Quantifying error introduced by iterative closest point image registration.

OBJECTIVES: The aim of this paper was to quantify the analysis error introduced by iterative closest point (ICP) image registration. We also investigated whether a subsequent subtraction process can reduce process error. METHODS: We tested metrology and two 3D inspection software using calibration standards at 0.39 µm, and 2.64 µm and mathematically perfect defects (softgauges) at 2 and 20 µm, on free form surfaces of increasing complexity and area, both with and without registration. Errors were calculated in percentage relative to the size of the defect being measured. Data were analysed in GraphPad Prism 9, normal and two-way ANOVA with post-hoc Tukey's was applied. Significance was inferred at p < 0.05. RESULTS: Using ICP registration introduced errors from 0 % to 15.63 % of the defect size depending on the surface complexity and size of the defect. Significant differences were observed in analysis measurements between metrology and 3D inspection software and within different 3D inspection software, however, one did not show clear superiority over another. Even in the absence of registration, defects at 0.39 µm, and 2.64 µm produced substantial measurement error (13.39-77.50 % of defect size) when using 3D inspection software. Adding an additional data subtraction process reduced registration error to negligible levels (<1 % independent of surface complexity or area). CONCLUSIONS: Commercial 3D inspection software introduces error during direct measurements below 3 µm. When using an ICP registration, errors over 15 % of the defect size can be introduced regardless of the accuracy of adjacent registration surfaces. Analysis output between software are not consistently repeatable or comparable and do not utilise ISO standards. Subtracting the datasets and analysing the residual difference reduced error to negligible levels. CLINICAL SIGNIFICANCE: This paper quantifies the significant errors and inconsistencies introduced during the registration process even when 3D datasets are true and precise. This may impact on research diagnostics and clinical performance. An additional data processing step of scan subtraction can reduce this error but increases computational complexity.

High background rates of positive tuberculosis-specific interferon-γ release assays in a low prevalence region of UK: a surveillance study.

BACKGROUND: Background rates of latent tuberculosis infection in low prevalence regions of Britain are unknown. These would be valuable data for interpreting positive IGRA results, and guiding cost-benefit analyses. The management of a large outbreak of tuberculosis occurring in a rural district hospital provided an opportunity to determine the background rates and epidemiology of IGRA-positivity amongst unselected hospital patients in a low-prevalence region of U.K. METHODS: As part of a public health surveillance project we identified 445 individuals exposed to the index cases for clinical assessment and testing by a TB-specific interferon-γ release assay (IGRA): T-Spot.TB. Uniquely, an additional comparator group of 191 age-matched individuals without specific recent exposure, but with a similar age distribution and demographic, were recruited from the same wards where exposure had previously occurred, to undergo assessment by questionnaire and IGRA. RESULTS: Rates of IGRA positivity were 8.7% (95%CI, 4.2-13, n=149) amongst unexposed patients, 9.5%(3.0-22, n=21) amongst unexposed staff, 22%(14-29, n=130) amongst exposed patients, 11%(6.1-16, n=142) amongst exposed staff. Amongst the individuals without history of recent exposure to the outbreak, IGRA-positivity was associated with prior TB treatment (OR11, P.04) and corticosteroid use (OR5.9, P.02). Background age-specific prevalences of IGRA-positivity amongst unexposed individuals were: age <40 0%(N/A), age 40-59 15%(12-29), age 60-79 7.0%(1.1-13), age≥80 10%(5.9-19). CONCLUSIONS: Background rates of IGRA-positivity remain high amongst unselected white-Caucasian hospital inpatients in U.K. These data will aid interpretation of future outbreak studies. As rates peak in the 5th and 6th decade, given an ageing population and increasing iatrogenic immunosuppression, reactivation of LTBI may be a persistent hazard in this population for several decades to come.

The measurement threshold and limitations of an intra-oral scanner on polished human enamel.

