Evaluation of the current use of MRI to aid the diagnosis of axial spondyloarthritis in the UK: results from a freedom of information request.

AIM: To evaluate the impact of recommendations from the 2019 consensus exercise conducted by radiologists and rheumatologists on the use of magnetic resonance imaging (MRI) to investigate axial spondyloarthritis (axSpA) in clinical practice. MATERIALS AND METHODS: A freedom of information (FOI) request was used to assess the use of MRI in the diagnosis of axSpA and radiologists' awareness of the 2019 guidance across all NHS Trusts and Health Boards in the UK, including England, Scotland, Northern Ireland, and Wales. RESULTS: The FOI request was sent to 150 Trusts/Health Boards, and 93 full responses were received. Of the 93 respondents (97%), 90 reported familiarity with the term axSpA and 70/93 (75%) reported familiarity with the 2019 recommendations. Awareness of recommendations regarding specific MRI features supportive of the diagnosis of axSpA was 74/93 (80%) for the sacroiliac joints (SIJs) and 66/93 (71%) for the spine. The median wait for MRI acquisition was 2-3 months. Fifty-two of the 93 (56%) reported at least some outsourcing of axSpA MRI (33%/29% for specialist/non-specialist outsourcing respectively); 32/93 (34%) reported some scans being reported in-house by non-musculoskeletal radiologists. CONCLUSION: There have been several positive developments in the understanding and use of MRI for the diagnosis of axSpA in the UK since the 2017 survey, although substantial scope for further improvement remains. Several new challenges have also emerged, including the increase in waiting times, reliance on outsourcing, and the reporting of MRI by non-musculoskeletal radiologists.

Quantifying bone structure, micro-architecture, and pathophysiology with MRI.

The radiology of bone has been transformed by magnetic resonance imaging, which has the ability to interrogate bone's complex architecture and physiology. New techniques provide information about both the macrostructure and microstructure of bone ranging from micrometre detail to the whole skeleton. Furthermore functional information about bone physiology can be used to detect disease early before structural changes occur. The future of bone imaging is in quantifying the anatomical and functional information to diagnose and monitor disease more precisely. This review explores the state of the art in quantitative MRI bone imaging.

Saccadic foraging: reduced reaction time to informative targets.

The study of saccadic reaction times has revealed a great deal about the neural mechanisms underlying neural decision, in terms of Bayesian factors such as prior probability and information supply. In addition, recent work has shown that saccades are faster to visual targets associated with conventional monetary or food rewards. However, because the purpose of saccades is to acquire information, it could be argued that this is an unnatural situation: the most natural and fundamental reward is the amount of information supplied by a target. Here, we report the results of a study investigating the hypothesis that a saccade to a target whose colour provides information about the location of a subsequent target is faster than to one that does not. We show that the latencies of saccades to a location that provides reliable information about the location of a future target are indeed shorter, their distributions being shifted in a way that implies that the rate of rise of the underlying decision signal is increased. In a race between alternative targets, this means that expected information will be an important factor in deciding where to look, so that 'foraging' saccades are more likely to be made to useful targets.

Multimodality imaging of pulmonary infarction.

The impact of absent pulmonary arterial and venous flow on the pulmonary parenchyma depends on a host of factors. These include location of the occlusive insult, the speed at which the occlusion develops and the ability of the normal dual arterial supply to compensate through increased bronchial arterial flow. Pulmonary infarction occurs when oxygenation is cut off secondary to sudden occlusion with lack of recruitment of the dual supply arterial system. Thromboembolic disease is the commonest cause of such an insult but a whole range of disease processes intrinsic and extrinsic to the pulmonary arterial and venous lumen may also result in infarcts. Recognition of the presence of infarction can be challenging as imaging manifestations often differ from the classically described wedge shaped defect and a number of weighty causes need consideration. This review highlights aetiologies and imaging appearances of pulmonary infarction, utilising cases to illustrate the essential role of a multimodality imaging approach in order to arrive at the appropriate diagnosis.

Admixture analysis in relation to pedigree studies of introgression in a minority British cattle breed: the Lincoln Red.

