Inclusion of the value of herd immunity in economic evaluations of vaccines. A systematic review of methods used.

OBJECTIVE: The objectives of this review were to identify vaccine economic evaluations that include herd immunity and describe the methodological approaches used. METHODS: We used Kim and Goldie's search strategy from a systematic review (1976-2007) of modelling approaches used in vaccine economic evaluations and additionally searched PubMed/MEDLINE and Embase for 2007-2015. Studies were classified according to modelling approach used. Methods for estimating herd immunity effects were described, in particular for the static models. RESULTS: We identified 625 economic evaluations of vaccines against human-transmissible diseases from 1976 to 2015. Of these, 172 (28%) included herd immunity. While 4% of studies included herd immunity in 2001, 53% of those published in 2015 did this. Pneumococcal, human papilloma and rotavirus vaccines represented the majority of studies (63%) considering herd immunity. Ninety-five of the 172 studies utilised a static model, 59 applied a dynamic model, eight a hybrid model and ten did not clearly state which method was used. Relatively crude methods and assumptions were used in the majority of the static model studies. CONCLUSION: The proportion of economic evaluations using a dynamic model has increased in recent years. However, 55% of the included studies used a static model for estimating herd immunity. Values from a static model can only be considered reliable if high quality surveillance data are incorporated into the analysis. Without this, the results are questionable and they should only be included in sensitivity analysis

Shanidar Cave and the Baradostian, a Zagros Aurignacian industry

Whilst there has been significant interest in the origins and spread of the Aurignacian industry, usually linked with the physical dispersal of anatomically modern humans into Europe, comparatively little attention has been paid to possible origins or movements further east. Recent work at Shanidar Cave, a site better known for the Neanderthal evidence discovered by Ralph Solecki in his 1951–1960 excavations, has recovered new information on the “Baradostian” Upper Palaeolithic in Iraq. This paper reviews the regional evidence for the Baradostian as an example of the Zagros Aurignacian and discusses its place in debates about Neanderthal/Modern Human relations.The financial support of the Leverhulme Trust (Research Grant RPG-2013-105), the Rust Family Foundation, and Natural Environment Research Council's Oxford Radiocarbon Dating Facility (grant NF/2016/2/14) is also gratefully acknowledged

DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure

Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1–p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer

Light responses and light adaptation in rat retinal rods at different temperatures

Rod responses to brief pulses of light were recorded as electroretinogram (ERG) mass potentials across isolated, aspartate-superfused rat retinas at different temperatures and intensities of steady background light. The objective was to clarify to what extent differences in sensitivity, response kineticsandlight adaptationbetweenmammalianandamphibianrods can be explained by temperature and outer-segment size without assuming functional differences in the phototransduction molecules. Corresponding information for amphibian rods from the literature was supplemented by new recordings from toad retina. All light intensities were expressed as photoisomerizations per rod (Rh∗). In the rat retina, an estimated34%of incident photons at the wavelength of peak sensitivity caused isomerizations in rods, as the (hexagonally packed) outer segments measured 1.7 μm×22 μm and had specific absorbance of 0.016 μm−1 on average. Fractional sensitivity (S) in darkness increased with cooling in a similar manner in rat and toad rods, but the rat function as a whole was displaced to a ca 0.7 log unit higher sensitivity level. This difference can be fully explained by the smaller dimensions of rat rod outer segments, since the same rate of phosphodiesterase (PDE) activation by activated rhodopsin will produce a faster drop in cGMP concentration, hence a larger response in rat than in toad. In the range 15–25◦C, the waveformand absolute time scale of dark-adapted dim-flash photoresponses at any given temperature were similar in rat and toad, although the overall temperature dependence of the time to peak (tp) was somewhat steeper in rat (Q10 ≈ 4 versus 2–3). Light adaptation was similar in rat and amphibian rods when measured at the same temperature. The mean background intensity that depressed S by 1 log unit at 12◦C was in the range 20–50 Rh∗ s−1 in both, compared with ca 4500 Rh∗ s−1 in rat rods at 36◦C. We conclude that it is not necessary to assume major differences in the functional properties of the phototransduction molecules to account for the differences in response properties of mammalian and amphibian rods

Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells

Background: Certain multi-walled carbon nanotubes (MWCNTs) have been shown to elicit asbestos-like toxicological effects. To reduce needs for risk assessment it has been suggested that the physicochemical characteristics or reactivity of nanomaterials could be used to predict their hazard. Fibre-shape and ability to generate reactive oxygen species (ROS) are important indicators of high hazard materials. Asbestos is a known ROS generator, while MWCNTs may either produce or scavenge ROS. However, certain biomolecules, such as albumin – used as dispersants in nanomaterial preparation for toxicological testing in vivo and in vitro - may reduce the surface reactivity of nanomaterials. Methods: Here, we investigated the effect of bovine serum albumin (BSA) and cell culture medium with and without BEAS 2B cells on radical formation/scavenging by five MWCNTs, Printex 90 carbon black, crocidolite asbestos, and glass wool, using electron spin resonance (ESR) spectroscopy and linked this to cytotoxic effects measured by trypan blue exclusion assay. In addition, the materials were characterized in the exposure medium (e.g. for hydrodynamic size-distribution and sedimentation rate). Results: The test materials induced highly variable cytotoxic effects which could generally be related to the abundance and characteristics of agglomerates/aggregates and to the rate of sedimentation. All carbon nanomaterials were found to scavenge hydroxyl radicals (•OH) in at least one of the solutions tested. The effect of BSA was different among the materials. Two types of long, needle-like MWCNTs (average diameter >74 and 64.2 nm, average length 5.7 and 4.0 µm, respectively) induced, in addition to a scavenging effect, a dose-dependent formation of a unique, yet unidentified radical in both absence and presence of cells, which also coincided with cytotoxicity. Conclusions: Culture medium and BSA affects scavenging/production of •OH by MWCNTs, Printex 90 carbon black, asbestos and glass-wool. An unidentified radical is generated by two long, needle-like MWCNTs and these two CNTs were more cytotoxic than the other CNTs tested, suggesting that this radical could be related to the adverse effects of MWCNTs