The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease

AbstractEthics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value

Rejection thresholds (RjT) of sweet likers and dislikers

Sweetness is generally a desirable taste, however consumers can be grouped into sweet likers and dislikers according to optimally preferred sucrose concentrations. Understanding the levels of sweetness in products that are acceptable and unacceptable to both consumer groups is important to product development and for influencing dietary habits. The concentrations at which sucrose decreases liking (the rejection threshold; RjT) in liquid and semi-solid matrices were investigated in this study. Thirty six consumers rated their liking of 5 sucrose aqueous solutions; this identified 36% sweet likers (SL) whose liking ratings increased with increasing sucrose and 64% sweet dislikers (SD) whose liking ratings decreased above 6% (w/v) sucrose. We hypothesized that SL and SD would have different RjT for sucrose in products. This was tested by preparing 8 levels of sucrose in orange juice and orange jelly and presenting each against the lowest level in forced choice preference tests. In orange juice, as sucrose increased from 33g/L to 75g/L the proportion of people preferring the sweeter sample increased in both groups. However, at higher sucrose levels, the proportion of consumers preferring the sweet sample decreased. For SD, a RjT was reached at 380 g/L, whereas a significant RjT for SL was not reached. RjT in jelly were not reached as the sweetness in orange jelly was significantly lower than for orange juice (p<0.001). Despite statistically significant differences in rated sweetness between SL and SD (p=0.019), the extent of difference between the two groups was minor. The results implied that sweet liker status was not substantially related to differences in sweetness perception. Self-reported dietary intake of carbohydrate, sugars and sucrose were not significantly affected by sweet liker status. However the failure to find an effect may be due to the small sample size and future studies within a larger, more representative population sample are justifiable from the results of this study

The Stripe 82 1-2 GHz Very Large Array Snapshot Survey: Multiwavelength Counterparts

We have combined spectrosopic and photometric data from the Sloan Digital Sky Survey (SDSS) with $1.4$ GHz radio observations, conducted as part of the Stripe 82 $1-2$ GHz Snapshot Survey using the Karl G. Jansky Very Large Array (VLA), which covers $\sim100$ sq degrees, to a flux limit of 88 $\mu$Jy rms. Cross-matching the $11\,768$ radio source components with optical data via visual inspection results in a final sample of $4\,795$ cross-matched objects, of which $1\,996$ have spectroscopic redshifts and $2\,799$ objects have photometric redshifts. Three previously undiscovered Giant Radio Galaxies (GRGs) were found during the cross-matching process, which would have been missed using automated techniques. For the objects with spectroscopy we separate radio-loud Active Galactic Nuclei (AGN) and star-forming galaxies (SFGs) using three diagnostics and then further divide our radio-loud AGN into the HERG and LERG populations. A control matched sample of HERGs and LERGs, matched on stellar mass, redshift and radio luminosity, reveals that the host galaxies of LERGs are redder and more concentrated than HERGs. By combining with near-infrared data, we demonstrate that LERGs also follow a tight $K-z$ relationship. These results imply the LERG population are hosted by population of massive, passively evolving early-type galaxies. We go on to show that HERGs, LERGs, QSOs and star-forming galaxies in our sample all reside in different regions of a WISE colour-colour diagram. This cross-matched sample bridges the gap between previous `wide but shallow' and `deep but narrow' samples and will be useful for a number of future investigations.Comment: 17 pages, 19 figures. Resubmitted to MNRAS after the initial comment

The role of orienting in vibrissal touch sensing

Rodents, such as rats and mice, are strongly tactile animals who explore the environment with their long mobile facial whiskers, or macrovibrissae, and orient to explore objects further with their shorter, more densely packed, microvibrissae. Although whisker motion (whisking) has been extensively studied, less is known about how rodents orient their vibrissal system to investigate unexpected stimuli. We describe two studies that address this question. In the first we seek to characterize how adult rats orient toward unexpected macrovibrissal contacts with objects and examine the microvibrissal exploration behavior following such contacts. We show that rats orient to the nearest macrovibrissal contact on an unexpected object, progressively homing in on the nearest contact point on the object in each subsequent whisk. Following contact, rats “dab” against the object with their microvibrissae at an average rate of approximately 8 Hz, which suggests synchronization of microvibrissal dabbing with macrovibrissal motion, and an amplitude of 5 mm. In study two, we examine the role of orienting to tactile contacts in developing rat pups for maintaining aggregations (huddles). We show that young pups are able to orient to contacts with nearby conspecifics before their eyes open implying an important role for the macrovibrissae, which are present from birth, in maintaining contact with conspecifics. Overall, these data suggest that orienting to tactile cues, detected by the vibrissal system, plays a crucial role throughout the life of a rat

