Differential locomotor activity responses to day-time light intensity in juvenile and adult solitary Cape mole-rats, Georychus capensis (Rodentia: Bathyergidae).

The Cape mole-rat (Georychus capensis) is a solitary, strictly subterranean rodent that is responsive to light and entrains to photic cues despite having a reduced visual system. Circadian entrainment is maintained throughout life, but age can alter the amplitude of the response and re-entrainment time. Mole-rats are long-lived for their size which raises questions regarding the robustness of their circadian rhythms and how impacts their locomotor activity rhythms. The locomotor activity rhythms of juvenile and adult Cape mole-rats were investigated. They were exposed to pre-experimental and post-experimental control cycles under fluorescent lights, six 12 h light:12 h dark cycles of decreasing intensities and a constant dark cycle (DD). All animals exhibited more activity during the dark phases of all light regimes. Juveniles were more active than adults and displayed more variable activity during both the light and dark phases. Adults exhibited relatively stable levels of activity under all experimental conditions, whereas juvenile activity decreased as the light intensity was reduced. The amplitude of Cape mole-rat rhythms was consistently low, but similar across light regimes and between adults and juveniles. Cape mole-rats have functional circadian systems, are primarily nocturnal and respond differentially to light intensity depending on their age. Light intensity does not affect the locomotor activity responses of Cape mole-rats in a predictable manner, and could indicate more complex interactions with light wavelengths. The circadian systems of juveniles appear to be more sensitive than those of adults, although the mechanism of the light response remains unclear.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

The best of both worlds: no apparent trade-off between immunity and reproduction in two group-living African mole-rat species.

Co-operatively breeding mammals often exhibit a female reproductive skew and suppression of the subordinate non-breeding group members. According to evolutionary theory and the immunity-fertility axis, an inverse relationship between reproductive investment and survival (through immunocompetence) is expected. As such, this study investigated if a trade-off between immunocompetence and reproduction arises in two co-operatively breeding African mole-rat species, namely the Damaraland mole-rat (Fukomys damarensis) and common mole-rat (Cryptomys hottentotus hottentotus), which possess female reproductive division of labour. This study also attempted to investigate the relationship between the immune and endocrine systems in Damaraland mole-rats. There was no trade-off between reproduction and immunocompetence in co-operatively breeding African mole-rat species, and in the case of the Damaraland mole-rats, breeding females (BFs) possessed increased immunocompetence compared with non-breeding females (NBFs). Furthermore, the increased levels of progesterone possessed by Damaraland mole-rat BFs compared with NBFs appear to be correlated to increased immunocompetence. In comparison, BF and NBF common mole-rats possess similar immunocompetence. The species-specific differences in the immunity-fertility axis may be due to variations in the strengths of reproductive suppression in each species. This article is part of the theme issue 'Evolutionary ecology of inequality'.

High resolution imaging with focused kV x-rays for small animal radio-neuromodulation.

BACKGROUND: High precision radiotherapy with small irradiator size has potential in many treatment applications involving small shallow targets, with small animal radio-neuromodulation as an intriguing example. A focused kV technique based on novel usage of polycapillary x-ray lenses can focus x-ray beams to <0.2 mm in diameter, which is ideal for such uses. PURPOSE: Such an application also requires high resolution CT images for treatment planning and setup. In this work, we demonstrate the feasibility of using a virtual focal spot generated with an x-ray lens to perform high-resolution CBCT acquisition. METHOD: The experiment with x-ray lens was set up on an x-ray tabletop system to generate a virtual focal spot. The flood field images with and without the x-ray lens were first compared. A pinhole image was acquired for the virtual focal spot and compared with the one acquired with the conventional focal spot without the lens. The planar imaging resolution with and without the lens were evaluated using a line pair resolution phantom. The spatial resolution of the two settings were estimated by reconstructing a 0.15-mm wire phantom and comparing its full width half maximum (FWHM). A CBCT scan of a rodent head was also acquired to further demonstrate the improved resolution using the x-ray lens. RESULT: The proposed imaging setup with x-ray lens had a limited exposure area of 5 cm by 5 cm on the detector, which was suitable for guiding radio-neuromodulation to a small target in rodent brain. Compared to conventional imaging acquisition with a measured x-ray focal spot of 0.395 mm FWHM, the virtual focal spot size was measured at 0.175 mm. The reduction in focal spot size with lens leads to an almost doubled planar imaging resolution and a 26% enhancement in 3D spatial resolution. A realistic CBCT acquisition of a rodent head mimicked the imaging acquisition step for radio-neuromodulation and further showed the improved visualization for fine structures. CONCLUSION: This work demonstrated that the focused kV x-ray technique was capable of generating small focal spot size of <0.2 mm, which substantially improved x-ray imaging resolution for small animal imaging.