Investigation of historic population processes using molecular data has been facilitated by the use of approximate Bayesian computation (ABC), which enables the consideration of multiple alternative demographic scenarios. The Lincoln Red cattle breed provides a relatively simple example of two well-documented admixture events. Using molecular data for this breed, we found that structure did not resolve very low (<5% levels) of introgression, possibly due to sampling limitations. We evaluated the performance of two ABC approaches (2BAD and DIYABC) against those of two earlier methodologies, ADMIX and LEADMIX, by comparing their interpretations with the conclusions drawn from herdbook analysis. The ABC methods gave credible values for the proportions of the Lincoln Red genotype that are attributable to Aberdeen Angus and Limousin, although estimates of effective population size and event timing were not realistic. We suggest ABC methods are a valuable supplement to pedigree-based studies but that the accuracy of admixture determination is likely to diminish with increasing complexity of the admixture scenario.

Dual energy imaging using a clinical on-board imaging system.

Dual energy (DE) imaging consists of obtaining kilovoltage (kV) x-ray images at two different diagnostic energies and performing a weighted subtraction of these images. A third image is then produced that highlights soft tissue. DE imaging has been used by radiologists to aid in the detection of lung malignancies. However, it has not been used clinically in radiotherapy. The goal of this study is to assess the feasibility of performing DE imaging using a commercial on-board imaging system. Both a simple and an anthropomorphic phantom were constructed for this analysis. Planar kV images of the phantoms were obtained using varied imaging energies and mAs. Software was written to perform DE subtraction using empirically determined weighting factors. Tumor detectability was assessed quantitatively using the signal-difference-to-noise ratio (SDNR). Overall DE subtraction suppressed high density objects in both phantoms. The optimal imaging technique, providing the largest SDNR with a dose less than our reference technique was 140 kVp, 1.0 mAs and 60 kVp, 3.2 mAs. Based on this analysis, DE subtraction imaging is feasible using a commercial on-board imaging system and may improve the visualization of tumors in lung cancer patients undergoing image-guided radiotherapy.

SU-E-J-44: Dual Energy Subtraction Imaging to Improve Tumor Visibility at Oblique Angles.

PURPOSE: To characterize the contrast improvement of simulated tumors in an anthropomorphic phantom using Dual Energy (DE) subtraction with a clinical on-board imager (OBI) at oblique angles. METHODS: An Alderson lung/chest anthropomorphic phantom with simulated tumors in the thoracic cavity was imaged using a sequential DE imaging methodology. High (120kVp) and low (60kVp) planar images were obtained in pairs every 100 in a full (3600) rotation using the OBI (Varian Medical Systems, Palo Alto, CA). Optimal mAs settings for DE component images were determined byvarying the x-ray exposure time, while maintaining a constant tube current. DE images were created to best suppress the bone overlaying the simulated tumors. Tumor visibility in DE images was quantified using the Contrast-to-Noise Ratio (CNR). The ratio of the CNR from the DE image relative to a single image (standard protocol) was evaluated as a function of gantry angle. RESULTS: CNR was improved with DE imaging by an average ratio of 1.66 over all gantry angles. The greatest improvement occurred at gantry angles where the tumor was obstructed by the ribs alone. More modest improvements were observed where the tumor overlapped other soft tissue structures (such as the heart) or the dense spine, on a given projection. CONCLUSIONS: This study illustrates the feasibility of performing DE imaging at oblique gantry angles using a clinical on-board imaging system. Incorporating DE imaging into clinical practice may allow for verification of tumor position at oblique gantry angles, and may facilitate the development of markerless motion tracking techniques. Supported by a grant from Varian Medical Systems.

2BAD: an application to estimate the parental contributions during two independent admixture events.

