Novel imaging techniques in refractory pituitary adenomas.

Accurate localization of the site(s) of active disease is key to informing decision-making in the management of refractory pituitary adenomas when autonomous hormone secretion and/or continued tumor growth challenge conventional therapeutic approaches. In this context, the use of non-standard MR sequences, alternative post-acquisition image processing, or molecular (functional) imaging may provide valuable additional information to inform patient management.

Modern imaging in Cushing's disease.

Management of Cushing's disease is informed by dedicated imaging of the sella and parasellar regions. Although magnetic resonance imaging (MRI) remains the investigation of choice, a significant proportion (30-50%) of corticotroph tumours are so small as to render MRI indeterminate or negative when using standard clinical sequences. In this context, alternative MR protocols [e.g. 3D gradient (recalled) echo, with acquisition of volumetric data] may allow detection of tumors that have not been previously visualized. The use of hybrid molecular imaging (e.g. 11C-methionine positron emission tomography coregistered with volumetric MRI) has also been proposed as an additional modality for localizing microadenomas.

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy.

PURPOSE: To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance. PATIENTS AND METHODS: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances. RESULTS: In all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment. CONCLUSIONS: In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Systematic Study of L-Shell Opacity at Stellar Interior Temperatures.

The first systematic study of opacity dependence on atomic number at stellar interior temperatures is used to evaluate discrepancies between measured and modeled iron opacity [J. E. Bailey et al., Nature (London) 517, 56 (2015)NATUAS0028-083610.1038/nature14048]. High-temperature (>180 eV) chromium and nickel opacities are measured with ±6%-10% uncertainty, using the same methods employed in the previous iron experiments. The 10%-20% experiment reproducibility demonstrates experiment reliability. The overall model-data disagreements are smaller than for iron. However, the systematic study reveals shortcomings in models for density effects, excited states, and open L-shell configurations. The 30%-45% underestimate in the modeled quasicontinuum opacity at short wavelengths was observed only from iron and only at temperature above 180 eV. Thus, either opacity theories are missing physics that has nonmonotonic dependence on the number of bound electrons or there is an experimental flaw unique to the iron measurement at temperatures above 180 eV.

Numerical investigations of potential systematic uncertainties in iron opacity measurements at solar interior temperatures.

Iron opacity calculations presently disagree with measurements at an electron temperature of ∼180-195 eV and an electron density of (2-4)×10^{22}cm^{-3}, conditions similar to those at the base of the solar convection zone. The measurements use x rays to volumetrically heat a thin iron sample that is tamped with low-Z materials. The opacity is inferred from spectrally resolved x-ray transmission measurements. Plasma self-emission, tamper attenuation, and temporal and spatial gradients can all potentially cause systematic errors in the measured opacity spectra. In this article we quantitatively evaluate these potential errors with numerical investigations. The analysis exploits computer simulations that were previously found to reproduce the experimentally measured plasma conditions. The simulations, combined with a spectral synthesis model, enable evaluations of individual and combined potential errors in order to estimate their potential effects on the opacity measurement. The results show that the errors considered here do not account for the previously observed model-data discrepancies.

Is the support that dental registrants in difficulty receive from postgraduate dental teams and other sources adequate?

Objective The aim of this research was to investigate the views of dental registrants in difficulty (DRiDS) on the support they received from postgraduate dental teams (PgDT) in Health Education England (HEE) and other sources. These data were complemented by the views of those appointed from the PgDT to support them on the service they provide.Method Qualitative data were collected by recording one-to-one semi structured telephone interviews, lasting approximately 30 minutes, with registrants in difficulty and supporters purposefully sampled from across England and Wales. Recordings were transcribed and the interview data analysed for recurring discourses and themes using thematic framework analysis.Setting and subjects All regional leads for DRiDs services in PgDT across the UK were asked to invite the DRiDs they were in contact with and the supporters they had appointed to contact the research team. Attempts were made to contact all who returned consent forms and six DRiDs and 11 supporters were eventually interviewed.Results Overall the DRiDs thought that the PgDT were very helpful. They were in many cases the only source of expert support and advice, particularly with regard to developing a personal development plan and collecting evidence about their practice to present to the regulator. There was a good match between the qualities that DRiDs wanted their supporters to have and the strengths supporters felt they brought to the role. The DRiDs had mixed views about the support provided by their indemnifiers and could not identify any other organisations that provided support once conditions had been imposed. Some had the support of peers; but both DRiDs and supporters felt there was a need for further support in addition to the educational support provided by PgDT and legal support provided by the indemnifier.Conclusion The DRiDS regarded the PgDT as their primary source of support and, in general, were very satisfied with the character and competence of the service.

Supporting dental registrants in difficulty: the service provided by postgraduate dental education teams.

