Patient weight has diverse effects on the prescribing of different antibiotics to dogs

IntroductionVarious factors including body weight-associated treatment cost may influence the probability of dispensing antibiotics to dogs in first-opinion practice, but their effect on specific drug choice remains unclear.MethodsMultiple membership regression modeling was used to investigate the probability of dispensing 12 different antibiotics to dogs of different weights in the context of various disease presentations, using anonymized data obtained from electronic health records of 18 clinics between 2020 and 2022. Data from 14,259 dogs were analyzed.ResultsTreatment choice varied significantly with animal weight. Higher body weight was associated with an increased likelihood of dispensing lower cost antimicrobials such as amoxicillin and trimethoprim sulfonamide, while use of higher cost antimicrobials such as cefovecin was strongly biased to smaller animals. However, these effects were limited when restricted treatment options were available for the target condition.ConclusionThis work demonstrates that anticipated financial costs may result in different treatment choices for canine patients depending on their body weight. Further work is needed to understand the impact of financial pressures on veterinarians’ treatment choices, and the implications for the optimization of antimicrobial stewardship in first opinion practice

A first direct measurement of the intergalactic medium temperature around a quasar at z=6

The thermal state of the intergalactic medium (IGM) provides an indirect probe of both the HI and HeII reionisation epochs. Current constraints on the IGM temperature from the Lya forest are restricted to the redshift range 2<z<4.5, limiting the ability to probe the thermal memory of HI reionisation toward higher redshift. In this work, we present the first direct measurement of the IGM temperature around a z=6 quasar by analysing the Doppler widths of Lya absorption lines in the proximity zone of SDSS J0818+1722. We use a high resolution (R= 40000) Keck/HIRES spectrum in combination with detailed numerical modelling to obtain the temperature at mean density, T_0=23600\pm^5000_6900K (\pm^9200_9300K) at 68 (95) per cent confidence assuming a prior probability 13500K<T_0<38500 K following HI and HeII reionisation. This enables us to place an upper limit on the redshift of HI reionisation, z_H, within 33 comoving Mpc of SDSS J0818+1722. If the quasar reionises the HeII in its vicinity, then in the limit of instantaneous reionisation we infer z_H<9.0 (11.0) at 68 (95) per cent confidence assuming photoheating is the dominant heat source and that HI reionisation is driven by ionising sources with soft spectra, typical of population II stars. If the HI and HeII in the IGM around SDSS J0818+1722 are instead reionised simultaneously by a population of massive metal-free stars, characterised by very hard ionising spectra, we obtain a tighter upper limit of z_H<8.4 (9.4). Initiating reionisation at higher redshifts produces temperatures which are too low with respect to our constraint unless the HI ionising sources or the quasar itself have spectra significantly harder than typically assumed.Comment: 15 pages, 9 figures, accepted to MNRA

Host Range and Genetic Diversity of Arenaviruses in Rodents, United Kingdom

During a study to extend our knowledge of the host range and genetic diversity of arenaviruses in Great Britain, 66 of 1,147 rodent blood samples tested for antibody, and 127 of 482 tested by PCR, were found positive. All sequences most closely resembled those of previously identified lymphocytic choriomeningitis virus

Minimal Peroxide Exposure of Neuronal Cells Induces Multifaceted Adaptive Responses

Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations

Thermal constraints on the reionisation of hydrogen by population-II stellar sources

Measurements of the intergalactic medium (IGM) temperature provide a potentially powerful constraint on the reionisation history due to the thermal imprint left by the photo-ionisation of neutral hydrogen. However, until recently IGM temperature measurements were limited to redshifts 2 < z < 4.8, restricting the ability of these data to probe the reionisation history at z > 6. In this work, we use recent measurements of the IGM temperature in the near-zones of seven quasars at z ~ 5.8 - 6.4, combined with a semi-numerical model for inhomogeneous reionisation, to establish new constraints on the redshift at which hydrogen reionisation completed. We calibrate the model to reproduce observational constraints on the electron scattering optical depth and the HI photo-ionisation rate, and compute the resulting spatially inhomogeneous temperature distribution at z ~ 6 for a variety of reionisation scenarios. Under standard assumptions for the ionising spectra of population-II sources, the near-zone temperature measurements constrain the redshift by which hydrogen reionisation was complete to be z > 7.9 (6.5) at 68 (95) per cent confidence. We conclude that future temperature measurements around other high redshift quasars will significantly increase the power of this technique, enabling these results to be tightened and generalised.Comment: 15 pages, 8 figures, accepted for publication in MNRA