OBJECTIVE: To investigate the measurement threshold of an intra-oral scanner (IOS) on polished human enamel. METHODS: The optical performance of an IOS was compared to a gold-standard non contacting laser profilometer (NCLP), on a painted microscope slide, compared to increasing particle size of silicon-carbide papers (21.8-269.0 µm) and separately on polished human enamel with increasing step-heights. The enamel samples were randomised (n = 80) and scanned using the IOS and NCLP at increasing step-height depths (µm) (1.87-86.46 µm) and quantified according to ISO:5436-1. The measurement threshold of the IOS was determined using a custom designed automated lesion localisation algorithm, corroborated by Gaussian skewness (Ssk) and kurtosis (Sku) analysis, to assess the minimum step-height measured on each enamel sample. RESULTS: The NCLP showed statistically increased Sq surface roughness for all silicon carbide particle sizes compared to the microscope slide, whereas, the IOS Sq roughness discriminated silicon-carbide particles above 68.0 µm compared to the glass slide (p ≤ 0.02). On polished enamel, the automated minimum detectable step-height measurable on each sample was 44 µm. No statistically significantly different step-height enamel lesion measurements were observed between NCLP and IOS above this threshold (p > 0.05). SIGNIFICANCE: This study revealed the fundamental optical metrological parameters for the IOS, was step-heights above 44 µm and this reflects the data acquisition of the system. These results highlight the limitations of IOS used in this study, mandating further research to optimise the performance of other IOS systems, for measuring wear of materials or tooth wear on human unpolished natural enamel surfaces.

Detection threshold of non-contacting laser profilometry and influence of thermal variation on characterisation of early surface form and textural changes in natural human enamel.

OBJECTIVES: To determine the detection threshold of non-contacting laser profilometry (NCLP) measuring surface form and surface roughness change in natural human enamel in vitro, characterise how ambient scanning thermal variation affects NCLP measurement, and calculate bulk enamel loss in natural human enamel. METHODS: NCLP repeatability and reproducibility accuracy was determined by consecutively scanning natural human enamel samples with/without sample repositioning. Ambient thermal variation and NCLP sensor displacement over short (30 s), medium (20 min), and long (2 h) scanning periods were evaluated for their standard deviation. Natural human enamel specimens (n = 12) were eroded using citric acid (0.3% w/w pH3.2) for 5, 10, and 15 min and characterised using surface profilometry, tandem scanning confocal microscopy (TSM), and optical coherence tomography (OCT). RESULTS: Repeatability and reproducibility error of NCLP for surface form was 0.28 µm and 0.43 µm, and for surface roughness 0.07 µm and 0.08 µm. Ambient thermal variation resulted in NCLP sensor displacement of 0.56 µm and 1.05 µm over medium and long scanning periods. Wear scar depth (µm) was calculated between 0.72-1.61 at 5 min, 1.72-3.06 at 10 min, and 3.40-7.06 at 15 min. Mean (SD) surface roughness (µm) was 1.13 (0.13), 1.52 (0.23), 1.44 (0.19), and 1.43 (0.21) at baseline, 5, 10, and 15 min. Qualitative image analysis indicated erosive change at the surface level, progressing after increasing erosion time. SIGNIFICANCE: Minimum detectable limits for NCLP measuring surface form and surface roughness changes were characterised. Ambient thermal variation, subsequent sensor displacement, and its impact on NCLP performance were characterised. Dental erosion lesions in natural human enamel could be characterised using surface profilometry, surface roughness, OCT, and TSM. Step height formation could be calculated within NCLP and temperature operating limits using profile superimposition and profile subtraction techniques. Natural enamel samples can now be used in in-vitro studies to investigate the formation and development of early acid erosive tooth wear, as well as the assessment of methods for enamel lesion remineralisation and repair.

Safer fluid prescribing at North Bristol Trust: Bringing practice in line with NICE Guidance with a redesign of the fluid prescription chart.