Single-Shot Quantitative X-ray Imaging Using a Primary Modulator and Dual-Layer Detector: Simulation and Phantom Studies.

Conventional x-ray imaging provides little quantitative information due to scatter, beam hardening, and overlaying tissues. A single-shot quantitative x-ray imaging (SSQI) method was previously developed to quantify material-specific densities in x-ray imaging by combining the use of a primary modulator (PM) and dual-layer (DL) detector. The feasibility of this concept was demonstrated with simulations using an iterative patch-based method. In this work, we propose a new algorithm pipeline for SSQI that enables accurate quantification and high computational efficiency. The DL images contain four measurements that are obtained behind the unattenuated and partially attenuated regions of the PM of each layer. Using the low-frequency property of scatter and a pre-calibrated material decomposition (MD), four unknowns (i.e., two scatter images and two material-specific images) are jointly recovered by directly solving four equations given by the four measurements. We tested this algorithm in simulations and further demonstrated its efficacy on chest phantom experiments. Through simulation, we show that the new method for MD is robust against scatter. Its performance improves with smaller PM pitch size and smaller focal spot blur. The RMSE in material-specific images compared to ground truth reduces by 52%-84% versus without scatter correction. For our experimental study, we successfully separated soft tissue and bone. The computational time for processing each view was ~8 s without optimization. The reported results further strengthen the potential of SSQI for widespread adoption, leading to quantitative imaging not only for x-ray imaging but also for real-time image guidance or cone-beam CT.

Who moves in vulnerable Caribbean neighborhoods? Positive deviance for physical activity: Findings from the Jamaica health and Lifestyle Survey 2017 (JHLS III).

Decreased physical activity (PA) has been associated with residents living in neighborhoods perceived as being disordered or having high crime levels. What is unknown are the characteristics of individuals who engage in moderate to vigorous levels of PA (MVPA) despite living in these vulnerable neighborhoods, or who may be referred to as positive deviants (PD). We examined the factors associated with PD for PA among Jamaicans. Between 2016 and 2017 the Jamaica Health and Lifestyle Survey, a cross-sectional nationally representative survey (n = 2807), was conducted on individuals aged 15 years and older. Regression analyses were performed to identify associations with PD, defined using engagement in MVPA among persons living in vulnerable neighborhoods (N = 1710). Being female (odds ratio [OR]a = 0.64 (0.48, 0.86); p = 0.003), obese while living in an urban area (ORa = 0.39; 95 % CI = 0.26, 0.59; p < 0.0001), unemployed (ORa = 0.53; 95 % CI = 0.39, 0.73; p < 0.0001), or a student (ORa = 0.62; 95 % CI = 0.39, 0.98); p = 0.041) was associated with a significantly lower likelihood of PD, while having a personal medical history of at least one chronic disease significantly increased likelihood (ORa = 1.43; 95 % CI = 1.08, 1.90; p = 0.014). Taking a PD approach may be one angle to consider in trying to determine what is working and for whom, so that this may be harnessed in policy, prevention and intervention programming to increase PA.

Robust deep learning-based protein sequence design using ProteinMPNN.

Although deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as Rosetta. Here, we describe a deep learning-based protein sequence design method, ProteinMPNN, that has outstanding performance in both in silico and experimental tests. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4% compared with 32.9% for Rosetta. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. We demonstrate the broad utility and high accuracy of ProteinMPNN using x-ray crystallography, cryo-electron microscopy, and functional studies by rescuing previously failed designs, which were made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers, tetrahedral nanoparticles, and target-binding proteins.

