates to a reservoir. We demonstrate the technique on a few donor triple QD tunnel coupled to a nearby single-electron transistor (SET) in silicon. The device was patterned using scanning tunneling microscopy-hydrogen lithography allowing for a direct measurement of the tunnel coupling for a given inter-dot distance. We extract t c = 5.5 1.8 GHz and t c = 2.2 1.3 GHz between each of the nearest-neighbour QDs which are separated by 14.5 nm and 14.0 nm, respectively. The technique allows for an accurate measurement of tc for nanoscale devices even when it is smaller than the electron temperature and is an ideal characterisation tool for multi-dot systems with a charge sensor.

The function of the interfacial transition zone (absorption layer) in resin-modified glass-ionomer cements bonded to deep dentin remains obscure. This study tested the hypotheses that the absorption layer is formed only in the presence of water derived from hydrated dentin and allows for better bonding of resin-modified glass-ionomer cements to dentin. Ten percent polyacrylic acid-conditioned, hydrated, and dehydrated deep dentin specimens were bonded with 2 resin-modified glass-ionomer cements and sealed with resins to prevent environmental water gain or loss. A non-particulate absorption layer was identified over hydrated dentin only, and was clearly discernible from the hybrid layer when bonded interfaces were examined with transmission electron microscopy. This layer was relatively more resistant to dehydration stresses, and remained intact over the dentin surface after tensile testing. The absorption layer mediates better bonding of resin-modified glass-ionomer cements to deep dentin, and functions as a stress-relieving layer to reduce stresses induced by desiccation and shrinkage.

Previous investigations have shown the potential for fluoride to be protective in an abrasion/erosion laboratory model. The aim of this study was to investigate the effect of high concentrations of fluoride delivered in a varnish on attrition of dentine. Fifteen caries-free, intact lower third molar teeth were sectioned and the enamel removed by a water-cooled diamond disc. Polished dentine surfaces were divided into 8 areas, 4 of which were randomly covered with a high-concentration fluoride varnish for 24 h. The samples were subjected to 5,000 cycles of attrition bathed under artificial saliva. Microhardness testing adjacent to the wear scars showed no statistical difference between the fluoride-treated (71.42 KHN, SD 10.52) and control surfaces (72.66 KHN, SD 9.69). The volume of the wear scar was statistically greater for the fluoride-treated surface at 9.6 µm 3 (SD 4.92) and 8.13 µm 3 (SD 5.54) for the control areas (p = 0.029). The low pH of the fluoride varnish appears to have increased the amount of wear from attrition in this laboratory study.

Background Immune checkpoint blockers (ICBs) activate CD8 + T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. Methods Retrospective evaluation of irAEs on survival was performed across primary ( N  = 144) and secondary ( N  = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8 + T cells was sequenced and differential gene expression according to irAE development assessed. Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P  < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached ( P  = 2.8 × 10 −6 ). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8 + T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment. Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.

Background: Children who are unwell often display signs of circulatory compromise. It has been observed that pronounced changes occur in the appearance of the photoplethysmogram (pulse oximeter tracing) in these children. The aim of the study was to discover if wavelet transforms can identify more subtle changes in the photoplethysmogram of children who are unwell. Methods: Photoplethysmograms were obtained from children attending a paediatric accident and emergency department with clinical features suggestive of significant bacterial illness or circulatory compromise. Photoplethysmograms were also obtained from a control group of well children. Wavelet transforms were applied to the traces in an attempt to separate the two groups. Results: 20 traces were obtained from unwell children and 12 from controls. Analysis of the entropy of the wavelet transform of the photoplethysmogram allows the differentiation of unwell children from controls (p = 0.00002). Conclusions: Wavelet transform of the photoplethysmogram offers the possibility of a rapid non-invasive method of screening children for significant illness.

A heparin binding mitogenic protein isolated from bovine uterus shares NH2-terminal amino acid sequence with a protein isolated from newborn rat brain. The cDNA's of the bovine, human, and rat genes have been isolated and encode extraordinarily conserved proteins unrelated to known growth or neurotrophic factors, although identity of nearly 50 percent has been found with the predicted sequence of a retinoic acid induced transcript in differentiating mouse embryonal carcinoma cells. Lysates of COS-7 cells transiently expressing this protein were mitogenic for NRK cells and initiated neurite outgrowth from mixed cultures of embryonic rat brain cells. RNA transcripts encoding this protein were widely distributed in tissues and were developmentally regulated. This protein, previously designated as heparin binding growth factor (HBGF)-8, is now renamed pleiotrophin (PTN) to reflect its diverse activities. PTN may be the first member of a family of developmentally regulated cytokines