A mathematical model of serotype replacement in pneumococcal carriage following vaccination

A number of childhood vaccination programmes have recently introduced vaccination against Streptococcus pneumoniae, the pneumococcus, a major cause of pneumonia and meningitis. The pneumococcal conjugate vaccines (PCVs) that are currently in use only protect against some serotypes of the bacterium, and there is now strong evidence that those serotypes not included in the vaccine increase in prevalence among most vaccinated populations. We present a mathematical model for the dynamics of nasopharyngeal carriage of S. pneumoniae that allows for carriage with multiple serotypes. The model is used to predict the prevalence of vaccine type (VT) and non-VT (NVT) serotypes following the introduction of PCV. Parameter estimates for the model are obtained by maximum likelihood using pre-vaccination data from The Gambia. The model predicts that low (1, 6A and 9V) and medium (4, 5, 7F, 14, 18C, 19A and 19F) prevalence serotypes can be eliminated through vaccination, but that the overall prevalence of carriage will be reduced only slightly because of an increase in the prevalence of NVT serotypes. Serotype replacement will be sequential, with high and medium prevalence NVT serotypes dominating initially, followed by an increase of serotypes of low prevalence. We examine the impact of a hypothetical vaccine that provides partial protection against all serotypes, and find that this reduces overall carriage, but is unable to eliminate low or medium prevalence serotypes.     

Four archetypes of process improvement: a Q-methodological study

This paper explores the process improvement approaches of organisations. It seeks to identify process redesign principles and the combinations of these principles that are used successfully in industry. We use Q-methodology to explore the viewpoints of a range of highly experienced process experts about the success of 16 improvement practices. Q-methodology enables the examination of the similarities and differences in the success of the improvement principles used by organisations in order to inform archetypes of process improvement. Overall, our findings suggest that process improvement is determined through the application of two foundational principles combined with one of four archetypes. ‘Remove non-value-adding tasks’ and ‘re-sequence tasks’ are described as foundational principles of process improvement, whilst outsourcing needs to be approached with caution. Furthermore, we articulate four distinctive archetypes comprising unique configurations of improvement principles that can be used to redesign operational processes. Based on this evidence we propose a typology of process improvement. This work suggests that rather than adopting generic improvement frameworks, managers should consult the typology to determine the archetype in closest proximity to their specific requirements. This study has several limitations including the small number of items populating the concourse and the fact that implementation problems are not taken into account.     

Predicting the chip flow for nose radius tools under oblique machining conditions

Abstract

A model is presented which predicts the chip flow direction for nose radius tools with inclination angles. Experimental verification was made in turning that cut on the bars. A comparison of the predicted and experimental results shows excellent agreement, and the results are consistent with previous findings of other workers. The usefulness of the present model is its capacity to predict the chip flow for a given general tool used with any combination of cutting conditions, without any prior knowledge of the work material properties or any machining tests required to determine an empirical formula.     

Multiply Methyl-Branched Fatty Acids and Diacids in the Polar Lipids of a Microaerophilic Subsurface Microbial Community

A previously unreported series of di- and tri-methylated fatty acids, as well as saturated and monounsaturated diacids were identified in polar lipids isolated from environmental subsurface sediment samples. Mechanisms are proposed for their formation, but their origin and role in cell membranes remains unknown.     

Quantification of NTproBNP in rat serum using immunoprecipitation and LC/MS/MS: a biomarker of drug-induced cardiac hypertrophy

Brain natriuretic peptide (BNP) and N-terminal proBNP (NTproBNP) are well established in the clinic as biomarkers of heart failure. BNP hormone and the inactive NTproBNP are predominantly secreted in the ventricles of the heart in response to pressure overload and, consequently, are being investigated as markers of drug-induced cardiac hypertrophy in rat to support drug development. In the work presented here, an immunoaffinity-based LC/MS/MS assay was developed and validated to measure a selective tryptic fragment of NTproBNP in rat serum. The assay covers the range of 13-329 pg/mL of the tryptic fragment LLELIR, corresponding to 0.1-2.5 ng/mL intact NTproBNP. A stable isotope-labeled version of NTproBNP containing the tryptic fragment LLELI[13C615N1]R was prepared by solid-phase peptide synthesis and was used as an internal standard to minimize assay variability. Due to endogenous NTproBNP present in rat serum, human serum was used as the control matrix, and parallelism between rat and human serum was established by standard addition. Assay accuracy (% RE) and precision (% CV) were measured at three concentrations on each of 4 days and did not exceed 4.2 and 14.5%, respectively. Additionally, study data are presented from the application of this assay in which rats demonstrated a significant increase in NTproBNP serum concentration following administration of an agent known to induce cardiac hypertrophy. In this study, the relationship between serum NTproBNP and cardiac hypertrophy was corroborated by increases in heart weight and magnetic resonance imaging of the test subjects' left ventricle. To our knowledge, this represents the first reported assay for NTproBNP in preclinical species for the assessment of cardiac hypertrophy.     

Pulsed terahertz attenuated total reflection spectroscopy

Pulsed terahertz attenuated total reflection (ATR) spectra of solid materials and liquids covering the 10 cm(-1) to 120 cm(-1) (0.3 THz to 3.6 THz) region of the electromagnetic spectrum are recorded using a terahertz pulsed spectrometer and silicon ATR modules. Pulsed terahertz ATR measurements are completed nondestructively using small amounts of sample (typically 1 mg for solids) and no sample preparation. Many terahertz analyses can be run in rapid sequence, minimizing the analysis time.