Minimax Current Density Coil Design

'Coil design' is an inverse problem in which arrangements of wire are designed to generate a prescribed magnetic field when energized with electric current. The design of gradient and shim coils for magnetic resonance imaging (MRI) are important examples of coil design. The magnetic fields that these coils generate are usually required to be both strong and accurate. Other electromagnetic properties of the coils, such as inductance, may be considered in the design process, which becomes an optimization problem. The maximum current density is additionally optimized in this work and the resultant coils are investigated for performance and practicality. Coils with minimax current density were found to exhibit maximally spread wires and may help disperse localized regions of Joule heating. They also produce the highest possible magnetic field strength per unit current for any given surface and wire size. Three different flavours of boundary element method that employ different basis functions (triangular elements with uniform current, cylindrical elements with sinusoidal current and conic section elements with sinusoidal-uniform current) were used with this approach to illustrate its generality.Comment: 24 pages, 6 figures, 2 tables. To appear in Journal of Physics D: Applied Physic

Conserved and Differential Effects of Dietary Energy Intake on the Hippocampal Transcriptomes of Females and Males

The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on either ad libitum (control), 20% caloric restriction (CR), 40% CR, intermittent fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1α and mTor pathways in both sexes. IF down-regulated many genes in males including those involved in protein degradation and apoptosis, but up-regulated many genes in females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability

Improved measurements of the intergalactic medium temperature around quasars: possible evidence for the initial stages of He II reionization at z ≃ 6

We present measurements of the intergalactic medium (IGM) temperature within ∼5 proper Mpc of seven luminous quasars at z ≃ 6. The constraints are obtained from the Doppler widths of Lyα absorption lines in the quasar near zones and build upon our previous measurement for the z = 6.02 quasar SDSS J0818+1722. The expanded data set, combined with an improved treatment of systematic uncertainties, yields an average temperature at the mean density of log(T_0/K) = 4.21±^(0.03)_(0.03)(±^(0.06)_(0.07)) at 68 (95) per cent confidence for a flat prior distribution over 3.2 ≤ log (T_0/K) ≤ 4.8. In comparison, temperatures measured from the general IGM at z ≃ 5 are ∼0.3 dex cooler, implying an additional source of heating around these quasars which is not yet present in the general IGM at slightly lower redshift. This heating is most likely due to the recent reionization of He ii in vicinity of these quasars, which have hard and non-thermal ionizing spectra. The elevated temperatures may therefore represent evidence for the earliest stages of He ii reionization in the most biased regions of the high-redshift Universe. The temperature as a function of distance from the quasars is consistent with being constant, log (T_0/K) ≃ 4.2, with no evidence for a line-of-sight thermal proximity effect. However, the limited extent of the quasar near zones prevents the detection of He III regions larger than ∼5 proper Mpc. Under the assumption that the quasars have reionized the He II in their vicinity, we infer that the data are consistent with an average optically bright phase of duration in excess of 10^(6.5) yr. These measurements represent the highest redshift IGM temperature constraints to date, and thus provide a valuable data set for confronting models of H I reionization

Stabilizing All Kahler Moduli in Type IIB Orientifolds

We describe a simple and robust mechanism that stabilizes all Kahler moduli in Type IIB orientifold compactifications. This is shown to be possible with just one non-perturbative contribution to the superpotential coming from either a D3-instanton or D7-branes wrapped on an ample divisor. This moduli-stabilization mechanism is similar to and motivated by the one used in the fluxless G_2 compactifications of M-theory. After explaining the general idea, explicit examples of Calabi-Yau orientifolds with one and three Kahler moduli are worked out. We find that the stabilized volumes of all two- and four-cycles as well as the volume of the Calabi-Yau manifold are controlled by a single parameter, namely, the volume of the ample divisor. This feature would dramatically constrain any realistic models of particle physics embedded into such compactifications. Broad consequences for phenomenology are discussed, in particular the dynamical solution to the strong CP-problem within the framework.Comment: RevTeX, 24 pages, 2 tables, 1 figure

Modulations in the radio light curve of the Type IIb Supernova 2001ig: Evidence for a Wolf-Rayet binary progenitor?

We describe the radio evolution of SN 2001ig in NGC 7424, from 700 days of multi-frequency monitoring with the Australia Telescope Compact Array (ATCA) and the Very Large Array (VLA). We find that deviations of the radio light curves at each frequency from the standard "minishell" model are consistent with density modulations in the circumstellar medium (CSM), which seem to recur with a period near 150 days. One possibility is that these are due to enhanced mass-loss from thermal pulses in an AGB star progenitor. A more likely scenario however is that the progenitor was a Wolf-Rayet star, whose stellar wind collided with that from a massive hot companion on an eccentric 100 day orbit, leading to a regular build-up of CSM material on the required time and spatial scales. Recent observations of "dusty pinwheels" in Wolf-Rayet binary systems lend credibility to this model. Since such binary systems are also thought to provide the necessary conditions for envelope-stripping which would cause the Wolf-Rayet star to appear as a Type Ib/c supernova event rather than a Type II, these radio observations of SN 2001ig may provide the key to linking Type Ib/c SNe to Type IIb events, and even to some types of Gamma-Ray Bursts.Comment: 10 pages, MNRAS, accepte