Understanding and optimising an identification/brief advice (IBA) service about alcohol in the community pharmacy setting

This is the final report of an evaluation into the identification/brief advice (IBA) service about alcohol in community pharmacy settings in the North West of England. Since 2007, almost 100 pharmacies in the North West have - at some point - been commissioned to provide an identification and brief advice (IBA) service for alcohol. This evaluation sought to understand how the service had been adapted for and implemented in the community pharmacy setting, and how its potential might be maximised. Its aims were: 1. To characterise, consolidate and optimise both the constant and variable elements of the pharmacy alcohol identification/brief advice (IBA) service in NHS Northwest, and 2. To inform planning for current and future pharmacy based services promoting safe consumption of alcohol. The evaluation was split into three main workstreams, supported by a preliminary scoping phase, and combined quantitative and qualitative methods: • Descriptive and comparative statistical analysis of pharmacy alcohol IBA data; • In-pharmacy work, including observation of staff engagement with customers, recording consultations between staff and customers, follow-up telephone interviews with customers, and group feedback interviews with pharmacy staff; • Stakeholder engagement through self-completion surveys, semi-structured interviews and a workshop. This report gives the background to the project, and details the methods, results and implications

LINE-1 and Alu retrotransposition exhibit clonal variation

BACKGROUND: The non-long terminal repeat (non-LTR) retrotransposons, long interspersed element-1 (LINE-1) and Alu are currently active retroelements in humans. We, and others, have observed that different populations of HeLa cells from different laboratories support retrotransposition of LINE-1 and Alu to varying degrees. We therefore tested whether individual cell clones of HeLa and HCT116 cell lines supported different levels of LINE-1 and Alu retrotransposition, and whether these variations were stable upon re-cloning. FINDINGS: Standard retrotransposition tissue culture assays were used to measure a cell’s ability to support LINE-1 and Alu retrotransposition in clonal HeLa and HCT116 cell lines. We observed that both LINE-1 and Alu retrotransposition exhibited clonal variation in HeLa cells, with certain HeLa cell clones supporting high levels of LINE-1 and Alu retrotransposition and other cell clones being essentially retrotransposition-dead. This clonal variation was similarly observed in HCT116 cells, although possibly not to the same extent. These patterns of clonal variation are relatively consistent upon re-cloning. CONCLUSIONS: Observations of the variability of LINE-1 and Alu retrotransposition in different populations of the same cell line are supported by our results that indicate in some cell types, individual cell clones can have dramatically differing capacity for retrotransposition. The mixed populations of cells commonly used in laboratories have often been passaged for many generations and accumulated significant genetic and epigenetic diversity. Our results suggest that the clonal variability observed by our cloning experiments may lead to a homogenization of retrotransposition capacity, with the resulting mixed population of cells being composed of individual variants having either increased or decreased retrotransposition potential compared to the starting population

Atomic Hydrogen Cleaning of Polarized GaAs Photocathodes

Atomic hydrogen cleaning followed by heat cleaning at 450$^\circ$C was used to prepare negative-electron-affinity GaAs photocathodes. When hydrogen ions were eliminated, quantum efficiencies of 15% were obtained for bulk GaAs cathodes, higher than the results obtained using conventional 600$^\circ$C heat cleaning. The low-temperature cleaning technique was successfully applied to thin, strained GaAs cathodes used for producing highly polarized electrons. No depolarization was observed even when the optimum cleaning time of about 30 seconds was extended by a factor of 100

A New Population of High Redshift, Dusty Lyman-Alpha Emitters and Blobs Discovered by WISE

We report a new technique to select 1.6<z<4.6 dusty Lyman-alpha emitters (LAEs), over a third of which are `blobs' (LABs) with emission extended on scales of 30-100kpc. Combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W.M. Keck telescope, we present a color criteria that yields a 78% success rate in identifying rare, dusty LAEs of which at least 37% are LABs. The objects have a surface density of only ~0.1 per square degree, making them rare enough that they have been largely missed in narrow surveys. We measured spectroscopic redshifts for 92 of these WISE-selected, typically radio-quiet galaxies and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel reveals that these galaxies have extreme far-infrared luminosities (L_IR>10^{13-14}L_sun) and warm colors, typically larger than submillimeter-selected galaxies (SMGs) and dust-obscured galaxies (DOGs). These traits are commonly associated with the dust being energized by intense AGN activity. We hypothesize that the combination of spatially extended Lyman-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing strong `feedback' transforming them from an extreme dusty starburst to a QSO.Comment: Submitted to ApJ Letters, 6 pages, 4 figures. Comments welcom