Several approaches have been developed to calculate the relative contributions of parental populations in single admixture event scenarios, including Bayesian methods. In many breeds and populations, it may be more realistic to consider multiple admixture events. However, no approach has been developed to date to estimate admixture in such cases. This report describes a program application, 2BAD (for 2-event Bayesian ADmixture), which allows the consideration of up to two independent admixture events involving two or three parental populations and a single admixed population, depending on the number of populations sampled. For each of these models, it is possible to estimate several parameters (admixture, effective sizes, etc.) using an approximate Bayesian computation approach. In addition, the program allows comparing pairs of admixture models, determining which is the most likely given data. The application was tested through simulations and was found to provide good estimates for the contribution of the populations at the two admixture events. We were also able to determine whether an admixture model was more likely than a simple split model.

The population genetic effects of ancestry and admixture in a subdivided cattle breed.

The genetic structure of the Dexter, a minority cattle breed with complex demographic history, was investigated using microsatellite markers and a range of statistical approaches designed to detect both admixture and genetic drift. Modern representatives of two putative ancestral populations, the Devon and Kerry, together with the different populations of the Dexter, which have experienced different demographic histories, were analysed. Breed units showed comparatively high levels of genetic variability (H(E) = 0.63-0.68); however, distinct genetic subgroups were detected within the Dexter, which could be attributed to known demographic events. Much lower diversity was identified in three small, isolated Dexter populations (H(E) = 0.52-0.55) and higher differentiation (F(ST) > 0.13) was found. For one of these populations, where strong selection has taken place, we also found evidence of a demographic bottleneck. Three methods for quantifying breed admixture were applied and substantial method-based variation in estimates for the genetic contribution of the two proposed ancestral populations for each subdivision of the Dexter was found. Results were consistent only in the case of a group consisting of selected Traditional Dexter animals, where the ancestor of the modern Kerry breed was also determined as the greater parental contributor to the Dexter. The inconsistency of estimation of admixture proportions between the methods highlights the potentially confounding role of genetic drift in shaping small population structure, and the consequences of accurately describing population histories from contemporary genetic data.

Transfusion medicine in India: a survey of current practice.

The new Indian National Blood Policy intends to improve the provision of easily accessible safe blood and blood components, available according to need. There is a requirement for information on patterns of blood transfusion in India, to help understand the potential for changes in transfusion practice and the organization of blood services, and to help ensure optimal use of this valuable and limited human resource. This study involved a questionnaire survey of blood transfusion practice with reference to Indian National AIDS Control Organisation clinical guidelines at selected blood centres in four study areas (Delhi, Bangalore, Nasik District and Imphal). Information on 1062 transfusion episodes was analysed. Adult recipients accounted for 87% of transfusions, and amongst the age group of 25-34, 73% of transfusions were to women. Anaemia was listed as a reason for 60% of transfusions, surgery for 42%, acute haemorrhage for 26% and pregnancy for 16%. Seventy-four per cent of adult transfusions were inappropriate when assessed against criteria derived from government transfusion guidelines. Possible common proximate causes for inappropriate transfusions include unnecessary transfusion for iron-deficiency anaemia and transfusion as a first choice for volume replacement. Options to promote good transfusion practice in India should be appraised.

Intervention to promote appropriate blood use in India.

The decision to transfuse should be guided by information on the risks and benefits of transfusion. Safer alternatives should be considered. Properly screened blood or components from a reputable source should be used. In this study, a simple, self-educating transfusion request form was developed, and its effects on transfusion practice were assessed, using a cluster-randomized trial. Transfusions at six study hospitals and six control hospitals at four locations in India (Delhi, Bangalore, Nasik and Imphal) were monitored over a 4-month pre-intervention period and a 5-month post-intervention period. During the trial, 56 171 units were transfused to in-patients at the participating hospitals. Among the six intervention hospitals, there was some evidence of a nonsignificant post-intervention reduction in all the three main outcome measures: number of transfusion requests per admission (P = 0.09), number of units transfused per admission (P = 0.11) and number of crossmatches per admission (P = 0.06). No such changes were seen at control sites over the same period. Simple interventions to promote good clinical practice can have an effect, but may be better placed within longer term, broad-based strategies that are able to consider some of the background factors. Lack of clinical training, the hospital environment and fragmented blood bank services influence the way blood is used in India. It is thought that the intervention was ultimately unsuccessful because these factors remained as detrimental influences. A focus on education, policy and infrastructure in line with the new National Blood Policy will be important in coming years.