The endocrine control of reproductive suppression in an aseasonally breeding social subterranean rodent, the Mahali mole-rat (Cryptomys hottentotus mahali).

Cooperative behaviour, sociality and reproductive suppression in African mole-rats have been extensively studied. Nevertheless, endocrine correlates of some species of social mole-rats have been neglected, and these species may hold the key to understanding the behavioural and physiological complexity that allows the maintenance of social groups in African mole-rats. In this study, we investigated endocrine correlates implicated in the suppression of reproduction and cooperative behaviours, namely glucocorticoids (a stress-related indicator) through faecal glucocorticoid metabolites (fGCMs), plasma testosterone (an indicator of aggression) and plasma prolactin in the Mahali mole-rat (Cryptomys hottentotus mahali) across reproductive classes (breeding females and males, non-breeding females and males) and season (wet and dry). Breeders possessed higher levels of testosterone than non-breeders. In reproductively suppressed non-breeding females, fGCMs were significantly higher than in breeders. Furthermore, an adrenocorticotropic hormone stimulation test (ACTH challenge test) on both male and female non-breeders revealed that female non-breeders show a more significant response to the ACTH challenge than males. At the same time, plasma prolactin levels were equally elevated to similar levels in breeding and non-breeding females. Chronically high levels of prolactin and fGCM are reported to cause reproductive suppression and promote cooperative behaviours in non-breeding animals. Furthermore, there was a negative relationship between plasma prolactin and progesterone in non-breeding females. However, during the wet season, a relaxation of suppression occurs through reduced prolactin which corresponds with elevated levels of plasma progesterone in non-breeding females. Therefore, prolactin is hypothesised to be the primary hormone controlling reproductive suppression and cooperative behaviours in non-breeding females. This study provides new endocrine findings for the maintenance of social suppression in the genus Cryptomys.

Species limits and phylogeographic structure in two genera of solitary African mole-rats Georychus and Heliophobius.

African mole-rats (Bathyergidae) are an intensively studied family of subterranean rodents including three highly social and three solitary genera. Although their phylogenetic interrelations are clear, genetic diversity and the number of species within each genus is much less certain. Among the solitary genera, Heliophobius and Georychus were for a long time considered as monotypic, but molecular studies demonstrated strong phylogeographic structure within each genus and proposed that they represent complexes of cryptic species. The present study re-evaluates their internal genetic/phylogenetic structure using a combination of methodological approaches. We generated datasets of one mitochondrial and six specifically selected nuclear markers as well as of a large number of double digest restriction site associated (ddRAD) loci and then applied species delimitation analyses based on the multispecies coalescent model or clustering on co-ancestry matrices. The population structure was largely congruent across all analyses, but the methods differed in their resolution scale when determining distinct gene pools. While the multispecies coalescent model distinguished five Georychus and between eleven to thirteen Heliophobius gene pools in both Sanger sequenced and ddRAD loci, two clustering algorithms revealed significantly finer or coarser structure in ddRAD based co-ancestry matrices. Tens of clusters were distinguished by fineRADstructure and one (in Georychus) or two clusters (in Heliophobius) by Infomap. The divergence dating of the bathyergid phylogeny estimated that diversification within both genera coincided with the onset of the Pleistocene and was likely driven by repeated large-scale climatic changes. Based on this updated genetic evidence, we suggest recognizing one species of Georychus and two species of Heliophobius, corresponding to a northern and southern major lineage, separated by the Eastern Arc Mountains. Yet, the final taxonomic revision should await integrated evidence stemming from e.g. morphological, ecological, or behavioral datasets.

Characterization of x-ray focal spots using a rotating edge.

