A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep

Chronic gonadotropin-releasing hormone agonist (GnRHa) administration is used where suppression of hypothalamic-pituitary-gonadal axis activity is beneficial, such as steroid-dependent cancers, early onset gender dysphoria, central precocious puberty and as a reversible contraceptive in veterinary medicine. GnRH receptors, however, are expressed outside the reproductive axis, e.g. brain areas such as the hippocampus which is crucial for learning and memory processes. Previous work, using an ovine model, has demonstrated that long-term spatial memory is reduced in adult rams (45 weeks of age), following peripubertal blockade of GnRH signaling (GnRHa: goserelin acetate), and this was independent of the associated loss of gonadal steroid signaling. The current study investigated whether this effect is reversed after discontinuation of GnRHa-treatment. The results demonstrate that peripubertal GnRHa-treatment suppressed reproductive function in rams, which was restored after cessation of GnRHa-treatment at 44 weeks of age, as indicated by similar testes size (relative to body weight) in both GnRHa-Recovery and Control rams at 81 weeks of age. Rams in which GnRHa-treatment was discontinued (GnRHa-Recovery) had comparable spatial maze traverse times to Controls, during spatial orientation and learning assessments at 85 and 99 weeks of age. Former GnRHa-treatment altered how quickly the rams progressed beyond a specific point in the spatial maze at 83 and 99 weeks of age, and the direction of this effect depended on gonadal steroid exposure, i.e. GnRHa-Recovery rams progressed quicker during breeding season and slower during non-breeding season, compared to Controls. The long-term spatial memory performance of GnRHa-Recovery rams remained reduced (P < 0.05, 1.5-fold slower) after discontinuation of GnRHa, compared to Controls. This result suggests that the time at which puberty normally occurs may represent a critical period of hippocampal plasticity. Perturbing normal hippocampal formation in this peripubertal period may also have long lasting effects on other brain areas and aspects of cognitive function

Automated design analysis, assembly planning and motion study analysis using immersive virtual reality

Previous research work at Heriot-Watt University using immersive virtual reality (VR) for cable harness design showed that VR provided substantial productivity gains over traditional computer-aided design (CAD) systems. This follow-on work was aimed at understanding the degree to which aspects of this technology were contributed to these benefits and to determine if engineering design and planning processes could be analysed in detail by nonintrusively monitoring and logging engineering tasks. This involved using a CAD-equivalent VR system for cable harness routing design, harness assembly and installation planning that can be functionally evaluated using a set of creative design-tasks to measure the system and users' performance. A novel design task categorisation scheme was created and formalised which broke down the cable harness design process and associated activities. The system was also used to demonstrate the automatic generation of usable bulkhead connector, cable harness assembly and cable harness installation plans from non-intrusive user logging. Finally, the data generated from the user-logging allowed the automated activity categorisation of the user actions, automated generation of process flow diagrams and chronocyclegraphs

X-ray image reconstruction from a diffraction pattern alone

A solution to the inversion problem of scattering would offer aberration-free diffraction-limited 3D images without the resolution and depth-of-field limitations of lens-based tomographic systems. Powerful algorithms are increasingly being used to act as lenses to form such images. Current image reconstruction methods, however, require the knowledge of the shape of the object and the low spatial frequencies unavoidably lost in experiments. Diffractive imaging has thus previously been used to increase the resolution of images obtained by other means. We demonstrate experimentally here a new inversion method, which reconstructs the image of the object without the need for any such prior knowledge.Comment: 5 pages, 3 figures, improved figures and captions, changed titl