Dietary zinc supplementation inhibits NFkappaB activation and protects against chemically induced diabetes in CD1 mice.

Zinc status in patients with Type I diabetes is significantly lower than healthy controls. Whether zinc supplementation can prevent the onset of Type I diabetes is unknown. Recent studies have suggested that the generation of reactive oxygen species (ROS) is a cause of beta cell death leading to Type I diabetes. In addition, we found that activation of NFkappaB (a ROS-sensitive transcription factor that regulates immune responses) may be the key cellular process that bridges oxidative stress and the death of beta cells. Zinc is a known antioxidant in the immune system. Therefore, this study is designed to test whether an increase in dietary zinc can prevent the onset of Type I diabetes by blocking NFkappaB activation in the pancreas. The results show that high zinc intake significantly reduced the severity of Type I diabetes (based on hyperglycemia, insulin level, and islet morphology) in alloxan and streptozotocin-induced diabetic models. Zinc supplementation also inhibited NFkappaB activation and decreased the expression of inducible NO synthase, a downstream target gene of NFkappaB. It is concluded that zinc supplementation can significantly inhibit the development of Type I diabetes. The ability of zinc to modulate NFkappaB activation in the diabetogenic pathway may be the key mechanism for zinc's protective effect. Inhibition of the NFkappaB pathway may prove to be an important criterion for choosing nutritional strategies for Type I diabetes prevention.

Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia.

Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins with potential antioxidant activity. Despite evidence that they are upregulated in pulmonary tissue after oxidative stress, little is known regarding their influence on trace metal homeostasis. In this study, we have used copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpressing and gene knockout mice and hyperoxia to investigate the effects of chronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and metallothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copper and iron as well as circulating copper homeostasis. These results suggest that ceruloplasmin and metallothionein may function as antioxidants independent of their role in trace metal homeostasis and that Cu/Zn SOD functions in copper homeostasis via mechanisms distinct from its superoxide scavenging properties.

Effect of conjugated linoleic acid on fungal delta6-desaturase activity in a transformed yeast system.

Conjugated linoleic acid (CLA; 18:2), a group of positional and geometric isomers of linoleic acid (LA; 18:2n-6), has been shown to modulate immune function through its effect on eicosanoid synthesis. This effect has been attributed to a reduced production of n-6 polyunsaturated fatty acid (PUFA), the precursor of eicosanoids. Since delta6-desaturase is the rate-limiting enzyme of the n-6 PUFA production, it is our hypothesis that CLA, which has similar chemical structure to LA, interacts directly with delta6-desaturase. A unique and simple model, i.e., baker's yeast (Saccharomyces cerevisiae) transformed with fungal delta6-desaturase gene, previously established, was used to investigate the direct effect of CLA on delta6-desaturase. This model allows LA to be converted to y-linolenic acid (GLA; 18:3n-6) but not GLA to its metabolite(s). No metabolites of CLA were found in the lipids of the yeast transformed with delta6-desaturase. The inability to convert CLA to conjugated GLA was not due to the failure of yeast cells to take up the CLA isomers. CLA mixture and individual isomers significantly inhibited the activity of delta6-desaturase of the transformed yeast in vivo. Even though its uptake by the yeast was low, CLA c9,t11 isomer was found to be the most potent inhibitor of the four isomers tested, owing to its high inhibitory effect on delta6-desaturase. Since CLA did not cause significant changes in the level of delta6-desaturase mRNA, the inhibition of GLA production could not be attributed to suppression of delta6-desaturase gene expression at the transcriptional level.

Inhibitory effect of conjugated linoleic acid on linoleic acid elongation in transformed yeast with human elongase.