Purpose: The focal spot size and shape of an x-ray system are critical factors to the spatial resolution. Conventional approaches to characterizing the focal spot use specialized tools that usually require careful calibration. We propose an alternative to characterize the x-ray source's focal spot, simply using a rotating edge and flat-panel detector. Methods: An edge is moved to the beam axis, and an edge spread function (ESF) is obtained at a specific angle. Taking the derivative of the ESF provides the line spread function, which is the Radon transform of the focal spot in the direction parallel to the edge. By rotating the edge about the beam axis for 360 deg, we obtain a complete Radon transform, which is used for reconstructing the focal spot. We conducted a study on a clinical C-arm system with three focal spot sizes (0.3, 0.6, and 1.0 mm nominal size), then compared the focal spot imaged using the proposed method against the conventional pinhole approach. The full width at half maximum (FWHM) of the focal spots along the width and height of the focal spot were used for quantitative comparisons. Results: Using the pinhole method as ground truth, the proposed method accurately characterized the focal spot shapes and sizes. Quantitatively, the FWHM widths were 0.37, 0.65, and 1.14 mm for the pinhole method and 0.33, 0.60, and 1.15 mm for the proposed method for the 0.3, 0.6, and 1.0 mm nominal focal spots, respectively. Similar levels of agreement were found for the FWHM heights. Conclusions: The method uses a rotating edge to characterize the focal spot and could be automated in the future using a system's built-in collimator. The method could be included as part of quality assurance tests of image quality and tube health.

Single-pass metal artifact reduction using a dual-layer flat panel detector.

PURPOSE: Metal artifact remains a challenge in cone-beam CT images. Many image domain-based segmentation methods have been proposed for metal artifact reduction (MAR), which require two-pass reconstruction. Such methods first segment metal from a first-pass reconstruction and then forward-project the metal mask to identify them in projections. These methods work well in general but are limited when the metal is outside the scan field-of-view (FOV) or when the metal is moving during the scan. In the former, even reconstructing with a larger FOV does not guarantee a good estimate of metal location in the projections; and in the latter, the metal location in each projection is difficult to identify due to motion. Single-pass methods that detect metal in single-energy projections have also been developed, but often have imperfect metal detection that leads to residual artifacts. In this work, we develop a MAR method using a dual-layer (DL) flat panel detector, which improves performance for single-pass reconstruction. METHODS: In this work, we directly detect metal objects in projections using dual-energy (DE) imaging that generates material-specific images (e.g., soft tissue and bone), where the metal stands out in bone images when nonuniform soft tissue background is removed. Metal is detected via simple thresholding, and entropy filtration is further applied to remove false-positive detections. A DL detector provides DE images with superior temporal and spatial registration and was used to perform the task. Scatter correction was first performed on DE raw projections to improve the accuracy of material decomposition. One phantom mimicking a liver biopsy setup and a cadaver head were used to evaluate the metal reduction performance of the proposed method and compared with that of a standard two-pass reconstruction, a previously published sinogram-based method using a Markov random field (MRF) model, and a single-pass projection-domain method using single-energy imaging. The phantom has a liver steering setup placed in a hollow chest phantom, with embedded metal and a biopsy needle crossing the phantom boundary. The cadaver head has dental fillings and a metal tag attached to its surface. The identified metal regions in each projection were corrected by interpolation using surrounding pixels, and the images were reconstructed using filtered backprojection. RESULTS: Our current approach removes metal from the projections, which is robust to FOV truncation during imaging acquisition. In case of FOV truncation, the method outperformed the two-pass reconstruction method. The proposed method using DE renders better accuracy in metal segmentation than the MRF method and single-energy method, which were prone to false-positive errors that cause additional streaks. For the liver steering phantom, the average spatial nonuniformity was reduced from 0.127 in uncorrected images to 0.086 using a standard two-pass reconstruction and to 0.077 using the proposed method. For the cadaver head, the average standard deviation within selected soft tissue regions ( σ s ) was reduced from 209.1 HU in uncorrected images to 69.1 HU using a standard two-pass reconstruction and to 46.8 HU using our proposed method. The proposed method reduced the processing time by 31% as compared with the two-pass method. CONCLUSIONS: We proposed a MAR method that directly detects metal in the projection domain using DE imaging, which is robust to truncation and superior to that of single-energy imaging. The method requires only a single-pass reconstruction that substantially reduces processing time compared with the standard two-pass metal reduction method.

Flexibility in body temperature rhythms of free-living natal mole-rats (Cryptomys hottentotus natalensis).