Magnetic Field Effects on the Far-Infrared Absorption in Mn_12-acetate

We report the far-infrared spectra of the molecular nanomagnet Mn_12-acetate (Mn_12) as a function of temperature (5-300 K) and magnetic field (0-17 T). The large number of observed vibrational modes is related to the low symmetry of the molecule, and they are grouped together in clusters. Analysis of the mode character based on molecular dynamics simulations and model compound studies shows that all vibrations are complex; motion from a majority of atoms in the molecule contribute to most modes. Three features involving intramolecular vibrations of the Mn_12 molecule centered at 284, 306 and 409 cm-1 show changes with applied magnetic field. The structure near 284 cm$^{-1}$ displays the largest deviation with field and is mainly intensity related. A comparison between the temperature dependent absorption difference spectra, the gradual low-temperature cluster framework distortion as assessed by neutron diffraction data, and field dependent absorption difference spectra suggests that this mode may involve Mn motion in the crown.Comment: 5 pages, 4 figures, PRB accepte

Studies of transverse and longitudinal relaxations of 55^{55}Mn in molecular cluster magnet Mn12_{12}Ac

The transverse and longitudinal relaxation rates 1/$T_2$ and 1/$T_1$ of $^{55}$Mn in molecular cluster magnet Mn$_{12}$Ac have been measured al low temperatures down to 200mK and in the fields upto 9T. Both of 1/$T_2$ and 1/$T_1$ exhibit remarkable decreases with decreasing temperature and with increasing field, with the relative relation $T_1/T_2 \approx 200$. In the analysis, we adopt a simple model that the thermal fluctuation of the cluster spin $S$=10 associated with the spin-phonon interactionis, is only due to the excitation to the first excited state from the ground state with the average life-times $\tau_ 1$ and $\tau_0$ ($\tau_ 0$$\gg$$\tau_1$). We show that 1/$T_2$ is interpreted in terms of the strong collision regime as given by 1/$\tau_ 0$, and that 1/$T_1$ is understood by the high-frequency limit based on standard perturbation treatment for the step-wise fluctuating field, thus being proportional to 1/$\tau_0\omega_N^2$.Comment: 12 pages, 11 fugures, revtex

A Formalization of the Theorem of Existence of First-Order Most General Unifiers

This work presents a formalization of the theorem of existence of most general unifiers in first-order signatures in the higher-order proof assistant PVS. The distinguishing feature of this formalization is that it remains close to the textbook proofs that are based on proving the correctness of the well-known Robinson's first-order unification algorithm. The formalization was applied inside a PVS development for term rewriting systems that provides a complete formalization of the Knuth-Bendix Critical Pair theorem, among other relevant theorems of the theory of rewriting. In addition, the formalization methodology has been proved of practical use in order to verify the correctness of unification algorithms in the style of the original Robinson's unification algorithm.Comment: In Proceedings LSFA 2011, arXiv:1203.542

Detection Limits for Super-Hubble Suppression of Causal Fluctuations

We investigate to what extent future microwave background experiments might be able to detect a suppression of fluctuation power on large scales in flat and open universe models. Such suppression would arise if fluctuations are generated by causal processes, and a measurement of a small suppression scale would be problematic for inflation models, but consistent with many defect models. More speculatively, a measurement of a suppression scale of the order of the present Hubble radius could provide independent evidence for a fine-tuned inflation model leading to a low-density universe. We find that, depending on the primordial power spectrum, a suppression scale modestly larger than the visible Horizon can be detected, but that the detectability drops very rapidly with increasing scale. For models with two periods of inflation, there is essentially no possibility of detecting a causal suppression scale.Comment: 8 pages, 4 figures, revtex, In Press Physical Review D 200

Access to Operative Intervention Reduces Mortality in Adult Burn Patients in a Resource-Limited Setting in Sub-Saharan Africa

