An exploratory interview study of researchers’ and technicians’ perceptions of rat tickling

This paper highlights the main themes which emerged from a study carried out with Animal Technicians and researchers to better understand:• perceptions of rat tickling• potential drivers and barriers to the uptake of ticklingin a laboratory environmentThe interviewees indicated they had positive attitudes towards rats and the idea of rat tickling with positive comments about rats’ social behaviour, their intelligence and their capacity to interact with Animal Technicians andresearchers.The participants indicated that barriers to wider uptake of rat tickling including time constraints, a lack of training in the specifics of rat tickling and how to interpret rat responses to tickling. In addition, there was mention of concerns over tickling affecting experimental integrity and the need to maintain professional detachment from rats as experimental animals

An exploratory interview study of researchers’ and technicians’ perceptions of rat tickling

This paper highlights the main themes which emerged from a study carried out with Animal Technicians and researchers to better understand:• perceptions of rat tickling• potential drivers and barriers to the uptake of ticklingin a laboratory environmentThe interviewees indicated they had positive attitudes towards rats and the idea of rat tickling with positive comments about rats’ social behaviour, their intelligence and their capacity to interact with Animal Technicians andresearchers.The participants indicated that barriers to wider uptake of rat tickling including time constraints, a lack of training in the specifics of rat tickling and how to interpret rat responses to tickling. In addition, there was mention of concerns over tickling affecting experimental integrity and the need to maintain professional detachment from rats as experimental animals

Utility analysis of disability caused by amblyopia and/or strabismus in a population-based, historic cohort

Background: Amblyopia (prevalence 3.4%) is in principle treatable, but approximately one quarter of children do not reach reading acuity in the amblyopic eye. Adults with persistent amblyopia and/or strabismus experience a decrease in quality of life. This was now quantified by patient-perceived utility values. Methods: Subjects were born 1962-1972 and had been treated by occlusion therapy for amblyopia by one orthoptist 30-35 years ago. All children in Waterland with amblyopia and/or strabismus had been referred to this orthoptist. Utilities were derived by methods of time trade-off, TTO (lifetime traded against perfect vision) and standard gamble, SG (death risk accepted for perfect vision). Most troubling eye disorder (low acuity of the amblyopic eye, lacking stereopsis or strabismus) was chosen and ranked among nine chronic disorders according to the subject's perceived severity. Results: From 201 patients that could be contacted 35 years after occlusion therapy - out of 471 who had been occluded - 135 were included: 17 could not be reached, 34 refused, and 15 had other reasons to not participate. Mean age was 40.86 years; 53% were male. Seventy percent were willing to trade lifetime according to the TTO method; its mean (log) utility was 0.963, i.e., a decrease in quality of life of 3.7%. Thirty-seven percent accepted death risk according to the SG method; its mean utility was 0.9996. TTO outcomes correlated with current near and distance visual acuity. Low acuity of the amblyopic eye, chosen as most troubling eye disorder, ranked slightly less severe than tooth decay. Conclusion: Amblyopia and/or strabismus patients had a slightly decreased utility. The decrease is small but still important in the cost-effectiveness of vision screening because these conditions occur very frequently

Geochemistry of Pegmatites associated with the cape coast granite complex in the Egyaa and Akim Oda areas of southern Ghana

The Cape Coast granite complex, which is associated with  metasedimentary rocks of the Birirmian in Ghana, is characterised by various minor intrusions that include pegmatites. The pegmatites, which are feldspar-rich, occur within, and at the margins of the granite batholiths and the surrounding schists. The major and trace element compositions of the pegmatites sampled from Egyaa and Akim Oda areas have been determined. The data indicates that the pegmatites from these areas have granitic compositions. The rocks are medium-K to high-K, calc-alkaline, S-type granitoids that are peraluminous and magnesian. Lower values of molar CaO/ (MgO + FeO <sub>tot</tot>) coupled with higher values of molar Al<sub>2</sub>O<sub>3</sub>/(MgO + FeO<sub>tot</sup>) suggest their derivation from partial melting from metapelitic sources, with the Birimian metasedimentary rocks being the likely source material. The rocks are depleted in Rb, Ba, Nb, Ce and Ti but rich in U, K, La, Hf and Y relative to primitive mantle. The data suggest that the pegmatites from these areas are late orogenic, and were emplaced at upper to middle crustal levels in a volcanic arc geotectonic environment

Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis.

Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60 mg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One-third of the increase came from increasing cortical density, and two-thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab-treated women at increased risk of fracture.This study was funded by Amgen Inc., Thousand Oaks, CA, USA. Cambridge Bone Group is supported by Arthritis Research UK, The Evelyn Trust, and Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.232

Experimental observation of nonlinear Thomson scattering

A century ago, J. J. Thomson showed that the scattering of low-intensity light by electrons was a linear process (i.e., the scattered light frequency was identical to that of the incident light) and that light's magnetic field played no role. Today, with the recent invention of ultra-high-peak-power lasers it is now possible to create a sufficient photon density to study Thomson scattering in the relativistic regime. With increasing light intensity, electrons quiver during the scattering process with increasing velocity, approaching the speed of light when the laser intensity approaches 10^18 W/cm^2. In this limit, the effect of light's magnetic field on electron motion should become comparable to that of its electric field, and the electron mass should increase because of the relativistic correction. Consequently, electrons in such high fields are predicted to quiver nonlinearly, moving in figure-eight patterns, rather than in straight lines, and thus to radiate photons at harmonics of the frequency of the incident laser light, with each harmonic having its own unique angular distribution. In this letter, we report the first ever direct experimental confirmation of these predictions, a topic that has previously been referred to as nonlinear Thomson scattering. Extension of these results to coherent relativistic harmonic generation may eventually lead to novel table-top x-ray sources.Comment: including 4 figure

Global sensitivity analysis of the impact of impurities on CO2 pipeline failure

This paper describes the testing, comparison and application of global sensitivity techniques for the study of the impact of the stream impurities on CO2 pipeline failure. Global sensitivity analysis through non-intrusive generalised polynomial chaos expansion with sparse grids is compared to more common techniques and is found to achieve superior convergence rate to crude Monte Carlo, quasi-Monte Carlo and EFAST for functions with up to a moderate level of “roughness”. This methodology is then applied to the hypothetical full bore rupture of a 1 km CO2 pipeline at 150 bara and 283.15 K. The sensitivity of the ensuing outflow to the composition of a quaternary mixture of CO2 with N2, CH4 and O2 as representative stream impurities. The results indicate that the outflow rate is highly sensitive to the composition during the early stages of depressurisation, where the effect of the impurities on phase equilibria has a significant impact on the outflow

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Vaccines for COVID-19

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus, at the end of 2019 there has been an explosion of vaccine development. By the 1st September 2020, a staggering number of vaccines (over 200) had started pre-clinical development of which 39 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socialising. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled up from a small number of pre-clinical doses to enough filled vials to immunise the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. It describes the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising pre-clinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began, we are at a point where pre-clinical and early clinical data is being generated for the vaccines, an overview of this important area will help our understanding of the next phases

Ecological and methodological drivers of species' distribution and phenology responses to climate change

Climate change is shifting species’ distribution and phenology. Ecological traits, such as mobility or reproductive mode, explain variation in observed rates of shift for some taxa. However, estimates of relationships between traits and climate responses could be influenced by how responses are measured. We compiled a global data set of 651 published marine species’ responses to climate change, from 47 papers on distribution shifts and 32 papers on phenology change. We assessed the relative importance of two classes of predictors of the rate of change, ecological traits of the responding taxa and methodological approaches for quantifying biological responses. Methodological differences explained 22% of the variation in range shifts, more than the 7.8% of the variation explained by ecological traits. For phenology change, methodological approaches accounted for 4% of the variation in measurements, whereas 8% of the variation was explained by ecological traits. Our ability to predict responses from traits was hindered by poor representation of species from the tropics, where temperature isotherms are moving most rapidly. Thus, the mean rate of distribution change may be underestimated by this and other global syntheses. Our analyses indicate that methodological approaches should be explicitly considered when designing, analysing and comparing results among studies. To improve climate impact studies, we recommend that (1) reanalyses of existing time series state how the existing data sets may limit the inferences about possible climate responses; (2) qualitative comparisons of species’ responses across different studies be limited to studies with similar methodological approaches; (3) meta-analyses of climate responses include methodological attributes as covariates; and (4) that new time series be designed to include the detection of early warnings of change or ecologically relevant change. Greater consideration of methodological attributes will improve the accuracy of analyses that seek to quantify the role of climate change in species’ distribution and phenology changes