The subterranean niche is a specialised and particularly challenging environment to obtain direct physiological and behavioural measurements from free-living animals. Rhythmicity has been examined in many mole-rat species in the laboratory, but field reports are relatively scarce. We implanted Natal mole-rats with temperature loggers in summer and winter to record core body temperature (Tb), before releasing the animals again. Animals were recaptured after two months to recover the loggers. Natal mole-rats can maintain rhythmicity of their Tb in their natural habitat and display seasonal differences in their Tb rhythms. During winter mole-rats have unimodal Tb rhythms, whereas in summer many animals have bimodal Tb patterns, which may be related to temperatures in the foraging burrows close to the soil surface. Individuals from the same colonies frequently exhibited similar rhythms, especially in the larger colonies, which may indicate social entrainment of rhythms. Males and females differ in their seasonal variation of Tb, with males having more variation in winter, while the opposite was true for females. Entire colonies may undergo sporadic torpor bouts, presumably to conserve energy, but the trigger for these events is unknown. This is the first report of torpor occurring in an African mole-rat species. The ability to respond to environmental and social cues, while rhythms remain flexible, can provide an adaptive advantage to animals living in challenging and energetically demanding habitats.

Deep learning-based reconstruction of interventional tools and devices from four X-ray projections for tomographic interventional guidance.

PURPOSE: Image guidance for minimally invasive interventions is usually performed by acquiring fluoroscopic images using a monoplanar or a biplanar C-arm system. However, the projective data provide only limited information about the spatial structure and position of interventional tools and devices such as stents, guide wires, or coils. In this work, we propose a deep learning-based pipeline for real-time tomographic (four-dimensional [4D]) interventional guidance at conventional dose levels. METHODS: Our pipeline is comprised of two steps. In the first one, interventional tools are extracted from four cone-beam CT projections using a deep convolutional neural network. These projections are then Feldkamp reconstructed and fed into a second network, which is trained to segment the interventional tools and devices in this highly undersampled reconstruction. Both networks are trained using simulated CT data and evaluated on both simulated data and C-arm cone-beam CT measurements of stents, coils, and guide wires. RESULTS: The pipeline is capable of reconstructing interventional tools from only four X-ray projections without the need for a patient prior. At an isotropic voxel size of 100 µ m , our methods achieve a precision/recall within a 100 µ m environment of the ground truth of 93%/98%, 90%/71%, and 93%/76% for guide wires, stents, and coils, respectively. CONCLUSIONS: A deep learning-based approach for 4D interventional guidance is able to overcome the drawbacks of today's interventional guidance by providing full spatiotemporal (4D) information about the interventional tools at dose levels comparable to conventional fluoroscopy.

African Naked Mole-Rats Demonstrate Extreme Tolerance to Hypoxia and Hypercapnia.

Naked mole-rats are extremely tolerant to low concentrations of oxygen (hypoxia) and high concentrations of carbon dioxide (hypercapnia), which is consistent with the environment that they inhabit. Naked mole-rats combine subterranean living with living in very densely populated colonies where oxygen becomes depleted and carbon dioxide accumulates. In the laboratory, naked mole-rats fully recover from 5 h exposure to 5% O2 and 5 h exposure to 80% CO2, whereas both conditions are rapidly lethal to similarly sized laboratory mice. During anoxia (0% O2) naked mole-rats enter a suspended animation-like state and switch from aerobic metabolism of glucose to anaerobic metabolism of fructose. Additional fascinating characteristics include that naked mole-rats show intrinsic brain tolerance to anoxia; a complete lack of hypoxia-induced and CO2-induced pulmonary edema; and reduced aversion to high concentrations of CO2 and acidic fumes. Here we outline a constellation of physiological and molecular adaptations that correlate with the naked mole-rat's hypoxic/hypercapnic tolerance and which offer potential targets for ameliorating pathological conditions in humans, such as the damage caused during cerebral ischemia.

A non-invasive assessment of essential trace element utilization at different trophic levels in African wildlife.