Introduction: Early excision and grafting remains the standard of care after burn injury. However, in a resource-limited setting, operative capacity often limits patient access to surgical intervention. This study sought to describe access to excision and grafting for adult burn patients in a sub-Saharan African burn unit and its relationship with burn-associated mortality. Methods: We analyzed patients recorded in the Kamuzu Central Hospital Burn Registry in Lilongwe, Malawi from 2011–2019. We examined patient characteristics, interventions, and outcomes for adults aged ≥16 years. Modified Poisson regression modeling was used to identify risk factors for mortality. Results: Five hundred and seventy-three patients were included. Median age was 30 years (IQR 23–40) with a male preponderance (63%). Median percent total body surface area burned (%TBSA) was 15% (IQR 8–26) and 68% of burns were caused by flame. 27% (n = 154) had burn excision with skin grafting, with a median time to operation of 18 days (IQR 9–38). When adjusted for age, %TBSA, and time to presentation, operative intervention conferred a survival benefit for patients with flame burns with a RR 0.16 (95% CI 0.06, 0.42). Conclusions: In a resource-limiting setting, access to the operating room is inadequate, and burn patients are not prioritized. While many scald burn patients may be managed with wound care alone, patients with flame burn require surgical intervention to improve clinical outcomes. Burn injury in this region continues to confer a high risk of mortality, and more investment in operative capacity is imperative

Genome editing poses ethical problems that we cannot ignore

The ability to precisely and accurately change almost any part of any genome, even in complex species such as humans, may soon become a reality through genome editing. But with great power comes great responsibility – and few subjects elicit such heated debates about moral rights and wrongs. Although genetic engineering techniques have been around for some time, genome editing can achieve this with lower error rates, more simply and cheaply than ever – although the technology is certainly not yet perfect. Genome editing offers a greater degree of control and precision in how specific DNA sequences are changed. It could be used in basic science, for human health, or improvements to crops. There are a variety of techniques but clustered regularly inter-spaced short palindromic repeats, or CRISPR, is perhaps the foremost. CRISPR has prompted recent calls for a genome editing moratorium from a group of concerned US academics. Because it is the easiest technique to set up and so could be quickly and widely adopted, the fear is that it may be put into use far too soon – outstripping our understanding of its safety implications and preventing any opportunity to think about how such powerful tools should be controlled. Ethical concerns over genetic modification are not new, particularly when it comes to humans. While we don’t think genome editing gives rise to any completely new ethical concerns, there is more to gene editing than just genetic modification..

Genetic and environmental variation in methane emissions of sheep at pasture

A total of 2,600 methane (CH4) and 1,847 CO2 measurements of sheep housed for 1 h in portable accumulation chambers (PAC) were recorded at 5 sites from the Australian Sheep CRC Information Nucleus, which was set up to test leading young industry sires for an extensive range of current and novel production traits. The final validated dataset had 2,455 methane records from 2,279 animals, which were the progeny of 187 sires and 1,653 dams with 7,690 animals in the pedigree file. The protocol involved rounding up animals from pasture into a holding paddock before the first measurement on each day and then measuring in groups of up to 16 sheep over the course of the day. Methane emissions declined linearly (with different slopes for each site) with time since the sheep were drafted into the holding area. After log transformation, estimated repeatability (rpt) and heritability (h(2)) of liveweight-adjusted CH4 emissions averaged 25% and 11.7%, respectively, for a single 1-h measurement. Sire × site interactions were small and nonsignificant. Correlations between EBV for methane emissions and Sheep Genetics Australia EBV for production traits were used as approximations to genetic correlations. Apart from small positive correlations with weaning and yearling weights (r = 0.21-0.25, P < 0.05), there were no significant relationships between production trait and methane EBV (calculated from a model adjusting for liveweight by fitting separate slopes for each site). To improve accuracy, future protocols should use the mean of 2 (rpt = 39%, h(2) = 18.6%) or 3 (rpt = 48%, h(2) = 23.2%) PAC measurements. Repeat tests under different pasture conditions and time of year should also be considered, as well as protocols measuring animals directly off pasture instead of rounding them up in the morning. Reducing the time in the PAC from 1 h to 40 min would have a relatively small effect on overall accuracy and partly offset the additional time needed for more tests per animal. Field testing in PAC has the potential to provide accurate comparisons of animal and site methane emissions, with potentially lower cost/increased accuracy compared to alternatives such as SF6 tracers or open path lasers. If similar results are obtained from tests with different protocols/seasonal conditions, use of PAC measurements in a multitrait selection index with production traits could potentially reduce methane emissions from Australian sheep for the same production level