The number of dental registrants in difficulty (DRiDs) has increased significantly in recent years and the General Dental Council or National Health Service organisations tasked with the management of dental services will, if appropriate, instruct the registrant to contact postgraduate dental teams (PgDT) based in regional offices of Health Education England and equivalent postgraduate deaneries in Wales and Scotland for assistance in meeting their conditions for continued registration. We surveyed DRiDs Leads within the PgDT with a view to understanding the current development of this important service. Results revealed that these managers had considerable relevant previous experience which underpinned their responsibility for DRiDs. Their responses indicated that there were notable differences between PgDT in the number of DRiDs seeking their help and that the development of the service and the resources deployed to help DRIDs also differed significantly. Those responsible were generally happy with the service they were providing and all were able to see DRiDs for an initial interview within four weeks of being contacted. However, weaknesses were identified such as insufficient time to support individual registrants, lack of consistent process across PgDT teams and a need for clinical training facilities.

Calibrated simulations of Z opacity experiments that reproduce the experimentally measured plasma conditions.

Recently, frequency-resolved iron opacity measurements at electron temperatures of 170-200 eV and electron densities of (0.7-4.0)×10(22)cm(-3) revealed a 30-400% disagreement with the calculated opacities [J. E. Bailey et al., Nature (London) 517, 56 (2015)]. The discrepancies have a high impact on astrophysics, atomic physics, and high-energy density physics, and it is important to verify our understanding of the experimental platform with simulations. Reliable simulations are challenging because the temporal and spatial evolution of the source radiation and of the sample plasma are both complex and incompletely diagnosed. In this article, we describe simulations that reproduce the measured temperature and density in recent iron opacity experiments performed at the Sandia National Laboratories Z facility. The time-dependent spectral irradiance at the sample is estimated using the measured time- and space-dependent source radiation distribution, in situ source-to-sample distance measurements, and a three-dimensional (3D) view-factor code. The inferred spectral irradiance is used to drive 1D sample radiation hydrodynamics simulations. The images recorded by slit-imaged space-resolved spectrometers are modeled by solving radiation transport of the source radiation through the sample. We find that the same drive radiation time history successfully reproduces the measured plasma conditions for eight different opacity experiments. These results provide a quantitative physical explanation for the observed dependence of both temperature and density on the sample configuration. Simulated spectral images for the experiments without the FeMg sample show quantitative agreement with the measured spectral images. The agreement in spectral profile, spatial profile, and brightness provides further confidence in our understanding of the backlight-radiation time history and image formation. These simulations bridge the static-uniform picture of the data interpretation and the dynamic-gradient reality of the experiments, and they will allow us to quantitatively assess the impact of effects neglected in the data interpretation.

Neural correlates of social exchanges during the Prisoner's Dilemma game in depression.

BACKGROUND: Depression is a disabling disorder that significantly impacts on the interpersonal functioning of individuals. However, little is known about the neural substrates of such difficulties. In the last few years neuroeconomics, which combines imaging with multiplayer behavioural economic paradigms, has been used to study the neural substrates of normal and abnormal interpersonal interactions. METHOD: This study used functional magnetic resonance imaging to investigate neural activity in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic game, the Prisoner's Dilemma. In this game, the participant and a co-player independently choose either to cooperate or not cooperate with each other. RESULTS: Depressed participants reported higher levels of negative feelings (betrayal, guilt) during the game than did controls. Neural activation was compared between 'imbalanced' events [when one of the players cooperated and the other defected ('CD' and 'DC')] and 'draw' events [when both players either cooperated or defected ('CC' and 'DD')]. Participants preferentially activated the anterior insula and the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and regulation of emotions. Importantly, compared to controls depressed participants showed reduced activation in the left DLPFC, with the extent of signal reduction correlating with increased self-report feelings of guilt associated with DC outcomes. CONCLUSIONS: Our findings suggest that depression is associated with reduced activation of the DLPFC during social events that involve unreciprocated cooperation. This abnormality may underlie anomalies in cognitive control and top-down regulation of emotions during challenging social exchanges.

Identification and quantification of factors affecting neonatal immunological transfer in dairy calves in the UK.

The object of the study was to quantify the prevalence of failure of passive transfer in UK dairy farms and to identify variables that had a significant impact on the rate of immunological transfer. In a six-month study of 444 calvings from seven UK dairy farms, 26 per cent of calves failed to receive adequate immunoglobulin transfer as judged by a plasma total protein (pTP) concentration less than 5.6 g/dl. Colostrum immunoglobulin concentration, indirectly measured using Brix refractometry, showed wide variations with samples ranging from 10.3 to 34.7 Brix units. Thirty-seven per cent of samples were below the suggested cut-off Brix score for colostrum quality of 22 per cent. Potential associations between covariates and plasma protein concentration were investigated using multiple linear regression models. The covariate with the greatest impact on the pTP concentration was the farm on which the calf was born (P<0.05). A significant but small association was demonstrated between colostrum immunoglobulin concentration and calf pTP concentration (P<0.01). Multiple linear regression models suggested that the time of colostrum collection after calving, parity of the dam, and the individual farm were associated with the Brix measurements (P<0.05). This study suggested that veterinary review of colostrum protocols on farm with emphasis on prompt collection and dosing after calving remains a simple and effective measure to improve passive transfer and thus calf health on UK dairy farms.