The complex relationships that exist between terrestrial mammals and their habitats make African ecosystems highly interactive environments. Anthropogenic activities including climate change have altered geochemical cycles, which influence nutrient availability and deficiency at local, regional and global scales. As synergistic and antagonistic interactions occur between essential elements at both deficiency and excess concentrations, the differences in feeding strategy between trophically distinct groups of terrestrial vertebrates are likely to influence the degree to which overall nutrient needs are met or may be deficient. The overall aim of this study was to investigate and compare quantitative differences of nine essential elements in terrestrial vertebrates occupying different trophic levels within two protected areas; Tswalu Kalahari Reserve (TKR) and Manyeleti Nature Reserve (MNR) South Africa, using faeces as an analytical matrix. Results from linear mixed effects models highlight that concentrations varied widely between individuals. Overall, measured concentrations above their respective means were evident for B and Mn in herbivores, Fe in omnivores and Cu, Co, Fe, Se and Zn in carnivores. Measured concentrations of Mo and Ni did not differ significantly between trophic groups. Although site-specific differences were evident for specific elements, measured mean concentrations of B, Co, Cu, Fe, Mo, Ni, Se and Zn were significantly higher overall at the MNR study site compared to the TKR site. This is the first study to non-invasively assess essential element concentrations across trophic levels in free ranging African wildlife species within protected areas of the savannah biome. Combined with the assessment of environmental matrices, this approach can be used as an effective diagnostic tool for the assessment of animal welfare and the management of protected areas globally.

Oxidative stress in response to heat stress in wild caught Namaqua rock mice, Micaelamys namaquensis.

Modelling of anthropogenic induced climate suggests more frequent and severe heatwaves in the future, which are likely to result in the mass die-off of several species of organisms. Oxidative stress induced by severe heat stress has previously been associated with a reduction in animal cognitive performance, depressed reproduction and lower life expectancy. Little is known about the non-lethal consequences of species should they survive extreme heat exposure. We investigated the oxidative stress experienced by the Namaqua rock mouse, a nocturnal rodent, using two experimental heat stress protocols, a 6 hour acute heat stress protocol without access to water and a 3-day heatwave simulation with ad libitum water. Oxidative stress was determined in the liver, kidney and brain using malondialdehyde (MDA) and protein carbonyl (PC) as markers of oxidative damage, and superoxide dismutase (SOD) and total antioxidant capacity (TAC) as markers of antioxidant defence. Incubator heat stress (heat and dehydration stress) was brought about by increasing the body temperatures of animals to 39-40.8 °C for 6 hours. Following incubator heat stress, significantly higher levels of MDA were observed in the liver. Dehydration did not explain the variation in oxidative markers and is likely a combined effect of thermal and dehydration stress. Individual body mass was significantly negatively correlated to kidney SOD and lipid peroxidation. A heatwave was simulated using a temperature cycle that would naturally occur during a heatwave in the species' local habitat, with a maximal ambient temperature of 38 °C. Following the simulated heatwave, SOD activity of the kidney demonstrated significantly lowered activity suggesting oxidative stress. Current heat waves in this species have the potential of causing oxidative stress. Heat and dehydration stress following exacerbated temperatures are likely to incur significant oxidative stress in multiple tissues demonstrating the importance of water availability to allow for rehydration to prevent oxidative stress.

A mixed-methods evaluation of the impact of a pharmacist-led feedback pilot intervention on insulin prescribing in a hospital setting.

AIMS: To explore the impact of a prescribing feedback intervention on insulin prescribing. METHODS: This was a mixed-methods study in a hospital setting. An insulin prescribing feedback intervention was delivered verbally and in writing to twelve doctors. Insulin prescribing error frequency was compared to ten doctors who had not received the feedback intervention. Insulin prescribing was audited over four weeks at the start and end of the intervention period. Semi-structured interviews were conducted with participating doctors who had received feedback, and qualitative data analysed thematically to explore the impact of the intervention on their prescribing practice. RESULTS: Prescribing data were collected on 370 insulin prescriptions with 241 errors identified. A significant reduction (χ2 = 22.6, p=<0.05) in insulin prescribing error frequency was observed in the intervention group, with a non-significant increase reported in the control group. Feedback was received positively and considered valuable by doctors, supporting development of their knowledge and skills and encouraging reflection on their prescribing performance. Doctors described enhanced confidence in insulin prescribing and a desire to improve as a prescriber and avoid harm, with feedback raising awareness of their development needs. Prescribers also described enhanced team work, with greater information and feedback seeking behavior to inform future prescribing decisions. CONCLUSIONS: Feedback has potential to improve insulin prescribing and is a valued and acceptable process intervention for doctors. The impact on insulin prescribing practice is varied and complex influencing the capability, opportunity and motivation of prescribers to adapt and evolve their behavior in response to ongoing feedback.