The National Institute of Clinical Excellence (NICE) released new fluid guidelines following data suggesting 20% of patients receiving fluids suffer adversely (2013). This quality improvement group assessed fluid prescribing in a tertiary teaching centre and introduced a new fluid- prescribing chart to align practice with NICE recommendations. Notes and corresponding fluid prescription charts were reviewed for evidence of (1) indication, (2) co-morbidities, and (3) further management as surrogate markers of safe prescribing in accordance with NICE. Overall, the data showed practice fell short and prompted a redesign of the Trust fluid prescription chart. Three different variations of the chart were issued consecutively using a PDSA method (plan, do, study, act) over a 6-month period. They all included indication, co-morbidities and further management plans as constant design features. Suggestions from interested parties were incorporated and an educational programme was implemented to promote awareness. Prior to our intervention, an indication for fluids was documented in 26% of notes, it took an average of 4.6 minutes to find co-morbidities, and further management plans were rarely documented. Following the new prescription chart, an indication was recorded in 72% of cases, co-morbidities noted on 63% of charts with 93.1% accuracy, and further management documented in 100% of cases. The new fluid prescription chart encourages prescribers to incorporate NICE recommendations when prescribing fluids. The new fluid prescription design has since been rolled out Trust wide.

Transient hydrogen bonding in uniformly ¹³C,¹5N-labeled carbohydrates in water.

We report NMR studies of transient hydrogen bonding in a polysaccharide (PS) dissolved in water without cosolvent at ambient temperature. The PS portion of the Escherichia coli O142 lipopolysaccharide is comprised of repeating pentasaccharide units of GalNAc (N-acetyl galactosamine), GlcNAc (N-acetyl glucosamine), and rhamnose in a 3:1:1 ratio, respectively. A 105-ns molecular dynamics (MD) simulation on one pentasaccharide repeat unit predicts transient inter-residue hydrogen bonds from the GalNAc NH groups in the PS. To investigate these predictions experimentally, the PS was uniformly ¹³C,¹5N enriched and the NH, carbonyl, C2, C4, and methyl resonances of the GalNAc and GlcNAc residues assigned using through-bond triple-resonance NMR experiments. Temperature dependence of amide NH chemical shifts and one-bond NH J couplings support that NH groups on two of the GalNAc residues are donors in transient hydrogen bonds. The remaining GalNAc and GlcNAc NHs do not appear to be donors from either temperature-dependent chemical shifts or one-bond NH J couplings. These results substantiate the presence of weak or partial hydrogen bonds in carbohydrates, and that MD simulations of repeating units in PSs provide insight into overall PS structure and dynamics.

Discriminating the helical forms of peptides by NMR and molecular dynamics simulation.

The HNCO NMR pulse sequence was applied to three selectively labeled (15)N and (13)C isotopic homologues of the peptide Ac-WAAAH(AAARA)(3)A-NH(2) to probe directly for hydrogen bonds between residues 8 and 11 (characteristic of a 3(10)-helix), 8 and 12 (alpha-helix), and 8 and 13 (pi-helix). The experiments demonstrate conclusively, and in agreement with circular dichroism studies, that the center of the peptide is alpha-helical; there is no discernible 3(10)- or pi-helix at these specific positions. Molecular dynamics simulations of the preceding peptide and Ac-(AAAAK)(3)A-NH(2) in water using the potential energy parameter set CHARMM22/CMAP correctly yield an alpha-helix, in contrast to simulations with the set CHARMM22, which result in a pi-helix.

Direct assignment of the absolute configuration of a distinct class of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus by M-GOESY nuclear magnetic resonance spectroscopy.

The determination of the absolute configuration of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus toward the synthesis of P-stereodifined phosphorothioated oligodeoxyribonucleotides is easily accomplished with computer-assisted molecular modeling and M-GOESY NMR spectroscopy. Specifically, computer-modeling diasteromeric phosphoramidite 3 has identifed a proximal (2.55 A) through-space interaction between benzylic H-5 and sugar H-2' ', which can predictably be detected by M-GOESY NMR in SP-3 but not in RP-3 because of being too distant (5.85 A). Consistent with computer-assisted modeling predictions, M-GOESY NMR spectra of SP-3 and RP-3 revealed NOE signals generated from nuclei near the selectively excited H-2' ' that are common to both SP-3 and RP-3, namely those of H-2', H-4', H-3', and H-1'. In addition, a diagnostic NOE signal at 5.5 ppm (benzylic H-5) is, as predicted, only detected in SP-3 and thus provides an unequivocal assessment of the configuration of the diastereomer at phosphorus. M-GOESY NMR data also confirm that the condensation of deoxyribonucleoside cyclic N-acylphosphoramidites with base-activated nucleosidic or nucleotidic 5'-hydroxyls proceeds via a single nucleophilic event.