Technical assessment of whole body angiography and cardiac function within a single MRI examination.

AIM: To evaluate a combined protocol for simultaneous cardiac MRI (CMR) and contrast-enhanced (CE) whole-body MR angiography (WB-MRA) techniques within a single examination. MATERIALS AND METHODS: Asymptomatic volunteers (n = 48) with low-moderate risk of cardiovascular disease (CVD) were recruited. The protocol was divided into four sections: (1) CMR of left ventricle (LV) structure and function; (2) CE-MRA of the head, neck, and thorax followed by the distal lower limbs; (3) CMR LV "late gadolinium enhancement" assessment; and (4) CE-MRA of the abdomen and pelvis followed by the proximal lower limbs. Multiple observers undertook the image analysis. RESULTS: For CMR, the mean ejection fraction (EF) was 67.3 ± 4.8% and mean left ventricular mass (LVM) was 100.3 ± 22.8 g. The intra-observer repeatability for EF ranged from 2.1-4.7% and from 9-12 g for LVM. Interobserver repeatability was 8.1% for EF and 19.1 g for LVM. No LV delayed myocardial enhancement was observed. For WB-MRA, some degree of luminal narrowing or stenosis was seen at 3.6% of the vessel segments (involving n = 29 of 48 volunteers) and interobserver radiological opinion was consistent in 96.7% of 1488 vessel segments assessed. CONCLUSION: Combined assessment of WB-MRA and CMR can be undertaken within a single examination on a clinical MRI system. The associated analysis techniques are repeatable and may be suitable for larger-scale cardiovascular MRI studies.

Supporting dental registrants in difficulty.

Over the past few years there has been a significant increase in the number of dentists and dental care professionals (registrants) having conditions placed on their practice either by the General Dental Council or NHS area teams. There are a number of reasons for this including the fact that patients complain more often, colleagues are now expected to alert the authorities if poor practice is detected and the demographics of the dental profession in the UK are changing. Steps have already been taken to prevent dentists getting into difficulty, such as the development of requirements for continued professional development by the GDC and past initiatives at a local level set up to assist dentist in difficulty. The regional offices of Health Education England and equivalent organisations in Wales and Scotland assist registrants in difficulty in meeting these conditions. Little published research has been carried out into this important service which has had to develop rapidly over the past few years. There is a need to investigate the current service, the views of those dental professionals being assisted and those providing the support to inform the further development of the service. This paper provides an introduction to a planned series of research papers reporting on our investigation into the service provided by HEE teams.

A higher-than-predicted measurement of iron opacity at solar interior temperatures.

Nearly a century ago it was recognized that radiation absorption by stellar matter controls the internal temperature profiles within stars. Laboratory opacity measurements, however, have never been performed at stellar interior conditions, introducing uncertainties in stellar models. A particular problem arose when refined photosphere spectral analysis led to reductions of 30-50 per cent in the inferred amounts of carbon, nitrogen and oxygen in the Sun. Standard solar models using the revised element abundances disagree with helioseismic observations that determine the internal solar structure using acoustic oscillations. This could be resolved if the true mean opacity for the solar interior matter were roughly 15 per cent higher than predicted, because increased opacity compensates for the decreased element abundances. Iron accounts for a quarter of the total opacity at the solar radiation/convection zone boundary. Here we report measurements of wavelength-resolved iron opacity at electron temperatures of 1.9-2.3 million kelvin and electron densities of (0.7-4.0) × 10(22) per cubic centimetre, conditions very similar to those in the solar region that affects the discrepancy the most: the radiation/convection zone boundary. The measured wavelength-dependent opacity is 30-400 per cent higher than predicted. This represents roughly half the change in the mean opacity needed to resolve the solar discrepancy, even though iron is only one of many elements that contribute to opacity.

Abnormal brain responses to social fairness in depression: an fMRI study using the Ultimatum Game.

BACKGROUND: Depression is a prevalent disorder that significantly affects the social functioning and interpersonal relationships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social difficulties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroimaging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates. METHOD: We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players. RESULTS: In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe. CONCLUSIONS: Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie abnormalities in processing information linked to the fairness and rewarding aspects of other people's decisions.