Conjugated linoleic acid (CLA; 18:2) refers to a group of positional and geometric isomers derived from linoleic acid (LA; delta9,12-18:2). Using a growing baker's yeast (Saccharomyces cerevisiae) transformed with human elongase gene, we examined the inhibitory effect of CLA at various concentrations (10, 25, 50, and 100 microM) on elongation of LA (25 microM) to eicosadienoic acid (EDA; delta11,14-20:2). Among four available individual CLA isomers, only c9,t11- and t10,c12-isomers inhibited elongation of LA to EDA. The extent of inhibition (ranging from 20 to 60%) was related to the concentration of CLA added to the medium. In the meantime, only these two isomers, when added at 50 microM to the media, were elongated to conjugated FDA (c11,t13- and t12,c14-20:2) by the same recombinant elongase at the rate of 28 and 24%, respectively. The inhibitory effect of CLA on LA elongation is possibly due to competition between CLA isomers and LA for the recombinant elongase. Thus, results from this study and a previous study suggest that the biological effect of CLA is exerted through its inhibitory effect on delta6-desaturation as well as elongation of LA which results in a decrease in long-chain n-6 fatty acids and consequently the eicosanoid synthesis.

Evaluation of the ability of orally administered aspirin to mitigate effects of 3-methylindole in feedlot cattle.

OBJECTIVE: To evaluate the ability of orally administered aspirin to mitigate 3-methylindole (3MI)-induced respiratory tract disease and reduced rate of gain in feedlot cattle. ANIMALS: 244 beef cattle. PROCEDURE: In a masked, randomized, controlled field trial, calves were untreated (controls) or received a single orally administered dose of aspirin (31.2 g) on entry into a feedlot. Serum 3MI concentrations were measured on days 0, 3, and 6. Rumen 3MI concentration was measured on day 3. Cattle were observed daily for clinical signs of respiratory tract disease. Lungs were evaluated at slaughter for gross pulmonary lesions. RESULTS: Mean daily gain (MDG) in cattle treated with aspirin, compared with control cattle, was 0.06 kg greater in the backgrounding unit and 0.03 kg greater for the overall feeding period. Neither serum nor rumen 3MI concentrations appeared to modify this effect. Cattle treated with aspirin were more likely to be treated for respiratory tract disease. Mortality rate, gross pulmonary lesions, and serum and rumen 3MI concentrations were similar between groups. Increased rumen 3MI concentration was associated with a small difference in risk of lung fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Cattle given a single orally administered dose of aspirin on feedlot entry had higher MDG in the backgrounding unit and for the overall feeding period, but this finding could not be attributed to mitigation of effects of 3MI. This may have been influenced by low peak 3MI production and slow rates of gain.

Effects of 3-methylindole production and immunity against bovine respiratory syncytial virus on development of respiratory tract disease and rate of gain of feedlot cattle.

OBJECTIVE: To determine whether immunity against bovine respiratory syncytial virus (BRSV) mitigates the effects of 3-methylindole (3MI) on occurrence of bovine respiratory tract disease (BRD) and rate of gain in feedlot cattle. ANIMALS: 254 mixed-breed beef cattle. PROCEDURE: Cattle were randomly assigned to 1 of 3 groups at the time of arrival at the feedlot. One group was vaccinated with an inactivated BRSV vaccine, another was vaccinated with a modified-live BRSV vaccine, and the third was maintained as unvaccinated control cattle. On days 0 and 28, serum BRSV antibody concentrations were measured, using serum neutralizing and ELISA techniques. Serum 3MI concentrations were measured at feedlot arrival and 3 days later. Cattle were monitored for development of BRD. At slaughter, lungs were evaluated grossly for chronic lesions. RESULTS: Higher serum 3MI concentrations early in the feeding period were associated with lower mean daily gain. Control cattle were more likely to be treated for BRD after day 3, compared with cattle vaccinated with the modified-live BRSV vaccine. Humoral immunity against BRSV did not appear to modify the effect of 3MI on development of BRD or mean daily gain. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that abrogating the effects of 3MI and BRSV infection may improve the health and growth performance of feedlot cattle. However, in this study, immunity against BRSV did not appear to protect against the potential synergism between 3MI and BRSV infection, possibly because of the slow rates of gain of cattle included in the study or timing of sample collection.