An analysis of scatter characteristics in x-ray CT spectral correction.

X-ray scatter remains a major physics challenge in volumetric computed tomography (CT), whose physical and statistical behaviors have been commonly leveraged in order to eliminate its impact on CT image quality. In this work, we conduct an in-depth derivation of how the scatter distribution and scatter to primary ratio (SPR) will change during the spectral correction, leading to an interesting finding on the property of scatter. Such a characterization of scatter's behavior provides an analytic approach of compensating for the SPR as well as approximating the change of scatter distribution after spectral correction, even though both of them might be significantly distorted as the linearization mapping function in spectral correction could vary a lot from one detector pixel to another. We conduct an evaluation of SPR compensations (SPRCs) on a Catphan phantom and an anthropomorphic chest phantom to validate the characteristics of scatter. In addition, this scatter property is also directly adopted into CT imaging using a spectral modulator with flying focal spot technology (SMFFS) as an example to demonstrate its potential in practical applications. For cone-beam CT (CBCT) scans at both 80 and 120 kVp, CT images with accurate CT numbers can be achieved after spectral correction followed by the appropriate SPRC based on our presented scatter property. In the case of the SMFFS based CBCT scan of the Catphan phantom at 120 kVp, after a scatter correction using an analytic algorithm derived from the scatter property, CT image quality was significantly improved, with the averaged root mean square error reduced from 297.9 to 6.5 Hounsfield units.

Densely sampled spectral modulation for x-ray CT using a stationary modulator with flying focal spot: a conceptual and feasibility study of scatter and spectral correction.

PURPOSE: Modulation of the x-ray source in computed tomography (CT) by a designated filter to achieve a desired distribution of photon flux has been greatly advanced in recent years. In this work, we present a densely sampled spectral modulation (DSSM) as a promising low-cost solution to quantitative CT imaging in the presence of scatter. By leveraging a special stationary filter (namely a spectral modulator) and a flying focal spot, DSSM features a strong correlation in the scatter distributions across focal spot positions and sees no substantial projection sparsity or misalignment in data sampling, making it possible to simultaneously correct for scatter and spectral effects in a unified framework. METHODS: The concept of DSSM is first introduced, followed by an analysis of the design and benefits of using the stationary spectral modulator with a flying focal spot (SMFFS) that dramatically changes the data sampling and its associated data processing. With an assumption that the scatter distributions across focal spot positions have strong correlation, a scatter estimation and spectral correction algorithm from DSSM is then developed, where a dual-energy modulator along with two flying focal spot positions is of interest. Finally, a phantom study on a tabletop cone-beam CT system is conducted to understand the feasibility of DSSM by SMFFS, using a copper modulator and by moving the x-ray tube position in the X direction to mimic the flying focal spot. RESULTS: Based on our analytical analysis of the DSSM by SMFFS, the misalignment of low- and high-energy projection rays can be reduced by a factor of more than 10 when compared with a stationary modulator only. With respect to modulator design, metal materials such as copper, molybdenum, silver, and tin could be good candidates in terms of energy separation at a given attenuation of photon flux. Physical experiments using a Catphan phantom as well as an anthropomorphic chest phantom demonstrate the effectiveness of DSSM by SMFFS with much better CT number accuracy and less image artifacts. The root mean squared error was reduced from 297.9 to 6.5 Hounsfield units (HU) for the Catphan phantom and from 409.3 to 39.2 HU for the chest phantom. CONCLUSIONS: The concept of DSSM using a SMFFS is proposed. Phantom results on its scatter estimation and spectral correction performance validate our main ideas and key assumptions, demonstrating its potential and feasibility for quantitative CT imaging.