Nuclear waste viewed in a new light; a synchrotron study of uranium encapsulated in grout.

How do you characterise the contents of a sealed nuclear waste package without breaking it open? This question is important when the contained corrosion products are potentially reactive with air and radioactive. Synchrotron X-rays have been used to perform micro-scale in-situ observation and characterisation of uranium encapsulated in grout; a simulation for a typical intermediate level waste storage packet. X-ray tomography and X-ray powder diffraction generated both qualitative and quantitative data from a grout-encapsulated uranium sample before, and after, deliberately constrained H2 corrosion. Tomographic reconstructions provided a means of assessing the extent, rates and character of the corrosion reactions by comparing the relative densities between the materials and the volume of reaction products. The oxidation of uranium in grout was found to follow the anoxic U+H2O oxidation regime, and the pore network within the grout was observed to influence the growth of uranium hydride sites across the metal surface. Powder diffraction analysis identified the corrosion products as UO2 and UH3, and permitted measurement of corrosion-induced strain. Together, X-ray tomography and diffraction provide means of accurately determining the types and extent of uranium corrosion occurring, thereby offering a future tool for isolating and studying the reactions occurring in real full-scale waste package systems.

Lightweight aerial vehicles for monitoring, assessment and mapping of radiation anomalies.

The Fukushima Daiichi nuclear power plant (FDNPP) incident released a significant mass of radioactive material into the atmosphere. An estimated 22% of this material fell out over land following the incident. Immediately following the disaster, there was a severe lack of information not only pertaining to the identity of the radioactive material released, but also its distribution as fallout in the surrounding regions. Indeed, emergency aid groups including the UN did not have sufficient location specific radiation data to accurately assign exclusion and evacuation zones surrounding the plant in the days and weeks following the incident. A newly developed instrument to provide rapid and high spatial resolution assessment of radionuclide contamination in the environment is presented. The device consists of a low cost, lightweight, unmanned aerial platform with a microcontroller and integrated gamma spectrometer, GPS and LIDAR. We demonstrate that with this instrument it is possible to rapidly and remotely detect ground-based radiation anomalies with a high spatial resolution (<1 m). Critically, as the device is remotely operated, the user is removed from any unnecessary or unforeseen exposure to elevated levels of radiation.

Effect and mode of action of the Texel muscling QTL (TM-QTL) on carcass traits in purebred Texel lambs.

TM-QTL is a quantitative trait locus (QTL) on ovine chromosome 18 (OAR18) known to affect loin muscling in Texel sheep. Previous work suggested that its mode of inheritance is consistent with paternal polar overdominance, but this has yet to be formally demonstrated. This study used purebred Texel sheep segregating for TM-QTL to confirm its presence in the chromosomal region in which it was first reported and to determine its pattern of inheritance. To do so, this study used the first available data from a Texel flock, which included homozygote TM-QTL carriers (TM/TM; n=34) in addition to homozygote non-carriers (+/+; n=40 and, heterozygote TM-QTL-carriers inheriting TM-QTL from their sire (TM/+; n=53) or their dam (+/TM; n=17). Phenotypes included a wide range of loin muscling, carcass composition and tissue distribution traits. The presence of a QTL affecting ultrasound muscle depth on OAR18 was confirmed with a paternal QTL effect ranging from +0.54 to +2.82 mm UMD (s.e. 0.37 to 0.57 mm) across the sires segregating for TM-QTL. Loin muscle width, depth and area, loin muscle volume and dissected M. longissimus lumborum weight were significantly greater for TM/+ than +/+ lambs (+2.9% to +7.9%; P<0.05). There was significant evidence that the effect of TM-QTL on the various loin muscling traits measured was paternally polar overdominant (P<0.05). In contrast, there was an additive effect of TM-QTL on both live weight at 20 weeks and carcass weight; TM/TM animals were significantly (P<0.05) heavier than +/+ (+11.1% and +7.3%, respectively) and +/TM animals (+11.9% and +11.7%, respectively), with TM/+ intermediate. Weights of the leg, saddle and shoulder region (corrected for carcass weight) were similar in the genotypic groups. There was a tendency for lambs inheriting TM-QTL from their sire to be less fat with slightly more muscle than non-carriers. For example, carcass muscle weight measured by live animal CT-scanning was 2.8% higher in TM/TM than +/+ lambs (P<0.05), carcass muscle weight measured by carcass CT-scanning was 1.36% higher in TM/+ than +/+ lambs (P<0.05), and weight of fat trimmed from the carcass cuts was significantly lower for TM/+ than +/+ lambs (-11.2%; P<0.05). No negative effects of TM-QTL on carcass traits were found. Optimal commercial use of TM-QTL within the sheep industry would require some consideration, due to the apparently different mode of action of the two main effects of TM-QTL (on growth and muscling).